Clinical characteristics of 138 Chinese female patients with idiopathic hypogonadotropic hypogonadism

PubMed Central

Tang, Rui-yi; Ma, Miao; Lin, Shou-qing; Zhang, Yi-wen; Wang, Ya-ping

2017-01-01

Objective To evaluate the clinical features of Chinese women with idiopathic hypogonadotropic hypogonadism (IHH). Methods We retrospectively reviewed the clinical characteristics, laboratory and imaging findings, therapeutic management and fertility outcomes of 138 women with IHH. All patients had been treated and followed up at an academic medical centre during 1990–2016. Results Among the 138 patients, 82 patients (59.4%) were diagnosed with normosmic IHH and 56 patients (40.6%) were diagnosed with Kallmann syndrome (KS). The patients with IHH experienced occasional menses (4.3%), spontaneous thelarche (45.7%) or spontaneous pubarche (50.7%). Women with thelarche had a higher percentage of pubarche (P < 0.001) and higher gonadotropin concentrations (P < 0.01). Olfactory bulb/sulci abnormalities were found during the magnetic resonance imaging (MRI) of all patients with KS. Most patients with IHH had osteopenia and low bone age. Among the 16 women who received gonadotropin-releasing hormone treatment, ovulation induction or assisted reproductive technology, the clinical pregnancy rate was 81.3% and the live birth rate was 68.8%. Conclusions The present study revealed that the phenotypic spectrum of women with IHH is broader than typical primary amenorrhoea with no secondary sexual development, including occasional menses, spontaneous thelarche or pubarche. MRI of the olfactory system can facilitate the diagnosis of KS. Pregnancy can be achieved after receiving appropriate treatment. PMID:29018155

Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism (4H) Syndrome With Vertebral Anomalies: A Novel Association.

PubMed

Muthusamy, Karthik; Sudhakar, Sniya V; Yoganathan, Sangeetha; Thomas, Maya Mary; Alexander, Mathew

2015-06-01

Hypomyelination, hypodontia, hypogonadotropic hypogonadism (4H) syndrome is a rare hypomyelination disorder with around 40 cases reported worldwide. Children with hypomyelination, hypodontia, hypogonadotropic hypogonadism syndrome present with varying degrees of developmental delay with a spastic ataxic syndrome with delayed eruption of teeth along with disruption in the eruption sequence, hypogonadotropic hypogonadism, and a fluctuating clinical course with intercurrent infections and varying periods of stability. The disorder is caused by mutations in POL3A and POL3B genes and is collectively termed as pol III-related leukodystrophies. Here we describe 2 children with hypomyelination, hypodontia, hypogonadotropic, hypogonadism syndrome and the association of multiple vertebral fusion anomalies in one of them, which has not been previously described in the literature. We conclude that the spectrum of the disorder is not limited to brain parenchyma alone and involves all the structures arising from neural ectoderm, and this needs further research. © The Author(s) 2014.

Hypogonadotropic Hypogonadism due to Novel FGFR1 Mutations.

PubMed

Akkuş, Gamze; Kotan, Leman Damla; Durmaz, Erdem; Mengen, Eda; Turan, İhsan; Ulubay, Ayça; Gürbüz, Fatih; Yüksel, Bilgin; Tetiker, Tamer; Topaloğlu, A Kemal

2017-06-01

The underlying genetic etiology of hypogonadotropic hypogonadism (HH) is heterogeneous. Fibroblast growth factor signaling is pivotal in the ontogeny of gonadotropin-releasing hormone neurons. Loss-of-function mutations in FGFR1 gene cause variable HH phenotypes encompassing pubertal delay to idiopathic HH (IHH) or Kallmann syndrome (KS). As FGFR1 mutations are common, recognizing mutations and associated phenotypes may enhance clinical management. Using a candidate gene approach, we screened 52 IHH/KS patients. We identified three novel (IVS3-1G>C and p.W2X, p.R209C) FGFR1 gene mutations. Despite predictive null protein function, patients from the novel mutation families had normosmic IHH without non-reproductive phenotype. These findings further emphasize the great variability of FGFR1 mutation phenotypes in IHH/KS.

Bone Mineral Density in Adolescent Girls with Hypogonadotropic and Hypergonadotropic Hypogonadism.

PubMed

Özbek, Mehmet Nuri; Demirbilek, Hüseyin; Baran, Rıza Taner; Baran, Ahmet

2016-06-05

Deficiency of sex steroids has a negative impact on bone mineral content. In studies conducted on postmenopausal women and animal studies, elevated follicle-stimulating hormone (FSH) levels were found to be correlated with a decrease in bone mineralization and osteoporosis. The aim of the present study was to evaluate bone mineral density (BMD) in adolescent girls with hypogonadotropic and hypergonadotropic hypogonadism and also to investigate the correlation between FSH level and BMD. The study group included 33 adolescent girls with hypogonadism (14 with hypogonadotropic hypogonadism and 19 with hypergonadotropic hypogonadism). FSH, luteinizing hormone, estradiol levels, and BMD (using dual energy x-ray absorptiometry) were measured. There were no statistically significant differences between the chronological age and bone age of the two patient groups, namely, with hypogonadotropic and hypergonadotropic hypogonadism. There was also no significant difference between BMD z-score values obtained from measurements from the spine and the femur neck of patients in the two groups (p-values were 0.841 and 0.281, respectively). In the hypergonadotropic group, a moderately negative correlation was detected between FSH level and BMD z-score measured from the femur neck (ρ=-0.69, p=0.001), whilst no correlation was observed between FSH levels and height adjusted BMD-z scores measured from the spine (ρ=0.17, p=0.493). FSH level was not found to be an independent variable affecting BMD z-score. BMD z-scores were detected to be similar in adolescent girls with hypogonadotropic and hypergonadotropic hypogonadism, and FSH levels were not found to have a clinically relevant impact on BMD.

Similarity of female central (hypogonadotropic) hypogonadism and postmenopause.

PubMed

Ilovayskaya, I; Zektser, V; Lazebnik, L

2017-08-01

Central (hypogonadotropic) hypogonadism in women could be a cause of persistent amenorrhea and hypoestrogenemia as observed in postmenopause. This study aimed to compare the clinical, hormonal and biochemical features in women with non-physiological (central hypogonadism) and physiological (postmenopause) hypoestrogenemia. A total of 161 young women, median age 24.9 years (interquartile range (IQR) 21.2; 30.5) with central hypogonadism (with isolated hypogonadotropic hypogonadism, n = 76, and with hypopituitarism, n = 85), 53 healthy young women, median age 23.9 years (IQR 23.1; 28.0) and 50 healthy postmenopausal women, median age 56.0 years (IQR 53.1; 58.5), were examined. Psychoemotional, neurovegetative and urogenital symptoms, sex steroid levels, parameters of lipid and mineral metabolism were evaluated. In young women with central hypogonadism, the frequencies of psychoemotional, neurovegetative and urogenital complaints differed significantly from those in healthy young women and were similar to those in postmenopausal women. Concentrations of estradiol, testosterone, dehydroepiandrosterone sulfate, parameters of lipid and mineral metabolism as well as quality of life in women with central hypogonadism were not typical of healthy young women but were similar to those of postmenopausal women of middle/old age. Despite the young age of women with central hypogonadism, clinical, hormonal and biochemical abnormalities were similar in many aspects to those in postmenopausal women at middle/old age. These revealed features could be considered as signs of premature aging in young amenorrheic women with low gonadotropin levels.

Bone Mineral Density in Adolescent Girls with Hypogonadotropic and Hypergonadotropic Hypogonadism

PubMed Central

Özbek, Mehmet Nuri; Demirbilek, Hüseyin; Baran, Rıza Taner; Baran, Ahmet

2016-01-01

Objective: Deficiency of sex steroids has a negative impact on bone mineral content. In studies conducted on postmenopausal women and animal studies, elevated follicle-stimulating hormone (FSH) levels were found to be correlated with a decrease in bone mineralization and osteoporosis. The aim of the present study was to evaluate bone mineral density (BMD) in adolescent girls with hypogonadotropic and hypergonadotropic hypogonadism and also to investigate the correlation between FSH level and BMD. Methods: The study group included 33 adolescent girls with hypogonadism (14 with hypogonadotropic hypogonadism and 19 with hypergonadotropic hypogonadism). FSH, luteinizing hormone, estradiol levels, and BMD (using dual energy x-ray absorptiometry) were measured. Results: There were no statistically significant differences between the chronological age and bone age of the two patient groups, namely, with hypogonadotropic and hypergonadotropic hypogonadism. There was also no significant difference between BMD z-score values obtained from measurements from the spine and the femur neck of patients in the two groups (p-values were 0.841 and 0.281, respectively). In the hypergonadotropic group, a moderately negative correlation was detected between FSH level and BMD z-score measured from the femur neck (ρ=-0.69, p=0.001), whilst no correlation was observed between FSH levels and height adjusted BMD-z scores measured from the spine (ρ=0.17, p=0.493). FSH level was not found to be an independent variable affecting BMD z-score. Conclusion: BMD z-scores were detected to be similar in adolescent girls with hypogonadotropic and hypergonadotropic hypogonadism, and FSH levels were not found to have a clinically relevant impact on BMD. PMID:27087454

Reversal of idiopathic hypogonadotropic hypogonadism: a cohort study in Chinese patients

PubMed Central

Mao, Jiang-Feng; Xu, Hong-Li; Duan, Jin; Chen, Rong-Rong; Li, Li; Li, Bin; Nie, Min; Min, Le; Zhang, Hong-Bing; Wu, Xue-Yan

2015-01-01

Although idiopathic hypogonadotropic hypogonadism (IHH) has traditionally been viewed as a life-long disease caused by a deficiency of gonadotropin-releasing hormone neurons, a portion of patients may gradually regain normal reproductive axis function during hormonal replacement therapy. The predictive factors for potential IHH reversal are largely unknown. The aim of our study was to investigate the incidence and clinical features of IHH male patients who had reversed reproductive axis function. In this retrospective cohort study, male IHH patients were classified into a reversal group (n = 18) and a nonreversal group (n = 336). Concentration of gonadotropins and testosterone, as well as testicle sizes and sperm counts, were determined. Of 354 IHH patients, 18 (5.1%) acquired normal reproductive function during treatment. The median age for reversal was 24 years old (range 21–34 years). Compared with the nonreversal group, the reversible group had higher basal luteinizing hormone (LH) (1.0 ± 0.7 IU l-1 vs 0.4 ± 0.4 IU l−1, P < 0.05) and stimulated LH (28.3 ± 22.6 IU l−1 vs 1.9 ± 1.1 IU l−1, P < 0.01) levels, as well as larger testicle size (5.1 ± 2.6 ml vs 1.5 ± 0.3 ml, P < 0.01), at the initial visit. In summary, larger testicle size and higher stimulated LH concentrations are favorite parameters for reversal. Our finding suggests that reversible patients may retain partially active reproductive axis function at initial diagnosis. PMID:25578938

Treatment preferences and outcome in male hypogonadotropic hypogonadism: an Indian perspective.

PubMed

Sanyal, D; Chatterjee, S

2016-06-01

This retrospective study assessed treatment preferences and outcome with testosterone or HCG / HCG-FSH combination in Indian male idiopathic hypogonadotropic hypogonadism (IHH) subjects (n = 31) above 18 years of age. 38.7% of IHH study subjects had no fertility plans and chose 3 monthly intramuscular testosterone undecanoate. 73.7% of subjects with fertility plans chose human chorionic gonadotropin (HCG) alone due to cost considerations. Spermatogenesis occurred in 21.4% on HCG alone and 60% of subjects on HCG with follicle-stimulating hormone (FSH) combination. Treatment failure is higher than published Western rates. FSH and HCG combination regimen is costly but superior to HCG alone. However, treatment failure still persists, suggesting unknown testicular defect in IHH. © 2015 Blackwell Verlag GmbH.

A Shared Genetic Basis for Self-Limited Delayed Puberty and Idiopathic Hypogonadotropic Hypogonadism

PubMed Central

Zhu, Jia; Choa, Ruth E.-Y.; Guo, Michael H.; Plummer, Lacey; Buck, Cassandra; Palmert, Mark R.; Hirschhorn, Joel N.; Seminara, Stephanie B.

2015-01-01

Context: Delayed puberty (DP) is a common issue and, in the absence of an underlying condition, is typically self limited. Alhough DP seems to be heritable, no specific genetic cause for DP has yet been reported. In contrast, many genetic causes have been found for idiopathic hypogonadotropic hypogonadism (IHH), a rare disorder characterized by absent or stalled pubertal development. Objective: The objective of this retrospective study, conducted at academic medical centers, was to determine whether variants in IHH genes contribute to the pathogenesis of DP. Subjects and Outcome Measures: Potentially pathogenic variants in IHH genes were identified in two cohorts: 1) DP family members of an IHH proband previously found to have a variant in an IHH gene, with unaffected family members serving as controls, and 2) DP individuals with no family history of IHH, with ethnically matched control subjects drawn from the Exome Aggregation Consortium. Results: In pedigrees with an IHH proband, the proband's variant was shared by 53% (10/19) of DP family members vs 12% (4/33) of unaffected family members (P = .003). In DP subjects with no family history of IHH, 14% (8/56) had potentially pathogenic variants in IHH genes vs 5.6% (1 907/33 855) of controls (P = .01). Potentially pathogenic variants were found in multiple DP subjects for the genes IL17RD and TAC3. Conclusions: These findings suggest that variants in IHH genes can contribute to the pathogenesis of self-limited DP. Thus, at least in some cases, self-limited DP shares an underlying pathophysiology with IHH. PMID:25636053

Wasting syndrome with deep bradycardia as presenting manifestation of long-standing severe male hypogonadotropic hypogonadism: a case series.

PubMed

Passeri, Elena; Bonomi, Marco; Dangelo, Francesco; Persani, Luca; Corbetta, Sabrina

2014-09-27

Physiological functioning of the testes is important for cardiac health besides for virilisation, physical strength, behavior and reproduction; moreover, hypogonadism has been demonstrated as a significant risk marker of increased all-cause and cardiovascular mortality. We reported two cases of long-standing hypogonadotropic hypogonadism presenting with wasting, bradycardia and heart failure. The two patients were admitted to emergency department for deep weakness, unresponsive anemia and severe bradycardia, requiring in one case the implanting of a monocameral pace-maker for treatment of heart failure. No previous cardiologic disorders were known and cardiac ischemia was ruled out in both patients. The first patient presented congenital hypogonadotropic hypogonadism combined with mild central hypothyroidism and growth hormone deficiency occurred in the peripubertal age, while the second one was diagnosed with isolated adult-onset severe central hypogonadism. Testosterone deficiency was the main feature in both patients as physical examination revealed clinical stigmata of hypogonadism and testosterone replacement induced a dramatic improvement of general condition. Genetic analysis of genes involved in hypogonadotropic hypogonadism failed to identify alterations. Long-standing hypogonadism in males can be associated with life threatening body alterations including severe bradycardia and heart failure.

Idiopathic hypogonadotropic hypogonadism in a mother and her monozygotic twins born after a single embryo transfer.

PubMed

Laitinen, Eeva-Maria; Tommiska, Johanna; Dunkel, Leo; Sankilampi, Ulla; Vaaralahti, Kirsi; Raivio, Taneli

2010-04-01

To describe a mother with idiopathic hypogonadotropic hypogonadism (IHH) and her monozygotic (MZ) twin boys who all have the same heterozygous fibroblast growth factor receptor-1 (FGFR1) gene mutation. Case report. University hospital. A 28-year-old mother with normosmic IHH gave birth to MZ twin boys after a transfer of a single frozen-thawed embryo. Clinical and biochemical evaluation of IHH. Sequence analysis of the 17 coding exons (exons 2-18) and exon-intron boundaries of FGFR1 from polymerase chain reaction-amplified genomic DNA from peripheral blood leukocytes of the subjects. Phenotypic features of the subjects. All subjects harbored a previously undescribed heterozygous FGFR1 mutation (c.2049-1 G-->C), leading to the skipping of exon 16 and thus a loss of amino acids 684-726 in the tyrosine kinase domain of the receptor. The absence of exon 16 was verified at the cDNA level. The twins manifested with microphallus, cryptorchidism, and deficient postnatal activation of the hypothalamic-pituitary-gonadal axis, findings consistent with IHH. Our report underlines that assisted reproductive techniques enable the inheritance of gene mutations causing infertility. This is the first report on the phenotypic features of MZ twins with an FGFR1 mutation. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

A case with central and peripheral hypomyelination with hypogonadotropic hypogonadism and hypodontia (4H syndrome) plus cataract.

PubMed

Sato, Ikuko; Onuma, Akira; Goto, Nobue; Sakai, Fumiaki; Fujiwara, Ikuma; Uematsu, Mitsugu; Osaka, Hitoshi; Okahashi, Satomi; Nonaka, Ikuya; Tanaka, Soichiro; Haginoya, Kazuhiro

2011-01-15

Hypomyelination with hypogonadotropic hypogonadism and hypodontia (4H syndrome) is a rare disease, characterized by both central and peripheral hypomyelination. We describe a 21-year-old male with mildly progressive ataxia, mental retardation, pituitary hypogonadotropic hypogonadism, delayed dentition, and cataract. Brain magnetic resonance imaging showed hypomyelinated white matter, cerebellar atrophy, and a thin corpus callosum. The literature suggests that abnormal findings upon sural nerve biopsy may indicate peripheral hypomyelination, even in the absence of clinically and physiologically evident peripheral neuropathy. A sural nerve biopsy of this patient was normal, and this finding is further discussed. Taken together with previous reports, this case suggests that 4H syndrome can be regarded as a spectrum disorder, the cardinal signs of which may be central hypomyelination, ataxia, hypogonadotropic hypogonadism, and hypodontia. Copyright © 2010 Elsevier B.V. All rights reserved.

CLOMIPHENE CITRATE IN THE TREATMENT OF IDIOPATHIC OR FUNCTIONAL HYPOGONADOTROPIC HYPOGONADISM IN MEN: A CASE SERIES AND REVIEW OF THE LITERATURE.

PubMed

Liel, Yair

2017-03-01

Late-onset hypogonadotropic hypogonadism (LOH) is a complex, heterogeneous entity. Whenever treatment is indicated, the endocrine literature has recommend testosterone replacement. We present our experience with clomiphene citrate treatment in patients with LOH and a review of the literature. This retrospective case series included 18 male patients with hypogonadotropic hypogonadism, roughly according to the European Male Aging Study criteria for LOH, attended at an academic hospital outpatient clinic. Data were retrieved from the patients' electronic medical records. The patients' mean age (±SD) was 44.3 ± 6.3 years (range 21-67 years) referred for evaluation of low testosterone together with decreased libido, erectile dysfunction, fatigue or tiredness, anxiety, and osteoporosis. Clomiphene was initially prescribed at doses between 25 mg 3 times a week and 50 mg/day. At 6 to 8 weeks following initiation of treatment, mean basal total-testosterone increased from 7.6 ± 2.6 to 19.3 ± 5.2 nmol/L (P<.0001). Mean basal luteinizing hormone (LH) increased from 2.7 ± 2.1 to 8.3 ± 3.5 nmol/L (P<.0001). Mean basal follicle-stimulating hormone (FSH) increased from 4.2 ± 3.6 to 8.6 ± 6.2 nmol/L (P = .007). Testosterone and LH responses were invariably observed, including 2 patients with history of nonpituitary cranial pathologies, 2 with somewhat elevated FSH, and 1 with an eating disorder. Twelve (67%) patients reported improvement in symptoms. Side effects included transient nipple tenderness in 1 patient. Available data suggest that clomiphene is an efficient and convenient alternative to testosterone replacement therapy in a substantial subset of patients with LOH. Additional long-term controlled studies should further establish the role of clomiphene in LOH. FSH = follicle-stimulating hormone LH = luteinizing hormone LOH = late-onset hypogonadotropic hypogonadism.

Application of hormonal treatment in hypogonadotropic hypogonadism: more than ten years experience.

PubMed

Yang, Luo; Zhang, Si Xiao; Dong, Qiang; Xiong, Zi Bing; Li, Xiang

2012-04-01

To demonstrate the efficacy of hormone treatment on the patients with hypogonadotropic hypogonadism (HH), we summarized our more than 10 years experience. A total of 242 male patients (age range 15-52 years old) with HH including two Kallmann syndrome treated at the andrology outpatient clinics of university hospital in the past 10 years were reviewed retrospectively. The patients were divided into three groups based on the different treatment strategy. There were 84 patients treated with human chorionic gonadotropin (hCG) (group 1, hCG treatment group), 74 patients treated with hCG plus human menopause gonadotropin (hMG) (group 2, hCG + hMG treatment group), and 84 patients treated with testosterone (group 3, T treatment group). Sex characteristics, testicular volume, and sperm production were determined before and after the treatments. The therapeutic effects in the three groups were analyzed statistically. In total, 42 patients of group 1 (50.0%) and 56 of group 2 (75.7%) had their testicular volumes increased after 6-18 months treatment, from 2.0 ± 1.1 to 6.8 ± 3.2 mL and 2.1 ± 1.1 to 8.8 ± 3.9 mL, respectively. Only six patients of group 3 had their testicular volumes increased but no statistically significant. Among the patients with testes growth, 34 patients of group 1 and 48 patients of group 2 achieved spermatogenesis, and three of them made their wives pregnant naturally. During the follow-up after treatment, there were 36 patients finally defined as delayed puberty, and 204 patients defined as idiopathic hypogonadotropic hypogonadism. For the hormonal treatment of HH, testosterone therapy could not stimulate testes growth and spermatogenesis, but HCG therapy and hCG/hMG combination therapy both are effective, while hCG/hMG combination therapy could achieve better therapeutic effects.

Deletion of Otx2 in GnRH neurons results in a mouse model of hypogonadotropic hypogonadism.

PubMed

Diaczok, Daniel; DiVall, Sara; Matsuo, Isao; Wondisford, Fredric E; Wolfe, Andrew M; Radovick, Sally

2011-05-01

GnRH is the central regulator of reproductive function responding to central nervous system cues to control gonadotropin synthesis and secretion. GnRH neurons originate in the olfactory placode and migrate to the forebrain, in which they are found in a scattered distribution. Congenital idiopathic hypogonadotropic hypogonadism (CIHH) has been associated with mutations or deletions in a number of genes that participate in the development of GnRH neurons and expression of GnRH. Despite the critical role of GnRH in mammalian reproduction, a comprehensive understanding of the developmental factors that are responsible for regulating the establishment of mature GnRH neurons and the expression of GnRH is lacking. orthodenticle homeobox 2 (OTX2), a homeodomain protein required for the formation of the forebrain, has been shown to be expressed in GnRH neurons, up-regulated during GnRH neuronal development, and responsible for increased GnRH promoter activity in GnRH neuronal cell lines. Interestingly, mutations in Otx2 have been associated with human hypogonadotropic hypogonadism, but the mechanism by which Otx2 mutations cause CIHH is unknown. Here we show that deletion of Otx2 in GnRH neurons results in a significant decrease in GnRH neurons in the hypothalamus, a delay in pubertal onset, abnormal estrous cyclicity, and infertility. Taken together, these data provide in vivo evidence that Otx2 is critical for GnRH expression and reproductive competence.

Male acquired hypogonadotropic hypogonadism: diagnosis and treatment.

PubMed

Salenave, Sylvie; Trabado, Sévérine; Maione, Luigi; Brailly-Tabard, Sylvie; Young, Jacques

2012-04-01

Acquired hypogonadotropic hypogonadism (AHH), contrary to congenital hypogonadotropic hypogonadism (CHH) is characterized by postnatal onset of disorders that damage or alter the function of gonadotropin-releasing hormone (GnRH) neurons and/or pituitary gonadotroph cells. AHH thus prevents the establishment of gonadotropin secretion at puberty, or its post-pubertal maintenance. Thus, postnatal AHH may prevent the onset of puberty or appear during pubertal development, but it usually emerges after the normal age of puberty. Although pituitary tumors, particularly prolactinoma, are the most common cause, sellar tumors or cyst of the hypothalamus or infundibulum, infiltrative, vascular, iron overload and other disorders may also cause AHH. Pituitary surgery and head trauma or cranial/pituitary radiation therapy are also usual causes of AHH. The clinical manifestations of AHH depend on age of onset, the degree of gonadotropin deficiency, the rapidity of its onset and the association to other pituitary function deficiencies or excess. Men with AHH have less stamina, decreased libido, erectile dysfunction and strength, and a worsened sense of well being leading to degraded quality of life. The physical examination is usually normal if hypogonadism is of recent onset. Diminished facial, body hair and muscle mass, fine facial wrinkles, gynecomastia, and hypotrophic testes are observed in long-standing and complete AHH. Spermatogenesis is impaired and the volume of ejaculate is decreased only when gonadotropins and testosterone levels are very low. Men with AHH may have normal or low serum LH and FSH concentrations, but normal gonadotropin values are inappropriate when associated with low serum testosterone. In the majority of AHH patients, serum inhibin B is "normal". The decrease of this sertolian hormone indicates a long-standing and severe gonadotropin deficiency. Symptoms, usually associated with significant testosterone deficiency in men with AHH, improve with

Peripheral and central hypomyelination with hypogonadotropic hypogonadism and hypodontia.

PubMed

Timmons, M; Tsokos, M; Asab, M Abu; Seminara, S B; Zirzow, G C; Kaneski, C R; Heiss, J D; van der Knaap, M S; Vanier, M T; Schiffmann, R; Wong, K

2006-12-12

We identified four unrelated patients (three female, one male) aged 20 to 30 years with hypomyelination, pituitary hypogonadotropic hypogonadism, and hypodontia. Electron microscopy and myelin protein immunohistochemistry of sural nerves showed granular debris-lined clefts, expanded abaxonal space, outpocketing with vacuolar disruption, and loss of normal myelin periodicity. Reduced galactocerebroside, sphingomyelin, and GM1-N-acetylglucosamine and increased esterified cholesterol were found. This is a clinically homogeneous progressive hypomyelinating disorder. The term 4H syndrome is suggested.

Application of gonadotropin releasing hormone in hypogonadotropic hypogonadism--diagnostic and therapeutic aspects.

PubMed

Delemarre-van de Waal, Henriette A

2004-11-01

Puberty is the result of reactivation of the gonadotropin releasing hormone (GnRH) pulse generator resulting in an increasing release of GnRH by the hypothalamus, which stimulates the gonadotropic cells of the pituitary to synthesize and secrete LH and FSH. Hypogonadotropic hypogonadism (HH) is often the result of GnRH deficiency. The clinical picture is characterized by the absence of pubertal development and infertility. It is difficult to differentiate HH from delayed puberty since low gonadotropin and low testosterone levels are found in both conditions. We hypothesized that long-term GnRH administration may differentiate between the two conditions by a difference in the increase of gonadotropins, the idea being that in normal delayed puberty the pituitary of the patient has been primed with GnRH during the fetal and early postnatal period. Seventeen adolescents suspected of having hypogonadotropic hypogonadism were treated with pulsatile GnRH for 7 days. At the present time, the diagnosis of these patients is known and the results of the long-term GnRH stimulation have been evaluated according to the present diagnosis. The results show that the increase in gonadotropins following GnRH treatment is similar in both conditions. Therefore, at a prepubertal age a normal delayed puberty cannot be distinguished from hypogonadotropic hypogonadism using long-term GnRH stimulation. Long-term pulsatile GnRH treatment is a physiological therapy for the induction of puberty. Unlike testosterone it has the advantage of stimulation of testicular growth and fertility, as well as virilization, in males. We have treated 68 male patients with HH with pulsatile GnRH. The results show testicular growth and virilization in all the patients and spermatogenesis in 58 patients. Wearing a portable pump is cumbersome. However, the patients were very motivated and adapted very easily to this inconvenience. When spermatogenesis had developed, GnRH treatment was changed to human chorionic

Targeted Disruption of ALK Reveals a Potential Role in Hypogonadotropic Hypogonadism

PubMed Central

Nord, Christoffer; Ahlgren, Ulf; Eriksson, Maria; Vernersson-Lindahl, Emma; Helland, Åslaug; Alexeyev, Oleg A.; Hallberg, Bengt; Palmer, Ruth H.

2015-01-01

Mice lacking ALK activity have previously been reported to exhibit subtle behavioral phenotypes. In this study of ALK of loss of function mice we present data supporting a role for ALK in hypogonadotropic hypogonadism in male mice. We observed lower level of serum testosterone at P40 in ALK knock-out males, accompanied by mild disorganization of seminiferous tubules exhibiting decreased numbers of GATA4 expressing cells. These observations highlight a role for ALK in testis function and are further supported by experiments in which chemical inhibition of ALK activity with the ALK TKI crizotinib was employed. Oral administration of crizotinib resulted in a decrease of serum testosterone levels in adult wild type male mice, which reverted to normal levels after cessation of treatment. Analysis of GnRH expression in neurons of the hypothalamus revealed a significant decrease in the number of GnRH positive neurons in ALK knock-out mice at P40 when compared with control littermates. Thus, ALK appears to be involved in hypogonadotropic hypogonadism by regulating the timing of pubertal onset and testis function at the upper levels of the hypothalamic-pituitary gonadal axis. PMID:25955180

Hypogonadotropic Hypogonadism and Short Stature in Patients with Diabetes Due to Neurogenin 3 Deficiency.

PubMed

Rubio-Cabezas, Oscar; Gómez, José Luis; Gleisner, Andrea; Hattersley, Andrew T; Codner, Ethel

2016-10-01

Biallelic mutations in NEUROG3 are known to cause early-onset malabsorptive diarrhea due to congenital anendocrinosis and diabetes mellitus at a variable age. No other endocrine disorders have been described so far. We report four patients with homozygous NEUROG3 mutations who presented with short stature and failed to show any signs of pubertal development. Four patients (two males, two females) were diagnosed with homozygous mutations in NEUROG3 on the basis of congenital malabsorptive diarrhea and diabetes. All four had severe short stature and failed to develop secondary sexual characteristics at an appropriate age, despite some having normal body mass index. The absence of gonadal function persisted into the third decade in one patient. Upon testing, both basal and stimulated LH and FSH levels were low, with the remaining pituitary hormones within the normal range. Magnetic resonance imaging scans of the hypothalamic-pituitary axis did not reveal structural abnormalities. A diagnosis of hypogonadotropic hypogonadism was made, and replacement therapy with sex hormones was started. The high reproducibility of this novel phenotype suggests that central hypogonadism and short stature are common findings in patients with mutations in NEUROG3. Growth rate needs to be carefully monitored in these patients, who also should be routinely screened for hypogonadism when they reach the appropriate age. NEUROG3 mutations expand on the growing number of genetic causes of acquired hypogonadotropic hypogonadism.

New understandings of the genetic basis of isolated idiopathic central hypogonadism.

PubMed

Bonomi, Marco; Libri, Domenico Vladimiro; Guizzardi, Fabiana; Guarducci, Elena; Maiolo, Elisabetta; Pignatti, Elisa; Asci, Roberta; Persani, Luca

2012-01-01

Idiopathic hypogonadotropic hypogonadism is a rare disease that is characterized by delayed/absent puberty and/or infertility due to an insufficient stimulation of an otherwise normal pituitary-gonadal axis by gonadotrophin-releasing hormone (GnRH) action. Because reduced or normal luteinizing hormone (LH)/follicle-stimulating hormone (FSH) levels may be observed in the affected patients, the term idiopathic central hypogonadism (ICH) appears to be more appropriate. This disease should be distinguished from central hypogonadism that is combined with other pituitary deficiencies. Isolated ICH has a complex pathogenesis and is fivefold more prevalent in males. ICH frequently appears in a sporadic form, but several familial cases have also been reported. This finding, in conjunction with the description of numerous pathogenetic gene variants and the generation of several knockout models, supports the existence of a strong genetic component. ICH may be associated with several morphogenetic abnormalities, which include osmic defects that, with ICH, constitute the cardinal manifestations of Kallmann syndrome (KS). KS accounts for approximately 40% of the total ICH cases and has been generally considered to be a distinct subgroup. However, the description of several pedigrees, which include relatives who are affected either with isolated osmic defects, KS, or normo-osmic ICH (nICH), justifies the emerging idea that ICH is a complex genetic disease that is characterized by variable expressivity and penetrance. In this context, either multiple gene variants or environmental factors and epigenetic modifications may contribute to the variable disease manifestations. We review the genetic mechanisms that are presently known to be involved in ICH pathogenesis and provide a clinical overview of the 227 cases that have been collected by the collaborating centres of the Italian ICH Network.

Congenital combined pituitary hormone deficiency patients have better responses to gonadotrophin-induced spermatogenesis than idiopathic hypogonadotropic hypogonadism patients.

PubMed

Mao, Jiangfeng; Xu, Hongli; Wang, Xi; Huang, Bingkun; Liu, Zhaoxiang; Zhen, Junjie; Nie, Min; Min, Le; Wu, Xueyan

2015-09-01

Do patients with congenital combined pituitary hormone deficiency (CCPHD) have different responses to gonadotrophin-induced spermatogenesis compared with those with idiopathic hypogonadotropic hypogonadism (IHH)? CCPHD patients have a better response to gonadotrophin therapy than IHH patients. Gonadotrophins are effective in inducing spermatogenesis in patients with hypogonadotropic hypogonadism. This retrospective cohort study included 75 patients, 53 of whom had IHH and 22 CCPHD. They were diagnosed, treated and followed up between January 2008 and December 2013. Combined gonadotrophin therapy, consisting of human chorionic gonadotrophin and human menopausal gonadotrophin, was administered for 24 months. The success rate of spermatogenesis (≥1 sperm in ejaculate), serum total testosterone level, testicle size and sperm concentration during the treatment, as well as the first time sperm were detected in the ejaculate, were compared between the two diagnostic groups. All patients were treated in Peking Union Medical College Hospital. Spermatogenesis was successfully induced in 85% of IHH patients and 100% of CCPHD patients after 24-month combined gonadotrophin treatment (P = 0.03). In comparison with IHH, CCPHD patients had larger mean testicle sizes during the gonadotrophin treatment at 6, 12, 18 and 24 months (all P < 0.05). The initial time for sperm appearance in IHH group (n = 45) and CCPHD group (n = 22) was 13.2 ± 5.9 versus 10.4 ± 3.8 months (P = 0.045). Generally, CCPHD patients had higher sperm counts [median (quartiles)] than IHH patients during the treatment, but the difference was only statistically significant at 12 months of treatment, 3.3 (1.8, 12.0) versus 1.0 (0.0, 4.6) million/ml, P = 0.001. There was a higher level of serum total testosterone [mean (SD)] in the CCPHD group than the IHH group (676 ± 245 versus 555 ± 209 ng/dl, P = 0.035). First, the inherent nature of a retrospective designed study was a main shortcoming. Secondly

Deficiency in GnRH receptor trafficking due to a novel homozygous mutation causes idiopathic hypogonadotropic hypogonadism in three prepubertal siblings.

PubMed

Zhang, Rui; Linpeng, Siyuan; Li, Zhuo; Cao, Yingxi; Tan, Hu; Liang, Desheng; Wu, Lingqian

2018-08-30

Idiopathic hypogonadotropic hypogonadism (IHH) is characterized by low levels of gonadotropins and delayed or absent sexual development. Most of the patients are diagnosed in late adolescence or early adulthood. Determining the diagnosis of IHH in prepubertal patients can be challenging. Making a timely, correct diagnosis has important clinical implications. Here we aimed to identify the genetic cause of IHH in three prepubertal siblings from a Chinese Han family and give appropriate treatment advice. Using whole exome sequencing (WES), we identified a novel homozygous GNRHR mutation (NM_000406; c.364C>T, p.L122F) in two prepubertal boys with cryptorchidism and micropenis. Sanger sequencing showed that their younger asymptomatic sister also had the homozygous GNRHR mutation. This mutation was inherited from the father and the mother. Immunofluorescence analysis showed that in permeabilized cells, expression of the mutant receptor on the cell membrane was significantly lower than that of wild-type. Calcium mobilization assays demonstrated that c.364C>T in the GNRHR gene is a complete loss-of-function mutation that caused IHH. These results may contribute to the genetic diagnosis of the three prepubertal siblings with IHH. According to this diagnosis, timely hormonal treatment can be given for the three prepubertal patients to induce pubertal development, especially for the asymptomatic female. Copyright © 2018 Elsevier B.V. All rights reserved.

Hypogonadotropic Hypogonadism and Short Stature in Patients with Diabetes Due to Neurogenin 3 Deficiency

PubMed Central

Rubio-Cabezas, Oscar; Gómez, José Luis; Gleisner, Andrea; Hattersley, Andrew T.

2016-01-01

Context: Biallelic mutations in NEUROG3 are known to cause early-onset malabsorptive diarrhea due to congenital anendocrinosis and diabetes mellitus at a variable age. No other endocrine disorders have been described so far. We report four patients with homozygous NEUROG3 mutations who presented with short stature and failed to show any signs of pubertal development. Case Description: Four patients (two males, two females) were diagnosed with homozygous mutations in NEUROG3 on the basis of congenital malabsorptive diarrhea and diabetes. All four had severe short stature and failed to develop secondary sexual characteristics at an appropriate age, despite some having normal body mass index. The absence of gonadal function persisted into the third decade in one patient. Upon testing, both basal and stimulated LH and FSH levels were low, with the remaining pituitary hormones within the normal range. Magnetic resonance imaging scans of the hypothalamic-pituitary axis did not reveal structural abnormalities. A diagnosis of hypogonadotropic hypogonadism was made, and replacement therapy with sex hormones was started. Conclusions: The high reproducibility of this novel phenotype suggests that central hypogonadism and short stature are common findings in patients with mutations in NEUROG3. Growth rate needs to be carefully monitored in these patients, who also should be routinely screened for hypogonadism when they reach the appropriate age. NEUROG3 mutations expand on the growing number of genetic causes of acquired hypogonadotropic hypogonadism. PMID:27533310

New understandings of the genetic basis of isolated idiopathic central hypogonadism

PubMed Central

Bonomi, Marco; Vladimiro Libri, Domenico; Guizzardi, Fabiana; Guarducci, Elena; Maiolo, Elisabetta; Pignatti, Elisa; Asci, Roberta; Persani, Luca

2012-01-01

Idiopathic hypogonadotropic hypogonadism is a rare disease that is characterized by delayed/absent puberty and/or infertility due to an insufficient stimulation of an otherwise normal pituitary–gonadal axis by gonadotrophin-releasing hormone (GnRH) action. Because reduced or normal luteinizing hormone (LH)/follicle-stimulating hormone (FSH) levels may be observed in the affected patients, the term idiopathic central hypogonadism (ICH) appears to be more appropriate. This disease should be distinguished from central hypogonadism that is combined with other pituitary deficiencies. Isolated ICH has a complex pathogenesis and is fivefold more prevalent in males. ICH frequently appears in a sporadic form, but several familial cases have also been reported. This finding, in conjunction with the description of numerous pathogenetic gene variants and the generation of several knockout models, supports the existence of a strong genetic component. ICH may be associated with several morphogenetic abnormalities, which include osmic defects that, with ICH, constitute the cardinal manifestations of Kallmann syndrome (KS). KS accounts for approximately 40% of the total ICH cases and has been generally considered to be a distinct subgroup. However, the description of several pedigrees, which include relatives who are affected either with isolated osmic defects, KS, or normo-osmic ICH (nICH), justifies the emerging idea that ICH is a complex genetic disease that is characterized by variable expressivity and penetrance. In this context, either multiple gene variants or environmental factors and epigenetic modifications may contribute to the variable disease manifestations. We review the genetic mechanisms that are presently known to be involved in ICH pathogenesis and provide a clinical overview of the 227 cases that have been collected by the collaborating centres of the Italian ICH Network. PMID:22138902

The Incidence of Hypogonadotropic Hypogonadism in Type 2 Diabetic Men in Polish Population

PubMed Central

Rabijewski, Michał; Zgliczyński, Wojciech; Piątkiewicz, Paweł

2013-01-01

The aim of this study was to investigate the incidence of hypogonadotropic hypogonadism (HH) in type 2 diabetic men (T2DM) in population of Polish men and examine the possible influence of estradiol levels and glycemic control. We evaluated TT, cfT, estradiol, and glycemic control (HbA1c) in 184 diabetic men and in 149 nondiabetic control group. The mean HbA1c was 8.6 ± 0.2% and 6.1 ± 0.3% and cfT concentration was 0.315 ± 0.08 nmol/L and 0.382 ± 0.07 nmol/L, respectively. T2DM had higher E2 concentration than nonobese control men (29.4 ± 3.7 pg/mL versus 24.5 ± 2.9 pg/mL). Forty-six percent of T2DM were hypogonadal and 93% had HH. We observed inverse relationship between BMI and cfT (r = −0.341, P < 0.01) and positive between BMI and E2 (r = 0.329, P < 0.01). E2 concentration was higher in T2DM with HH versus T2DM with normal TT/cfT concentration (34.5 ± 5.2 versus 27.4 ± 3.4 pg/mL). We observed negative correlation between HbA1c and cfT (r = −0.336, P < 0.005) but positive between HbA1c and E2 levels (r = 0.337, P < 0.002). The prevalence of obesity, hypertension, and CVD was higher in men with hypogonadism. High incidence of hypogonadotropic hypogonadism in type 2 diabetic men in Polish population is associated with poor glycemic control and can be secondary to an increase in estradiol concentrations. PMID:24222915

Effects of androgen replacement therapy on cornea and tear function in men with idiopathic hypogonadotropic hypogonadism.

PubMed

Gokce, Gokcen; Hurmeric, Volkan; Mumcuoglu, Tarkan; Ozge, Gokhan; Basaran, Yalcin; Unal, Hilmi Umut; Bolu, Erol; Mutlu, Fatih Mehmet

2015-05-01

Idiopathic hypogonadotropic hypogonadism (IHH) is an endocrine disorder defined with the presence of typical clinical signs and symptoms plus laboratory confirmation of serum testosterone (T) levels lower than 300 ng/dl. Androgen replacement therapy (ART) is the first-step treatment of male IHH. To date, no clinical trial, which investigates the changes on corneal structure and tear function, of systemic ART in men have been published. The objective of this study was to investigate the effects of ART on cornea and tear function in patients with IHH. This prospective, interventional study was conducted at the Gulhane Military Medical Academy, Ankara, Turkey, a tertiary referral military hospital. Thirty-four eyes of 17 men with IHH patients were evaluated with Schirmer I test, ultrasound pachymeter, applanation tonometer and confocal microscopy. A Testosterone compound (Sustanon® 250 mg) was administered by intramuscular injection in the course of a 3-week period to induce puberty, and human chorionic gonadotropin (Pregnyl® 5000 IU) was administered twice weekly for 3 months to induce fertility. The patients were re-evaluated at the third month of the treatment. Main Outcome Measures were Schirmer score, central corneal thickness (CCT), intraocular pressure (IOP), endothelial cell density, coefficient of variation and cell shape. Schirmer scores showed similar results after the treatment compared to pre-treatment levels (p = 0.14). There was no statistically significant difference in CCT and IOP compared to baseline data (p = 0.96, p = 0.73, respectively), and no significant differences were found in corneal endothelial cell density, percentage of cell size variability or hexagonality (p = 0.83, p = 0.58, p = 0.64, respectively). This is the first study that investigates the effects of ART on corneal structure and tear function in men. ART seems to have no short-term effects on corneal structure and tear function. Further publications of larger, long-term and

[Spermatogenesis of pulsatile gonadotropin-releasing hormone infusion versus gonadotropin therapy in male idiopathic hypogonadotropic hypogonadism].

PubMed

Huang, Bingkun; Mao, Jiangfeng; Xu, Hongli; Wang, Xi; Liu, Zhaoxiang; Nie, Min; Wu, Xueyan

2015-05-26

To compare the efficacies of pulsatile gonadotropin-releasing hormone (GnRH) versus human chorionic gonadotropin/human menopausal gonadotropin (HCG/HMG) for spermatogenesis in male idiopathic hypogonadotropic hypogonadism (IHH). For this retrospective study, a total of 92 male IHH outpatients from May 2010 to October 2014 were recruited and categorized into GnRH (n = 40) and HCG/HMG (n = 52) groups. Each subject selected one specific therapy voluntarily. The gonadotropin levels were measured in the first week and monthly post-treatment in GnRH group. And serum total testosterone (TT), testicular volume (TV) and rate of spermatogenesis were observed monthly post-treatment in two groups. Spermatogenesis, TT and TV were compared between two groups. All IHH patients were treated for over 3 months. The median follow-up periods in GnRH and HCG/HMG groups was 8.2 (3.0-18.4) and 9.2 (3.0-18.6) months respectively (P = 0.413). In GnRH group, LH ((0.5 ± 0.6) vs (3.4 ± 2.4) U/L, P < 0.01) and FSH ((1.3 ± 1.1) vs (5.8 ± 3.8) U/L, P < 0.01) increased after 1-week treatment. In GnRH group, at the end of follow-up, TT ((1.0 ± 1.0) vs (7.4 ± 5.2) nmol/L, P < 0.01) and TV ((2.3 ± 1.5) vs (8.1 ± 4.0) ml, P < 0.01) significantly increased compared to baseline. In HCG/HMG group, TT ((0.8 ± 0.6) vs (14.4 ± 8.0) nmol/L, P < 0.01) and TV ((2.3 ± 2.1) vs (7.6 ± 4.2) ml, P < 0.01) significantly increased after therapy. The success rate of spermatogenesis was 50.0% (20/40) in GnRH group versus 28.8% (15/52) in HCG/HMG group (P = 0.038). GnRH group required a shorter treatment time for initial sperm appearance than HCG/HMG group ((6.5 ± 3.1) vs (10.8 ± 3.7) months, P = 0.001). Pulsatile GnRH requires a shorter time for initiation of spermatogenesis than gonadotropin therapy in IHH male patients.

Transient hypogonadotropic hypogonadism in an amateur kickboxer after head trauma.

PubMed

Tanriverdi, F; Unluhizarci, K; Selcuklu, A; Casanueva, F F; Kelestimur, F

2007-02-01

Traumatic brain injury (TBI) is a frequent health problem and increased prevalence of neurendocrine dysfunction in patients with TBI has been reported. Sports injuries and particularly boxing may result in pituitary dysfunction. However, transient hypogonadotropic hypogonadism after an acute head trauma due to boxing and/or kickboxing has not been defined yet. We describe the case of a 20-yr-old male amateur kickboxer who was admitted to hospital complaining of decreased libido and impotence 2 weeks after an intensive bout. Basal hormone levels were compatible with mild hyperprolactinemia and hypogonadotpopic hypogonadism. GH axis was evaluated by GHRH+GHRP-6 test and peak GH level was within normal reference range. Three months later his complaints improved and abnormalities in basal hormone levels normalized. He was also re-evaluated 9 months after the first evaluation; basal hormone levels were within normal ranges and he had no complaints. In conclusion acute head trauma due to kickboxing may cause transient gonadotropin deficiency. Therefore, screening the pituitary functions of sportsmen dealing with combative sports is crucial.

New mutations of DAX-1 genes in two Japanese patients with X-linked congenital adrenal hypoplasia and hypogonadotropic hypogonadism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yanase, Toshihiko; Takayanagi, Ryoichi; Oba, Koichi

Congenital adrenal hypoplasia, an X-linked disorder, is characterized by primary adrenal insufficiency and frequent association with hypogonadotropic hypogonadism. The X-chromosome gene DAX-1 has been most recently identified and shown to be responsible for this disorder. We analyzed the DAX-1 genes of two unrelated Japanese patients with congenital adrenal hypoplasia and hypogonadotropic hypogonadism by using PCR amplification of genomic DNA and its complete exonic sequencing. In a family containing several affected individuals, the proband male patient had a stop codon (TGA) in place of tryptophan (TGG) at amino acid position 171. As expected, his mother was a heterozygous carrier for themore » mutation, whereas his father and unaffected brother did not carry this mutation. In another male patient with noncontributory family history, sequencing revealed a 1-bp (T) deletion at amino acid position 280, leading to a frame shift and, subsequently a premature stop codon at amino acid position 371. The presence of this mutation in the patients` genome was further confirmed by digestion of genomic PCR product with MspI created by this mutation. Family studies using MspI digestion of genomic PCR products revealed that neither parent of this individual carried the mutation. These results clearly indicate that congenital adrenal hypoplasia and hypogonadotropic hypogonadism result from not only inherited but also de novo mutation in the DAX-1 gene. 31 refs., 4 figs., 2 tabs.« less

MANAGEMENT OF ENDOCRINE DISEASE: Reversible hypogonadotropic hypogonadism.

PubMed

Dwyer, Andrew A; Raivio, Taneli; Pitteloud, Nelly

2016-06-01

Congenital hypogonadotropic hypogonadism (CHH) is characterized by lack of puberty and infertility. Traditionally, it has been considered a life-long condition yet cases of reversibility have been described wherein patients spontaneously recover function of the reproductive axis following treatment. Reversibility occurs in both male and female CHH cases and appears to be more common (~10-15%) than previously thought. These reversal patients span a range of GnRH deficiency from mild to severe and many reversal patients harbor mutations in genes underlying CHH. However, to date there are no clear factors for predicting reversible CHH. Importantly, recovery of reproductive axis function may not be permanent. Thus, CHH is not always life-long and the incidence of reversal warrants periodic treatment withdrawal with close monitoring and follow-up. Reversible CHH highlights the importance of environmental (epigenetic) factors such as sex steroid treatment on the reproductive axis in modifying the phenotype. This review provides an overview and an update on what is known about this phenomenon. © 2016 European Society of Endocrinology.

Central body fat changes in men affected by post-surgical hypogonadotropic hypogonadism undergoing testosterone replacement therapy are modulated by androgen receptor CAG polymorphism.

PubMed

Tirabassi, G; delli Muti, N; Buldreghini, E; Lenzi, A; Balercia, G

2014-08-01

Little is known about the effect of androgen receptor (AR) gene CAG repeat polymorphism in conditioning body composition changes after testosterone replacement therapy (TRT). In this study, we aimed to clarify this aspect by focussing our attention on male post-surgical hypogonadotropic hypogonadism, a condition often associated with partial or total hypopituitarism. Fourteen men affected by post-surgical hypogonadotropic hypogonadism and undergoing several replacement hormone therapies were evaluated before and after TRT. Dual-energy X-ray absorptiometry (DEXA)-derived body composition measurements, pituitary-dependent hormones and AR gene CAG repeat polymorphism were considered. While testosterone and insulin-like growth factor-1 (IGF-1) levels increased after TRT, cortisol concentration decreased. No anthropometric or body composition parameters varied significantly, except for abdominal fat decrease. The number of CAG triplets was positively and significantly correlated with this abdominal fat decrease, while the opposite occurred between the latter and Δ-testosterone. No correlation of IGF-1 or cortisol variation (Δ-) with Δ-abdominal fat was found. At multiple linear regression, after correction for Δ-testosterone, the positive association between CAG triplet number and abdominal fat change was confirmed. In male post-surgical hypogonadotropic hypogonadism, shorter length of AR CAG repeat tract is independently associated with a more marked decrease of abdominal fat after TRT. Copyright © 2014 Elsevier B.V. All rights reserved.

The Role of Prokineticins in the Pathogenesis of Hypogonadotropic Hypogonadism

PubMed Central

Abreu, Ana Paula; Kaiser, Ursula B.; Latronico, Ana Claudia

2010-01-01

The prokineticin system comprises two multifunctional secreted proteins, prokineticin-1 (PROK1) and prokineticin-2 (PROK2), and their cognate G protein-coupled receptors. The prokineticins were originally identified as endogenous regulators of gastrointestinal motility. Currently, these bioactive peptides are involved in a wide spectrum of biological functions, including angiogenesis, neurogenesis, circadian rhythms, nociception, hematopoiesis and immune response. Mice homozygous for null mutations in Prokr2 or Prok2 recapitulate the human phenotype of Kallmann syndrome, exhibiting severe atrophy of the reproductive system and hypoplastic olfactory bulbs. Indeed, the evidence from several naturally inactivating mutations in the PROK2 and PROKR2 genes in patients with Kallmann syndrome and normosmic hypogonadotropic hypogonadism also indicate the essential role of PROK2 in olfactory bulb morphogenesis and GnRH secretion in humans. PMID:20502053

Persistent Hypogonadotropic Hypogonadism in Men After Severe Traumatic Brain Injury: Temporal Hormone Profiles and Outcome Prediction.

PubMed

Barton, David J; Kumar, Raj G; McCullough, Emily H; Galang, Gary; Arenth, Patricia M; Berga, Sarah L; Wagner, Amy K

2016-01-01

To (1) examine relationships between persistent hypogonadotropic hypogonadism (PHH) and long-term outcomes after severe traumatic brain injury (TBI); and (2) determine whether subacute testosterone levels can predict PHH. Level 1 trauma center at a university hospital. Consecutive sample of men with severe TBI between 2004 and 2009. Prospective cohort study. Post-TBI blood samples were collected during week 1, every 2 weeks until 26 weeks, and at 52 weeks. Serum hormone levels were measured, and individuals were designated as having PHH if 50% or more of samples met criteria for hypogonadotropic hypogonadism. At 6 and 12 months postinjury, we assessed global outcome, disability, functional cognition, depression, and quality of life. We recruited 78 men; median (interquartile range) age was 28.5 (22-42) years. Thirty-four patients (44%) had PHH during the first year postinjury. Multivariable regression, controlling for age, demonstrated PHH status predicted worse global outcome scores, more disability, and reduced functional cognition at 6 and 12 months post-TBI. Two-step testosterone screening for PHH at 12 to 16 weeks postinjury yielded a sensitivity of 79% and specificity of 100%. PHH status in men predicts poor outcome after severe TBI, and PHH can accurately be predicted at 12 to 16 weeks.

Persistent hypogonadotropic hypogonadism in men after severe traumatic brain injury: temporal hormone profiles and outcome prediction

PubMed Central

Barton, David J.; Kumar, Raj G.; McCullough, Emily H.; Galang, Gary; Arenth, Patricia M.; Berga, Sarah L.; Wagner, Amy K.

2015-01-01

Objective (1) Examine relationships between persistent hypogonadotropic hypogonadism (PHH) and long-term outcomes after severe traumatic brain injury (TBI); (2) determine if sub-acute testosterone levels can predict PHH. Setting Level 1 trauma center at a university hospital. Participants Consecutive sample of men with severe TBI between 2004 and 2009. Design Prospective cohort study. Main Measures Post-TBI blood samples were collected during week 1, every 2 weeks until 26 weeks, and at 52 weeks. Serum hormone levels were measured, and individuals were designated as having PHH if ≥50% of samples met criteria for hypogonadotropic hypogonadism. At 6 and 12 months post-injury, we assessed global outcome, disability, functional cognition, depression, and quality-of-life. Results We recruited 78 men; median (IQR) age was 28.5 (22–42) years. 34 patients (44%) had PHH during the first year post-injury. Multivariable regression, controlling for age, demonstrated PHH status predicted worse global outcome scores, more disability, and reduced functional cognition at 6 and 12 months post-TBI. Two-step testosterone screening for PHH at 12–16 weeks post-injury yielded a sensitivity of 79% and specificity of 100%. Conclusion PHH status in men predicts poor outcome after severe TBI, and PHH can accurately be predicted at 12–16 weeks. PMID:26360007

Phenotypic spectrum of POLR3B mutations: isolated hypogonadotropic hypogonadism without neurological or dental anomalies.

PubMed

Richards, Mary R; Plummer, Lacey; Chan, Yee-Ming; Lippincott, Margaret F; Quinton, Richard; Kumanov, Philip; Seminara, Stephanie B

2017-01-01

A constellation of neurodegenerative disorders exists (Gordon Holmes syndrome, 4H leucodystrophy, Boucher-Neuhauser syndrome) in which patients suffer from both neurological disease (typically manifested by ataxia) and reproductive failure (idiopathic hypogonadotropic hypogonadism (IHH)). POLR3B, which encodes the second largest subunit of RNA polymerase III (pol III), and POLR3A, which forms the pol III catalytic centre, are associated with 4H leucodystrophy. Whole exome sequencing was performed on a large cohort of subjects with IHH (n=565). Detailed neuroendocrine studies were performed in some individuals within this cohort. Four individuals (two of them siblings) were identified with two rare nucleotide variants in POLR3B. On initial evaluation, all subjects were free of neurological disease. One patient underwent treatment with exogenous pulsatile gonadotropin-releasing hormone for 8 weeks which failed to result in normalisation of his sex steroid milieu due to pituitary resistance. These findings suggest that the spectrum of phenotypes resulting from POLR3B mutations is wider than previously believed and that POLR3B can be associated exclusively with disorders characterised by abnormal gonadotropin secretion. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Novel FGFR1 mutations in Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism: evidence for the involvement of an alternatively spliced isoform.

PubMed

Gonçalves, Catarina; Bastos, Margarida; Pignatelli, Duarte; Borges, Teresa; Aragüés, José M; Fonseca, Fernando; Pereira, Bernardo D; Socorro, Sílvia; Lemos, Manuel C

2015-11-01

To determine the prevalence of fibroblast growth factor receptor 1 (FGFR1) mutations and their predicted functional consequences in patients with idiopathic hypogonadotropic hypogonadism (IHH). Cross-sectional study. Multicentric. Fifty unrelated patients with IHH (21 with Kallmann syndrome and 29 with normosmic IHH). None. Patients were screened for mutations in FGFR1. The functional consequences of mutations were predicted by in silico structural and conservation analysis. Heterozygous FGFR1 mutations were identified in six (12%) kindreds. These consisted of frameshift mutations (p.Pro33-Alafs*17 and p.Tyr654*) and missense mutations in the signal peptide (p.Trp4Cys), in the D1 extracellular domain (p.Ser96Cys) and in the cytoplasmic tyrosine kinase domain (p.Met719Val). A missense mutation was identified in the alternatively spliced exon 8A (p.Ala353Thr) that exclusively affects the D3 extracellular domain of FGFR1 isoform IIIb. Structure-based and sequence-based prediction methods and the absence of these variants in 200 normal controls were all consistent with a critical role for the mutations in the activity of the receptor. Oligogenic inheritance (FGFR1/CHD7/PROKR2) was found in one patient. Two FGFR1 isoforms, IIIb and IIIc, result from alternative splicing of exons 8A and 8B, respectively. Loss-of-function of isoform IIIc is a cause of IHH, whereas isoform IIIb is thought to be redundant. Ours is the first report of normosmic IHH associated with a mutation in the alternatively spliced exon 8A and suggests that this disorder can be caused by defects in either of the two alternatively spliced FGFR1 isoforms. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Hypogonadism and non-alcoholic fatty liver disease.

PubMed

Mintziori, Gesthimani; Poulakos, Pavlos; Tsametis, Christos; Goulis, Dimitrios G

2017-06-01

Non-alcoholic fatty liver disease (NAFLD) is more common in men than in women. Thus, it has been suggested that sex steroids do have a role in the development of NAFLD. The aim of the current paper is to illustrate the association between NAFLD and hypogonadism, by reviewing data derived from both human and animal studies. The prevalence of NAFLD is high in men with hypogonadism, including those with idiopathic hypogonadotropic hypogonadism (IHH), as well as in women in post-menopause, those under estrogen receptor antagonist treatment or women with Turner syndrome. Estrogens seem to play a pivotal role in hepatic lipid homeostasis, as demonstrated in animal models with diminished ovarian estrogens (i.e., ovariectomized mice) and low serum testosterone (T) concentration is independently associated with NAFLD. The elucidation of the exact role of sex steroids in NAFLD pathogenesis would create a unique opportunity to develop novel therapies to tackle NAFLD disease.

A novel heterozygous SOX2 mutation causing congenital bilateral anophthalmia, hypogonadotropic hypogonadism and growth hormone deficiency.

PubMed

Macchiaroli, Annamaria; Kelberman, Daniel; Auriemma, Renata Simona; Drury, Suzanne; Islam, Lily; Giangiobbe, Sara; Ironi, Gabriele; Lench, Nicholas; Sowden, Jane C; Colao, Annamaria; Pivonello, Rosario; Cavallo, Luciano; Gasperi, Maurizio; Faienza, Maria Felicia

2014-01-25

Heterozygous de novo mutations in SOX2 have been reported in approximately 10-20% of patients with unilateral or bilateral anophthalmia or microphthalmia. An additional phenotype of hypopituitarism, with anterior pituitary hypoplasia and hypogonadotropic hypogonadism, has been reported in patients carrying SOX2 alterations. We report a novel heterozygous mutation in the SOX2 gene in a male affected with congenital bilateral anophthalmia, hypogonadotrophic hypogonadism and growth hormone deficiency. The mutation we describe is a cytosine deletion in position 905 (c905delC) which causes frameshift and an aberrant C-terminal domain. Our report highlights the fact that subjects affected with eye anomalies and harboring SOX2 mutations are at high risk for gonadotropin deficiency, which has important implications for their clinical management. Copyright © 2013 Elsevier B.V. All rights reserved.

Effects of testosterone replacement therapy on bone metabolism in male post-surgical hypogonadotropic hypogonadism: focus on the role of androgen receptor CAG polymorphism.

PubMed

Tirabassi, G; delli Muti, N; Gioia, A; Biagioli, A; Lenzi, A; Balercia, G

2014-04-01

The relationship between androgen receptor (AR) CAG polymorphism and bone metabolism is highly controversial. We, therefore, aimed to evaluate the independent role of AR CAG repeat polymorphism on bone metabolism improvement induced by testosterone replacement therapy (TRT) in male post-surgical hypogonadotropic hypogonadism, a condition frequently associated with hypopituitarism and in which the effects of TRT have to be distinguished from those resulting from concomitant administration of pituitary function replacing hormones. 12 men affected by post-surgical hypogonadotropic hypogonadism [mean duration of hypogonadism 8.3 ± 2.05 (SD) months] were retrospectively assessed before and after TRT (from 74 to 84 weeks after the beginning of therapy). The following measures were studied: parameters of bone metabolism [serum markers and bone mineral density (BMD)], pituitary dependent hormones and genetic analysis (AR CAG repeat number). Total testosterone, estradiol, free T4 (FT4) and insulin-like growth factor-1 (IGF-1) increased between the two phases, while follicle stimulating hormone (FSH) decreased. While serum markers did not vary significantly between the two phases, BMD improved slightly but significantly in all the studied sites. The number of CAG triplets correlated negatively and significantly with all the variations (Δ-) of BMDs. Conversely, Δ-testosterone correlated positively and significantly with all studied Δ-BMDs, while Δ-FSH, Δ-estradiol, Δ-FT4, and Δ-IGF-1 did not correlate significantly with any of the Δ-BMDs. Multiple linear regression analysis, after correction for Δ-testosterone, showed that CAG repeat length was negatively and significantly associated with ∆-BMD of all measured sites. Our data suggest that, in post-surgical male hypogonadotropic hypogonadism, shorter AR CAG tract is independently associated with greater TRT-induced improvement of BMD.

Treatment of idiopathic hypogonadotropic hypogonadism in men with luteinizing hormone-releasing hormone: a comparison of treatment with daily injections and with the pulsatile infusion pump.

PubMed

Shargil, A A

1987-03-01

Thirty husbands in childless couples, aged 24 to 35 years, were treated with luteinizing hormone-releasing hormone (LH-RH) for idiopathic hypogonadotropic hypogonadism (IHH) of peripubertal (incomplete) type. They were azoospermic or oligospermic, with less than 1.5 X 10(6)/ml nonmotile spermatozoa. The diagnosis of IHH was based on clinical and laboratory features and testicular biopsy specimen study and was further supported by results of stimulation tests and gonadotropin-releasing hormone (GnRH) test. Two treatment modalities were used: subcutaneous injections of 500 micrograms LH-RH twice daily; and perpetual subcutaneous injection, via portable infusion pump, of 25 ng/kg LH-RH, at 90-minute intervals. Two patients required a short second period of pulsatile treatment to cause a second pregnancy of their spouses. The pump proved to yield better results, compared with intermittent injections, in respect to endocrine responses, spermatogenesis, and fertility capacity. Normal levels of luteinizing hormone and follicle-stimulating hormone were reached in 2 to 3 weeks and normal testosterone levels in 8 to 10 weeks from the start of treatment. Sperm counts rose to greater than 60 X 10(6)/ml viable spermatozoa with less than 15% of abnormal forms in 3 to 5 months, and the wives conceived. Of a total of 18 deliveries of healthy infants, 12 offspring were identified genetically with their fathers. Four women were still pregnant at the conclusion of the study. The pump was well tolerated, without special operational problems to the patients. Pulsatile treatment is therefore recommended in the treatment of well-diagnosed and carefully selected cases of incomplete IHH.

Androgen receptor gene CAG repeat polymorphism independently influences recovery of male sexual function after testosterone replacement therapy in postsurgical hypogonadotropic hypogonadism.

PubMed

Tirabassi, Giacomo; Delli Muti, Nicola; Corona, Giovanni; Maggi, Mario; Balercia, Giancarlo

2014-05-01

Few and contradictory studies have evaluated the possible influence of androgen receptor (AR) gene CAG repeat polymorphism on male sexual function. In this study we evaluated the role of AR gene CAG repeat polymorphism in the recovery of sexual function after testosterone replacement therapy (TRT) in men affected by postsurgical hypogonadotropic hypogonadism, a condition which is often associated with hypopituitarism and in which the sexual benefits of TRT must be distinguished from those of pituitary-function replacement therapies. Fifteen men affected by postsurgical hypogonadotropic hypogonadism were retrospectively assessed before and after TRT. Main outcome measures included sexual parameters as assessed by the International Index of Erectile Function questionnaire, levels of pituitary dependent hormones (total testosterone, free T3, free T4, cortisol, insulin-like growth factor-1 [IGF-1], prolactin), and results of genetic analysis (AR gene CAG repeat number). Plasma concentrations of free T3, free T4, cortisol, and prolactin did not vary significantly between the two phases, while testosterone and IGF-1 increased significantly after TRT. A significant improvement in all sexual parameters studied was found. The number of CAG triplets was negatively and significantly correlated with changes in all the sexual parameters, while opposite correlations were found between changes in sexual parameters and changes in testosterone levels; no correlation of change in IGF1 with change in sexual parameters was reported. On multiple linear regression analysis, after correction for changes in testosterone, nearly all the associations between the number of CAG triplets and changes in sexual parameters were confirmed. Shorter length AR gene CAG repeat number is associated with the recovery of sexual function after TRT in postsurgical male hypogonadotropic hypogonadism, independently of the effects of concomitant pituitary-replacement therapies. © 2014 International Society

Anosmia predicts hypogonadotropic hypogonadism in CHARGE syndrome.

PubMed

Bergman, Jorieke E H; Bocca, Gianni; Hoefsloot, Lies H; Meiners, Linda C; van Ravenswaaij-Arts, Conny M A

2011-03-01

To test the hypothesis that a smell test could predict the occurrence of hypogonadotropic hypogonadism (HH) in patients with CHARGE syndrome, which is a variable combination of ocular coloboma, heart defects, choanal atresia, retardation of growth/development, genital hypoplasia, and ear anomalies or hearing loss caused by mutations in the CHD7 (chromodomain helicase DNA binding protein 7) gene. We performed endocrine studies and smell testing (University of Pennsylvania Smell Identification Test) in 35 adolescent patients with molecularly confirmed CHARGE syndrome. Complete data on smell and puberty were available for 15 patients; 11 patients had both anosmia and HH, whereas 4 patients had normosmia/hyposmia and spontaneous puberty. In addition, 7 boys were highly suspected of having HH (they were too young for definite HH diagnosis, but all had cryptorchidism, micropenis, or both) and had anosmia. The type of CHD7 mutation could not predict HH because a father and daughter with the same CHD7 mutation were discordant for HH and anosmia. Anosmia and HH were highly correlated in our cohort, and therefore smell testing seems to be an attractive method for predicting the occurrence of HH in patients with CHARGE syndrome. The use of this test could prevent delay of hormonal pubertal induction, resulting in an age-appropriate puberty. Copyright © 2011 Mosby, Inc. All rights reserved.

[Clinical values of single or repeated triptorelin stimulating test in the differential diagnosis between idiopathic hypogonadotropic hypogonadism and constitutional delayed puberty].

PubMed

Mao, Jiang-Feng; Wu, Xue-Yan; Lu, Shuang-Yu; Nie, Min

2011-10-01

To investigate the values of single or repeated luteinizing hormone (LH) releasing hormone analogue (triptorelin) stimulating test in the differential diagnosis between idiopathic hypogonadotropic hypogonadism (IHH) and constitutional delayed puberty (CDP). Male patients (n = 133) without puberty onset after the age of 14 were recruited for triptorelin stimulating test and were followed up for 24 - 48 months until the diagnosis were confirmed: 86 were IHH and the other 47 were CDP. Repeated triptorelin stimulating tests were conducted in 9 IHH patients and 13 CDP patients one year after the first stimulating tests with an attempt to evaluate the dynamic change of hypothalamus-pituitary-testis axis function. The relationship between the final diagnosis and the peak LH value (LH(max)), and the changes of repeated LH(max) were investigated. In the single triptorelin stimulating test, LH(max) was (1.9 +/- 1.2) U/L in IHH group, which was significantly lower than that in CDP group [(13.7 +/- 8.3) U/L] (P < 0.01); 75 IHH patients (87.2%) had a LH(max) lower than 4 U/L, while only 2 CDP patients (4.3%) had a LH(max) lower than 4 U/L. When LH(max) < 4U/L was used as a criteria for the diagnosis of IHH, the single triptorelin stimulating test had a sensitivity of 87.2%, a specificity of 95.7%, and a positive predictive value of 97.4%. The repeated triptorelin stimulating tests performed one year later showed that the LH(max) in the 9 IHH patients increased from (4.7 +/- 2.5) U/L to (5.1 +/- 3.3) U/L (P = 0.78), while that in the 13 CDP patients increased from (10.7 +/- 3.3) U/L to (24.5 +/- 5.7) U/L (P < 0.05). A single triptorelin stimulating test is highly effective in differentiating IHH from CDP. For some patients without definitive diagnosis, a repeated triptorelin stimulating test performed one year later may provide more valuable information on the dynamic change of the hypothalamus-pituitary-testis axis function.

[Anabolic steroid induced hypogonadism in men: overview and case report].

PubMed

Stárka, Luboslav; Dušková, Michaela; Kolátorová, Lucie; Lapčík, Oldřich

An important potential consequence of the anabolic steroid misuse is hypogonadotropic hypogonadism due to the inhibition of pituitary secretion of gonadotropins. By the symptoms as testicular atrophy, spermatogenic and fertility disturbances or dysfunction in sexual life, the anabolic steroids induced hypogonadism (ASIH) could be differentiated from organic hypogonadotropic hypogonadism only with difficulty unless the misuse is reported by the user. When diagnosed, the crucial step in the therapy is the stop of anabolic use. Convalescence lasts usually several months or even more than one year. First could be seen the retreat of testicular atrophy followed by the rearrangement of spermatogenesis. The users mainly well informed from internet use for amelioration of the symptoms injections of human choriogonadotropin (hCG), selective estrogen receptor modulators (SERM) or aromatase inhibitors.Key words: anabolic steroids - doping - hypogonadotropic hypogonadism - side effects.

Genetics of congenital hypogonadotropic hypogonadism in Denmark.

PubMed

Tommiska, Johanna; Känsäkoski, Johanna; Christiansen, Peter; Jørgensen, Niels; Lawaetz, Jacob Gerner; Juul, Anders; Raivio, Taneli

2014-07-01

Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder characterized by incomplete/absent puberty caused by deficiency or defective action of gonadotropin-releasing hormone (GnRH). The phenotypic features of patients with CHH vary from genital hypoplasia and absent puberty to reversal of HH later in life. We examined the genetics and clinical features of CHH in Denmark. Forty-one male patients were screened for mutations in KAL1, FGFR1, FGF8, PROK2, PROKR2, GNRHR, TAC3, TACR3, and KISS1R. CHD7 was screened in two patients with hearing loss. In 12 patients, a molecular genetic cause for CHH was found. Four patients had mutations in KAL1 (C105VfsX13, C53X, ex5-8del, R257X), and five in FGFR1 (G97S, R209C, A512V, R646W, and c.1614C>T, (p.I538I), predicted to affect splicing). All 9 had severe HH (cryptorchidism and/or micropenis), and 2 had cleft lip/palate. One patient with a previously reported homozygous R262Q mutation in GNRHR displayed fascinating temporal variation in his phenotype. Two patients with hearing loss had CHD7 mutations (c.7832_7841del (p.K2611MfsX25) and c.2443-2A>C), confirming that CHH patients with CHARGE syndrome-associated features should be screened for mutations in CHD7. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

[Central female hypogonadism as a model of premature aging].

PubMed

Ilovayskaya, I A; Lazebnik, L B; Kulikov, A V

Central (hypogonadotropic) hypogonadism in women could also be a cause of persistent amenorrhea and hypoestrogenemia. The aim of this study was to evaluate symptoms of premature aging in women of young age with central hypogonadism. 88 young women (25 [21; 30] y.o.) with central hypogonadism (with isolated hypogonadotropic hypogonadism n=42, and associated with the other types of pituitary insufficiencies n=46), 53 healthy young women (24 [23; 28] y.o.) and 50 healthy postmenopausal women (56 [53; 58] y.o.) were examined. In young women with central hypogonadism frequency of psychoemotional, neurovegetative and urogenital disorders, peripheral sex steroid concentrations, lipid and mineral homeostasis parameters differed significantly from the healthy young women of similar age and were comparable with postmenopausal women of middle/older age. Thus, according to clinical, hormonal and biochemical abnormalities biological age of female patients with central hypogonadism advanced significantly chronological young age and corresponded to middle/older age. The central female hypogonadism is a model of premature aging.

Isolated hypogonadotropic hypogonadism with SOX2 mutation and anophthalmia/microphthalmia in offspring

PubMed Central

Stark, Zornitza; Storen, Rebecca; Bennetts, Bruce; Savarirayan, Ravi; Jamieson, Robyn V

2011-01-01

Isolated hypogonadotropic hypogonadism (IHH) is a genetically heterogeneous condition in which patients frequently require assisted reproduction to achieve fertility. In patients with IHH who are otherwise well, no particular increased risk of congenital anomalies in the resultant offspring has been highlighted. Heterozygous mutations in SOX2 are the commonest single-gene cause of anophthalmia/microphthalmia (A/M) and sometimes result in pituitary abnormalities. We report a family with a novel frameshift mutation in the SOX2 transactivation domain, p.Gly280AlafsX91, resulting in bilateral anophthalmia and subtle endocrinological abnormalities in a male sibling, and unilateral microphthalmia in a female sibling. The mutation is present in their mother who has IHH, but has no eye disorders or other anomalies. She underwent assisted reproduction to achieve fertility. This report has important implications for the evaluation of patients with IHH, particularly in the setting of planned infertility treatment. PMID:21326281

Isolated hypogonadotropic hypogonadism with SOX2 mutation and anophthalmia/microphthalmia in offspring.

PubMed

Stark, Zornitza; Storen, Rebecca; Bennetts, Bruce; Savarirayan, Ravi; Jamieson, Robyn V

2011-07-01

Isolated hypogonadotropic hypogonadism (IHH) is a genetically heterogeneous condition in which patients frequently require assisted reproduction to achieve fertility. In patients with IHH who are otherwise well, no particular increased risk of congenital anomalies in the resultant offspring has been highlighted. Heterozygous mutations in SOX2 are the commonest single-gene cause of anophthalmia/microphthalmia (A/M) and sometimes result in pituitary abnormalities. We report a family with a novel frameshift mutation in the SOX2 transactivation domain, p.Gly280AlafsX91, resulting in bilateral anophthalmia and subtle endocrinological abnormalities in a male sibling, and unilateral microphthalmia in a female sibling. The mutation is present in their mother who has IHH, but has no eye disorders or other anomalies. She underwent assisted reproduction to achieve fertility. This report has important implications for the evaluation of patients with IHH, particularly in the setting of planned infertility treatment.

Reversible Congenital Hypogonadotropic Hypogonadism in Patients with CHD7, FGFR1 or GNRHR Mutations

PubMed Central

Laitinen, Eeva-Maria; Tommiska, Johanna; Sane, Timo; Vaaralahti, Kirsi; Toppari, Jorma; Raivio, Taneli

2012-01-01

Background Congenital hypogonadotropic hypogonadism (HH) is a rare cause for delayed or absent puberty. These patients may recover from HH spontaneously in adulthood. To date, it is not possible to predict who will undergo HH reversal later in life. Herein we investigated whether Finnish patients with reversal of congenital hypogonadotropic hypogonadism (HH) have common phenotypic or genotypic features. Methods and Findings Thirty-two male HH patients with anosmia/hyposmia (Kallmann Syndrome, KS; n = 26) or normal sense of smell (nHH; n = 6) were enrolled (age range, 18–61 yrs). The patients were clinically examined, and reversal of HH was assessed after treatment withdrawal. KAL1, FGFR1, FGF8, PROK2, PROKR2, CHD7, WDR11, GNRHR, GNRH1, KISS1R, KISS1, TAC3, TACR3, and LHβ were screened for mutations. Six HH patients (2 KS, 4 nHH) were verified to have reversal of HH. In the majority of cases, reversal occurred early in adulthood (median age, 23 yrs; range, 21–39 yrs). All had spontaneous testicular growth while on testosterone replacement therapy (TRT). One nHH subject was restarted on TRT due to a decline in serum T. Two reversal variants had a same GNRHR mutation (R262Q), which was accompanied by another GNRHR mutation (R139H or del309F). In addition, both of the KS patients had a mutation in CHD7 (p.Q51X) or FGFR1 (c.91+2T>A). Conclusions Considerable proportion of patients with HH (8% of KS probands) may recover in early adulthood. Spontaneous testicular enlargement during TRT was highly suggestive for reversal of HH. Those with the GNRHR mutation R262Q accompanied by another GNRHR mutation may be prone to reversal, although even patients with a truncating mutation in CHD7 or a splice-site mutation in FGFR1 can recover. We recommend that all adolescents and young adults with congenital HH should be informed on the possibility of reversal. PMID:22724017

Transition of Care from Childhood to Adulthood: Congenital Hypogonadotropic Hypogonadism.

PubMed

Dwyer, Andrew A; Pitteloud, Nelly

2018-01-01

Passage from childhood to adult life involves biological changes culminating in full reproductive capacity as well as psychosocial development. For patients with congenital hypogonadotropic hypogonadism (CHH), this can be an emotionally challenging time as their pubertal failure results in striking physical differences from their peers. CHH is difficult to differentiate from common disorders of puberty such as constitutional delay of growth and puberty. As such, delays in diagnosis are frequent, and it is a common source of stress and frustration for these adolescents. While effective treatments are available for inducing puberty and attaining fertility is possible in most cases, patients may find it difficult to cope with living with CHH. A critical issue for adolescents with CHH is the risk for being lost to follow-up during the transition from pediatric-centered care to adult care. This article will review the state of the art in diagnosis and treatment of patients with CHH with a particular focus on supporting an effective transition from pediatric-centered care to adult-oriented endocrine services. A synthesis of best practices is offered to help guide clinicians in supporting patients and families during this challenging period of care. © 2018 S. Karger AG, Basel.

The Effects of Gonadotropin Replacement Therapy on Metabolic Parameters and Body Composition in Men with Idiopathic Hypogonadotropic Hypogonadism.

PubMed

Bayram, F; Elbuken, G; Korkmaz, C; Aydogdu, A; Karaca, Z; Cakır, I

2016-02-01

Testosterone replacement therapy (TRT) in idiopathic hypogonadotrophic hypogonadism (IHH) slows the process of metabolic syndrome (MetS), diabetes mellitus, and cardiovascular diseases by its inversing effects on insulin resistance, dyslipidemia, and blood pressure. Since there are not enough data regarding the effects of gonadotropin replacement therapy (GRT), we aimed to investigate the impact of GRT on MetS parameters in IHH patients. Sixteen patients with IHH and 20 age and body mass index (BDI)-matched healthy controls were enrolled into the study. Patients were evaluated at baseline and 6 months after the GRT. Sex hormones, insulin like growth factor-1, prolactin, insulin, C-reactive protein (CRP), homocysteine, and lipid levels were measured at baseline and after the treatment. Anthropometric measurements, including BMI, body fat ratio (BFR), fat free mass (FFM), waist circumference, and waist-to-hip ratio (WHR), were also performed. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index was calculated. Body fat ratio, triglyceride, HOMA-IR, and CRP levels were higher, whereas bone age, fat free mass, and creatinine levels were lower in the patients with hypogonadism. HOMA-IR indices and basal insulin levels decreased significantly after 6 months of GRT compared with baseline levels. Triglyceride levels, and BFRs diminished significantly by an accompanying decline in WHR. FFM of the patients increased following the GRT. No significant changes were detected in CRP, homocysteine, total and LDL-cholesterol levels. Similar to TRT, hCG treatment decreases HOMA-IR, triglyceride levels, BFR and WHRs, and increases FFM in patients with IHH. © Georg Thieme Verlag KG Stuttgart · New York.

Persistent hypogonadism influences estradiol synthesis, cognition and outcome in males after severe TBI.

PubMed

Wagner, Amy K; Brett, Christopher A; McCullough, Emily H; Niyonkuru, Christian; Loucks, Tammy L; Dixon, C Edward; Ricker, Joseph; Arenth, Patricia; Berga, Sarah L

2012-01-01

Acute hypogonadotropic hypogonadism (AHH) occurs frequently after TBI, as does chronic hypogonadotropic hypogonadism. However, AHH and persistent hypogonadotropic hypogonadism (PHH) after TBI are not well studied. The objective of this study was to characterize longitudinal hormone profiles and the impact of AHH and PHH on outcome. In this prospective cohort study, men with severe TBI (n = 38) had serum gonadal and gonadotropic hormones measured during weeks 1-52 post-injury. AHH, PHH and/or early resolving hypogonadotropic hypogonadism (ERHH) were based on temporal hormone assessments. PHH and hormone profiles were then compared to multiple outcome measures 6-12 months post-TBI. AHH affected 100% of the population, while 37% subsequently developed PHH. Acute testosterone (TEST) and estradiol/testosterone (E2/TEST) ratios were associated with PHH and outcome. Over time, post-acute TEST and E2 levels for the ERHH group approached normal range, while levels for the PHH group remained low. Post-acute gonadotrophin levels were within the normal range for both groups. PHH, along with lower post-acute TEST and E2 profiles, was associated with worse functional and cognitive outcomes at 6 and 12 months post-injury. These results support screening for post-acute secondary hypogonadism and further research to assess the mechanisms underlying PHH and associated functional and cognitive deficits.

Characteristics of a nationwide cohort of patients presenting with isolated hypogonadotropic hypogonadism (IHH).

PubMed

Bonomi, Marco; Vezzoli, Valeria; Krausz, Csilla; Guizzardi, Fabiana; Vezzani, Silvia; Simoni, Manuela; Bassi, Ivan; Duminuco, Paolo; Di Iorgi, Natascia; Giavoli, Claudia; Pizzocaro, Alessandro; Russo, Gianni; Moro, Mirella; Fatti, Letizia; Ferlin, Alberto; Mazzanti, Laura; Zatelli, Maria Chiara; Cannavò, Salvo; Isidori, Andrea M; Pincelli, Angela Ida; Prodam, Flavia; Mancini, Antonio; Limone, Paolo; Tanda, Maria Laura; Gaudino, Rossella; Salerno, Mariacarolina; Francesca, Pregnolato; Maghnie, Mohamad; Maggi, Mario; Persani, Luca

2018-01-01

Isolated hypogonadotropic hypogonadism (IHH) is a rare disorder with pubertal delay, normal (normoosmic-IHH, nIHH) or defective sense of smell (Kallmann syndrome, KS). Other reproductive and non-reproductive anomalies might be present although information on their frequency are scanty, particularly according to the age of presentation. Observational cohort study carried out between January 2008 and June 2016 within a national network of academic or general hospitals. We performed a detailed phenotyping of 503 IHH patients with: (1) manifestations of hypogonadism with low sex steroid hormone and low/normal gonadotropins; (2) absence of expansive hypothalamic/pituitary lesions or multiple pituitary hormone defects. Cohort was divided on IHH onset (PPO, pre-pubertal onset or AO, adult onset) and olfactory function: PPO-nIHH ( n  = 275), KS ( n  = 184), AO-nIHH ( n  = 36) and AO-doIHH (AO-IHH with defective olfaction, n  = 8). 90% of patients were classified as PPO and 10% as AO. Typical midline and olfactory defects, bimanual synkinesis and familiarity for pubertal delay were also found among the AO-IHH. Mean age at diagnosis was significantly earlier and more frequently associated with congenital hypogonadism stigmata in patients with Kallmann's syndrome (KS). Synkinesis, renal and male genital tract anomalies were enriched in KS. Overweight/obesity are significantly associated with AO-IHH rather than PPO-IHH. Patients with KS are more prone to develop a severe and complex phenotype than nIHH. The presence of typical extra-gonadal defects and familiarity for PPO-IHH among the AO-IHH patients indicates a common predisposition with variable clinical expression. Overall, these findings improve the understanding of IHH and may have a positive impact on the management of patients and their families. © 2018 European Society of Endocrinology.

Genetic testing facilitates prepubertal diagnosis of congenital hypogonadotropic hypogonadism.

PubMed

Xu, C; Lang-Muritano, M; Phan-Hug, F; Dwyer, A A; Sykiotis, G P; Cassatella, D; Acierno, J; Mohammadi, M; Pitteloud, N

2017-08-01

Neonatal micropenis and cryptorchidism raise the suspicion of congenital hypogonadotropic hypogonadism (CHH), a rare genetic disorder caused by gonadotropin-releasing hormone deficiency. Low plasma testosterone levels and low gonadotropins during minipuberty provide a clinical diagnostic clue, yet these tests are seldomly performed in general practice. We report a male neonate with no family history of reproductive disorders who was born with micropenis and cryptorchidism. Hormonal testing at age 2.5 months showed low testosterone (0.3 nmol/L) and undetectable gonadotropins (luteinizing hormone and follicle-stimulating hormone both <0.5 U/L), suggestive of CHH. Genetic testing identified a de novo, heterozygous mutation in fibroblast growth factor receptor 1 (FGFR1 p.L630P). L630 resides on the ATP binding cleft of the FGFR1 tyrosine kinase domain, and L630P is predicted to cause a complete loss of receptor function. Cell-based assays confirmed that L630P abolishes FGF8 signaling activity. Identification of a loss-of-function de novo FGFR1 mutation in this patient confirms the diagnosis of CHH, allowing for a timely hormonal treatment to induce pubertal development. Therefore, genetic testing can complement clinical and hormonal assessment for a timely diagnosis of CHH in childhood. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Clinical review: Distinguishing constitutional delay of growth and puberty from isolated hypogonadotropic hypogonadism: critical appraisal of available diagnostic tests.

PubMed

Harrington, Jennifer; Palmert, Mark R

2012-09-01

Determining the etiology of delayed puberty during initial evaluation can be challenging. Specifically, clinicians often cannot distinguish constitutional delay of growth and puberty (CDGP) from isolated hypogonadotropic hypogonadism (IHH), with definitive diagnosis of IHH awaiting lack of spontaneous puberty by age 18 yr. However, the ability to make a timely, correct diagnosis has important clinical implications. The aim was to describe and evaluate the literature regarding the ability of diagnostic tests to distinguish CDGP from IHH. A PubMed search was performed using key words "puberty, delayed" and "hypogonadotropic hypogonadism," and citations within retrieved articles were reviewed to identify studies that assessed the utility of basal and stimulation tests in the diagnosis of delayed puberty. Emphasis was given to a test's ability to distinguish prepubertal adolescents with CDGP from those with IHH. Basal gonadotropin and GnRH stimulation tests have limited diagnostic specificity, with overlap in gonadotropin levels between adolescents with CDGP and IHH. Stimulation tests using more potent GnRH agonists and/or human chorionic gonadotropin may have better discriminatory value, but small study size, lack of replication of diagnostic thresholds, and prolonged protocols limit clinical application. A single inhibin B level in two recent studies demonstrated good differentiation between groups. Distinguishing IHH from CDGP is an important clinical issue. Basal inhibin B may offer a simple, discriminatory test if results from recent studies are replicated. However, current literature does not allow for recommendation of any diagnostic test for routine clinical use, making this an important area for future investigation.

Boucher Neuhäuser Syndrome - A rare cause of inherited hypogonadotropic hypogonadism. A case of two adult siblings with two novel mutations in PNPLA6.

PubMed

Langdahl, Jakob H; Frederiksen, Anja L; Nguyen, Nina; Brusgaard, Klaus; Juhl, Claus B

2017-02-01

Boucher Neuhäuser Syndrome (BNS) is a rare clinical syndrome with autosomal recessive inheritance defined by early-onset ataxia, hypogonadism and chorioretinal dystrophy. We present two siblings diagnosed with BNS in late adult life identified with compound heterozygous state of two novel PNPLA6 mutations. Five healthy siblings were non- or heterozygous carriers of the mutations. The cases, which presented with ataxia in childhood and hypogonadotropic hypogonadism (HH), were diagnosed at age 17 and 25, respectively, when examined for delayed puberty. The youngest case, a 55-year old male, was referred to our department in 2006 for evaluation of secondary causes of osteoporosis, which he developed despite adequate testosterone replacement therapy. The unusual medical history with childhood ataxia and hypogonadotropic hypogonadism lead to further examinations and eventually the diagnosis of BNS. The older sister of the proband also displayed the triad of ataxia, HH and chorioretinal dystrophy accompanied by cerebellar atrophy and in 2014, we found the mutations in PNPLA6. BNS is a rare cause of HH and secondary osteoporosis, but should be considered in patients presenting with one or more of the key features. Genetic screening is becoming increasingly available and inexpensive and accordingly this may be considered earlier and by broader indication in unusual phenotypic presentations. The increasing knowledge of causes for inherited diseases should extend the use of genetic screening, as the correct diagnosis will benefit the patients. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Isolated cryptorchidism: no evidence for involvement of genes underlying isolated hypogonadotropic hypogonadism.

PubMed

Laitinen, Eeva-Maria; Tommiska, Johanna; Virtanen, Helena E; Oehlandt, Heidi; Koivu, Rosanna; Vaaralahti, Kirsi; Toppari, Jorma; Raivio, Taneli

2011-07-20

Mutations in FGFR1, GNRHR, PROK2, PROKR2, TAC3, or TACR3 underlie isolated hypogonadotropic hypogonadism (IHH) with clinically variable phenotypes, and, by causing incomplete intrauterine activation of the hypothalamic-pituitary-gonadal axis, may lead to cryptorchidism. To investigate the role of defects in these genes in the etiology of isolated cryptorchidism, we screened coding exons and exon-intron boundaries of these genes in 54 boys or men from 46 families with a history of cryptorchidism. Control subjects (200) included 120 males. None of the patients carried mutation(s) in FGFR1, PROK2, PROKR2, TAC3 or TACR3. Two of the 46 index subjects with unilateral cryptorchidism were heterozygous carriers of a single GNRHR mutation (Q106R or R262Q), also present in male controls with a similar frequency (3/120; p=0.62). No homozygous or compound heterozygous GNRHR mutations were found. In conclusion, cryptorchidism is not commonly caused by defects in genes involved in IHH. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Congenital hypogonadotropic hypogonadism, functional hypogonadotropism or constitutional delay of growth and puberty? An analysis of a large patient series from a single tertiary center.

PubMed

Varimo, Tero; Miettinen, Päivi J; Känsäkoski, Johanna; Raivio, Taneli; Hero, Matti

2017-01-01

What diagnoses underlie delayed puberty (DP) and predict its outcome? A multitude of different diagnoses underlie DP, and in boys a history of cryptorchidism, small testicular size and slow growth velocity (GV) predict its clinical course. DP is caused by a variety of underlying etiologies. Hormonal markers can be used in the differential diagnosis of DP but none of them have shown complete diagnostic accuracy. Medical records of 589 patients evaluated for DP in a single tertiary care center between 2004 and 2014 were retrospectively reviewed. Clinical and biochemical data of 174 boys and 70 girls who fulfilled the criteria of DP were included in the analyses. We characterized the frequencies of underlying conditions and evaluated the predictive efficacy of selected clinical and hormonal markers. Thirty etiologies that underlie DP were identified. No markers of clinical value could be identified in the girls, whereas a history of cryptorchidism in the boys was associated with an increase in the risk of permanent hypogonadism (odds ratio 17.2 (95% CI; 3.4-85.4, P < 0.001)). The conditions that cause functional hypogonadotropic hypogonadism were more frequent in boys with a GV below 3 cm/yr than in those growing faster (19% vs 4%, P < 0.05). In this series, the most effective markers to discriminate the prepubertal boys with constitutional delay of growth and puberty (CDGP) from those with congenital hypogonadotropic hypogonadism (CHH) were testicular volume (cut-off 1.1 ml with a sensitivity of 100% and a specificity of 91%), GnRH-induced maximal LH (cut-off 4.3 IU/L; 100%, 75%) and basal inhibin B (INHB) level (cut-off 61 ng/L; 90%, 83%). The main limitation of the study is the retrospective design. Prior cryptorchidism and slow GV are two important clinical cues that may help clinicians to predict the clinical course of DP in boys, whereas markers of similar value could not be identified in girls. In prepubertal boys, testicular size appeared as effective as INHB

Multiple Fractures in Patient with Graves' Disease Accompanied by Isolated Hypogonadotropic Hypogonadism.

PubMed

Yi, Hyon-Seung; Kim, Ji Min; Ju, Sang Hyeon; Lee, Younghak; Kim, Hyun Jin; Kim, Koon Soon

2016-02-01

Isolated hypogonadotropic hypogonadism (IHH) is known to decrease bone mineral density due to deficiency of sex steroid hormone. Graves' disease is also an important cause of secondary osteoporosis. However, IHH does not preclude the development of primary hyperthyroidism caused by Graves' disease, leading to more severe osteoporosis rapidly. Here, we describe the first case of 35-year-old Asian female patient with IHH accompanied by Graves' disease and osteoporosis-induced multiple fractures. Endocrine laboratory findings revealed preserved anterior pituitary functions except for secretion of gonadotropins and showed primary hyperthyroidism with positive autoantibodies. Sella magnetic resonance imaging showed slightly small sized pituitary gland without mass lesion. Dual energy X-ray absorptiometry revealed severe osteoporosis in lumbar spine and femur neck of the patient. Plain film radiography of the pelvis and shoulder revealed a displaced and nondisplaced fracture, respectively. After surgical fixation with screws for the femoral fracture, the patient was treated with antithyroid medication, calcium, and vitamin D until now and has been recovering fairly well. We report a patient of IHH with Graves' disease and multiple fractures that is a first case in Korea.

Psychosexual Development in Men with Congenital Hypogonadotropic Hypogonadism on Long-Term Treatment: A Mixed Methods Study

PubMed Central

Dwyer, Andrew A; Quinton, Richard; Pitteloud, Nelly; Morin, Diane

2015-01-01

Introduction Congenital hypogonadotropic hypogonadism (CHH) is a rare, genetic, reproductive endocrine disorder characterized by absent puberty and infertility. Limited information is available on the psychosocial impact of CHH and psychosexual development in these patients. Aim The aim of this study was to determine the impact of CHH on psychosexual development in men on long-term treatment. Methods A sequential mixed methods explanatory design was used. First, an online survey (quantitative) was used to quantify the frequency of psychosexual problems among CHH men. Second, patient focus groups (qualitative) were conducted to explore survey findings in detail and develop a working model to guide potential nursing and interdisciplinary interventions. Main Outcome Measures Patient characteristics, frequency of body shame, difficulty with intimate relationships, and never having been sexually active were assessed. Additionally, we collected subjective patient-reported outcomes regarding the impact of CHH on psychological/emotional well-being, intimate relationships, and sexual activity. Results A total of 101 CHH men on long-term treatment (>1 year) were included for the analysis of the online survey (mean age 37 ± 11 years, range 19–66, median 36). Half (52/101, 51%) of the men had been seen at a specialized academic center and 37/101 (37%) reported having had fertility-inducing treatment. A high percentage of CHH men experience psychosexual problems including difficulty with intimate relationships (70%) and body image concerns/body shame (94/101, 93%), and the percentage of men never having been sexually active is five times the rate in a reference group (26% vs. 5.4%, P < 0.001). Focus groups revealed persisting body shame and low self-esteem despite long-term treatment that has lasting impact on psychosexual functioning. Conclusions CHH men frequently experience psychosexual problems that pose barriers to intimate relationships and initiating sexual

Newly recognized recessive syndrome characterized by dysmorphic features, hypogonadotropic hypogonadism, severe microcephaly, and sensorineural hearing loss maps to 3p21.3.

PubMed

Jenkinson, Emma M; Kingston, Helen; Urquhart, Jill; Khan, Naz; Melville, Athalie; Swinton, Martin; Crow, Yanick J; Davis, Julian R E; Trump, Dorothy; Newman, William G

2011-12-01

We present a newly recognized, likely autosomal recessive, pleiotropic disorder seen in four individuals (three siblings and their nephew) from a consanguineous family of Pakistani origin. The condition is characterized by hypogonadotropic hypogonadism, severe microcephaly, sensorineural deafness, moderate learning disability, and distinctive facial dysmorphic features. Autozygosity mapping using SNP array genotyping defined a single, large autozygous region of 13.1 Mb on chromosome 3p21 common to the affected individuals. The critical region contains 227 genes and initial sequence analysis of a functional candidate gene has not identified causative mutations. Copyright © 2011 Wiley Periodicals, Inc.

Telltale teeth: Idiopathic Hypergonadotropic Hypogonadism.

PubMed

Lele, G S; Lakade, L S

2014-01-01

The detection of any atypical extraoral or intraoral features warrants a thorough investigation, even if the patient is asymptomatic or unaware of these. At times, dental findings help in the diagnosis of an underlying systemic problem. These findings may or may not be associated with any syndrome. Thus, thorough examination and exhaustive investigations should be carried out for every atypical finding to ensure optimal oral and general health for the patient. This is a case report of seventeen year old male who presented with peculiar/atypical dentition which 'told the tale' and led to the diagnosis of underlying endocrinological problem about which the parents were totally unaware. The patient was short with central obesity and microcephaly. Intraorally, there was presence of thirty six microdonts. Consultation with pediatrician and endocrinologist, and thorough investigations confirmed the condition to be of 'Idiopathic Hypergonadotropic Hypogonadism'. The patient underwent not only oral rehabilitation, but also timely consultation and treatment from a pediatrician and an endocrinologist.

[Children with idiopathic hypogonadotropic hypogonadism: clinical data analysis and mutations analysis of KAL1 and FGFR1 gene].

PubMed

Qin, Miao; Gong, Chunxiu; Qi, Zhan; Wu, Di; Liu, Min; Gu, Yi; Cao, Bingyan; Li, Wenjing; Liang, Xuejun

2014-12-01

To summarize the clinical features of idiopathic hypogonadotropic hypogonadism (IHH) diagnosed during childhood, and detect mutations in KAL1 and FGFR1, acting as key clues for diagnoses. We collected and analyzed clinical data of 21 cases (including demographic data, chief complaint, history of present illness, family history, physical examination, laboratory tests and imaging studies, etc.) diagnosed with IHH from December 2008 to February 2013. Polymerase chain reaction and gene sequencing was applied to detect mutations on KAL1 and FGFR1. Fifty healthy unrelated individuals were choosen as controls. Of 21 patients with IHH, 19 were males and 2 females, they visited us initially from 8-17 years old, with an average of (13.58 ± 2.38) years old. Sixteen cases were KS patients (76%). One boy reported abnormal sense of smelling but having olfactory perfect picture on MRI; 2/19 male cases had no puberty when they were over 13-14 years old without abnormal external genitalia. 8/19 cases only had small penis, 8/19 had both of cryptorchidism and small penis, and the Case 2 also had hypospadias. One boy had cryptorchidism combined with a normal penis. Only 2 girls diagnosed as IHH who visited us because of no puberty signs when they were 13 and 16 years old, respectively. Other clinical manifestations included: one with gynecomastia, 2 had mental retardation, and one was deaf; one with high palatal arch; one with mirror-movement and one with left renal agenesis but normal renal function respectively. Laboratory tests showed that the basic testosterone (T) is low and with inappropriately low or normal gonadotropin hormones. The results of cases of standard human chorionic gonadotropin (HCG) test of 7 cases out of 19 male children's were normal (testosterone>1 100 ng/L), and another nine cases continued to complete the extended HCG test, and the testosterone levels of two of them (cases 6, 8) were still lower than 1 000 ng/L. Family history: the parents in 9/21 family had

Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism--pathogenesis, diagnosis and treatment.

PubMed

Boehm, Ulrich; Bouloux, Pierre-Marc; Dattani, Mehul T; de Roux, Nicolas; Dodé, Catherine; Dunkel, Leo; Dwyer, Andrew A; Giacobini, Paolo; Hardelin, Jean-Pierre; Juul, Anders; Maghnie, Mohamad; Pitteloud, Nelly; Prevot, Vincent; Raivio, Taneli; Tena-Sempere, Manuel; Quinton, Richard; Young, Jacques

2015-09-01

Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder caused by the deficient production, secretion or action of gonadotropin-releasing hormone (GnRH), which is the master hormone regulating the reproductive axis. CHH is clinically and genetically heterogeneous, with >25 different causal genes identified to date. Clinically, the disorder is characterized by an absence of puberty and infertility. The association of CHH with a defective sense of smell (anosmia or hyposmia), which is found in ∼50% of patients with CHH is termed Kallmann syndrome and results from incomplete embryonic migration of GnRH-synthesizing neurons. CHH can be challenging to diagnose, particularly when attempting to differentiate it from constitutional delay of puberty. A timely diagnosis and treatment to induce puberty can be beneficial for sexual, bone and metabolic health, and might help minimize some of the psychological effects of CHH. In most cases, fertility can be induced using specialized treatment regimens and several predictors of outcome have been identified. Patients typically require lifelong treatment, yet ∼10-20% of patients exhibit a spontaneous recovery of reproductive function. This Consensus Statement summarizes approaches for the diagnosis and treatment of CHH and discusses important unanswered questions in the field.

High frequency of association of rheumatic/autoimmune diseases and untreated male hypogonadism with severe testicular dysfunction

PubMed Central

Jimenez-Balderas, F Javier; Tapia-Serrano, Rosario; Fonseca, M Eugenia; Arellano, Jorge; Beltran, Arturo; Yañez, Patricia; Camargo-Coronel, Adolfo; Fraga, Antonio

2001-01-01

Our goal in the present work was to determine whether male patients with untreated hypogonadism have an increased risk of developing rheumatic/autoimmune disease (RAD), and, if so, whether there is a relation to the type of hypogonadism. We carried out neuroendocrine, genetic, and rheumatologic investigations in 13 such patients and 10 healthy male 46,XY normogonadic control subjects. Age and body mass index were similar in the two groups. Nine of the 13 patients had hypergonadotropic hypogonadism (five of whom had Klinefelter's syndrome [karyotype 47,XXY]) and 4 of the 13 had hypogonadotropic hypogonadism (46,XY). Of these last four, two had Kallmann's syndrome and two had idiopathic cryptorchidism. Eight (61%) of the 13 patients studied had RADs unrelated to the etiology of their hypogonadism. Of these, four had ankylosing spondylitis and histocompatibility B27 antigen, two had systemic lupus erythematosus (in one case associated with antiphospholipids), one had juvenile rheumatoid arthritis, and one had juvenile dermatomyositis. In comparison with the low frequencies of RADs in the general population (about 0.83%, including systemic lupus erythematosus, 0.03%; dermatomyositis, 0.04%; juvenile rheumatoid arthritis, 0.03%; ankylosing spondylitis, 0.01%; rheumatoid arthritis, 0.62%; and other RAD, 0.1%), there were surprisingly high frequencies of such disorders in this small group of patients with untreated hypogonadism (P < 0.001) and very low serum testosterone levels (P = 0.0005). The presence of RADs in these patients was independent of the etiology of their hypogonadism and was associated with marked gonadal failure with very low testosterone levels. PMID:11714390

Successful pregnancy and live birth from a hypogonadotropic hypogonadism woman with low serum estradiol concentrations despite numerous oocyte maturations: a case report.

PubMed

Matsumoto, Kaori; Imakawa, Kazuhiko; Hayashi, Chuyu

2017-09-20

The increase in serum estradiol (E 2 ) concentrations during the follicular phase becomes the index of oocyte maturation in vivo. When ovarian stimulation is performed to hypogonadotropic hypogonadism (HH) patients with only follicle stimulating hormone (FSH), proper increase in serum E 2 concentrations is not observed. Even if oocytes are obtained, which usually have low fertilization rate. In this report, we would like to present an unique case, in which under low E 2 concentrations and without luteinizing hormone (LH) administration, numerous mature oocytes could be obtained and a healthy baby delivered. During controlled ovarian stimulation (COS) with only recombinant follicular stimulating hormone (rFSH) administrations, a 26-year-old Japanese woman with hypothalamic amenorrhea (i.e., hypogonadotropic hypogonadism) developed numerous follicles despite low serum E 2 , 701 pg/ml, and high progesterone (P 4 ) concentrations, 2.11 ng/ml, on the day of induced ovulation. However, 33 cumulus-oocyte complexes (COCs) were successfully obtained; following the embryo culture, four early embryos and six blastocysts were cryopreserved. This patient received hormone replacement therapy (HRT), during which one of six cryopreserved blastocysts was thawed and transferred into the uterine lumen. The patient became pregnant from the first transfer, went through her pregnancy without any complications, and delivered a healthy male baby in the 39th week. Low E 2 concentrations in follicular fluids (FFs) are suggestive that aromatase and/or 17β-hydroxysteroid dehydrogenase (17β-HSD) could be low. Serum E 2 concentrations may not be the most important index for oocyte maturation during COS, and suggested that oocyte maturation was in progress even under low serum E 2 and high P 4 conditions. Even if serum E 2 concentrations did not properly increase, numerous mature oocytes could be obtained, resulting in the birth of a healthy baby.

Hormonal control of spermatogenesis in men: therapeutic aspects in hypogonadotropic hypogonadism.

PubMed

Pitteloud, Nelly; Dwyer, Andrew

2014-05-01

During the first two trimesters of intrauterine life, fetal sex steroid production is driven by maternal human chorionic gonadotropin (hCG). The HPG axis is activated around the third trimester and remains active for the first 6-months of neonatal life. This so-called mini-puberty is a developmental window that has profound effects on future potential for fertility. In early puberty, GnRH secretion is reactivated first at night and then night and day. Pulsatile GnRH stimulates both LH and FSH, which induce maturation of the seminiferous tubules and Leydig cells. Congenital hypogonadotropic hypogonadism (CHH) results from GnRH deficiency. Men with CHH lack the mini-pubertal and pubertal periods of Sertoli Cell proliferation and thus present with prepubertal testes (<4mL) and low inhibin serum levels --reflecting diminished SC numbers. To induce full maturation of the testes, GnRH-deficient patients can be treated with either pulsatile GnRH, hCG or combined gonadotropin therapy (FSH+hCG). Fertility outcomes with each of these regimens are highly variable. Recently, a randomized, open label treatment study (n=13) addressed the question of whether a sequential treatment with FSH alone prior to LH and FSH (via GnRH pump) could enhance fertility outcomes. All men receiving the sequential treatment developed sperm in the ejaculate, whereas 2/6 men in the other group remained azoospermic. A large, multicenter clinical trial is needed to definitively prove the optimal treatment approach for severe CHH. Copyright © 2014. Published by Elsevier Masson SAS.

Hypogonadotropic Hypogonadism in Non-Functioning Pituitary Adenomas: Impact of Intervention.

PubMed

Monteiro, Diana Margarida; Freitas, Paula; Vieira, Romana; Carvalho, Davide

2017-06-01

To determine the prevalence of hypogonadotropic hypogonadism (HH) among patients with non-functioning pituitary adenomas (NFPA) and the post-surgery outcome on pituitary gonadotropins secretion (PGS); to determine the prevalence of erectile dysfunction (ED) on male patients with NFPA, to evaluate the impact of testosterone replacement therapy (TRT) in those with HH. Retrospective evaluation of gonadal function in 109 NFPA patients (45 males), with a mean age of 51.8 years, diagnosed on the last 10 years. ED questionnaire applied to 34 male patients. Male patients with NFPA were significantly older (males 58.1±15.8 vs. females 47.4±16.94; p=0.001). Most patients had macroadenomas (67%; p=0.001) and only a minority were incidentalomas (19%; p<0.001). Prevalence of HH was 40% (60% on males, 25% on females; p<0.001). Surgery was performed in 54% of all patients (71% of males, 42% of females; p<0.003). After intervention, 14% became HH, 69% maintained previous function and 17% improved. On the questionnaire, 76% reported having ED, 54% of which had HH and 21% were under TRT. Of the patients under TRT, 79% still had ED. Median age of patients with ED was significantly higher [with ED 65 vs. without 49 years; p=0.012). There was no BMI difference between patients with or without TRT (28.0 vs. 27.4 Kg/m 2 ). NFPA was more frequent in older rather than younger patients. Males were older, had more HH and surgery. There was no significant improvement of pituitary function with surgery (17%) and 13% became iatrogenic HH. TRT had a low efficacy to improve ED in these patients. © Georg Thieme Verlag KG Stuttgart · New York.

[Early-onset and late-onset male hypogonadotropic hypogonadism and osteoporosis].

PubMed

Okada, Hiroshi; Shin, Takeshi; Kobori, Yoshitomo

2016-07-01

Hypogonadism is classified into two major clinical entities, namely early-onset hypogonadism and late-onset hypogonadism. The former is characterized by the malfunction of hypothalamo-pituitary-gonadal(testicular)axis or by the primary hypofunction of testes(e.g. Klinefelter's syndrome). The latter is summarized as LOH syndrome which is attributed to the dropped level of bioavailable testosterone. In these diseases testosterone is the key molecule which may cause various symptoms relating not only to physical health but also to mental or psychologic health. In this review issues concerning bone health in these disease are described.

Estrogen Metabolism and Prostate Cancer Risk

DTIC Science & Technology

2001-04-01

prior the diagnosis), or affected with metabolic diseases affecting endocrine profile (i.e., hypogonadism , hyperadrenalism) were excluded. Those...Klibanski A., Neer R.M. Osteoporosis in men with idiopathic hypogonadotropic hypogonadism . Ann. Intern. Med. 1987; 106:354-361 Finkelstein J.S., Neer...in ageing Caucasian and African populations Lancet 1979; 2:1326-1330 Stanley H.L., Schmitt B.P., Poses R.M. Does hypogonadism contribute to the

A novel loss-of-function mutation in GPR54/KISS1R leads to hypogonadotropic hypogonadism in a highly consanguineous family.

PubMed

Nimri, Revital; Lebenthal, Yael; Lazar, Liora; Chevrier, Lucie; Phillip, Moshe; Bar, Meytal; Hernandez-Mora, Eva; de Roux, Nicolas; Gat-Yablonski, Galia

2011-03-01

The G protein-coupled receptor 54 (GPR54), the kisspeptin receptor, is essential for stimulation of GnRH secretion and induction of puberty. Recently loss-of-function mutations of the GPR54 have been implicated as a cause of isolated idiopathic hypogonadotropic hypogonadism (IHH). The objective of the study was to identify the genetic cause of IHH in a consanguineous pedigree and to characterize the phenotypic features from infancy through early adulthood. In six patients with normosmic IHH belonging to two families of Israeli Muslim-Arab origin highly related to one another, DNA was analyzed for mutations in the GnRHR and GPR54 genes, with functional analysis of the mutation found. The five males underwent comprehensive endocrine evaluation and were under longitudinal follow-up; the one female presented in early adulthood. A new homozygous mutation (c.T815C) in GPR54 leading to a phenylalanine substitution by serine (p.F272S) was detected in all patients. Functional analysis showed an almost complete inhibition of kisspeptin-induced GPR54 signaling and a dramatic decrease of the mutated receptor expression at the cell surface. The males exhibited the same clinical features from infancy to adulthood, characterized by cryptorchidism, a relatively short penis, and no spontaneous pubertal development. The female patient presented at 18 yr with impuberism and primary amenorrhea. Repeated stimulation tests demonstrated complete gonadotropin deficiency throughout follow-up. A novel loss-of-function mutation (p.F272S) in the GPR54 gene is associated with familial normosmic IHH. Underdeveloped external genitalia and impuberism point to the major role of GPR54 in the activation of the gonadotropic axis from intrauterine life to adulthood.

The effectiveness of zinc supplementation in men with isolated hypogonadotropic hypogonadism.

PubMed

Liu, Yan-Ling; Zhang, Man-Na; Tong, Guo-Yu; Sun, Shou-Yue; Zhu, Yan-Hua; Cao, Ying; Zhang, Jie; Huang, Hong; Niu, Ben; Li, Hong; Guo, Qing-Hua; Gao, Yan; Zhu, Da-Long; Li, Xiao-Ying

2017-01-01

A multicenter, open-label, randomized, controlled superiority trial with 18 months of follow-up was conducted to investigate whether oral zinc supplementation could further promote spermatogenesis in males with isolated hypogonadotropic hypogonadism (IHH) receiving sequential purified urinary follicular-stimulating hormone/human chorionic gonadotropin (uFSH/hCG) replacement. Sixty-seven Chinese male IHH patients were recruited from the Departments of Endocrinology in eight tertiary hospitals and randomly allocated into the sequential uFSH/hCG group (Group A, n = 34) or the sequential uFSH plus zinc supplementation group (Group B, n = 33). In Group A, patients received sequential uFSH (75 U, three times a week every other 3 months) and hCG (2000 U, twice a week) treatments. In Group B, patients received oral zinc supplementation (40 mg day-1 ) in addition to the sequential uFSH/hCG treatment given to patients in Group A. The primary outcome was the proportion of patients with a sperm concentration ≥1.0 × 106 ml-1 during the 18 months. The comparison of efficacy between Groups A and B was analyzed. Nineteen of 34 (55.9%) patients receiving sequential uFSH/hCG and 20 of 33 (60.6%) patients receiving sequential uFSH/hCG plus zinc supplementation achieved sperm concentrations ≥1.0 × 106 ml-1 by intention to treat analyses. No differences between Group A and Group B were observed as far as the efficacy of inducing spermatogenesis (P = 0.69). We concluded that the sequential uFSH/hCG plus zinc supplementation regimen had a similar efficacy to the sequential uFSH/hCG treatment alone. The additional improvement of 40 mg day-1 oral zinc supplementation on spermatogenesis and masculinization in male IHH patients is very subtle.

[Hypogonadotropic hypogonadism: new aspects in the regulation of hypothalamic-pituitary-gonadal axis].

PubMed

Brioude, F; Bouvattier, C-E; Lombès, M

2010-09-01

Hypogonadotropic hypogonadism (HH) is defined by the absence of sex steroid synthesis associated with the lack of appropriate gonadotrophin secretion. This leads to a variable degree of impuberism, often diagnosed during childhood or adolescence. Genetics of HH involve many genes. However, molecular defects have been identified in only 30 % of patients. Kallmann syndrome (KS) is defined by the association of HH and anosmia. Six genes are involved in KS (KAL1, FGFR1, FGF8, PROK2, PROKR2 and CHD7). However, genetics of KS is complex, because of the variability of the phenotype for a similar molecular defect. Otherwise, heterozygous anomalies are frequently described. Identification in the same patient of several mutations in some of these genes (digenism) could account for this variability. Autosomal recessive transmission is frequently observed in familial cases of HH without anosmia. Molecular alterations have been identified for several neuropeptides or their corresponding receptors, which are involved in the physiology of the gonadotropic axis : GNRHR, KISS1R/GPR54, neurokinin B (TAC3), TACR3 and GNRH1 (and PROK2, PROKR2 and CHD7). Anomalies of leptin or its receptor are also involved in HH cases. A new negative regulating element has been recently identified in humans : RFRP3, which is ortholog of the avian GnIH (gonadotrophin inhibitory hormone). Recent progress about these neuropeptides leads to a new model of comprehension of the gonadotropic axis physiology, from a linear model to a network model, which regulates the central element of regulation of the gonadotropic axis, represented by the GnRH neurons. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Hypogonadotropic hypogonadism: new identification of testicular blood flow and varicocele after treatment with gonadotropins.

PubMed

ur Rehman, Khaleeq; Shahid, Khubaib; Humayun, Hina

2014-09-01

To investigate testicular changes in patients with hypogonadotropic hypogonadism (HH) after treatment with gonadotropins. Patients with HH were investigated and followed before and after treatment. Urology and andrology clinic of a teaching hospital. Consecutive male patients with diagnosed HH. All patients were treated with gonadotropins during the study period and later. The hormonal status and scrotal color Doppler ultrasound (CDUS) of patients was recorded before and after treatment. Twenty-six patients with HH (ages 18-43 years) were followed for 8-29 months. After treatment, serum T and secondary sex characters improved in all and spermatogenesis developed in 61.5% of patients. Before treatment, testicular (intraparenchymal blood flow) was undetectable in all and barely detectable in three patients. This improved significantly to 4.53±5.44 and 4.27±4.97 cm/second, respectively, after treatment. Subcapsular arterial flow and testicular size also improved significantly. Similarly, after treatment, transverse epididymal diameter (TED) increased significantly. At baseline, no patient had detectable varicocele on CDUS. After treatment, varicocele was demonstrable in 23% of patients. This finding was further evaluated retrospectively from our 76 HH patient files. None of them had varicocele before treatment, but after treatment 19.73% were found to have varicocele. Patients with HH responded to gonadotropins by improvement in testicular blood flow and increase in TED. In some patients, varicocele was found to develop after treatment. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Increases in bone density during treatment of men with idiopathic hypogonadotropic hypogonadism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Finkelstein, J.S.; Klibanski, A.; Neer, R.M.

To assess the effects of gonadal steroid replacement on bone density in men with osteoporosis due to severe hypogonadism, we measured cortical bone density in the distal radius by 125I photon absorptiometry and trabecular bone density in the lumbar spine by quantitative computed tomography in 21 men with isolated GnRH deficiency while serum testosterone levels were maintained in the normal adult male range for 12-31 months (mean +/- SE, 23.7 +/- 1.1). In men who initially had fused epiphyses (n = 15), cortical bone density increased from 0.71 +/- 0.02 to 0.74 +/- 0.01 g/cm2 (P less than 0.01), whilemore » trabecular bone density did not change (116 +/- 9 compared with 119 +/- 7 mg/cm3). In men who initially had open epiphyses (n = 6), cortical bone density increased from 0.62 +/- 0.01 to 0.70 +/- 0.03 g/cm2 (P less than 0.01), while trabecular bone density increased from 96 +/- 13 to 109 +/- 12 mg/cm3 (P less than 0.01). Cortical bone density increased 0.03 +/- 0.01 g/cm2 in men with fused epiphyses and 0.08 +/- 0.02 g/cm2 in men with open epiphyses (P less than 0.05). Despite these increases, neither cortical nor trabecular bone density returned to normal levels. Histomorphometric analyses of iliac crest bone biopsies demonstrated that most of the men had low turnover osteoporosis, although some men had normal to high turnover osteoporosis. We conclude that bone density increases during gonadal steroid replacement of GnRH-deficient men, particularly in men who are skeletally immature.« less

A successful healthy live birth from a female patient with hypogonadotropic hypogonadism and oocytes with unusually large cytoplasmic inclusions.

PubMed

Duvan, Candan İltemir; Pekel, Aslıhan; Ercan, Ummu Gulsum; Arıkan, Yuksel Onaran

2016-03-01

This study aimed to report the case of a successful live birth from a woman having oocytes with abnormally large cytoplasmic inclusions. The patient described in this case is a 28 year-old woman with hypogonadotropic hypogonadism (HH) with a history of two previous unsuccessful in vitro fertilization (IVF) attempts offered an antagonist protocol. Stimulation was performed with human menopausal gonadotropin 300 IU/day. The intracytoplasmic sperm injection (ICSI) procedure was performed 4-6 hours after oocyte aspiration for all mature oocytes. Six oocytes were retrieved, five of which mature (MII). All oocytes had abnormal cytoplasmic structures. Two were fertilized after ICSI and two top quality embryos were transferred on Day 2. Our case report suggests that HH patients with refractile bodies/lipofuscin in their oocytes may not have their pregnancies negatively affected. While there have been several reports of successful births from dysmorphic oocytes, no cases of successful pregnancies followed by live births from young women with HH and oocytes with large cytoplasmic inclusions had been reported to date.

Switch to restoration therapy in a testosterone treated central hypogonadism with erythrocytosis.

PubMed

Cangiano, B; Cacciatore, C; Persani, L; Bonomi, M

2017-01-01

We describe a case of severe erythrocytosis caused by testosterone replacement therapy in a 66-year-old man affected with hypogonadotropic hypogonadism (HH) determining osteoporosis, resolved by switching to restoration therapy with clomiphene citrate. The patient complained fatigue, loss of libido and defective erections and a spontaneous vertebral fracture despite bisphosphonate therapy and vitamin D supplementation. The examinations proved isolated HH and he was therefore treated with testosterone gel with regression of specific manifestations but elevated hemoglobin and hematocrit values. Therefore, it was decided to switch to a restoration therapy with clomiphene citrate 25 mg/die, which resulted in the resolution of symptoms without evident side effects. In a couple of months, the patient showed normalization of testosterone levels and increment of testicular volume. Since secondary hypogonadism is the consequence of an insufficient stimulation of the gonads by hypothalamic-pituitary axis, therapeutic approaches aimed to restore endogenous testosterone production should be considered in alternative to testosterone replacement, particularly if side effects intervene. Among these strategies, clomiphene citrate seems to have a high efficacy and safety profile also in the elderly with isolated HH and no evident pituitary lesion. Hypogonadism should always be assessed in patients with severe loss in BMD and undergo appropriate medical treatment.In hypogonadotropic hypogonadism, more approaches are available other than testosterone replacement therapy alone.In patients with severe late-onset central hypogonadism presenting with erythrocytosis even at low doses of replacement therapy, restoration therapy with clomiphene could prove to be an effective solution, particularly in patients with a reversible disruption of GNRH/gonadotropin functions.Clomiphene citrate increases gonadotropin levels and testicular volume and should therefore be considered in hypogonadal

An uncommon phenotype with familial central hypogonadism caused by a novel PROP1 gene mutant truncated in the transactivation domain.

PubMed

Reynaud, Rachel; Barlier, Anne; Vallette-Kasic, Sophie; Saveanu, Alexandru; Guillet, Marie-Pierre; Simonin, Gilbert; Enjalbert, Alain; Valensi, Paul; Brue, Thierry

2005-08-01

PROP1 gene mutations are usually associated with childhood onset GH and TSH deficiencies, whereas gonadotroph deficiency is diagnosed at pubertal age. We report a novel PROP1 mutation revealed by familial normosmic hypogonadotropic hypogonadism. We performed in vitro transactivation and DNA binding experiments to study functional consequences of this mutation. Three brothers were followed in the Department of Endocrinology of a French university hospital. These patients from a consanguineous kindred were referred for cryptorchidism and/or delayed puberty. Initial investigations revealed hypogonadotropic hypogonadism. One of the patients had psychomotor retardation, intracranial hypertension, and minor renal malformations. The brothers reached normal adult height and developed GH and TSH deficiencies after age 30. A novel homozygous nonsense mutation (W194X) was found in the PROP1 gene, indicating that the protein is truncated in its transactivation domain. Transfection studies confirmed the deleterious effect of this mutation, whose transactivation capacity was only 34.4% of that of the wild-type. Unexpectedly altered DNA-binding properties suggested that the C-terminal end of the factor plays a role in protein-DNA interaction. PROP1 mutations should be considered among the growing number of genetic causes of initially isolated hypogonadotropic hypogonadism. This report extends the phenotype variability associated with PROP1 mutations.

Induction of puberty with human chorionic gonadotropin and follicle-stimulating hormone in adolescent males with hypogonadotropic hypogonadism.

PubMed

Barrio, R; de Luis, D; Alonso, M; Lamas, A; Moreno, J C

1999-02-01

To evaluate the clinical and hormonal responses of adolescent males with hypogonadotropic hypogonadism (HH) in response to gonadotropin replacement with the use of long-term combined hCG and FSH therapy. Prospective clinical study. Clinical pediatric department providing tertiary care. Seven prepubertal males with isolated HH with a mean (+/-SD) age of 15.44+/-1.97 years and seven prepubertal males with panhypopituitarism-associated HH with a mean (+/-SD) age of 18.1+/-3.24 years were studied. Human chorionic gonadotropin (1,000-1,500 IU IM) and FSH (75-100 IU SC) were administered every alternate day of the week until the total induction of puberty and spermatogenesis was achieved. Serum testosterone levels, testicular volume, penis length, and sperm count were evaluated after the administration of hCG and FSH. All patients achieved normal sexual maturation and normal or nearly normal adult male levels of testosterone. The increase in testicular size was significant in both groups. Positive sperm production was assessed in four of five patients with isolated HH and in three of three patients with panhypopituitarism-associated HH. Long-term combined hCG and FSH therapy is effective in inducing puberty, increasing testicular volume, and stimulating spermatogenesis in adolescent males with isolated HH and panhypopituitarism-associated HH.

Hypogonadotropic hypogonadism and metabolic syndrome: insights from the high-fat diet experimental rabbit animal model.

PubMed

Morelli, Annamaria; Vignozzi, Linda; Maggi, Mario

2016-06-01

The etiology of metabolic syndrome (MetS) is complex and involves the interplay between environmental, lifestyle and genetic determinants. MetS in men can be associated with a biochemical pattern of partial hypogonadotropic hypogonadism (HH). A similar pattern has been noted in both men and women with a variety of acute illnesses and chronic diseases, and there is ongoing debate regarding whether this phenomenon might adaptive (e.g. diverting resources from reproduction into survival), or maladaptive (e.g. anemia, sarcopenia, osteopenia and fatigue of androgen-deficiency amplify and widen the adverse consequences of the original disease-trigger). In women with hypothalamic amenorrhea (HA-HH secondary to chronic bioenergetic deficit from dietary restriction and/or intensive exercise), a genetic link to congenital HH (CHH) was recently established; women carrying monoallelic CHH gene mutations will typically not develop CHH, but are significantly more susceptible to HA. However, the male reproductive axis seems to be more resistant to similar environmental insults. In contrast, MetS-associated HH (mHH) is specifically a male phenomenon; the reproductive phenotype of females with MetS tending instead towards hyperandrogenism, rather than hypogonadism. The underlying pathogenic mechanisms responsible for mHH have not been clearly identified and, as yet, there has been no investigation of a potential role for CHH mutation carriage in its etiology. Over the decades, the use of either genetic- or diet-induced obesity and/or MetS animal models has greatly helped to illuminate the complex etiology of metabolic dysregulation, but the strong relationship between obesity/MetS and mHH in males has been largely neglected, with little or no information about the regulation of reproductive function by metabolic factors under conditions of bioenergetic excess. However, the pathogenic link between MetS and HH in males has been recently investigated in an animal model of high fat

Pulsatile GnRH Is Superior to hCG in Therapeutic Efficacy in Adolescent Boys With Hypogonadotropic Hypogonadodism.

PubMed

Gong, Chunxiu; Liu, Ying; Qin, Miao; Wu, Di; Wang, Xiaoling

2015-07-01

We investigated the efficacy and safety of two different treatments that have not been evaluated in peripuberty boys with hypogonadotropic hypogonadism (HH). The objective of the study was to assess the effectiveness and safety of GnRH or human chorionic gonadotropin (hCG) treatment in adolescent boys with HH. Twelve patients received 8-10 μg of GnRH, sc injected every 90 minutes using a pump. Another 22 patients received hCG, injected im as follows: for the first 3 months, 1000 IU of hCG was injected two times per week and then once every other day for the next 3 months. The dose of hCG was increased to 2000 IU after a 6-month treatment and the above cycle was repeated for another 6 months. All patients were treated for 12-14 months and followed up every 3 months. Thirty-five participants were chosen from Beijing Children's Hospital from 2008 to 2014. Twenty-three patients with Kallmann syndrome and 12 with normosmic idiopathic hypogonadotropic hypogonadism. The age ranged from 10 to 16 years. Twelve patients were treated with pulsatile pump GnRH (group 1), and 22 patients were treated with im hCG (group 2). One patient was treated successively with hCG and GnRH, which was removed in data analysis. Testicular volume was measured by an orchidometer. The levels of T, LH, and FSH serum were measured with a chemiluminesent immunoassay. Bone age was measured by x-ray. Patients treated with GnRH showed larger testes than those treated with hCG. Patients in both groups showed a significantly increased length of penis and T levels. But the difference of the two groups was not statistically significant. There was no significant difference in side effects in both groups. Boys with HH may be effectively treated with GnRH. We suggested that GnRH exhibits higher efficacy in treating adolescent boys with HH than hCG.

Prevalence of olfactory and other developmental anomalies in patients with central hypogonadotropic hypogonadism.

PubMed

Della Valle, Elisa; Vezzani, Silvia; Rochira, Vincenzo; Granata, Antonio Raffaele Michele; Madeo, Bruno; Genovese, Elisabetta; Pignatti, Elisa; Marino, Marco; Carani, Cesare; Simoni, Manuela

2013-01-01

Hypogonadotropic hypogonadism (HH) is a heterogeneous disease caused by mutations in several genes. Based on the presence of hyposmia/anosmia it is distinguished into Kallmann syndrome (KS) and isolated HH. The prevalence of other developmental anomalies is not well established. We studied 36 patients with HH (31 males, 5 females, mean age 41.5), 9 with familial and 27 with sporadic HH (33 congenital, 3 adult-onset), by physical examination, smell test (BSIT Sensonics), audiometry, renal ultrasound, and magnetic resonance imaging of the olfactory structures. Based on the smell test, patients were classified as normosmic (n = 21, 58.3%) and hypo/anosmic (n = 15, 41.6%). Hypoplasia/agenesis of olfactory bulbs was found in 40% of patients (10/25; 75% hypo/anosmic, 7.6% normosmic, p < 0.01, Fisher's test). Remarkably, olfactory structures were normal in two anosmic patients, while one normosmic patient presented a unilateral hypoplastic bulb. Fourteen of 33 patients (42.4%) presented neurosensorial hearing loss of various degrees (28.5% hypo/anosmic, 52.6% normosmic, p = NS). Renal ultrasound revealed 27.7% of cases with renal anomalies (26.6% hypo/anosmic, 28.5% normosmic, p = NS). At least one midline defect was found in 50% of the patients (53.3% hypo/anosmic, 47.6% normosmic, p = NS), including abnormal palate, dental anomalies, pectus excavatum, bimanual synkinesis, iris coloboma, and absent nasal cartilage. Anamnestically 4/31 patients reported cryptorchidism (25% hypo/anosmic, 5.2% normosmic, p = NS). Hypo/anosmia is significantly related to anatomical anomalies of the olfactory bulbs/tracts but the prevalence of other developmental anomalies, especially midline defects and neurosensorial hearing loss, is high both in HH and KS and independent of the presence of anosmia/hyposmia. From the clinical standpoint KS and normosmic HH should be considered as the same complex, developmental disease.

Efficacy and Outcome Predictors of Gonadotropin Treatment for Male Congenital Hypogonadotropic Hypogonadism

PubMed Central

Liu, Zhaoxiang; Mao, Jangfeng; Wu, Xueyan; Xu, Hongli; Wang, Xi; Huang, Bingkun; Zheng, Junjie; Nie, Min; Zhang, Hongbing

2016-01-01

Abstract Gonadotropin induces masculinization and spermatogenesis in men with congenital hypogonadotropic hypogonadism (CHH). However, large cohort studies for the efficacy and reliable predictors of this therapy need to be conducted. The aim of this study was to investigate the efficacy of gonadotropin treatment in a large cohort of male CHH patients and analyze putative predictors for successful spermatogenesis. This retrospective study included 223 CHH azoospermic patients without puberty development treated between 2005 and 2014. All patients received combined human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) and were followed up for >6 months (5109 person-months). Serum total testosterone level, testicular size, spermatogenesis, and pregnancy outcome were recorded at each visit. After gonadotropin therapy, testicular size was enlarged from 2.1 ± 1.6 to 8.1 ± 4.6 mL (P < 0.001) and serum total testosterone was elevated from 0.9 ± 0.5 to 15.1 ± 8.2 nmol/L (P < 0.001). Spermatogenesis (>0/mL) occurred at a median period of 15 months (95% confidence interval 13.5–16.5). Larger basal testicular volume (P = 0.012) and noncryptorchidism history (P = 0.028) are independent predictors for earlier sperm appearance. Sixty four percent (143/223) of patients succeeded in producing sperms and the average time for initial sperm detection was 14 ± 8 months. However, their sperm concentrations (11.7 [2.1, 24.4] million/mL) and sperm progressive motility (A + B 36.9% ± 20.2%) are significantly lower than World Health Organization standards. Of the 34 patients who desired for fathering children, 19 patients impregnanted their partners during the treatment. Gonadotropin therapy induces spermatogenesis in male CHH patients. A larger basal testicular size and noncryptorchidism history are favorable indicators for earlier spermatogenesis. PMID:26945370

Congenital Hypogonadotropic Hypogonadism during Childhood: Presentation and Genetic Analyses in 46 Boys

PubMed Central

Vizeneux, Audrey; Hilfiger, Aude; Bouligand, Jérôme; Pouillot, Monique; Brailly-Tabard, Sylvie; Bashamboo, Anu; McElreavey, Ken; Brauner, Raja

2013-01-01

Background The majority of the patients reported with mutations in isolated hypogonadotropic hypogonadism (HH) are adults. We analysed the presentation and the plasma inhibin B and anti-müllerian hormone (AMH) concentrations during childhood and adolescence, and compared them to the genetic results. Methods This was a retrospective, single-center study of 46 boys with HH. Results Fourteen (30.4%) had Kallmann syndrome (KS), 4 (8.7%) had CHARGE syndrome and 28 (60.9%) had HH without olfaction deficit nor olfactive bulb hypoplasia. Eighteen (39%) had an associated malformation or syndromes. At diagnosis, 22 (47.8%) boys were aged

Recommendations on the diagnosis, treatment and monitoring of hypogonadism in men.

PubMed

Lunenfeld, Bruno; Mskhalaya, George; Zitzmann, Michael; Arver, Stefan; Kalinchenko, Svetlana; Tishova, Yuliya; Morgentaler, Abraham

2015-03-01

Hypogonadism or Testosterone Deficiency (TD) in adult men as defined by low levels of serum testosterone accompanied by characteristic symptoms and/or signs as detailed further on can be found in long-recognized clinical entities such as Klinefelter syndrome, Kallmann syndrome, pituitary or testicular disorders, as well as in men with idiopathic, metabolic or iatrogenic conditions that result in testosterone deficiency. These recommendations do not encompass the full range of pathologies leading to hypogonadism (testosterone deficiency), but instead focus on the clinical spectrum of hypogonadism related to metabolic and idiopathic disorders that contribute to the majority of cases that occur in adult men.

Responsiveness to a Physiological Regimen of GnRH Therapy and Relation to Genotype in Women With Isolated Hypogonadotropic Hypogonadism

PubMed Central

Abel, Brent S.; Shaw, Natalie D.; Brown, Jenifer M.; Adams, Judith M.; Alati, Teresa; Martin, Kathryn A.; Pitteloud, Nelly; Seminara, Stephanie B.; Plummer, Lacey; Pignatelli, Duarte; Crowley, William F.; Welt, Corrine K.

2013-01-01

Context: Isolated hypogonadotropic hypogonadism (IHH) is caused by defective GnRH secretion or action resulting in absent or incomplete pubertal development and infertility. Most women with IHH ovulate with physiological GnRH replacement, implicating GnRH deficiency as the etiology. However, a subset does not respond normally, suggesting the presence of defects at the pituitary or ovary. Objectives: The objective of the study was to unmask pituitary or ovarian defects in IHH women using a physiological regimen of GnRH replacement, relating these responses to genes known to cause IHH. Design, Setting, and Subjects: This study is a retrospective analysis of 37 IHH women treated with iv pulsatile GnRH (75 ng/kg per bolus). Main Outcome Measures: Serum gonadotropin and sex steroid levels were measured, and 14 genes implicated in IHH were sequenced. Results: During their first cycle of GnRH replacement, normal cycles were recreated in 60% (22 of 37) of IHH women. Thirty percent of women (12 of 37) demonstrated an attenuated gonadotropin response, indicating pituitary resistance, and 10% (3 of 37) exhibited an exaggerated FSH response, consistent with ovarian resistance. Mutations in CHD7, FGFR1, KAL1, TAC3, and TACR3 were documented in IHH women with normal cycles, whereas mutations were identified in GNRHR, PROKR2, and FGFR1 in those with pituitary resistance. Women with ovarian resistance were mutation negative. Conclusions: Although physiological replacement with GnRH recreates normal menstrual cycle dynamics in most IHH women, hypogonadotropic responses in the first week of treatment identify a subset of women with pituitary dysfunction, only some of whom have mutations in GNRHR. IHH women with hypergonadotropic responses to GnRH replacement, consistent with an additional ovarian defect, did not have mutations in genes known to cause IHH, similar to our findings in a subset of IHH men with evidence of an additional testicular defect. PMID:23341491

Hypothesis: kisspeptin mediates male hypogonadism in obesity and type 2 diabetes.

PubMed

George, Jyothis T; Millar, Robert P; Anderson, Richard A

2010-01-01

Hypogonadism occurs commonly in men with type 2 diabetes (T2DM) and severe obesity. Current evidence points to a decreased secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus and thereby decreased secretion of gonadotropins from the pituitary gland as a central feature of the pathophysiology in these men. Hyperglycaemia, inflammation, leptin and oestrogen-related feedback have been proposed to make aetiological contributions to the hypogonadotropic hypogonadism of T2DM. However, the neuroendocrine signals that link these factors with modulation of GnRH neurons have yet to be identified. Kisspeptins play a central role in the modulation of GnRH secretion and, thus, downstream regulation of gonadotropins and testosterone secretion in men. Inactivating mutations of the kisspeptin receptor have been shown to cause hypogonadotropic hypogonadism in man, whilst an activating mutation is associated with precocious puberty. Data from studies in experimental animals link kisspeptin expression with individual factors known to regulate GnRH secretion, including hyperglycaemia, inflammation, leptin and oestrogen. We therefore hypothesise that decreased endogenous kisspeptin secretion is the common central pathway that links metabolic and endocrine factors in the pathology of testosterone deficiency seen in men with obesity and T2DM. We propose that the kisspeptin system plays a central role in integrating a range of metabolic inputs, thus constituting the link between energy status with the hypothalamic-pituitary-gonadal axis, and put forward potential clinical studies to test the hypothesis. Copyright 2010 S. Karger AG, Basel.

Plasma kisspeptin levels in male cases with hypogonadism.

PubMed

Kotani, Masato; Katagiri, Fumihiko; Hirai, Tsuyoshi; Kagawa, Jiro

2014-01-01

The hypothalamic hormone kisspeptin (metastin) regulates human reproduction by modulating gonadotropin-releasing hormone (GnRH) secretion. Kisspeptin is detected in peripheral blood, although GnRH is not. In this study, we measured plasma kisspeptin levels in four male cases with hypogonadism and seven normal male controls using enzyme immunoassay (EIA) to elucidate the clinical implications of kisspeptin levels in male hypogonadism. The results showed a variety of plasma kisspeptin levels: 6.0 fmol/mL in a male with isolated hypogonadotropic hypogonadism (IHH), 43.2 fmol/mL in a male with Kallmann's syndrome, 40.7 fmol/mL in a male with azoospermia, 323.2 fmol/mL in a male with hypergonadotropic hypogonadism, and 12.3 ± 2.5 fmol/mL (mean ± SD) in seven normal controls. Except for the case with IHH, the plasma kisspetin levels were elevated in the three cases with Kallmann's syndrome, azoospermia, and hypergonadotropic hypogonadism. The reason why the three cases had high values was their lesions were downstream of the kisspeptin neuron in the hypothalamic-pituitary-gonadal axis, suggesting that elevated kisspeptin levels were implicated in hypothalamic kisspeptin secretion under decreased negative feedback of gonadal steroids. The result that the plasma kisspeptin levels were decreased by gonadotropin therapy in the case with Kallmann's syndrome supported this hypothesis. In conclusion, to measure plasma kisspeptin levels could be useful for better understanding of male hypogonadism.

Recommendations on the diagnosis, treatment and monitoring of hypogonadism in men

PubMed Central

Lunenfeld, Bruno; Zitzmann, Michael; Arver, Stefan; Kalinchenko, Svetlana; Tishova, Yuliya; Morgentaler, Abraham

2015-01-01

Hypogonadism or Testosterone Deficiency (TD) in adult men as defined by low levels of serum testosterone accompanied by characteristic symptoms and/or signs as detailed further on can be found in long-recognized clinical entities such as Klinefelter syndrome, Kallmann syndrome, pituitary or testicular disorders, as well as in men with idiopathic, metabolic or iatrogenic conditions that result in testosterone deficiency. These recommendations do not encompass the full range of pathologies leading to hypogonadism (testosterone deficiency), but instead focus on the clinical spectrum of hypogonadism related to metabolic and idiopathic disorders that contribute to the majority of cases that occur in adult men. PMID:25657080

Bone mineral density, body composition and bone turnover in patients with congenital hypogonadotropic hypogonadism.

PubMed

Laitinen, E-M; Hero, M; Vaaralahti, K; Tommiska, J; Raivio, T

2012-08-01

Patients with congenital hypogonadotropic hypogonadism (HH) may have reduced peak bone mass in early adulthood, and increased risk for osteoporosis despite long-term hormonal replacement therapy (HRT). To investigate the relationship between HRT history and measures of bone health in patients with HH, we recruited 33 subjects (24 men, nine women; mean age 39.8 years, range: 24.0-69.1) with congenital HH (Kallmann syndrome or normosmic HH). They underwent clinical examination, were interviewed and medical charts were reviewed. Twenty-six subjects underwent dual-energy X-ray absorptiometry for evaluation of BMD of lumbar spine, hip, femoral neck and whole body; body composition and vertebral morphology were evaluated in 22 and 23 subjects, respectively. Circulating PINP, ICTP and sex hormone levels were measured. HRT history clearly associated to bone health: BMDs of lumbar spine, femoral neck, hip and whole body were lower in subjects (n = 9) who had had long (≥5 years) treatment pauses or low dose testosterone (T) treatment as compared to subjects without such history (n = 17; all p-values < 0.05). In addition, fat mass and body mass index (BMI) were significantly higher in men with deficient treatment history (median fat mass: 37.5 vs. 23.1%, p = 0.005; BMI: 32.6 vs. 25.2 kg/m(2), p < 0.05). Serum PINP correlated with ICTP (r(s) = 0.61; p < 0.005) in men, but these markers correlated neither with circulating T, nor with serum estradiol levels in women. In conclusion, patients with congenital HH require life-long follow-up to avoid inadequate HRT, long treatment pauses and further morbidity. © 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology.

Mutation screening of SEMA3A and SEMA7A in patients with congenital hypogonadotropic hypogonadism.

PubMed

Känsäkoski, Johanna; Fagerholm, Rainer; Laitinen, Eeva-Maria; Vaaralahti, Kirsi; Hackman, Peter; Pitteloud, Nelly; Raivio, Taneli; Tommiska, Johanna

2014-05-01

Congenital hypogonadotropic hypogonadism (HH), a rare disorder characterized by absent, partial, or delayed puberty, can be caused by the lack or deficient number of hypothalamic gonadotropin-releasing hormone (GnRH) neurons. SEMA3A was recently implicated in the etiology of the disorder, and Sema7A-deficient mice have a reduced number of GnRH neurons in their brains. SEMA3A and SEMA7A were screened by Sanger sequencing in altogether 50 Finnish HH patients (34 with Kallmann syndrome (KS; HH with hyposmia/anosmia) and 16 with normosmic HH (nHH)). In 20 patients, mutation(s) had already been found in genes known to be implicated in congenital HH. Three heterozygous variants (c.458A>G (p.Asn153Ser), c.1253A>G (p.Asn418Ser), and c.1303G>A (p.Val435Ile)) were found in SEMA3A in three KS patients, two of which also had a mutation in FGFR1. Two rare heterozygous variants (c.442C>T (p.Arg148Trp) and c.1421G>A (p.Arg474Gln)) in SEMA7A were found in one male nHH patient with a previously identified KISS1R nonsense variant and one male KS patient with a previously identified mutation in KAL1, respectively. Our results suggest that heterozygous missense variants in SEMA3A and SEMA7A may modify the phenotype of KS but most likely are not alone sufficient to cause the disorder.

Emerging medication for the treatment of male hypogonadism.

PubMed

Aydogdu, Aydogan; Swerdloff, Ronald S

2016-09-01

Male hypogonadism is characterized by inadequate production of Testosterone (T) (hypoandrogenism) and deficiencies in spermatogenesis. The main treatment of male hypogonadism is T replacement therapy (TRT), but for some of the patients, alternative drugs may be more suitable. The available literature of T and alternative treatments for male hypogonadism are discussed. Transdermal application of T gels are the most commonly used route of T administration. Some oral T formulations are either associated with hepatic toxicity (i.e. methyltestosterone) or short half-lives that require multiple doses per day (i.e. oral testosterone undecanoate). Short acting, injectable T formulations are also available. If the patient prefers not to use daily drugs or short acting injectable formulations, depot formulations such as injectable testosterone undecanoate (TU) may be a good alternative. If the patient has hypogonadotropic hypogonadism and desires fertility or if he is adolescent, instead of TRT, gonadotropins can be started to stimulate testicular growth and spermatogenesis. In obese patients or for the patients having high risks for TRT, off label aromatase inhibitors (AI) and clomiphene citrate (CC), may be considered to stimulate LH, FSH and T levels. In patients with high prostate disease risk, selective androgen receptor modulators may be an alternative treatment but these latter treatments have not had high level evidence.

A genetic basis for functional hypothalamic amenorrhea.

PubMed

Caronia, Lisa M; Martin, Cecilia; Welt, Corrine K; Sykiotis, Gerasimos P; Quinton, Richard; Thambundit, Apisadaporn; Avbelj, Magdalena; Dhruvakumar, Sadhana; Plummer, Lacey; Hughes, Virginia A; Seminara, Stephanie B; Boepple, Paul A; Sidis, Yisrael; Crowley, William F; Martin, Kathryn A; Hall, Janet E; Pitteloud, Nelly

2011-01-20

Functional hypothalamic amenorrhea is a reversible form of gonadotropin-releasing hormone (GnRH) deficiency commonly triggered by stressors such as excessive exercise, nutritional deficits, or psychological distress. Women vary in their susceptibility to inhibition of the reproductive axis by such stressors, but it is unknown whether this variability reflects a genetic predisposition to hypothalamic amenorrhea. We hypothesized that mutations in genes involved in idiopathic hypogonadotropic hypogonadism, a congenital form of GnRH deficiency, are associated with hypothalamic amenorrhea. We analyzed the coding sequence of genes associated with idiopathic hypogonadotropic hypogonadism in 55 women with hypothalamic amenorrhea and performed in vitro studies of the identified mutations. Six heterozygous mutations were identified in 7 of the 55 patients with hypothalamic amenorrhea: two variants in the fibroblast growth factor receptor 1 gene FGFR1 (G260E and R756H), two in the prokineticin receptor 2 gene PROKR2 (R85H and L173R), one in the GnRH receptor gene GNRHR (R262Q), and one in the Kallmann syndrome 1 sequence gene KAL1 (V371I). No mutations were found in a cohort of 422 controls with normal menstrual cycles. In vitro studies showed that FGFR1 G260E, FGFR1 R756H, and PROKR2 R85H are loss-of-function mutations, as has been previously shown for PROKR2 L173R and GNRHR R262Q. Rare variants in genes associated with idiopathic hypogonadotropic hypogonadism are found in women with hypothalamic amenorrhea, suggesting that these mutations may contribute to the variable susceptibility of women to the functional changes in GnRH secretion that characterize hypothalamic amenorrhea. Our observations provide evidence for the role of rare variants in common multifactorial disease. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT00494169.).

American Association of Clinical Endocrinologists Medical Guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients--2002 update.

PubMed

Petak, Steven M; Nankin, Howard R; Spark, Richard F; Swerdloff, Ronald S; Rodriguez-Rigau, Luis J

2002-01-01

In these clinical practice guidelines, specific recommendations are made for determining the most effective methods of diagnosing and treating hypogonadism in adult male patients. The target populations for these guidelines include the following: (1) men with primary testicular failure requiring testosterone replacement (hypergonadotropic hypogonadism); (2) male patients with gonadotropin deficiency or dysfunction who may have received testosterone replacement therapy or treatment for infertility (hypogonadotropic hypogonadism); and (3) aging men with symptoms relating to testosterone deficiency who could benefit from testosterone replacement therapy. Initial hormonal evaluation generally consists of a testosterone determination, in conjunction with a free testosterone or sex hormone-binding globulin level, inpatients with clear symptoms and signs but normal-range total testosterone, follicle-stimulating hormone, luteinizing hormone, and prolactin levels. Other possible tests include semen analysis, pituitary imaging studies, genetic studies, bone densitometry, testicular ultrasonography,testicular biopsy, and specialized hormonal dynamic testing. Therapeutic options generally consist of testosterone replacement by injections, patches, or topically applied gel in hypergonadotropic patients and in hypogonadotropic patients not interested in fertility. In hypogonadotropic patients interested in fertility, gonadal stimulation option scan be considered, including human chorionic gonadotropin stimulation therapy with or without human menopausal gonadotropin (or follicle-stimulating hormone) or gonadotropin-releasing hormone pump therapy. These therapies may be combined with assisted reproductive technologies such as in vitro fertilization with intracytoplasmic sperm injection, which may allow pregnancy to occur with very low numbers of sperm.

Oxidative stress status in congenital hypogonadism: an appraisal.

PubMed

Haymana, C; Aydoğdu, A; Soykut, B; Erdem, O; Ibrahimov, T; Dinc, M; Meric, C; Basaran, Y; Sonmez, A; Azal, O

2017-07-01

Patients with hypogonadism are at increased risk of cardiac and metabolic diseases. However, the pathogenesis of increased cardiometabolic risk in patients with hypogonadism is not clear. Oxidative stress plays an important role in the pathogenesis of cardiometabolic diseases. This study aimed to investigate possible differences in oxidative stress conditions between patients with hypogonadism and healthy controls. In this study, 38 male patients with congenital hypogonadotropic hypogonadism (CHH) (mean age: 21.7 ± 1.6 years) and 44 healthy male controls (mean age: 22.3 ± 1.4 years) with almost equal body mass index were enrolled. The demographic parameters, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total and free testosterone, homeostatic model assessment of insulin resistance (HOMA-IR) and oxidative stress parameters, such as superoxide dismutase, catalase (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA), were compared between both groups. Compared to the healthy controls, triglycerides (p = .02), insulin levels, HOMA-IR values, CAT activities and MDA levels (p < .001 for all) were significantly higher and HDL cholesterol (p = .04), total and free testosterone, FSH, LH levels and GPx activity were significantly lower (p < .001 for all) in patients with CHH. There were significant correlations between total testosterone levels and CAT activity (r = -.33 p = .01), GPx activity (r = .36 p = .007) and MDA (r = -.47 p < .001) levels. The results of this study showed that young and treatment-naïve patients with congenital hypogonadism had an increased status of oxidative stress.

Hypogonadotropic hypogonadism due to a novel missense mutation in the first extracellular loop of the neurokinin B receptor.

PubMed

Guran, Tulay; Tolhurst, Gwen; Bereket, Abdullah; Rocha, Nuno; Porter, Keith; Turan, Serap; Gribble, Fiona M; Kotan, L Damla; Akcay, Teoman; Atay, Zeynep; Canan, Husniye; Serin, Ayse; O'Rahilly, Stephen; Reimann, Frank; Semple, Robert K; Topaloglu, A Kemal

2009-10-01

The neurokinin B (NKB) receptor, encoded by TACR3, is widely expressed within the central nervous system, including hypothalamic nuclei involved in regulating GnRH release. We have recently reported two mutations in transmembrane segments of the receptor and a missense mutation in NKB in patients with normosmic isolated hypogonadotropic hypogonadism (nIHH). We sequenced the TACR3 gene in a family in which three siblings had nIHH. The novel mutant receptor thus identified was studied in a heterologous expression system using calcium flux as the functional readout. All affected siblings were homozygous for the His148Leu mutation, in the first extracellular loop of the NKB receptor. The His148Leu mutant receptor exhibited profoundly impaired signaling in response to NKB (EC(50) = 3 +/- 0.1 nm and >5 microm for wild-type and His148Leu, respectively). The location of the mutation in an extracellular part of the receptor led us also to test whether senktide, a synthetic NKB analog, may retain ability to stimulate the mutant receptor. However, the signaling activity of the His148Leu receptor in response to senktide was also severely impaired (EC(50) = 1 +/- 1 nm for wild-type and no significant response of His148Leu to 10 microm). Homozygosity for the TACR3 His148Leu mutation leads to failure of sexual maturation in humans, whereas signaling by the mutant receptor in vitro in response to either NKB or senktide is severely impaired. These observations further strengthen the link between NKB, the NKB receptor, and regulation of human reproductive function.

Congenital hypogonadotropic hypogonadism and Kallmann syndrome as models for studying hormonal regulation of human testicular endocrine functions.

PubMed

Trabado, Séverine; Lamothe, Sophie; Maione, Luigi; Bouvattier, Claire; Sarfati, Julie; Brailly-Tabard, Sylvie; Young, Jacques

2014-05-01

Men with Kallmann syndrome (KS) and those with congenital isolated hypogonadotropic hypogonadism with normal olfaction share a chronic, usually profound deficit, in FSH and LH, the two pituitary gonadotropins. Many studies indicate that this gonadotropin deficiency is already present during fetal life, thus explaining the micropenis, cryptorchidism and marked testicular hypotrophy already present at birth. In addition, neonatal activation of gonadotropin secretion is compromised in boys with severe CHH/Kallmann, preventing the first phase of postnatal testicular activation. Finally, CHH is characterized by the persistence, in the vast majority of cases, of gonadotropin deficiency at the time of puberty and during adulthood. This prevents the normal pubertal testicular reactivation required for physiological sex steroid and testicular peptide production, and for spermatogenesis. CHH/KS thus represents a pathological paradigm that can help to unravel, in vivo, the role of each gonadotropin in human testicular exocrine and endocrine functions at different stages of development. Recombinant gonadotropins with pure LH or FSH activity have been used to stimulate Leydig's cells and Sertoli's cells, respectively, and thereby to clarify their paracrine interaction in vivo. The effects of these pharmacological probes can be assessed by measuring the changes they provoke in circulating testicular hormone concentrations. This review discusses the impact of chronic gonadotropin deficiency on the endocrine functions of the interstitial compartment, which contains testosterone-, estradiol- and INSL3-secreting Leydig's cells. It also examines the regulation of inhibin B and anti-Mullerian hormone (AMH) secretion in the seminiferous tubules, and the insights provided by studies of human testicular stimulation with recombinant gonadotropins, used either individually or in combination. Copyright © 2014. Published by Elsevier Masson SAS.

Osteopenia and bone fractures in a man with anorexia nervosa and hypogonadism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rigotti, N.A.; Neer, R.M.; Jameson, L.

Women with anorexia nervosa have reduced skeletal mass. Both anorexia and osteopenia are less common in men. We describe a 22-year-old man with anorexia nervosa and severe osteopenia involving both cortical and trabecular bone who developed a pelvic fracture and multiple vertebral compression fractures. He was found to have secondary hypogonadotropic hypogonadism that was reversible with weight gain. This case illustrates the need to consider osteopenia as a potential complication of anorexia nervosa in males as well as females.

A Genetic Basis for Functional Hypothalamic Amenorrhea

PubMed Central

Caronia, Lisa M.; Martin, Cecilia; Welt, Corrine K.; Sykiotis, Gerasimos P.; Quinton, Richard; Thambundit, Apisadaporn; Avbelj, Magdalena; Dhruvakumar, Sadhana; Plummer, Lacey; Hughes, Virginia A.; Seminara, Stephanie B.; Boepple, Paul A.; Sidis, Yisrael; Crowley, William F.; Martin, Kathryn A.; Hall, Janet E.; Pitteloud, Nelly

2011-01-01

BACKGROUND Functional hypothalamic amenorrhea is a reversible form of gonadotropin-releasing hormone (GnRH) deficiency commonly triggered by stressors such as excessive exercise, nutritional deficits, or psychological distress. Women vary in their susceptibility to inhibition of the reproductive axis by such stressors, but it is unknown whether this variability reflects a genetic predisposition to hypothalamic amenorrhea. We hypothesized that mutations in genes involved in idiopathic hypogonadotropic hypogonadism, a congenital form of GnRH deficiency, are associated with hypothalamic amenorrhea. METHODS We analyzed the coding sequence of genes associated with idiopathic hypogonadotropic hypogonadism in 55 women with hypothalamic amenorrhea and performed in vitro studies of the identified mutations. RESULTS Six heterozygous mutations were identified in 7 of the 55 patients with hypothalamic amenorrhea: two variants in the fibroblast growth factor receptor 1 gene FGFR1 (G260E and R756H), two in the prokineticin receptor 2 gene PROKR2 (R85H and L173R), one in the GnRH receptor gene GNRHR (R262Q), and one in the Kall-mann syndrome 1 sequence gene KAL1 (V371I). No mutations were found in a cohort of 422 controls with normal menstrual cycles. In vitro studies showed that FGFR1 G260E, FGFR1 R756H, and PROKR2 R85H are loss-of-function mutations, as has been previously shown for PROKR2 L173R and GNRHR R262Q. CONCLUSIONS Rare variants in genes associated with idiopathic hypogonadotropic hypogonadism are found in women with hypothalamic amenorrhea, suggesting that these mutations may contribute to the variable susceptibility of women to the functional changes in GnRH secretion that characterize hypothalamic amenorrhea. Our observations provide evidence for the role of rare variants in common multifactorial disease. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT00494169.) PMID:21247312

Adding liraglutide to lifestyle changes, metformin and testosterone therapy boosts erectile function in diabetic obese men with overt hypogonadism.

PubMed

Giagulli, V A; Carbone, M D; Ramunni, M I; Licchelli, B; De Pergola, G; Sabbà, C; Guastamacchia, E; Triggiani, V

2015-11-01

The aim of this retrospective observational study was to evaluate whether adding liraglutide to lifestyle changes, metformin (Met) and testosterone replacement therapy (TRT), by means of improving weight and glycaemic control, could boost erectile function in type 2 diabetic obese men with overt hypogonadism and erectile dysfunction (ED) in a 'real-life setting'. Forty-three obese, diabetic and hypogonadal men (aged 45-59 years) were evaluated because of complaining about the recent onset of ED. They were subdivided into two groups according to whether hypogonadism occurred after puberty (G1; n = 30: 25 with dysfunctional hypogonadism and 5 with acquired hypogonadotropic hypogonadism) or before puberty (G2; n = 13: 10 with Klinefelter's syndrome and 3 with idiopathic hypogonadotropic hypogonadism). Both G1 and G2 patients were given a combination of testosterone (T) [testosterone undecanoate (TU) 1000 mg/every 12 weeks] and Met (2000-3000 mg/day) for 1 year. In the poor responders (N) to this therapy in terms of glycaemic target (G1N: n = 16; G2N: n = 10), liraglutide (L) (1.2 μg/day) was added for a second year, while the good responders (Y) to T + Met (G1Y: 14/30 and G2Y: 3/13) continued this two drugs regimen therapy for another year. All patients were asked to fill in the International Index of Erectile Function (IIEF 15) questionnaire before starting TU plus Met (T1) and after 12 months (T2) and 24 months (T3) of treatment. Patients underwent a clinical examination and a determination of serum sex hormone binding globulin (SHBG), total testosterone (T) and glycosylated haemoglobin (HbA1c) at T1, T2 and T3. At T2, each patient obtained an improvement of ED (p < 0.01) and of the metabolic parameters without reaching, however, the glycaemic goals [HbA1c = >7.5% (>58 mmol/mol)], while T turned out to be within the range of young men. L added to TU and Met regimen in G1N and G2N allowed these patients to reach not only the glycaemic target [HbA1c = <7.5% (<58 nmol

Congenital hypogonadotropic hypogonadism with split hand/foot malformation: a clinical entity with a high frequency of FGFR1 mutations

PubMed Central

Villanueva, Carine; Jacobson-Dickman, Elka; Xu, Cheng; Manouvrier, Sylvie; Dwyer, Andrew A.; Sykiotis, Gerasimos P.; Beenken, Andrew; Liu, Yang; Tommiska, Johanna; Hu, Youli; Tiosano, Dov; Gerard, Marion; Leger, Juliane; Drouin-Garraud, Valérie; Lefebvre, Hervé; Polak, Michel; Carel, Jean-Claude; Phan-Hug, Franziska; Hauschild, Michael; Plummer, Lacey; Rey, Jean-Pierre; Raivio, Taneli; Bouloux, Pierre; Sidis, Yisrael; Mohammadi, Moosa; de Roux, Nicolas; Pitteloud, Nelly

2014-01-01

Purpose Congenital hypogonadotropic hypogonadism (CHH) and split hand/foot malformation (SHFM) are two rare genetic conditions. Here we report a clinical entity comprising CHH and SHFM. Methods We identified patients with CHH and SHFM through international collaboration. Probands and available family members underwent phenotyping and screening for FGFR1 mutations. The impact of identified mutations was assessed by sequence- and structure-based predictions, and/or functional assays. Results We identified 8 probands with CHH with (n=3, Kallmann Syndrome) or without anosmia (n=5) and SHFM, 7 of whom (88%) harbor FGFR1 mutations: one individual is homozygous for p.V429E; six individuals are heterozygous for p.G348R, p.G485R, p.Q594*, p.E670A, p.V688L, and p.L712P. All mutations were predicted to be loss-of-function by in silico analysis. Probands with FGFR1 mutations have severe GnRH deficiency (absent puberty and/or cryptorchidism and/or micropenis). SHFM in both hands and feet was only observed in the patient with the homozygous p.V429E mutation; V429 maps to the FRS2α binding domain of FGFR1, and functional studies of the p.V429E mutation demonstrated that it decreased recruitment and phosphorylation of FRS2α to FG FR 1 , thereby resulting in reduced MAPK signaling. Conclusion FGFR1 should be prioritized for genetic testing in patients with CHH and SHFM, because the likelihood of a mutation increases from 10% in the general CHH population to 88%. PMID:25394172

Vitamin D deficiency in type 2 diabetic patients with hypogonadism.

PubMed

Bellastella, Giuseppe; Maiorino, Maria Ida; Olita, Laura; Capuano, Annalisa; Rafaniello, Concetta; Giugliano, Dario; Esposito, Katherine

2014-02-01

Both type 2 diabetes and secondary hypogonadism may be associated with low vitamin D levels. The aim of this study was to evaluate 25-hydroxyvitamin D (25(OH)D) concentrations in type 2 diabetic males with and without hypogonadism. We performed a case-control study among 122 male adults with type 2 diabetes, 51 with associated hypogonadism (Group 1) and 71 with normal gonadal function (Group 2). One hundred age-matched nondiabetic males with normal gonadal function served as a control group. Levels of 25(OH)D were assessed by a chemiluminescent immunoassay in all patients. Morning testosterone, pituitary, thyroid, parathyroid hormones, fasting glucose, and hemoglobin A1c were also evaluated. The overall diabetic population showed a mean 25(OH)D concentration (22.3 ± 6.09 ng/mL) significantly lower than the control group (34.3 ± 7.2, P < 0.001), with 81% of diabetic patients presenting 25(OH)D deficiency (<20 ng/mL) or insufficiency (20-29.9 ng/mL). The lowest 25(OH)D concentration was found in Group 1 (20.1 ± 6.58 ng/mL). Concentration of 25(OH)D was significantly lower in the 42 patients with hypogonadotropic hypogonadism as compared with the 9 patients with hypergonadotropic hypogonadism (19.4 ± 7.06 vs. 23.8 ± 6.11 ng/mL, P < 0.001). No difference in erectile dysfunction (ED) prevalence between Group 1 and Group 2 was found, nor was there a correlation between the severity of ED and vitamin D levels (r = -0.10, P = 0.39). These results show that type 2 diabetic patients with hypogonadism present lower 25(OH)D concentration and higher prevalence of vitamin D deficiency, compared with patients without hypogonadism. The finding that 25(OH)D concentrations were similar between type 2 diabetic patients with hypergonadotropic hypogonadism and those with normal gonadal function deserves further study. © 2013 International Society for Sexual Medicine.

Uterine Development After Estrogen Replacement Therapy in Women with Different Etiologies of Primary Hypogonadism.

PubMed

Kim, Hyo Jeong; Lee, Dong-Yun; Yoon, Byung-Koo; Choi, DooSeok

2016-08-01

To evaluate uterine development with estrogen replacement therapy in patients with primary amenorrhea due to hypogonadism. Retrospective study. Thirty-five women. Women who were younger than 20 years of age and who had primary amenorrhea and an immaturely shaped uterus were included. Changes in uterine cross-sectional area (UXA) and uterine maturity in pelvic ultrasound after 2 year of estrogen replacement therapy were assessed on the basis of the etiology of primary hypogonadism. Patients were classified into three groups according to the etiology of primary hypogonadism: Turner syndrome (n = 19), hypogonadotropic hypogonadism after brain surgery (n = 10), and premature ovarian insufficiency after cancer treatment (n = 6). Overall, the mean UXA significantly increased (from 3.1 ± 1.8 to 11.6 ± 4.9 cm(2)) after estrogen replacement therapy (P < .001), but the final UXA was significantly smaller in patients with premature ovarian insufficiency compared with other etiologies. In logistic regression analysis, etiology and the cumulative dose of estrogen were associated with uterine maturation (P = .011 and .004, respectively). Estrogen replacement therapy induced growth of the uterus in patients with primary hypogonadism. However, the response to estrogen replacement therapy varied on the basis of the total cumulative dose of estrogen and etiology of primary hypogonadism. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Efficacy and Outcome Predictors of Gonadotropin Treatment for Male Congenital Hypogonadotropic Hypogonadism: A Retrospective Study of 223 Patients.

PubMed

Liu, Zhaoxiang; Mao, Jangfeng; Wu, Xueyan; Xu, Hongli; Wang, Xi; Huang, Bingkun; Zheng, Junjie; Nie, Min; Zhang, Hongbing

2016-03-01

Gonadotropin induces masculinization and spermatogenesis in men with congenital hypogonadotropic hypogonadism (CHH). However, large cohort studies for the efficacy and reliable predictors of this therapy need to be conducted. The aim of this study was to investigate the efficacy of gonadotropin treatment in a large cohort of male CHH patients and analyze putative predictors for successful spermatogenesis. This retrospective study included 223 CHH azoospermic patients without puberty development treated between 2005 and 2014. All patients received combined human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) and were followed up for >6 months (5109 person-months). Serum total testosterone level, testicular size, spermatogenesis, and pregnancy outcome were recorded at each visit. After gonadotropin therapy, testicular size was enlarged from 2.1 ± 1.6 to 8.1 ± 4.6 mL (P < 0.001) and serum total testosterone was elevated from 0.9 ± 0.5 to 15.1 ± 8.2 nmol/L (P < 0.001). Spermatogenesis (>0/mL) occurred at a median period of 15 months (95% confidence interval 13.5-16.5). Larger basal testicular volume (P = 0.012) and noncryptorchidism history (P = 0.028) are independent predictors for earlier sperm appearance. Sixty four percent (143/223) of patients succeeded in producing sperms and the average time for initial sperm detection was 14 ± 8 months. However, their sperm concentrations (11.7 [2.1, 24.4] million/mL) and sperm progressive motility (A + B 36.9% ± 20.2%) are significantly lower than World Health Organization standards. Of the 34 patients who desired for fathering children, 19 patients impregnanted their partners during the treatment. Gonadotropin therapy induces spermatogenesis in male CHH patients. A larger basal testicular size and noncryptorchidism history are favorable indicators for earlier spermatogenesis.

Congenital hypogonadotropic hypogonadism with split hand/foot malformation: a clinical entity with a high frequency of FGFR1 mutations.

PubMed

Villanueva, Carine; Jacobson-Dickman, Elka; Xu, Cheng; Manouvrier, Sylvie; Dwyer, Andrew A; Sykiotis, Gerasimos P; Beenken, Andrew; Liu, Yang; Tommiska, Johanna; Hu, Youli; Tiosano, Dov; Gerard, Marion; Leger, Juliane; Drouin-Garraud, Valérie; Lefebvre, Hervé; Polak, Michel; Carel, Jean-Claude; Phan-Hug, Franziska; Hauschild, Michael; Plummer, Lacey; Rey, Jean-Pierre; Raivio, Taneli; Bouloux, Pierre; Sidis, Yisrael; Mohammadi, Moosa; de Roux, Nicolas; Pitteloud, Nelly

2015-08-01

Congenital hypogonadotropic hypogonadism (CHH) and split hand/foot malformation (SHFM) are two rare genetic conditions. Here we report a clinical entity comprising the two. We identified patients with CHH and SHFM through international collaboration. Probands and available family members underwent phenotyping and screening for FGFR1 mutations. The impact of identified mutations was assessed by sequence- and structure-based predictions and/or functional assays. We identified eight probands with CHH with (n = 3; Kallmann syndrome) or without anosmia (n = 5) and SHFM, seven of whom (88%) harbor FGFR1 mutations. Of these seven, one individual is homozygous for p.V429E and six individuals are heterozygous for p.G348R, p.G485R, p.Q594*, p.E670A, p.V688L, or p.L712P. All mutations were predicted by in silico analysis to cause loss of function. Probands with FGFR1 mutations have severe gonadotropin-releasing hormone deficiency (absent puberty and/or cryptorchidism and/or micropenis). SHFM in both hands and feet was observed only in the patient with the homozygous p.V429E mutation; V429 maps to the fibroblast growth factor receptor substrate 2α binding domain of FGFR1, and functional studies of the p.V429E mutation demonstrated that it decreased recruitment and phosphorylation of fibroblast growth factor receptor substrate 2α to FGFR1, thereby resulting in reduced mitogen-activated protein kinase signaling. FGFR1 should be prioritized for genetic testing in patients with CHH and SHFM because the likelihood of a mutation increases from 10% in the general CHH population to 88% in these patients.

Occurrence, patterns & predictors of hypogonadism in patients with HIV infection in India.

PubMed

Dutta, Deep; Sharma, Lokesh Kumar; Sharma, Neera; Gadpayle, Adesh K; Anand, Atul; Gaurav, Kumar; Gupta, Ankit; Poondla, Yashwanth; Kulshreshtha, Bindu

2017-06-01

Data on hypogonadism among human immunodeficiency virus (HIV)-infected Indians are not available. This study was aimed to evaluate the occurrence, pattern and predictors of hypogonadism in HIV-infected Indians. Consecutive stable HIV-infected patients, 18-70 yr age, without any severe comorbid state, having at least one year follow up data at the antiretroviral therapy clinic, underwent clinical assessment and hormone assays. From initially screened 527 patients, 359 patients (225 males; 134 females), having disease duration of 61.44±39.42 months, 88.58 per cent on highly active antiretroviral therapy (HAART), 40.67 per cent having tuberculosis history and 89.69 per cent with vitamin D insufficiency were analyzed. Testosterone <300 ng/dl was documented in 39.11 per cent males. Primary, hypogonadotropic hypogonadism (HypoH) and compensated hypogonadism were observed in 7.56, 31.56 and 12.44 per cent males, respectively. Males with hypogonadism were significantly older (P=0.009), and had higher opportunistic infections (P<0.001) with longer disease duration (P=0.05). Menstrual abnormalities were observed in 40.3 per cent females, who were significantly older (P<0.001), had lower CD4 count (P=0.038) and higher tuberculosis history (P=0.005). Nearly 46.3, 16.2 and 13 per cent women with menstrual abnormalities were in peri-/post-menopausal state, premature ovarian insufficiency (POI) and HypoH, respectively. Age, CD4 count at diagnosis and 25(OH)D were best predictors of male hypogonadism. Age and CD4 count increment in first 6-12 months following HAART were the best predictors of POI. Hypogonadism was observed to be a significant problem in HIV-infected men and women in India, affecting 39 and 29 per cent patients, respectively. HypoH was the most common form in males whereas ovarian failure being the most common cause in females.

Effects of two-year testosterone replacement therapy on cognition, emotions and quality of life in young and middle-aged hypogonadal men.

PubMed

Lašaitė, L; Čeponis, J; Preikša, R T; Žilaitienė, B

2017-04-01

The aim of the study was to examine the effects of two-year testosterone replacement therapy on cognitive functioning, emotional state and quality of life in young and middle-aged men with hypogonadotropic hypogonadism. Nineteen males diagnosed with hypogonadotropic hypogonadism participated in the study. Cognitive functions were assessed by Trail Making Test and Digit Span Test of Wechsler Adult Intelligence Scale. Emotional state was evaluated by Profile of Mood States. Quality of life was evaluated by WHO Brief Quality of Life Questionnaire. Changes after two-year testosterone replacement therapy were detected in Trail Making A (42.9 ± 22.3 vs. 36.2 ± 22.5, p = .050) and B (90.6 ± 55.3 vs. 65.6 ± 21.4, p = .025) tests, showing improvement in attention and visual scanning abilities, executive function and psychomotor speed, as well as in Digit Span Test forward score (5.4 ± 2.0 vs. 6.1 ± 2.6, p = .046), showing improvement in attention capacity and psychomotor speed. No significant differences were observed in emotional state and quality of life. In conclusion, beneficial effect in cognitive functioning (improved attention and visual scanning ability, executive function and psychomotor speed), but not in emotional state and quality of life, was observed in young and middle-aged hypogonadal men after two-year testosterone replacement therapy. © 2016 Blackwell Verlag GmbH.

Transition in Pediatric and Adolescent Hypogonadal Girls: Gynecological Aspects, Estrogen Replacement Therapy, and Contraception.

PubMed

Tønnes Pedersen, Anette; Cleemann, Line; Main, Katharina M; Juul, Anders

2018-01-01

Hypogonadism may be suspected if puberty is delayed. Pubertal delay may be caused by a normal physiological variant, by primary ovarian insufficiency (Turner syndrome), or reflect congenital hypogonadotropic hypogonadism (HH; genetic) or acquired HH (brain lesions). Any underlying chronic disease like inflammatory bowel disease, celiac disease, malnutrition (anorexia or orthorexia), or excessive physical activity may also result in functional HH. Thus, girls with delayed puberty should be evaluated for an underlying pathology before any treatment, including oral contraception, is initiated. Estrogen replacement is important and natural 17β-estradiol, preferably transdermally, is the preferred choice, whereas the oral route can be used as an alternative depending on patient preference and compliance. Sexual activity is often delayed in the hypogonadal adolescent girl. In the adolescent hypogonadal girl, hormone replacement therapy (HRT) most likely has been initiated at the time she becomes sexually active. If a risk of unwanted pregnancy cannot be ruled out, there is a need to consider contraception. This consideration does not contradict the principles of HRT but can be included as a part of the substitution, e.g. oral contraceptives containing 17β-estradiol or a progestogen intrauterine device combined with continuous 17β-estradiol (transdermal or oral). © 2018 S. Karger AG, Basel.

4H Syndrome

MedlinePlus

... syndrome? 4H syndrome is short for hypomyelination, hypogonadotropic hypogonadism and hypodontia. Hypomyelination means that there is lack ... myelin in the central nervous system. In hypogonadotropic hypogonadism, normal puberty development is absent because the central ...

Male hypogonadism at a tertiary care hospital in Karachi, Pakistan.

PubMed

Ram, Nanik; Asghar, Ali; Hashmi, Fauzan; Islam, Najmul

2012-01-01

Male hypogonadism is defined as 'inadequate gonadal function, manifested by deficiency in gametogenesis and/or secretion of gonadal hormones'. Signs and symptoms of hypogonadism depend primarily on the age of onset. It can be classified according to the site primarily involved: the gonads, the hypothalamus, or the pituitary gland. The objective this study was to determine the presentation and aetiology of male hypogonadism seen in a tertiary care hospital. This cross-sectional study was conducted at Endocrine Clinics, Aga Khan University Hospital Karachi. Data of male patients with hypogonadism who attended clinics during January 2009 to August 2011 were reviewed. All male patients with clinical and biochemical evidence of hypogonadism were included in the study. Patients with Diabetes Mellitus, Metabolic Syndrome, Andropause, AIDS, Chronic Renal Failure, and Cirrhosis were excluded. Mean +/- SD were computed for quantitative variables. Frequency and percentages were computed for qualitative variables. Aetiology of male hypogonadism was categorised as primary and secondary hypogonadism. A total of 85 patients with male hypogonadism attended the endocrine clinic. Mean age of patients was 25 +/- 10 years. Clinical presentations were small genitalia (65%), absent secondary sexual characteristics (53%), not attained puberty (47%), infertility (53%), erectile dysfunction (41%) and loss of libido (29%). Seventy-three (86%) patients had hypogonadotrophic hypogonadism (secondary hypogonadism) and 12 (14%) patients had hypergonadotrophic hypogonadism (primary hypogonadism). Among the patients with hypogonadotrophic hypogonadism 38 had idiopathic hypogonadotrophic hypogonadsim, 7 had pituitary adenoma, 6 had empty sella syndrome, 3 had Kallman's syndrome, and 1 patient had haemosiderosis due to thalassaemia major; 18 patients did not undergo brain imaging. Small genitalia, absent secondary sexual characteristics and infertility were the main presenting features of hypogonad

Insulin Resistance and Inflammation in Hypogonadotropic Hypogonadism and Their Reduction After Testosterone Replacement in Men With Type 2 Diabetes

PubMed Central

Dhindsa, Sandeep; Ghanim, Husam; Batra, Manav; Kuhadiya, Nitesh D.; Abuaysheh, Sanaa; Sandhu, Sartaj; Green, Kelly; Makdissi, Antoine; Hejna, Jeanne; Chaudhuri, Ajay; Punyanitya, Mark

2016-01-01

OBJECTIVE One-third of men with type 2 diabetes have hypogonadotropic hypogonadism (HH). We conducted a randomized placebo-controlled trial to evaluate the effect of testosterone replacement on insulin resistance in men with type 2 diabetes and HH. RESEARCH DESIGN AND METHODS A total of 94 men with type 2 diabetes were recruited into the study; 50 men were eugonadal, while 44 men had HH. Insulin sensitivity was calculated from the glucose infusion rate (GIR) during hyperinsulinemic-euglycemic clamp. Lean body mass and fat mass were measured by DEXA and MRI. Subcutaneous fat samples were taken to assess insulin signaling genes. Men with HH were randomized to receive intramuscular testosterone (250 mg) or placebo (1 mL saline) every 2 weeks for 24 weeks. RESULTS Men with HH had higher subcutaneous and visceral fat mass than eugonadal men. GIR was 36% lower in men with HH. GIR increased by 32% after 24 weeks of testosterone therapy but did not change after placebo (P = 0.03 for comparison). There was a decrease in subcutaneous fat mass (−3.3 kg) and increase in lean mass (3.4 kg) after testosterone treatment (P < 0.01) compared with placebo. Visceral and hepatic fat did not change. The expression of insulin signaling genes (IR-β, IRS-1, AKT-2, and GLUT4) in adipose tissue was significantly lower in men with HH and was upregulated after testosterone treatment. Testosterone treatment also caused a significant fall in circulating concentrations of free fatty acids, C-reactive protein, interleukin-1β, tumor necrosis factor-α, and leptin (P < 0.05 for all). CONCLUSIONS Testosterone treatment in men with type 2 diabetes and HH increases insulin sensitivity, increases lean mass, and decreases subcutaneous fat. PMID:26622051

Genetics Home Reference: Gordon Holmes syndrome

MedlinePlus

... production of hormones that direct sexual development (hypogonadotropic hypogonadism). Many affected individuals have a delay in development ... a lack of RNF216 protein function causes hypogonadotropic hypogonadism or cerebellar ataxia. The PNPLA6 gene provides instructions ...

Occurrence, patterns & predictors of hypogonadism in patients with HIV infection in India

PubMed Central

Dutta, Deep; Sharma, Lokesh Kumar; Sharma, Neera; Gadpayle, Adesh K; Anand, Atul; Gaurav, Kumar; Gupta, Ankit; Poondla, Yashwanth; Kulshreshtha, Bindu

2017-01-01

Background & objectives: Data on hypogonadism among human immunodeficiency virus (HIV)-infected Indians are not available. This study was aimed to evaluate the occurrence, pattern and predictors of hypogonadism in HIV-infected Indians. Methods: Consecutive stable HIV-infected patients, 18-70 yr age, without any severe comorbid state, having at least one year follow up data at the antiretroviral therapy clinic, underwent clinical assessment and hormone assays. Results: From initially screened 527 patients, 359 patients (225 males; 134 females), having disease duration of 61.44±39.42 months, 88.58 per cent on highly active antiretroviral therapy (HAART), 40.67 per cent having tuberculosis history and 89.69 per cent with vitamin D insufficiency were analyzed. Testosterone <300 ng/dl was documented in 39.11 per cent males. Primary, hypogonadotropic hypogonadism (HypoH) and compensated hypogonadism were observed in 7.56, 31.56 and 12.44 per cent males, respectively. Males with hypogonadism were significantly older (P=0.009), and had higher opportunistic infections (P<0.001) with longer disease duration (P=0.05). Menstrual abnormalities were observed in 40.3 per cent females, who were significantly older (P<0.001), had lower CD4 count (P=0.038) and higher tuberculosis history (P=0.005). Nearly 46.3, 16.2 and 13 per cent women with menstrual abnormalities were in peri-/post-menopausal state, premature ovarian insufficiency (POI) and HypoH, respectively. Age, CD4 count at diagnosis and 25(OH)D were best predictors of male hypogonadism. Age and CD4 count increment in first 6-12 months following HAART were the best predictors of POI. Interpretation & conclusions: Hypogonadism was observed to be a significant problem in HIV-infected men and women in India, affecting 39 and 29 per cent patients, respectively. HypoH was the most common form in males whereas ovarian failure being the most common cause in females. PMID:29067983

Treatment of hypogonadotropic male hypogonadism: Case-based scenarios

PubMed Central

Crosnoe-Shipley, Lindsey E; Elkelany, Osama O; Rahnema, Cyrus D; Kim, Edward D

2015-01-01

The aim of this study is to review four case-based scenarios regarding the treatment of symptomatic hypogonadism in men. The article is designed as a review of published literature. We conducted a PubMed literature search for the time period of 1989-2014, concentrating on 26 studies investigating the efficacy of various therapeutic options on semen analysis, pregnancy outcomes, time to recovery of spermatogenesis, as well as serum and intratesticular testosterone levels. Our results demonstrated that exogenous testosterone suppresses intratesticular testosterone production, which is an absolute prerequisite for normal spermatogenesis. Cessation of exogenous testosterone should be recommended for men desiring to maintain their fertility. Therapies that protect the testis involve human chorionic gonadotropin (hCG) therapy or selective estrogen receptor modulators (SERMs), but may also include low dose hCG with exogenous testosterone. Off-label use of SERMs, such as clomiphene citrate, are effective for maintaining testosterone production long-term and offer the convenience of representing a safe, oral therapy. At present, routine use of aromatase inhibitors is not recommended based on a lack of long-term data. We concluded that exogenous testosterone supplementation decreases sperm production. It was determined that clomiphene citrate is a safe and effective therapy for men who desire to maintain fertility. Although less frequently used in the general population, hCG therapy with or without testosterone supplementation represents an alternative treatment. PMID:25949938

Congenital hypogonadotropic hypogonadism: implications of absent mini-puberty.

PubMed

Dwyer, Andrew A; Jayasena, Channa N; Quinton, Richard

2016-06-01

The phenomenon known as "mini-puberty" refers to activation of the neonatal hypothalamo-pituitary axis causing serum concentrations of gonadotrophins and testosterone (T) to approach adult male levels. This early neonatal period is a key proliferative window for testicular germ cells and immature Sertoli cells. Although failure to spontaneously initiate (adolescent) puberty is the most evident consequence of a defective gonadotropin-releasing hormone (GnRH) neurosecretory network, absent mini-puberty is also likely to have a major impact on the reproductive phenotype of men with congenital hypogonadotrophic hypogonadism (CHH). Furthermore, the phase of male mini-puberty represents a key window-of-opportunity to identify congenital GnRH deficiency (either isolated CHH, or as part of combined pituitary hormone deficiency) in childhood. Among male neonates exhibiting "red flag" indicators for CHH (i.e. maldescended testes with or without cryptorchidism) a single serum sample (between 4-8 weeks of life) can pinpoint congenital GnRH deficiency far more rapidly and with much greater accuracy than dynamic tests performed in later childhood or adolescence. Potential consequences for missing absent mini-puberty in a male neonate include the lack of monitoring of pubertal progression/lack of progression, and the missed opportunity for early therapeutic intervention. This article will review our current understanding of the mechanisms and clinical consequences of mini-puberty. Furthermore, evidence for the optimal clinical management of patients with absent mini-puberty will be discussed.

GENETICS IN ENDOCRINOLOGY: Genetic counseling for congenital hypogonadotropic hypogonadism and Kallmann syndrome: new challenges in the era of oligogenism and next-generation sequencing.

PubMed

Maione, Luigi; Dwyer, Andrew A; Francou, Bruno; Guiochon-Mantel, Anne; Binart, Nadine; Bouligand, Jérôme; Young, Jacques

2018-03-01

Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are rare, related diseases that prevent normal pubertal development and cause infertility in affected men and women. However, the infertility carries a good prognosis as increasing numbers of patients with CHH/KS are now able to have children through medically assisted procreation. These are genetic diseases that can be transmitted to patients' offspring. Importantly, patients and their families should be informed of this risk and given genetic counseling. CHH and KS are phenotypically and genetically heterogeneous diseases in which the risk of transmission largely depends on the gene(s) responsible(s). Inheritance may be classically Mendelian yet more complex; oligogenic modes of transmission have also been described. The prevalence of oligogenicity has risen dramatically since the advent of massively parallel next-generation sequencing (NGS) in which tens, hundreds or thousands of genes are sequenced at the same time. NGS is medically and economically more efficient and more rapid than traditional Sanger sequencing and is increasingly being used in medical practice. Thus, it seems plausible that oligogenic forms of CHH/KS will be increasingly identified making genetic counseling even more complex. In this context, the main challenge will be to differentiate true oligogenism from situations when several rare variants that do not have a clear phenotypic effect are identified by chance. This review aims to summarize the genetics of CHH/KS and to discuss the challenges of oligogenic transmission and also its role in incomplete penetrance and variable expressivity in a perspective of genetic counseling. © 2018 European Society of Endocrinology.

Endocrine Society of Australia position statement on male hypogonadism (part 1): assessment and indications for testosterone therapy.

PubMed

Yeap, Bu B; Grossmann, Mathis; McLachlan, Robert I; Handelsman, David J; Wittert, Gary A; Conway, Ann J; Stuckey, Bronwyn Ga; Lording, Douglas W; Allan, Carolyn A; Zajac, Jeffrey D; Burger, Henry G

2016-08-15

This article, Part 1 of the Endocrine Society of Australia's position statement on male hypogonadism, focuses on assessment of male hypogonadism, including the indications for testosterone therapy. (Part 2 will deal with treatment and therapeutic considerations.) Key points and recommendations are:Pathological hypogonadism arises due to diseases of the hypothalamus or pituitary gland (hypogonadotropic hypogonadism) or testes (hypergonadotropic hypogonadism). It is a clinical diagnosis with a pathological basis, confirmed by hormone assays.Hormonal assessment is based on measurement of circulating testosterone, luteinising hormone (LH) and follicle-stimulating hormone (FSH) concentrations. Measurement of sex hormone-binding globulin levels can be informative, but use of calculated free testosterone is not recommended for clinical decision making.Testosterone replacement therapy is warranted in men with pathological hypogonadism, regardless of age.Currently, there are limited data from high-quality randomised controlled trials with clinically meaningful outcomes to justify testosterone treatment in older men, usually with chronic disease, who have low circulating testosterone levels but without hypothalamic, pituitary or testicular disease.Obesity, metabolic syndrome and type 2 diabetes are associated with lowering of circulating testosterone level, but without elevation of LH and FSH levels. Whether these are non-specific consequences of non-reproductive disorders or a correctable deficiency state is unknown, but clear evidence for efficacy and safety of testosterone therapy in this setting is lacking.Glucocorticoid and opioid use is associated with possibly reversible reductions in circulating testosterone level, without elevation of LH and FSH levels. Where continuation of glucocorticoid or opioid therapy is necessary, review by an endocrinologist may be warranted.Changes in management as result of the position statement: Men with pathological hypogonadism should

Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 Are Identified in Individuals with Congenital Hypogonadotropic Hypogonadism

PubMed Central

Miraoui, Hichem; Dwyer, Andrew A.; Sykiotis, Gerasimos P.; Plummer, Lacey; Chung, Wilson; Feng, Bihua; Beenken, Andrew; Clarke, Jeff; Pers, Tune H.; Dworzynski, Piotr; Keefe, Kimberley; Niedziela, Marek; Raivio, Taneli; Crowley, William F.; Seminara, Stephanie B.; Quinton, Richard; Hughes, Virginia A.; Kumanov, Philip; Young, Jacques; Yialamas, Maria A.; Hall, Janet E.; Van Vliet, Guy; Chanoine, Jean-Pierre; Rubenstein, John; Mohammadi, Moosa; Tsai, Pei-San; Sidis, Yisrael; Lage, Kasper; Pitteloud, Nelly

2013-01-01

Congenital hypogonadotropic hypogonadism (CHH) and its anosmia-associated form (Kallmann syndrome [KS]) are genetically heterogeneous. Among the >15 genes implicated in these conditions, mutations in FGF8 and FGFR1 account for ∼12% of cases; notably, KAL1 and HS6ST1 are also involved in FGFR1 signaling and can be mutated in CHH. We therefore hypothesized that mutations in genes encoding a broader range of modulators of the FGFR1 pathway might contribute to the genetics of CHH as causal or modifier mutations. Thus, we aimed to (1) investigate whether CHH individuals harbor mutations in members of the so-called “FGF8 synexpression” group and (2) validate the ability of a bioinformatics algorithm on the basis of protein-protein interactome data (interactome-based affiliation scoring [IBAS]) to identify high-quality candidate genes. On the basis of sequence homology, expression, and structural and functional data, seven genes were selected and sequenced in 386 unrelated CHH individuals and 155 controls. Except for FGF18 and SPRY2, all other genes were found to be mutated in CHH individuals: FGF17 (n = 3 individuals), IL17RD (n = 8), DUSP6 (n = 5), SPRY4 (n = 14), and FLRT3 (n = 3). Independently, IBAS predicted FGF17 and IL17RD as the two top candidates in the entire proteome on the basis of a statistical test of their protein-protein interaction patterns to proteins known to be altered in CHH. Most of the FGF17 and IL17RD mutations altered protein function in vitro. IL17RD mutations were found only in KS individuals and were strongly linked to hearing loss (6/8 individuals). Mutations in genes encoding components of the FGF pathway are associated with complex modes of CHH inheritance and act primarily as contributors to an oligogenic genetic architecture underlying CHH. PMID:23643382

[The application of gonadotropin in treatment of male central hypogonadism].

PubMed

Di, Fu-song; Cui, Yu-gui; Jia, Yue

2005-11-01

To observe the efficacy of human chorionic gonadotrophin (hCG) and hCG plus human menopausal gonadotropin (HMG) for central hypogonadism in male patients. 64 men with central hypogonadism were recruited in this study, including 19 patients with Kallmann syndrome, 41 patients with idiopathic hypogonadotrophic hypogonadism (IHH) and 4 patients with hypogonadism after brain surgery. 33 patients were treated with hCG 1500 IU intramuscularly twice a week, whereas 31 patients were treated with intramuscular hCG 1500 IU plus HMG 75 IU twice a week, for at least 6 months. After treatment, all patients felt stronger physically and 42/64 patients developed beard, pubes or armpit hair. The testis volume enlarged significantly [(3.08 +/- 2.44) ml vs (8.92 +/- 5.37) ml, P < 0.001], and serum follicle-stimulating hormone, luteinizing hormone and testosterone concentrations were higher significantly than those before treatment (P < 0.05). 6/64 patients underwent spermatorrhea and 2 patient were found to have spermatogenesis. If judged by the testis volume, 52 patients (81.2%) were effective and 12 patients were ineffective. For male patients with the central hypogonadism, hCG and hCG plus HMG can promote the pubertal development and maturation of second sex characteristics, as well as enhance the physical strength; in some patients both androgen production and spermatogenesis can be achieved.

Hypogonadotropic hypogonadism

MedlinePlus

... lack of sex hormones. This prevents normal sexual maturity in children and normal function of the testicles ... self-esteem due to late start of puberty (emotional support may be helpful) Sexual problems, such as ...

[Ovulation induction by pulsatile GnRH therapy in 2014: literature review and synthesis of current practice].

PubMed

Gronier, H; Peigné, M; Catteau-Jonard, S; Dewailly, D; Robin, G

2014-10-01

The hypogonadotropic hypogonadism is an easily treatable form of female infertility. The most common cause of hypogonadotropic hypogonadism is functional hypothalamic amenorrhea. The GnRH pump is a simple and effective treatment to restore fertility of patients with hypothalamic amenorrhea: cumulative pregnancy rate is estimated between 70 and 100% after 6 cycles, compared to a low rate of complications and multiple pregnancies. While only 2.8 cycles are on average required to achieve a pregnancy with a pump, this induction of ovulation stays underused in France. The objective of this paper is to propose a practical manual of pulsatile GnRH, in order to improve the accessibility of pulsatile GnRH for patients with hypogonadotropic hypogonadism. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

[Central hypomyelination, hypogonadotrophic hypogonadism and hypodontia: a new leukodystrophy].

PubMed

Vázquez-López, M; Ruiz-Martín, Y; de Castro-Castro, P; Garzo-Fernández, C; Martín-del Valle, F; Márquez-de la Plata, L

To report one patient with slowly progressive encephalopathy, ataxia, central hypomyelination, hypodontia and hypogonadotropic hypogonadism, the 4H syndrome. This clinical picture has been described recently and there are only four patients reported previously. A girl with a previously normal early psychomotor development, presented a slowly progressive deterioration since 15 months of age. Now, she is 14 years old, and has a severe cerebellar ataxia, with tremor and dysmetria. She can't neither walk nor remain standing alone. She has lost the sphincter control and has an immature expressive language. She has no puberal development and definitive hypodontia of upper central incisors. The brain magnetic resonance imaging shows a diffuse hypomyelination, that is confirmed with diffusion and spectroscopy studies. The hypomyelinating leukoencephalopathies are disorders with abnormally low amount of myelin. The diagnosis is difficult in most of the patients. The hypomyelinating leukoencephalopathies include classic disorders and new leukoencephalopathies, described in the past few years.

Multiple forms of hypogonadism of central, peripheral or combined origin in males with Prader-Willi syndrome.

PubMed

Radicioni, A F; Di Giorgio, G; Grugni, G; Cuttini, M; Losacco, V; Anzuini, A; Spera, S; Marzano, C; Lenzi, A; Cappa, M; Crinò, A

2012-01-01

Hypogonadism in Prader-Willi syndrome (PWS) is generally attributed to hypothalamic dysfunction or to primary gonadal defect, but pathophysiology is still unclear. To investigate the aetiology of hypothalamic-pituitary-gonadal axis dysfunction in PWS males. Clinical examination and blood sampling for luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, inhibin B and sexhormone-binding globulin (SHBG) were performed in 34 PWS patients, age 5·1-42·7 years, and in 125 healthy males of same age range. All participants were divided into two groups : < or ≥13·5 years. Pubertal PWS patients showed an arrest of pubertal development. Patients <13·5 years had normal LH, FSH, testosterone and 7/10 had low inhibin B. Among those ≥13·5 years, 8/24 patients had normal LH and testosterone, high FSH and low inhibin B. 5/24 had low FSH, LH, testosterone and inhibin B; one showed normal LH and FSH despite low testosterone and inhibin B; 4/24 had low testosterone and LH but normal FSH despite low inhibin B; 6/24 showed high FSH, low inhibin B and normal LH despite low testosterone. Compared with controls, patients <13·5 years had lower LH, inhibin B, similar FSH, testosterone, SHBG levels and testicular volume; those ≥13·5 years had smaller testicular volume, near-significantly lower LH, testosterone, SHBG, inhibin B and higher FSH. PWS patients display heterogeneity of hypogonadism: (i) hypogonadotropic hypogonadism of central origin for LH and/or FSH; (ii) early primary testicular dysfunction (Sertoli cells damage); and (iii) a combined hypogonadism (testicular origin for FSH-inhibin B axis and central origin for LH-T axis). © 2011 Blackwell Publishing Ltd.

Is late-onset hypogonadotropic hypogonadism a specific age-dependent disease, or merely an epiphenomenon caused by accumulating disease-burden?

PubMed

Corona, Giovanni; Maseroli, Elisa; Rastrelli, Giulia; Francomano, Davide; Aversa, Antonio; Hackett, Geoffrey I; Ferri, Simona; Sforza, Alessandra; Maggi, Mario

2016-06-01

The aim of this paper is to summarize the available evidence supporting the link between late onset hypogonadism (LOH) and associated common clinical illnesses, focusing on metabolic diseases. The possible benefits or risks related to testosterone replacement therapy (TRT) in these conditions will also be analyzed. An extensive Medline search was performed. LOH is closely associated with a worse metabolic profile and a higher cardiovascular risk. The relationship between hypogonadism obesity and insulin resistance is complex and bidirectional. Emerging evidence suggests a positive role of TRT in improving body composition and metabolic outcomes in subjects with LOH. Despite the aforementioned data, it is not completely known whether reduced testosterone levels in elderly males might play a direct pathogenetic role in these conditions or whether low T and associated morbidities are concomitant conditions, both associated with the aging process. Further and longer studies are advisable to confirm the preliminary results.

Male hypogonadism.

PubMed

Basaria, Shehzad

2014-04-05

Male hypogonadism is a clinical syndrome that results from failure to produce physiological concentrations of testosterone, normal amounts of sperm, or both. Hypogonadism may arise from testicular disease (primary hypogonadism) or dysfunction of the hypothalamic-pituitary unit (secondary hypogonadism). Clinical presentations vary dependent on the time of onset of androgen deficiency, whether the defect is in testosterone production or spermatogenesis, associated genetic factors, or history of androgen therapy. The clinical diagnosis of hypogonadism is made on the basis of signs and symptoms consistent with androgen deficiency and low morning testosterone concentrations in serum on multiple occasions. Several testosterone-replacement therapies are approved for treatment and should be selected according to the patient's preference, cost, availability, and formulation-specific properties. Contraindications to testosterone-replacement therapy include prostate and breast cancers, uncontrolled congestive heart failure, severe lower-urinary-tract symptoms, and erythrocytosis. Treatment should be monitored for benefits and adverse effects. Copyright © 2014 Elsevier Ltd. All rights reserved.

An open-label clinical trial to investigate the efficacy and safety of corifollitropin alfa combined with hCG in adult men with hypogonadotropic hypogonadism.

PubMed

Nieschlag, Eberhard; Bouloux, Pierre-Marc G; Stegmann, Barbara J; Shankar, R Ravi; Guan, Yanfen; Tzontcheva, Anjela; McCrary Sisk, Christine; Behre, Hermann M

2017-03-07

Hypogonadotropic hypogonadism (HH) in men results in insufficient testicular function and deficiencies in testosterone and spermatogenesis. Combinations of human chorionic gonadotropin (hCG) and recombinant follicle-stimulating hormone (recFSH) have been successful in the treatment of HH. Corifollitropin alfa is a long-acting FSH-analog with demonstrated action in women seeking infertility care. The aim of this study was to investigate the efficacy and safety of corifollitropin alfa combined with hCG to increase testicular volume and induce spermatogenesis in men with HH. This was a Phase III, multi-center, open-label, single-arm trial of corifollitropin alfa in azoospermic men aged 18 to 50 years with HH. After 16 weeks of pretreatment of 23 subjects with hCG alone, 18 subjects with normalized testosterone (T) levels who remained azoospermic entered the 52-week combined treatment phase with hCG twice-weekly and 150 μg corifollitropin alfa every other week. The increase in testicular volume (primary efficacy endpoint) and induction of spermatogenesis resulting in a sperm count ≥1 × 10 6 /mL (key secondary efficacy endpoint) during 52 weeks of combined treatment were assessed. Safety was evaluated by the presence of anti-corifollitropin alfa antibodies and the occurrence of adverse events (AEs). Mean (±SD) testicular volume increased from 8.6 (±6.09) mL to 17.8 (±8.93) mL (geometric mean fold increase, 2.30 [95% CI: 2.03, 2.62]); 14 (77.8%) subjects reached a sperm count ≥1 × 10 6 /mL. No subject developed confirmed anti-corifollitropin alfa antibodies during the trial. Treatment was generally well tolerated. Corifollitropin alfa 150 μg administrated every other week combined with twice-weekly hCG for 52 weeks increased testicular volume significantly, and induced spermatogenesis in >75% of men with HH who had remained azoospermic after hCG treatment alone. ClinicalTrials.gov: NCT01709331 .

Genetics Home Reference: PMM2-congenital disorder of glycosylation

MedlinePlus

... vision loss. Females with PMM2 -CDG have hypergonadotropic hypogonadism, which affects the production of hormones that direct ... Additional Information & Resources MedlinePlus (3 links) Encyclopedia: Hypogonadotropic Hypogonadism Health Topic: Genetic Brain Disorders Health Topic: Metabolic ...

The genetic basis of female reproductive disorders: Etiology and clinical testing ☆

PubMed Central

Layman, Lawrence C.

2013-01-01

With the advent of improved molecular biology techniques, the genetic basis of an increasing number of reproductive disorders has been elucidated. Mutations in at least 20 genes cause hypogonadotropic hypogonadism including Kallmann syndrome in about 35–40% of patients. The two most commonly involved genes are FGFR1 and CHD7. When combined pituitary hormone deficiency includes hypogonadotropic hypogonadism as a feature, PROP1 mutations are the most common of the six genes involved. For hypergonadotropic hypogonadism, mutations in 14 genes cause gonadal failure in 15% of affected females, most commonly in FMR1. In eugonadal disorders, activating FSHR mutations have been identified for spontaneous ovarian hyperstimulation syndrome; and WNT4 mutations have been described in mullerian aplasia. For other eugonadal disorders, such as endometriosis, polycystic ovary syndrome, and leiomyomata, specific germline gene mutations have not been identified, but some chromosomal regions are associated with the corresponding phenotype. Practical genetic testing is possible to perform in both hypogonadotropic and hypergonadotropic hypogonadism and spontaneous ovarian hyperstimulation syndrome. However, clinical testing for endometriosis, polycystic ovary syndrome, and leiomyomata is not currently practical for the clinician. PMID:23499866

Kisspeptin and KISS1R: a critical pathway in the reproductive system

PubMed Central

Gianetti, Elena; Seminara, Stephanie

2010-01-01

In 2003, three groups around the world simultaneously discovered that KISS1R (GPR54) is a key gatekeeper of sexual maturation in both mice and men. Developmental changes in the expression of the ligand for KISS1R, kisspeptin, support its critical role in the pubertal transition. In addition, kisspeptin, a powerful stimulus of GNRH-induced gonadotropin secretion and may modulate both positive and negative sex steroid feedback effects at the hypothalamic level. Genetic studies in humans have revealed both loss-of-function and gain-of-function mutations in patients with idiopathic hypogonadotropic hypogonadism and precocious puberty respectively. This review examines the kisspeptin/KISS1R pathway in the reproductive system. PMID:18515314

Mutational Analysis of TAC3 and TACR3 Genes in Patients with Idiopathic Central Pubertal Disorders

PubMed Central

Tusset, Cintia; Noel, Sekoni D.; Trarbach, Ericka B.; Silveira, Letícia F. G.; Jorge, Alexander A. L.; Brito, Vinicius N.; Cukier, Priscila; Seminara, Stephanie B.; de Mendonça, Berenice B.; Kaiser, Ursula B.; Latronico, Ana Claudia

2013-01-01

Aim To investigate the presence of variants in the TAC3 and TACR3 genes, which encode NKB and its receptor (NK3R), respectively, in a large cohort of patients with idiopathic central pubertal disorders. Patients and Methods Two hundred and thirty seven patients were studied: 114 with central precocious puberty (CPP), 73 with normosmic isolated hypogonadotropic hypogonadism (IHH) and 50 with constitutional delay of growth and puberty (CDGP). The control group consisted of 150 Brazilian individuals with normal pubertal development. Genomic DNA was extracted from peripheral blood and the entire coding region of both TAC3 and TACR3 genes were amplified and automatically sequenced. Results We identified one variant (p.A63P) in NKB and four variants, p.G18D, p.L58L (c.172C>T), p.W275* and p.A449S in NK3R, which were absent in the control group. The p.A63P variant was identified in a girl with CPP, and p.A449S in a girl with CDGP. The known p.G18D, p.L58L and p.W275* variants were identified in three unrelated males with normosmic IHH. Conclusion Rare variants in the TAC3 and TACR3 genes were identified in patients with central pubertal disorders. Loss-of-function variants of TACR3 were associated with the normosmic IHH phenotype. PMID:23329188

Effects of Head Trauma and Brain Injury on Neuroendocrinologic Function

DTIC Science & Technology

1986-10-31

severity of hypogonadism is dependent upon the degree of neurologic impairment, that there is a significant negative correlation between changes in...A. Gonadal studies. Our investigation of the transient hypogonadotropic hypogonadism occurring in the post-injury setting is complete. In our...sympathetic nervous system activation. We found that the severity of the hypogonadism is dependent on the magnitude of the neurologic impairment since

[Current genetic issues and phenotypic variants in Kallmann syndrome].

PubMed

Gutiérrez-Amavizca, Bianca Ethel; Figuera, Luis E; Orozco-Castellanos, Ricardo

2012-01-01

Kallmann syndrome is characterized by hypogonadotropic hypogonadism and anosmia/hyposmia. The hypogonadotropic hypogonadism is due to deficiency of gonadotropin-releasing hormone, caused by a defect in the migration of neurons synthesizing gonadotropin-releasing hormone, and anosmia/hyposmia is related to the absence or hypoplasia of the olfactory bulb and tracts. Some patients may have other associated abnormalities such as renal agenesis, cleft palate, dental agenesis, synkinesis, shortening of metacarpal, sensory neural hearing loss and seizures. The aim of this paper is to present an updated review of the clinical and molecular basis, highlighting the relevance of knowledge of phenotypic variants in Kallmann syndrome.

Insulin-like peptide 3 (INSL3) in men with congenital hypogonadotropic hypogonadism/Kallmann syndrome and effects of different modalities of hormonal treatment: a single-center study of 281 patients.

PubMed

Trabado, Séverine; Maione, Luigi; Bry-Gauillard, Hélène; Affres, Hélène; Salenave, Sylvie; Sarfati, Julie; Bouvattier, Claire; Delemer, Brigitte; Chanson, Philippe; Le Bouc, Yves; Brailly-Tabard, Sylvie; Young, Jacques

2014-02-01

Insulin-like factor 3 (INSL3) is a testicular hormone secreted during fetal life, the neonatal period, and after puberty. To measure INSL3 levels in a large series of men with congenital hypogonadotropic hypogonadism (CHH)/ Kallmann syndrome (KS), in order to assess its diagnostic value and to investigate its regulation. We studied 281 CHH/KS patients (91 untreated, 96 receiving T, and 94 receiving combined gonadotropin therapy [human chorionic gonadotropin, hCG, and FSH]) and 72 age-matched healthy men. Serum INSL3 was immunoassayed with a validated RIA. Mean (±SD) INSL3 levels (pg/mL) were 659 ± 279 in controls and lower (60 ± 43; P < .001) in untreated CHH/KS patients, with no overlap between the two groups, when the threshold of 250 pg/mL was used. Basal INSL3 levels were lower in both untreated CHH/KS men with cryptorchidism than in those with intrascrotal testes and in patients with testicular volumes below 4 mL. Significant positive correlations between INSL3 and both serum total T and LH levels were observed in untreated CHH/KS. Mean INSL3 levels remained low in T-treated CHH/KS patients and were significantly higher in men receiving combined hCG-FSH therapy (P < .001), but the increase was lower cryptorchid patients. FSH-hCG combination therapy or hCG monotherapy, contrary to T and FSH monotherapies, significantly increased INSL3 levels in CHH/KS. INSL3 is as sensitive a marker as T for the evaluation of altered Leydig cell function in CHH/KS patients. INSL3 levels correlate with LH levels in CHH/KS men showing, together with the rise in INSL3 levels during hCG therapy, that INSL3 secretion seems not constitutively secreted during adulthood but is dependence on pituitary LH.

The Role of Nuclear Receptor Coactivators in Recurrent Prostate Cancer

DTIC Science & Technology

2006-02-01

hyp- oplasia congenita and hypogonadotropic hypogonadism (34). From an evolutionary perspective, the AR AF2 region of the ligand binding domain is more...linked adrenal hypoplasia congenita and hypogo- nadotropic hypogonadism . Nature 372:672–676. 35. Muscatelli, F., A. P. Walker, E. De Plaen, A. N

Obesity-related hypogonadism: a reversible condition.

PubMed

Zouras, Stamatios; Stephens, Jeffrey W; Price, David

2017-06-23

Obesity is associated with hypogonadism. While this association is widely accepted, the underlying mechanisms remain unclear. Furthermore, obesity is a risk factor for hypogonadism and conversely hypogonadism may be a risk factor for obesity. We present the case of a morbidly obese man aged 30 years with hypogonadotrophic hypogonadism that underwent a Roux-en-Y gastric bypass operation. Following the surgical treatment of his obesity, the testosterone level returned to normal with improvements in hypogonadal symptoms, which allowed discontinuation of exogenous testosterone therapy. This case report demonstrates reversal of hypogonadism following weight loss with restoration of gonadal function. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Testicular growth and spermatogenesis: new goals for pubertal hormone replacement in boys with hypogonadotropic hypogonadism? -a multicentre prospective study of hCG/rFSH treatment outcomes during adolescence.

PubMed

Rohayem, Julia; Hauffa, Berthold P; Zacharin, Margaret; Kliesch, Sabine; Zitzmann, Michael

2017-01-01

Testosterone treatment for pubertal induction in boys with hypogonadotropic hypogonadism (HH) provides virilization, but does not induce testicular growth or fertility. Larger studies evaluating the outcomes of gonadotropin replacement during adolescence have not been reported to date; whether previous testosterone substitution affects testicular responses is unresolved. We aimed to assess the effects of human chorionic gonadotropin (hCG) and recombinant FSH (rFSH) in boys and adolescents with HH with respect to a) testicular growth, b) spermatogenesis, c) quality of life (QoL) and to identify factors influencing therapeutic success. A prospective case study was conducted in 26 paediatric endocrine centres PATIENTS/INTERVENTIONS: HCG and rFSH were administered until cessation of testicular growth and plateauing of spermatogenesis to (1) prepubertal HH boys with absent or early arrested puberty (group A) and to (2) HH adolescents who had previously received full testosterone replacement (group B). Bi-testicular volumes (BTVs), sperm concentrations and QoL. Sixty (34 A/26 B) HH patients aged 14-22 years were enrolled. BTVs rose from 5 ± 5 to 34 ± 3 ml in group A vs 5 ± 3 to 32 ± 3 ml in group B, with normal final BTVs (≥24 ml) attained in 74%/70% after 25/23 months in A/B, respectively. Sperm in the ejaculate were found in 21/23(91%)/18/19(95%), with plateauing concentrations after 31/30 months of hCG and 25/25 months of combined treatment in A/B. Sperm concentrations were normal (≥15 mill/ml) in 61%/32%, with mean concentrations of 40 ± 73 vs 19 ± 38 mill/ml in A/B (n.s.). Outcomes were better in patients without bilateral cryptorchidism, with non-congenital HH causes, higher baseline BTVs, and higher baseline inhibin B and AMH levels. QoL increased in both groups. HCG/rFSH replacement during adolescence successfully induces testicular growth and spermatogenesis, irrespective of previous testosterone replacement, and enhances QoL. © 2016 John Wiley & Sons

Identifying the unmet health needs of patients with congenital hypogonadotropic hypogonadism using a web-based needs assessment: implications for online interventions and peer-to-peer support

PubMed Central

2014-01-01

Background Patients with rare diseases such as congenital hypogonadotropic hypogonadism (CHH) are dispersed, often challenged to find specialized care and face other health disparities. The internet has the potential to reach a wide audience of rare disease patients and can help connect patients and specialists. Therefore, this study aimed to: (i) determine if web-based platforms could be effectively used to conduct an online needs assessment of dispersed CHH patients; (ii) identify the unmet health and informational needs of CHH patients and (iii) assess patient acceptability regarding patient-centered, web-based interventions to bridge shortfalls in care. Methods A sequential mixed-methods design was used: first, an online survey was conducted to evaluate health promoting behavior and identify unmet health and informational needs of CHH men. Subsequently, patient focus groups were held to explore specific patient-identified targets for care and to examine the acceptability of possible online interventions. Descriptive statistics and thematic qualitative analyses were used. Results 105 male participants completed the online survey (mean age 37 ± 11, range 19–66 years) representing a spectrum of patients across a broad socioeconomic range and all but one subject had adequate healthcare literacy. The survey revealed periods of non-adherence to treatment (34/93, 37%) and gaps in healthcare (36/87, 41%) exceeding one year. Patient focus groups identified lasting psychological effects related to feelings of isolation, shame and body-image concerns. Survey respondents were active internet users, nearly all had sought CHH information online (101/105, 96%), and they rated the internet, healthcare providers, and online community as equally important CHH information sources. Focus group participants were overwhelmingly positive regarding online interventions/support with links to reach expert healthcare providers and for peer-to-peer support. Conclusion The web

Hypogonadism: Its Prevalence and Diagnosis.

PubMed

Ross, Anna; Bhasin, Shalender

2016-05-01

Hypogonadism is a clinical syndrome, which results from the failure of the testes to produce physiologic levels of testosterone and a normal number of spermatozoa due to defects at one or more levels of the hypothalamic-pituitary-gonadal axis. Primary hypogonadism results from malfunction at the level of the testes due to a genetic cause, injury, inflammation, or infection. Hypothalamic and/or pituitary failure leads to secondary hypogonadism, most often as a result of genetic defects, neoplasm, or infiltrative disorders. The signs and symptoms of hypogonadism depend on the age of onset, severity of androgen deficiency, and underlying cause of androgen deficiency. Copyright © 2016 Elsevier Inc. All rights reserved.

Adolescent gynecomastia is associated with a high incidence of obesity, dysglycemia, and family background of diabetes mellitus

PubMed Central

Kulshreshtha, Bindu; Arpita, Arora; Rajesh, Patnaik T.; Sameek, Bhattacharya; Dutta, Deep; Neera, Sharma; Mohd, Mohsin

2017-01-01

Background: Gynecomastia during adolescence is common though etiology is not clear. We studied the clinical and hormonal profile of adolescent patients with gynecomastia. Methodology: Patients who had onset of breast development between age 10 and 20 years were included in this study. Their clinical profile, biochemical, and hormonal parameters were studied. Results: Of 94 patients with gynecomastia, 4 had hypogonadotropic hypogonadism, 4 had hypergonadotropic hypogonadism, and 1 had fibroadenosis, but in majority (90.4%), no apparent cause for breast enlargement was evident. In the idiopathic group, majority were obese (63%). Fourteen (16%) patients had impaired fasting glucose or impaired glucose tolerance. Another twenty patients had subtle abnormalities (high 1 h glucose or glucose peak at 2 h). Twenty-nine percent of lean and 38% of obese patients had mild abnormalities in glucose profile. Sixty percent of patients had family background of diabetes. Obese patients had lower testosterone as compared to lean patients; however, estradiol, luteinizing hormone, and follicle-stimulating hormone levels were similar in the two groups. Conclusion: Gynecomastia during adolescence is associated with obesity, dysglycemia, and family background of diabetes mellitus. PMID:28217517

Anabolic steroid induced hypogonadism in young men.

PubMed

Coward, Robert M; Rajanahally, Saneal; Kovac, Jason R; Smith, Ryan P; Pastuszak, Alexander W; Lipshultz, Larry I

2013-12-01

The use of anabolic androgenic steroids has not been traditionally discussed in mainstream medicine. With the increased diagnosis of hypogonadism a heterogeneous population of men is now being evaluated. In this larger patient population the existence of anabolic steroid induced hypogonadism, whether transient or permanent, should now be considered. We performed an initial retrospective database analysis of all 6,033 patients who sought treatment for hypogonadism from 2005 to 2010. An anonymous survey was subsequently distributed in 2012 to established patients undergoing testosterone replacement therapy. Profound hypogonadism, defined as testosterone 50 ng/dl or less, was identified in 97 men (1.6%) in the large retrospective cohort initially reviewed. The most common etiology was prior anabolic androgenic steroid exposure, which was identified in 42 men (43%). Because of this surprising data, we performed an anonymous followup survey of our current hypogonadal population of 382 men with a mean±SD age of 49.2±13.0 years. This identified 80 patients (20.9%) with a mean age of 40.4±8.4 years who had prior anabolic androgenic steroid exposure. Hypogonadal men younger than 50 years were greater than 10 times more likely to have prior anabolic androgenic steroid exposure than men older than 50 years (OR 10.16, 95% CI 4.90-21.08). Prior anabolic androgenic steroid use significantly correlated negatively with education level (ρ=-0.160, p=0.002) and number of children (ρ=-0.281, p<0.0001). Prior anabolic androgenic steroid use is common in young men who seek treatment for symptomatic hypogonadism and anabolic steroid induced hypogonadism is the most common etiology of profound hypogonadism. These findings suggest that it is necessary to refocus the approach to evaluation and treatment paradigms in young hypogonadal men. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Etiology and treatment of hypogonadism in adolescents.

PubMed

Viswanathan, Vidhya; Eugster, Erica A

2009-12-01

Adequate functioning at all levels of the hypothalamic-pituitary-gonadal axis is necessary for normal gonadal development and subsequent sex steroid production. Deficiencies at any level of the axis can lead to a hypogonadal state. The causes of hypogonadism are heterogeneous and may involve any level of the reproductive system. This review discusses various causes of hypogonadism, describes the evaluation of hypogonadal states, and outlines treatment options for the induction of puberty in affected adolescents. Whereas some conditions are clearly delineated, the exact etiology and underlying pathogenesis of many disorders is unknown.

Genetics Home Reference: Kallmann syndrome

MedlinePlus

... a part of the brain called the hypothalamus. Males born with hypogonadotropic hypogonadism often have an unusually ... facial hair and deepening of the voice in males, the start of monthly periods (menstruation) and breast ...

Characteristics of compensated hypogonadism in patients with sexual dysfunction.

PubMed

Corona, Giovanni; Maseroli, Elisa; Rastrelli, Giulia; Sforza, Alessandra; Forti, Gianni; Mannucci, Edoardo; Maggi, Mario

2014-07-01

In the last few years, a view that subclinical endocrine disorders represent milder forms of the clinically overt disease has emerged. Accordingly, it has been proposed that compensated hypogonadism represents a genuine clinical subset of late-onset hypogonadism. The aim of the present study is to investigate the associations of compensated hypogonadism with particular clinical and psychological characteristics of male subjects complaining of sexual dysfunction. After excluding documented genetic causes of hypogonadism, an unselected consecutive series of 4,173 patients consulting our unit for sexual dysfunction was studied. Compensated hypogonadism was identified according to the European Male Ageing study criteria: total testosterone ≥10.5 nmol/L and luteinizing hormone >9.4 U/L. Several hormonal, biochemical, and instrumental (penile Doppler ultrasound) parameters were studied, along with results of the Structured Interview on Erectile Dysfunction (SIEDY) and ANDROTEST. One hundred seventy (4.1%) subjects had compensated hypogonadism, whereas 827 (19.8%) had overt hypogonadism. After adjustment for confounding factors, no specific sexual symptoms were associated with compensated hypogonadism. However, compensated hypogonadism individuals more often reported psychiatric symptoms, as detected by Middlesex Hospital Questionnaire score, when compared with both eugonadal and overt hypogonadal subjects (adjusted odds ratios = 1.018 [1.005;1.031] and 1.014 [1.001;1.028], respectively; both P < 0.005). In addition, subjects with compensated or overt hypogonadism had an increased predicted risk of cardiovascular events (as assessed by Progetto Cuore risk algorithm) when compared with eugonadal individuals. Accordingly, mortality related to major adverse cardiovascular events (MACEs), but not MACE incidence, was significantly higher in subjects with both compensated and overt hypogonadism when compared with eugonadal subjects. The present data do not support

Etiology and treatment of hypogonadism in adolescents.

PubMed

Viswanathan, Vidhya; Eugster, Erica A

2011-10-01

Adequate functioning at all levels of the hypothalamic-pituitary-gonadal axis is necessary for normal gonadal development and subsequent sex steroid production. Deficiencies at any level of the axis can lead to a hypogonadal state. The causes of hypogonadism are heterogeneous and may involve any level of the reproductive system. This review discusses various causes of hypogonadism, describes the evaluation of hypogonadal states, and outlines treatment options for the induction of puberty in affected adolescents. Whereas some conditions are clearly delineated, the exact etiology and underlying pathogenesis of many disorders is unknown. Copyright © 2011 Elsevier Inc. All rights reserved.

Association between Use of Exogenous Testosterone Therapy and Risk of Venous Thrombotic Events among Exogenous Testosterone Treated and Untreated Men with Hypogonadism.

PubMed

Li, Hu; Benoit, Karin; Wang, Wei; Motsko, Stephen

2016-04-01

Limited information exists about whether exogenous testosterone therapy is associated with a risk of venous thrombotic events. We investigated via cohort and nested case-control analyses whether exogenous testosterone therapy is associated with the risk of venous thrombotic events in men with hypogonadism. Databases were reviewed to identify men prescribed exogenous testosterone therapy and/or men with a hypogonadism diagnosis. Propensity score 1:1 matching was used to select patients for cohort analysis. Cases (men with venous thrombotic events) were matched 1:4 with controls (men without venous thrombotic events) for the nested case-control analysis. Primary outcome was defined as incident idiopathic venous thrombotic events. Cox regression and conditional logistic regression were used to assess HRs and ORs, respectively. Sensitivity analyses were also performed. A total of 102,650 exogenous testosterone treated and 102,650 untreated patients were included in cohort analysis after matching, and 2,785 cases and 11,119 controls were included in case-control analysis. Cohort analysis revealed a HR of 1.08 for all testosterone treated patients (95% CI 0.91, 1.27, p = 0.378). Case-control analysis resulted in an OR of 1.02 (95% CI 0.92, 1.13, p = 0.702) for current exogenous testosterone therapy exposure and an OR of 0.92 (95% CI 0.82, 1.03, p = 0.145) for past exogenous testosterone therapy exposure. These results remained nonstatistically significant after stratifying by exogenous testosterone therapy administration route and age category. Most sensitivity analyses yielded consistent results. No significant association was found between exogenous testosterone therapy and incidents of idiopathic or overall venous thrombotic events in men with hypogonadism. However, some discrepant findings exist for the association between injectable formulations and the risk of overall venous thrombotic events. Copyright © 2016 American Urological Association Education and Research

Evaluation and treatment of male hypogonadism in primary care.

PubMed

Pickett, Kim Anne

2016-08-18

Male hypogonadism is increasing in prevalence, particularly in the older male population. Signs and symptoms associated with hypogonadism are often nonspecific and may be difficult to categorize. This article discusses parameters for screening patients at risk, reviews how to establish the diagnosis of primary or secondary male hypogonadism, and offers important considerations for treatment of patients with hypogonadism.

Obesity and Hypogonadism.

PubMed

Lamm, Steven; Chidakel, Aaron; Bansal, Rohan

2016-05-01

The relationship between obesity and hypogonadism is complicated. The relationship is bidirectional and there are numerous causative and correlative factors on both sides of the equation. Obesity is increasing in prevalence in epidemic proportions. Likewise, we are beginning to see the rapid increase in the incidence of male hypogonadism. It is only recently that we are learning the ways in which these 2 conditions exacerbate each other, and we are only beginning to understand how by treating one of these conditions, we can help to treat the other as well. Copyright © 2016 Elsevier Inc. All rights reserved.

An update on male hypogonadism therapy.

PubMed

Surampudi, Prasanth; Swerdloff, Ronald S; Wang, Christina

2014-06-01

Men who have symptoms associated with persistently low serum total testosterone level should be assessed for testosterone replacement therapy. Acute and chronic illnesses are associated with low serum testosterone and these should be recognized and treated. Once the diagnosis of male hypogonadism is made, the benefits of testosterone treatment usually outweigh the risks. Without contraindications, the patient should be offered testosterone replacement therapy. The options of testosterone delivery systems (injections, transdermal patches/gels, buccal tablets, capsules and implants) have increased in the last decade. Testosterone improves symptoms and signs of hypogonadism such as sexual function and energy, increases bone density and lean mass and decreases visceral adiposity. In men who desire fertility and who have secondary hypogonadism, testosterone can be withdrawn and the patients can be placed on gonadotropins. New modified designer androgens and selective androgen receptor modulators have been in preclinical and clinical trials for some time. None of these have been assessed for the treatment of male hypogonadism. Despite the lack of prospective long-term data from randomized, controlled clinical trials of testosterone treatment on prostate health and cardiovascular disease risk, the available evidence suggests that testosterone therapy should be offered to symptomatic hypogonadal men.

Adult-Onset Hypogonadism.

PubMed

Khera, Mohit; Broderick, Gregory A; Carson, Culley C; Dobs, Adrian S; Faraday, Martha M; Goldstein, Irwin; Hakim, Lawrence S; Hellstrom, Wayne J G; Kacker, Ravi; Köhler, Tobias S; Mills, Jesse N; Miner, Martin; Sadeghi-Nejad, Hossein; Seftel, Allen D; Sharlip, Ira D; Winters, Stephen J; Burnett, Arthur L

2016-07-01

In August 2015, an expert colloquium commissioned by the Sexual Medicine Society of North America (SMSNA) convened in Washington, DC, to discuss the common clinical scenario of men who present with low testosterone (T) and associated signs and symptoms accompanied by low or normal gonadotropin levels. This syndrome is not classical primary (testicular failure) or secondary (pituitary or hypothalamic failure) hypogonadism because it may have elements of both presentations. The panel designated this syndrome adult-onset hypogonadism (AOH) because it occurs commonly in middle-age and older men. The SMSNA is a not-for-profit society established in 1994 to promote, encourage, and support the highest standards of practice, research, education, and ethics in the study of human sexual function and dysfunction. The panel consisted of 17 experts in men's health, sexual medicine, urology, endocrinology, and methodology. Participants declared potential conflicts of interest and were SMSNA members and nonmembers. The panel deliberated regarding a diagnostic process to document signs and symptoms of AOH, the rationale for T therapy, and a monitoring protocol for T-treated patients. The evaluation and management of hypogonadal syndromes have been addressed in recent publications (ie, the Endocrine Society, the American Urological Association, and the International Society for Sexual Medicine). The primary purpose of this document was to support health care professionals in the development of a deeper understanding of AOH, particularly in how it differs from classical primary and secondary hypogonadism, and to provide a conceptual framework to guide its diagnosis, treatment, and follow-up. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

[Gender differences in cognitive functions and influence of sex hormones].

PubMed

Torres, A; Gómez-Gil, E; Vidal, A; Puig, O; Boget, T; Salamero, M

2006-01-01

To review scientific evidence on gender differences in cognitive functions and influence of sex hormones on cognitive performance. Systematical search of related studies identified in Medline. Women outperform men on verbal fluency, perceptual speed tasks, fine motor skills, verbal memory and verbal learning. Men outperform women on visuospatial ability, mathematical problem solving and visual memory. No gender differences on attention and working memory are found. Researchers distinguish four methods to investigate hormonal influence on cognitive performance: a) patient with hormonal disorders; b) neuroimaging in individuals during hormone administration; c) in women during different phases of menstrual cycle, and d) in patients receiving hormonal treatment (idiopathic hypogonadotropic hypogonadism, postmenopausal women and transsexuals). The findings mostly suggest an influence of sex hormones on some cognitive functions, but they are not conclusive because of limitations and scarcity of the studies. There are gender differences on cognitive functions. Sex hormones seem to influence cognitive performance.

An update on male hypogonadism therapy

PubMed Central

Surampudi, Prasanth; Swerdloff, Ronald S; Wang, Christina

2014-01-01

Introduction Men who have symptoms associated with persistently low serum total testosterone level should be assessed for testosterone replacement therapy. Areas covered Acute and chronic illnesses are associated with low serum testosterone and these should be recognized and treated. Once the diagnosis of male hypogonadism is made, the benefits of testosterone treatment usually outweigh the risks. Without contraindications, the patient should be offered testosterone replacement therapy. The options of testosterone delivery systems (injections, transdermal patches/gels, buccal tablets, capsules and implants) have increased in the last decade. Testosterone improves symptoms and signs of hypogonadism such as sexual function and energy, increases bone density and lean mass and decreases visceral adiposity. In men who desire fertility and who have secondary hypogonadism, testosterone can be withdrawn and the patients can be placed on gonadotropins. New modified designer androgens and selective androgen receptor modulators have been in preclinical and clinical trials for some time. None of these have been assessed for the treatment of male hypogonadism. Expert opinion Despite the lack of prospective long-term data from randomized, controlled clinical trials of testosterone treatment on prostate health and cardiovascular disease risk, the available evidence suggests that testosterone therapy should be offered to symptomatic hypogonadal men. PMID:24758365

Hypogonadism and metabolic syndrome: implications for testosterone therapy.

PubMed

Makhsida, Nawras; Shah, Jay; Yan, Grace; Fisch, Harry; Shabsigh, Ridwan

2005-09-01

Metabolic syndrome, characterized by central obesity, insulin resistance, dyslipidemia and hypertension, is highly prevalent in the United States. When left untreated, it significantly increases the risk of diabetes mellitus and cardiovascular disease. It has been suggested that hypogonadism may be an additional component of metabolic syndrome. This has potential implications for the treatment of metabolic syndrome with testosterone. We reviewed the available literature on metabolic syndrome and hypogonadism with a particular focus on testosterone therapy. A comprehensive MEDLINE review of the world literature from 1988 to 2004 on hypogonadism, testosterone and metabolic syndrome was performed. Observational data suggest that metabolic syndrome is strongly associated with hypogonadism in men. Multiple interventional studies have shown that exogenous testosterone has a favorable impact on body mass, insulin secretion and sensitivity, lipid profile and blood pressure, which are the parameters most often disturbed in metabolic syndrome. Hypogonadism is likely a fundamental component of metabolic syndrome. Testosterone therapy may not only treat hypogonadism, but may also have tremendous potential to slow or halt the progression from metabolic syndrome to overt diabetes or cardiovascular disease via beneficial effects on insulin regulation, lipid profile and blood pressure. Furthermore, the use of testosterone to treat metabolic syndrome may also lead to the prevention of urological complications commonly associated with these chronic disease states, such as neurogenic bladder and erectile dysfunction. Physicians must be mindful to evaluate hypogonadism in all men diagnosed with metabolic syndrome as well as metabolic syndrome in all men diagnosed with hypogonadism. Future research in the form of randomized clinical trials should focus on further defining the role of testosterone for metabolic syndrome.

Hypogonadism in Patients with Sickle Cell Disease: Central or Peripheral?

PubMed Central

Taddesse, A.; Woldie, I.L.; Khana, P.; Swerdlow, P.S.; Chu, J.-W.; Abrams, J.; Abou-Samra, A.-B.

2013-01-01

There is conflicting evidence in the literature on the etiology of hypogonadism in patients with sickle cell disease (SCD). A cross-sectional study was done to determine whether hypogonadism in male patients with SCD is due to primary testicular failure or secondary pituitary/hypothalamic dysfunction and assess the association between hypogonadism and serum ferritin levels. Hormonal assessment for serum concentrations of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) was done for 34 men with SCD and their charts were reviewed for relevant clinical variables. Eight men (24%) were classified hypogonadal based on their serum testosterone levels. These men have significantly lower LH (p = 0.001) and FSH (p = 0.01) levels than normogonadal men, indicating a central etiology. There was no significant difference between hypogonadal and normogonadal men with respect to ferritin levels (p = 0.71). Our study indicates a central etiology of hypogonadism in patients with SCD. In this small study ferritin level was not significantly related to hypogonadism. PMID:22678347

Male hypogonadism and metabolic syndrome.

PubMed

Naifar, M; Rekik, N; Messedi, M; Chaabouni, K; Lahiani, A; Turki, M; Abid, M; Ayedi, F; Jamoussi, K

2015-06-01

The role of androgens in cardiovascular disease is still controversial in men. In this study, we investigated metabolic disorders in Tunisian hypogonadal men compared with healthy controls. Forty hypogonadal men and 80 control subjects were enrolled. Patients with a history of pre-existing panhypopituitarism, thyroid dysfunction or inflammatory disease were excluded. Glycaemia, glycated haemoglobin (HbA1c), high-sensitive C-reactive protein (hsCRP), lipid profile, insulin, testosterone and gonadotrophins were measured. Insulin resistance was assessed by homoeostasis model assessment of insulin resistance (Homa IR). Waist circumference, body mass index and blood pressure were significantly higher in patients compared with controls. Glycemia, HbA1c, fasting serum insulin and Homa IR were significantly increased among hypogonadal men. In univariate analysis, testosterone levels were inversely correlated with body mass index, waist circumference, blood pressure, glycaemia, HbA1C, insulin, Homa IR and hsCRP. In multivariate analysis including all significant variables, initial testosterone level was the only independent risk factor for developing dyslipidaemia. With logistic regression, male hypogonadism was an independent risk factor for MS (P < 0.001). We conclude that low testosterone level plays a central role in the development of metabolic syndrome. Further prospective data are required to establish the causative link. © 2014 Blackwell Verlag GmbH.

Serum vitamin D levels and hypogonadism in men.

PubMed

Lerchbaum, E; Pilz, S; Trummer, C; Rabe, T; Schenk, M; Heijboer, A C; Obermayer-Pietsch, B

2014-09-01

There is inconsistent evidence on a possible association of vitamin D and androgen levels in men. We therefore aim to investigate the association of 25-hydroxyvitamin D (25(OH)D) with androgen levels in a cohort of middle-aged men. This cross-sectional study included 225 men with a median (interquartile range) age of 35 (30-41) years. We measured 25(OH)D, total testosterone (TT) and SHBG concentrations. Hypogonadism was defined as TT <10.4 nmol/L. We found no significant correlation of 25(OH)D and androgen levels. Furthermore, androgen levels were not significantly different across 25(OH)D quintiles. The overall prevalence of hypogonadism was 21.5% and lowest in men within 25(OH)D quintile 4 (82-102 nmol/L). We found a significantly increased risk of hypogonadism in men within the highest 25(OH)D quintile (>102 nmol/L) compared to men in quintile 4 (reference) in crude (OR 5.10, 1.51-17.24, p = 0.009) as well as in multivariate adjusted analysis (OR 9.21, 2.27-37.35, p = 0.002). We found a trend towards increased risk of hypogonadism in men within the lowest 25(OH)D quintile (≤43.9 nmol/L). In conclusion, our data suggest that men with very high 25(OH)D levels (>102 nmol/L) might be at an increased risk of hypogonadism. Furthermore, we observed a trend towards increased risk of hypogonadism in men with very low vitamin D levels indicating a U-shaped association of vitamin D levels and hypogonadism. With respect to risk of male hypogonadism, our results suggest optimal serum 25(OH)D concentrations of 82-102 nmol/L. © 2014 American Society of Andrology and European Academy of Andrology.

Hypogonadism in patients with sickle cell disease: central or peripheral?

PubMed

Taddesse, A; Woldie, I L; Khana, P; Swerdlow, P S; Chu, J-W; Abrams, J; Abou-Samra, A-B

2012-01-01

There is conflicting evidence in the literature on the etiology of hypogonadism in patients with sickle cell disease (SCD). A cross-sectional study was done to determine whether hypogonadism in male patients with SCD is due to primary testicular failure or secondary pituitary/hypothalamic dysfunction and assess the association between hypogonadism and serum ferritin levels. Hormonal assessment for serum concentrations of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) was done for 34 men with SCD and their charts were reviewed for relevant clinical variables. Eight men (24%) were classified hypogonadal based on their serum testosterone levels. These men have significantly lower LH (p = 0.001) and FSH (p = 0.01) levels than normogonadal men, indicating a central etiology. There was no significant difference between hypogonadal and normogonadal men with respect to ferritin levels (p = 0.71). Our study indicates a central etiology of hypogonadism in patients with SCD. In this small study ferritin level was not significantly related to hypogonadism. Copyright © 2012 S. Karger AG, Basel.

Content Validity of the Hypogonadism Impact of Symptoms Questionnaire (HIS-Q): A Patient-Reported Outcome Measure to Evaluate Symptoms of Hypogonadism.

PubMed

Gelhorn, Heather L; Vernon, Margaret K; Stewart, Katie D; Miller, Michael G; Brod, Meryl; Althof, Stanley E; DeRogatis, Leonard R; Dobs, Adrian; Seftel, Allen D; Revicki, Dennis A

2016-04-01

Hypogonadism, or low testosterone, is a common disorder. There are currently no patient-reported outcome (PRO) instruments designed to comprehensively evaluate the symptoms of hypogonadism and to detect changes in these symptoms in response to treatment. The purpose of this study was to develop a PRO instrument, the Hypogonadism Impact of Symptoms Questionnaire (HIS-Q) and to assess its content validity. A literature review, expert clinician input, and qualitative concept elicitation with 39 male hypogonadism patients (four focus groups: n = 25; individual interviews: n = 14; mean age 52.3 ± 14.3 years) from the USA were used to develop the draft HIS-Q. Subsequent cognitive interviews (n = 29; mean age 51.5 ± 15.4 years) were used to evaluate content validity. Emergent discussion with participants yielded symptoms within the sexual, physical, energy, sleep, cognition, and mood domains. Low libido and tiredness were most commonly reported. The initial version of the HIS-Q includes 53 items that were consistently understood by the participants, who found the instrument to be relevant to their experiences with hypogonadism and comprehensive in the content coverage of symptoms. The HIS-Q is a comprehensive PRO measure of hypogonadism symptom severity in males. Its design elements, including the response options and recall period, were suitable, and content validity was confirmed.

Clinicopathologic assessment of hypogonadism in men with type 2 diabetes mellitus

PubMed Central

Ugwu, Theophilus E.; Ikem, Rosemary T.; Kolawole, Babatope A.; Ezeani, Ignatius U.

2016-01-01

Objective: To determine the prevalence of hypogonadism in men with type 2 diabetes mellitus and evaluate its clinical and pathologic correlates. Subjects and Methods: In a cross-sectional survey of 200 type 2 diabetic males aged 32–69 years, total testosterone (TT), follicle stimulating hormone, luteinizing hormone, waist circumference (WC), glycated hemoglobin, and lipids were measured. Clinical assessment of androgen deficiency was done using the androgen deficiency in aging male (ADAM) questionnaire. Overt hypogonadism was defined as a combination of positive ADAM score and TT < 8 nmol/L while possible hypogonadism was defined as positive ADAM score with TT 8–12 nmol/L. Results: Overt and possible hypogonadism occurred in 29.5% and 23% of the participants, respectively. Majority (76.3%) of the subjects who had overt hypogonadism had the hypogonadotrophic pattern. Hypogonadal subjects were significantly older (P = 0.014) and had higher mean WC (P = 0.009) than eugonadal ones. Erectile dysfunction was the most common symptom, occurring in 79.7% of overtly hypogonadal subjects. There was a significant negative correlation between WC and serum TT (r = −0.41, P = 0.001). Conclusion: There is a high frequency of symptomatic hypogonadism in men with type 2 diabetes and the frequency increases with advancing age and visceral adiposity. PMID:27730078

Anabolic steroid-induced hypogonadism: diagnosis and treatment.

PubMed

Rahnema, Cyrus D; Lipshultz, Larry I; Crosnoe, Lindsey E; Kovac, Jason R; Kim, Edward D

2014-05-01

To develop an understanding of hypogonadal men with a history of anabolic-androgenic steroid (AAS) use and to outline recommendations for management. Review of published literature and expert opinions. Intended as a meta-analysis, but no quality studies met the inclusion criteria. Not applicable. Men seeking treatment for symptomatic hypogonadism who have used nonprescribed AAS. History and physical examination followed by medical intervention if necessary. Serum testosterone and gonadotropin levels, symptoms, and fertility restoration. Symptomatic hypogonadism is a potential consequence of AAS use and may depend on dose, duration, and type of AAS used. Complete endocrine and metabolic assessment should be conducted. Management strategies for anabolic steroid-associated hypogonadism (ASIH) include judicious use of testosterone replacement therapy, hCG, and selective estrogen receptor modulators. Although complications of AAS use are variable and patient specific, they can be successfully managed. Treatment of ASIH depends on the type and duration of AAS use. Specific details regarding a patient's AAS cycle are important in medical management. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Hypogonadism in aged hospitalized male patients: prevalence and clinical outcome.

PubMed

Iglesias, P; Prado, F; Macías, M C; Guerrero, M T; Muñoz, A; Ridruejo, E; Tajada, P; García-Arévalo, C; Díez, J J

2014-02-01

Male hypogonadism is common in the elderly and has been associated with increased risk of mortality. Our objective has been to assess the prevalence of primary and central hypogonadism in elderly male patients admitted to the hospital because of acute illness. We also evaluated the relationships between gonadal dysfunction and in-hospital mortality. 150 patients, aged ≥65 years, admitted during 2010 and 2011 in our geriatric unit, were studied. Serum concentrations total, bioavailable and free testosterone, as well as of follicle-stimulating hormone and luteinizing hormone were quantified in every patient. Hypogonadism was defined by the presence of serum testosterone levels lower than 200 ng/dl. Hypogonadism was found in 80 patients (53.3 %). Serum gonadotropin concentrations were elevated in 43.7 % of these patients, whereas 41.3 % of hypogonadic patients showed normal and 15 % low gonadotropin concentrations. Respiratory tract infection and congestive heart failure were the main causes of hospitalization in hypogonadal men, whereas acute cerebrovascular disease was the main reason for admission in eugonadal patients. Of the 13 patients who died during hospitalization, 12 were hypogonadic. Patients who died showed significantly lower serum levels of total, free and bioavailable testosterone than those found in patients who survived. Our results show that about half of patients admitted for acute illness have hypogonadism, mainly of non-hypergonadotropic type. Gonadal hypofunction is significantly related with in-hospital mortality. A low value of serum testosterone may be a predictor for mortality in elderly male patients.

Hypogonadism after traumatic brain injury.

PubMed

Hohl, Alexandre; Mazzuco, Tânia Longo; Coral, Marisa Helena César; Schwarzbold, Marcelo; Walz, Roger

2009-11-01

Traumatic brain injury (TBI) is the most common cause of death and disability in young adults. Post-TBI neuroendocrine disorders have been increasingly acknowledged in recent years due to their potential contribution to morbidity and, probably, to mortality after trauma. Marked alterations of the hypothalamic-pituitary axis during the post-TBI acute and chronic phases have been reported. Prospective and longitudinal studies have shown that some abnormalities are transitory. On the other hand, there is a high frequency (15% to 68%) of pituitary hormone deficiency among TBI survivors in a long term setting. Post-TBI hypogonadism is a common finding after cranial trauma, and it is predicted to develop in 16% of the survivors in the long term. Post-TBI hypogonadism has been associated with adverse results in the acute and chronic phases after injury. These data reinforce the need for identification of hormonal deficiencies and their proper treatment, in order to optimize patient recovery, improve their life quality, and avoid the negative consequences of non-treated hypogonadism in the long term.

Prevalence of hypogonadism in males aged at least 45 years: the HIM study

PubMed Central

MULLIGAN, T; FRICK, MF; ZURAW, QC; STEMHAGEN, A; MCWHIRTER, C

2006-01-01

The Hypogonadism in Males study estimated the prevalence of hypogonadism [total testosterone (TT) <300 ng/dl] in men aged ≥45 years visiting primary care practices in the United States. A blood sample was obtained between 8 am and noon and assayed for TT, free testosterone (FT) and bioavailable testosterone (BAT). Common symptoms of hypogonadism, comorbid conditions, demographics and reason for visit were recorded. Of 2162 patients, 836 were hypogonadal, with 80 receiving testosterone. Crude prevalence rate of hypogonadism was 38.7%. Similar trends were observed for FT and BAT. Among men not receiving testosterone, 756 (36.3%) were hypogonadal; odds ratios for having hypogonadism were significantly higher in men with hypertension (1.84), hyperlipidaemia (1.47), diabetes (2.09), obesity (2.38), prostate disease (1.29) and asthma or chronic obstructive pulmonary disease (1.40) than in men without these conditions. The prevalence of hypogonadism was 38.7% in men aged ≥45 years presenting to primary care offices. PMID:16846397

Hypogonadism and fertility issues following primary treatment for testicular cancer.

PubMed

Oldenburg, Jan

2015-09-01

The majority of testicular cancer (TC) patients are cured and expected to live for decades after treatment, such that knowledge about hypogonadism and fertility issues is particularly important for the group of testicular cancer survivors (TCSs). Hypogonadism and fertility issues are related to treatment intensity. In order to give an overview about hypogonadism in testicular cancer survivors (TCSs) the literature was reviewed. Testicular dysfunction was defined as inadequate spermatogenesis, as reflected by increased levels of Follicle Stimulating Hormone (FSH) and reduced fertility and/with or without insufficient testosterone (T) production with or without compensatory increased Luteinizing Hormone (LH) levels. Hypogonadism may lead to reduced sexual functioning and well-being, fertility problems, muscle weakness, loss of energy, and depression. Furthermore, hypogonadism also increases the risk of osteoporosis and is associated with the metabolic syndrome and cardiovascular disease (CVD). The hypothesized "Testicular Dysgenesis Syndrome" comprising low sperm counts, hypospadias, cryptorchidism, and finally TC, probably contributes to hypogonadism independent of applied TC treatment. Recently, an increased risk of accelerated hormonal ageing has been reported in TCSs in the very long term, i.e. 20 years after TC treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

Hypogonadism and the risk of rheumatic autoimmune disease

PubMed Central

Snih, Soham Al; Raji, Mukaila A.; Urban, Randall J.; Sharma, Gulshan; Sheffield-Moore, Melinda; Lopez, David S.; Baillargeon, Gwen; Kuo, Yong-Fang

2017-01-01

Testosterone deficiency has been linked with autoimmune disease and an increase in inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor, and interleukin-6 (IL-6). However, no large-scale longitudinal studies have examined this association. We examined whether untreated hypogonadism was associated with an increased risk of rheumatic autoimmune disease in a large nationally representative cohort. Using one of the nation’s largest commercial insurance databases, we conducted a retrospective cohort study in which we identified 123,460 men diagnosed with hypogonadism between January 1, 2002 and December 31, 2014 and with no prior history of rheumatic autoimmune disease. We matched this cohort to 370,380 men without hypogonadism, at a 1 to 3 ratio, on age and index/diagnosis date. All patients were followed until December 31, 2014 or until they lost insurance coverage or were diagnosed with a rheumatic autoimmune disease. Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHRs). Untreated hypogonadism was associated with an increased risk of developing any rheumatic autoimmune disease (HR = 1.33, 95 % CI = 1.28, 1.38), rheumatoid arthritis (HR = 1.31, 95 % CI = 1.22, 1.44), and lupus (HR = 1.58, 95 % CI = 1.28, 1.94). These findings persisted using latency periods of 1 and 2 years. Hypogonadism was not associated with the control outcome, epilepsy (HR = 1.04, 95 % CI = 0.96, 1.15). Patients diagnosed with hypogonadism who were not treated with testosterone had an increased risk of developing any rheumatic autoimmune disease, rheumatoid arthritis, and lupus. Future research should further examine this association, with particular attention to underlying mechanisms. PMID:27325124

Trace Element Levels in Congenital Hypogonadotrophic Hypogonadism.

PubMed

Aydogdu, A; Haymana, C; Soykut, B; Erdem, O; Basaran, Y; Baskoy, K; Dinc, M; Taslipinar, A; Sonmez, A; Bolu, E; Azal, O

2016-05-01

Cardiometabolic diseases are prevalent in hypogonadism. The pathophysiologic mechanism of increased cardiometabolic risk in hypogonadal patients is not clear. Recently, trace elements have been linked to the development of chronic disease especially cardiovascular disease. We investigated the trace element levels in an unconfounded population of congenital hypogonadotrophic hypogonadism (CHH) and also searched for the relationship with metabolic risk factors. A total of 89 patients with CHH (mean age 21.8 ± 2.0 years) and 80 healthy control subjects (mean age 21.3 ± 1.1 years) were enrolled. The demographic parameters, homeostatic model assessment of insulin resistance (HOMA-IR) levels and plasma zinc, copper, and selenium levels, were measured in patients and healthy controls. The patients had higher waist circumferences (p = 0.014), triglyceride (p = 0.04), insulin (p = 0.004), HOMA-IR levels (p = 0.001), and lower selenium (p = 0.049), zinc (p = 0.004), and copper (p = 0.012) levels when compared to the healthy controls. There was a significant relationship between zinc levels and HOMA-IR levels (p = 0.015). In the regression analysis, zinc levels were independently associated with the calculated HOMA-IR levels (p = 0.015). The results of the present study show that plasma selenium, zinc, and copper levels are decreased in patients with CHH. Also, plasma zinc levels are independently associated with insulin resistance in patients with hypogonadism. Long-term follow-up studies are warranted to investigate the effect of trace elements on the increased cardiometabolic risk in hypogonadism.

Leydig Cell Aging and Hypogonadism

PubMed Central

Beattie, M.C.; Adekola, L.; Papadopoulos, V.; Chen, H.; Zirkin, B.R.

2015-01-01

Leydig cell testosterone (T) production is reduced with age, resulting in reduced serum T levels (hypogonadism). A number of cellular changes have been identified in the steroidogenic pathway of aged Leydig cells that are associated with reduced T formation, including reductions in luteinizing hormone (LH)-stimulated cAMP production, the cholesterol transport proteins steroidogenic acute regulatory (STAR) protein and translocator protein (TSPO), and downstream steroidogenic enzymes of the mitochondria and smooth endoplasmic reticulum. Many of the changes in steroid formation that characterize aged Leydig cells can be elicited by the experimental alteration of the redox environment of young cells, suggesting that changes in the intracellular redox balance may cause reduced T production. Hypogonadism is estimated to affect about 5 million American men, including both aged and young. This condition has been linked to mood changes, worsening cognition, fatigue, depression, decreased lean body mass, reduced bone mineral density, increased visceral fat, metabolic syndrome, decreased libido, and sexual dysfunction. Exogenous T administration is now used widely to elevate serum T levels in hypogonadal men and thus to treat symptoms of hypogonadism. However, recent evidence suggests that men who take exogenous T may face increased risk of stroke, heart attack, and prostate tumorigenesis. Moreover, it is well established that administered T can have suppressive effects on LH, resulting in lower Leydig cell T production, reduced intratesticular T concentration, and reduced spermatogenesis. This makes exogenous T administration inappropriate for men who wish to father children. There are promising new approaches to increase serum T by directly stimulating Leydig cell T production rather than by exogenous T therapy, thus potentially avoiding some of its negative consequences. PMID:25700847

Leydig cell aging and hypogonadism.

PubMed

Beattie, M C; Adekola, L; Papadopoulos, V; Chen, H; Zirkin, B R

2015-08-01

Leydig cell testosterone (T) production is reduced with age, resulting in reduced serum T levels (hypogonadism). A number of cellular changes have been identified in the steroidogenic pathway of aged Leydig cells that are associated with reduced T formation, including reductions in luteinizing hormone (LH)-stimulated cAMP production, the cholesterol transport proteins steroidogenic acute regulatory (STAR) protein and translocator protein (TSPO), and downstream steroidogenic enzymes of the mitochondria and smooth endoplasmic reticulum. Many of the changes in steroid formation that characterize aged Leydig cells can be elicited by the experimental alteration of the redox environment of young cells, suggesting that changes in the intracellular redox balance may cause reduced T production. Hypogonadism is estimated to affect about 5 million American men, including both aged and young. This condition has been linked to mood changes, worsening cognition, fatigue, depression, decreased lean body mass, reduced bone mineral density, increased visceral fat, metabolic syndrome, decreased libido, and sexual dysfunction. Exogenous T administration is now used widely to elevate serum T levels in hypogonadal men and thus to treat symptoms of hypogonadism. However, recent evidence suggests that men who take exogenous T may face increased risk of stroke, heart attack, and prostate tumorigenesis. Moreover, it is well established that administered T can have suppressive effects on LH, resulting in lower Leydig cell T production, reduced intratesticular T concentration, and reduced spermatogenesis. This makes exogenous T administration inappropriate for men who wish to father children. There are promising new approaches to increase serum T by directly stimulating Leydig cell T production rather than by exogenous T therapy, thus potentially avoiding some of its negative consequences. Copyright © 2015 Elsevier Inc. All rights reserved.

Male partial hypogonadotrophic hypogonadism with gynaecomastia and metabolic syndrome.

PubMed

Ahsan, Tasnim; Banu, Zeenat

2012-02-01

The causal association of childhood obesity and hypogonadotrophic hypogonadism needs to be studied to unravel the cause and effect relationship between the two conditions. The relationship of hypogonadism to the Metabolic Syndrome (MetS) remains valid even when using different definitions of MetS, and following the patients prospectively for over 10 years. This is a case of 19 years male who presented with micropenis, marked gynaecomastia and weight gain. Childhood obesity and family history of diabetes predisposed him to future MetS. Presence of micropenis reflects intrauterine hypogonadotrophic hypogonadism. Both entities exacerbated each other.

Hypogonadism associated with long-term opioid therapy: A systematic review.

PubMed

Birthi, Pravardhan; Nagar, Vittal R; Nickerson, Robert; Sloan, Paul A

2015-01-01

Sexual dysfunction and Opioid-Induced Sexual Hormone Deficiency (OPISHD) have been associated with patients on long-term opioid pain therapy. There have been few comprehensive reviews to establish a relation between hypogonadism with chronic opioid pain management. The OPISHD is often not treated and literature guiding this topic is scarce. To investigate hypogonadism associated with long-term opioid therapy based on qualitative data analysis of the available literature. Systematic review. The review included relevant literature identified through searches of PubMed, Cochrane, Clinical Trials, US National Guideline Clearinghouse, and EMBASE, for the years 1960 to September 2013. The quality assessment and clinical relevance criteria used were the Cochrane Musculoskeletal Review Group Criteria for randomized control trials and the Newcastle-Ottawa Scale Criteria for observational studies. The level of evidence was classified as good, fair, and poor, based on the quality of evidence. The primary outcome measures were clinical symptoms and laboratory markers of hypogonadism. Secondary outcome measure was management of OPISHD. Thirty-one studies were identified, of which 14 studies met inclusion criteria. There were no randomized control trials and eight of 14 studies were of moderate quality. The remaining studies were of poor quality. Four studies report most patients on long-term oral opioid therapy have associated hypogonadism and three studies of patients receiving intrathecal opioid therapy suggest that hypogonadism is common. There is lack of high-quality studies to associate chronic opioid pain management with hypogonadism. At present, there is fair evidence to associate hypogonadism with chronic opioid pain management, and only limited evidence for treatment of OPISHD.

Hypogonadism and the risk of rheumatic autoimmune disease.

PubMed

Baillargeon, Jacques; Al Snih, Soham; Raji, Mukaila A; Urban, Randall J; Sharma, Gulshan; Sheffield-Moore, Melinda; Lopez, David S; Baillargeon, Gwen; Kuo, Yong-Fang

2016-12-01

Testosterone deficiency has been linked with autoimmune disease and an increase in inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor, and interleukin-6 (IL-6). However, no large-scale longitudinal studies have examined this association. We examined whether untreated hypogonadism was associated with an increased risk of rheumatic autoimmune disease in a large nationally representative cohort. Using one of the nation's largest commercial insurance databases, we conducted a retrospective cohort study in which we identified 123,460 men diagnosed with hypogonadism between January 1, 2002 and December 31, 2014 and with no prior history of rheumatic autoimmune disease. We matched this cohort to 370,380 men without hypogonadism, at a 1 to 3 ratio, on age and index/diagnosis date. All patients were followed until December 31, 2014 or until they lost insurance coverage or were diagnosed with a rheumatic autoimmune disease. Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHRs). Untreated hypogonadism was associated with an increased risk of developing any rheumatic autoimmune disease (HR = 1.33, 95 % CI = 1.28, 1.38), rheumatoid arthritis (HR = 1.31, 95 % CI = 1.22, 1.44), and lupus (HR = 1.58, 95 % CI = 1.28, 1.94). These findings persisted using latency periods of 1 and 2 years. Hypogonadism was not associated with the control outcome, epilepsy (HR = 1.04, 95 % CI = 0.96, 1.15). Patients diagnosed with hypogonadism who were not treated with testosterone had an increased risk of developing any rheumatic autoimmune disease, rheumatoid arthritis, and lupus. Future research should further examine this association, with particular attention to underlying mechanisms.

Hypogonadism in a patient with mild hereditary haemochromatosis.

PubMed

Wlazlo, N; Peters, W; Bravenboer, B

2012-09-01

Hypogonadism is a potential complication of haemochromatosis, usually seen in patients with severe iron overload and liver cirrhosis. We describe the diagnostic workup of a patient with an early stage of hereditary haemochromatosis, presenting with only mildly elevated liver enzymes and central hypogonadism in the absence of cirrhosis or diabetes, but with concurrent sarcoidosis.

[Hypogonadism, a serious complication of chronic renal insufficiency].

PubMed

Zofková, I; Bubenícek, P; Sotorník, I

2007-06-01

Hypogonadism is a frequent complication in patients with chronic renal insufficiency (CHRI). From a pathogenetic point of view, it is a disorder at the level of the hypothalamus caused by central inhibition of the pulsatile generation of gonadotropin releasing hormone (GnRH) and by a primary disorder of gonads. The cause of hypogonadism in dialysed patients is not completely known. The effect of inhibition of erythropoietin production is believed to be one of the factors, as well as the adverse effects of complicated therapeutic procedures and malnutrition. In men, the affection manifests itself as a disorder of sexual functions, inhibition ofspermatogenesis, premature andropause and severe fatigue syndrome. Menstruation disorders, premature menopause and anovulation cycles are frequent symptoms in dialysed women. Androgen or estrogen substitution improves the quality of life in both sexes and slows down the loss of bone mass. Complete remission of hypogonadism is obtained, in the majority of patients, by renal transplant. The overview study deals with the pathogenesis, diagnosis and treatment of hypogonadism in dialysed patients.

Visceral fat dysfunction is positively associated with hypogonadism in Chinese men.

PubMed

Wang, Ningjian; Zhai, Hualing; Han, Bing; Li, Qin; Chen, Yi; Chen, Yingchao; Xia, Fangzhen; Lin, Dongping; Lu, Yingli

2016-01-22

Visceral adiposity index (VAI) well mirrors visceral fat dysfunction. No study explored the association between low androgen and VAI. We aimed to determine whether VAI was associated with hypogonadism and sex hormones, and also whether it better predicted hypogonadism than other obesity indices. Our data were collected from 16 sites in East China. 2,759 men were enrolled. Hypogonadism was defined as total testosterone < 11.3 nmol/L. VAI was calculated in male: (waist circumference/(39.68 + (1.88 × BMI)) × (triglycerides/1.03) × (1.31/HDL). 484 (17.5%) hypogonadal men had significantly higher VAI. After adjusting for age, smoking, neck and hip circumference, diabetes and hypertension, VAI was inversely associated with total testosterone, estradiol and SHBG (P < 0.01). Higher quartiles of VAI were associated with significantly increasing odds of hypogonadism (P for trend < 0.01). The fully adjusted odds ratio was 5.88 (95 CI% 4.09, 8.46) for the highest quartile compared with the lowest quartile of VAI. Among all the indices investigated, VAI showed the largest area under the curve (P < 0.001). In conclusion, the VAI was significantly associated with a higher prevalence of hypogonadism in Chinese men. VAI also best predicted hypogonadism among obesity indices (waist, hip and neck circumference, BMI, waist-hip ratio and body adiposity index).

The complex association between metabolic syndrome and male hypogonadism.

PubMed

Dimopoulou, Christina; Goulis, Dimitrios G; Corona, Giovanni; Maggi, Mario

2018-04-12

The complex association between metabolic syndrome (MetS) and male hypogonadism is well established. A number of observational studies show that low testosterone is associated with insulin resistance and an increased risk for diabetes mellitus and MetS in men. To elucidate the association between MetS and male hypogonadism, present epidemiological data on the co-existence of the two comorbidities, enlighten the underlying pathophysiology and appraise the effects of testosterone supplementation therapy (TTh) and lifestyle modifications on MetS and body composition in men. Systematic search to PubMed and Medline databases for publications reporting data on association between MetS and male hypogonadism. Both MetS and male hypogonadism have a high prevalence in the general population and are frequently co-existing e.g. in males with diabetes. Accumulating evidence from animal and human studies suggests that MetS is involved in the pathogenesis of hypogonadism in males as well as the other way around. On the other hand, there is evidence for a favorable effect of testosterone supplementation in testosterone deficient men with MetS and/or diabetes mellitus. Studies with superior methodological characteristics are needed in order to establish a role for testosterone supplementation in men with MetS and/or diabetes mellitus. Copyright © 2018 Elsevier Inc. All rights reserved.

Novel Therapy for Male Hypogonadism.

PubMed

Carrasquillo, Robert; Chu, Kevin; Ramasamy, Ranjith

2018-06-09

Hypogonadism and the treatment of low testosterone is increasingly a subject of medical inquiry and controversy. The few treatments that are FDA-approved such as testosterone topicals, injections, and pellets create significant demand from patients for treatments with more convenient means of administration, fewer adverse effects, and the ability to maintain male fertility. Off-label drugs are in abundant use for low testosterone, including selective estrogen receptor modulators, gonadotropins, and aromatase inhibitors. In this review, we summarize the evidence in support of commonly used treatments for male hypogonadism, as well as discuss recent updates in the development of novel therapeutics. New therapies include nasal testosterone, new oral testosterone formulations, anabolic-androgenic steroids, and selective androgen receptor modulators.

High risk of hypogonadism after traumatic brain injury: clinical implications.

PubMed

Agha, Amar; Thompson, Christopher J

2005-01-01

Several recent studies have convincingly documented a close association between traumatic brain injury (TBI) and pituitary dysfunction. Post-traumatic hypogonadism is very common in the acute post-TBI phase, though most cases recover within six to twelve months following trauma. The functional significance of early hypogonadism, which may reflect adaptation to acute illness, is not known. Hypogonadism persists, however, in 10-17% of long-term survivors. Sex steroid deficiency has implications beyond psychosexual function and fertility for survivors of TBI. Muscle weakness may impair functional recovery from trauma and osteoporosis may be exacerbated by immobility secondary to trauma. Identification and appropriate and timely management of post-traumatic hypogonadism is important in order to optimise patient recovery from head trauma, improve quality of life and avoid the long-term adverse consequences of untreated sex steroid deficiency.

Induction of spermatogenesis and fertility in hypogonadotropic azoospermic men by intravenous pulsatile gonadotropin-releasing hormone (GnRH).

PubMed

Blumenfeld, Z; Makler, A; Frisch, L; Brandes, J M

1988-06-01

Gonadotropin-releasing hormone (GnRH) has only recently become a helpful tool in the medication of hypogonadotropic hypogonadism (HH). Two azoospermic patients with HH who had previously been treated with hCG/hMG because of delayed puberty and each of whom had fathered a child after previous gonadotropin therapy were referred due to secondary failure of hCG/hMG treatment to induce spermatogenesis and fertility. A pulse study where blood was drawn every 15 minutes for LH, FSH and PRL RIAs was performed in each patient, and afterwards a bolus of i.v. GnRH was injected to assess gonadotropin responsiveness. A portable GnRH pump was connected to each patient so that it administered 5-20 micrograms of GnRH i.v. every 89 minutes. Spermatogenesis was first detected after 42 and 78 days respectively in the 2 treated HH men and 4 1/2 months from the start of treatment their wives became pregnant. No thrombophlebitis or other complications of the i.v. therapy occurred. In the case of the first patient, the semen was washed and concentrated and intra-uterine inseminations were carried out in an attempt to shorten the time needed to achieve fertility. The first pregnancy was successfully terminated at 38 weeks with the delivery of 2 heterozygotic normal male babies. The second pregnancy ended in spontaneous delivery of a healthy female. We conclude that i.v. pulsatile, intermittent GnRH administration is a safe, efficient and highly successful means of treating azoospermic men with HH.

Visceral fat dysfunction is positively associated with hypogonadism in Chinese men

PubMed Central

Wang, Ningjian; Zhai, Hualing; Han, Bing; Li, Qin; Chen, Yi; Chen, Yingchao; Xia, Fangzhen; Lin, Dongping; Lu, Yingli

2016-01-01

Visceral adiposity index (VAI) well mirrors visceral fat dysfunction. No study explored the association between low androgen and VAI. We aimed to determine whether VAI was associated with hypogonadism and sex hormones, and also whether it better predicted hypogonadism than other obesity indices. Our data were collected from 16 sites in East China. 2,759 men were enrolled. Hypogonadism was defined as total testosterone < 11.3 nmol/L. VAI was calculated in male: (waist circumference/(39.68 + (1.88 × BMI))) × (triglycerides/1.03) × (1.31/HDL). 484 (17.5%) hypogonadal men had significantly higher VAI. After adjusting for age, smoking, neck and hip circumference, diabetes and hypertension, VAI was inversely associated with total testosterone, estradiol and SHBG (P < 0.01). Higher quartiles of VAI were associated with significantly increasing odds of hypogonadism (P for trend < 0.01). The fully adjusted odds ratio was 5.88 (95 CI% 4.09, 8.46) for the highest quartile compared with the lowest quartile of VAI. Among all the indices investigated, VAI showed the largest area under the curve (P < 0.001). In conclusion, the VAI was significantly associated with a higher prevalence of hypogonadism in Chinese men. VAI also best predicted hypogonadism among obesity indices (waist, hip and neck circumference, BMI, waist-hip ratio and body adiposity index). PMID:26796865

The role of hypogonadism in Klinefelter syndrome.

PubMed

Høst, Christian; Skakkebæk, Anne; Groth, Kristian A; Bojesen, Anders

2014-01-01

Klinefelter syndrome (KS) (47, XXY) is the most abundant sex-chromosome disorder, and is a common cause of infertility and hypogonadism in men. Most men with KS go through life without knowing the diagnosis, as only 25% are diagnosed and only a few of these before puberty. Apart from hypogonadism and azoospermia, most men with KS suffer from some degree of learning disability and may have various kinds of psychiatric problems. The effects of long-term hypogonadism may be diffi cult to discern from the gene dose effect of the extra X-chromosome. Whatever the cause, alterations in body composition, with more fat and less muscle mass and diminished bone mineral mass, as well as increased risk of metabolic consequences, such as type 2 diabetes and the metabolic syndrome are all common in KS. These findings should be a concern as they are not simply laboratory findings; epidemiological studies in KS populations show an increased risk of both hospitalization and death from various diseases. Testosterone treatment should be offered to KS patients from early puberty, to secure a proper masculine development, nonetheless the evidence is weak or nonexisting, since no randomized controlled trials have ever been published. Here, we will review the current knowledge of hypogonadism in KS and the rationale for testosterone treatment and try to give our best recommendations for surveillance of this rather common, but often ignored, syndrome.

Monoamines and neurosteroids in sexual function during induced hypogonadism in healthy men.

PubMed

Bloch, Miki; Rubinow, David R; Berlin, Kate; Kevala, Karl R; Kim, Hee-Yong; Schmidt, Peter J

2006-04-01

Although the behavioral effects of high-dose androgen administration may involve alterations in serotonergic activity, few studies have investigated the impact of androgen withdrawal on the central nervous system in humans. To examine the effects of pharmacologically induced hypogonadism on several cerebrospinal fluid (CSF) systems that could mediate the behavioral concomitants of hypogonadism. Double-blind assessment of the effects of the short-term induction of hypogonadism and subsequent replacement with testosterone and placebo in a crossover design. National Institutes of Health, Bethesda, Md. Twelve healthy male volunteers. We administered the gonadotropin-releasing hormone agonist leuprolide acetate (7.5 mg intramuscularly every 4 weeks) to the healthy male volunteers, creating a hypogonadal state, and then either replaced testosterone (200 mg intramuscularly) or administered a placebo every 2 weeks for 1 month. Mood and behavioral symptoms were monitored with daily self-ratings, and lumbar punctures were performed during both hypogonadal (placebo) and testosterone-replaced conditions for CSF levels of steroids and monoamine metabolites. The CSF testosterone, dihydrotestosterone, and androsterone levels were significantly lower during hypogonadism (P=.002, .04, and .046, respectively), but no significant changes were observed in CSF measures of 5-hydroxyindoleacetic acid, homovanillic acid, dehydroepiandrosterone, or pregnenolone. Decreased sexual interest was observed during the hypogonadal state compared with both baseline and testosterone replacement (P=.009) and correlated significantly with CSF measures of androsterone during both hypogonadism and testosterone replacement (r = -0.76 and -0.81, respectively; P<.01). Moreover, the change in severity of decreased sexual interest correlated significantly with the change in CSF androsterone levels between testosterone replacement and hypogonadism (r = -0.68; P<.05). The CSF 5-hydroxyindoleacetic acid and

Late-Onset Hypogonadism and Testosterone Replacement in Older Men.

PubMed

Bhattacharya, Rajib K; Bhattacharya, Shelley B

2015-11-01

Late-onset hypogonadism is an underdiagnosed and easily treated condition defined by low serum testosterone levels in men older than 65 years. When treated, a significant improvement in quality of life may be reached in this rapidly rising sector of the population. During the evaluation, laboratory tests and a full medication review should be performed to exclude other illnesses or adverse effects from medications. The major goal of treatment in this population is treating the symptoms related to hypogonadism. There has not been clear evidence supporting universally giving older men with low serum testosterone levels and hypogonadal symptoms testosterone replacement therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

The prevalence of Hypogonadism among diabetic and non-diabetic men in Jordan.

PubMed

Al Hayek, Ayman A; Khawaja, Nahla M; Khader, Yousef S; Jaffal, Sahar K; Ajlouni, Kamel M

2014-01-01

Determine the prevalence of hypogonadism among diabetic and non-diabetic men in Jordan. A cross-sectional study of 1717 men (1089 participants with type 2 diabetes and 628 non-diabetic subjects). Both groups were inquired to answer the Androgen Deficiency for aging male (ADAM) questionnaire. Early morning Total testosterone, prolactin, sex hormone binding globulin, follicle stimulating hormone, leutinizing hormone, HbA1c and fasting blood sugar were measured. Hypogonadism was defined as total testosterone <3 ng/ml and calculated free testosterone <5 ng/dl. The prevalence of Hypogonadism among all study participants was 18.5%. The prevalence of Hypogonadism in diabetic and non-diabetic men was 24.3% and 8.3%, respectively. The mean (SD) total testosterone concentration of diabetic and non-diabetic men was 3.78 ng/ml (1.7) and 4.92 ng/ml (2.5), respectively (P- value <0.005). In response to (ADAM) questionnaire, 19.8% of diabetics and 3% of the non-diabetics had symptomatic androgen deficiency (P value <0.005). Hypogonadism and symptomatic androgen deficiency were negatively and significantly related to diabetes, monthly income and age (P value <0.005). Hypogonadism is a prevalent disorder among Jordanian diabetic population. Symptoms of androgen deficiency should be corroborated with testosterone level to establish a multidisciplinary approach for management of hypogonadism. Copyright © 2014 Elsevier Inc. All rights reserved.

Tale of two rare diseases

PubMed Central

Shukla, Ravindra; Basu, Asish Kumar; Mandal, Biplab; Mukhopadhyay, Pradip; Maity, Animesh; Sinha, Anirban

2013-01-01

Idiopathic Hypogonadotropic hypogonadism (IHH) phenotype is variable &various genes have been decribed in association with IHH. We describe association of IHH with mosaic trisomy 13. A 20 year old male presented with lack of development of secondary sexual characters, normal height, micropenis, small testes, gynaecomastia, absence of axillary and pubic hairs, hyposmia, synkinesis, bilateral horizontal nystagmus and high arched palate. Investigations showed low gonadotropin, low total testosterone, LH after stimulation with 100 mcg tryptorelin sc was 11.42 mU/mL at 40 min. MRI of hypothalamo-pituitary region showed normal olfactory bulb and tract but shallow olfactory sulcus. Karyotype showed homologous Robertsonian translocation of chromosome 13. This case fits classical IHH except for LH rise on stimulation. Features of Patau syndrome which is associated with trisomy 13 are absent in our case. Mosaic trisomy 13, which can otherwise be rare incidental finding, has not been described in association with IHH. Causal association of novel mutation on chromosome 13 leading to aforementioned phenotype cannot be rule out. PMID:24251138

Central causes of hypogonadism--functional and organic.

PubMed

Warren, Michelle P; Vu, Caroline

2003-09-01

Whether caused by environmental factors, lesions, genetic mutations, drug interactions, or unknown origins, the path of the central causes of hypogonadism frequently leads back to the GnRH pulse generator. In some cases, the cause can be unequivocally traced to a single factor, such as some of the congenital syndromes previously described. In most instances, however, hypogonadism is occult or functional. Because of the wide spectrum and complexity of underlying causes, a definitive diagnosis, especially in functional causes of the disorder, is not always attainable.

When is a varicocele repair indicated: the dilemma of hypogonadism and erectile dysfunction?

PubMed

Dabaja, Ali A; Goldstein, Marc

2016-01-01

In the past, the indications for varicocelectomy are primarily for infertility with abnormal semen parameters, testicular hypotrophy/atrophy in adolescents, and/or pain. The surgical treatment of varicocele for hypogonadism is controversial and debated. Recently, multiple reports in the literature have suggested that varicocele is associated with hypogonadism and varicocele repair can increase testosterone levels. Men with hypogonadal symptoms should have at least two serum testosterone levels. Microsurgical varicocelectomy may be beneficial for men with clinically palpable varicoceles with documented hypogonadism. In this review, we summarize the most recent literature linking varicocele to hypogonadism and sexual dysfunction and the impact of repair on serum testosterone levels. We performed a search of the published English literature. The key words used were "varicocele and hypogonadism" and "varicocele surgery and testosterone." We included published studies after 1998. We, also, evaluated the effect of surgery on the changes in the serum testosterone level regardless of the indication for the varicocele repair.

Human Immunodeficiency Virus Infection and Male Hypogonadism: A Review.

PubMed

Kietsiriroje, Noppadol

2015-10-01

Hypogonadism is a common complication among HIV infected patients. The prevalence of hypogonadism is 30 to 50% in HIV infected men with wasting syndrome and 20 to 25% in those without wasting syndrome. HIV infection affects the entire hypothalamus-pituitary-gonadal axis via both direct and indirect effects, which are defined in four categories, 1) direct effect of HIV particles, 2) opportunistic infections, 3) HIV-related malignancy and its treatment, and 4) medications that are used for HIV infection or its opportunistic infection. The association between HIV infection, hypogonadism, and cardiovascular diseases has yet to be determined; however, there are data that HIV infection and its treatment, particularly protease inhibitors, worsened the metabolic profiles, which were surrogate markers of cardiovascular diseases. Considerably more attention should be paid to the diagnosis of hypogonadism in this group particularly because HIV infection increases both sex hormone-binding globulin and total testosterone level. Testosterone replacement shows benefits on mood, body composition, and seems to benefit the metabolic profile in HIV infected men with low body mass index.

Hypogonadism: Therapeutic Risks, Benefits, and Outcomes.

PubMed

Sigalos, John T; Pastuszak, Alexander W; Khera, Mohit

2018-03-01

Hypogonadism is a common condition defined by the presence of low serum testosterone levels and hypogonadal symptoms, and most commonly treated using testosterone therapy (TTh). The accuracy of diagnosis and appropriateness of treatment, along with proper follow-up, are increasingly important given the large increase in testosterone prescriptions and the recent concern for cardiovascular (CV) risk associated with TTh. In March of 2015, the US Food and Drug Administration required that testosterone product labels disclose a potential CV risk, despite the evidence base for this association being weak and inconclusive. However, TTh may improve CV outcomes rather than increase risks. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of hypogonadism in Klinefelter Syndrome

PubMed Central

Høst, Christian; Skakkebæk, Anne; Groth, Kristian A; Bojesen, Anders

2014-01-01

Klinefelter syndrome (KS) (47, XXY) is the most abundant sex-chromosome disorder, and is a common cause of infertility and hypogonadism in men. Most men with KS go through life without knowing the diagnosis, as only 25% are diagnosed and only a few of these before puberty. Apart from hypogonadism and azoospermia, most men with KS suffer from some degree of learning disability and may have various kinds of psychiatric problems. The effects of long-term hypogonadism may be difficult to discern from the gene dose effect of the extra X-chromosome. Whatever the cause, alterations in body composition, with more fat and less muscle mass and diminished bone mineral mass, as well as increased risk of metabolic consequences, such as type 2 diabetes and the metabolic syndrome are all common in KS. These findings should be a concern as they are not simply laboratory findings; epidemiological studies in KS populations show an increased risk of both hospitalization and death from various diseases. Testosterone treatment should be offered to KS patients from early puberty, to secure a proper masculine development, nonetheless the evidence is weak or nonexisting, since no randomized controlled trials have ever been published. Here, we will review the current knowledge of hypogonadism in KS and the rationale for testosterone treatment and try to give our best recommendations for surveillance of this rather common, but often ignored, syndrome. PMID:24407186

Inactivating KISS1 mutation and hypogonadotropic hypogonadism.

PubMed

Topaloglu, A Kemal; Tello, Javier A; Kotan, L Damla; Ozbek, Mehmet N; Yilmaz, M Bertan; Erdogan, Seref; Gurbuz, Fatih; Temiz, Fatih; Millar, Robert P; Yuksel, Bilgin

2012-02-16

Gonadotropin-releasing hormone (GnRH) is the central regulator of gonadotropins, which stimulate gonadal function. Hypothalamic neurons that produce kisspeptin and neurokinin B stimulate GnRH release. Inactivating mutations in the genes encoding the human kisspeptin receptor (KISS1R, formerly called GPR54), neurokinin B (TAC3), and the neurokinin B receptor (TACR3) result in pubertal failure. However, human kisspeptin loss-of-function mutations have not been described, and contradictory findings have been reported in Kiss1-knockout mice. We describe an inactivating mutation in KISS1 in a large consanguineous family that results in failure of pubertal progression, indicating that functional kisspeptin is important for puberty and reproduction in humans. (Funded by the Scientific and Technological Research Council of Turkey [TÜBİTAK] and others.).

Male and female hypogonadism are highly prevalent in South Africans with Addison's disease.

PubMed

Ross, I L; Levitt, N S; Blom, D J; Haarburger, D

2014-09-01

Hypogonadism may complicate Addison's disease (primary hypoadrenalism), but prevalence and metabolic sequelae of hypogonadism in Addison's disease are poorly described. We recruited patients from the South African Addison's disease national registry who received stable replacement doses of hydrocortisone and had no acute illness. Male biochemical testosterone deficiency was defined as an early morning basal testosterone<9.9 nmol/l and premature ovarian failure (POF) when menopause occurred before 40 years of age. Cardiometabolic risk variables were measured in males only. Male hypogonadism prevalence was 33% (14/42), and 10 patients had newly diagnosed hypogonadism. Two untreated patients had elevated FSH or LH (>10 or 12 IU/l). Testosterone deficiency did not correlate with age, disease duration or hydrocortisone dose. Untreated male hypogonadal subjects had a higher (mean ± standard deviation) BMI compared to eugonadal subjects 29.2 ± 4.9 kg/m(2) vs. 24.7 ± 3.4 kg/m(2) (p=0.01) and a higher median (interquartile range) high-sensitive-CRP 6.4 (2.5-14.0) mg/l vs. 1.45 (0.6-2.8) mg/l (p=0.002). There were no differences between the 2 groups in lipids, lipoproteins and fasting glucose. The median (interquartile range) DHEAS was lower in the hypogonadal 0.31 (0.27-0.37) μmol/l, compared with the eugonadal group 0.75 (0.50-1.51) μmol/l (p=0.005). POF was documented in 11% of female patients. Male testosterone deficiency was highly prevalent in this cohort and was primarily due to secondary hypogonadism. Only BMI and hs-CRP were increased in untreated male hypogonadal subjects. Male and female hypogonadism appears to be a common complication of Addison's disease and may contribute to its morbidity. © Georg Thieme Verlag KG Stuttgart · New York.

Profile of follitropin alpha/lutropin alpha combination for the stimulation of follicular development in women with severe luteinizing hormone and follicle-stimulating hormone deficiency

PubMed Central

Rinaldi, Leonardo; Selman, Helmy

2016-01-01

A severe gonadotropin deficiency together with chronic estradiol deficiency leading to amenorrhea characterizes patients suffering from hypogonadotropic hypogonadism. Administration of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to these patients has been shown to be essential in achieving successful stimulation of follicular development, ovulation, and rescue of fertility. In recent years, the availability of both recombinant FSH (rFSH) and recombinant LH (rLH) has provided a new therapeutic option for the stimulation of follicular growth in hypopituitary–hypogonadotropic women (World Health Organization Group I). In this article, we review the data reported in the literature to highlight the role and the efficacy of using recombinant gonadotropins, rFSH and rLH, in the treatment of women with severe LH/FSH deficiency. Although the studies on this issue are limited and the experiences available in the literature are few due to the small number of such patients, it is clearly evident that the recombinant gonadotropins rFSH and rLH are efficient in treating patients affected by hypogonadotropic hypogonadism. The results observed in the studies reported in this review suggest that recombinant gonadotropins are able to induce proper follicular growth, oocyte maturation, and eventually pregnancy in this group of women. Moreover, the clinical use of recombinant gonadotropins in this type of patients has given more insight into some endocrinological aspects of ovarian function that have not yet been fully understood. PMID:27307766

Hypogonadism in DM1 and its relationship to erectile dysfunction.

PubMed

Antonini, Giovanni; Clemenzi, Alessandro; Bucci, Elisabetta; De Marco, Emanuela; Morino, Stefania; Di Pasquale, Antonella; Latino, Pamela; Ruga, Gilda; Lenzi, Andrea; Vanacore, Nicola; Radicioni, Antonio F

2011-07-01

Myotonic dystrophy type 1 (DM1) is characterized by both a premature appearance of age-related phenotypes and multiple organ involvement, which affects skeletal and smooth muscle as well as the eye, heart, central nervous system, and endocrine system. Although erectile dysfunction (ED) is a frequent complaint in patients with DM1, it has not been investigated in great depth. Hypogonadism, which is reported to be one of the physical causes of ED in the general population, frequently occurs in DM1. We planned this case-control study to evaluate the relationship between hypogonadism, as defined by the sexual hormone profile (FSH, LH, testosterone (T) and prolactin) and ED, as assessed by means of an internationally validated self-administered questionnaire (IIEF). DM1 patients had significantly increased mean levels of both gonadotropins (FSH and LH) (p < 0.0001) and a reduced mean level of T (p < 0.0001) when compared to controls. Twelve patients were eugonadic (normal LH, T, and FSH), while 18 displayed hormonal evidence of hypogonadism, characterized by tubular failure (increased FSH) in all the subjects and associated with interstitial failure in 14 subjects: seven with primary hypogonadism (increased LH and reduced T) and seven with compensated hypogonadism (increased LH and normal T). Patients with hormonal evidence of interstitial failure had a larger CTG expansion (p = 0.008), longer disease duration (p = 0.013), higher grade of disease (p = 0.004) and lower erectile function score (p = 0.02) than eugonadic patients. Impotence occurred in 13/14 hypogonadic patients with interstitial failure and in 5/12 eugonadic patients (p = 0.017, OR = 18.2).

Circulating endothelial cells as marker of endothelial damage in male hypogonadism.

PubMed

Milardi, Domenico; Grande, Giuseppe; Giampietro, Antonella; Vendittelli, Francesca; Palumbo, Sara; Tartaglione, Linda; Marana, Riccardo; Pontecorvi, Alfredo; de Marinis, Laura; Zuppi, Cecilia; Capoluongo, Ettore

2012-01-01

Testosterone deficiency has become a frequently diagnosed condition in today's society affected by epidemic obesity, and is associated with cardiovascular risk. Recent studies have established the importance of altered vascular endothelium function in cardiovascular disease. The damage to the endothelium might also cause endothelial cell detachment, resulting in increased numbers of circulating endothelial cells (CEC) within the bloodstream. To evaluate whether hypogonadism could modify CEC count in peripheral bloodstream, we investigated peripheral blood CEC count using the CellSearch System, a semiautomatic method to accurately and reliably enumerate CECs, which are sorted based on a CD146(+), CD105(+), DAPI(+), CD45(-) phenotype, in a population of 20 patients with hypogonadism. The control group comprised 10 age- and sex-matched healthy participants. CEC count per milliliter was significantly increased in patients with hypogonadism vs the control group. In the group with hypogonadism, an inverse exponential correlation was present between testosterone levels and CEC count per milliliter. A direct linear correlation was present between waist circumference and CECs and between body mass index and CECs. The regression analysis showed that testosterone was the significant independent determinant of CECs. Our results underline that male hypogonadism is associated with endothelial dysfunction. The correlation between CEC and waist circumference underlines that visceral obesity may be synergically implicated in this regulation. Future studies are required to unveil the mechanisms involved in the pathogenesis of testosterone-induced endothelial disfunction, which may provide novel therapeutic targets to be incorporated in the management of hypogonadism.

Phase II drugs currently being investigated for the treatment of hypogonadism.

PubMed

Udedibia, Emeka; Kaminetsky, Jed

2014-12-01

Hypogonadism is the most common endocrine disorder, which affects men of all age groups. Recent shifts in public awareness, increased screening and recognition of symptoms and updated diagnostic criteria have led to an increase in men diagnosed as hypogonadal, including middle-aged and older men who previously would have been considered eugonadal. The increase in testosterone replacement therapy (TRT) has paralleled an increase in advancements of treatment options. Although current therapies are highly efficacious for many men, there remains a need for newer therapies that are more cost-effective, preserve ease of use and administration, mitigate undesirable effects and closely mimic physiological levels of testosterone. In this review, the authors discuss current TRTs and therapies in development for the treatment of hypogonadism. The focus is on therapies under Phase II investigation or those who have recently completed Phase II study. With several new therapies in development, the authors expect advancements in achieving treatment benchmarks that meet the needs of the individual symptomatic hypogonadal male. Increased public awareness of hypogonadism and TRT has led to a welcomed expansion in the choice of TRT options. These include new delivery systems, formulations, routes of administration and non-testosterone modalities.

Influence of testosterone gel treatment on spermatogenesis in men with hypogonadism.

PubMed

George, Mskhalaya; Yulia, Tishova; Svetlana, Kalinchenko

2014-10-01

The prevalence of androgen deficiency in reproductive-aged men is increasing and needs new approach to long-term hypogonadism treatment that can preserve fertility. An open non-controlled pilot study included 18 men with eugonadotropic hypogonadism, who received transdermal testosterone gel treatment for 3 months. Sperm analysis was made before treatment and after 3 month of testosterone therapy. Testosterone level was normalized in all patients, but no negative effect was observed on spermatogenesis. Testosterone gel therapy may be a therapy of choice in hypogonadal men of reproductive age but further studies are needed.

Development of and Recovery from Secondary Hypogonadism in Aging Men: Prospective Results from the EMAS.

PubMed

Rastrelli, Giulia; Carter, Emma L; Ahern, Tomas; Finn, Joseph D; Antonio, Leen; O'Neill, Terence W; Bartfai, Gyorgy; Casanueva, Felipe F; Forti, Gianni; Keevil, Brian; Maggi, Mario; Giwercman, Aleksander; Han, Thang S; Huhtaniemi, Ilpo T; Kula, Krzysztof; Lean, Michael E J; Pendleton, Neil; Punab, Margus; Vanderschueren, Dirk; Wu, Frederick C W

2015-08-01

Secondary hypogonadism is common in aging men; its natural history and predisposing factors are unclear. The objectives were 1) to identify factors that predispose eugonadal men (T ≥ 10.5 nmol/L) to develop biochemical secondary hypogonadism (T < 10.5 nmol/L; LH ≤ 9.4 U/L) and secondary hypogonadal men to recover to eugonadism; and 2) to characterize clinical features associated with these transitions. The study was designed as a prospective observational general population cohort survey. The setting was clinical research centers. The participants were 3369 community-dwelling men aged 40-79 years in eight European centers. Interventions included observational follow-up of 4.3 years. Subjects were categorized according to change/no change in biochemical gonadal status during follow-up as follows: persistent eugonadal (n = 1909), incident secondary hypogonadal (n = 140), persistent secondary hypogonadal (n = 123), and recovered from secondary hypogonadism to eugonadism (n = 96). Baseline predictors and changes in clinical features associated with incident secondary hypogonadism and recovery from secondary hypogonadism were analyzed by regression models. The incidence of secondary hypogonadism was 155.9/10 000/year, whereas 42.9% of men with secondary hypogonadism recovered to eugonadism. Incident secondary hypogonadism was predicted by obesity (body mass index ≥ 30 kg/m(2); odds ratio [OR] = 2.86 [95% confidence interval, 1.67; 4.90]; P < .0001), weight gain (OR = 1.79 [1.15; 2.80]; P = .011), and increased waist circumference (OR = 1.73 [1.07; 2.81], P = .026; and OR = 2.64 [1.66; 4.21], P < .0001, for waist circumference 94-102 and ≥102 cm, respectively). Incident secondary hypogonadal men experienced new/worsening sexual symptoms (low libido, erectile dysfunction, and infrequent spontaneous erections). Recovery from secondary hypogonadism was predicted by nonobesity (OR = 2.28 [1.21; 4.31]; P = .011), weight loss (OR = 2.24 [1.04; 4.85]; P = .042), normal

Sertoli cell markers in the diagnosis of paediatric male hypogonadism.

PubMed

Grinspon, Romina P; Loreti, Nazareth; Braslavsky, Débora; Bedecarrás, Patricia; Ambao, Verónica; Gottlieb, Silvia; Bergadá, Ignacio; Campo, Stella M; Rey, Rodolfo A

2012-01-01

During childhood, the pituitary-testicular axis is partially dormant: testosterone secretion decreases following a drop in luteinising hormone levels; follicle-stimulating hormone (FSH) levels also go down. Conversely, Sertoli cells are most active, as revealed by the circulating levels of anti-Müllerian hormone (AMH) and inhibin B. Therefore, hypogonadism can best be evidenced, without stimulation tests, if Sertoli cell function is assessed. Serum AMH is high from fetal life until mid-puberty. Testicular AMH production increases in response to FSH and is potently inhibited by androgens. Inhibin B is high in the first years of life, then decreases partially while remaining clearly higher than in females, and increases again at puberty. Serum AMH and inhibin B are undetectable in anorchid patients. In primary or central hypogonadism affecting the whole gonad established in fetal life or childhood, all testicular markers are low. Conversely, when hypogonadism only affects Leydig cells, serum AMH and inhibin B are normal. In males of pubertal age with central hypogonadism, AMH and inhibin B are low. Treatment with FSH provokes an increase in serum levels of both Sertoli cell markers, whereas human chorionic gonadotrophin (hCG) administration increases testosterone levels. In conclusion, measurement of serum AMH and inhibin B is helpful in assessing testicular function, without need for stimulation tests, and orientates the aetiological diagnosis of paediatric male hypogonadism.

Hypogonadism in a male-to-female transsexual with super obesity.

PubMed

Ayanian, S; Irwig, M S

2013-08-01

The global obesity epidemic is having a profound impact on the health of populations. From a reproductive standpoint, obesity has been associated with infertility and hypogonadism. We present the case of a 29-year-old male-to-female transsexual with super obesity (body mass index >50) who was found to have profound hypogonadism with total and free testosterone levels in the normal female reference range. There is virtually no literature on the hormonal sequelae of obesity in transsexual people. The patient was prescribed an aromatase inhibitor, letrozole 2.5 mg twice daily for 2 weeks, to determine the role of oestrogen in the hypogonadism. The aromatase inhibitor reduced the serum oestradiol concentration from 125 to 6.9 pm. There were dramatic corresponding rises in total testosterone (2.8 to 10.7 nm), luteinising hormone (4.1 to 20.5 mIU ml(-1) ) and follicle stimulating hormone (1.8 to 15.3 mIU ml(-1) ). This diagnostic test demonstrated the important role of oestrogen in mediating the hypogonadism. After the testing, the patient was started on oestrogen therapy after a careful discussion of the benefits versus risks of oestrogen therapy. We anticipate that similar cases of hypogonadism in male-to-female transsexuals will likely become more common in an era of increased obesity rates. © 2012 Blackwell Verlag GmbH.

Familial idiopathic gonadotropin deficiency not linked to gene for gonadotropin-releasing hormone (GnRH) in Brazilian kindred

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faraco, J.; Francke, U.; Toledo, S.

Familial idiopathic gonadotropin deficiency (FIGD) is an autosomal recessive disorder which results in failure to develop secondary sexual characteristics. The origin is a hypothalamic defect resulting in insufficient secretion of gonadotropin-releasing hormone GnRH (also called LHRH, luteinizing hormone releasing hormone) and follicle-stimuating hormone (FSH). FIGD has been determined to be a separate entity from Kallmann syndrome which presents with hypogonadism as well as anosmia. The FIGD phenotype appears to be analogous to the phenotype of the hpg (hypogonadal) mouse. Because the hpg phenotype is the result of a structurally abnormal GnRH gene, we have studied the GnRH gene in individualsmore » from a previously reported Brazilian FIGD family. An informative dimorphic marker in the signal peptide sequence of the GnRH gene allowed assessment of linkage between the disease gene and the GnRH locus in this pedigree. We have concluded that the GnRH locus is not linked to the disease-causing mutation in these hypogonadal individuals. Recent evidence suggests that neuropeptide Y (NPY) may play a role in the initiation of puberty. We hypothesize that mutations in NPY may result in failure to secrete GnRH. We have characterized three diallelic frequent-cutter restriction fragment length polymorphisms within the human NPY locus, and are currently using these markers to determine if the NPY gene is linked to, and possibly the site of the disease mutation in this kindred.« less

[Hypogonadism in patients with testicular tumors and prostate cancer].

PubMed

Radko, Marcin; Syryło, Tomasz; Zieliński, Henryk

Hypogonadism is defined as an array of symptoms arising from a deficiency of androgens. It is caused by a hormonal and spermatogenic dysfunction of the testes. It results in impaired fertility and has a negative impact on the functions of multiple organs and systems, physical well-being, sexual functions and also mental state. Particularly patients with a history of cancer have a high risk of developing hypogonadism as a result of not only the nature of the disease, but mainly its treatment. While leaving the patient with cancer without treatment does not fall within the concept of the art of medicine and the ethical canon of a physician, the symptoms of hypogonadism are often ignored and left untreated. Among urological patients special attention should be given to those with testicular tumors and prostate cancer.

A practical guide to male hypogonadism in the primary care setting

PubMed Central

Dandona, P; Rosenberg, M T

2010-01-01

There is a high prevalence of hypogonadism in the older adult male population and the proportion of older men in the population is projected to rise in the future. As hypogonadism increases with age and is significantly associated with various comorbidities such as obesity, type 2 diabetes, hypertension, osteoporosis and metabolic syndrome, the physician is increasingly likely to have to treat hypogonadism in the clinic. The main symptoms of hypogonadism are reduced libido/erectile dysfunction, reduced muscle mass and strength, increased adiposity, osteoporosis/low bone mass, depressed mood and fatigue. Diagnosis of the condition requires the presence of low serum testosterone levels and the presence of hypogonadal symptoms. There are a number of formulations available for testosterone therapy including intramuscular injections, transdermal patches, transdermal gels, buccal patches and subcutaneous pellets. These are efficacious in establishing eugonadal testosterone levels in the blood and relieving symptoms. Restoration of testosterone levels to the normal range improves libido, sexual function, and mood; reduces fat body mass; increases lean body mass; and improves bone mineral density. Testosterone treatment is contraindicated in subjects with prostate cancer or benign prostate hyperplasia and risks of treatment are perceived to be high by many physicians. These risks, however, are often exaggerated and should not outweigh the benefits of testosterone treatment. PMID:20518947

Diagnosis of varicoceles in men undergoing vasectomy may lead to earlier detection of hypogonadism.

PubMed

Liu, Joceline S; Jones, Madeline; Casey, Jessica T; Fuchs, Amanda B; Cashy, John; Lin, William W

2014-06-01

To determine the temporal relationship between vasectomy, varicocele, and hypogonadism diagnosis. Many young men undergo their first thorough genitourinary examination in their adult lives at the time of vasectomy consultation, providing a unique opportunity for diagnosis of asymptomatic varicoceles. Varicoceles have recently been implicated as a possible reversible contributor to hypogonadism. Hypogonadism may be associated with significant adverse effect, including decreased libido, impaired cognitive function, and increased cardiovascular events. Early diagnosis and treatment of hypogonadism may prevent these adverse sequelae. Data were collected from the Truven Health Analytics MarketScan database, a large outpatient claims database. We reviewed records between 2003 and 2010 for male patients between the ages of 25 and 50 years with International Classification of Diseases, Ninth Revision codes for hypogonadism, vasectomy, and varicocele, and queried dates of first claim. A total of 15,679 men undergoing vasectomies were matched with 156,790 men with nonvasectomy claims in the same year. Vasectomy patients were diagnosed with varicocele at an earlier age (40.9 vs 42.5 years; P=.009). We identified 224,817 men between the ages of 25 and 50 years with a claim of hypogonadism, of which 5883 (2.6%) also had a claim of varicocele. Men with hypogonadism alone were older at presentation compared with men with an accompanying varicocele (41.3 [standard deviation±6.5] vs 34.9 [standard deviation±6.1]; P<.001). Men undergoing vasectomies are diagnosed with varicoceles at a younger age than age-matched controls. Men with varicoceles present with hypogonadism earlier than men without varicoceles. Earlier diagnosis of varicocele at the time of vasectomy allows for earlier detection of hypogonadism. Copyright © 2014 Elsevier Inc. All rights reserved.

Bone benefits of testosterone replacement therapy in male hypogonadism.

PubMed

Tirabassi, G; Biagioli, A; Balercia, G

2014-06-01

Osteoporosis is an asymptomatic, systemic bone disease characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in increased bone fragility. Such condition is often underdiagnosed and undertreated, especially in men, therefore considerably increasing the fracture risk. Of note, fracture-related morbidity and mortality is generally higher in men, partly due to greater frailty. On the other hand, male hypogonadism is defined as the failure of the testes to produce androgens, sperm, or both and it is often due to the ageing process. This disorder, in turn, causes many systemic disorders, and it is the condition mainly associated with male osteoporosis. Testosterone replacement therapy (TRT) is usually prescribed to restore optimal hormone levels, but conflicting data are available about the efficacy of TRT treatment on bone mineral density. In this review we extensively examined literature data about the usefulness of TRT in improving hypogonadism-associated low bone mineral density. Furthermore, we considered the complex relationship between male osteoporosis and hypogonadism, by specifically addressing the role of androgens in male bone physiology and the diagnostic approach to male osteoporosis and hypogonadism and also by dealing with some new related aspects such as the new endocrine pathways between bone and testis and the role of androgen receptor CAG polymorphism on bone density.

Hypogonadism in the Aging Male Diagnosis, Potential Benefits, and Risks of Testosterone Replacement Therapy

PubMed Central

Surampudi, Prasanth N.; Wang, Christina; Swerdloff, Ronald

2012-01-01

Hypogonadism in older men is a syndrome characterized by low serum testosterone levels and clinical symptoms often seen in hypogonadal men of younger age. These symptoms include decreased libido, erectile dysfunction, decreased vitality, decreased muscle mass, increased adiposity, depressed mood, osteopenia, and osteoporosis. Hypogonadism is a common disorder in aging men with a significant percentage of men over 60 years of age having serum testosterone levels below the lower limits of young male adults. There are a variety of testosterone formulations available for treatment of hypogonadism. Data from many small studies indicate that testosterone therapy offers several potential benefits to older hypogonadal men. A large multicenter NIH supported double blind, placebo controlled study is ongoing, and this study should greatly enhance the information available on efficacy and side effects of treatment. While safety data is available across many age groups, there are still unresolved concerns associated with testosterone therapy. We have reviewed the diagnostic methods as well as benefits and risks of testosterone replacement therapy for hypogonadism in aging men. PMID:22505891

Diminished androgen and estrogen receptors and aromatase levels in hypogonadal diabetic men: reversal with testosterone.

PubMed

Ghanim, Husam; Dhindsa, Sandeep; Abuaysheh, Sanaa; Batra, Manav; Kuhadiya, Nitesh D; Makdissi, Antoine; Chaudhuri, Ajay; Dandona, Paresh

2018-03-01

One-third of males with type 2 diabetes (T2DM) have hypogonadism, characterized by low total and free testosterone concentrations. We hypothesized that this condition is associated with a compensatory increase in the expression of androgen receptors (AR) and that testosterone replacement reverses these changes. We also measured estrogen receptor and aromatase expression. This is a randomized double-blind placebo-controlled trial. Thirty-two hypogonadal and 32 eugonadal men with T2DM were recruited. Hypogonadal men were randomized to receive intramuscular testosterone or saline every 2 weeks for 22 weeks. We measured AR, ERα and aromatase expression in peripheral blood mononuclear cells (MNC), adipose tissue and skeletal muscle in hypogonadal and eugonadal males with T2DM at baseline and after 22 weeks of treatment in those with hypogonadism. The mRNA expression of AR, ERα (ESR1) and aromatase in adipose tissue from hypogonadal men was significantly lower as compared to eugonadal men, and it increased significantly to levels comparable to those in eugonadal patients with T2DM following testosterone treatment. AR mRNA expression was also significantly lower in MNC from hypogonadal patients compared to eugonadal T2DM patients. Testosterone administration in hypogonadal patients also restored AR mRNA and nuclear extract protein levels from MNC to that in eugonadal patients. In the skeletal muscle, AR mRNA and protein expression are lower in men with hypogonadism. Testosterone treatment restored AR expression levels to that comparable to levels in eugonadal men. We conclude that, contrary to our hypothesis, the expression of AR, ERα and aromatase is significantly diminished in hypogonadal men as compared to eugonadal men with type 2 diabetes. Following testosterone replacement, there is a reversal of these deficits. © 2018 European Society of Endocrinology.

Assessment of Hypogonadism in Men With Type 2 Diabetes: A Cross-Sectional Study From Saudi Arabia

PubMed Central

Al Hayek, Ayman Abdullah; Robert, Asirvatham Alwin; Alshammari, Ghazi; Hakami, Husain; Al Dawish, Mohamed Abdulaziz

2017-01-01

BACKGROUND/OBJECTIVES A high incidence of hypogonadism in men with type 2 diabetes (T2D) has been globally reported. This study aimed to determining the frequency of hypogonadism and related risk factors among men with T2D in a single-site hospital in Saudi Arabia. DESIGN AND METHODS A cross-sectional study was performed on 157 men with T2D (between 30 and 70 years of age). Using a prestructured questionnaire, the demographic features of these patients were gathered and their medical records were referred to gather information regarding the duration of the diabetes, smoking habits, and the presence of retinopathy, neuropathy, and nephropathy. Besides these, the biochemical parameters, total testosterone (TT), free testosterone, sex hormone–binding globulin, follicle-stimulating hormone, luteinizing hormone, prolactin, serum lipids, and glycosylated hemoglobin were also recorded. All the patients submitted the fully completed Androgen Deficiency in Aging Male (ADAM) questionnaire. The combination of symptoms (positive ADAM score) plus a TT level ⩽8 nmol/L constituted the condition of hypogonadism. RESULTS The total frequency of hypogonadism was 22.9% (36/157). Of the 157 total patients, 123 (78.3%) were shown to be ADAM positive, and of these, 90 (73.2%) exhibited decreased libido, 116 (94.3%) had weak erections, and 99 (80.5%) reported more than 3 symptoms of ADAM. Of these hypogonadic patients, 22.2% (n = 8) revealed primary hypogonadism, whereas 77.8% (n = 28) showed secondary hypogonadism. From the univariate analysis conducted, significant relationship was observed between treatment type, body mass index (BMI), and hypogonadism. The regression analysis showed BMI acting an independent risk factor of hypogonadism. CONCLUSIONS Saudi men with T2D revealed a high incidence of hypogonadism. Body mass index was identified as an independent risk factor for hypogonadism. PMID:28579862

Cognitive Performance in Healthy Women During Induced Hypogonadism and Ovarian Steroid Addback

PubMed Central

Schmidt, Peter J.; Keenan, PA; Schenkel, Linda A; Berlin, Kate; Gibson, Carolyn; Rubinow, David R.

2012-01-01

Background Gynecology clinic-based studies have consistently demonstrated that induced hypogonadism is accompanied by a decline in cognitive test performance. However, a recent study in healthy asymptomatic controls observed that neither induced hypogonadism nor estradiol replacement influenced cognitive performance. Thus the effects of induced hypogonadism on cognition might not be uniformly experienced across individual women. Moreover, discrepancies in the effects of hypogonadism on cognition also could suggest the existence of specific risk phenotypes that predict a woman’s symptomatic experience during the menopause. In this study, we examined the effects of induced hypogonadism and ovarian steroid replacement on cognitive performance in healthy premenopausal women. Methods Ovarian suppression was induced with a GnRH agonist (Lupron) and then physiologic levels of estradiol and progesterone were re-introduced in 23 women. Cognitive tests were administered during each hormone condition. To evaluate possible practice effects arising during repeated testing, an identical battery of tests was administered at the same time intervals in 11 untreated women. Results With the exception of an improved performance on mental rotation during estradiol, we observed no significant effects of estradiol or progesterone on measures of attention, concentration, or memory compared with hypogonadism. Conclusions In contrast to studies in which a decline in cognitive performance was observed in women receiving ovarian suppression therapy for an underlying gynecologic condition, we confirm a prior report demonstrating that short term changes in gonadal steroids have a limited effect on cognition in young, healthy, women. Differences in the clinical characteristics of the women receiving GnRH agonists could predict a risk for ovarian steroid-related changes in cognitive performance during induced, and possibly, natural menopause. Key Words: estradiol, hypogonadism, progesterone

Adult-onset hypogonadism: evaluation and role of testosterone replacement therapy.

PubMed

Davidiuk, Andrew J; Broderick, Gregory A

2016-12-01

Testosterone deficiency (TD) has become a growing concern in the field of men's sexual health, with an increasing number of men presenting for evaluation of this condition. Given the increasing demand for testosterone replacement therapy (TRT), a panel of experts met in August of 2015 to discuss the treatment of men who present for evaluation in the setting of low or normal gonadotropin levels and the associated signs and symptoms of hypogonadism. This constellation of factors can be associated with elements of both primary and secondary hypogonadism. Because this syndrome commonly occurs in men who are middle-aged and older, it was termed adult-onset hypogonadism (AOH). AOH can be defined by the following elements: low levels of testosterone, associated signs and symptoms of hypogonadism, and low or normal gonadotropin levels. Although there are significant benefits of TRT for patients with AOH, candidates also need to understand the potential risks. Patients undergoing TRT will need to be monitored regularly because there are potential complications that can develop with long-term use. This review is aimed at providing a deeper understanding of AOH, discussing the benefits and risks of TRT, and outlining each modality of TRT in use for AOH.

ENU Mutagenesis in Mice Identifies Candidate Genes For Hypogonadism

PubMed Central

Weiss, Jeffrey; Hurley, Lisa A.; Harris, Rebecca M.; Finlayson, Courtney; Tong, Minghan; Fisher, Lisa A.; Moran, Jennifer L.; Beier, David R.; Mason, Christopher; Jameson, J. Larry

2012-01-01

Genome-wide mutagenesis was performed in mice to identify candidate genes for male infertility, for which the predominant causes remain idiopathic. Mice were mutagenized using N-ethyl-N-nitrosourea (ENU), bred, and screened for phenotypes associated with the male urogenital system. Fifteen heritable lines were isolated and chromosomal loci were assigned using low density genome-wide SNP arrays. Ten of the fifteen lines were pursued further using higher resolution SNP analysis to narrow the candidate gene regions. Exon sequencing of candidate genes identified mutations in mice with cystic kidneys (Bicc1), cryptorchidism (Rxfp2), restricted germ cell deficiency (Plk4), and severe germ cell deficiency (Prdm9). In two other lines with severe hypogonadism candidate sequencing failed to identify mutations, suggesting defects in genes with previously undocumented roles in gonadal function. These genomic intervals were sequenced in their entirety and a candidate mutation was identified in SnrpE in one of the two lines. The line harboring the SnrpE variant retains substantial spermatogenesis despite small testis size, an unusual phenotype. In addition to the reproductive defects, heritable phenotypes were observed in mice with ataxia (Myo5a), tremors (Pmp22), growth retardation (unknown gene), and hydrocephalus (unknown gene). These results demonstrate that the ENU screen is an effective tool for identifying potential causes of male infertility. PMID:22258617

Association of hypogonadism and type II diabetes in men attending an outpatient erectile dysfunction clinic.

PubMed

Corona, G; Mannucci, E; Petrone, L; Ricca, V; Balercia, G; Mansani, R; Chiarini, V; Giommi, R; Forti, G; Maggi, M

2006-01-01

Patients with diabetes mellitus (DM) were more often hypogonadal than normal fasting glucose subjects. The aim of this investigation is the assessment of characteristics and psychobiological correlates of DM associated with hypogonadism (DMAH). The Structured Interview SIEDY was used along with several biochemical, psychological and instrumental investigations in a series of more than 1200 patients with erectile dysfunction (ED); 16% of whom with type II DM. Hypogonadism was defined as circulating total testosterone (T) below 10.4 nmol/l. The prevalence of hypogonadism was 24.5% in DM versus 12.6% in the rest of the sample (P < 0.0001); differences in the prevalence of hypogonadism retained significance after adjustment for age and BMI. DMAH was associated with typical hypogonadism-related symptoms, such as reduction in sexual desire, leading to a decreased number of sexual attempts, and with higher depressive symptomatology. In DMAH, testis size and LH concentrations were significantly reduced, suggesting a central origin of the disease. At penile Duplex ultrasound examination, diabetic patients and in particular hypogonadal type II diabetic patients showed lower levels of basal and dynamic (after PGE1 injection) peak systolic velocity and acceleration, when compared to the rest of the sample, even after adjustment for age and BMI. Our results show that hypogonadism is frequently associated with type II DM, at least in the 6th decade. DMAH might exacerbate sexual dysfunction by reducing libido and mood and further compromising penile vascular reactivity.

Klinefelter Syndrome and medical treatment: hypogonadism and beyond.

PubMed

Chang, Simon; Skakkebæk, Anne; Gravholt, Claus Højbjerg

2015-01-01

Klinefelter syndrome (KS), though described more than 70 years ago, still imposes significant diagnostic challenges. Based on data from epidemiological studies, KS is associated with increased morbidity and mortality. Although the pathophysiology and etiology behind these observations are as yet not well understood, a significant contribution of hypogonadism, central to the syndrome, is traditionally suspected. However, other unknown effects inherent to the syndrome also seem to modify the disease pattern. Herein we show that KS is under-diagnosed since only roughly 25% of patients are diagnosed and the mean age of diagnosis is during adult life. KS is associated with increased morbidity resulting in loss of 2-5 years in lifespan with increased mortality from different diseases and a poor socioeconomic profile. Small testes, hypergonadothrophic hypogonadism and cognitive impairment are usually found. The accompanying hypogonadism can lead to altered body composition and a risk of developing metabolic syndrome, type 2 diabetes and cardiovascular disease. Cancer risk is generally not different from that observed in the background population, although specific cancers like breast cancer and extragonadal germ cell tumors are seen more frequently in KS. The mainstay of medical treatment is testosterone replacement therapy to both attenuate acute and long-term consequences of hypogonadism and possibly prevent the frequent comorbidity. We believe that the diagnostic challenges should be tackled more efficiently, while there is also a pressing need to generate better evidence for timing and the proper dose of testosterone replacement. We advocate for a multidisciplinary setup with the inclusion of pediatricians, speech therapists, general practitioners, psychologists, infertility specialists, urologists and endocrinologists.

Selective androgen receptor modulators for the treatment of late onset male hypogonadism.

PubMed

Coss, Christopher C; Jones, Amanda; Hancock, Michael L; Steiner, Mitchell S; Dalton, James T

2014-01-01

Several testosterone preparations are used in the treatment of hypogonadism in the ageing male. These therapies differ in their convenience, flexibility, regional availability and expense but share their pharmacokinetic basis of approval and dearth of long-term safety data. The brevity and relatively reduced cost of pharmacokinetic based registration trials provides little commercial incentive to develop improved novel therapies for the treatment of late onset male hypogonadism. Selective androgen receptor modulators (SARMs) have been shown to provide anabolic benefit in the absence of androgenic effects on prostate, hair and skin. Current clinical development for SARMs is focused on acute muscle wasting conditions with defi ned clinical endpoints of physical function and lean body mass. Similar regulatory clarity concerning clinical deficits in men with hypogonadism is required before the beneficial pharmacology and desirable pharmacokinetics of SARMs can be employed in the treatment of late onset male hypogonadism.

Selective androgen receptor modulators for the treatment of late onset male hypogonadism

PubMed Central

Coss, Christopher C; Jones, Amanda; Hancock, Michael L; Steiner, Mitchell S; Dalton, James T

2014-01-01

Several testosterone preparations are used in the treatment of hypogonadism in the ageing male. These therapies differ in their convenience, flexibility, regional availability and expense but share their pharmacokinetic basis of approval and dearth of long-term safety data. The brevity and relatively reduced cost of pharmacokinetic based registration trials provides little commercial incentive to develop improved novel therapies for the treatment of late onset male hypogonadism. Selective androgen receptor modulators (SARMs) have been shown to provide anabolic benefit in the absence of androgenic effects on prostate, hair and skin. Current clinical development for SARMs is focused on acute muscle wasting conditions with defined clinical endpoints of physical function and lean body mass. Similar regulatory clarity concerning clinical deficits in men with hypogonadism is required before the beneficial pharmacology and desirable pharmacokinetics of SARMs can be employed in the treatment of late onset male hypogonadism. PMID:24407183

Spreading the Clinical Window for Diagnosing Fetal-Onset Hypogonadism in Boys

PubMed Central

Grinspon, Romina P.; Loreti, Nazareth; Braslavsky, Débora; Valeri, Clara; Schteingart, Helena; Ballerini, María Gabriela; Bedecarrás, Patricia; Ambao, Verónica; Gottlieb, Silvia; Ropelato, María Gabriela; Bergadá, Ignacio; Campo, Stella M.; Rey, Rodolfo A.

2014-01-01

In early fetal development, the testis secretes – independent of pituitary gonadotropins – androgens and anti-Müllerian hormone (AMH) that are essential for male sex differentiation. In the second half of fetal life, the hypothalamic–pituitary axis gains control of testicular hormone secretion. Follicle-stimulating hormone (FSH) controls Sertoli cell proliferation, responsible for testis volume increase and AMH and inhibin B secretion, whereas luteinizing hormone (LH) regulates Leydig cell androgen and INSL3 secretion, involved in the growth and trophism of male external genitalia and in testis descent. This differential regulation of testicular function between early and late fetal periods underlies the distinct clinical presentations of fetal-onset hypogonadism in the newborn male: primary hypogonadism results in ambiguous or female genitalia when early fetal-onset, whereas it becomes clinically undistinguishable from central hypogonadism when established later in fetal life. The assessment of the hypothalamic–pituitary–gonadal axis in male has classically relied on the measurement of gonadotropin and testosterone levels in serum. These hormone levels normally decline 3–6 months after birth, thus constraining the clinical evaluation window for diagnosing male hypogonadism. The advent of new markers of gonadal function has spread this clinical window beyond the first 6 months of life. In this review, we discuss the advantages and limitations of old and new markers used for the functional assessment of the hypothalamic–pituitary–testicular axis in boys suspected of fetal-onset hypogonadism. PMID:24847309

Pituitary iron and volume predict hypogonadism in transfusional iron overload.

PubMed

Noetzli, Leila J; Panigrahy, Ashok; Mittelman, Steven D; Hyderi, Aleya; Dongelyan, Ani; Coates, Thomas D; Wood, John C

2012-02-01

Hypogonadism is the most common morbidity in patients with transfusion-dependent anemias such as thalassemia major. We used magnetic resonance imaging (MRI) to measure pituitary R2 (iron) and volume to determine at what age these patients develop pituitary iron overload and volume loss. We recruited 56 patients (47 with thalassemia major, five with chronically transfused thalassemia intermedia and four with Blackfan-Diamond syndrome) to have pituitary MRIs to measure pituitary R2 and volume. Hypogonadism was defined clinically based on the timing of secondary sexual characteristics or the need for sex hormone replacement therapy. Patients with transfusional iron overload begin to develop pituitary iron overload in the first decade of life; however, clinically significant volume loss was not observed until the second decade of life. Severe pituitary iron deposition (Z > 5) and volume loss (Z < -2.5) were independently predictive of hypogonadism. Pituitary R2 correlated significantly with serum ferritin as well as liver, pancreatic, and cardiac iron deposition by MRI. Log pancreas R2* was the best single predictor for pituitary iron, with an area under the receiving operator characteristic curve of 0.88, but log cardiac R2* and ferritin were retained on multivariate regression with a combined r(2) of 0.71. Pituitary iron overload and volume loss were independently predictive of hypogonadism. Many patients with moderate-to-severe pituitary iron overload retained normal gland volume and function, representing a potential therapeutic window. The subset of hypogonadal patients having preserved gland volumes may also explain improvements in pituitary function observed following intensive chelation therapy. Copyright © 2011 Wiley Periodicals, Inc.

Pharmacologically Induced Hypogonadism and Sexual Function in Healthy Young Women and Men

PubMed Central

Schmidt, Peter J; Steinberg, Emma M; Negro, Paula Palladino; Haq, Nazli; Gibson, Carolyn; Rubinow, David R

2008-01-01

Studies fail to find uniform effects of age-related or induced hypogonadism on human sexual function. We examined the effects of induced hypogonadism on sexual function in healthy men and women and attempted to identify predictors of the sexual response to induced hypogonadism or hormone addback. The study design used was a double-blind, controlled, crossover (self-as-own control). The study setting was an ambulatory care clinic in a research hospital, and the participants were 20 men (average ± SD age = 28.5 ± 6.2 years) and 20 women (average ± SD age = 33.5 ± 8.7 years), all healthy and with no history of psychiatric illness. A multidimensional scale assessing several domains of sexual function was the main outcome measure. Participants of the study received depot leuprolide acetate (Lupron) every 4 weeks for 3 months (men) or 5 months (women). After the first month of Lupron alone, men received (in addition to Lupron) testosterone enanthate (200 mg intramuscularly) or placebo every 2 weeks for 1 month each. Women received Lupron alone for 2 months, and then, in addition to Lupron, they received estradiol and progesterone for 5 weeks each. The results of the study: in women, hypogonadism resulted in a significant decrease in global measures of sexual functioning, principally reflecting a significant decrease in the reported quality of orgasm. In men, hypogonadism resulted in significant reductions in all measured domains of sexual function. Testosterone restored sexual functioning scores in men to those seen at baseline, whereas neither estradiol nor progesterone significantly improved the reduced sexual functioning associated with hypogonadism in women. Induced hypogonadism decreased sexual function in a similar number of men and women. No predictors of response were identified except for levels of sexual function at baseline. In conclusion, our data do not support a simple deficiency model for the role of gonadal steroids in human sexual function; moreover

The Triglycerides and Glucose Index rather than HOMA-IR is more associated with Hypogonadism in Chinese men.

PubMed

Zhang, Kun; Chen, Yi; Liu, Lijie; Lu, Meng; Cheng, Jing; Gao, Fengbin; Wang, Ningjian; Shen, Zhoujun; Lu, Yingli

2017-11-20

Previous studies have reported that insulin resistant and low testosterone are related. The triglyceride and glucose index (TyG) well mirrors insulin sensitivity. No study investigated the application of TyG in male hypogonadism. We aimed to explore whether TyG was associated with hypogonadism, and also evaluate the ability of TyG compared to HOMA-IR as a possible hypogonadism predictor. A total of 4299 male subjects were enrolled from 22 sites in East China. Hypogonadism was defined as total testosterone <11.3 nmol/L. 695 (16.2%) hypogonadal men had significantly higher TyG index. The prevalence of hypogonadism stepwise increased across increasing TyG quartiles (P < 0.01). TyG was negatively associated with sex hormones and hypogonadism after adjustment for age, current smoking status, hypertension and overweight/obesity (all P for trend <0.01). The full-adjusted odds ratio was 6.1 for the highest quartile compared with the lowest quartile of TyG (95% CI 4.51, 8.25, P < 0.001). On ROC curve analysis, a larger area under the curve was found for TyG (0.71, 95% CI 0.69,0.73) than for HOMA-IR (0.68, 95% CI 0.66,0.70). Thus, the TyG was significantly associated with a higher prevalence of hypogonadism in Chinese men. TyG had a better predictive power for hypogonadism than HOMA-IR.

Male hypogonadism: an extended classification based on a developmental, endocrine physiology-based approach.

PubMed

Rey, R A; Grinspon, R P; Gottlieb, S; Pasqualini, T; Knoblovits, P; Aszpis, S; Pacenza, N; Stewart Usher, J; Bergadá, I; Campo, S M

2013-01-01

Normal testicular physiology results from the integrated function of the tubular and interstitial compartments. Serum markers of interstitial tissue function are testosterone and insulin-like factor 3 (INSL3), whereas tubular function can be assessed by sperm count, morphology and motility, and serum anti-Müllerian hormone (AMH) and inhibin B. The classical definition of male hypogonadism refers to testicular failure associated with androgen deficiency, without considering potential deficiencies in germ and Sertoli cells. Furthermore, the classical definition does not consider the fact that low basal serum testosterone cannot be equated to hypogonadism in childhood, because Leydig cells are normally quiescent. A broader clinical definition of hypogonadism that could be applied to male patients in different periods of life requires a comprehensive consideration of the physiology of the hypothalamic-pituitary-testicular axis and its disturbances along development. Here we propose an extended classification of male hypogonadism based on the pathophysiology of the hypothalamic-pituitary-testicular axis in different periods of life. The clinical and biochemical features of male hypogonadism vary according to the following: (i) the level of the hypothalamic-pituitary-testicular axis primarily affected: central, primary or combined; (ii) the testicular cell population initially impaired: whole testis dysfunction or dissociated testicular dysfunction, and: (iii) the period of life when the gonadal function begins to fail: foetal-onset or postnatal-onset. The evaluation of basal testicular function in infancy and childhood relies mainly on the assessment of Sertoli cell markers (AMH and inhibin B). Hypergonadotropism should not be considered a sine qua non condition for the diagnosis of primary hypogonadism in childhood. Finally, the lack of elevation of gonadotropins in adolescents or adults with primary gonadal failure is indicative of a combined hypogonadism involving

Systematic literature review of the risk factors, comorbidities, and consequences of hypogonadism in men.

PubMed

Zarotsky, V; Huang, M-Y; Carman, W; Morgentaler, A; Singhal, P K; Coffin, D; Jones, T H

2014-11-01

The objective of this review was to summarize the literature on the risk factors, comorbidities, and consequences of male hypogonadism, which is defined as a syndrome complex that includes biochemical confirmation of low testosterone (T) and the consistent symptoms and signs associated with low T. A systematic literature search was performed in PubMed/MEDLINE, EMBASE, Cochrane Library for articles published in the last 10 years on risk factors, comorbidities, and consequences of male hypogonadism. Of the 53 relevant studies identified, nine examined potential risk factors, 14 examined potential comorbidities, and 30 examined potential consequences of male hypogonadism. Based on studies conducted in Asia, Australia, Europe, and North & South America, the important factors that predicted and correlated with hypogonadism were advanced age, obesity, a diagnosis of metabolic syndrome (MetS), and a poor general health status. Diabetes mellitus was correlated with hypogonadism in most studies, but was not established as a risk factor. Although diseases, such as coronary heart disease, hypertension, stroke, and peripheral arterial disease did not predict hypogonadism, they did correlate with incident low T. The data reviewed on potential consequences suggest that low T levels may be linked to earlier all-cause and cardiovascular related mortality among men. This literature review suggests that men with certain factors, such as advanced age, obesity, MetS, and poor general health, are more likely to have and develop hypogonadism. Low levels of T may have important long-term negative health consequences. © 2014 American Society of Andrology and European Academy of Andrology.

20 years of leptin: role of leptin in human reproductive disorders.

PubMed

Chou, Sharon H; Mantzoros, Christos

2014-10-01

Leptin, as a key hormone in energy homeostasis, regulates neuroendocrine function, including reproduction. It has a permissive role in the initiation of puberty and maintenance of the hypothalamic-pituitary-gonadal axis. This is notable in patients with either congenital or acquired leptin deficiency from a state of chronic energy insufficiency. Hypothalamic amenorrhea is the best-studied, with clinical trials confirming a causative role of leptin in hypogonadotropic hypogonadism. Implications of leptin deficiency have also emerged in the pathophysiology of hypogonadism in type 1 diabetes. At the other end of the spectrum, hyperleptinemia may play a role in hypogonadism associated with obesity, polycystic ovarian syndrome, and type 2 diabetes. In these conditions of energy excess, mechanisms of reproductive dysfunction include central leptin resistance as well as direct effects at the gonadal level. Thus, reproductive dysfunction due to energy imbalance at both ends can be linked to leptin. © 2014 Society for Endocrinology.

Clinical Characteristics, Health Care Utilization and Costs Among Men with Primary or Secondary Hypogonadism in a US Commercially Insured Population.

PubMed

Grabner, Michael; Bodhani, Amit; Khandelwal, Nikhil; Palli, Swetha; Bonine, Nicole; Khera, Mohit

2017-01-01

Hypogonadism is broadly associated with increases in chronic comorbid conditions and health care costs. Little is known about the specific impact of primary and secondary hypogonadism on health care costs. To characterize the health care cost and utilization burden of primary and secondary hypogonadism in a population of US men with commercial insurance. Newly diagnosed patients with International Classification of Diseases, Ninth Revision, Clinical Modification codes associated with specific medical conditions known to have a high prevalence of testosterone deficiency (ie, relating to primary or secondary hypogonadism) or who had fills for testosterone replacement therapy from January 1, 2007 through April 30, 2013 were identified in administrative claims data from the HealthCore Integrated Research Database. A cohort of patients without hypogonadism was matched on demographics and comorbidities. The matched hypogonadism and non-hypogonadism cohorts (n = 5,777 in each cohort) were compared during a 12-month follow-up period. Direct health care expenditures and utilization were assessed for all causes and for hypogonadism-related claims. Costs included out-of-pocket patient expenditures and those paid by the insurer. Hypogonadism and matched non-hypogonadism cohorts were similar in demographics (mean age = 50 years) and diagnosed comorbid conditions in the 12 months preceding the index date. In the year after the index date, mean all-cause expenditures for patients with hypogonadism increased by 62% (from $5,425 to $8,813) compared with 25% for the matched controls (from $4,786 to $5,992; P < .01 for follow-up difference between groups). Approximately 16% of total mean costs ($1,377), primarily outpatient and pharmacy costs, were identifiable as related to hypogonadism. These data from a population of US men with commercial insurance coverage showed a greater resource use burden for patients with primary and secondary hypogonadism compared with similar patients

CAG repeat testing of androgen receptor polymorphism: is this necessary for the best clinical management of hypogonadism?

PubMed

Francomano, Davide; Greco, Emanuela A; Lenzi, Andrea; Aversa, Antonio

2013-10-01

It is controversial whether or not testing the length of the androgen receptor polymorphism in clinical practice is useful for correct diagnosis and treatment of hypogonadism. To describe the molecular and clinical implications of testing the length of the androgen receptor polymorphism for treatment of hypogonadism in both male and female subjects. A systematic Medline search was conducted using several terms related to and including the terms "androgen receptor," "CAG-repeat polymorphism," "male hypogonadism," "female hypogonadism," and "neurodegenerative disease." Clinical evidence that demonstrates the importance of CAG repeat number investigation in male and female hypogonadism. A thorough review of the clinical utility of CAG repeat polymorphism investigation in men and women with hypogonadism is presented. The role of AR CAG repeat number investigation in hypogonadism (male and female) is not yet established in the clinical practice. In both sexes, a role during clinical management of hormonal replacement therapies may be hypothesized, but the CAG repeat number's relationship with the presence or absence of hypogonadal symptoms remains unclear. Pharmacogenomic investigations of the AR polymorphism may be a future option to tailor testosterone titration individually and to better identify subjects as potentially more or less responsive to treatments; also, investigation may be important to individually predict beneficial and side effects in special subpopulations, specifically, obese men and postmenopausal women. © 2013 International Society for Sexual Medicine.

Hypogonadism as a possible link between metabolic diseases and erectile dysfunction in aging men.

PubMed

Corona, Giovanni; Bianchini, Silvia; Sforza, Alessandra; Vignozzi, Linda; Maggi, Mario

2015-01-01

There is evidence demonstrating that sexual complaints represent the most specific symptoms associated with late onset hypogonadism, while central obesity is the most specific sign. In obese men, hypogonadism can further worsen the metabolic profile and increase abdominal fat. In addition, although hypogonadism can exacerbate obesity-associated erectile dysfunction (ED), recent data suggest that a direct contribution of fat-derived factors could be hypothesized. In particular, an animal model recently documented that fat accumulation induces several hepatic pro-inflammatory genes closely linked to corpora cavernosa endothelial dysfunction. Lifestyle modifications and weight loss are the first steps in the treatment of ED patients with obesity or metabolic diseases. In symptomatic hypogonadal men with metabolic impairment and obesity, combining the effect of testosterone substitution with lifestyle modifications could result in better outcomes.

[The treatment of hypogonadism and maintenance of fertility in men].

PubMed

Rabijewski, Michał

2016-03-01

In past few years we observed the increasing of population of men, who are treated with testosterone due to hypogonadism associated with aging but the most of them have no indications to testosterone replacement therapy. The classical symptoms of hypogonadism including depression, loss of libido, erectile dysfunction, and fatigue may be related to any others diseases. The increase in prevalence of androgenic anabolic steroids specifically among younger athletes is also observed. Exogenous testosterone and anabolic androgenic steroids can inhibit the hypothalamic-pituitary-gonadal axis leading to decreasing of endogenous testosterone synthesis and impaired spermatogenesis. In hypogonadal men who are in reproduction age the goal of therapy should be not only replacement therapy but also achiving and/or maintaining of spermatogenesis. Human chorionic gonadotropin (hCG) and selective estrogens receptor modulators (SERM) are efficacy in treatment of clinical signs and symptoms of hypoigonadism, has been shown to reverse spermatogenesis disturbances and can to maintain elevated intratesticular testosterone levels necessary to optimal spermatogenesis. © 2016 MEDPRESS.

Anorexia Nervosa and its Associated Endocrinopathy in Young People

PubMed Central

Misra, Madhusmita; Klibanski, Anne

2016-01-01

Anorexia nervosa (AN) is a condition of severe undernutrition associated with adaptive changes in many endocrine axes. These changes include hypogonadotropic hypogonadism, acquired growth hormone resistance with low insulin like growth factor-1 (IGF-1) levels, hypercortisolemia, altered secretion of adipokines and appetite regulating hormones, and low bone mineral density (BMD). Bone health is impaired subsequent to low BMI, decreased lean mass, and the endocrine changes described above. In addition to low areal BMD, AN is characterized by a decrease in volumetric BMD, changes in bone geometry, and reductions in strength estimates, leading to an increased risk for fracture. Weight restoration is essential for restoration of normal endocrine function; however, hypercortisolemia, high PYY levels, and ghrelin dynamics may not completely normalize. In some patients, hypogonadotropic hypogonadism persists despite weight restoration. Weight gain and menstrual recovery are critical for improving bone health in AN, however, residual deficits may persist. Physiologic estrogen replacement using transdermal, but not oral, estrogen increases bone accrual in adolescents with AN, while bisphosphonates improve BMD in adults. Recombinant human IGF-1 and teriparatide have been used in a few studies as bone anabolic therapies. More data are necessary to determine the optimal therapeutic strategies for low BMD in AN. PMID:26863308

Risk Factors for Hypogonadism in Male Patients with Type 2 Diabetes

PubMed Central

Zheng, Rendong; Cao, Lin; Cao, Wen; Chu, Xiaoqiu; Hu, Yongxin; Zhang, Huifeng; Xu, Juan; Sun, Hongping; Bao, Weiping; Liu, Kemian; Liu, Chao

2016-01-01

Background. Male hypogonadism is an endocrine disease characterized by low levels of serum testosterone and is closely related to the development of diabetes. The purpose of the present study was to observe the risk factors for hypogonadism in male patients with type 2 diabetes. Methods. A total of 213 patients with type 2 diabetes were enrolled and divided into a low total testosterone (TT) group (=75) and a normal TT group (=138). The patients' blood glucose, blood lipids, serum insulin, and sex hormones were measured. The correlations between the patients' metabolic index and sex hormone levels were analyzed. Results. Compared with the normal TT group, body mass index (BMI), fasting insulin (FINS), and HOMA insulin resistance index (HOMA-IR) levels were significantly higher, but the luteinizing hormone (LH) levels were significantly lower in the low TT group (p < 0.05). Correlation analyses found that TT was negatively correlated with BMI, waist circumference (WC), FINS, and HOMA-IR. TT was positively correlated with LH and follicle-stimulating hormone (FSH). Conclusions. Several risk factors of diabetes associated closely with hypogonadism. BMI, metabolic syndrome (MS), HOMA-IR, and LH are independent risk factors for hypogonadism in male patients with type 2 diabetes. PMID:27006953

Registry of Hypogonadism in Men (RHYME): design of a multi-national longitudinal, observational registry of exogenous testosterone use in hypogonadal men.

PubMed

Rosen, Raymond C; Wu, Frederick C W; Behre, Hermann M; Roehrborn, Claus G; Schröder, Fritz H; Siami, Flora S; Martha, Julia F; Finn, Joseph D; Araujo, Andre B

2013-03-01

Despite the prevalence of hypogonadism (HG) and widespread use of testosterone therapy, little is known about the safety/effectiveness of long-term testosterone use. The Registry of Hypogonadism in Men (RHYME) is a multi-national patient registry assessing prostate health and other outcomes associated with testosterone treatment in men. Observational patient disease registry. RHYME is a non-interventional disease registry with longitudinal data collection on a large sample (N = 999) of well-characterized, hypogonadal men aged 18 years or older. The Registry will prospectively evaluate male patients diagnosed with HG, who have not previously been treated with testosterone therapy. Key design features include: (1) broad inclusion/exclusion criteria, (2) standardized central laboratory hormone assays, (3) independent adjudication of prostate biopsies and mortalities, (4) standard of care treatment, (5) comprehensive medical record and questionnaire data at six months and annually post-enrollment and (6) adequate statistical power for assessing prostate endpoints at 36 months. A total of 25 clinical sites in six European countries (Germany, Italy, the Netherlands, Spain, Sweden and the United Kingdom) have completed recruitment for the study. Recruitment was initiated in May 2009, and completed in December 2011. Data collection is ongoing with a minimum of two years of follow-up on all patients.

Clinical Use of Aromatase Inhibitors in Adult Males.

PubMed

Tan, Ronny B W; Guay, Andre T; Hellstrom, Wayne J G

2014-04-01

There is a growing interest in the treatment of late-onset hypogonadism, another name for the study of testosterone deficiency in an older age group. Initial attempts at testosterone replacement have also brought attention to the possible adverse effects on the patients' cardiovascular risk factors and their prostate health. The "female" hormone estradiol is no longer considered as the feminizing hormone, as it has been identified to have an effect on the sexual and general well-being of adult males. Urologists and endocrinologists alike have started to pay attention to the serum T/E 2 (testosterone : estradiol) ratio that appears to be more important than the respective individual hormonal levels. Therein lies the possible role of aromatase inhibitors (AIs) in restoring the normal balance of serum testosterone and estradiol levels for the adequate treatment of late-onset hypogonadism, while limiting the potential adverse effects. Currently, other established clinical indications of AIs include the treatment of breast cancer in female patients and developmental growth problems in pediatric patients. This review evaluates the role of AIs as a treatment option for late-onset hypogonadism and the evidence for its other clinical uses in men, including its possible adverse effects. A literature review was performed with regards to the use of aromatase inhibitors in adult males, the role of estrogens in adult males, as well as adverse effect of AIs on bone health in adult males. To evaluate the evidence for the use of AIs in adult males to treat late-onset hypogonadism, obesity-related hypogonadotropic hypogonadism, gynecomastia, and male subfertility. To evaluate the evidence for the possible adverse effects on the bone health of adult males with the use of AIs. Currently there is no literature to recommend the use of AIs in adult males to treat late-onset hypogonadism, obesity-related hypogonadotropic hypogonadism, gynecomastia, or male subfertility, although some

Readability, credibility and quality of patient information for hypogonadism and testosterone replacement therapy on the Internet.

PubMed

McBride, J A; Carson, C C; Coward, R M

2017-05-01

The incidence of hypogonadism and use of testosterone replacement therapy (TRT) are rising, while data evaluating the complexity and quality of health-care information available to patients on the Internet for hypogonadism or TRT are lacking. This study focuses on characterizing the readability, credibility and quality of patient-centered information for hypogonadism on the Internet. A Google search was performed to identify top-ranked websites offering patient-centered information on hypogonadism and TRT. Readability was quantified by reading grade level using several validated instruments. Credibility and quality were determined by several additional criteria, including authorship, references, health-care information quality certification and breadth of topic discussion. Twenty of 75 total sites identified (27%) met the inclusion and exclusion criteria and were evaluated. The mean reading grade level was 13.1 (interquartile range 11.7-15.1), with all websites demonstrating reading levels significantly above recommended levels. Less than half (45%) of the sites were neither authored nor reviewed by a physician, 60% contained at least one reference and 40% were certified for displaying quality health-care information. Over half (55%) did not comprehensively discuss management of hypogonadism or mention treatment-associated risks. In conclusion, the majority of patient-centered information available on the Internet regarding hypogonadism or TRT is of poor quality and too complex for the average patient to comprehend. These results highlight a critical shortage in easily accessible, high-quality, comprehensible online patient health-care information on hypogonadism and TRT.

Anti-müllerian hormone and sertoli cell function in paediatric male hypogonadism.

PubMed

Grinspon, Romina P; Rey, Rodolfo A

2010-01-01

In the prepubertal male, Sertoli cells are the most active testicular cell population. Without stimulation tests, prepubertal hypogonadism can only be evidenced if Sertoli cell function is assessed. Anti-müllerian hormone (AMH) is a distinctive marker of the prepubertal Sertoli cell. Serum AMH is high from fetal life until puberty. In postnatal life, AMH testicular production is stimulated by FSH and potently inhibited by androgens. In anorchid patients, AMH is undetectable. In prepubertal males with fetal- or childhood-onset primary or central hypogonadism affecting the whole gonad, serum AMH is low. Conversely, when hypogonadism only affects Leydig cells (i.e., LH/human chorionic gonadotrophin receptor or steroidogenic enzyme defects), serum AMH is normal/high. AMH is also normal/high in patients with androgen insensitivity. In patients of pubertal age with central hypogonadism, AMH is low for Tanner stage - reflecting lack of FSH stimulus, - but high for age - reflecting lack of testosterone inhibitory effect. FSH treatment results in serum AMH rise, whereas human chorionic gonadotrophin treatment increases testosterone levels which inhibit AMH production. In conclusion, AMH determination is helpful in assessing gonadal function, without need for stimulation tests, and orientates the aetiological diagnosis of paediatric male hypogonadism. Furthermore, serum AMH is an excellent marker of FSH and androgen action in the testis. Copyright 2010 S. Karger AG, Basel.

MMACHC gene mutation in familial hypogonadism with neurological symptoms.

PubMed

Shi, Changhe; Shang, Dandan; Sun, Shilei; Mao, Chengyuan; Qin, Jie; Luo, Haiyang; Shao, Mingwei; Chen, Zhengguang; Liu, Yutao; Liu, Xinjing; Song, Bo; Xu, Yuming

2015-12-15

Recent studies have convincingly documented that hypogonadism is a component of various hereditary disorders and is often recognized as an important clinical feature in combination with various neurological symptoms, yet, the causative genes in a few related families are still unknown. High-throughput sequencing has become an efficient method to identify causative genes in related complex hereditary disorders. In this study, we performed exome sequencing in a family presenting hypergonadotropic hypogonadism with neurological presentations of mental retardation, epilepsy, ataxia, and leukodystrophy. After bioinformatic analysis and Sanger sequencing validation, we identified compound heterozygous mutations: c.482G>A (p.R161Q) and c.609G>A (p.W203X) in MMACHC gene in this pedigree. MMACHC was previously confirmed to be responsible for methylmalonic aciduria (MMA) combined with homocystinuria, cblC type (cblC disease), a hereditary vitamin B12 metabolic disorder. Biochemical and gas chromatography-mass spectrometry (GC-MS) examinations in this pedigree further supported the cblC disease diagnosis. These results indicated that hypergonadotropic hypogonadism may be a novel clinical manifestation of cblC disease, but more reports on additional patients are needed to support this hypothesis. Copyright © 2015 Elsevier B.V. All rights reserved.

Natural course of hypogonadism diagnosed during hospitalization in aged male patients.

PubMed

Iglesias, P; Prado, F; Muñoz, A; Guerrero, M T; Macías, M C; Ridruejo, E; Tajada, P; García-Arévalo, C; Díez, J J

2015-04-01

Our aim was to assess short-term natural course of hypogonadism diagnosed during hospitalization for acute disease in aged male patients after discharge. A group of 43 hypogonadal males, aged 86.7±5.7 year, was studied. Serum concentrations of testosterone (T) and gonadotropins (follicle-stimulating hormone, FSH, and luteinizing hormone, LH) were measured in every patient both at admission and one month after discharge. Mean serum T at entry was 115.4±48.0 ng/dl. Hypogonadism was hyper-, hypo-, and normogonadotropic in 20 (46.5%), 20 (46.5%), and 3 (7.0%) patients, respectively. One month after discharge serum T concentrations increased significantly (230.9±135.6 ng/dl, p<0.001). At this point, more than half of the patients (n=27, 62.8%) showed normal serum T concentrations. Both gonadotropins, FSH (p<0.001), and LH (p=0.04) also increased one month after discharge. Approximately, half of the patients (13, 48.1%) who normalized serum T concentrations also showed normal serum gonadotropin concentrations. Patients who normalized their serum T concentrations one month after discharge showed significantly higher baseline values of T (134.7±33.9 ng/dl) than those who persisted with hypogonadism (n=16, 32.7%; 82.8±51.6 ng/dl, p<0.001). Lastly, serum T was the only independent predictor for achieving eugonadal status (OR 1.030; CI 95%, 1.010-1.050; p<0.001). In conclusion, about 63% of aged patients hospitalized for acute illness with hypogonadism discovered during hospitalization spontaneously normalize their serum T concentrations one month after discharge. Serum gonadotropin concentrations also increased after discharge. Serum T levels at admission was an independent predictor for the normalization of serum T concentrations.

Male Hypogonadism and Osteoporosis: The Effects, Clinical Consequences, and Treatment of Testosterone Deficiency in Bone Health

PubMed Central

Houdek, Devon

2017-01-01

It is well recognized that bone loss accelerates in hypogonadal states, with female menopause being the classic example of sex hormones affecting the regulation of bone metabolism. Underrepresented is our knowledge of the clinical and metabolic consequences of overt male hypogonadism, as well as the more subtle age-related decline in testosterone on bone quality. While menopause and estrogen deficiency are well-known risk factors for osteoporosis in women, the effects of age-related testosterone decline in men on bone health are less well known. Much of our knowledge comes from observational studies and retrospective analysis on small groups of men with variable causes of primary or secondary hypogonadism and mild to overt testosterone deficiencies. This review aims to present the current knowledge of the consequences of adult male hypogonadism on bone metabolism. The direct and indirect effects of testosterone on bone cells will be explored as well as the important differences in male osteoporosis and assessment as compared to that in females. The clinical consequence of both primary and secondary hypogonadism, as well as testosterone decline in older males, on bone density and fracture risk in men will be summarized. Finally, the therapeutic options and their efficacy in male osteoporosis and hypogonadism will be discussed. PMID:28408926

[Andrologic consequences of chronic renal failure: State of the art for the yearly scientific report of the French National Association of Urology].

PubMed

Neuzillet, Y; Thuret, R; Kleinclauss, F; Timsit, M-O

2016-11-01

To describe the state of the art of current knowledge regarding gonadal consequences of end-stage chronic kidney disease (CKD) and renal transplantation. A systematic review of the literature search was performed from the databases Medline (NLM, Pubmed) and Embase, focused on the following keywords: "chronic kidney disease"; "chronic renal failure"; "hypogonadism"; "kidney transplantation"; "testicular dysfunction"; "testosterone". Publications obtained were selected based on methodology, language, date of publication (last 10 years) and relevance. Prospective and retrospective studies, in English or French, review articles; meta-analysis and guidelines were selected and analyzed. This search found 383 articles. After reading titles and abstracts, 51 were included in the text, based on their relevance. The prevalence of hypogonadism in CKD is reported between 24 % and 66 %, and decreases partially after renal transplantation. This is a hypogonadotropic hypogonadism whose pathophysiology is multifactorial, involving mainly a primitive testicular deficit, a hypothalamic-pituitary dysregulation, and an hyperprolactinemia. The consequences of this hypogonadism are not only sexual but also contribute to anemia, sarcopenia, atherosclerosis, and potentially in the progression of CKD. Hypogonadism is an independent risk factor for mortality in CKD patients. CKD is frequently associated with an hypogonadism whose correction is validated only in the setting of erectile dysfunction treatment. The other benefits of the correction of hypogonadism in the CKD patients, including overall survival, needs to be evaluated. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Connecting the Lines between Hypogonadism and Atherosclerosis

PubMed Central

Fahed, Akl C.; Gholmieh, Joanna M.; Azar, Sami T.

2012-01-01

Epidemiological studies show that atherosclerotic cardiovascular disease is a leading cause of morbidity and mortality worldwide and point to gender differences with ageing males being at highest risk. Atherosclerosis is a complex process that has several risk factors and mediators. Hypogonadism is a commonly undiagnosed disease that has been associated with many of the events, and risk factors leading to atherosclerosis. The mechanistic relations between testosterone levels, atherosclerotic events, and risk factors are poorly understood in many instances, but the links are clear. In this paper, we summarize the research journey that explains the link between hypogonadism, each of the atherosclerotic events, and risk factors. We look into the different areas from which lessons could be learned, including epidemiological studies, animal and laboratory experiments, studies on androgen deprivation therapy patients, and studies on testosterone-treated patients. We finish by providing recommendations for the clinician and needs for future research. PMID:22518131

46,XY hypergonadotropic hypogonadism and myasthenia gravis.

PubMed

Lichiardopol, Corina; Herlea, V; Ioan, Virginia; Tomulescu, V; Mixich, F

2006-01-01

Both hypergonadotropic hypogonadism and myasthenia gravis can be parts of type II autoimmune polyendocrine syndrome and association between the two disorders has been reported in few cases. A 14 year old male patient with a personal history of bilateral cryptorchidism and ptosis was referred for delayed puberty. Clinical examination revealed eunuchoid habitus, small, soft testes, gynecomastia, ptosis, a myasthenic deficit score of 22.5 points and an IQ of 84 points. Decreased testosterone (0.064 ng/mL) and elevated LH (64.5 mUI/mL) were consistent with hypergonadotropic hypogonadism and karyotype was normal: 46,XY. Thyroid function, haematologic evaluation, BUN, electrolytes, and glycemia were in the normal range. Therapy consisted of anticholinesterase inhibitors, immunosuppressants, corticotherapy, testosterone; thoracoscopic thymectomy was performed showing thymic lymphoid hyperplasia on histopathologic examination. Myasthenic score improved (12.5 points), progressive virilization occurred, and a year later the patient presented with cushingoid features and obesity.

Cardiovascular issues in hypogonadism and testosterone therapy.

PubMed

Shabsigh, Ridwan; Katz, Mark; Yan, Grace; Makhsida, Nawras

2005-12-26

A systematic literature search was conducted to investigate the cardiovascular issues related to hypogonadism and testosterone therapy. Vascular cells contain sex steroid hormone receptors. Testosterone can exert effects on the vascular wall, either by itself or through aromatization as estrogen. Hypogonadism is associated with central obesity; insulin resistance; low levels of high-density lipoprotein (HDL); high cholesterol levels; and high levels of low-density lipoprotein (LDL), triglycerides, fibrinogen, and plasminogen activator-1. Some observational studies show a correlation between low testosterone and cardiovascular disease (CVD), and others show no correlation. Interventional studies do not reveal a direct long-term relation between testosterone therapy and CVD. Short-term data suggest cardiovascular benefits of testosterone. Testosterone therapy has beneficial and deleterious effects on cardiovascular risk factors. It improves insulin sensitivity, central obesity, and lowers total cholesterol and LDL. In some studies, testosterone therapy has an HDL-lowering effect, and in other studies this effect is insignificant. This should not be assumed to be atherogenic because it might be related to reverse cholesterol transport and effects on the HDL(3) subfraction. The cardiovascular effects of testosterone therapy may be neutral to beneficial. There is no contraindication for testosterone therapy in men with CVD and diagnosed hypogonadism with or without erectile dysfunction. Caution should be exercised regarding occasional increases in hematocrit levels, especially in patients with congestive heart failure. Conversely, evidence does not support testosterone therapy in aging men for the purpose of cardiovascular benefit, despite claims to this effect. Further research on the cardiovascular benefits and risks of testosterone is strongly recommended.

Idiopathic ophthalmodynia and idiopathic rhinalgia: two topographic facial pain syndromes.

PubMed

Pareja, Juan A; Cuadrado, María L; Porta-Etessam, Jesús; Fernández-de-las-Peñas, César; Gili, Pablo; Caminero, Ana B; Cebrián, José L

2010-09-01

To describe 2 topographic facial pain conditions with the pain clearly localized in the eye (idiopathic ophthalmodynia) or in the nose (idiopathic rhinalgia), and to propose their distinction from persistent idiopathic facial pain. Persistent idiopathic facial pain, burning mouth syndrome, atypical odontalgia, and facial arthromyalgia are idiopathic facial pain syndromes that have been separated according to topographical criteria. Still, some other facial pain syndromes might have been veiled under the broad term of persistent idiopathic facial pain. Through a 10-year period we have studied all patients referred to our neurological clinic because of facial pain of unknown etiology that might deviate from all well-characterized facial pain syndromes. In a group of patients we have identified 2 consistent clinical pictures with pain precisely located either in the eye (n=11) or in the nose (n=7). Clinical features resembled those of other localized idiopathic facial syndromes, the key differences relying on the topographic distribution of the pain. Both idiopathic ophthalmodynia and idiopathic rhinalgia seem specific pain syndromes with a distinctive location, and may deserve a nosologic status just as other focal pain syndromes of the face. Whether all such focal syndromes are topographic variants of persistent idiopathic facial pain or independent disorders remains a controversial issue.

Testosterone Therapy and Glucose Homeostasis in Men with Testosterone Deficiency (Hypogonadism).

PubMed

Saad, Farid

2017-01-01

Since the early 1990s, it has been recognized that testosterone (T) levels are lower in men with type 2 diabetes mellitus (T2DM) compared with nondiabetic men (controls). Hypogonadism has been reported in approximately 50% of men with T2DM with robust correlations with measures of obesity, such as waist circumference and body mass index (BMI). In longitudinal studies, hypogonadism has been identified as a predictor of incident T2DM. Experimental withdrawal of T led to acute decreased insulin sensitivity, which can be reversed by normalization of T concentrations. Androgen deprivation therapy, commonly used in men with advanced prostate cancer, increases the risk of incident T2DM significantly.While short-term studies of T therapy in hypogonadal men with T2DM show only minor effects, long-term administration of T leads to meaningful and sustained improvements of glycemic control with parallel reductions in body weight and waist circumference. The more insulin-resistant and obese a patient is at the time of initiation of T therapy, the more improvements are noted. The observed effects are likely mediated by the increase in lean body mass invariably achieved by T therapy, as well as the improvement in energy and motivation, referred to as the psychotropic effects of T. As recommended by various guidelines, measuring T levels and, if indicated, restoring men's T levels into the normal physiological range can have a substantial impact on ameliorating T2DM in hypogonadal men.

Varicocele is associated with hypogonadism and impaired erectile function: a prospective comparative study.

PubMed

Ji, B; Jin, X-B

2017-08-01

We conducted this prospective comparative study to examine the hypothesis that varicocele was associated with hypogonadism and impaired erectile function as reflected in International Index of Erectile Function-5 (IIEF-5) scores as well as nocturnal penile tumescence and rigidity (NPTR) parameters. From December 2014 to December 2015, a total of 130 males with varicocele complaining of infertility or scrotal discomfort and 130 age-matched healthy males chosen from volunteer healthy hospital staff as controls were recruited in this study. Serum testosterone (TT) levels and IIEF-5 scores as well as NPTR parameters were evaluated and compared between varicocele and control subjects. All participants were further grouped into hypogonadism based on the cut-off value 300 ng/dL. A total of 45 of 130 patients were identified as hypogonadism, while it was not found in control subjects. A multivariate logistic regression with likelihood ratio test revealed that TT levels as well as grade III and II varicocele posed significant indicators for hypogonadism occurrence (chi-square of likelihood ratio = 12.40, df = 3, p < .01). Furthermore, TT levels and infertility duration were associated with IIEF-5 scores in a multivariate linear regression analysis (adjusted R 2  = 0.545). In conclusion, the correlation of grade III and II varicocele with an increased risk of hypogonadism was confirmed in this study and an impaired erectile function correlated with TT levels and infertility duration was also observed. © 2016 Blackwell Verlag GmbH.

Hypogonadism associated with muscle atrophy, physical inactivity and ESA hyporesponsiveness in men undergoing haemodialysis.

PubMed

Cobo, Gabriela; Gallar, Paloma; Di Gioia, Cristina; García Lacalle, Concepción; Camacho, Rosa; Rodriguez, Isabel; Ortega, Olimpia; Mon, Carmen; Vigil, Ana; Lindholm, Bengt; Carrero, Juan Jesús

Testosterone deficiency (hypogonadism) is common among men undergoing haemodialysis, but its clinical implications are not well characterized. Testosterone is an anabolic hormone that induces erythrocytosis and muscle synthesis. We hypothesized that testosterone deficiency would be associated with low muscle mass, physical inactivity and higher dosages of erythropoietin-stimulating agents (ESA). Single-center cross-sectional study of 57 male haemodialysis patients. None of the patients was undergoing testosterone replacement therapy. Total testosterone was measured in serum. Body composition (by bioelectrical impedance analysis) and physical activity (by the use of pedometers) were assessed. Patients with testosterone levels below the normal range were considered hypogonadal. Mean testosterone level was 321±146ng/dL; 20 patients (35%) were hypogonadal. Hypogonadal patients were older and had lower mean arterial blood pressure, higher interleukin-6 levels, lower lean body mass and higher fat body mass. A negative association between testosterone and normalized ESA dose was found in uni- and multivariate regression analyses. Testosterone levels directly correlated with lean body mass regardless of confounders. Hypogonadal patients had lower physical activity than their counterparts [2753±1784 vs. 4291±3225steps/day (p=0.04)]. The relationship between testosterone and physical activity was independent of age, comorbidities and inflammatory markers, but dependent on the proportion of muscle mass. Hypogonadism is common in our male haemodialysis population and is associated with higher ESA doses, reduced muscle mass and lower physical activity. The link between low testosterone levels and physical inactivity may conceivably relate to reduced muscle mass due to inadequate muscle protein synthesis. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Risk factors associated with hypogonadism in β-thalassemia major patients: predictors for a frequent complication of a rare disease.

PubMed

Albu, Alice; Barbu, Carmen Gabriela; Antonie, Lavinia; Vladareanu, Florentina; Fica, Simona

2014-09-01

β-Thalassemia major (BTM) is a rare disease that challenges clinicians because of the high prevalence of complications despite progress in the development of new therapeutic methods. The aim of this study was to identify clinical and hematological parameters associated with hypogonadism, the most frequent iron overload-related complication found in Romanian patients. Patients with BTM were evaluated in the Endocrinology Department of Elias Hospital between February 2004 and December 2013. Only patients who provided written informed consent were included in the study. A complete physical and hormonal evaluation was performed on all patients, and data regarding treatment of the hematological disease were collected. Of the evaluable patients, 85 were included in the study (median age, 21[10] years; range, 13-36 years). We found that 30.6% of the study participants (26 of 85) had normal gonadal status, 54.1% (46 of 85) had early forms of hypogonadism (delayed or arrested puberty), and 15.3% (n = 13) developed hypogonadism after complete sexual maturation. Patients with any form of hypogonadism were older (median age 22 vs 16.5 years, P = 0.047), had significantly lower average hemoglobin levels (P = 0.003), and had higher levels of serum ferritin (P = 0.006) versus patients without hypogonadism. Patients with delayed puberty were associated with increased average serum ferritin levels (P = 0.007), decreased hemoglobin levels (P = 0.001), and increased age at initiation of iron chelation therapy (P < 0.01). We found no significant differences between patients with early forms of hypogonadism and those with hypogonadism after complete sexual maturation, with respect to the analyzed parameters. Patients with adult hypogonadism were significantly older (median age 26 vs 16.5 years, P = 0.007) and tended to have higher serum ferritin levels (P = 0.056) compared with patients without hypogonadism. Our data show that hypogonadism is highly prevalent among Romanian patients

Hormonal development therapy (HDT) in hypogonadism in long-term view.

PubMed

Heinz, Marlene

2010-04-01

Since the 1960s, oestrogen deficiency in hypogonadism in girls has been successfully treated by a sort of analogous application of the menopausal hormone replacement therapy (HRT) scheme, here however, to induce and support sexual development in puberty and adolescence. The essential distinction between goals, ways and means of the two distinct hormonal treatments caused by menopause and by hypogonadism in puberty also suggests that the latter treatment is more characteristic of defining hormonal development therapy (HDT). Moreover, specific HDT in hypogonadism is essential for longitudinal growth of girls, functions of female reproductive system, bone and lipid metabolism and the immune, central nervous and cardiovascular systems. By contrast, the aim of menopausal replacement therapy in elderly women is treating negative effects of physiological loss of oestrogens as hot flush, lacks of female well-being and osteoporosis, while in hypogonadal girls there is of course nothing that might be replaced eventually. Especially in cases of absolute oestrogen deficiency, as in Turner syndrome and in other cases of premature ovarian failure, HDT has to be started at the age of expected puberty. An international consensus suggests possibly lifelong HDT for the lasting support of female development and functions. However, neither reliable studies about possible risks and side effects of continuous hormonal therapy in adult women with hypogonadismus nor a more precise consensus have emerged yet. Emphasising the term HDT particularly aims at putting more effort in getting over these paucities simultaneously. Indications, hormonal therapy, dosage, application and timing in puberty are described in this article. Aspects of long-term hormonal treatment are critically discussed. Copyright 2010 Elsevier Ltd. All rights reserved.

Hypogonadism as a new comorbidity in male patient's selection for bariatric surgery: towards an extended concept of metabolic surgery?

PubMed

Lucchese, M; Maggi, M

2013-12-01

Hypogonadism and subfertility can be frequently associated to obesity. These endocrine alterations may have consequences in the health and quality of life of obese men since they may result in impaired fertility and poor sexual life. As many clinical reports suggest, weight loss can ameliorate hypogonadism and, more generally, alterations in sex hormones. This effect is evident even when weight loss is induced by bariatric surgery. The evidence that hypogonadism in morbidly obese patients can regress after bariatric surgery should lead us to consider it as a modifiable comorbidity associated to obesity. This would have as a consequence that obese male patients with symptomatic hypogonadism could be candidates for bariatric surgery even with a BMI < 40 kg/m(2). Controlled clinical trials, involving obese hypogonadal males, should be encouraged.

HIV and hypogonadism: a new challenge for young-aged and middle-aged men on effective antiretroviral therapy.

PubMed

Lachâtre, Marie; Pasquet, Armelle; Ajana, Faïza; Soudan, Benoit; Lion, Georges; Bocket, Laurence; Cornavin, Pauline; Senneville, Eric; Boufassa, Faroudy; Chéret, Antoine

2017-01-28

Male hypogonadism is poorly defined in people living with HIV. Using a reliable free-testosterone assay, we examined the prevalence and risk factors of male hypogonadism among people living with HIV on effective antiretroviral therapy. Male hypogonadism was found in 12.4% of patients, twice the rate reported in the general population of the same age. Two risk thresholds, namely 5 years of antiretroviral therapy and 19% total body fat, may help to identify patients at risk.

Homozygous Loss-of-function Mutations in SOHLH1 in Patients With Nonsyndromic Hypergonadotropic Hypogonadism

PubMed Central

Bayram, Yavuz; Gulsuner, Suleyman; Guran, Tulay; Abaci, Ayhan; Yesil, Gozde; Gulsuner, Hilal Unal; Atay, Zeynep; Pierce, Sarah B.; Gambin, Tomasz; Lee, Ming; Turan, Serap; Bober, Ece; Atik, Mehmed M.; Walsh, Tom; Karaca, Ender; Pehlivan, Davut; Jhangiani, Shalini N.; Muzny, Donna; Bereket, Abdullah; Buyukgebiz, Atilla; Boerwinkle, Eric; Gibbs, Richard A.

2015-01-01

Context: Hypergonadotropic hypogonadism presents in females with delayed or arrested puberty, primary or secondary amenorrhea due to gonadal dysfunction, and is further characterized by elevated gonadotropins and low sex steroids. Chromosomal aberrations and various specific gene defects can lead to hypergonadotropic hypogonadism. Responsible genes include those with roles in gonadal development or maintenance, sex steroid synthesis, or end-organ resistance to gonadotropins. Identification of novel causative genes in this disorder will contribute to our understanding of the regulation of human reproductive function. Objectives: The aim of this study was to identify and report the gene responsible for autosomal-recessive hypergonadotropic hypogonadism in two unrelated families. Design and Participants: Clinical evaluation and whole-exome sequencing were performed in two pairs of sisters with nonsyndromic hypergonadotropic hypogonadism from two unrelated families. Results: Exome sequencing analysis revealed two different truncating mutations in the same gene: SOHLH1 c.705delT (p.Pro235fs*4) and SOHLH1 c.27C>G (p.Tyr9stop). Both mutations were unique to the families and segregation was consistent with Mendelian expectations for an autosomal-recessive mode of inheritance. Conclusions: Sohlh1 was known from previous mouse studies to be a transcriptional regulator that functions in the maintenance and survival of primordial ovarian follicles, but loss-of-function mutations in human females have not been reported. Our results provide evidence that homozygous-truncating mutations in SOHLH1 cause female nonsyndromic hypergonadotropic hypogonadism. PMID:25774885

Diversity of Pubertal Development in Cartilage-Hair Hypoplasia; Two Illustrative Cases.

PubMed

Holopainen, Elina; Vakkilainen, Svetlana; Mäkitie, Outi

2018-08-01

Cartilage-hair hypoplasia (CHH) is a rare chondrodysplasia, including disproportionate short stature, hypoplastic hair, immunodeficiency, and increased risk of malignancies. Absent pubertal growth spurt and absent pubic hair complicate monitoring of pubertal development in these patients. Two CHH patients with delayed puberty and excessive growth failure are described. One of the girls had hypogonadotropic hypogonadism whereas the other had hyponormogonadotropic hypogonadism with no spontaneous pubertal development and slow response to estrogen therapy, both requiring permanent replacement therapy. Careful follow-up of pubertal development in individuals with CHH and other growth-restricting bone diseases is needed. In delayed pubertal development timely hormone therapy is essential to ensure maximal growth and well developed secondary sex characteristics. Copyright © 2018 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Diabetes Mellitus-Associated Functional Hypercortisolism Impairs Sexual Function in Male Late-Onset Hypogonadism.

PubMed

Tirabassi, G; Corona, G; Lamonica, G R; Lenzi, A; Maggi, M; Balercia, G

2016-01-01

Functional hypercortisolism is generated by conditions able to chronically activate hypothalamic-pituitary-adrenal axis and has been proven to have a negative role in several complications. However, no study has evaluated the possible influence of diabetes mellitus-associated functional hypercortisolism on male hypogonadism and sexual function. We aimed to identify any association of hypothalamic-pituitary-adrenal axis dysregulation measures with testosterone and sexual function in men simultaneously affected by diabetes mellitus and late-onset hypogonadism. Fifteen diabetes mellitus and late-onset hypogonadism subjects suffering from functional hypercortisolism and fifteen diabetes mellitus and late-onset hypogonadism subjects who were free of functional hypercortisolism were retrospectively reviewed. Clinical, hormonal, and sexual parameters were considered. Hypercortisolemic subjects showed higher values of body mass index, waist, and glycated hemoglobin and lower ones of testosterone compared to normocortisolemic ones. All sexual parameters, except for orgasmic function, were significantly worse in hypercortisolemic than in normocortisolemic subjects. Hypercortisolemic patients showed higher values of cortisol after dexamethasone and urinary free cortisol as well as a lesser ACTH response after corticotropin releasing hormone test (ACTH area under curve) compared to normocortisolemic ones. No significant association was found at Poisson regression analysis between hormonal and sexual variables in normocortisolemic patients. In hypercortisolemic subjects, negative and significant associations of cortisol response after corticotropin releasing hormone (cortisol area under curve) with erectile function (β: -0.0008; p: 0.015) and total international index of erectile function score (β: -0.0006; p: 0.001) were evident. This study suggests for the first time the impairing influence of the dysregulated hypothalamic-pituitary-adrenal axis on sexual function in

High prevalence of hypogonadism and associated impaired metabolic and bone mineral status in subfertile men.

PubMed

Bobjer, Johannes; Bogefors, Karolina; Isaksson, Sigrid; Leijonhufvud, Irene; Åkesson, Kristina; Giwercman, Yvonne Lundberg; Giwercman, Aleksander

2016-08-01

It is yet unknown to which degree young subfertile men present with signs of hypogonadism and whether low testosterone concentration, like in older men, is associated with risk of osteoporosis and metabolic derangements in those subjects. The objective was therefore to investigate the prevalence of hypogonadism and its association with metabolic and bone parameters in young subfertile men. Cross-sectional case-control study. Men from infertile couples (n = 192); 18-50 years; sperm concentration <20 × 10(6) /ml and population-based age-matched controls (n = 199). Blood sampling, anthropometrics, blood pressure, ankle-brachial index and assessment by dual-energy X-ray absorptiometry were undertaken. Odds ratios of biochemical hypogonadism (total testosterone <8·0 nmol/l and/or luteinizing hormone ≥8·6 IU/l and/or ongoing androgen replacement therapy) were calculated. Serum concentrations of sex hormones, lipids, glucose, insulin and HbA1c were assessed and bone mineral density (BMD) evaluated. Compared to controls, the risk of hypogonadism was increased among subfertile men (OR 10; 95% CI, 5·1, 22), being highest in those with nonobstructive azoospermia. Hypogonadal men had higher HbA1c concentration (mean diff. 2·8 mmol/mol; 95% CI, 0·64, 4·9; P = 0·011) and lower lumbar spine BMD (mean diff. 0·05 g/cm(2) ; 95% CI, 0·01, 0·10; P = 0·032) compared to eugonadal subfertile men, even more pronounced in subfertile men with subnormal testosterone levels. Young subfertile men have 10 times increased OR of hypogonadism, which is linked to increased HbA1c and decreased bone mineralization. Endocrine assessment and, if needed, measures to prevent metabolic sequelae and osteoporosis should be included in the routine management of men from infertile couples. © 2016 John Wiley & Sons Ltd.

Causes of gynaecomastia in young adult males and factors associated with idiopathic gynaecomastia.

PubMed

Ersöz, Halil önder; Onde, Mehmet Emin; Terekeci, Hakan; Kurtoglu, Soner; Tor, Hayati

2002-10-01

Gynaecomastia is a common clinical condition. Persistent pubertal or late onset idiopathic gynaecomastia is the leading cause of gynaecomastia in different series. The aim of this study was the assessment of the prevalence and characteristics of different causes of gynaecomastia in young adult males, and evaluation of the factors associated with idiopathic gynaecomastia. Fifty-three male patients (mean age 22.04 +/- 2.22, range 19-29), who had been admitted to our outpatient clinics with gynaecomastia as the main presenting symptom were enrolled in the study. Patients were evaluated with breast palpation, breast ultrasonography, anthropometric measurements and sex steroid levels. Secondary causes of gynaecomastia were ruled out. Thirty age-matched healthy individuals were also studied as healthy control group. Idiopathic gynaecomastia was diagnosed in 31 of 53 patients (58%), with 17 (32%) persistent pubertal and 14 (24%) late onset course. Other causes of gynaecomastia were hypogonadism in 13 cases (25%), hyperprolactinaemia in five (9%), chronic liver disease in two (4%), and drug induced (prolonged use of H2 antagonists) in two (4%). Patients with idiopathic gynaecomastia, either pubertal or late onset, were compared with the healthy control group in order to find out associated factors. Anthropometric measurements revealed a significant increase in body weight and body mass index (BMI) in the patient group compared with healthy controls (72.4 +/- 13.3 vs. 63.6 +/- 7.9 kg, p = 0.0086 and 25.2 +/- 4.0 vs. 21.5 +/- 2.7 kg/m2, p = 0.0001). Total skin fold thickness (SFT) of four different regions were also higher in the patient group (50.9 +/- 22.1 vs. 32.6 +/- 10.2 mm, p = 0.0006) indicating a higher body fat percentage. Total serum testosterone (4.76 +/- 1.31 vs. 5.70 +/- 1.06 microg/mL, p = 0.0038) and luteinizing hormone (LH) (4.80 +/- 1.92 vs. 7.32 +/- 1.90 mIU/mL, p < 0.0001) levels were significantly lower in the patient group while oestradiol levels were

Pharmacologic Therapy in Men's Health: Hypogonadism, Erectile Dysfunction, and Benign Prostatic Hyperplasia.

PubMed

Berkseth, Kathryn E; Thirumalai, Arthi; Amory, John K

2016-07-01

This article reviews current pharmacologic treatment options for 3 common men's health concerns: hypogonadism, erectile dysfunction (ED), and benign prostatic hyperplasia (BPH). Specific topics addressed include: management of male hypogonadism using testosterone replacement therapy, use of oral phosphodiesterase inhibitors as first-line therapy for men with ED and the utility of intraurethral and intrapenile alprostadil injections for patients who do not respond to oral medications, and the role of alpha1-adrenergic antagonists, 5-alpha-reductase inhibitors, anticholinergic agents, and herbal therapies in the management of BPH. Copyright © 2016 Elsevier Inc. All rights reserved.

Visceral adiposity index and triglyceride/high-density lipoprotein cholesterol ratio in hypogonadism.

PubMed

Haymana, Cem; Sonmez, Alper; Aydogdu, Aydogan; Tapan, Serkan; Basaran, Yalcin; Meric, Coskun; Baskoy, Kamil; Dinc, Mustafa; Yazici, Mahmut; Taslipinar, Abdullah; Barcin, Cem; Yilmaz, Mahmut Ilker; Bolu, Erol; Azal, Omer

2017-01-01

Cardiometabolic risk is high in patients with hypogonadism. Visceral adiposity index (VAI) and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio are the practical markers of atherosclerosis and insulin resistance and independent predictors of cardiaovascular risk. To date, no study has evaluated VAI levels and TG/HDL-C ratio in hypogonadism. A total of 112 patients with congenital hypogonadotrophic hypogonadism (CHH) (mean age, 21.7 ± 2.06 years) and 124 healthy subjects (mean age, 21.5 ± 1.27 years) were enrolled. The demographic parameters, VAI, TG/HDL-C ratio, asymmetric dimethylarginine (ADMA), high-sensitivity C-reactive protein (hs-CRP), and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured for all participants. The patients had higher total cholesterol (p = 0.04), waist circumference, triglycerides, insulin, and HOMA-IR levels (p = 0.001 for all) than the healthy subjects. VAI and ADMA and TG/HDL-C levels were also higher in patients than in healthy subjects (p < 0.001 for all). VAI was weakly correlated with ADMA (r = 0.27, p = 0.015), HOMA-IR (r = 0.22, p = 0.006), hs-CRP (r = 0.19, p = 0.04), and total testosterone (r = -0.21, p = 0.009) levels, whereas TG/HDL-C ratio was weakly correlated weakly with ADMA (r = 0.30, p = 0.003), HOMA-IR (r = 0.22, p = 0.006), and total testosterone (r = -0.16, p = 0.03) levels. Neither VAI nor TG/HDL-C ratio determined ADMA, HOMA-IR, and hs-CRP levels. The results of this study demonstrate that patients with hypogonadism have elevated VAI and TG/HDL-C ratio. These values are significantly correlated with the surrogate markers of endothelial dysfunction, inflammation, and insulin resistance. However, the predictive roles of VAI and TG/HDL-C ratio are not significant. Prospective follow-up studies are warranted to clarify the role of VAI and TG/HDL-C ratio in predicting cardiometabolic risk in patients with hypogonadism.

Pharmacological management of late-onset hypogonadism.

PubMed

Rastrelli, Giulia; Maggi, Mario; Corona, Giovanni

2018-04-01

The frequency of late-onset hypogonadism (LOH) ranges between 2 and 15%. Up to 85% of LOH is due to a functional impairment of the hypothalamus-pituitary-testicular axis, mostly secondary to metabolic conditions. Areas covered: This paper provides a comprehensive review of all the available medications for treating LOH, including antiestrogens, gonadotropins and testosterone therapy (TTh). In addition, the evidence on clinical outcomes of these treatments is provided by meta-analyzing the results from the available randomized clinical trials. Expert commentary: The present data indicate that antiestrogens are able to increase testosterone levels without changing gonadotropins or even increasing them. Therefore, they may maintain, and even to stimulate spermatogenesis. However, their efficacy in treating LOH-associated symptoms has been scarcely tested and their use in LOH is off-label. In contrast, gonadotropins are indicated for hypogonadism, in particular when fertility is required. Information on the effects of gonadotropins on LOH is scanty and the impractical administration limits their use. TTh can be administered with different modalities, making it a suitable option for LOH, when fertility is not desired. The available meta-analyses show that TTh is able to improve sexual function and body composition, with more evident results obtained with transdermal and injectable preparations.

Idiopathic anaphylaxis.

PubMed

Fenny, Nana; Grammer, Leslie C

2015-05-01

Idiopathic anaphylaxis is a diagnosis of exclusion after other causes have been thoroughly evaluated and excluded. The pathogenesis of idiopathic anaphylaxis remains uncertain, although increased numbers of activated lymphocytes and circulating histamine-releasing factors have been implicated. Signs and symptoms of patients diagnosed with idiopathic anaphylaxis are indistinguishable from the manifestations of other forms of anaphylaxis. Treatment regimens are implemented based on the frequency and severity of patient symptoms and generally include the use of epinephrine autoinjectors, antihistamines, and steroids. The prognosis of idiopathic anaphylaxis is generally favorable with well-established treatment regimens and effective patient education. Copyright © 2015 Elsevier Inc. All rights reserved.

An Adult with Polyneuropathy and Hypogonadism due to Poems Syndrome.

PubMed

Zaidi, Saba; Sattar, Sidra; Asumal, Khealani Bhojo

2017-10-01

POEMS (acronym for polyneuropathy, organomegaly, endocrinopathy, M protein myeloma and skin changes), is a rare disease which occurs in the setting of plasma cell dyscrasias. We describe a case of an adult lady who presented with gradual onset weakness of all four limbs and multisystem involvement characterized by pedal edema, ascites, hyperpigmentation and hypogonadism. Nerve conduction study showed severe sensorimotor polyneuropathy. Serum immunofixation showed lambda light chain restricted monoclonal gammopathy. Bone marrow biopsy consistent with plasma cell dyscrasia. Hormonal assay showed decreased FSH, LH and estradiol levels which led us to diagnosis of hypogonadotrophic hypogonadism. The patient responded well to combination therapy of thalidomide, melphalan and dexamethasone. Eight months after the therapy, she noted decreased paresthesias and increased strength. She had reduced edema and ascites.

[Impact of androgen therapy on metabolic and inflammatory profiles in male hypogonadism].

PubMed

Chaabouni, Khansa; Naifar, Manel; Mejdoub, Nabila; Lahyani, Amina; Messedi, Mariem; Elleuch, Aida; Turki, Mouna; Jamoussi, Kamel; Abid, Mohamed; Ayedi, Fatma

2014-01-01

This study aims to evaluate the impact of androgen therapy on metabolic and inflammatoy profiles in male hypogonadic patients. Forty cases with isolated hypogonadism and 80 controls were enrolled. Clinical data were collected (age, weight, height, waist circonference and androgenothearapy). Blood tests were performed to evaluate testosterone, homeostasis index modal assessment (HOMA-IR), lipids and C reactive protein (CRP). Among hypogonadic patients, 14 of them were treated for 4 +/- 3.4 years. Amongst them testosterone levels were significantly elevated comparatively to non-treated patients and significantly lower than controls. Significant differences were noted on waist circumference between non treated patients and controls. Body mass index and HOMA-IR were significantly higher in non-treated patients. Triglycerides and HDLc were significantly decreased respectively in treated and non-treated patients. However, CRP levels were significantly decreased in controls. In conclusion, androgen therapy appeared to protect against obesity, insulin resistance, and hyperlipidemia. Effects on systemic inflammation seemed to be more discrete. Testosterone substitution should be strongly indicated in daily practice with careful prostate monitoring.

Establishing the content validity of the Sexual Arousal, Interest, and Drive Scale and the Hypogonadism Energy Diary.

PubMed

Hayes, R P; Henne, J; Kinchen, K S

2015-04-01

The aim of this qualitative analysis was to establish the content validity of two new patient-reported outcome (PRO) measures: Sexual Arousal, Interest, and Drive Scale (SAID) and Hypogonadism Energy Diary (HED). Four separate qualitative studies were conducted with 125 men with hypogonadism (mean age: 53 years, 85% adult onset). Study 1 used focus groups/interviews to identify important and relevant concepts related to the experience of hypogonadism and its treatment in men primarily with adult-onset hypogonadism. Study 2 tested items generated for assessments of low sex drive and low energy. Study 3 used interviews to confirm in men with early-onset hypogonadism that low sex drive and low energy were also important and relevant symptoms. Study 4 tested final versions of the two PROs and determined equivalency of paper-based and electronic versions of the two PROs. Of the concepts emerging in Studies 1 and 3, low sex drive and low energy were the symptoms most often spontaneously mentioned. Coding of transcripts from Studies 1 and 3 led to the generation of items for the SAID and HED. After item testing (Studies 2 and 4), the final SAID included five items pertaining to arousal, interest in sex and sex drive with a 7-day recall period and the final HED included two items (energy, tired/exhausted) to be administered three times per day. The SAID and HED have content validity established according to regulatory guidance and, therefore, the potential to provide the patient perspective of treatments for hypogonadism. © 2014 John Wiley & Sons Ltd.

Hypogonadism in testicular cancer patients is associated with risk factors of cardiovascular disease and the metabolic syndrome.

PubMed

Bogefors, C; Isaksson, S; Bobjer, J; Kitlinski, M; Leijonhufvud, I; Link, K; Giwercman, A

2017-07-01

More than 95% of testicular cancer are cured but they are at increased long-term risk of cardiovascular disease. The risk of cardiovascular disease and treatment intensity was reported, but it is unknown whether this effect of cancer therapy is direct or indirect, mediated through androgen deficiency. Our aim was, therefore, to evaluate whether testicular cancer patients have increased the prevalence of risk factors of cardiovascular disease and if these risk factors are associated with hypogonadism and/or the cancer treatment given. In 92 testicular cancer patients (mean 9.2 years follow-up) and age-matched controls, blood samples were analysed for lipids, total testosterone, luteinizing hormone (LH), glucose and insulin. An estimate of insulin resistance, HOMAir was calculated. Hypogonadism was defined as total testosterone < 10 nmol/L and/or LH > 10 IU/L and/or androgen replacement. In testicular cancer men with hypogonadism, compared with eugonadal patients, higher insulin (mean difference: 3.10 mIU/L; p = 0.002) and HOMAir (mean difference: 0.792; p = 0.007) were detected. Hypogonadism group presented with increased risk (OR = 4.4; p = 0.01) of metabolic syndrome. Most associations between the treatment given and the metabolic parameters became statistically non-significant after adjustment for hypogonadism. In conclusion, testicular cancer patients with signs of hypogonadism presented with significantly increased risk of metabolic syndrome and investigation of endocrine and metabolic parameters is warranted in these patients. © 2017 American Society of Andrology and European Academy of Andrology.

Basic consensus document on late-onset hypogonadism.

PubMed

Becerra Fernández, Antonio; Enríquez Acosta, Luis

2008-01-01

One of the most important elements in men's live is the ability to engage in normal sexual activity; loss of this activity has always been considered especially important. The relationship between sexual activity, as well as other masculine characteristics, and the testicles has been well known since ancient times and has been related to the slow decrease in testosterone secretion with advanced age. Male hypogonadism is one of the most frequent and under-diagnosed endocrine diseases. Several terms have been proposed to refer to clinical situations caused by the age-related decline in male gonadal function; currently, the most widely accepted term is late-onset hypogonadism (LOH). LOH consists of a clinical and biochemical syndrome associated with advanced age (in men), characterized by typical symptoms and reduced serum testosterone concentrations, which can affect multiple organs and systems and reduce quality of life. This syndrome can be treated and the alterations produced can be reversed. To achieve this, a diagnostic protocol that approaches the multiple factors related to the risks and benefits of treatment is required. Copyright © 2008 Sociedad Española de Endocrinología y Nutrición. Published by Elsevier Espana. All rights reserved.

Idiopathic Ophthalmodynia and Idiopathic Rhinalgia: A Prospective Series of 16 New Cases.

PubMed

Pareja, Juan A; Montojo, Teresa; Guerrero, Ángel L; Álvarez, Mónica; Porta-Etessam, Jesús; Cuadrado, María L

2015-01-01

Idiopathic ophthalmodynia and idiopathic rhinalgia were described a few years ago. These conditions seem specific pain syndromes with a distinctive location in the eye or in the nose. We aimed to present a new prospective series in order to verify the consistency of these syndromes. We performed a descriptive study of all patients referred to our regional neurologic clinics from 2010 to 2014 because of facial pain exclusively felt in the eye or in the nose fulfilling the proposed diagnostic criteria for idiopathic ophthalmodynia and idiopathic rhinalgia. There were 9 patients with idiopathic ophthalmodynia and 7 patients with idiopathic rhinalgia, with a clear female preponderance, and a mean age at onset in the fifth decade. The pain was usually moderate and the temporal pattern was generally chronic. Only one patient reported accompaniments (hypersensitivity to the light and to the flow of air in the symptomatic eye). Preventive treatment with amitriptyline, pregabalin, or gabapentin was partially or totally effective. The clinical features of this new series parallels those of the original description, thus indicating that both idiopathic ophthalmodynia and idiopathic rhinalgia have clear-cut clinical pictures with excellent consistency both inter- and intra-individually. © 2015 American Headache Society.

How to recognize late-onset hypogonadism in men with sexual dysfunction

PubMed Central

Corona, Giovanni; Rastrelli, Giulia; Vignozzi, Linda; Mannucci, Edoardo; Maggi, Mario

2012-01-01

Late-onset hypogonadism (LOH) has been considered the most common form of male hypogonadism with a prevalence of approximately 1 in 100 men. Diagnosis of LOH should be made in symptomatic men with unequivocally low serum testosterone (T) levels. However, its clinical presentation is often insidious and difficult to recognize because it is characterized by nonspecific symptoms that make differential diagnosis with physiological ageing problematic. Sexual dysfunction is the most important determinant for medical consultation and the most specific symptom associated with low T. We therefore analysed a consecutive series of 1734 subjects who attended our unit for sexual dysfunction to investigate the associations between low T (different thresholds), sexual parameters, medical history data (delayed puberty, pituitary disease or cryptorchidism) and their physical exam results. Metabolic parameters, in particular waist circumference, display the greatest accuracy in detecting low T. We found that only the association of several symptoms and signs could significantly raise the clinical suspicion of low T. Structured inventories, which cluster together symptoms and signs of hypogonadism, can help clinicians suspect androgen deficiency. In particular, structured interviews, such as ANDROTEST, have been demonstrated to have a greater accuracy when compared to self reported questionnaires in detecting low T levels. PMID:22286862

Optimal diagnostic measures and thresholds for hypogonadism in men with HIV/AIDS: comparison between 2 transdermal testosterone replacement therapy gels.

PubMed

Blick, Gary

2013-03-01

To determine the incidence of hypogonadism in men with human immunodeficiency virus (HIV)/acquired immunodeficiency virus (AIDS), the most useful serum testosterone measurement and threshold for diagnosing hypogonadism, and the comparative efficacy of 2 testosterone replacement therapy (TRT) 1% gels (AndroGel® [Abbott Laboratories] and Testim® [Auxilium Pharmaceuticals, Inc.]). This was a 2-stage observational study. In stage 1, patient records from 2 medical practices specializing in HIV/AIDS were reviewed. Eligible patients were aged ≥ 18 years; had HIV-seropositive status confirmed by enzyme-linked immunosorbent assay and western blot test or HIV-1 viremia confirmed by HIV-1 RNA polymerase chain reaction; and had prior baseline testosterone assessments for hypogonadism (ie, presence of signs/symptoms of hypogonadism as well as total testosterone [TT] and free testosterone [FT] level measurements). Stage 2 included the evaluation of patients from stage 1 who were treated with 5 to 10 g/day of TRT. The stage 2 inclusion criteria were a diagnosis of low testosterone (defined as TT level < 300 ng/dL and/or FT level < 50 pg/mL, as per The Endocrine Society guidelines and presence/absence of hypogonadal signs and symptoms); ≥ 12 months of evaluable sign and symptom assessments and TT/FT level measurements while on TRT with either Testim® or AndroGel®; and ≥ 4 weeks on initial TRT if the initial TRT was switched or discontinued. Four hundred one of 422 patients met the stage 1 inclusion criteria and 167 of 401 patients (AndroGel®, n = 92; Testim®, n = 75) met the stage 2 inclusion criteria. Total testosterone level < 300 ng/dL alone identified 24% (94 of 390) of patients as hypogonadal, but failed to diagnose an additional 111 patients (67.7%) with FT levels < 100 pg/mL and hypogonadal symptoms. Through month 12, AndroGel® increased mean TT levels by +42.8% and FT levels by +66.9%, compared with +178.7% (P = 0.017) and +191% (P = 0.039), respectively, for

New perspectives in the diagnosis of pediatric male hypogonadism: the importance of AMH as a Sertoli cell marker.

PubMed

Grinspon, Romina P; Rey, Rodolfo A

2011-11-01

Sertoli cells are the most active cell population in the testis during infancy and childhood. In these periods of life, hypogonadism can only be evidenced without stimulation tests, if Sertoli cell function is assessed. AMH is a useful marker of prepubertal Sertoli cell activity and number. Serum AMH is high from fetal life until mid-puberty. Testicular AMH production increases in response to FSH and is potently inhibited by androgens. Serum AMH is undetectable in anorchidic patients. In primary or central hypogonadism affecting the whole gonad and established in fetal life or childhood, serum AMH is low. Conversely, when hypogonadism affects only Leydig cells (e.g. LHβ mutations, LH/CG receptor or steroidogenic enzyme defects), serum AMH is normal or high. In pubertal males with central hypogonadism, AMH is low for Tanner stage (reflecting lack of FSH stimulus), but high for the age (indicating lack of testosterone inhibitory effect). Treatment with FSH provokes an increase in serum AMH, whereas hCG administration increases testosterone levels, which downregulate AMH. In conclusion, assessment of serum AMH is helpful to evaluate gonadal function, without the need for stimulation tests, and guides etiological diagnosis of pediatric male hypogonadism. Furthermore, serum AMH is an excellent marker of FSH and androgen action on the testis.

Enclomiphene Citrate for the Treatment of Secondary Male Hypogonadism

PubMed Central

Rodriguez, Katherine M.; Pastuszak, Alexander W.; Lipshultz, Larry I.

2016-01-01

Introduction Hypogonadism is a growing concern in an aging male population. Historically treated using exogenous testosterone, concerns about possible adverse effects of testosterone have led physicians to seek alternative treatment approaches. Areas Covered Enclomiphene citrate is the trans isomer of clomiphene citrate, a non-steroidal estrogen receptor antagonist that is FDA-approved for the treatment of ovarian dysfunction in women. Clomiphene citrate has also been used off-label for many years to treat secondary male hypogonadism, particularly in the setting of male infertility. Here we review the literature examining the efficacy and safety of enclomiphene citrate in the setting of androgen deficiency. Expert Opinion Initial results support the conclusion that enclomiphene citrate increases serum testosterone levels by raising luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, without negatively impacting semen parameters. The ability to treat testosterone deficiency in men while maintaining fertility supports a role for enclomiphene citrate in the treatment of men in whom testosterone therapy is not a suitable option. PMID:27337642

Iron overload induces hypogonadism in male mice via extrahypothalamic mechanisms.

PubMed

Macchi, Chiara; Steffani, Liliana; Oleari, Roberto; Lettieri, Antonella; Valenti, Luca; Dongiovanni, Paola; Romero-Ruiz, Antonio; Tena-Sempere, Manuel; Cariboni, Anna; Magni, Paolo; Ruscica, Massimiliano

2017-10-15

Iron overload leads to multiple organ damage including endocrine organ dysfunctions. Hypogonadism is the most common non-diabetic endocrinopathy in primary and secondary iron overload syndromes. To explore the molecular determinants of iron overload-induced hypogonadism with specific focus on hypothalamic derangements. A dysmetabolic male murine model fed iron-enriched diet (IED) and cell-based models of gonadotropin-releasing hormone (GnRH) neurons were used. Mice fed IED showed severe hypogonadism with a significant reduction of serum levels of testosterone (-83%) and of luteinizing hormone (-86%), as well as reduced body weight gain, body fat and plasma leptin. IED mice had a significant increment in iron concentration in testes and in the pituitary. Even if iron challenge of in vitro neuronal models (GN-11 and GT1-7 GnRH cells) resulted in 10- and 5-fold iron content increments, respectively, no iron content changes were found in vivo in hypothalamus of IED mice. Conversely, mice placed on IED showed a significant increment in hypothalamic GnRH gene expression (+34%) and in the intensity of GnRH-neuron innervation of the median eminence (+1.5-fold); similar changes were found in the murine model HFE -/- , resembling human hemochromatosis. IED-fed adult male mice show severe impairment of hypothalamus-pituitary-gonadal axis without a relevant contribution of the hypothalamic compartment, which thus appears sufficiently protected from systemic iron overload. Copyright © 2017 Elsevier B.V. All rights reserved.

Can treatment of nocturia increase testosterone level in men with late onset hypogonadism?

PubMed

Kim, Jong Wook; Chae, Ji Yun; Kim, Jin Wook; Yoon, Cheol Yong; Oh, Mi Mi; Park, Hong Seok; Kim, Je Jong; Moon, Du Geon

2014-04-01

To assess the effect of desmopressin on serum testosterone level in men with nocturia and late onset hypogonadism. We prospectively enrolled men with nocturia and symptoms of late onset hypogonadism. Desmopressin (0.1 mg) was administered once daily to patients for 12 weeks, and we then compared serum testosterone levels, electrolytes, frequency volume chart indices, and changes in the International Prostate Symptom Score (IPSS), International Index of Erectile Function, and Aging Male's Symptom scales before and after treatment. Patients with a history of cardiovascular disease or hyponatremia, those using hypnotics, and those who had primary hypogonadism or hypogonadotrophic hypogonadism were excluded from the study. Sixty-two men (mean age, 68.4 years) completed pre- and post-treatment questionnaires and underwent laboratory testing. At the end of the study, the testosterone levels in men with low testosterone levels (<3.5 ng/mL) increased after the 12-week desmopressin treatment (2.85 ± 0.58 to 3.97 ± 1.44 ng/mL; P = .001). Mean scores had decreased from 17.7 to 13.9 (IPSS), 3.8 to 3.2 (IPSS-Quality of Life), and 33.7 to 31.1 (Aging Male's Symptom). On the frequency volume chart, nocturnal urine volume, nocturnal polyuria index, actual number of nocturia events, nocturia index, and nocturnal bladder capacity index were significantly decreased. Desmopressin improved nocturia and other urinary symptoms. Moreover, serum testosterone levels increased significantly in men with low testosterone levels after 12-week desmopressin treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

[Phenotype of patients with gynecomastia].

PubMed

Czajka-Oraniec, Izabella; Zgliczyński, Wojciech

2008-01-01

Gynecomastia, a benign enlargement of the breast glandular tissue in men. The aim of the study was to evaluate the phenotype of patients with gynecomastia, in particular antropometric assessment, breast ultrasound examination and hormonal testing, as well as to estimate possible causes of gynecomastia in studied population. Two hundred-twenty men were enrolled in the study: 126 patients with gynecomastia and 94 healthy volunteers as a control group. Detailed medical examination, breast ultrasound and hormonal assays for T, E2, LH, FSH, SHBG, S-DHEA, PRL and TSH were performed. Calculation of free testosterone concentration was done. The results of clinical and hormonal evaluation enabled to divide the cases into three groups: patients with idiopathic gynecomastia (58 subjects, 46%), with hypogonadism (34 subjects, 27%) and drug-induced or associated with other disorders gynecomastia (34 subjects, 27%). We found that men with gynecomastia, particularly associated with hypogonadism, had significantly higher BMI compared with control group. Ultrasound examination revealed the positive correlation between breast tissue volume and BMI, duration of gynecomastia and estradiol level, while negative correlation with testosterone level. We demonstrated significant differences in LH, T, SHBG, fT and S-DHEA levels between cases and controls. There were no differences in PRL, FSH and TSH levels among groups. Significant elevation of SHBG concentration in all groups of patients, including idiopathic gynecomastia cases, compared with controls, was remarkable. Clinical evaluation and hormonal profile can help to classify patient with gynecomastia into one of three groups: idiopathic gynecomastia, associated with hypogonadism, and drug-induced or associated with other diseases. Idiopathic gynecomastia - of unknown etiology is diagnosed in almost half of all cases (46%). We showed that apart from well known hormonal disturbances leading to gynecomastia, like hypogonadism or

Germline prokineticin receptor 2 (PROKR2) variants associated with central hypogonadism cause differental modulation of distinct intracellular pathways.

PubMed

Libri, Domenico Vladimiro; Kleinau, Gunnar; Vezzoli, Valeria; Busnelli, Marta; Guizzardi, Fabiana; Sinisi, Antonio Agostino; Pincelli, Angela Ida; Mancini, Antonio; Russo, Gianni; Beck-Peccoz, Paolo; Loche, Sandro; Crivellaro, Claudio; Maghnie, Mohamad; Krausz, Csilla; Persani, Luca; Bonomi, Marco

2014-03-01

Defects of prokineticin pathway affect the neuroendocrine control of reproduction, but their role in the pathogenesis of central hypogonadism remains undefined, and the functional impact of the missense PROKR2 variants has been incompletely characterized. In a series of 246 idiopathic central hypogonadism patients, we found three novel (p.V158I, p.V334M, and p.N15TfsX30) and six already known (p.L173R, p.T260M, p.R268C, p.V274D, p.V331M, and p.H20MfsX23) germline variants in the PROKR2 gene. We evaluated the effects of seven missense alterations on two different prokineticin receptor 2 (PROKR2)-dependent pathways: inositol phosphate-Ca(2+) (Gq coupling) and cAMP (Gs coupling). PROKR2 variants were found in 16 patients (6.5%). Expression levels of variants p.V158I and p.V331M were moderately reduced, whereas they were markedly impaired in the remaining cases, except p.V334M, which was significantly overexpressed. The variants p.T260M, p.R268C, and p.V331M showed no remarkable changes in cAMP response (EC50) whereas the IP signaling appeared more profoundly affected. In contrast, cAMP accumulation cannot be stimulated through the p.L173R and p.V274D, but IP EC50 was similar to wt inp.L173R and increased by 10-fold in p.V274D. The variant p.V334M led to a 3-fold increase of EC50 for both cAMP and IP. Our study shows that single PROKR2 missense allelic variants can either affect both signaling pathways differently or selectively. Thus, the integrity of both PROKR2-dependent cAMP and IP signals should be evaluated for a complete functional testing of novel identified allelic variants.

Spino-Cerebellar Degeneration, Hormonal Disorder, Hypogonadism, Deaf Mutism and Mental Deficiency

ERIC Educational Resources Information Center

Sylvester, P. E.

1972-01-01

Post mortem examinations were done on two adult siblings (one female and one male) who had been clinically described as suffering from mental handicap, deaf mutism, ataxia, hypogonadism, and hormonal disorders. (DB)

Hypogonadal men with type 2 diabetes mellitus have smaller bone size and lower bone turnover.

PubMed

Colleluori, Georgia; Aguirre, Lina; Dorin, Richard; Robbins, David; Blevins, Dean; Barnouin, Yoann; Chen, Rui; Qualls, Clifford; Villareal, Dennis T; Armamento-Villareal, Reina

2017-06-01

Both hypogonadism and type 2 diabetes mellitus (T2D) are associated with increased fracture risk. Emerging data support the negative effect of low testosterone on glucose metabolism, however, there is little information on the bone health of hypogonadal men with diabetes. We evaluated the bone mineral density (BMD), bone geometry and bone turnover of hypogonadal men with T2D compared to hypogonadal men without diabetes. Cross-sectional study, men 40-74years old, with average morning testosterone (done twice) of<300ng/dl. Areal BMD (aBMD) was measured by DXA; volumetric BMD (vBMD) and bone geometry by peripheral-quantitative-computed-tomography; serum C-telopeptide (CTX), osteocalcin, sclerostin and sex hormone-binding globulin (SHBG) by ELISA, testosterone and 25-hydroxyvitamin D (25OHD) by automated immunoassay and estradiol by liquid-chromatography/mass-spectrometry. Groups were compared by ANOVA adjusted for covariates. One-hundred five men, 49 with and 56 without diabetes were enrolled. Adjusted vBMD at 38% tibia was higher in diabetic than non-diabetic men (857.3±69.0mg/cm 3 vs. 828.7±96.7mg/cm 3 , p=0.02). Endosteal (43.9±5.8mm vs. 47.1±7.8mm, p=0.04) and periosteal (78.4±5.0mm vs. 81.3±6.5mm, p=0.02) circumferences and total area (491.0±61.0mm 2 vs. 527.7±87.2mm 2 , p=0.02) at 38% tibia, were lower in diabetic men even after adjustments for covariates. CTX (0.25±0.14ng/ml vs. 0.40±0.19ng/ml, p<0.001) and osteocalcin (4.8±2.8ng/ml vs. 6.8±3.5ng/ml, p=0.006) were lower in diabetic men; there were no differences in sclerostin and 25OHD. Circulating gonadal hormones were comparable between the groups. Among hypogonadal men, those with T2D have higher BMD, poorer bone geometry and relatively suppressed bone turnover. Studies with larger sample size are needed to verify our findings and possible even greater risk for fractures among hypogonadal diabetic men. Published by Elsevier Inc.

Late onset hypogonadism of men is not equivalent to the menopause.

PubMed

Saad, Farid; Gooren, Louis J

2014-09-01

Some men between the ages 45 and 60 years develop complaints and symptoms reminiscent of menopausal complaints in women. So, parallels were sought between the changes in female and male endocrinology during that period of life. Indeed, men do show a decline of serum testosterone from age 40 to 50 years onwards but it is a slow decline of 1-2% per year and over time it may amount to hypogonadism. The mechanism of a decline in serum testosterone in men does not resemble the menopause; it is partially an aging neuroendocrine system with a less efficient testosterone production but equally or more important, the result of inhibition of testosterone production by metabolic factors in relation to visceral obesity. These effects are in part reversible with weight loss. A hypogonadal state in aging men has deleterious effects. Mortality of all causes is highest in men with low testosterone impacting on their metabolic state leading to diabetes mellitus, cardiovascular disease, osteoporosis, and sexual dysfunction. Normalization of testosterone in aging hypogonadal men has a beneficial effect on the above pathologies. The fear that testosterone treatment of elderly men would lead to prostate disease has not been substantiated in studies. So, while men do not have a 'menopause', testosterone deficiency in old age deserves serious attention. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Low incidence of new biochemical hypogonadism after intensity modulated radiation therapy for prostate cancer.

PubMed

Markovina, Stephanie; Weschenfelder, Débora Cristina; Gay, Hiram; McCandless, Audrey; Carey, Bethany; DeWees, Todd; Knutson, Nels; Michalski, Jeff

2014-01-01

To evaluate serum testosterone and the incidence of biochemical hypogonadism in men treated with intensity modulated radiation therapy (IMRT) for prostate cancer. Serum testosterone was evaluated prospectively in 51 men at pretreatment and at 6-month time points for 2 years posttreatment with IMRT for prostate cancer. Forty-one patients (80%) were treated with definitive intent and 10 patients with postprostatectomy radiation to median total doses of 7380 cGy and 6480 cGy, respectively. No patients received hormone therapy within 12 months of any serum testosterone value. Biochemical hypogonadism was defined as a total serum testosterone level ≤ 300 ng/dL. Incidental testicular dose was calculated using planning software when computed tomography information was available (n = 21) and using a published method of estimation when not available (n = 24), and was available for 45 patients. A statistically significant decrease in testosterone, though small in magnitude, was seen at 6 months after completion of therapy, with no significant difference by 1 year after completion of therapy. There was no increase in biochemical hypogonadism after IMRT. Below-normal pretreatment testosterone was not associated with a transient decrease. Estimated cumulative testicular dose, including dose from daily imaging, was not associated with a change in testosterone, nor was radiation therapy prescription dose or treatment intent (postoperative vs definitive). The mild transient decrease in serum testosterone following IMRT monotherapy for prostate cancer is not associated with new biochemical hypogonadism.

Multi-Institutional Survey of Medical Treatment for Late-Onset Hypogonadism in Japan.

PubMed

Taniguchi, Hisanori; Matsuda, Tadashi

2017-03-01

The adequate criteria for late-onset hypogonadism (LOH) diagnosis, including serum testosterone levels, type (total or free testosterone) and duration of androgen replacement therapy, and evaluations of treatment effectiveness remain controversial. To evaluate the current status of medical treatment for LOH in Japan, the first nationwide survey were performed. A total of 35 questionnaires answered by urologists in high-volume facilities were analyzed. The median numbers of patients with hypogonadism-related symptoms per month were 10. Aging Male Symptom Score, International Index of Erectile Function, and International Prostate Symptom Score questionnaires were widely used for questionnaires. The diagnostic criteria for LOH varied. Among the patients who presented with hypogonadism-related symptoms, the mean proportion of patients undergoing treatment for LOH was 62.3%. In Japan, LOH was treated not only with testosterone enanthate injections or testosterone ointment but also with Kampo medicine. In many facilities, LOH treatment effectiveness was assessed after a 3-month period. Efficacy was assessed in different ways. Treatment effectiveness rate ranged from 30% to 80%. The duration of LOH treatment was not fixed and was established individually by both the patient and treating physician. This study showed that the real clinical practices for LOH are very diverse, and a general consensus is needed.

Mutations of the KISS1 gene in disorders of puberty.

PubMed

Silveira, L G; Noel, S D; Silveira-Neto, A P; Abreu, A P; Brito, V N; Santos, M G; Bianco, S D C; Kuohung, W; Xu, S; Gryngarten, M; Escobar, M E; Arnhold, I J P; Mendonca, B B; Kaiser, U B; Latronico, A C

2010-05-01

Kisspeptin, encoded by the KISS1 gene, is a key stimulatory factor of GnRH secretion and puberty onset. Inactivating mutations of its receptor (KISS1R) cause isolated hypogonadotropic hypogonadism (IHH). A unique KISS1R-activating mutation was described in central precocious puberty (CPP). Our objective was to investigate KISS1 mutations in patients with idiopathic CPP and normosmic IHH. Eighty-three children with CPP (77 girls) and 61 patients with IHH (40 men) were studied. The control group consisted of 200 individuals with normal pubertal development. The promoter region and the three exons of KISS1 were amplified and sequenced. Cells expressing KISS1R were stimulated with synthetic human wild-type or mutant kisspeptin-54 (kp54), and inositol phosphate accumulation was measured. In a second set of experiments, kp54 was preincubated in human serum before stimulation of the cells. Two novel KISS1 missense mutations, p.P74S and p.H90D, were identified in three unrelated children with idiopathic CPP. Both mutations were absent in 400 control alleles. The p.P74S mutation was identified in the heterozygous state in a boy who developed CPP at 1 yr of age. The p.H90D mutation was identified in the homozygous state in two unrelated girls with CPP. In vitro studies revealed that the capacity of the P74S and H90D mutants to stimulate IP production was similar to the wild type. After preincubation of wild-type and mutant kp54 in human serum, the capacity to stimulate signal transduction was significantly greater for P74S compared with the wild type, suggesting that the p.P74S variant is more stable. Only polymorphisms were found in the IHH group. Two KISS1 mutations were identified in unrelated patients with idiopathic CPP. The p.P74S variant was associated with higher kisspeptin resistance to degradation in comparison with the wild type, suggesting a role for this mutation in the precocious puberty phenotype.

Vitamin D is associated with testosterone and hypogonadism in Chinese men: Results from a cross-sectional SPECT-China study.

PubMed

Wang, Ningjian; Han, Bing; Li, Qin; Chen, Yi; Chen, Yingchao; Xia, Fangzhen; Lin, Dongping; Jensen, Michael D; Lu, Yingli

2015-07-16

To date, no study has explored the association between androgen levels and 25-hydroxyvitamin D (25(OH)D) levels in Chinese men. We aimed to investigate the relationship between 25(OH)D levels and total and free testosterone (T), sex hormone binding globulin (SHBG), estradiol, and hypogonadism in Chinese men. Our data, which were based on the population, were collected from 16 sites in East China. There were 2,854 men enrolled in the study, with a mean (SD) age of 53.0 (13.5) years. Hypogonadism was defined as total T <11.3 nmol/L or free T <22.56 pmol/L. The 25(OH)D, follicle-stimulating hormone, luteinizing hormone, total T, estradiol and SHBG were measured using chemiluminescence and free T by enzyme-linked immune-sorbent assay. The associations between 25(OH)D and reproductive hormones and hypogonadism were analyzed using linear regression and binary logistic regression analyses, respectively. A total of 713 (25.0 %) men had hypogonadism with significantly lower 25(OH)D levels but greater BMI and HOMA-IR. Using linear regression, after fully adjusting for age, residence area, economic status, smoking, BMI, HOMA-IR, diabetes and systolic pressure, 25(OH)D was associated with total T and estradiol (P < 0.05). In the logistic regression analyses, increased quartiles of 25(OH)D were associated with significantly decreased odds ratios of hypogonadism (P for trend <0.01). This association, which was considerably attenuated by BMI and HOMA-IR, persisted in the fully adjusted model (P for trend <0.01) in which for the lowest compared with the highest quartile of 25(OH)D, the odds ratio of hypogonadism was 1.50 (95 % CI, 1.14, 1.97). A lower vitamin D level was associated with a higher prevalence of hypogonadism in Chinese men. This association might, in part, be explained by adiposity and insulin resistance and warrants additional investigation.

The use of Data Mining in the categorization of patients with Azoospermia.

PubMed

Mikos, Themistoklis; Maglaveras, Nikolaos; Pantazis, Konstantinos; Goulis, Dimitrios G; Bontis, John N; Papadimas, John

2005-01-01

Data Mining is a relatively new field of Medical Informatics. The aim of this study was to compare Data Mining diagnosis with clinical diagnosis by applying a Data Miner (DM) to a clinical dataset of infertile men with azoospermia. One hundred and forty-seven azoospermic men were clinically classified into four groups: a) obstructive azoospermia (n=63), b) non-obstructive azoospermia (n=71), c) hypergonadotropic hypogonadism (n=2), and d) hypogonadotropic hypogonadism (n=11). The DM (IBM's DB2/Intelligent Miner for Data 6.1) was asked to reproduce a four-cluster model. DM formed four groups of patients: a) eugonadal men with normal testicular volume and normal FSH levels (n=86), b) eugonadal men with significantly reduced testicular volume (median 6.5 cm3) and very high FSH levels (n=29), c) eugonadal men with moderately reduced testicular volume (median 14.5 cm3) and raised FSH levels (n=20), and d) hypogonadal men (n=12). Overall DM concordance rate in hypogonadal men was 92%, in obstructive azoospermia 73%, and in non-obstructive azoospermia 69%. Data Mining produces clinically meaningful results but different from those of the clinical diagnosis. It is possible that the use of large sets of structured and formalised data and continuous evaluation of DM results will generate a useful methodology for the Clinician.

Pubertal induction in hypogonadism: Current approaches including use of gonadotrophins.

PubMed

Zacharin, Margaret

2015-06-01

Primary disorders of the gonad or those secondary to abnormalities of the hypothalamic pituitary axis result in hypogonadism. The range of health problems of childhood and adolescence that affect this axis has increased, as most children now survive chronic illness, but many have persisting deficits in gonadal function as a result of their underlying condition or its treatment. An integrated approach to hormone replacement is needed to optimize adult hormonal and bone health, and to offer opportunities for fertility induction and preservation that were not considered possible in the past. Timing of presentation ranges from birth, with disorders of sexual development, through adolescent pubertal failure, to adult fertility problems. This review addresses diagnosis and management of hypogonadism and focuses on new management strategies to address current concerns with fertility preservation. These include Turner syndrome, and fertility presevation prior to childhood cancer treatment. New strategies for male hormone replacement therapy that may impinge upon future fertility are emphasized. Copyright © 2015 Elsevier Ltd. All rights reserved.

Visceral Adipose Tissue and Leptin Hyperproduction Are Associated With Hypogonadism in Men With Chronic Kidney Disease.

PubMed

Cobo, Gabriela; Cordeiro, Antonio C; Amparo, Fernanda Cassulo; Amodeo, Celso; Lindholm, Bengt; Carrero, Juan Jesús

2017-07-01

Hypogonadism is a common endocrine disorder in men with chronic kidney disease (CKD), but its pathophysiology is poorly understood. We here explore the plausible contribution of abdominal adiposity and leptin hyperproduction to testosterone deficiency in this patient population. Cross-sectional analysis with all men included the Malnutrition, Inflammation and Vascular Calcification cohort, which enrolled consecutive nondialyzed patients with CKD stages 3-5. A total of 172 men with CKD stages 3-5 nondialysis (median age 61 [45-75] years, median glomerular filtration rate 24 [9-45] mL/min/1.73 m 2 ). In them, serum levels of total testosterone, estrogen, sex hormone binding globulin, and leptin were quantified, together with visceral adipose tissue (VAT) by thoracic and abdominal CT scan. None, observational study. Total testosterone, hypogonadism. The median level of total testosterone was 11.7 (7.3-18.4) nmol/L, with hypogonadism (<10 nmol/L) present in 52 (30%) patients. Testosterone-deficient patients presented with significantly higher body mass index, waist circumference, and VAT. An inverse correlation between testosterone and VAT (rho = -0.25, P = .001) or waist circumference (rho = -0.20, P = .008) was found, also after multivariate adjustment including sex hormone binding globulin and estrogen. Total testosterone was inversely correlated with serum leptin (rho = -0.22, P = .003), and the ratio of leptin/VAT, an index of leptin hyperproduction, was strongly and independently associated with the prevalence of hypogonadism in multivariable regression analyses. Visceral adiposity independently associated with lower testosterone levels among men with CKD stage 3-5 nondialysis. The observed link between hyperleptinemia and hypogonadism is in line with previous evidence on direct effects of leptin on testosterone production. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Endocrine Society of Australia position statement on male hypogonadism (part 2): treatment and therapeutic considerations.

PubMed

Yeap, Bu B; Grossmann, Mathis; McLachlan, Robert I; Handelsman, David J; Wittert, Gary A; Conway, Ann J; Stuckey, Bronwyn Ga; Lording, Douglas W; Allan, Carolyn A; Zajac, Jeffrey D; Burger, Henry G

2016-09-05

Part 1 of this position statement dealt with the assessment of male hypogonadism, including the indications for testosterone therapy. This article, Part 2, focuses on treatment and therapeutic considerations for male hypogonadism and identifies key questions for future research. Key points and recommendations are:Excess cardiovascular events have been reported in some but not all studies of older men without pathological hypogonadism who were given testosterone treatment. Additional studies are needed to clarify whether testosterone therapy influences cardiovascular risk.Testosterone is the native hormone that should be replaced in men being treated for pathological hypogonadism. Convenient and cost-effective treatment modalities include depot intramuscular injection and transdermal administration (gel, cream or liquid formulations).Monitoring of testosterone therapy is recommended for efficacy and safety, focusing on ameliorating symptoms, restoring virilisation, avoiding polycythaemia and maintaining or improving bone mineral density.Treatment aims to relieve an individual's symptoms and signs of androgen deficiency by administering standard doses and maintaining circulating testosterone levels within the reference interval for eugonadal men.Evaluation for cardiovascular disease and prostate cancer risks should be undertaken as appropriate for eugonadal men of similar age. Nevertheless, when there is a reasonable possibility of substantive pre-existing prostate disease, digital rectal examination and prostate-specific antigen testing should be performed before commencing testosterone treatment.Changes in management as result of the position statement: Treatment aims to relieve symptoms and signs of androgen deficiency, using convenient and effective formulations of testosterone. Therapy should be monitored for efficacy and safety.

A Perspective on Middle-Aged and Older Men With Functional Hypogonadism: Focus on Holistic Management.

PubMed

Grossmann, Mathis; Matsumoto, Alvin M

2017-03-01

Middle-aged and older men (≥50 years), especially those who are obese and suffer from comorbidities, not uncommonly present with clinical features consistent with androgen deficiency and modestly reduced testosterone levels. Commonly, such men do not demonstrate anatomical hypothalamic-pituitary-testicular axis pathology but have functional hypogonadism that is potentially reversible. Literature review from 1970 to October 2016. Although definitive randomized controlled trials are lacking, evidence suggests that in such men, lifestyle measures to achieve weight loss and optimization of comorbidities, including discontinuation of offending medications, lead to clinical improvement and a modest increase in testosterone. Also, androgen deficiency-like symptoms and end-organ deficits respond to targeted treatments (such as phosphodiesterase-5 inhibitors for erectile dysfunction) without evidence that hypogonadal men are refractory. Unfortunately, lifestyle interventions remain difficult and may be insufficient even if successful. Testosterone therapy should be considered primarily for men who have significant clinical features of androgen deficiency and unequivocally low testosterone levels. Testosterone should be initiated either concomitantly with a trial of lifestyle measures, or after such a trial fails, after a tailored diagnostic work-up, exclusion of contraindications, and appropriate counseling. There is modest evidence that functional hypogonadism responds to lifestyle measures and optimization of comorbidities. If achievable, these interventions may have demonstrable health benefits beyond the potential for increasing testosterone levels. Therefore, treatment of underlying causes of functional hypogonadism and of symptoms should be used either as an initial or adjunctive approach to testosterone therapy.

Juvenile Idiopathic Arthritis

MedlinePlus

... Is Juvenile Idiopathic Arthritis the same as Juvenile Rheumatoid Arthritis? Yes, Juvenile Idiopathic Arthritis (JIA) is a new ... of chronic inflammatory diseases that affect children. Juvenile Rheumatoid Arthritis (JRA) is the older term that was used ...

Idiopathic Intracranial Hypertension (Pseudotumor Cerebri)

MedlinePlus

... Asked Questions Español Condiciones Chinese Conditions Idiopathic Intracranial Hypertension (Pseudotumor Cerebri) En Español Read in Chinese What is idiopathic intracranial hypertension? Idiopathic intracranial hypertension (IIH) is a disorder that ...

The inter-relational effect of metabolic syndrome and sexual dysfunction on hypogonadism in type II diabetic men.

PubMed

Amidu, N; Owiredu, W K B A; Gyasi-Sarpong, C K; Alidu, H; Antuamwine, B B; Sarpong, C

2017-05-01

We sought to establish the interplay of metabolic syndrome (MetS) and/or sexual dysfunction (SD) on hypogonadism. Sexual functioning was assessed using Golombok Rust Inventory of Sexual Satisfaction in 274 consecutive diabetic men visiting the diabetic clinic of the Tema General Hospital between November 2010 and March 2011. MetS was assessed employing the criteria of World Health Organization, International Diabetic Federation and the National Cholesterol Education Program Adult Treatment Panel III while testosterone levels were estimated. The mean ages and duration of diabetes from this study were 59.9±11.3 and 6.8±5.9 years, respectively. The prevalence of hypogonadism was 7.3%, with the -SD/+MetS subjects showing the highest prevalence of hypogonadism, irrespective of the criteria used. Additionally, subjects with MetS and its components had a significantly lower level of testosterone compared with those without MetS and its components. Using standard nine-point scale, it was observed that subjects who avoided sexual act had significantly (P=0.0410) lower testosterone values (5.8±2.3 ng ml -1 ) than subjects who did not avoid sexual act (6.4±2.6 ng ml -1 ). MetS alone impacted more on hypogonadism than SD alone or both conditions altogether.

[Testosterone replacement therapy for late-onset hypogonadism after radical prostatectomy: a case report].

PubMed

Nakano, Kosuke; Kiuchi, Hiroshi; Miyagawa, Yasushi; Tsujimura, Akira; Nonomura, Norio

2014-08-01

A 53-year-old man presented to our hospital with a few-month history of fatigue and anorexia. His aging male's symptoms (AMS) score was 57, and the free testosterone value was low (6.5 pg/ml). He was diagnosed with severe late-onset hypogonadism indicative of androgen replacement therapy (ART). His serum prostate specific antigen was 8.7 ng/ml, and pelvic magnetic resonance imaging showed a low intensity area in the peripheral zone of the prostate. A systematic 10-core prostate biopsy revealed one core of adenocarcinoma with a Gleason score of 3 + 3=6. Imaging examination revealed organ-confined prostate cancer that was cT2aN0M0. Given his desire for ART for the treatment of hypogonadism, the patient underwent open radical prostatectomy. Pathologic examination demonstrated prostate adenocarcinoma that was pT2aN0, and Gleason score of 3 + 3=6. After confirming that the prostate specific antigen value was under 0.01 ng/ml for three years after prostatectomy, the patient received 125 mg methyltestosterone monthly. His hypogonadism-related symptoms diminished and AMS score dropped to 48. During a three-year follow-up of ART, no biochemical recurrence was found.

[Hypogonadism and the quality of life in male patients with type-2 diabetes mellitus].

PubMed

Zhang, Lu-Yao; He, Wei; Wan, Jian-Xin; Yin, Qi-Qi; Cheng, Zhen; Chen, Guan-Ming; Ji, Wen; Li, Hai; Li, Yan-Bing; Liao, Zhi-Hong

2016-12-01

To compare the level of testosterone between type-2 diabetes mellitus (T2DM) patients and healthy controls and to investigate the status of hypogonadism and the influence of hypopgonadism on the quality of life. We collected serum total testosterone (TT), free testosterone (FT), sex hormone-binding globulin (SHBG), and other clinical data from 166 T2DM patients aged over 30 years and 186 age-matched healthy controls. We investigated the quality of life (QoL) of the two groups of subjects using the questionnaires of Androgen Deficiency in Aging Males (ADAM), Aging Male Symptoms (AMS), 36-Item Short-Form Health Survey (SF-36), and Special Quality of Life for Diabetes Mellitus (DSQL). The level of calculated FT (cFT) was remarkably lower in the T2DM patients than in the healthy controls (P<0.05), but no statistically significant differences were observed between the two groups in the levels of TT, bio-available testosterone (Bio-T), and SHBG. The T2DM males with hypogonadism showed significant differences from those without in age, height, systolic blood pressure, and creatinine (P<0.05). Based on the criteria of cFT <0.3 nmol/L and AMS score ≥27, the incidence rate of hypogonadism was 51.81% in the T2DM patients, 31.58% in the 30－39 yr group, 32.50% in the 40－49 yr group, 50% in the 50－59 yr group, 69.23% in the 60－69 yr group, and 77.27% in the ≥70 yr group, elevated by 77.4% with the increase of 10 years of age (OR = 1.774, P<0.001). The AMS score was significantly correlated with the scores of DSQL (r = 0.557, P<0.001) and SF-36 (r = －0.739, P<0.001) in the T2DM patients. T2DM patients have lower levels of cFT than healthy men, accompanied with a higher incidence of hypogonadism. Age is a main risk factor of hypogonadism. Severer testosterone deficiency symptoms are associated with lower scores of QoL in T2DM males.

Juvenile idiopathic arthritis.

PubMed

Boros, Christina; Whitehead, Ben

2010-09-01

Juvenile idiopathic arthritis is the most common rheumatic disease in childhood, occurring in approximately 1:500 children. Despite a recent expansion in treatment options and improvement of outcomes, significant morbidity still occurs. This article outlines the clinical manifestations, assessment, detection of complications, treatment options and monitoring requirements, with the aid of guidelines recently published by The Royal Australian College of General Practitioners, which provide practical support for general practitioners to ensure best practice care and to prevent lifelong disability in patients with juvenile idiopathic arthritis. General practice plays an important role in the early detection, initial management and ongoing monitoring of children with juvenile idiopathic arthritis. Early detection involves understanding the classification framework for subtypes of juvenile idiopathic arthritis, and being aware of the clinical manifestations and how to look for them, through history, examination and appropriate investigation. The major extra-articular manifestations of juvenile idiopathic arthritis are uveitis and growth disturbance. Treatment options include nonsteroidal anti-inflammatory drugs, methotrexate, biologic agents, and corticosteroids. Management using a multidisciplinary approach can prevent long term sequelae. Unfortunately, approximately 50% of children will have active disease as adults.

Effects of Male Hypogonadism on Regional Adipose Tissue Fatty Acid Storage and Lipogenic Proteins

PubMed Central

Santosa, Sylvia; Jensen, Michael D.

2012-01-01

Testosterone has long been known to affect body fat distribution, although the underlying mechanisms remain elusive. We investigated the effects of chronic hypogonadism in men on adipose tissue fatty acid (FA) storage and FA storage factors. Twelve men with chronic hypogonadism and 13 control men matched for age and body composition: 1) underwent measures of body composition with dual energy x-ray absorptiometry and an abdominal CT scan; 2) consumed an experimental meal containing [3H]triolein to determine the fate of meal FA (biopsy-measured adipose storage vs. oxidation); 3) received infusions of [U-13C]palmitate and [1-14C]palmitate to measure rates of direct free (F)FA storage (adipose biopsies). Adipose tissue lipoprotein lipase, acyl-CoA synthetase (ACS), and diacylglycerol acetyl-transferase (DGAT) activities, as well as, CD36 content were measured to understand the mechanism by which alterations in fat storage occur in response to testosterone deficiency. Results of the study showed that hypogonadal men stored a greater proportion of both dietary FA and FFA in lower body subcutaneous fat than did eugonadal men (both p<0.05). Femoral adipose tissue ACS activity was significantly greater in hypogonadal than eugonadal men, whereas CD36 and DGAT were not different between the two groups. The relationships between these proteins and FA storage varied somewhat between the two groups. We conclude that chronic effects of testosterone deficiency has effects on leg adipose tissue ACS activity which may relate to greater lower body FA storage. These results provide further insight into the role of androgens in body fat distribution and adipose tissue metabolism in humans. PMID:22363653

Vocal cord paralysis: What matters between idiopathic and non-idiopathic cases?

PubMed

Özbal Koç, Ayça Eltaf; Türkoğlu, Seda Babakurban; Erol, Ozan; Erbek, Selim

2016-01-01

This study aims to evaluate the demographic and clinical characteristics of patients with idiopathic and non-idiopathic vocal cord paralysis (VCP). This retrospective cohort was performed on data extracted from medical files of 92 consecutive patients (43 males, 49 females; median age 52.1±23.1 years; min. 1 - max. 87) with VCP diagnosed in the otorhinolaryngology department between April 2012 and December 2015. Diagnoses associated with VCP, side of involvement (right, left or bilateral) and previous medical histories were noted and compared between patients with idiopathic and non-idiopathic VCP. Vocal cord paralysis occurred on the left side (n=56, 60.9%), right side (n=28, 30.4%) or bilaterally (n=8, 8.7%). A clinical entity related with VCP was identified in 63 patients (68.5%), while 29 (31.5%) patients had idiopathic VCP. Most common etiologies for VCP were thyroid surgery (n=32, 34.8%), cardiovascular surgery (n=9, 9.8%), lung cancer (n=6, 6.5%) and cardiac anomalies (n=4, 4.3%), respectively. Patients with idiopathic VCP were significantly older (p<0.001), while gender distribution (p=0.121) and side of involvement (p=0.340) did not differ between two groups. Vocal cord paralysis is a relatively common clinical entity with substantial rate of morbidity. Identification of the underlying etiology and awareness on the clinical characteristics are keystones for foreseeing complications and determining the appropriate therapeutic modality.

A Perspective on Middle-Aged and Older Men With Functional Hypogonadism: Focus on Holistic Management

PubMed Central

Matsumoto, Alvin M.

2017-01-01

Abstract Context: Middle-aged and older men (≥50 years), especially those who are obese and suffer from comorbidities, not uncommonly present with clinical features consistent with androgen deficiency and modestly reduced testosterone levels. Commonly, such men do not demonstrate anatomical hypothalamic–pituitary–testicular axis pathology but have functional hypogonadism that is potentially reversible. Evidence Acquisition: Literature review from 1970 to October 2016. Evidence Synthesis: Although definitive randomized controlled trials are lacking, evidence suggests that in such men, lifestyle measures to achieve weight loss and optimization of comorbidities, including discontinuation of offending medications, lead to clinical improvement and a modest increase in testosterone. Also, androgen deficiency–like symptoms and end-organ deficits respond to targeted treatments (such as phosphodiesterase-5 inhibitors for erectile dysfunction) without evidence that hypogonadal men are refractory. Unfortunately, lifestyle interventions remain difficult and may be insufficient even if successful. Testosterone therapy should be considered primarily for men who have significant clinical features of androgen deficiency and unequivocally low testosterone levels. Testosterone should be initiated either concomitantly with a trial of lifestyle measures, or after such a trial fails, after a tailored diagnostic work-up, exclusion of contraindications, and appropriate counseling. Conclusions: There is modest evidence that functional hypogonadism responds to lifestyle measures and optimization of comorbidities. If achievable, these interventions may have demonstrable health benefits beyond the potential for increasing testosterone levels. Therefore, treatment of underlying causes of functional hypogonadism and of symptoms should be used either as an initial or adjunctive approach to testosterone therapy. PMID:28359097

Idiopathic hypersomnia.

PubMed

Billiard, Michel; Sonka, Karel

2016-10-01

Idiopathic hypersomnia continues to evolve from the concept of "sleep drunkenness" introduced by Bedrich Roth in Prague in 1956 and the description of idiopathic hypersomnia with two forms, polysymptomatic and monosymptomatic, by the same Bedrich Roth in 1976. The diagnostic criteria of idiopathic hypersomnia have varied with the successive revisions of the International classifications of sleep disorders, including the recent 3rd edition. No epidemiological studies have been conducted so far. Disease onset occurs most often during adolescence or young adulthood. A familial background is often present but rigorous studies are still lacking. The key manifestation is hypersomnolence. It is often accompanied by sleep of long duration and debilitating sleep inertia. Polysomnography (PSG) followed by a multiple sleep latency test (MSLT) is mandatory, as well as a 24 h PSG or a 2-wk actigraphy in association with a sleep log to ensure a total 24-h sleep time longer than or equal to 66O minutes, when the mean sleep latency on the MSLT is longer than 8 min. Yet, MSLT is neither sensitive nor specific and the polysomnographic diagnostic criteria require continuous readjustment and biologic markers are still lacking. Idiopathic hypersomnia is most often a chronic condition though spontaneous remission may occur. The condition is disabling, sometimes even more so than narcolepsy type 1 or 2. Based on neurochemical, genetic and immunological analyses as well as on exploration of the homeostatic and circadian processes of sleep, various pathophysiological hypotheses have been proposed. Differential diagnosis involves a number of diseases and it is not yet clear whether idiopathic hypersomnia and narcolepsy type 2 are not the same condition. Until now, the treatment of idiopathic hypersomnia has mirrored that of the sleepiness of narcolepsy type 1 or 2. The first randomized, double-blind, placebo-controlled trials of modafinil have just been published, as well as a double

[Nebido in the treatment of hypogonadism syndrome and its complications in men].

PubMed

Dedov, I I; Kurbatov, D G; Rozhivanov, R V; Lepetukhin, A E; Dubskiĭ, S A; Goncharov, N P

2011-01-01

The article presents original experience with use of undecanoate (nebido, BayerHealthcare Pharmaceuticals, Germany) in androgenic testosteron replacement therapy in males with hypogonadism. Prospective studies of nebido efficacy were made in males with vein-occlusive erectile dysfunction (n = 20), chronic pelvic pain syndrome (n = 77), metabolic syndrome (n = 170). Retrospective studies assessed efficacy of nebido monotherapy in patients with erectile dysfunction and hypogonadism (n = 34), hematological and urological safety of the drug (n = 40). Laboratory monitoring was performed in all the studies according to ISSAM recommendations. The patients were not included in contraindications to androgenic therapy. Nebido treatment significantly improved libido and erectile function, efficacy of phosphodiesterase of type 5 inhibiors used in moderate and severe erectile dysfunction. Depressive, asthenic, pain symptoms declined in males with chronic pelvic pain. Body fat reduced in metabolic syndrome with alleviation of its other components. Insignificant rise of hemoglobin level and packed cell volume was observed in some patients while a PSA level increase was clinically significant in 10% patients who had initial PSA > 2.5 ng/ml and acromegalia. Also, nebido depressed production of gonadotropins and spermatogenesis. Thus, nebido is highly effective in sexual dysfunction and other somatic disorders caused by hypogonadism. Nebido does not induce severe side effects, but clinically significant rise of PSA level requires treatment discontinuation and more careful urological examination. In view of nebido ability to suppress spermatogenesis, the drug should not be used in reproductively active men.

Delayed puberty, eroticism, and sense of smell: A psychological study of hypogonadotropinism, osmatic and anosmatic (Kallmann's syndrome).

PubMed

Bobrow, N A; Money, J; Lewis, V G

1971-12-01

In 13 male patients with a diagnosis of hypogonadotropic hypogonadism, associated in five cases with verified hyposmia (Kallmann's syndrome), social development and participation were delayed. The patients associated the lack of visible signs of male puberty with their delayed sociosexual maturation. However, the evidence of physical maturation after treatment did not have the ameliorative effect on their social behavior one would have liked to predict. Dating behavior was limited before and after treatment for all the patients, and sexual interest was low even for the three married ones. The experience of falling in love was notably absent in the relationships described. Two characteristic social reaction patterns were social introversion and hostile rejection of agemates. Intellectual functioning and the incidence of personality pathology were not diagnostically noteworthy. None of the patients had any problems with gender identity except for erotic apathy which extended to masturbation. There was an absence of homosexuality. Possibly hypogonadotropic patients have a primary defect of the hypothalamus, manifesting itself as a dysfunction of the behavioral concomitants of puberty as well as a failure of hormonal puberty.

Sex differences in visuospatial abilities persist during induced hypogonadism

PubMed Central

Guerrieri, Gioia M.; Wakim, Paul G.; Keenan, P.A.; Schenkel, Linda A; Berlin, Kate; Gibson, Carolyn J.; Rubinow, David R.; Schmidt, Peter J.

2016-01-01

Background Despite well-established sex differences in the performance on tests of several cognitive domains (e.g., visuospatial ability), few studies in humans have evaluated if these sex differences are evident both in the presence of circulating sex hormones and during sex steroid hormonal suppression. Sex differences identified in the relative absence of circulating levels of estradiol and testosterone suggest that differences in brain structure or function exist independent of current hormonal environment and are more likely a reflection of differing developmental exposures and/or genetic substrates. Objective To evaluate cognitive performance in healthy eugonadal men and women before and again during GnRH agonist-induced hypogonadism. Methods Men (n = 16) and women (n = 15) without medical or psychiatric illness were matched for IQ. Cognitive tests were performed at baseline (when eugonadal) and after 68 weeks of GnRH agonist-induced gonadal suppression. The test batteries included measures of verbal and spatial memory, spatial ability, verbal fluency, motor speed/dexterity, and attention/concentration. Data were analyzed using repeated-measures models. Results During both eugonadism and hypogonadism, men performed significantly better than women on several measures of visuospatial performance including mental rotation, line orientation, Money Road Map, Porteus maze, and complex figure drawing. Although some test performances showed an effect of hormone treatment, the majority of these differences reflected an improved performance during hypogonadism compared with baseline (and probably reflected practice effects). Conclusion The well-documented male advantage in visuospatial performance, which we observed during eugonadal conditions, was maintained in the context of short-term suppression of gonadal function in both men and women. These findings suggest that, in humans, sex differences in visuospatial performance are not merely dependent on differences in

Sex differences in visuospatial abilities persist during induced hypogonadism.

PubMed

Guerrieri, Gioia M; Wakim, Paul G; Keenan, P A; Schenkel, Linda A; Berlin, Kate; Gibson, Carolyn J; Rubinow, David R; Schmidt, Peter J

2016-01-29

Despite well-established sex differences in the performance on tests of several cognitive domains (e.g., visuospatial ability), few studies in humans have evaluated if these sex differences are evident both in the presence of circulating sex hormones and during sex steroid hormonal suppression. Sex differences identified in the relative absence of circulating levels of estradiol and testosterone suggest that differences in brain structure or function exist independent of current hormonal environment and are more likely a reflection of differing developmental exposures and/or genetic substrates. To evaluate cognitive performance in healthy eugonadal men and women before and again during GnRH agonist-induced hypogonadism. Men (n=16) and women (n=15) without medical or psychiatric illness were matched for IQ. Cognitive tests were performed at baseline (when eugonadal) and after 6-8 weeks of GnRH agonist-induced gonadal suppression. The test batteries included measures of verbal and spatial memory, spatial ability, verbal fluency, motor speed/dexterity, and attention/concentration. Data were analyzed using repeated-measures models. During both eugonadism and hypogonadism, men performed significantly better than women on several measures of visuospatial performance including mental rotation, line orientation, Money Road Map, Porteus maze, and complex figure drawing. Although some test performances showed an effect of hormone treatment, the majority of these differences reflected an improved performance during hypogonadism compared with baseline (and probably reflected practice effects). The well-documented male advantage in visuospatial performance, which we observed during eugonadal conditions, was maintained in the context of short-term suppression of gonadal function in both men and women. These findings suggest that, in humans, sex differences in visuospatial performance are not merely dependent on differences in the current circulating sex steroid environment. Thus

Prevalence and Etiology of Hypogonadism in Young Men With Chronic Spinal Cord Injury: A Cross-Sectional Analysis From Two University-Based Rehabilitation Centers.

PubMed

Sullivan, Shannon D; Nash, Mark S; Tefera, Eshetu; Tinsley, Emily; Blackman, Marc R; Groah, Suzanne

2017-08-01

Spinal cord injury (SCI) triggers an "accelerated aging" process that may include development of hypogonadism, even among younger men with SCI; however, few studies have investigated the prevalence or etiology of hypogonadism in men with SCI. Young men with SCI also are at increased risk for developing metabolic dysfunction after injury, which may be exacerbated by concomitant testosterone (T) deficiency, thus identifying the prevalence and risk factors for T deficiency in men with SCI is important for their long-term health. To investigate the prevalence, risk factors, and etiology of T deficiency (hypogonadism) in otherwise-healthy men with chronic, motor complete SCI. Secondary cross-sectional analysis. Rehabilitation research centers in Washington, DC, and Miami, Florida. Men (n = 58) aged 18-45 years with chronic (≥1 year), motor complete SCI without comorbidities or use of testosterone therapy. Plasma concentrations of hormones were measured with standardized assays. Body composition was assessed with dual-energy x-ray absorptiometry scan. Serum total T and calculated free T. T deficiency was more common in men after SCI than in a matched cohort of similarly-aged men without SCI (25%, SCI versus 6.7%, non-SCI, P < .001). The risk of hypogonadism appeared to be increased in men with more extensive injury and with higher percent body fat. The majority of men with SCI with low T had low serum LH levels, suggesting that central suppression of the hypothalamic-pituitary-gonadal axis may be the most common etiology of hypogonadism after SCI. Hypogonadism is more common in young men with SCI than in similarly aged men without SCI, suggesting that SCI should be identified as a risk factor for T deficiency and that routine screening for hypogonadism should be performed in the SCI population. II. Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Correlates and prevalence of hypogonadism in patients with early- and late-onset type 2 diabetes.

PubMed

Li, Y; Zhang, M; Liu, X; Cui, W; Rampersad, S; Li, F; Lin, Z; Yang, P; Li, H; Sheng, C; Cheng, X; Qu, S

2017-07-01

This study aims to compare the prevalence of hypogonadism between male patients with early-onset type 2 diabetes mellitus (T2DM) and late-onset type 2 diabetes. A total of 122 male patients with early-onset T2DM (diagnosis age ≤40 years) and 100 male patients with late-onset T2DM (diagnosis age >40 years) were recruited from our in-patient department between 1 January 2013 and 28 December 2015. Serum FSH, LH, testosterone, lipid profile, uric acid, HbA1c, and beta-cell function were determined in blood samples. The diagnosis of hypogonadism was based on the levels of LH, FSH, and total testosterone. The mean onset age was 29.86 ± 6.31 and 54.47 ± 9.97 years old in the early-onset group and late-onset group, respectively. Compared with late-onset T2DM, those with early-onset T2DM had a higher proportion of new-onset diabetes, were more likely to be obese, and had worse glycemic control, lipid control, and lower sex hormone-binding globulin (SHBG). The prevalence of hypogonadism was much higher in the early-onset group than in the late-onset group (48.0% vs. 26.7%, p < 0.05). The rate of secondary hypogonadism in the early-onset group and late-onset group were 44.3% and 25.0%, respectively (p < 0.05). Obesity, waist circumference, and SHBG were significantly associated with serum total testosterone level in all, early-onset, and late-onset T2DM. Both all and early-onset T2DM groups had positive correlations between total testosterone and fasting C-peptide, total cholesterol, triglycerides, and uric acid. Our results indicate that in a population of admission to a large urban hospital in China, the prevalence of hypogonadism was higher in the patients with early-onset T2DM than that of late-onset T2DM. This prevalence might be attributable to greater obesity, worse lipid control, and lower SHBG levels in those patients. © 2017 American Society of Andrology and European Academy of Andrology.

Effect of testosterone replacement therapy on vitamin D and FGF-23 levels in congenital hypogonadism.

PubMed

Haymana, Cem; Sonmez, Alper; Aydogdu, Aydogan; Tapan, Serkan; Basaran, Yalcin; Meric, Coskun; Baskoy, Kamil; Taslipinar, Abdullah; Yilmaz, Mahmut Ilker; Azal, Omer

2017-01-01

Patients with hypogonadism are at increased risk of cardiac and metabolic diseases and osteoporosis. Vitamin D and Fibroblast growth factor-23 (FGF-23) play role in the regulation of bone mineral metabolism and endothelial functions. Low vitamin D levels are reported in hypogonadism, while there is no data about the effect of testosterone replacement therapy (TRT). We investigated the effect of TRT on vitamin D and FGF-23 levels along with endothelial functions and insulin resistance in hypogonadal patients. Patients with congenital hypogonadotrophic hypogonadism (CHH) (n=32, age 20.6 ±1.58 years) were enrolled. TRT was implemented in transdermal form. The demographic parameters, FGF-23, 25(OH)D3, Asymmetric dimethylarginine (ADMA) and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured both before and after TRT. After a follow-up period of 3.63±1.33 months, ADMA and FGF-23 levels were significantly increased (p=0.03 and p=0.005 respectively), while the 25(OH)D3 and HOMA-IR index were not significantly changed. The body mass index and waist circumference levels of the patients were also increased (p<0.001 and p=0.02) along with a significant decrease in the HDL cholesterol levels (p=0.006). The results show that a short term TRT increases plasma FGF-23 and ADMA levels, in young, treatment naive patients with CHH. Whether this is an early implication of TRT related adverse effects in this very young and treatment naïve population of CHH is not clear. Future prospective studies are required to find out the long-term effects of TRT on cardio-metabolic morbidity and mortality in this specific population.

Endocrine manifestations related to inherited metabolic diseases in adults

PubMed Central

2012-01-01

Most inborn errors of metabolism (IEM) are recessive, genetically transmitted diseases and are classified into 3 main groups according to their mechanisms: cellular intoxication, energy deficiency, and defects of complex molecules. They can be associated with endocrine manifestations, which may be complications from a previously diagnosed IEM of childhood onset. More rarely, endocrinopathies can signal an IEM in adulthood, which should be suspected when an endocrine disorder is associated with multisystemic involvement (neurological, muscular, hepatic features, etc.). IEM can affect all glands, but diabetes mellitus, thyroid dysfunction and hypogonadism are the most frequent disorders. A single IEM can present with multiple endocrine dysfunctions, especially those involving energy deficiency (respiratory chain defects), and metal (hemochromatosis) and storage disorders (cystinosis). Non-autoimmune diabetes mellitus, thyroid dysfunction and/or goiter and sometimes hypoparathyroidism should steer the diagnosis towards a respiratory chain defect. Hypogonadotropic hypogonadism is frequent in haemochromatosis (often associated with diabetes), whereas primary hypogonadism is reported in Alström disease and cystinosis (both associated with diabetes, the latter also with thyroid dysfunction) and galactosemia. Hypogonadism is also frequent in X-linked adrenoleukodystrophy (with adrenal failure), congenital disorders of glycosylation, and Fabry and glycogen storage diseases (along with thyroid dysfunction in the first 3 and diabetes in the last). This is a new and growing field and is not yet very well recognized in adulthood despite its consequences on growth, bone metabolism and fertility. For this reason, physicians managing adult patients should be aware of these diagnoses. PMID:22284844

Argirein alleviates stress-induced and diabetic hypogonadism in rats via normalizing testis endothelin receptor A and connexin 43.

PubMed

Xu, Ming; Hu, Chen; Khan, Hussein-hamed; Shi, Fang-hong; Cong, Xiao-dong; Li, Qing; Dai, Yin; Dai, De-zai

2016-02-01

Argirein (rhein-arginine) is a derivative of rhein isolated from Chinese rhubarb (Rheum Officinale Baill.) that exhibits antioxidant and anti-inflammatory activities. In the present study we investigated the effects of argirein on stress-induced (hypergonadotrophic) and diabetic (hypogonadotrophic) hypogonadism in male rats. Stress-induced and diabetic hypogonadism was induced in male rats via injection of isoproterenol (ISO) or streptozotocin (STZ). ISO-injected rats were treated with argirein (30 mg·kg(-1)·d(-1), po) or testosterone replacement (0.5 mg·kg(-1)·d(-1), sc) for 5 days, and STZ-injected rats were treated with argirein (40-120 mg·kg(-1)·d(-1), po) or aminoguanidine (100 mg·kg(-1)·d(-1), po) for 4 weeks. After the rats were euthanized, blood samples and testes were collected. Serum hormone levels were measured, and the expression of endothelin receptor A (ETA), connexin 43 (Cx43) and other proteins in testes was detected. For in vitro experiments, testis homogenate was prepared from normal male rats, and incubated with ISO (1 μmol/L) or high glucose (27 mmol/L). ISO injection induced hyper-gonadotrophic hypogonadism characterized by low testosterone and high FSH and LH levels in the serum, whereas STZ injection induced hypogonadotrophic hypogonadism as evidenced by low testosterone and low FSH and LH levels in the serum. In the testes of ISO- and STZ-injected rats, the expression of ETA, MMP-9, NADPH oxidase and pPKCε was significantly increased, and the expression of Cx43 was decreased. Administration of argirein attenuated both the abnormal serum hormone levels and the testis changes in ISO- and STZ-injected rats, and aminoguanidine produced similar actions in STZ-injected rats; testosterone replacement reversed the abnormal serum hormone levels, but did not affect the testis changes in ISO-injected rats. Argirein (0.3-3 μmol/L) exerted similar effects in testis homogenate incubated with ISO or high glucose in vitro. Two types of

Hypogonadism Makes Dyslipidemia in Klinefelter's Syndrome.

PubMed

Lee, Hyo Serk; Park, Chan Woo; Lee, Joong Shik; Seo, Ju Tae

2017-11-01

Klinefelter's syndrome (KS) is a genetic syndrome that presents with hypogonadism and is associated with metabolic syndrome. Patients demonstrating hypogonadism show a greater prevalence of metabolic syndrome due to changes in body composition. We aimed to determine the association between KS and dyslipidemia. The KS group comprised 55 patients who visited the infertility clinic for an infertility evaluation and were confirmed as having a diagnosis of KS. The control group comprised 120 patients who visited the clinic for health screening. Patient characteristics were compared between the two groups with respect to height, weight, body mass index (BMI), testosterone, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride (TG) levels. Height and weight were significantly greater in patients belonging to the KS group, but no statistically significant difference was found with respect to the BMI. Testosterone levels in patients belonging to the KS group were significantly lower compared to the control group (2.4 ± 2.6 vs. 5.2 ± 1.8 ng/mL, P < 0.001). Compared to the control group, TG levels in patients belonging to the KS group were increased (134.9 ± 127.8 vs. 187.9 ± 192.1 mg/dL, P = 0.004) and HDL cholesterol was significantly decreased (51.2 ± 22.0 vs. 44.0 ± 9.5 mg/dL, P = 0.009). LDL cholesterol and total cholesterol were not significantly different between the two groups (P = 0.076 and P = 0.256, respectively). Significant differences were noted between patients belonging to the KS group and normal control group with respect to elevated TG and decreased HDL cholesterol levels. © 2017 The Korean Academy of Medical Sciences.

Gynaecomastia with hypergonadotrophic hypogonadism and Leydig cell insufficiency in recipients of high-dose chemotherapy or chemo-radiotherapy.

PubMed

Harris, E; Mahendra, P; McGarrigle, H H; Linch, D C; Chatterjee, R

2001-12-01

Late side-effects of stem cell transplantation include hypogonadism with infertility and sexual dysfunction, but gynaecomastia is less well recognised. We report five cases of gynaecomastia with features of hypergonadotrophic hypogonadism (primary testicular failure), who received either a TBI/cyclophosphamide conditioned allograft (n = 3) or a BEAM autograft (n = 2). Patients receiving an allograft had gynaecomastia, Leydig cell insufficiency (LCI) diminished libido and erectile dysfunction. Surgery was required in one case, while in two cases the gynaecomastia resolved spontaneously after 6 months. Two patients also had gynaecomastia and sexual dysfunction, severe hypogonadism, very low testosterone levels and marked hyperprolactinaemia following autoBMT. Both responded well to testosterone replacement therapy (TRT). As a group, all patients had primary testicular failure and all except one, had LCI (compensated or frank). However, there was no correlation between the severity of gynaecomastia and the degree of endocrine dysfunction. This preliminary study is the first to suggest that gynaecomastia, due to primary hypogonadism and LCI, may be a significant complication of myeloablative conditioning therapy. Therefore gynaecomastia in BMT recipients must always be treated as a pathological entity as it may be the external manifestation of a complex endocrine pathology. It is a potentially treatable condition. Although spontaneously reversible, some patients may require TRT or even surgery. We recommend comprehensive endocrine testing in conjunction with a reproductive endocrinologist and prompt intervention to alleviate embarrassment and anxiety in afflicted BMT recipients.

Idiopathic Inflammatory Myopathies

PubMed Central

Dimachkie, Mazen M.; Barohn, Richard J.

2012-01-01

The idiopathic inflammatory myopathies are a group of rare disorders including polymyositis (PM), dermatomyositis (DM), and autoimmune necrotizing myopathies (NMs). The idiopathic inflammatory myopathies share many similarities. They present acutely, subacutely, or chronically with marked proximal and symmetric muscle weakness, except for associated distal and asymmetric weakness in inclusion body myositis. The idiopathic inflammatory myopathies also share a variable degree of creatine kinase (CK) elevation and a nonspecifically abnormal electromyogram demonstrating an irritative myopathy. The muscle pathology demonstrates inflammatory exudates of variable distribution within the muscle fascicle. Despite these similarities, the idiopathic inflammatory myopathies are a heterogeneous group. The overlap syndrome (OS) refers to the association of PM, DM, or NM with connective tissue disease, such as scleroderma or systemic lupus erythematosus. In addition to elevated antinuclear antibodies (ANA), patients with OS may be weaker in the proximal arms than the legs mimicking the pattern seen in some muscular dystrophies. In this review, we focus on DM, PM, and NM and examine current and promising therapies. PMID:23117947

Bone mineral density in human immunodeficiency virus-1 infected men with hypogonadism prior to highly-active-antiretroviral-therapy (HAART)

PubMed Central

2009-01-01

Alterations of bone metabolism have been observed in numerous studies of HIV-infected patients. Sex steroids are known to profoundly influence bone mass and bone turnover. Hypogonadism is common in HIV-infection. Therefore, we performed a cross sectional study of 80 male HIV-infected patients without wasting syndrome, and 20 healthy male controls, in whom we analyzed urine and serum samples for both calciotropic hormones and markers of bone metabolism and of endocrine testicular function. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry both in the lumbar spine and Ward's triangle of the left hip. None of the patients received highly-active-antiretroviral-therapy (HAART). Compared to eugonadal HIV-infected patients, subjects with hypogonadism (n = 32; 40%) showed statistically significant decrease of serum osteocalcin (p < 0.05) and elevated urinary excretion of crosslinks (p < 0.05). However, we found 13 and 15, respectively, patients with osteopenia (t-score -1.0 to -2.5 SD below normal) of the lumbar spine. The dissociation between bone formation and resorption and the reduction of of BMD (p < 0.05) is stronger expressed in patients with hypogonadism. Habitual hypogonadism appears to be of additional relevance for bone metabolism of male HIV-positive patients prior to HAART. PMID:19258214

Study of smell and reproductive organs in a mouse model for CHARGE syndrome

PubMed Central

Bergman, Jorieke EH; Bosman, Erika A; van Ravenswaaij-Arts, Conny MA; Steel, Karen P

2010-01-01

CHARGE syndrome is a multiple congenital anomaly syndrome characterised by Coloboma, Heart defects, Atresia of choanae, Retardation of growth and/or development, Genital hypoplasia, and Ear anomalies often associated with deafness. It is caused by heterozygous mutations in the CHD7 gene and shows a highly variable phenotype. Anosmia and hypogonadotropic hypogonadism occur in the majority of the CHARGE patients, but the underlying pathogenesis is unknown. Therefore, we studied the ability to smell and aspects of the reproductive system (reproductive performance, gonadotropin-releasing hormone (GnRH) neurons and anatomy of testes and uteri) in a mouse model for CHARGE syndrome, the whirligig mouse (Chd7Whi/+). We showed that Chromodomain Helicase DNA-binding protein 7 (Chd7) is expressed in brain areas involved in olfaction and reproduction during embryonic development. We observed poorer performance in the smell test in adult Chd7Whi/+ mice, secondary either to olfactory dysfunction or to balance disturbances. Olfactory bulb and reproductive organ abnormalities were observed in a proportion of Chd7Whi/+ mice. Hypothalamic GnRH neurons were slightly reduced in Chd7Whi/+ females and reproductive performance was slightly less in Chd7Whi/+ mice. This study shows that the penetrance of anosmia and hypogonadotropic hypogonadism is lower in Chd7Whi/+ mice than in CHARGE patients. Interestingly, many phenotypic features of the Chd7 mutation showed incomplete penetrance in our model mice, despite the use of inbred, genetically identical mice. This supports the theory that the extreme variability of the CHARGE phenotype in both humans and mice might be attributed to variations in the fetal microenvironment or to purely stochastic events. PMID:19809474

The identification of HESX1 mutations in Kallmann syndrome

PubMed Central

Newbern, Kayce; Natrajan, Nithya; Kim, Hyung-Goo; Chorich, Lynn .P.; Halvorson, Lisa; Cameron, Richard S.; Layman, Lawrence C.

2013-01-01

Objective To determine if HESX1 mutations are present in patients with idiopathic hypogonadotropic hypogonadism (IHH)/Kallmann syndrome (KS). HESX1 mutations have previously been characterized in patients with septo-optic dysplasia (SOD), isolated growth hormone deficiency (IGHD), and combined pituitary hormone deficiency (CPHD). We hypothesized that IHH/KS represents a milder phenotypic variant of SOD. Design PCR-based DNA sequencing was performed on 217 well-characterized IHH/KS patients. Putative missense mutations were analyzed by sorting intolerant from tolerant (SIFT) and Clustal Ω. Setting An academic medical center Patients 217 IHH/KS and 192 controls Interventions DNA was extracted from patients and controls; genotype/phenotype comparisons were made Main Outcome Measures DNA sequence of HESX1, SIFT analysis, and ortholog alignment Results Two novel heterozygous missense mutations (p.H42Y and p.V75L) and previously reported heterozygous missense mutation p.Q6H in HESX1 were identified in 3/217 (1.4%) patients. All were males with KS. Both p.Q6H and p.H42Y were predicted to be deleterious by SIFT, while p.V75L was conserved in 8/9 species. No other IHH/KS gene mutations were present. Conclusions HESX1 mutations may cause KS in addition to more severe phenotypes. Our findings expand the phenotypic spectrum of HESX1 mutations in humans, thereby broadening its role in development. PMID:23465708

Study clarifies associations between hypogonadism and health in aging men.

PubMed

Amory, John K

2012-11-01

Tajar and colleagues present the associations between moderate and severe hypogonadism, symptoms of androgen deficiency and the prevelence of end-organ evidence of androgen deficency in 2966 older men in the European Male Aging Study. They find lower muscle mass, reduced bone mineral density, anemia, insulin resistence, metabolic syndrome and cardiovascular disease, with greater risks of these signs of androgen deficiency at lower serum testosterone concentrations.

Comparison of monocyte gene expression among patients with neurocysticercosis-associated epilepsy, Idiopathic Epilepsy and idiopathic headaches in India.

PubMed

Prabhakaran, Vasudevan; Drevets, Douglas A; Ramajayam, Govindan; Manoj, Josephine J; Anderson, Michael P; Hanas, Jay S; Rajshekhar, Vedantam; Oommen, Anna; Carabin, Hélène

2017-06-01

Neurocysticercosis (NCC), a neglected tropical disease, inflicts substantial health and economic costs on people living in endemic areas such as India. Nevertheless, accurate diagnosis using brain imaging remains poorly accessible and too costly in endemic countries. The goal of this study was to test if blood monocyte gene expression could distinguish patients with NCC-associated epilepsy, from NCC-negative imaging lesion-free patients presenting with idiopathic epilepsy or idiopathic headaches. Patients aged 18 to 51 were recruited from the Department of Neurological Sciences, Christian Medical College and Hospital, Vellore, India, between January 2013 and October 2014. mRNA from CD14+ blood monocytes was isolated from 76 patients with NCC, 10 Recovered NCC (RNCC), 29 idiopathic epilepsy and 17 idiopathic headaches patients. A preliminary microarray analysis was performed on six NCC, six idiopathic epilepsy and four idiopathic headaches patients to identify genes differentially expressed in NCC-associated epilepsy compared with other groups. This analysis identified 1411 upregulated and 733 downregulated genes in patients with NCC compared to Idiopathic Epilepsy. Fifteen genes up-regulated in NCC patients compared with other groups were selected based on possible relevance to NCC, and analyzed by qPCR in all patients' samples. Differential gene expression among patients was assessed using linear regression models. qPCR analysis of 15 selected genes showed generally higher gene expression among NCC patients, followed by RNCC, idiopathic headaches and Idiopathic Epilepsy. Gene expression was also generally higher among NCC patients with single cyst granulomas, followed by mixed lesions and single calcifications. Expression of certain genes in blood monocytes can distinguish patients with NCC-related epilepsy from patients with active Idiopathic Epilepsy and idiopathic headaches. These findings are significant because they may lead to the development of new tools to

Argirein alleviates stress-induced and diabetic hypogonadism in rats via normalizing testis endothelin receptor A and connexin 43

PubMed Central

Xu, Ming; Hu, Chen; Khan, Hussein-hamed; Shi, Fang-hong; Cong, Xiao-dong; Li, Qing; Dai, Yin; Dai, De-zai

2016-01-01

Aim: Argirein (rhein-arginine) is a derivative of rhein isolated from Chinese rhubarb (Rheum Officinale Baill.) that exhibits antioxidant and anti-inflammatory activities. In the present study we investigated the effects of argirein on stress-induced (hypergonadotrophic) and diabetic (hypogonadotrophic) hypogonadism in male rats. Methods: Stress-induced and diabetic hypogonadism was induced in male rats via injection of isoproterenol (ISO) or streptozotocin (STZ). ISO-injected rats were treated with argirein (30 mg·kg−1·d−1, po) or testosterone replacement (0.5 mg·kg−1·d−1, sc) for 5 days, and STZ-injected rats were treated with argirein (40–120 mg·kg−1·d−1, po) or aminoguanidine (100 mg·kg−1·d−1, po) for 4 weeks. After the rats were euthanized, blood samples and testes were collected. Serum hormone levels were measured, and the expression of endothelin receptor A (ETA), connexin 43 (Cx43) and other proteins in testes was detected. For in vitro experiments, testis homogenate was prepared from normal male rats, and incubated with ISO (1 μmol/L) or high glucose (27 mmol/L). Results: ISO injection induced hyper-gonadotrophic hypogonadism characterized by low testosterone and high FSH and LH levels in the serum, whereas STZ injection induced hypogonadotrophic hypogonadism as evidenced by low testosterone and low FSH and LH levels in the serum. In the testes of ISO- and STZ-injected rats, the expression of ETA, MMP-9, NADPH oxidase and pPKCε was significantly increased, and the expression of Cx43 was decreased. Administration of argirein attenuated both the abnormal serum hormone levels and the testis changes in ISO- and STZ-injected rats, and aminoguanidine produced similar actions in STZ-injected rats; testosterone replacement reversed the abnormal serum hormone levels, but did not affect the testis changes in ISO-injected rats. Argirein (0.3–3 μmol/L) exerted similar effects in testis homogenate incubated with ISO or high glucose in

Examining the effect of the computer-based educational package on quality of life and severity of hypogonadism symptoms in males.

PubMed

Afsharnia, Elahe; Pakgohar, Minoo; Khosravi, Shahla; Haghani, Hamid

2018-06-01

The objective of this study was to determine the effect of the computer-based educational package on men's QoL and the severity of their hypogonadism symptoms. A quasi-experimental study was conducted on 80 male employees. The data collection tool included the 'Aging Male Symptoms' (AMS) and 'Short Form-36' (SF36) questionnaires. Four sessions were held for the intervention group over a period of 4 weeks. Two months after training, QoL and the severity of hypogonadism symptoms were measured in both the intervention and control groups. The data were analyzed with SPSS 22 software and statistical tests, such as χ 2 , independent t-test, Fisher's exact test, and paired t-tests. Significant statistical changes were observed in the intervention group before and 2 months after the training in the QoL score in the overall dimensions of physical-psychological health and all its domains except for three domains of emotional role, social function, and pain. Furthermore, the paired t-tests showed significant differences between 2 months before and after the training in all the domains and the overall hypogonadism score in the intervention group. Based on our findings, the computer-based educational package has a positive effect on QoL and reduction of hypogonadism symptoms.

Long-Term Follow-Up of Primary Medical Versus Surgical Treatment of Prolactinomas in Men: Effects on Hyperprolactinemia, Hypogonadism, and Bone Health.

PubMed

Andereggen, Lukas; Frey, Janine; Andres, Robert H; El-Koussy, Marwan; Beck, Jürgen; Seiler, Rolf W; Christ, Emanuel

2017-01-01

In men with prolactinomas, impaired bone density is the principle consequence of hyperprolactinemia-induced hypogonadism. Although dopamine agonists (DAs) are the first-line approach in prolactinomas, surgery can be considered in selected cases. In this study, we aimed to investigate the long-term control of hyperprolactinemia, hypogonadism, and bone health comparing primary medical and surgical therapy in men who had not had prior DA treatment. This is a retrospective case-note study of 44 consecutive men with prolactinomas and no prior DAs managed in a single tertiary referral center. Clinical, biochemical, and radiologic response to the first-line approach were analyzed in the 2 cohorts. Mean age at diagnosis was 47 years (range, 22-78 years). The prevalence of hypogonadism was 86%, and 27% of patients had pathologic bone density at baseline. The primary therapeutic strategy was surgery for 34% and DAs for 66% of patients. Median long-term follow-up was 63 months (range, 17-238 months). Long-term control of hyperprolactinemia required DAs in 53% of patients with primary surgical therapy, versus 90% of patients with primary medical therapy (P = 0.02). Hypogonadism was controlled in 73% of patients. The prevalence of patients with pathologic bone density was 37% at last follow-up, with no differences between the 2 therapeutic cohorts (P = 0.48). Despite control of hyperprolactinemia and hypogonadism in most patients independent of the primary treatment modality, the prevalence of impaired bone health status remains high, and osteodensitometry should be recommended. Copyright © 2016 Elsevier Inc. All rights reserved.

Adherence to treatment in men with hypogonadotrophic hypogonadism.

PubMed

Dwyer, Andrew A; Tiemensma, Jitske; Quinton, Richard; Pitteloud, Nelly; Morin, Diane

2017-03-01

Men with congenital hypogonadotrophic hypogonadism (CHH) typically require lifelong hormonal therapy, and discontinuing treatment can have negative health consequences. Little is known about adherence to treatment or the psychosocial impact of CHH. A sequential, multiple methods approach was used. A quantitative online survey assessed adherence to treatment, depressive symptoms and illness perceptions. Subsequently, qualitative focus groups explored patient-reported factors for adherence. Adult men with CHH on at least 1 year of treatment were recruited internationally. Adherence (Morisky medication adherence scale), depressive symptoms (Zung self-rating depression scale) and patient perception of CHH (revised illness perception questionnaire) were assessed in an online survey, and comparisons were made to reference groups. Patient focus group discussions were conducted and thematic analysis was employed to identify patient-reported factors for adherence. In total, 101 men on long-term treatment were included (mean age 37 ± 11 years). Forty three percent (43/101) exhibited low medication adherence and a significantly elevated prevalence of mild, moderate or severe depressive symptoms (27%, 17%, 20%, respectively, all P < 0·001 vs reference population). Patients reported negative illness perceptions and significant psychosocial consequences. Focus group discussions (n = 3, 26 total patients) identified patient-, health professional- and healthcare system-related barriers as targets for improving adherence. Congenital hypogonadotrophic hypogonadism men are challenged to adhere to long-term treatment. Poor adherence may contribute to adverse effects on bone, sexual and psychological health. The psychosocial morbidity of CHH is significant and appears to be underappreciated by healthcare providers. © 2016 John Wiley & Sons Ltd.

Mutations of the KISS1 Gene in Disorders of Puberty

PubMed Central

Silveira, L. G.; Noel, S. D.; Silveira-Neto, A. P.; Abreu, A. P.; Brito, V. N.; Santos, M. G.; Bianco, S. D. C.; Kuohung, W.; Xu, S.; Gryngarten, M.; Escobar, M. E.; Arnhold, I. J. P.; Mendonca, B. B.; Kaiser, U. B.; Latronico, A. C.

2010-01-01

Context: Kisspeptin, encoded by the KISS1 gene, is a key stimulatory factor of GnRH secretion and puberty onset. Inactivating mutations of its receptor (KISS1R) cause isolated hypogonadotropic hypogonadism (IHH). A unique KISS1R-activating mutation was described in central precocious puberty (CPP). Objective: Our objective was to investigate KISS1 mutations in patients with idiopathic CPP and normosmic IHH. Patients: Eighty-three children with CPP (77 girls) and 61 patients with IHH (40 men) were studied. The control group consisted of 200 individuals with normal pubertal development. Methods: The promoter region and the three exons of KISS1 were amplified and sequenced. Cells expressing KISS1R were stimulated with synthetic human wild-type or mutant kisspeptin-54 (kp54), and inositol phosphate accumulation was measured. In a second set of experiments, kp54 was preincubated in human serum before stimulation of the cells. Results: Two novel KISS1 missense mutations, p.P74S and p.H90D, were identified in three unrelated children with idiopathic CPP. Both mutations were absent in 400 control alleles. The p.P74S mutation was identified in the heterozygous state in a boy who developed CPP at 1 yr of age. The p.H90D mutation was identified in the homozygous state in two unrelated girls with CPP. In vitro studies revealed that the capacity of the P74S and H90D mutants to stimulate IP production was similar to the wild type. After preincubation of wild-type and mutant kp54 in human serum, the capacity to stimulate signal transduction was significantly greater for P74S compared with the wild type, suggesting that the p.P74S variant is more stable. Only polymorphisms were found in the IHH group. Conclusion: Two KISS1 mutations were identified in unrelated patients with idiopathic CPP. The p.P74S variant was associated with higher kisspeptin resistance to degradation in comparison with the wild type, suggesting a role for this mutation in the precocious puberty phenotype

Association of carotene rich diet with hypogonadism in a male athlete.

PubMed

Adamopoulos, Dimitrios; Venaki, Evangelia; Koukkou, Eftychia; Billa, Evangelia; Kapolla, Niki; Nicopoulou, Stamatina

2006-07-01

To report on a unique case of hypogonadism associated with excessive carotene intake in a young male athlete. A 20-year-old patient presented with a gradual decline in muscular and physical activity, sexual interest and erectile ability associated with a high in carotene and low in animal fat diet of his own design a year prior to the clinical manifestations. Clinically, he presented with very overt signs of carotene excess: his palms and soles were yellow. Moreover, 2 weeks after normalization of his diet, carotene B levels were at the upper end of the normal range. Repeated stimulation tests of hypothalamic, pituitary and testicular function were performed before and at 3, 6 and 12 months after the introduction of a balanced diet. Very low basal and stimulated values for gonadotropins and gonadal steroids were found at the initial evaluation with a progressive recovery shown after months of a balanced diet and carotene B restoration. Complete androgen secretion and sexual response recovery were observed only after 9-12 months from diagnosis. This is the first report associating excessive carotene intake with a hypothalamic form of hypogonadism in a young man.

Radiological features of the skull in Klinefelter's syndrome and male hypogonadism.

PubMed

Kosowicz, J; Rzymski, K

1975-07-01

Skull radiographs were performed in 21 cases of Klinefelter's syndrome and in 30 cases of eunuchoidism. The radiographic changes of the skull in Klinefelter's syndrome are: temporal flattening, decreased width of the vault, narrowing of the mandible, decreased length of the skull, shortening of the anterior fossa cranii, decrease in the angle of the base, thinning of the vault bones at the major fontanelle, premature and excessive calcification of the coronal suture, deepening of the posterior fossa and shortening of the mandibular rami. In hypogonadotropic eunuchoidism the skull radiographs show: small mastoid processes, fine bones of the vault, small sella turcica, club-shaped clinoid processes, excessive development of sphenoidal sinuses and in the fourth and later decades of life a diminished bone density (osteoporosis).

Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism.

PubMed

Kristensen, David Møbjerg; Desdoits-Lethimonier, Christèle; Mackey, Abigail L; Dalgaard, Marlene Danner; De Masi, Federico; Munkbøl, Cecilie Hurup; Styrishave, Bjarne; Antignac, Jean-Philippe; Le Bizec, Bruno; Platel, Christian; Hay-Schmidt, Anders; Jensen, Tina Kold; Lesné, Laurianne; Mazaud-Guittot, Séverine; Kristiansen, Karsten; Brunak, Søren; Kjaer, Michael; Juul, Anders; Jégou, Bernard

2018-01-23

Concern has been raised over increased male reproductive disorders in the Western world, and the disruption of male endocrinology has been suggested to play a central role. Several studies have shown that mild analgesics exposure during fetal life is associated with antiandrogenic effects and congenital malformations, but the effects on the adult man remain largely unknown. Through a clinical trial with young men exposed to ibuprofen, we show that the analgesic resulted in the clinical condition named "compensated hypogonadism," a condition prevalent among elderly men and associated with reproductive and physical disorders. In the men, luteinizing hormone (LH) and ibuprofen plasma levels were positively correlated, and the testosterone/LH ratio decreased. Using adult testis explants exposed or not exposed to ibuprofen, we demonstrate that the endocrine capabilities from testicular Leydig and Sertoli cells, including testosterone production, were suppressed through transcriptional repression. This effect was also observed in a human steroidogenic cell line. Our data demonstrate that ibuprofen alters the endocrine system via selective transcriptional repression in the human testes, thereby inducing compensated hypogonadism. Copyright © 2018 the Author(s). Published by PNAS.

Oestrogen supplementation attenuates responses to psychological stress in elderly men rendered hypogonadal after treatment for prostate cancer.

PubMed

Komesaroff, Paul A; Fullerton, Meryl; Esler, Murray D; Jennings, Garry; Sudhir, Krishnankutty

2002-06-01

We have shown previously that oestrogens attenuate cardiovascular and hormonal responses to stress in perimenopausal women. The cardiovascular role of oestrogens in men is uncertain, despite preliminary evidence that endogenous oestrogens produced by aromatization of androgenic precursors are of physiological importance; hypogonadal men have very low levels of circulating oestrogen. We therefore studied the haemodynamic and hormonal responses to a standardized laboratory mental stress test in 12 men (mean age 68.9 +/- 2.6 SEM years) rendered hypogonadal as a result of treatment for prostatic cancer, before and after 8 weeks of oestrogen supplementation (oestradiol valerate 1 mg daily, n = 7) or placebo (n = 5). The stress was administered as a standard mental arithmetic test of 10 minutes' duration. Blood pressure, cortisol and ACTH were measured at baseline, and following 5 minutes and 10 minutes of stress, and ACTH again at 25 minutes on both days. Noradrenaline and adrenaline responses to mental stress, as well as changes in total body and forearm spillover of noradrenaline and noradrenaline clearance, were also measured. Oestrogen supplementation was well tolerated, with minimal adverse effects. Mean oestradiol levels increased from < 30 pmol/l to 308 +/- 65 pmol/l after oestrogen treatment. Oestradiol significantly attenuated the mental stress-induced increase in both systolic and diastolic blood pressures. Oestradiol also attenuated mental stress-induced increases in ACTH, cortisol and adrenaline, but did not influence either total body or forearm spillover of noradrenaline. Responses to stress were unchanged after administration of placebo. We conclude that oestrogen supplementation in men rendered hypogonadal as a result of treatment for prostate cancer is well tolerated and significantly attenuates blood pressure and hormonal responses to psychological stress. These findings suggest the need for further studies to examine a possible clinical role for

Androgen replacement therapy in late-onset hypogonadism: current concepts and controversies - a mini-review.

PubMed

Mäkinen, Juuso I; Huhtaniemi, Ilpo

2011-01-01

Normal testicular function is essential for the maintenance of male physical strength and behaviour irrespective of age. A new term of late-onset hypogonadism (LOH) has been coined for the condition of decreased testosterone (T) and hypogonadal symptoms in ageing men. The most important testicular hormone, T, is responsible for the gender-specific androgenic-anabolic effects in men. Testicular T production remains stable until around the age of 40 years after which it declines by 1-2% annually. Despite this age-related decline, serum T levels in most older men remain within the reference range of younger men. The decreasing androgen levels are paralleled by well-defined objective biological and nonspecific subjective signs and symptoms of ageing. Because these symptoms are similar to those observed in young men with documented hypogonadism, androgen replacement therapy (ART) has been considered a logical way to treat them. A thorough review of the existing literature was performed to evaluate the current concepts and controversies related to ageing men and ART. Although it is intuitively logical that the symptoms of LOH are due to the ageing-related deficiency of T, and that they can be reversed by ART, the evidence for this is still variable and often weak. In particular, evidence-based information about long-term benefits and risks of ART in ageing men is largely missing. Despite widespread use, evidence-based proof for the objective benefits and side effects of ART of elderly men is still scanty, and such treatments should be considered experimental. Copyright © 2010 S. Karger AG, Basel.

Natural history of idiopathic diabetes insipidus.

PubMed

Richards, Gail E; Thomsett, Michael J; Boston, Bruce A; DiMeglio, Linda A; Shulman, Dorothy I; Draznin, Martin

2011-10-01

To determine what percentage of diabetes insipidus (DI) in childhood is idiopathic and to assess the natural history of idiopathic DI. We conducted a retrospective chart review of 105 patients with DI who were born or had DI diagnosed between 1980-1989 at 3 medical centers. A second cohort of 30 patients from 6 medical centers in whom idiopathic DI was diagnosed after 1990 was evaluated retrospectively for subsequent etiologic diagnoses and additional hypothalamic/pituitary deficiencies and prospectively for quality of life. In the first cohort, 11% of patients had idiopathic DI. In the second cohort, additional hypothalamic/pituitary hormone deficiencies developed in 33%, and 37% received an etiologic diagnosis for DI. Health-related quality of life for all the patients with idiopathic DI was comparable with the healthy reference population. Only a small percentage of patients with DI will remain idiopathic after first examination. Other hormone deficiencies will develop later in one-third of those patients, and slightly more than one-third of those patients will have an etiology for the DI diagnosed. Long-term surveillance is important because tumors have been diagnosed as long as 21 years after the onset of DI. Quality of life for these patients is as good as the reference population. Copyright © 2011 Mosby, Inc. All rights reserved.

A neutral effect of testosterone therapy on macroprolactin content in men with macroprolactinemia and late-onset hypogonadism.

PubMed

Krysiak, Robert; Kowalska, Beata; Szkróbka, Witold; Okopień, Bogusław

2016-02-01

In the light of recent studies, macroprolactinemia seems to occur much more frequently than previously thought. In women, oral contraceptive pills exhibit a stimulatory effect on macroprolactin production. No previous study has investigated macroprolactin levels in androgen-treated hypogonadal men. We studied 10 men with isolated macroprolactinemia and 14 men with normal prolactin levels who because of late-onset hypogonadism were treated with intramuscular testosterone enanthate. Serum prolactin, macroprolactin content, serum testosterone and gonadotropin levels were assessed at baseline and after 4 months of therapy. Although baseline levels of testosterone and gonadotropins were similar in men with and without macroprolactinemia, clinical symptoms were more severe in patients with elevated big-big prolactin levels. As expected, testosterone treatment increased serum testosterone, slightly reduced serum gonadotropins, as well as improved clinical condition in both patients with and without macroprolactinemia, with no difference between the groups. However, testosterone therapy did not affect serum prolactin and macroprolactin content, even after replacing intramuscular testosterone enanthate with oral testosterone undecanoate. Our results suggest a negligible effect of testosterone replacement on macroprolactin levels in macroprolactinemic men with late-onset hypogonadism. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Vitamin D deficiency in chronic idiopathic urticaria.

PubMed

Movahedi, Masoud; Tavakol, Marzieh; Hirbod-Mobarakeh, Armin; Gharagozlou, Mohammad; Aghamohammadi, Asghar; Tavakol, Zahra; Momenzadeh, Kaveh; Nabavi, Mohammad; Dabbaghzade, Abbas; Mosallanejad, Asieh; Rezaei, Nima

2015-04-01

Chronic urticaria is the most common skin diseases, characterized by chronic cutaneous lesions which severely debilitates patients in several aspects of their everyday life. Vitamin D is known to exert several actions in the immune system and to influence function and differentiation of mast cells, central role players in the pathogenesis of chronic idiopathic urticaria. This study was performed to evaluate the relationship between vitamin D levels and susceptibility to chronic idiopathic urticaria. One hundred and fourteen patients with chronic idiopathic urticaria were recruited in this study along with one hundred and eighty seven sex-matched and age-matched healthy volunteers as the control group. For each patient, urticaria activity score was calculated and autologous serum skin test was done. Vitamin D metabolic statue was measured in serum as 25 hydroxyvitamin D using enzyme immunoassay method. Patients with chronic idiopathic urticaria significantly showed lower levels of vitamin D. Vitamin D deficiency was significantly associated with increased susceptibility to chronic idiopathic urticaria. There was a significant positive correlation between vitamin D levels and urticaria activity score. This study showed that patients with chronic idiopathic urticaria had reduced levels of vitamin D, while vitamin D deficiency could increase susceptibility to chronic idiopathic urticaria.

The safety of available treatments of male hypogonadism in organic and functional hypogonadism.

PubMed

Corona, G; Rastrelli, G; Reisman, Y; Sforza, A; Maggi, M

2018-03-01

In the case of primary male hypogonadism (HG), only testosterone (T) replacement therapy (TRT) is possible whereas when the problem is secondary to a pituitary or hypothalamus alteration both T production and fertility can be, theoretically, restored. We here systematically reviewed and discussed the advantages and limits of medications formally approved for the treatment of HG. Areas covered: Data derived from available meta-analyses of placebo controlled randomized trials (RCTs) were considered and analyzed. Gonadotropins are well-toleratedand their use is mainly limited by higher costs and a more cumbersome treatment schedule than TRT. Available RCTs on TRT suggest that cardiovascular (CV) and venous thromboembolism risk is not a major issue and that prostate safety is guaranteed. The risk of increased hematocrit is mainly limited to the use of short terminjectable preparations. Expert opinion: In the last few years the concept of 'organic' irreversible HG and 'functional' or age- and comorbidity-related HG has been introduced. This definition is not evidence-based. The majority of RCTs enrolled patients with 'functional' HG. Considering the significant improvement in body composition, glucose metabolism and sexual activity, TRT should not be limited to 'organic' HG, but also offered for 'functional'.

Idiopathic ventricular tachycardia and fibrillation.

PubMed

Belhassen, B; Viskin, S

1993-06-01

Important data have recently been added to our understanding of sustained ventricular tachyarrhythmias occurring in the absence of demonstrable heart disease. Idiopathic ventricular tachycardia (VT) is usually of monomorphic configuration and can be classified according to its site of origin as either right monomorphic (70% of all idiopathic VTs) or left monomorphic VT. Several physiopathological types of monomorphic VT can be presently individualized, according to their mode of presentation, their relationship to adrenergic stress, or their response to various drugs. The long-term prognosis is usually good. Idiopathic polymorphic VT is a much rarer type of arrhythmia with a less favorable prognosis. Idiopathic ventricular fibrillation may represent an underestimated cause of sudden cardiac death in ostensibly healty patients. A high incidence of inducibility of sustained polymorphic VT with programmed ventricular stimulation has been found by our group, but not by others. Long-term prognosis on Class IA antiarrhythmic medications that are highly effective at electrophysiologic study appears excellent.

Cavernous neurotomy in the rat is associated with the onset of an overt condition of hypogonadism.

PubMed

Vignozzi, Linda; Filippi, Sandra; Morelli, Annamaria; Marini, Mirca; Chavalmane, Aravinda; Fibbi, Benedetta; Silvestrini, Enrico; Mancina, Rosa; Carini, Marco; Vannelli, G Barbara; Forti, Gianni; Maggi, Mario

2009-05-01

Most men following radical retropubic prostatectomy (RRP) are afflicted by erectile dysfunction (ED). RRP-related ED occurs as a result of surgically elicited neuropraxia, leading to histological changes in the penis, including collagenization of smooth muscle and endothelial damage. To verify whether hypogonadism could contribute to the pathogenesis of RRP-ED. Effects of testosterone (T), alone or in association with long-term tadalafil (Tad) treatment in a rat model of bilateral cavernous neurotomy (BCN). Penile tissues from rats were harvested for vasoreactivity studies 3 months post-BCN. Penile oxygenation was evaluated by hypoxyprobe immunostaining. Phosphodiesterase type 5 (PDE5), endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) mRNA expression were quantified by Real Time quantitative reverse transcription polymerase chain reaction (qRT-PCR). In BCN rats, we observed the onset of an overt condition of hypogonadism, characterized by reduced T plasma level, reduced ventral prostate weight, reduced testis function (including testis weight and number of Leydig cells), with an inadequate compensatory increase of luteinizing hormone. BCN induced massive penile hypoxia, decreased muscle/fiber ratio, nNOS, eNOS, PDE5 expression, increased sensitivity to the nitric oxide donor, sodium nitroprusside (SNP), and reduced the relaxant response to acetylcholine (Ach), as well as unresponsiveness to acute Tad dosing. In BCN rats, chronic Tad-administration normalizes penile oxygenation, smooth muscle loss, PDE5 expression, SNP sensitivity, and the responsiveness to the acute Tad administration. Chronic Tad treatment was ineffective in counteracting the reduction of nNOS and eNOS expression, along with Ach responsiveness. T supplementation, in combination with Tad, reverted some of the aforementioned alterations, restoring smooth muscle content, eNOS expression, as well as the relaxant response of penile strips to Ach, but not n

Relation between adolescent idiopathic scoliosis and morphologic somatotypes.

PubMed

LeBlanc, R; Labelle, H; Rivard, C H; Poitras, B

1997-11-01

A prospective and controlled comparative study. To verify the difference in morphologic appearance between a group of adolescents with progressive adolescent idiopathic scoliosis and a control group of normal adolescents. In a previous retrospective study, the possibility of a relation between progressive adolescent idiopathic scoliosis and specific morphotypes was demonstrated. Fifty-two adolescent girls with progressive adolescent idiopathic scoliosis were compared with an age-matched control group of 62 unaffected girls using a classification technique based on morphologic somatotypes. Morphotypes were evaluated with standardized pre-established criteria based on Sheldon's technique. Patients with progressive adolescent idiopathic scoliosis showed significantly less mesomorphism (mean value of 0.88 +/- 0.51) than control girls (mean value of 1.72 +/- 0.52). Adolescent girls with progressive adolescent idiopathic scoliosis have a morphologic somatotype that is different from the normal adolescent population. Subjects with progressive adolescent idiopathic scoliosis are significantly less mesomorphic than control girls. This observation may be of value as a predictive factor for early identification of subjects with adolescent idiopathic scoliosis at greater risk of progression.

Perspective: Update on Idiopathic Intracranial Hypertension

PubMed Central

Bruce, Beau B.; Biousse, Valérie; Newman, Nancy J.

2011-01-01

Purpose Provide an update on various features of idiopathic intracranial hypertension. Design Perspective. Methods Selected articles on the epidemiology, clinical and imaging features, natural history, pathophysiology, and treatment of idiopathic intracranial hypertension were reviewed and interpreted in the context of the authors’ clinical and research experience. Results Idiopathic intracranial hypertension is primarily a disease of obese women of childbearing age, but it can affect patients of any weight, sex, and age. Although a relatively rare disorder, idiopathic intracranial hypertension’s associated costs in the U.S. entail hundreds of millions of dollars. Even following treatment, headaches are frequently persistent and may require the continued involvement of a neurologist. Quality of life reductions and depression are common among idiopathic intracranial hypertension patients. However, visual dysfunction, especially visual field abnormalities, represents the major morbidity of this disorder, and serial automated perimetry remains the primary mode of patient monitoring. Patients who are men, black, very obese, or anemic are at higher risk of visual loss. Vitamin A metabolism, adipose tissue as an actively secreting endocrine tissue, and cerebral venous abnormalities are areas of active study regarding idiopathic intracranial hypertension’s pathophysiology. Treatment studies show that lumbar puncture is a valuable treatment (in addition to its crucial diagnostic role) and that weight management is critical. However, open questions remain regarding the efficacy of acetazolamide, CSF diversion procedures, and cerebral venous stenting. Conclusions Many questions remain unanswered about idiopathic intracranial hypertension. Ongoing studies, especially an ongoing NIH-funded clinical trial of acetazolamide, should provide more insight into this important, yet poorly understood syndrome of isolated intracranial hypertension. PMID:21696699

Loss of microRNA-7a2 induces hypogonadotropic hypogonadism and infertility

PubMed Central

Ahmed, Kashan; LaPierre, Mary P.; Denzler, Rémy; Yang, Yinjie; Rülicke, Thomas; Latreille, Mathieu

2017-01-01

MicroRNAs (miRNAs) are negative modulators of gene expression that fine-tune numerous biological processes. miRNA loss-of-function rarely results in highly penetrant phenotypes, but rather, influences cellular responses to physiologic and pathophysiologic stresses. Here, we have reported that a single member of the evolutionarily conserved miR-7 family, miR-7a2, is essential for normal pituitary development and hypothalamic-pituitary-gonadal (HPG) function in adulthood. Genetic deletion of mir-7a2 causes infertility, with low levels of gonadotropic and sex steroid hormones, small testes or ovaries, impaired spermatogenesis, and lack of ovulation in male and female mice, respectively. We found that miR-7a2 is highly expressed in the pituitary, where it suppresses golgi glycoprotein 1 (GLG1) expression and downstream bone morphogenetic protein 4 (BMP4) signaling and also reduces expression of the prostaglandin F2a receptor negative regulator (PTGFRN), an inhibitor of prostaglandin signaling and follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretion. Our results reveal that miR-7a2 critically regulates sexual maturation and reproductive function by interconnecting miR-7 genomic circuits that regulate FSH and LH synthesis and secretion through their effects on pituitary prostaglandin and BMP4 signaling. PMID:28218624

Hormone Replacement Therapy and Opioid Tapering for Opioid-Induced Hypogonadism Among Patients with Chronic Noncancer Pain: A Systematic Review.

PubMed

AminiLari, Mahmood; Manjoo, Priya; Craigie, Samantha; Couban, Rachel; Wang, Li; Busse, Jason W

2018-05-02

To systematically review evidence addressing the efficacy of testosterone replacement therapy (TRT) and opioid tapering for opioid-induced hypogonadism among patients with chronic noncancer pain. Systematic review of randomized controlled trials (RCTs) and observational studies. We searched MEDLINE, CINAHL, AMED, CENTRAL, CINAHL, DARE, EMBASE, and PsycINFO through August 2017. Eligible studies enrolled ≥10 patients with chronic noncancer pain and opioid-induced hypogonadism and reported the effect of TRT or opioid tapering on a patient-important outcome collected ≥14 days after treatment. Pairs of reviewers independently screened for eligible studies, assessed risk of bias, and extracted data. We used the GRADE approach to rate quality of evidence. Of 666 abstracts reviewed, five studies including one RCT (N = 84) and four observational studies (N = 157) were eligible. No studies explored the effect of opioid tapering for opioid-induced hypogonadism. Very low-quality evidence found that TRT was associated with improvements in pain (median reduction of 2 points on the 11-point numerical rating scale for pain; 95% confidence interval [CI] = -1.4 to -2.6; minimally important difference [MID] = 2 points), and emotional functioning (mean increase of 9 points on the 100-point SF-36 Mental Component Summary score; 95% CI = 4.40 to 13.60; MID = 5 points). Low-quality evidence suggested that TRT had no effect on sleep quality, sexual function, physical functioning, role functioning, or social functioning; very low-quality evidence suggested no association with depressive symptoms. Low-quality to very low-quality evidence suggests that TRT may improve pain and emotional functioning, but not other outcomes, in chronic noncancer pain patients with opioid-induced hypogonadism.

Testosterone treatment is not associated with increased risk of adverse cardiovascular events: results from the Registry of Hypogonadism in Men (RHYME).

PubMed

Maggi, Mario; Wu, Frederick C W; Jones, Thomas H; Jackson, Graham; Behre, Hermann M; Hackett, Geoffrey; Martin-Morales, Antonio; Balercia, Giancarlo; Dobs, Adrian S; Arver, Stefan T E; Maggio, Marcello; Cunningham, Glenn R; Isidori, Andrea M; Quinton, Richard; Wheaton, Olivia A; Siami, Flora S; Rosen, Raymond C

2016-10-01

The aim of this study was to assess cardiovascular (CV) safety of testosterone replacement therapy (TRT) in a large, diverse cohort of European men with hypogonadism (HG). The Registry of Hypogonadism in Men (RHYME) was designed as a multi-national, longitudinal disease registry of men diagnosed with hypogonadism (HG) at 25 clinical sites in six European countries. Data collection included a complete medical history, physical examination, blood sampling and patient questionnaires at multiple study visits over 2-3 years. Independent adjudication was performed on all mortalities and CV outcomes. Of 999 patients enrolled with clinically diagnosed HG, 750 (75%) initiated some form of TRT. Registry participants, including both treated and untreated patients, contributed 23 900 person-months (99.6% of the targeted) follow-up time. A total of 55 reported CV events occurred in 41 patients. Overall, five patients died of CV-related causes (3 on TRT, 2 untreated) and none of the deaths were adjudicated as treatment-related. The overall CV incidence rate was 1522 per 100 000 person-years. CV event rates for men receiving TRT were not statistically different from untreated men (P=.70). Regardless of treatment assignment, CV event rates were higher in older men and in those with increased CV risk factors or a prior history of CV events. Age and prior CV history, not TRT use, were predictors of new-onset CV events in this multi-national, prospective hypogonadism registry. © 2016 John Wiley & Sons Ltd.

The Natural History of Idiopathic Scoliosis During Growth: A Meta-Analysis.

PubMed

Di Felice, Francesca; Zaina, Fabio; Donzelli, Sabrina; Negrini, Stefano

2018-05-01

The aim of the study was to provide a meta-analysis of current literature concerning the natural history of idiopathic scoliosis during growth. A comprehensive search of Medline, Embase, And Scopus databases was conducted up to November 2016. Eligible works were prospective or retrospective studies that enrolled patients with infantile idiopathic scoliosis, juvenile idiopathic scoliosis, or adolescent idiopathic scoliosis, followed up without any treatment from the time of detection. A meta-analysis for proportion was performed. The following studies were grouped per diagnosis: infantile idiopathic scoliosis, juvenile idiopathic scoliosis, and adolescent idiopathic scoliosis. Of the 1797 citations screened, we assessed 61 full-text articles and included 13 of these (2301 participants). Three studies included infantile idiopathic scoliosis patients (347 participants), five studies included a mixed population of juvenile idiopathic scoliosis and adolescent idiopathic scoliosis (1330 participants), and five studies included adolescent idiopathic scoliosis patients only (624 participants). The random pooled estimated progression rate was 49% (95% confidence interval = 1%-97%) for infantile idiopathic scoliosis, 49% in a mixed group of patients affected by juvenile idiopathic scoliosis or adolescent idiopathic scoliosis (95% confidence interval = 19%-79%), and 42% in adolescent idiopathic scoliosis (95% confidence interval = 11%-73%). During growth, idiopathic scoliosis tends to progress in a high percentage of cases. The progression rate varies according to the age at diagnosis, with infantile scoliosis being the most unpredictable. There are many confounders, such as age, Risser sign and baseline Cobb angles that were not consistent among studies, making the data very heterogeneous.

Diagnosing hypogonadism and treating decisions in different parts of the world: shifts in patterns between 2006 and 2015.

PubMed

Gooren, Louis

2016-01-01

Variations in diagnosing and treating testosterone (T) deficiency between different regions of the world were analyzed in 2006, and repeated in 2010. At present, the changes since 2006 were analyzed. About 731 physicians were interviewed in Europe, South Africa, Central and South America regarding factors determining: (1) prescription of T or withholding T, (2) factors in the long-term use of T and the role of T formulations therein, (3) awareness of the wider spectrum of action of T (cardiometabolic disease) (4) reimbursement of T and its impact on (continued) use and (5) best strategies for information on T for physicians. Total T was a key factor in identifying hypogonadism, but for >80% of physicians, clinical symptoms were weighed during diagnosis. Once diagnosed, >85% received T treatment, but the treatment compliance was problematic. Of these patients, 36% decided not to start or continue the treatment. More hypogonadal men are treated than before, but ∼20% goes unidentified. Physicians have a greater awareness that T deficiency can be an element in cardiovascular and metabolic disease, but more education of physicians on diagnosis and treatment of hypogonadism are needed. Problems with reimbursement of T are barriers in the prescription of T and its use by patients.

The low density lipoprotein receptor modulates the effects of hypogonadism on diet-induced obesity and related metabolic perturbations

PubMed Central

Constantinou, Caterina; Mpatsoulis, Diogenis; Natsos, Anastasios; Petropoulou, Peristera-Ioanna; Zvintzou, Evangelia; Traish, Abdulmaged M.; Voshol, Peter J.; Karagiannides, Iordanes; Kypreos, Kyriakos E.

2014-01-01

Here, we investigated how LDL receptor deficiency (Ldlr−/−) modulates the effects of testosterone on obesity and related metabolic dysfunctions. Though sham-operated Ldlr−/− mice fed Western-type diet for 12 weeks became obese and showed disturbed plasma glucose metabolism and plasma cholesterol and TG profiles, castrated mice were resistant to diet-induced obesity and had improved glucose metabolism and reduced plasma TG levels, despite a further deterioration in their plasma cholesterol profile. The effect of hypogonadism on diet-induced weight gain of Ldlr−/− mice was independent of ApoE and Lrp1. Indirect calorimetry analysis indicated that hypogonadism in Ldlr−/− mice was associated with increased metabolic rate. Indeed, mitochondrial cytochrome c and uncoupling protein 1 expression were elevated, primarily in white adipose tissue, confirming increased mitochondrial metabolic activity due to thermogenesis. Testosterone replacement in castrated Ldlr−/− mice for a period of 8 weeks promoted diet-induced obesity, indicating a direct role of testosterone in the observed phenotype. Treatment of sham-operated Ldlr−/− mice with the aromatase inhibitor exemestane for 8 weeks showed that the obesity of castrated Ldlr−/− mice is independent of estrogens. Overall, our data reveal a novel role of Ldlr as functional modulator of metabolic alterations associated with hypogonadism. PMID:24837748

Idiopathic Hypersomnia: A Study of 77 Cases

PubMed Central

Anderson, Kirstie N.; Pilsworth, Samantha; Sharples, Linda D.; Smith, Ian E.; Shneerson, John M.

2007-01-01

Study Objectives: To review the clinical and polysomnographic characteristics of idiopathic hypersomnia as well as the long-term response to treatment. Setting: The Respiratory Support and Sleep Centre at Papworth Hospital, Cambridge, UK. Patients and Design: A large database of more than 6000 patients with sleep disorders was reviewed. A retrospective study of the clinical and polysomnographic characteristics of 77 patients with idiopathic hypersomnia was performed. Comparison with a similar group of patients with narcolepsy was performed. The response to drug treatment was assessed in 61 patients over a mean follow-up of 3.8 years. Measurements and Results: Idiopathic hypersomnia was 60% as prevalent as narcolepsy. Comparison with a similar group of patients with narcolepsy showed that those with idiopathic hypersomnia were more likely to have prolonged unrefreshing daytime naps, a positive family history, increased slow-wave sleep, and a longer sleep latency on the Multiple Sleep Latency Test. The results of the Multiple Sleep Latency Test were not helpful in predicting disease severity or treatment response. The clinical features were heterogeneous and of variable severity. The majority of patients with idiopathic hypersomnia had symptoms that remained stable over many years, but 11% had spontaneous remission, which was never seen in narcolepsy. Two thirds of patients with idiopathic hypersomnolence had a sustained improvement in daytime somnolence with medication, although a third needed high doses or combinations of drugs. Conclusions: Idiopathic hypersomnolence has characteristic clinical and polysomnographic features but the prolonged latency on the Multiple Sleep Latency Test raises doubt about the validity of this test within the current diagnostic criteria. The disease often responds well to treatment and a substantial minority of patients appear to spontaneously improve. Citation: Anderson KN; Pilsworth S; Sharples LD; Smith IE; Shneerson JM. Idiopathic

Aetiology of idiopathic granulomatous mastitis.

PubMed

Altintoprak, Fatih; Kivilcim, Taner; Ozkan, Orhan Veli

2014-12-16

Idiopathic granulomatous mastitis is a rare chronic inflammatory lesion of the breast that can clinically and radiographically mimic breast carcinoma. The most common clinical presentation is an unilateral, discrete breast mass, nipple retraction and even a sinus formation often associated with an inflammation of the overlying skin. The etiology of idiopathic granulomatous mastitis is still obscure. Its treatment remains controversial. The cause may be the autoimmune process, infection, a chemical reaction associated with oral contraceptive pills, or even lactation. Various factors, including hormonal imbalance, autoimmunity, unknown microbiological agents, smoking and α 1-antitrypsin deficiency have been suggested to play a role in disease aetiology. In this review, causing factors in the aetiology of idiopathic granulomatous mastitis are reviewed in detail.

Aetiology of idiopathic granulomatous mastitis

PubMed Central

Altintoprak, Fatih; Kivilcim, Taner; Ozkan, Orhan Veli

2014-01-01

Idiopathic granulomatous mastitis is a rare chronic inflammatory lesion of the breast that can clinically and radiographically mimic breast carcinoma. The most common clinical presentation is an unilateral, discrete breast mass, nipple retraction and even a sinus formation often associated with an inflammation of the overlying skin. The etiology of idiopathic granulomatous mastitis is still obscure. Its treatment remains controversial. The cause may be the autoimmune process, infection, a chemical reaction associated with oral contraceptive pills, or even lactation. Various factors, including hormonal imbalance, autoimmunity, unknown microbiological agents, smoking and α 1-antitrypsin deficiency have been suggested to play a role in disease aetiology. In this review, causing factors in the aetiology of idiopathic granulomatous mastitis are reviewed in detail. PMID:25516860

Potential role of gender specific effect of leptin receptor deficiency in an extended consanguineous family with severe early-onset obesity.

PubMed

Dehghani, Mohammad Reza; Mehrjardi, Mohammad Yahya Vahidi; Dilaver, Nafi; Tajamolian, Masoud; Enayati, Samaneh; Ebrahimi, Pirooz; Amoli, Mahsa M; Farooqi, Sadaf; Maroofian, Reza

2018-03-12

Congenital Leptin receptor (LEPR) deficiency is a rare genetic cause of early-onset morbid obesity characterised by severe early onset obesity, major hyperphagia, hypogonadotropic hypogonadism and immune and neuroendocrine/metabolic dysfunction. We identified a homozygous loss-of-function mutation, NM_002303.5:c.464 T > G; p.(Tyr155*), in the LEPR in an extended consanguineous family with multiple individuals affected by early-onset severe obesity and hyperphagia. Interestingly, the LEPR-deficient adult females have extremely high body mass index (BMI) with hypogonadal infertility, the BMI of the affected males began to decline around the onset of puberty (13-15 years) with fertility being preserved. These findings lead to the speculation that LEPR deficiency may have a gender-specific effect on the regulation of body weight. In order to elucidate gender-specific effects of LEPR deficiency on reproduction further investigations are needed. The limitations of this study are that our conclusion is based on observations of two males and two females. Further LEPR deficient males and females are required for comparison in order to support this finding more confidently. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Responses to constant infusion of LH-RH in girls with primary hypogonadism.

PubMed

Reiter, E O; Duckett, G E; Root, A W

1980-09-01

To further assess quantitative pituitary gonadotropin release in patients with primary hypogonadism, a 3-hour constant infusion of the synthetic gonadotropin-releasing hormone, LH-RH, was administered to 12 functionally agonadal girls (11 with Turner syndrome and 1 who had been overiectomized), aged 9.5 to 19.42 years. Gonadotropin and sex steroid responses were determined before and during the infusion and contrasted to those in normal pubertal females. in girls with skeletal age under 11 years, mean control LH increased (P < .001) from 2.2 +/- 0.3 (mean +/- SEM) mIU/ml to 21.3 +/- 7.3 during LH-RH infusion, while luteinizing hormone (LH) rose (P < .001) from 89.2 +/- 24.6 to 276.5 +/- 42.6 girls with skeletal age over 11 years. This age-related augmentation is an exaggeration of data in normal girls and occcurs despite minimal gonadal secretion of sex steroids. A similar age-related discrepancy was not seen in follicle-stimulating hormone (FSH) secretion evoked by LH-RH; all girls had FSH increments into the castrate range with a rise from mean control levels of 78.6 +/- 6.7 to 133.9 +/- 8.3. These data demonstrate an age-related increase in LH-RH-evoked LH secretion, but not of FSH, in children and adolescents with primary hypogonadism.

Vanishing testes syndrome-related osteoporosis and high cardio-metabolic risk in an adult male with long term untreated hypergonadotropic hypogonadism.

PubMed

Carsote, Mara; Capatina, Cristina; Valea, Ana; Dumitrascu, Anda

2016-02-01

The male hypogonadism-related bone mass loss is often under diagnosed. Peak bone mass is severely affected if the hypogonadism occurs during puberty and is left untreated. We present an interesting; almost bizarre case of a male with non-functional testes early during childhood and undiagnosed and untreated hypogonadism until his fifth decade of life. Forty six year male is referred for goitre, complaining of back pain. Phenotype suggested intersexuality: gynoid proportions, micropenis, no palpable testes into the scrotum, no facial or truncal hair. His medical history had been unremarkable until the previous year when primary hypothyroidism was diagnosed and levothyroxine replacement was initiated. Later, he was diagnosed with ischemic heart disease, with inaugural unstable angina. On admission, the testosterone was 0.2 ng/mL (normal: 1.7-7.8 ng/mL), FSH markedly increased (56 mUI/mL), with normal adrenal axis, and TSH (under thyroxine replacement). High bone turnover markers, and blood cholesterol, and impaired glucose tolerance were diagnosed. The testes were not present in the scrotum. Abdominal computed tomography suggested bilateral masses of 1.6 cm diameter within the abdominal fat that were removed but no gonadal tissue was confirmed histopathologically. Vanishing testes syndrome was confirmed. The central DXA showed lumbar bone mineral density of 0.905 g/cm2, Z-score of -2.9SD. The spine profile X-Ray revealed multiple thoracic vertebral fractures. Alendronate therapy together with vitamin D and calcium supplements and trans-dermal testosterone were started. Four decades of hypogonadism associate increased cardiac risk, as well as decreased bone mass and high fracture risk.

The effect of physiotherapy in addition to testosterone replacement therapy on the efficiency of the motor system in men with hypogonadism.

PubMed

Bacevičienė, Rasa; Valonytė, Laura; Ceponis, Jonas

2013-01-01

The aim of this study was to analyze whether the addition of physiotherapy to testosterone replacement therapy provides added benefit in improving functional capacity of the motor system in men with hypogonadism. The study involved 3 groups of subjects: group 1, healthy men (n=20); group 2, men with hypogonadism who underwent testosterone replacement therapy with physiotherapy (TRT+PT) (n=8); and group 3, men with hypogonadism who underwent testosterone replacement therapy alone (TRT) (n=10). Physical activity (International Physical Activity Questionnaire [IPAQ]) and body composition (X-SCAN analysis) were analyzed; the vertical jump test (Leonardo Mechanography®) was applied. The application of testosterone replacement therapy together with physiotherapy for 6 months significantly increased the maximum and relative power of jump in the subjects in the TRT+PT group; however, in the TRT group, no statistically significant difference was observed. The maximum jump height for the subjects in the TRT+PT group significantly increased 6 months after the intervention; however, in the TRT group, this index remained unaltered. The lean body mass of the subjects in the TRT+PT group increased (P<0.05); however, in the TRT group, it did not change. The relative fat body mass in the TRT+PT group decreased significantly (P<0.05), but, in the TRT group, it had a tendency to increase, though insignificantly. Our results suggest that the application of testosterone replacement therapy together with physiotherapy (1 hour twice weekly) in men with hypogonadism may lead to earlier and better results in comparison with testosterone replacement therapy applied alone.

Diagnosis of hypogonadism: clinical assessments and laboratory tests.

PubMed

Carnegie, Christina

2004-01-01

Hypogonadism can be of hypothalamic-pituitary origin or of testicular origin, or a combination of both, which is increasingly common in the aging male population. In the postpubertal male, testosterone replacement therapy can be used to treat the signs and symptoms of low testosterone, which include loss of libido, erectile dysfunction, diminished intellectual capacity, depression, lethargy, osteoporosis, loss of muscle mass and strength, and some regression of secondary sexual characteristics. Before initiation of testosterone replacement therapy, an examination of the prostate and assessment of prostate symptoms should be performed, and both the hematocrit and lipid profile should be measured. Absolute contraindications to testosterone replacement therapy are prostate or breast cancer, a hematocrit of 55% or greater, or sensitivity to the testosterone formulation.

Acute Idiopathic Scrotal Edema: Systematic Literature Review.

PubMed

Santi, Maristella; Lava, Sebastiano A G; Simonetti, Giacomo D; Bianchetti, Mario G; Milani, Gregorio P

2018-06-01

 Existing information on acute idiopathic scrotal edema relies on small case series and textbooks.  We searched reports with no date limits on acute idiopathic scrotal edema.  Thirty-seven studies were included. Sixteen case series addressed the prevalence of acute idiopathic scrotal edema among males with acute scrotum: among 3,403 cases, the diagnosis of acute idiopathic scrotal edema was made in 413 cases (12%). Twenty-four reports addressed history, findings, management, and course of acute idiopathic scrotal edema in 311 patients. The patients mostly ranged in age from 5 to 8 years, presented with acute scrotal redness and swelling, associated or not with mild pain. Ninety percent or more of the cases developed in patients without atopic diathesis and were not preceded by inguinoscrotal surgery, acute febrile illnesses, or trauma. They were afebrile; in good general condition; and presented without pruritus, nausea or vomiting, or abdominal pain. The lesions were bilateral in two-thirds and unilateral in one-third of the cases. The condition resolved spontaneously within 2 to 3 days without sequelae. Approximately 10% of the cases experienced a recurrence.  Acute idiopathic scrotal edema is a self-limiting condition that accounts for ≥ 10% of cases of acute scrotum in children and adolescents. Georg Thieme Verlag KG Stuttgart · New York.

Supernumerary impacted teeth in a patient with SOX2 anophthalmia syndrome.

PubMed

Numakura, Chikahiko; Kitanaka, Sachiko; Kato, Mitsuhiro; Ishikawa, Shigeo; Hamamoto, Yoshioki; Katsushima, Yuriko; Kimura, Toshiyuki; Hayasaka, Kiyoshi

2010-09-01

SOX2 anophthalmia syndrome characteristically presents as anophthalmia or microphthalmia, with various extraocular symptoms, such as hypogonadotropic hypogonadism, brain anomaly, and esophageal abnormalities. In this report, we describe a patient with SOX2 anophthalmia syndrome complicated with a dental anomaly, multiple supernumerary impacted teeth, and persistence of deciduous teeth. Multiple supernumerary teeth are usually not solitary symptoms, but indicate systemic syndrome such as cleidocranial dysplasia. In odontogenesis, many transcriptional factors, such as BMPs, FGFs, and Wnts, play significant roles and SOX2 is known to interact with some of them. The role of SOX2 in dental development remains unknown, however, multiple supernumerary teeth can be considered as extraocular symptoms of SOX2 anophthalmia syndrome, rather than the coincidence of two rare diseases.

Homozygous G320V mutation in the HJV gene causing juvenile hereditary haemochromatosis type A. A case report.

PubMed

Militaru, Mariela S; Popp, Radu A; Trifa, Adrian P

2010-06-01

While classical hereditary haemochromatosis, usually associated with mutations in the HFE gene, has an adult age onset and a long, progressive evolution, juvenile haemochromatosis, most often associated with mutations in the HJV gene, is a more severe, rapidly progressive condition and has an onset before the age of 30. We report a 26-year old woman with a severe iron overload, affected by hypogonadotropic hypogonadism and moderate dilative cardiomyopathy, in whom the molecular analysis revealed a homozygous genotype for G320V mutation in the HJV gene. As juvenile haemochromatosis is a severe disease, death usually occurring from cardiac involvement, an efficient iron removal from the body strategy should be started as soon as possible, in order to prevent irreversible damage.

Idiopathic hypersomnia: a study of 77 cases.

PubMed

Anderson, Kirstie N; Pilsworth, Samantha; Sharples, Linda D; Smith, Ian E; Shneerson, John M

2007-10-01

To review the clinical and polysomnographic characteristics of idiopathic hypersomnia as well as the long-term response to treatment. The Respiratory Support and Sleep Centre at Papworth Hospital, Cambridge, UK. A large database of more than 6000 patients with sleep disorders was reviewed. A retrospective study of the clinical and polysomnographic characteristics of 77 patients with idiopathic hypersomnia was performed. Comparison with a similar group of patients with narcolepsy was performed. The response to drug treatment was assessed in 61 patients over a mean follow-up of 3.8 years. Idiopathic hypersomnia was 60% as prevalent as narcolepsy. Comparison with a similar group of patients with narcolepsy showed that those with idiopathic hypersomnia were more likely to have prolonged unrefreshing daytime naps, a positive family history, increased slow-wave sleep, and a longer sleep latency on the Multiple Sleep Latency Test. The results of the Multiple Sleep Latency Test were not helpful in predicting disease severity or treatment response. The clinical features were heterogeneous and of variable severity. The majority of patients with idiopathic hypersomnia had symptoms that remained stable over many years, but 11% had spontaneous remission, which was never seen in narcolepsy. Two thirds of patients with idiopathic hypersomnolence had a sustained improvement in daytime somnolence with medication, although a third needed high doses or combinations of drugs. Idiopathic hypersomnolence has characteristic clinical and polysomnographic features but the prolonged latency on the Multiple Sleep Latency Test raises doubt about the validity of this test within the current diagnostic criteria. The disease often responds well to treatment and a substantial minority of patients appear to spontaneously improve.

Retro- and orthonasal olfactory function in relation to olfactory bulb volume in patients with hypogonadotrophic hypogonadism.

PubMed

Salihoglu, Murat; Kurt, Onuralp; Ay, Seyid Ahmet; Baskoy, Kamil; Altundag, Aytug; Saglam, Muzaffer; Deniz, Ferhat; Tekeli, Hakan; Yonem, Arif; Hummel, Thomas

2017-08-24

Idiopathic hypogonadotrophic hypogonadism (IHH) with an olfactory deficit is defined as Kallmann syndrome (KS) and is distinct from normosmic IHH. Because olfactory perception not only consists of orthonasally gained impressions but also involves retronasal olfactory function, in this study we decided to comprehensively evaluate both retronasal and orthonasal olfaction in patients with IHH. This case-control study included 31 controls and 45 IHH patients. All participants whose olfactory and taste functions were evaluated with orthonasal olfaction (discrimination, identification and threshold), retronasal olfaction, taste function and olfactory bulb volume (OBV) measurement. The patients were separated into three groups according to orthonasal olfaction: anosmic IHH (aIHH), hyposmic IHH (hIHH) and normosmic IHH (nIHH). Discrimination, identification and threshold scores of patients with KS were significantly lower than controls. Threshold scores of patients with nIHH were significantly lower than those of controls, but discrimination and identification scores were not significantly different. Retronasal olfaction was reduced only in the aIHH group compared to controls. Identification of bitter, sweet, sour, and salty tastes was not significantly different when compared between the anosmic, hyposmic, and normosmic IHH groups and controls. OBV was lower bilaterally in all patient groups when compared with controls. The OBV of both sides was found to be significantly correlated with TDI scores in IHH patients. 1) There were no significant differences in gustatory function between controls and IHH patients; 2) retronasal olfaction was reduced only in anosmic patients but not in orthonasally hyposmic participants, possibly indicating presence of effective compensatory mechanisms; 3) olfactory bulb volumes were highly correlated with olfaction scores in the HH group. The current results indicate a continuum from anosmia to normosmia in IHH patients. Copyright © 2017

[Idiopathic facial paralysis in children].

PubMed

Achour, I; Chakroun, A; Ayedi, S; Ben Rhaiem, Z; Mnejja, M; Charfeddine, I; Hammami, B; Ghorbel, A

2015-05-01

Idiopathic facial palsy is the most common cause of facial nerve palsy in children. Controversy exists regarding treatment options. The objectives of this study were to review the epidemiological and clinical characteristics as well as the outcome of idiopathic facial palsy in children to suggest appropriate treatment. A retrospective study was conducted on children with a diagnosis of idiopathic facial palsy from 2007 to 2012. A total of 37 cases (13 males, 24 females) with a mean age of 13.9 years were included in this analysis. The mean duration between onset of Bell's palsy and consultation was 3 days. Of these patients, 78.3% had moderately severe (grade IV) or severe paralysis (grade V on the House and Brackmann grading). Twenty-seven patients were treated in an outpatient context, three patients were hospitalized, and seven patients were treated as outpatients and subsequently hospitalized. All patients received corticosteroids. Eight of them also received antiviral treatment. The complete recovery rate was 94.6% (35/37). The duration of complete recovery was 7.4 weeks. Children with idiopathic facial palsy have a very good prognosis. The complete recovery rate exceeds 90%. However, controversy exists regarding treatment options. High-quality studies have been conducted on adult populations. Medical treatment based on corticosteroids alone or combined with antiviral treatment is certainly effective in improving facial function outcomes in adults. In children, the recommendation for prescription of steroids and antiviral drugs based on adult treatment appears to be justified. Randomized controlled trials in the pediatric population are recommended to define a strategy for management of idiopathic facial paralysis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Early weight loss predicts the reduction of obesity in men with erectile dysfunction and hypogonadism undergoing long-term testosterone replacement therapy.

PubMed

Salman, Mahmoud; Yassin, Dany-Jan; Shoukfeh, Huda; Nettleship, Joanne Elisabeth; Yassin, Aksam

2017-03-01

We and others have previously shown that testosterone replacement therapy (TRT) results in sustained weight loss in the majority of middle-aged hypogonadal men. Previously, however, a small proportion failed to lose at least 5% of their baseline weight. The reason for this is not yet understood. In the present study, we sought to identify early indicators that may predict successful long-term weight loss, defined as a reduction of at least 5% of total body weight relative to baseline weight (T0), in men with hypogonadism undergoing TRT. Eight parameters measured were assessed as potential predictors of sustained weight loss: loss of 3% or more of baseline weight after 1 year of TU treatment, severe hypogonadism, BMI, waist circumference, International Prostate Symptom Score (IPSS), glycated hemoglobin (HbA 1C ), age and use of vardenafil. Among the eight measured parameters, three factors were significantly associated with sustained weight loss over the entire period of TU treatment: (1) a loss of 3% of the baseline body weight after 1 year of TRT; (2) baseline BMI over 30; and (3) a waist circumference >102 cm. Age was not a predictor of weight loss.

[Hypogonadism caused by Gorlin-Goltz syndrome].

PubMed

Marín Romero, Olivia; Hernández Marín, Imelda; Ayala Ruiz, Aquiles R

2006-09-01

The Gorlin-Goltz syndrome is a dominant autosomic disorder characterized by cancerigenic predisposition and multiple development defects, apparently without reproductive compromise. The complex is characterized by four primary symptoms, which include nevoid basal cell epitheliomas malignantly prone, keratocystic jaw, skeletal abnormalities and intracranial calcifications. Apparently, reproductive problems reported had been rarely associated with this syndrome. We present the case of a patient with clinic stigmatae of Gorlin-Goltz syndrome, who had a characteristic progress as seen in the literature; he was the fifth product of a 43 year-old female (father was 48 years old); who at birth disclosed right eye microftalmy, bilateral cryptorchidism surgically treated at age of six. At puberty, an odontogenic cyst of the jaw was noted and enucleated. He also showed facial nevi in neck, thorax and abdomen. When he was admitted being 14 years old in our clinic, he had recurrent bilateral cryptorchidism, sexual immatturity and infertility. It is important to take into consideration Gorlin-Goltz stigmatae in cases of hypogonadism in order to recognize a further genetic influence.

Pharmacokinetics of Modified Slow-Release Oral Testosterone Over 9 Days in Normal Men With Experimental Hypogonadism

PubMed Central

Lee, Ada; Rubinow, Katya; Clark, Richard V.; Caricofe, Ralph B.; Bush, Mark A.; Zhi, Hui; Roth, Mara Y; Page, Stephanie T.; Bremner, William J.; Amory, John K.

2014-01-01

Oral administration of testosterone has potential use for the treatment of hypogonadism. We have recently demonstrated that a novel formulation of oral testosterone transiently normalized serum testosterone in a single-dose pharmacokinetic study. In this report, we present the steady-state pharmacokinetics of this formulation. Twelve healthy young men were rendered hypogonadal with the gonadotropin-releasing hormone antagonist acyline (300 µg/kg subcutaneously) and administered 300 mg of oral testosterone 3 times daily for 9 days. Serum testosterone, dihydrotestosterone (DHT), estradiol, and sex hormone–binding globulin (SHBG) were measured before and 1, 2, 4, 5, 6, 8, 10, 11, 12, 14, 16, and 24 hours on the first and ninth day of dosing. Before testosterone administration, all men had serum testosterone under 75 ng/dL. Over day 1, the 24-hour average (geometric mean [%CV]) serum total testosterone was 378 (45) ng/dL. This decreased to 315 (41) ng/dL after 9 days of continuous treatment (P = .1 compared with day 1). The 24-hour average serum SHBG was 27 (46) nmol/L on day 1 and was significantly reduced to 19 (47) nmol/L by day 9 (P > .01). As a result, the calculated free testosterone values were similar between day 1 and day 9: 8.7 (43) and 8.3 (37) ng/dL, respectively. DHT was in the reference range and estradiol was slightly below on day 9. Oral testosterone (300 mg) dosed 3 times daily normalized serum testosterone in men with experimentally induced hypogonadism after 9 days of dosing and significantly suppressed SHBG. This formulation of oral testosterone may have efficacy for the treatment of testosterone deficiency. PMID:21868746

Ataxia and hypogonadism caused by the loss of ubiquitin ligase activity of the U box protein CHIP.

PubMed

Shi, Chang-He; Schisler, Jonathan C; Rubel, Carrie E; Tan, Song; Song, Bo; McDonough, Holly; Xu, Lei; Portbury, Andrea L; Mao, Cheng-Yuan; True, Cadence; Wang, Rui-Hao; Wang, Qing-Zhi; Sun, Shi-Lei; Seminara, Stephanie B; Patterson, Cam; Xu, Yu-Ming

2014-02-15

Gordon Holmes syndrome (GHS) is a rare Mendelian neurodegenerative disorder characterized by ataxia and hypogonadism. Recently, it was suggested that disordered ubiquitination underlies GHS though the discovery of exome mutations in the E3 ligase RNF216 and deubiquitinase OTUD4. We performed exome sequencing in a family with two of three siblings afflicted with ataxia and hypogonadism and identified a homozygous mutation in STUB1 (NM_005861) c.737C→T, p.Thr246Met, a gene that encodes the protein CHIP (C-terminus of HSC70-interacting protein). CHIP plays a central role in regulating protein quality control, in part through its ability to function as an E3 ligase. Loss of CHIP function has long been associated with protein misfolding and aggregation in several genetic mouse models of neurodegenerative disorders; however, a role for CHIP in human neurological disease has yet to be identified. Introduction of the Thr246Met mutation into CHIP results in a loss of ubiquitin ligase activity measured directly using recombinant proteins as well as in cell culture models. Loss of CHIP function in mice resulted in behavioral and reproductive impairments that mimic human ataxia and hypogonadism. We conclude that GHS can be caused by a loss-of-function mutation in CHIP. Our findings further highlight the role of disordered ubiquitination and protein quality control in the pathogenesis of neurodegenerative disease and demonstrate the utility of combining whole-exome sequencing with molecular analyses and animal models to define causal disease polymorphisms.

Ataxia and hypogonadism caused by the loss of ubiquitin ligase activity of the U box protein CHIP

PubMed Central

Shi, Chang-He; Schisler, Jonathan C.; Rubel, Carrie E.; Tan, Song; Song, Bo; McDonough, Holly; Xu, Lei; Portbury, Andrea L.; Mao, Cheng-Yuan; True, Cadence; Wang, Rui-Hao; Wang, Qing-Zhi; Sun, Shi-Lei; Seminara, Stephanie B.; Patterson, Cam; Xu, Yu-Ming

2014-01-01

Gordon Holmes syndrome (GHS) is a rare Mendelian neurodegenerative disorder characterized by ataxia and hypogonadism. Recently, it was suggested that disordered ubiquitination underlies GHS though the discovery of exome mutations in the E3 ligase RNF216 and deubiquitinase OTUD4. We performed exome sequencing in a family with two of three siblings afflicted with ataxia and hypogonadism and identified a homozygous mutation in STUB1 (NM_005861) c.737C→T, p.Thr246Met, a gene that encodes the protein CHIP (C-terminus of HSC70-interacting protein). CHIP plays a central role in regulating protein quality control, in part through its ability to function as an E3 ligase. Loss of CHIP function has long been associated with protein misfolding and aggregation in several genetic mouse models of neurodegenerative disorders; however, a role for CHIP in human neurological disease has yet to be identified. Introduction of the Thr246Met mutation into CHIP results in a loss of ubiquitin ligase activity measured directly using recombinant proteins as well as in cell culture models. Loss of CHIP function in mice resulted in behavioral and reproductive impairments that mimic human ataxia and hypogonadism. We conclude that GHS can be caused by a loss-of-function mutation in CHIP. Our findings further highlight the role of disordered ubiquitination and protein quality control in the pathogenesis of neurodegenerative disease and demonstrate the utility of combining whole-exome sequencing with molecular analyses and animal models to define causal disease polymorphisms. PMID:24113144

Serum immunoreactive inhibin levels in polycystic ovarian disease (PCOD) and hypogonadotropic amenorrhea.

PubMed

Mizunuma, H; Andoh, K; Obara, M; Yamaguchi, M; Kamijo, T; Hasegawa, Y; Ibuki, Y

1994-08-01

To evaluate the physiological significance of inhibin in various types of amenorrhea, serum immunoreactive (IR)-inhibin levels were measured and compared with those in normal cycling women. Amenorrheic women were as follows: (1) 23 women with PCOD, 11 women with hypogonadotropic amenorrhea (HA, n = 23) and 11 women with regular menstrual cycles. Women with HA were further divided into 2 groups according to the presence or absence of withdrawal bleeding (WDB) after progesterone administration. HA with WDB was categorized as HA1, while HA without as HA 2. Serum IR-inhibin levels in women with PCOD were significantly higher than those in HA 2 and normal women at days 2 to 5 from the onset of menstruation and significantly lower than those in normal women in the mid-luteal phase. A significant positive correlation was obtained between IR-inhibin and FSH in HA 2 (r = 0.681) and HA 1 (r = 0.658), but no significant correlation between these two hormones in PCOD and normal women. These results indicated that basal IR-inhibin levels vary with types of amenorrhea. High IR-inhibin levels in PCOD patients suggest that inhibin plays a part in the discordant gonadotropin secretion in these patients.

Is testosterone replacement therapy in males with hypogonadism cost-effective? An analysis in Sweden.

PubMed

Arver, Stefan; Luong, Ba; Fraschke, Anina; Ghatnekar, Ola; Stanisic, Sanja; Gultyev, Dmitry; Müller, Elvira

2014-01-01

Testosterone replacement therapy (TRT) has been recommended for the treatment of primary and secondary hypogonadism. However, long-term implications of TRT have not been investigated extensively. The aim of this analysis was to evaluate health outcomes and costs associated with life-long TRT in patients suffering from Klinefelter syndrome and late-onset hypogonadism (LOH). A Markov model was developed to assess cost-effectiveness of testosterone undecanoate (TU) depot injection treatment compared with no treatment. Health outcomes and associated costs were modeled in monthly cycles per patient individually along a lifetime horizon. Modeled health outcomes included development of type 2 diabetes, depression, cardiovascular and cerebrovascular complications, and fractures. Analysis was performed for the Swedish health-care setting from health-care payer's and societal perspective. One-way sensitivity analyses evaluated the robustness of results. The main outcome measures were quality-adjusted life-years (QALYs) and total cost in TU depot injection treatment and no treatment cohorts. In addition, outcomes were also expressed as incremental cost per QALY gained for TU depot injection therapy compared with no treatment (incremental cost-effectiveness ratio [ICER]). TU depot injection compared to no-treatment yielded a gain of 1.67 QALYs at an incremental cost of 28,176 EUR (37,192 USD) in the Klinefelter population. The ICER was 16,884 EUR (22,287 USD) per QALY gained. Outcomes in LOH population estimated benefits of TRT at 19,719 EUR (26,029 USD) per QALY gained. Results showed to be considerably robust when tested in sensitivity analyses. Variation of relative risk to develop type 2 diabetes had the highest impact on long-term outcomes in both patient groups. This analysis suggests that lifelong TU depot injection therapy of patients with hypogonadism is a cost-effective treatment in Sweden. Hence, it can support clinicians in decision making when considering

Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: efficacy and treatment cost.

PubMed

Taylor, Frederick; Levine, Laurence

2010-01-01

The efficacy of oral clomiphene citrate (CC) in the treatment of male hypogonadism and male infertility (MI) with low serum testosterone and normal gonadotropin levels has been reported. The aim of this article is to evaluate CC and testosterone gel replacement therapy (TGRT) with regard to biochemical and clinical efficacy and cost. The main outcome measures were change in serum testosterone with CC and TGRT therapy, and change in the androgen deficiency in aging male (ADAM) questionnaire scores with CC therapy. Men receiving CC or TGRT with either Androgel 1% or Testim 1% for hypogonadism (defined as testosterone < 300 ng/mL) or MI were included. Serum values were collected 1-2 months after treatment initiation and semi-annually thereafter. Retrospective data collection was performed via chart review. Subjective follow up of patients receiving CC was performed via telephone interview using the ADAM questionnaire. A hundred and four men (65 CC and 39 TGRT) were identified who began CC (50 mg every other day) or TGRT (5 g). Average age (years) was 42(CC) vs. 57 (TGRT). Average follow up was 23 months (CC, range 8-40 months) vs. 46 months (TGRT, range 6-149 months). Average posttreatment testosterone was 573 ng/dL in the CC group and 553 ng/dL in the TGRT group (P value < 0.001). The monthly cost of Testim 1% (5 gm daily) is $270, Androgel 1% (5 gm daily) is $265, and CC (50 mg every other day) is $83. Among CC patients, the average pretreatment ADAM score was 4.9 vs. 2.1 at follow up (P < 0.05). Average pretreatment ADAM sexual function domain score was 0.76 vs. 0.23 at follow up (P < 0.05). There were no adverse events reported. CC represents a treatment option for men with hypogonadism, demonstrating biochemical and clinical efficacy with few side effects and lower cost as compared with TGRT.

Juvenile idiopathic arthritis

MedlinePlus

... www.ncbi.nlm.nih.gov/pubmed/21452260 . Long AR, Rouster-Stevens KA. The role of exercise therapy ... nlm.nih.gov/pubmed/21131338 . Wu EY, Bryan AR, Rabinovich CE. Juvenile idiopathic arthritis. In: Kliegman RM, ...

A rare challenging case of co-existent craniopharyngioma, acromegaly and squamous cell lung cancer.

PubMed

Fountas, Athanasios; Chai, Shu Teng; Ayuk, John; Gittoes, Neil; Chavda, Swarupsinh; Karavitaki, Niki

2018-01-01

Co-existence of craniopharyngioma and acromegaly has been very rarely reported. A 65-year-old man presented with visual deterioration, fatigue and frontal headaches. Magnetic resonance imaging revealed a suprasellar heterogeneous, mainly cystic, 1.9 × 2 × 1.9 cm mass compressing the optic chiasm and expanding to the third ventricle; the findings were consistent with a craniopharyngioma. Pituitary hormone profile showed hypogonadotropic hypogonadism, mildly elevated prolactin, increased insulin-like growth factor 1 (IGF-1) and normal thyroid function and cortisol reserve. The patient had transsphenoidal surgery and pathology of the specimen was diagnostic of adamantinomatous craniopharyngioma. Post-operatively, he had diabetes insipidus, hypogonadotropic hypogonadism and adrenocorticotropic hormone and thyroid-stimulating hormone deficiency. Despite the hypopituitarism, his IGF-1 levels remained elevated and subsequent oral glucose tolerance test did not show complete growth hormone (GH) suppression. Further review of the pre-operative imaging revealed a 12 × 4 mm pituitary adenoma close to the right carotid artery and no signs of pituitary hyperplasia. At that time, he was also diagnosed with squamous cell carcinoma of the left upper lung lobe finally managed with radical radiotherapy. Treatment with long-acting somatostatin analogue was initiated leading to biochemical control of the acromegaly. Latest imaging has shown no evidence of craniopharyngioma regrowth and stable adenoma. This is a unique case report of co-existence of craniopharyngioma, acromegaly and squamous lung cell carcinoma that highlights diagnostic and management challenges. Potential effects of the GH hypersecretion on the co-existent tumours of this patient are also briefly discussed. Although an extremely rare clinical scenario, craniopharyngioma and acromegaly can co-exist; aetiopathogenic link between these two conditions is unlikely.Meticulous review of unexpected

G protein-coupled receptor mutations and human genetic disease.

PubMed

Thompson, Miles D; Hendy, Geoffrey N; Percy, Maire E; Bichet, Daniel G; Cole, David E C

2014-01-01

Genetic variations in G protein-coupled receptor genes (GPCRs) disrupt GPCR function in a wide variety of human genetic diseases. In vitro strategies and animal models have been used to identify the molecular pathologies underlying naturally occurring GPCR mutations. Inactive, overactive, or constitutively active receptors have been identified that result in pathology. These receptor variants may alter ligand binding, G protein coupling, receptor desensitization and receptor recycling. Receptor systems discussed include rhodopsin, thyrotropin, parathyroid hormone, melanocortin, follicle-stimulating hormone (FSH), luteinizing hormone, gonadotropin-releasing hormone (GNRHR), adrenocorticotropic hormone, vasopressin, endothelin-β, purinergic, and the G protein associated with asthma (GPRA or neuropeptide S receptor 1 (NPSR1)). The role of activating and inactivating calcium-sensing receptor (CaSR) mutations is discussed in detail with respect to familial hypocalciuric hypercalcemia (FHH) and autosomal dominant hypocalemia (ADH). The CASR mutations have been associated with epilepsy. Diseases caused by the genetic disruption of GPCR functions are discussed in the context of their potential to be selectively targeted by drugs that rescue altered receptors. Examples of drugs developed as a result of targeting GPCRs mutated in disease include: calcimimetics and calcilytics, therapeutics targeting melanocortin receptors in obesity, interventions that alter GNRHR loss from the cell surface in idiopathic hypogonadotropic hypogonadism and novel drugs that might rescue the P2RY12 receptor congenital bleeding phenotype. De-orphanization projects have identified novel disease-associated receptors, such as NPSR1 and GPR35. The identification of variants in these receptors provides genetic reagents useful in drug screens. Discussion of the variety of GPCRs that are disrupted in monogenic Mendelian disorders provides the basis for examining the significance of common

Effect of aromatase inhibition on bone metabolism in elderly hypogonadal men.

PubMed

Leder, Benjamin Z; Finkelstein, Joel S

2005-12-01

Both estrogens and androgens play important roles in skeletal development and maintenance in men. The relative importance of estrogens and androgens in male bone metabolism, however, remains undefined. Anastrozole is an oral aromatase inhibitor that decreases estrogen production and increases androgen production in men. Currently, anastrozole is being investigated as a potential agent for the treatment of hypogonadism in aging men. Because anastrozole lowers estrogen levels and raises androgen levels, its effect on bone metabolism is difficult to predict. To assess the effects of anastrozole on bone turnover, we randomized 37 elderly (ages 62-74) mildly hypogonadal men (serum testosterone <350 ng/dl) to receive either anastrozole 1 mg daily (n=12), anastrozole 1 mg twice weekly (n=11), or daily placebo (n=14) for 12 weeks. Serum gonadal steroid levels, serum and urine biochemical markers of bone turnover, serum osteoprotegerin, and total body bone mineral density were measured at baseline and week 12. Mean serum levels of total and bioavailable testosterone increased substantially in both treated groups. Specifically, mean +/- SD bioavailable testosterone levels increased from 99+/-31 ng/dl to 207+/-65 ng/dl in the group receiving 1 mg of anastrozole daily and from 115+/-37 ng/dl to 178+/-55 ng/dl in the subjects receiving 1 mg of anastrozole twice weekly ( p <0.001 vs placebo for both groups). Serum estradiol levels decreased modestly in both treated groups (from 26+/-8 pg/ml to 17+/-6 pg/ml in the daily treatment group and from 27+/-8 pg/ml to 17+/-5 pg/ml in the twice-weekly treatment group, p <0.001 vs placebo for both groups). Despite these hormonal changes, no increases in biochemical markers of bone resorption were observed. Specifically, mean serum N-telopeptide and urinary deoxypyridinoline concentrations remained stable in both treated groups over the 12-week treatment period. Similarly, serum biochemical markers of bone formation (osteocalcin and amino

Intraspinal anomalies in early-onset idiopathic scoliosis.

PubMed

Pereira, E A C; Oxenham, M; Lam, K S

2017-06-01

In the United Kingdom, lower incidences of intraspinal abnormalities in patients with early onset idiopathic scoliosis have been observed than in studies in other countries. We aimed to determine the rates of these abnormalities in United Kingdom patients diagnosed with idiopathic scoliosis before the age of 11 years. This retrospective study of patients attending an urban scoliosis clinic identified 71 patients satisfying a criteria of: clinical diagnosis of idiopathic scoliosis; age of onset ten years and 11 months or less; MRI screening for intraspinal abnormalities. United Kingdom census data combined with patient referral data was used to calculate incidence. Mean age at diagnosis was six years with 39 right-sided and 32 left-sided curves. Four patients (5.6%) were found to have intraspinal abnormalities on MRI. These consisted of: two combined Arnold-Chiari type 1 malformations with syrinx; one syrinx with a low lying conus; and one isolated syrinx. Overall annual incidence of early onset idiopathic scoliosis was one out of 182 000 (0.0006%). This study reports the lowest rates to date of intraspinal anomalies in patients with early onset idiopathic scoliosis, adding to knowledge regarding current incidences of these abnormalities as well as any geographical variation in the nature of the disease. Cite this article: Bone Joint J 2017;99-B:829-33. ©2017 The British Editorial Society of Bone & Joint Surgery.

Effects of adolescence-onset hypogonadism on metabolism, bone mineral density and quality of life in adulthood.

PubMed

Tam, Friederike I W; Huebner, Angela; Hofbauer, Lorenz C; Rohayem, Julia

2015-09-01

In a cross-sectional study of 54 patients with adolescence-onset hypogonadism (33 females, 21 males; age range: 19-40 years), medical care, quality of life, and health status were assessed. Most patients had received adequate medical care with short cumulative periods of interruption of hormone replacement. The prevalence of the metabolic syndrome was 27% in females and 19% in males. In comparison to the general population, females had both a lower bone mineral density (dual-energy X-ray absorptiometry, Z-score=-0.8, p<0.001) and a higher prevalence of obesity (age 19-29 years: study population 35%, general population 4%). The body fat percentage (dual-energy X-ray absorptiometry) was significantly elevated (age 19-29 years: females Z-score=+1.8, p<0.001, males Z-score=+2.4, p=0.001). Quality of life (SF-36) was normal. Despite adequate treatment, patients with early-onset hypogonadism are prone to develop signs and symptoms consistent with inadequate hormone replacement. A successful transition from pediatric to adult medicine seems important to optimize treatment outcomes.

Testosterone Replacement in Hypogonadal Men With Type 2 Diabetes and/or Metabolic Syndrome (the TIMES2 Study)

PubMed Central

Jones, T. Hugh; Arver, Stefan; Behre, Hermann M.; Buvat, Jacques; Meuleman, Eric; Moncada, Ignacio; Morales, Antonio Martin; Volterrani, Maurizio; Yellowlees, Ann; Howell, Julian D.; Channer, Kevin S.

2011-01-01

OBJECTIVE This study evaluated the effects of testosterone replacement therapy (TRT) on insulin resistance, cardiovascular risk factors, and symptoms in hypogonadal men with type 2 diabetes and/or metabolic syndrome (MetS). RESEARCH DESIGN AND METHODS The efficacy, safety, and tolerability of a novel transdermal 2% testosterone gel was evaluated over 12 months in 220 hypogonadal men with type 2 diabetes and/or MetS in a multicenter, prospective, randomized, double-blind, placebo-controlled study. The primary outcome was mean change from baseline in homeostasis model assessment of insulin resistance (HOMA-IR). Secondary outcomes were measures of body composition, glycemic control, lipids, and sexual function. Efficacy results focused primarily on months 0−6 (phase 1; no changes in medication allowed). Medication changes were allowed in phase 2 (months 6−12). RESULTS TRT reduced HOMA-IR in the overall population by 15.2% at 6 months (P = 0.018) and 16.4% at 12 months (P = 0.006). In type 2 diabetic patients, glycemic control was significantly better in the TRT group than the placebo group at month 9 (HbA1c: treatment difference, −0.446%; P = 0.035). Improvements in total and LDL cholesterol, lipoprotein a (Lpa), body composition, libido, and sexual function occurred in selected patient groups. There were no significant differences between groups in the frequencies of adverse events (AEs) or serious AEs. The majority of AEs (>95%) were mild or moderate. CONCLUSIONS Over a 6-month period, transdermal TRT was associated with beneficial effects on insulin resistance, total and LDL-cholesterol, Lpa, and sexual health in hypogonadal men with type 2 diabetes and/or MetS. PMID:21386088

Angiopoietin-2 polymorphism in women with idiopathic recurrent miscarriage.

PubMed

Pietrowski, Detlef; Tempfer, Clemens; Bettendorf, Hertha; Bürkle, Bernd; Nagele, Fritz; Unfried, Gertrud; Keck, Christoph

2003-10-01

To investigate the relationship between idiopathic recurrent miscarriage and a polymorphism of the gene encoding for angiopoietin-2 (ANGPT2), an autochthonous modulator of angiogenesis during pregnancy. Prospective case control study. Academic research institution. One hundred thirty-one women with a history of three or more consecutive pregnancy losses before 20 weeks' gestation, and 125 healthy, postmenopausal controls with at least two live births and no history of pregnancy loss. Peripheral venous puncture. Polymerase chain reaction and restriction fragment length polymorphism analysis were performed to identify the different ANGPT2 alleles. No association between mutant (mt) allele and the occurrence of idiopathic recurrent miscarriage was found. Between women with primary and secondary idiopathic recurrent miscarriage, no statistically significant differences with respect to allele frequencies were observed. This is the first report on the ANGPT2 gene polymorphism in women with idiopathic recurrent miscarriage, demonstrating that the investigated polymorphism is not associated with idiopathic recurrent miscarriage in a white population.

Management of testosterone therapy in adolescents and young men with hypogonadism: are we following adult clinical practice guidelines?

PubMed

Nahata, Leena; Yu, Richard N; Bhasin, Shalender; Cohen, Laurie E

2015-05-01

Male hypogonadism is a common disorder that is associated with low bone density, poor muscle mass, anemia, and sexual dysfunction. The Endocrine Society recently published a Clinical Practice Guideline for testosterone therapy in androgen-deficient men. Because treatment is frequently initiated in adolescence, the goal of this quality improvement initiative was to assess whether pediatric endocrinologists at a large tertiary care center follow these guidelines and to identify opportunities for improvement. We performed a retrospective chart review at Boston Children's Hospital. Inclusion criteria were as follows: current age ≥16 years, diagnosis of hypogonadism, and testosterone replacement therapy. Data were collected about current age, age at treatment initiation, diagnoses, pre- and on-treatment testosterone levels, route of testosterone administration and dose, bone density, hematocrit levels, and adherence with therapy. Fifty-nine patients were included. Fourteen (24%) were prescribed lower testosterone doses than those recommended in the Clinical Practice Guideline. Seven (12%) had no pre-treatment testosterone levels, and 10 (17%) had no on-treatment levels. In 49 patients with on-treatment testosterone levels, 36 had at least one value that was lower than the adult reference range. Ten (28%) of the 36 men with low testosterone levels had no dose adjustments. Thirty-seven (63%) of the 59 patients had no dual-energy X-ray absorptiometry scans, and 18 (31%) did not have hematocrit levels. Pediatric endocrinologists in this review did not consistently follow the Clinical Practice Guideline for testosterone therapy in hypogonadal adult males. Strategies that improve adherence to guidelines could help maximize the benefits of therapy and minimize treatment-associated risks.

Validation of the German version of the 'Hypogonadism Related Symptom Scale' (HRS) in andrological patients with infertility, HIV infection and metabolic syndrome.

PubMed

Alidjanov, J; Wolf, J; Schuppe, H-C; Weidner, W; Diemer, T; Linn, T; Halefeldt, I; Wagenlehner, F; Wiltink, J; Pilatz, A

2014-12-01

As commonly used self-reported screening instruments for male hypogonadism demonstrated lack of specificity, a Hypogonadism Related Symptom Scale (HRS) was developed in 2009 as a novel self-rating screening tool. As the questionnaire has not been validated, the purpose of our study was to perform a validation in patients presenting with different disorders (e.g. infertility, HIV infection or metabolic syndrome) and disease-related risk to develop hypogonadism. Two hundred and eighteen patients aged 19-71 years (40.1 ± 9.5) who completed the HRS and other common questionnaires [International Index Of Erectile Function (IIEF), National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), Hospital Anxiety and Depression Scale (HADS), short form (SF)-12] were included. In all patients, blood levels of total testosterone, luteinizing hormone, follicle-stimulating hormone, oestradiol and sex hormone-binding globulin were determined and free testosterone was calculated. Cronbach's α for the scale was 0.896, split-half 0.871 for the 1st half and 0.807 for the 2nd half. Spearman-Brown coefficient was 0.767, and Guttman split-half coefficient was 0.759. Consistent correlations were found between HRS and IIEF5 (ρ = 0.57, P < 0.001), and HADS (ρ = -0.6, P < 0.001). In addition, HRS was significantly correlated with total testosterone (ρ = 0.135, P < 0.05), free testosterone (ρ = 0.148, P < 0.05) and oestradiol (ρ = -0.134, P < 0.05). Our validation study confirms the data from the initial development of the HRS questionnaire. Clinicians might have an additional advantage from the HRS when investigating males with suspected hypogonadism. © 2014 Blackwell Verlag GmbH.

Juvenile parkinsonism, hypogonadism and Leigh-like MRI changes in a patient with m.4296G>A mutation in mitochondrial DNA.

PubMed

Martikainen, Mika H; Kytövuori, Laura; Majamaa, Kari

2013-03-01

Leigh syndrome is a mitochondrial disease with considerable clinical and genetic variation. We present a 16-year-old boy with Leigh-like syndrome and broad developmental retardation, parkinsonism and hypogonadism. Sequencing of the entire mitochondrial DNA from blood revealed the m.4296G>A mutation in the MT-TI gene. The mutation was heteroplasmic with a 95% proportion of the mutant genome, while the proportion was 58% in the blood of the patient's clinically healthy mother. Our results suggest that m.4296G>A is pathogenic in humans, and that the phenotype related to this change includes Leigh-like syndrome in adolescence with parkinsonism and hypogonadism, in addition to the previously reported early infantile Leigh syndrome. Copyright © 2013 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Comparison of CSF Distribution between Idiopathic Normal Pressure Hydrocephalus and Alzheimer Disease.

PubMed

Yamada, S; Ishikawa, M; Yamamoto, K

2016-07-01

CSF volumes in the basal cistern and Sylvian fissure are increased in both idiopathic normal pressure hydrocephalus and Alzheimer disease, though the differences in these volumes in idiopathic normal pressure hydrocephalus and Alzheimer disease have not been well-described. Using CSF segmentation and volume quantification, we compared the distribution of CSF in idiopathic normal pressure hydrocephalus and Alzheimer disease. CSF volumes were extracted from T2-weighted 3D spin-echo sequences on 3T MR imaging and quantified semi-automatically. We compared the volumes and ratios of the ventricles and subarachnoid spaces after classification in 30 patients diagnosed with idiopathic normal pressure hydrocephalus, 10 with concurrent idiopathic normal pressure hydrocephalus and Alzheimer disease, 18 with Alzheimer disease, and 26 control subjects 60 years of age or older. Brain to ventricle ratios at the anterior and posterior commissure levels and 3D volumetric convexity cistern to ventricle ratios were useful indices for the differential diagnosis of idiopathic normal pressure hydrocephalus or idiopathic normal pressure hydrocephalus with Alzheimer disease from Alzheimer disease, similar to the z-Evans index and callosal angle. The most distinctive characteristics of the CSF distribution in idiopathic normal pressure hydrocephalus were small convexity subarachnoid spaces and the large volume of the basal cistern and Sylvian fissure. The distribution of the subarachnoid spaces in the idiopathic normal pressure hydrocephalus with Alzheimer disease group was the most deformed among these 3 groups, though the mean ventricular volume of the idiopathic normal pressure hydrocephalus with Alzheimer disease group was intermediate between that of the idiopathic normal pressure hydrocephalus and Alzheimer disease groups. The z-axial expansion of the lateral ventricle and compression of the brain just above the ventricle were the common findings in the parameters for differentiating

Compound heterozygous PNPLA6 mutations cause Boucher-Neuhäuser syndrome with late-onset ataxia.

PubMed

Deik, A; Johannes, B; Rucker, J C; Sánchez, E; Brodie, S E; Deegan, E; Landy, K; Kajiwara, Y; Scelsa, S; Saunders-Pullman, R; Paisán-Ruiz, C

2014-12-01

PNPLA6 mutations, known to be associated with the development of motor neuron phenotypes, have recently been identified in families with Boucher-Neuhäuser syndrome. Boucher-Neuhäuser is a rare autosomal recessive syndrome characterized by the co-occurrence of cerebellar ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy. Gait ataxia in Boucher-Neuhäuser usually manifests before early adulthood, although onset in the third or fourth decade has also been reported. However, given the recent identification of PNPLA6 mutations as the cause of this condition, the determining factors of age of symptom onset still need to be established. Here, we have identified a sporadic Boucher-Neuhäuser case with late-onset gait ataxia and relatively milder retinal changes due to compound heterozygous PNPLA6 mutations. Compound heterozygosity was confirmed by cloning and sequencing the patient's genomic DNA from coding exons 26-29. Furthermore, both mutations (one novel and one known) fell in the phospholipase esterase domain, where most pathogenic mutations seem to cluster. Taken together, we herein confirm PNPLA6 mutations as the leading cause of Boucher-Neuhäuser syndrome and suggest inquiring about a history of hypogonadism or visual changes in patients presenting with late-onset gait ataxia. We also advocate for neuroophthalmologic evaluation in suspected cases.

Recovery of spermatogenesis following testosterone replacement therapy or anabolic-androgenic steroid use

PubMed Central

McBride, J Abram; Coward, Robert M

2016-01-01

The use of testosterone replacement therapy (TRT) for hypogonadism continues to rise, particularly in younger men who may wish to remain fertile. Concurrently, awareness of a more pervasive use of anabolic-androgenic steroids (AAS) within the general population has been appreciated. Both TRT and AAS can suppress the hypothalamic-pituitary-gonadal (HPG) axis resulting in diminution of spermatogenesis. Therefore, it is important that clinicians recognize previous TRT or AAS use in patients presenting for infertility treatment. Cessation of TRT or AAS use may result in spontaneous recovery of normal spermatogenesis in a reasonable number of patients if allowed sufficient time for recovery. However, some patients may not recover normal spermatogenesis or tolerate waiting for spontaneous recovery. In such cases, clinicians must be aware of the pathophysiologic derangements of the HPG axis related to TRT or AAS use and the pharmacologic agents available to reverse them. The available agents include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their off-label use is poorly described in the literature, potentially creating a knowledge gap for the clinician. Reviewing their use clinically for the treatment of hypogonadotropic hypogonadism and other HPG axis abnormalities can familiarize the clinician with the manner in which they can be used to recover spermatogenesis after TRT or AAS use. PMID:26908067

Intestinal Volvulus in Idiopathic Steatorrhea

PubMed Central

Warner, H. A.; Kinnear, D. G.; Cameron, D. G.

1963-01-01

Volvulus of the intestine has recently been observed in three patients with idiopathic steatorrhea in relapse. Two patients gave a history of intermittent abdominal pain, distension and obstipation. Radiographic studies during these attacks revealed obstruction at the level of the sigmoid colon. Reduction under proctoscopic control was achieved in one instance, spontaneous resolution occurring in the other. The third patient presented as a surgical emergency and underwent operative reduction of a small intestinal volvulus. Persistence of diarrhea and weight loss postoperatively led to further investigation and a diagnosis of idiopathic steatorrhea. In all cases, treatment resulted in clinical remission with a coincident disappearance of obstructive intestinal symptoms. The pathogenesis of volvulus in sprue is poorly understood. Atonicity and dilatation of the bowel and stretching of the mesentery likely represent important factors. The symptoms of recurrent abdominal pain and distension in idiopathic steatorrhea necessitate an increased awareness of intestinal volvulus as a complication of this disease. ImagesFig. 1Fig. 2Fig. 3Figs. 4 and 5Fig. 6 PMID:13998948

Transient pituitary enlargement with central hypogonadism secondary to bilateral cavernous sinus thrombosis: pituitary oedema?

PubMed

Joubert, Michael; Verdon, Renaud; Reznik, Yves

2009-05-01

Design We report the case of an incidental pituitary mass discovered in the context of bilateral cavernous sinus thrombosis due to a bacterial pansinusitis. Conclusions Magnetic resonance imaging features of the pituitary lesion, together with transient central hypogonadism and total regression of the mass after anticoagulation and antimicrobial therapy, suggest that this lesion is a pituitary oedema of vascular mechanism. Other possible causes of pituitary mass in such a situation are also discussed.

Metabolic Syndrome in Male Hypogonadism.

PubMed

Rastrelli, Giulia; Filippi, Sandra; Sforza, Alessandra; Maggi, Mario; Corona, Giovanni

2018-01-01

Metabolic syndrome (MetS) and hypogonadism (HG) are frequently comorbid. In this review, we summarize interconnections between the construct of MetS and the presence of HG, as well as the effect of specific treatments for each condition on this association. Data from meta-analytic studies suggest a bidirectional pathogenic relationship. In fact, reduced T (-2.21 [-2.43 to -1.98] nmol/L) at baseline predicts incident MetS. On the other hand, MetS at study entry increases the risk of developing HG (OR 2.46 [1.77-3.42]). The bidirectional pathogenic link between MetS and HG is further confirmed by the fact that treating MetS with insulin sensitizer is associated with an increase in T. In addition, a huge effect on increasing T is found in obese men undergoing procedures for losing weight, with more dramatic results obtained after bariatric surgery than after low calorie diet (increase in T 8.73 [6.51-10.95] nmol/L and 2.87 [1.68-4.07] nmol/L, respectively, according to a recent meta-analysis). On the other hand, there is evidence of an improvement in several metabolic derangements characterizing MetS in subjects treated with T. However, the latter results are still not conclusive and need further evidence from randomized clinical trials. © 2018 S. Karger AG, Basel.

Psychometric Evaluation of the Hypogonadism Impact of Symptoms Questionnaire Short Form (HIS-Q-SF).

PubMed

Gelhorn, Heather L; Roberts, Laurie J; Khandelwal, Nikhil; Revicki, Dennis A; DeRogatis, Leonard R; Dobs, Adrian; Hepp, Zsolt; Miller, Michael G

2017-08-01

The Hypogonadism Impact of Symptoms Questionnaire Short Form (HIS-Q-SF) is a patient-reported outcome measurement designed to evaluate the symptoms of hypogonadism. The HIS-Q-SF is an abbreviated version including17 items from the original 28-item HIS-Q. To conduct item analyses and reduction, evaluate the psychometric properties of the HIS-Q-SF, and provide guidance on score interpretation. A 12-week observational longitudinal study of hypogonadal men was conducted as part of the original HIS-Q psychometric evaluation. Participants completed the original HIS-Q every 2 weeks. Blood samples were collected to evaluate testosterone levels. Participants completed the Aging Male's Symptoms Scale, the International Index of Erectile Function, the Short Form-12, and the PROMIS Sexual Activity, Satisfaction with Sex Life, Sleep Disturbance, and Applied Cognition Scales (baseline and weeks 6 and 12). Clinicians completed the Clinical Global Impression of Severity and Change scales and a clinical form. Item performance was evaluated using descriptive statistics and Rasch analyses. Reliability (internal consistency and test-retest), validity (concurrent and know groups), and responsiveness were assessed. One hundred seventy-seven men participated (mean age = 54.1 years, range = 23-83). Similar to the full HIS-Q, the final abbreviated HIS-Q-SF instrument includes five domains (sexual, energy, sleep, cognition, and mood) with two sexual subdomains (libido and sexual function). For key domains, test-retest reliability was very good, and construct validity was good for all domains. Known-groups validity was demonstrated for all domain scores, subdomain scores, and total score based on the Clinical Global Impression-Severity. All domains and subdomains were responsive to change based on patient-rated anchor questions. The HIS-Q-SF could be a useful tool in clinical practice, epidemiologic studies, and other academic research settings. Careful consideration was given to the

Nonsurgical Management of Adolescent Idiopathic Scoliosis.

PubMed

Gomez, Jaime A; Hresko, M Timothy; Glotzbecker, Michael P

2016-08-01

Pediatric patient visits for spinal deformity are common. Most of these visits are for nonsurgical management of scoliosis, with approximately 600,000 visits for adolescent idiopathic scoliosis (AIS) annually. Appropriate management of scoliotic curves that do not meet surgical indication parameters is essential. Renewed enthusiasm for nonsurgical management of AIS (eg, bracing, physical therapy) exists in part because of the results of the Bracing in Adolescent Idiopathic Scoliosis Trial, which is the only randomized controlled trial available on the use of bracing for AIS. Bracing is appropriate for idiopathic curves between 20° and 40°, with successful control of these curves reported in >70% of patients. Patient adherence to the prescribed duration of wear is essential to maximize the effectiveness of the brace. The choice of brace type must be individualized according to the deformity and the patient's personality as well as the practice setting and brace availability.

Occurrence of idiopathic pulmonary fibrosis during immunosuppressive treatment: a case report.

PubMed

Cerri, Stefania; Sgalla, Giacomo; Richeldi, Luca; Luppi, Fabrizio

2016-05-25

Immunosuppressive therapy has been-until the recent release of new guidelines on diagnosis and management-the recommended treatment for idiopathic pulmonary fibrosis. However, its efficacy in patients with idiopathic pulmonary fibrosis has always been a matter of debate. We report the occurrence of idiopathic pulmonary fibrosis in a white man receiving chronic immunosuppressive treatment following a heart transplant. This case report suggests that the immune mechanisms targeted by azathioprine and cyclosporine do not play a role in the pathogenesis of idiopathic pulmonary fibrosis.

IgG abnormality in narcolepsy and idiopathic hypersomnia.

PubMed

Tanaka, Susumu; Honda, Makoto

2010-03-05

A close association between narcolepsy and the Human Leukocyte Antigen (HLA)-DQB1*0602 allele suggests the involvement of the immune system, or possibly an autoimmune process. We investigated serum IgG levels in narcolepsy. We measured the serum total IgG levels in 159 Japanese narcolepsy-cataplexy patients positive for the HLA-DQB1*0602 allele, 28 idiopathic hypersomnia patients with long sleep time, and 123 healthy controls (the HLA-DQB1*0602 allele present in 45 subjects). The serum levels of each IgG subclass were subsequently measured. The distribution of serum IgG was significantly different among healthy controls negative for the HLA-DQB1*0602 allele (11.66+/-3.55 mg/ml), healthy controls positive for the HLA-DQB1*0602 allele (11.45+/-3.43), narcolepsy patients (9.67+/-3.38), and idiopathic hypersomnia patients (13.81+/-3.80). None of the following clinical variables, age, disease duration, Epworth Sleepiness Scale, smoking habit and BMI at the time of blood sampling, were associated with IgG levels in narcolepsy or idiopathic hypersomnia. Furthermore we found the decrease in IgG1 and IgG2 levels, stable expression of IgG3, and the increase in the proportion of IgG4 in narcolepsy patients with abnormally low IgG levels. The increase in the proportion of IgG4 levels was also found in narcolepsy patients with normal serum total IgG levels. Idiopathic hypersomnia patients showed a different pattern of IgG subclass distribution with high IgG3 and IgG4 level, low IgG2 level, and IgG1/IgG2 imbalance. Our study is the first to determine IgG abnormalities in narcolepsy and idiopathic hypersomnia by measuring the serum IgG levels in a large number of hypersomnia patients. The observed IgG abnormalities indicate humoral immune alterations in narcolepsy and idiopathic hypersomnia. Different IgG profiles suggest immunological differences between narcolepsy and idiopathic hypersomnia.

Prevention of CCl4 induced hypogonadism with Raphanus sativus seeds in rat.

PubMed

Tabassum, Farhana; Khan, Muhammad Rashid

2017-03-01

Raphanus sativus seeds are used as condiment and to treat hypogonadism, various ailments of liver and kidneys. The aim of this study was to evaluate the potential protective effects of methanol extract of R. sativus seeds (RSME) against hypogonadism induced with carbon tetrachloride (CCl 4 ) in Sprague-Dawley male rats. Thirty six rats were divided in to six groups with six animals in each. Animals of Group I were control and treated with saline, Group II, III and IV were given orally CCl 4 (1 ml/kg bw; 10% in corn oil). Rats of Group III and IV were also simultaneously given RSME at 100 mg/kg bw and 200 mg/kg bw respectively. However, Group V and VI received RSME (100; 200 mg/kg bw, respectively) alone. All treatments were given at alternate days for 15 days. Treatment of CCl4 to rats decreased (P < 0.001) the level of CAT, POD, SOD, GST, GSH-Px and GSR antioxidant enzymes in testes of rat. Concentration of lipid peroxides (TBARS) was increased (P < 0.001) whereas concentration of GSH was decreased (P < 0.001) in testes of CCl4 treated animals. Concentration of testosterone, FSH and LH in serum was decreased (P < 0.001) while the level of estradiol and prolactin was increased (P < 0.001) in CCl4 treated rats. Injuries in seminiferous tubules were determined in histopathology of testes. Administration of RSME, dose dependently, markedly ameliorated the oxidative stress of CCl4 thereby restoring the level of antioxidant enzymes, lipid peroxides, reduced glutathione, male hormones and alterations in histopathology.

Pathology of idiopathic non-cirrhotic portal hypertension.

PubMed

Guido, Maria; Sarcognato, Samantha; Sacchi, Diana; Colloredo, Guido

2018-04-12

Idiopathic non-cirrhotic portal hypertension is an under-recognized vascular liver disease of unknown etiology, characterized by clinical signs of portal hypertension in the absence of cirrhosis. By definition, any disorder known to cause portal hypertension in the absence of cirrhosis and any cause of chronic liver disease must be excluded to make a diagnosis of idiopathic non-cirrhotic portal hypertension. However, the diagnosis is often difficult because the disease resembles cirrhosis and there is no gold standard test. Liver biopsy is an essential tool: it is able to exclude cirrhosis and other causes of portal hypertension and it allows the identification of the characteristic lesions. Nonetheless, the histological diagnosis of idiopathic non-cirrhotic portal hypertension is not always straightforward, in particular by needle biopsy samples, because there is no pathognomonic lesion, but rather a variety of vascular changes which are unevenly distributed, very subtle, and not all necessarily identified in a single specimen. Pathologists should be able to recognize several patterns of injury, involving portal/periportal areas as well as parenchymal structures.The histological features of idiopathic non-cirrhotic portal hypertension are described in this review, focusing on their interpretation in needle biopsy specimens.

[Adolescent idiopathic scoliosis].

PubMed

2016-12-01

Adolescent idiopathic scoliosis is a 3D spinal deformity in frontal, sagittal and axial planes, with high relevance in the pediatric population especially in adolescents and females between 10 years of age and the end of growth spurt and skeletal maturity. The radiographic manifestation is a curve greater than 10° measured by Cobb method associated with vertebral rotation. "Idiopathic" diagnosis has to be done after neuroanatomical anomalies of the posterior cerebral fosa and spinal canal have been ruled out. The physical finding of a thoracic or lumbar hump is the clinical manifestation of vertebral rotation seen in a forward bending test (Adam's Test). It is recommended that all curves with a magnitude greater than 20° have to be controlled and treated by a spinal surgeon being observation, bracing and surgery the different treatment options based on the extent, progression of deformity and basically the clinical condition of the patient. Sociedad Argentina de Pediatría.

Idiopathic pulmonary fibrosis.

PubMed

Xaubet, Antoni; Ancochea, Julio; Molina-Molina, María

2017-02-23

Idiopathic pulmonary fibrosis is a fibrosing interstitial pneumonia associated with the radiological and/or histological pattern of usual interstitial pneumonia. Its aetiology is unknown, but probably comprises the action of endogenous and exogenous micro-environmental factors in subjects with genetic predisposition. Its diagnosis is based on the presence of characteristic findings of high-resolution computed tomography scans and pulmonary biopsies in absence of interstitial lung diseases of other aetiologies. Its clinical evolution is variable, although the mean survival rate is 2-5 years as of its clinical presentation. Patients with idiopathic pulmonary fibrosis may present complications and comorbidities which modify the disease's clinical course and prognosis. In the mild-moderate disease, the treatment consists of the administration of anti-fibrotic drugs. In severe disease, the best therapeutic option is pulmonary transplantation. In this paper we review the diagnostic and therapeutic aspects of the disease. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Idiopathic toe walking.

PubMed

Oetgen, Matthew E; Peden, Sean

2012-05-01

Toe walking is a bilateral gait abnormality in which a normal heel strike is absent and most weight bearing occurs through the forefoot. This abnormality may not be pathologic in patients aged <2 years, but it is a common reason for referral to an orthopaedic surgeon. Toe walking can be caused by several neurologic and developmental abnormalities and may be the first sign of a global developmental problem. Cases that lack a definitive etiology are categorized as idiopathic. A detailed history, with careful documentation of the developmental history, and a thorough physical examination are required in the child with a primary report of toe walking. Treatment is based on age and the severity of the abnormality. Management includes observation, stretching, casting, bracing, chemodenervation, and surgical lengthening of the gastrocnemius-soleus complex and/or Achilles tendon. An understanding of idiopathic toe walking as well as treatment options and their outcomes can help the physician individualize treatment to achieve optimal results.

CLINICAL CHARACTERISTICS OF IDIOPATHIC FOVEOMACULAR RETINOSCHISIS.

PubMed

Maruko, Ichiro; Morizane, Yuki; Kimura, Shuhei; Shiode, Yusuke; Hosokawa, Mio; Sekiryu, Tetsuju; Iida, Tomohiro; Shiraga, Fumio

2016-08-01

To describe the clinical features of idiopathic foveomacular retinoschisis not in association with myopia, glaucoma, optic disk pit, or juvenile retinoschisis. Retrospective observational case series. Five eyes of five patients with idiopathic foveomacular retinoschisis were included. The patients were 2 men and 3 women (average age, 75.2 years; range, 71-78 years). The average spherical equivalent was +2.40 diopters (range, +0.88 to +5.75 diopters), and the average axial length was 22.0 mm (range, 21.1-23.1 mm). All patients had retinoschisis from the macula to the optic disk in the affected eye. No patients had retinoschisis in the fellow eye. The average best-corrected visual acuity was 20/44 (68 Early Treatment Diabetic Retinopathy Study letter score). Idiopathic foveomacular retinoschisis is not inherited or associated with myopia, vitreomacular traction syndrome, optic pit, or glaucoma but is associated with older age, unilaterality, hyperopia with short axial length, complete posterior vitreous detachment, and weak leakage from the optic disk on fluorescein angiography.

Optimal management of idiopathic scoliosis in adolescence

PubMed Central

Kotwicki, Tomasz; Chowanska, Joanna; Kinel, Edyta; Czaprowski, Dariusz; Tomaszewski, Marek; Janusz, Piotr

2013-01-01

Idiopathic scoliosis is a three-dimensional deformity of the growing spine, affecting 2%–3% of adolescents. Although benign in the majority of patients, the natural course of the disease may result in significant disturbance of body morphology, reduced thoracic volume, impaired respiration, increased rates of back pain, and serious esthetic concerns. Risk of deterioration is highest during the pubertal growth spurt and increases the risk of pathologic spinal curvature, increasing angular value, trunk imbalance, and thoracic deformity. Early clinical detection of scoliosis relies on careful examination of trunk shape and is subject to screening programs in some regions. Treatment options are physiotherapy, corrective bracing, or surgery for mild, moderate, or severe scoliosis, respectively, with both the actual degree of deformity and prognosis being taken into account. Physiotherapy used in mild idiopathic scoliosis comprises general training of the trunk musculature and physical capacity, while specific physiotherapeutic techniques aim to address the spinal curvature itself, attempting to achieve self-correction with active trunk movements developed in a three-dimensional space by an instructed adolescent under visual and proprioceptive control. Moderate but progressive idiopathic scoliosis in skeletally immature adolescents can be successfully halted using a corrective brace which has to be worn full time for several months or until skeletal maturity, and is able to prevent more severe deformity and avoid the need for surgical treatment. Surgery is the treatment of choice for severe idiopathic scoliosis which is rapidly progressive, with early onset, late diagnosis, and neglected or failed conservative treatment. The psychologic impact of idiopathic scoliosis, a chronic disease occurring in the psychologically fragile period of adolescence, is important because of its body distorting character and the onerous treatment required, either conservative or surgical

[Oral Testosterone Undecanoate Capsules combined with Qilin Pills for late-onset hypogonadism in males].

PubMed

Mao, Jun-Biao; Chen, Xiao-Gang; Gui, Ding-Wen; Peng, Wei; Zheng, Jie

2017-05-01

To investigate the clinical effects of oral Testosterone Undecanoate Capsules (TUC) combined with Qilin Pills (QLP) on late-onset hypogonadism (LOH) in men. Sixty-three LOH patients meeting the inclusion criteria were randomly divided into a control group (aged ［48.4 ± 6.2］ yr, n = 32) and an experimental group (aged ［47.2 ± 5.6］ yr, n = 31) to be treated with oral TUC (80 mg, qd) and TUC + QLP (6g, tid), respectively, both for 3 months. Comparisons were made between the two groups of patients in the IIEF-5 scores, total testosterone (TT) levels, and scores in the Aging Males' Symptoms (AMS) scale before and after treatment. After treatment, the patients of the experimental group, as compared with the controls, showed a significantly increased IIEF-5 score (21.7 ± 5.8 vs 15.9 ± 4.7, P <0.05) and TT level (［16.7 ± 2.2］ vs ［13.1 ± 2.8］ nmol/L, P <0.05), but a decreased AMS score (20.7 ± 5.7 vs 31.3±6.5, P <0.05). TUC combined with Qilin Pills has a better effect and a lower rate of adverse reactions than TUC used alone in the treatment of late-onset hypogonadism in males.

Treatment of the idiopathic scoliosis with brace and physiotherapy.

PubMed

Hundozi-Hysenaj, Hajrije; Dallku, Iliriana Boshnjaku; Murtezani, Ardiana; Rrecaj, Shkurte

2009-01-01

Scoliosis is a three-dimensional deformation of the spine with a lateral curvature or deviation greater than 10 degrees and associated with vertebral rotation. Many conservative treatments are available for adolescents with idiopathic scoliosis, but the evidence for their effectiveness is still questioned. The objective of this study was to define the effectiveness of braces and individual physiotherapy for the comprehensive treatment of idiopathic scoliosis in adolescents. A retrospective study of 57 children with idiopathic thoracic dextroscoliosis with the magnitude of the thoracic curve between 20 degrees-35 degrees, treated in Orthopedic and Physiatrist Clinic as well as National Ortho-prosthetic Center within University Clinical Center of Kosova in Prishtina, during the period of 2003-2006. Inclusion of kinesitherapy in the comprehensive management of idiopathic scoliosis varied in the improvement of the muscle strength (satisfied and moderate) in almost 80% of the children while the correction of the curve was small in approximately 42.1% of cases. For children with idiopathic scoliosis, who require braces, an exercise program helps chest mobility, muscle strength, proper breathing flexibility in the spine, correct posture and keeps muscles in tone so that the transition period after brace removal is easier.

Acute exacerbation of idiopathic pulmonary fibrosis triggered by Aspergillus empyema.

PubMed

Suzuki, Atsushi; Kimura, Tomoki; Kataoka, Kensuke; Matsuda, Toshiaki; Yokoyama, Toshiki; Mori, Yuta; Kondoh, Yasuhiro

2018-01-01

Acute exacerbation (AE) is a severe and life-threatening complication of idiopathic pulmonary fibrosis (IPF). In 2016, the definition and diagnostic criteria for AE-IPF were updated by an international working group. The new definition includes any acute, clinically significant respiratory deterioration (both idiopathic and triggered events) characterized by evidence of new widespread alveolar abnormality in patients with IPF. There are no currently proven beneficial management strategies for idiopathic and triggered AE-IPF. This is the first report describing AE-IPF triggered by Aspergillus empyema, which was improved by a combination of corticosteroid, systemic antifungal therapy, local antifungal therapy, and additional pharmacological therapies. Future research may reveal optimal strategies for both idiopathic and triggered AE-IPF.

Idiopathic intracranial hypertension and sickle cell disease: two case reports.

PubMed

Segal, Laura; Discepola, Marino

2005-12-01

Two patients with sickle cell disease presented with headaches and visual disturbances, typical complaints of this disorder. However, prompt diagnosis of idiopathic intracranial hypertension and initiation of medical therapy lead to improved symptoms and restored vision. Ophthalmologists should consider sickle cell disease to be an independent risk factor for idiopathic intracranial hypertension when a patient is being assessed for visual disturbances. Although a rare condition, idiopathic intracranial hypertension has several key signs useful in establishing a diagnosis. It is critical to recognize the warning signs and symptoms to prevent devastating ophthalmologic complications. We report the first cases of idiopathic intracranial hypertension in patients with the novel Quebec-Chori beta-chain variant of sickle cell disease.

Guidelines for the medical treatment of idiopathic pulmonary fibrosis.

PubMed

Xaubet, Antoni; Molina-Molina, María; Acosta, Orlando; Bollo, Elena; Castillo, Diego; Fernández-Fabrellas, Estrella; Rodríguez-Portal, José Antonio; Valenzuela, Claudia; Ancochea, Julio

2017-05-01

Idiopathic pulmonary fibrosis is defined as chronic fibrosing interstitial pneumonia limited to the lung, with poor prognosis. The incidence has been rising in recent years probably due to improved diagnostic methods and increased life expectancy. In 2013, the SEPAR guidelines for the diagnosis and treatment for idiopathic pulmonary fibrosis were published. Since then, clinical trials and meta-analyses have shown strong scientific evidence for the use of pirfenidone and nintedanib in the treatment of idiopathic pulmonary fibrosis. In 2015, the international consensus of 2011 was updated and new therapeutic recommendations were established, prompting us to update our recommendation for the medical treatment of idiopathic pulmonary fibrosis accordingly. Diagnostic aspects and non-pharmacological treatment will not be discussed as no relevant developments have emerged since the 2013 guidelines. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Low incidence of new biochemical and clinical hypogonadism following hypofractionated stereotactic body radiation therapy (SBRT) monotherapy for low- to intermediate-risk prostate cancer

PubMed Central

2011-01-01

Background The CyberKnife is an appealing delivery system for hypofractionated stereotactic body radiation therapy (SBRT) because of its ability to deliver highly conformal radiation therapy to moving targets. This conformity is achieved via 100s of non-coplanar radiation beams, which could potentially increase transitory testicular irradiation and result in post-therapy hypogonadism. We report on our early experience with CyberKnife SBRT for low- to intermediate-risk prostate cancer patients and assess the rate of inducing biochemical and clinical hypogonadism. Methods Twenty-six patients were treated with hypofractionated SBRT to a dose of 36.25 Gy in 5 fractions. All patients had histologically confirmed low- to intermediate-risk prostate adenocarcinoma (clinical stage ≤ T2b, Gleason score ≤ 7, PSA ≤ 20 ng/ml). PSA and total testosterone levels were obtained pre-treatment, 1 month post-treatment and every 3 months thereafter, for 1 year. Biochemical hypogonadism was defined as a total serum testosterone level below 8 nmol/L. Urinary and gastrointestinal toxicity was assessed using Common Toxicity Criteria v3; quality of life was assessed using the American Urological Association Symptom Score, Sexual Health Inventory for Men and Expanded Prostate Cancer Index Composite questionnaires. Results All 26 patients completed the treatment with a median 15 months (range, 13-19 months) follow-up. Median pre-treatment PSA was 5.75 ng/ml (range, 2.3-10.3 ng/ml), and a decrease to a median of 0.7 ng/ml (range, 0.2-1.8 ng/ml) was observed by one year post-treatment. The median pre-treatment total serum testosterone level was 13.81 nmol/L (range, 5.55 - 39.87 nmol/L). Post-treatment testosterone levels slowly decreased with the median value at one year follow-up of 10.53 nmol/L, significantly lower than the pre-treatment value (p < 0.013). The median absolute fall was 3.28 nmol/L and the median percent fall was 23.75%. There was no increase in biochemical hypogonadism

Recommendations on the diagnosis, treatment and monitoring of late-onset hypogonadism in men - a suggested update.

PubMed

Lunenfeld, Bruno; Mskhalaya, George; Kalinchenko, Svetlana; Tishova, Yulia

2013-12-01

Recommendations on the diagnosis, treatment and monitoring of late-onset hypogonadism (LOH) in men were first published by ISSAM in 2002 In 2005, and, in 2008, updated recommendations were published in the International Journal of Andrology, the Journal of Andrology, the Aging Male and European Urology. Towards discussions at the next ISSAM/ESSAM meeting in Moscow, 29 November 2013, we suggest the following update.

Maternal asthma and idiopathic preterm labor.

PubMed

Kramer, M S; Coates, A L; Michoud, M C; Dagenais, S; Moshonas, D; Davis, G M; Hamilton, E F; Nuwayhid, B; Joshi, A K; Papageorgiou, A

1995-11-15

Previous studies suggest that women with asthma are at increased risk of preterm birth. Moreover, drugs (especially beta-agonists) used to treat asthma are also used to treat preterm labor. The authors carried out a case-control study of 555 women from three hospital centers with idiopathic preterm labor (< 37 weeks), including two overlapping (i.e., non-mutually exclusive) subsamples: cases with early idiopathic preterm labor (< 34 weeks) and cases with idiopathic recurrent preterm labor (< 37 weeks plus a previous history of preterm delivery or second-trimester miscarriage). Controls were matched to cases according to race and smoking history prior to and during pregnancy. All subjects responded in person to questions about atopic, respiratory, obstetric, and sociodemographic histories. Subjects in the early and recurrent preterm labor subsamples were also asked to undergo spirometric testing with methacholine challenge 6-12 weeks after delivery. Cases were significantly more likely to report histories of asthma symptoms and physician-diagnosed asthma (matched odds ratios of 2-3) than controls, particularly those cases with recurrent preterm labor. No significant associations were observed, however, with methacholine responsiveness. These results could not be explained by residual confounding by smoking or other variables, nor by selective recall of asthma symptoms and histories by cases. Women with asthma are at increased risk of idiopathic preterm labor. The fact that no such association was seen with methacholine responsiveness suggests that nonatopic, noncholinergic mechanisms may link bronchial and uterine smooth muscle lability.

Altered Regional Cerebral Blood Flow in Idiopathic Hypersomnia.

PubMed

Boucetta, Soufiane; Montplaisir, Jacques; Zadra, Antonio; Lachapelle, Francis; Soucy, Jean-Paul; Gravel, Paul; Dang-Vu, Thien Thanh

2017-10-01

Idiopathic hypersomnia is characterized by excessive daytime sleepiness, despite normal or long sleep time. Its pathophysiological mechanisms remain unclear. This pilot study aims at characterizing the neural correlates of idiopathic hypersomnia using single photon emission computed tomography. Thirteen participants with idiopathic hypersomnia and 16 healthy controls were scanned during resting wakefulness using a high-resolution single photon emission computed tomography scanner with 99mTc-ethyl cysteinate dimer to assess cerebral blood flow. The main analysis compared regional cerebral blood flow distribution between the two groups. Exploratory correlations between regional cerebral blood flow and clinical characteristics evaluated the functional correlates of those brain perfusion patterns. Significance was set at p < .05 after correction for multiple comparisons. Participants with idiopathic hypersomnia showed regional cerebral blood flow decreases in medial prefrontal cortex and posterior cingulate cortex and putamen, as well as increases in amygdala and temporo-occipital cortices. Lower regional cerebral blood flow in the medial prefrontal cortex was associated with higher daytime sleepiness. These preliminary findings suggest that idiopathic hypersomnia is characterized by functional alterations in brain areas involved in the modulation of vigilance states, which may contribute to the daytime symptoms of this condition. The distribution of regional cerebral blood flow changes was reminiscent of the patterns associated with normal non-rapid-eye-movement sleep, suggesting the possible presence of incomplete sleep-wake transitions. These abnormalities were strikingly distinct from those induced by acute sleep deprivation, suggesting that the patterns seen here might reflect a trait associated with idiopathic hypersomnia rather than a non-specific state of sleepiness. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep

Idiopathic Hypersomnia: Clinical Features and Response to Treatment

PubMed Central

Ali, Mohsin; Auger, R. Robert; Slocumb, Nancy L.; Morgenthaler, Timothy I.

2009-01-01

Objective: A recent American Academy of Sleep Medicine publication identified a need for research regarding idiopathic hypersomnia. We describe various clinical and polysomnographic features of patients with idiopathic hypersomnia, with an emphasis on response to pharmacotherapy. Methods: A retrospective review of our database initially identified 997 patients, utilizing “idiopathic hypersomnia,” “hypersomnia NOS,” and “primary hypersomnia” as keywords. The charts of eligible patients were examined in detail, and data were abstracted and analyzed. Response to treatment was graded utilizing an internally developed scale. Results: Eighty-five patients were ultimately identified (65% female). Median (interquartile range) ages of onset and diagnosis were 19.6 (15.5) and 33.7 (15.5), respectively. During a median follow-up duration of 2.4 (4.7) years, 65% of patients demonstrated a “complete response” to pharmacotherapy as assessed by the authors' grading schema. Methylphenidate was most commonly used as a first-line agent prior to December 1998, but subsequently, modafinil became the most common first drug. At the last recorded follow-up visit, 92% of patients were on monotherapy, with greater representation of methylphenidate versus modafinil (51% vs. 32%). Among these patients, methylphenidate produced a higher percentage of “complete” or “partial” responses than modafinil, although statistical significance was not reached (38/40 [ 95%] vs 22/25 [88%], respectively, p = 0.291). Conclusions: The majority of patients with idiopathic hypersomnia respond well to treatment. Methylphenidate is chosen more often than modafinil as final monotherapy in the treatment of idiopathic hypersomnia, despite the fact that it is less commonly used initially. Further prospective comparisons of medications should be explored. Citation: Ali M; Auger RR; Slocumb NL; Morgenthaler TI. Idiopathic hypersomnia: clinical features and response to treatment. J Clin Sleep

Treatment of idiopathic pulmonary fibrosis with losartan: a pilot project.

PubMed

Couluris, Marisa; Kinder, Brent W; Xu, Ping; Gross-King, Margaret; Krischer, Jeffrey; Panos, Ralph J

2012-10-01

Idiopathic pulmonary fibrosis is a progressive interstitial lung disease with no current effective therapies. Treatment has focused on antifibrotic agents to stop proliferation of fibroblasts and collagen deposition in the lung. We present the first clinical trial data on the use of losartan, an antifibrotic agent, to treat idiopathic pulmonary fibrosis. The primary objective was to evaluate the effect of losartan on progression of idiopathic pulmonary fibrosis measured by the change in percentage of predicted forced vital capacity (%FVC) after 12 months. Secondary outcomes included the change in forced expiratory volume at 1 second, diffusing capacity of carbon monoxide, 6-minute walk test distance, and baseline/transition dyspnea index. Patients with idiopathic pulmonary fibrosis and a baseline %FVC of ≥50 % were treated with losartan 50 mg by mouth daily for 12 months. Pulmonary function testing, 6-minute walk, and breathlessness indices were measured every 3 months. Twenty participants with idiopathic pulmonary fibrosis were enrolled and 17 patients were evaluable for response. Twelve patients had a stable or improved %FVC at study month 12. Similar findings were observed in secondary end-point measures, including 58, 71, and 65 % of patients with stable or improved forced expiratory volume at 1 second, diffusing capacity for carbon monoxide, and 6-minute walk test distance, respectively. No treatment-related adverse events that resulted in early study discontinuation were reported. Losartan stabilized lung function in patients with idiopathic pulmonary fibrosis over 12 months. Losartan is a promising agent for the treatment of idiopathic pulmonary fibrosis and has a low toxicity profile.

Brain MRI findings in patients with idiopathic hypersomnia.

PubMed

Trotti, Lynn Marie; Bliwise, Donald L

2017-06-01

Proper diagnosis of idiopathic hypersomnia necessitates the exclusion of neurologic or medical causes of sleepiness that better explain the clinical syndrome. However, there are no formal guidelines regarding the use of neuroimaging to identify such secondary causes of symptoms. We sought to characterize brain MRI findings in a series of patients with idiopathic hypersomnia. We reviewed medical records on a consecutive series of 61 patients diagnosed with idiopathic hypersomnia to determine the frequency and results of brain magnetic resonance imaging (MRI). One-third of patients had undergone brain MRI, with focal neurologic signs or symptoms being the most common indication for neuroimaging. Although seven patients had an identifiable finding on neuroimaging (e.g., chronic microvascular ischemic changes), clinical management was changed as a result of imaging in only three cases. In all three, the imaging finding was predated by clear clinical abnormalities. Neuroimaging may be a complementary part of an idiopathic hypersomnia evaluation, but the decision to pursue imaging should be made on a case-by-case basis. Copyright © 2017 Elsevier B.V. All rights reserved.

Hypogonadism and Sex Steroid Replacement Therapy in Girls with Turner Syndrome.

PubMed

Gawlik, Aneta; Hankus, Magdalena; Such, Kamila; Drosdzol-Cop, Agnieszka; Madej, Paweł; Borkowska, Marzena; Zachurzok, Agnieszka; Malecka-Tendera, Ewa

2016-12-01

Turner syndrome is the most common example of hypergonadotropic hypogonadism resulting from gonadal dysgenesis. Most patients present delayed, or even absent, puberty. Premature ovarian failure can be expected even if spontaneous menarche occurs. Laboratory markers of gonadal dysgenesis are well known. The choice of optimal hormone replacement therapy in children and adolescents remains controversial, particularly regarding the age at which therapy should be initiated, and the dose and route of estrogen administration. On the basis of a review of the literature, we present the most acceptable schedule of sex steroid replacement therapy in younger patients with Turner syndrome. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Idiopathic granulomatous mastitis: an institutional experience

PubMed Central

Prasad, Seetharam; Jaiprakash, Padmapriya; Dave, Aniket; Pai, Deepti

2017-01-01

Objective To study idiopathic granulomatous mastitis with respect to its various clinical features, etiologic factors, treatment modalities and complications. Material and methods Retrospective study of all patients who were diagnosed with idiopathic granulomatous mastitis from 1st January 2006 to 31st December 2014 at Kasturba Hospital, Manipal, India (a tertiary care referral centre). The research was performed according to the World Medical Association Declaration of Helsinki. Informed consent was taken from the patient before invasive procedures including surgery. Data was analysed using the Statistical Package for Social Sciences version 16.0 wherever appropriate. Results 73 patients diagnosed with idiopathic granulomatous mastitis during the time period were included. One patient was a male (1.37%), rest were all females (98.63%). The mean age of presentation was 32.67 years (range 23 to 66 years). 70 patients (95.89%) were parous females. Average duration since last childbirth was 4.6 years (range: 3 months to 33 years). 8 patients (10.95%) were lactating. History of oral contraceptive pill use was present in 40 patients (54.79%). The right breast was affected in 44 patients (60.27%), and the left breast in 29 patients (39.73%). None of the patients had bilateral disease. The most common symptom was a painless lump (61.64%). Rest of the patients (38.36%) presented with features of a breast abscess. 19 out of 39 FNACs done (48.72%) were positive for granulomatous mastitis. 59 were primarily managed surgically (lumpectomy/wide excision-33, incision & drainage-26). One patient was treated primarily with prednisolone. 13 patients did not receive specific treatment, and were only kept on regular follow-up. Patients managed with lumpectomy/wide excision had the least rate of complications & recurrence (18.18%). Conclusion Patients with idiopathic granulomatous mastitis can present with a wide variety of symptoms which mimic other more common conditions. Surgical

Idiopathic granulomatous mastitis: a diagnostic dilemma for the breast radiologist.

PubMed

Sripathi, Smiti; Ayachit, Anurag; Bala, Archana; Kadavigere, Rajagopal; Kumar, Sandeep

2016-08-01

Idiopathic granulomatous mastitis is a chronic inflammatory disease of the breast, which is often difficult to differentiate both clinically and radiologically from infectious aetiologies such as tuberculosis, fungal infections, and also from malignancy, thus posing a diagnostic dilemma. We present a pictorial review of the commonly encountered imaging findings in idiopathic granulomatous mastitis on mammography and ultrasound. Mammographic and ultrasound findings of histopathologically proven cases of granulomatous mastitis are discussed. Idiopathic granulomatous mastitis has varied and non-specific appearances on ultrasound and mammography. Histopathology is essential to establish diagnosis. • Idiopathic granulomatous mastitis often poses a diagnostic dilemma for the radiologist by mimicking malignancy. • It has varied and non-specific appearances on mammography and ultrasound. • Histopathology is mandatory to establish the diagnosis and decide management.

Idiopathic scrotal elephantiasis.

PubMed

Hornberger, Brad J; Elmore, James M; Roehrborn, Claus G

2005-02-01

Scrotal lymphedema (scrotal elephantiasis) is a condition that has historically been described in areas endemic to filariasis. We present a unique case of a 22-year-old man with idiopathic lymphedema isolated to the scrotum. After acquired causes of lymphedema were ruled out, the patient was treated with scrotectomy and scrotal reconstruction.

Idiopathic diaphragmatic paralysis: Bell's palsy of the diaphragm?

PubMed

Crausman, Robert S; Summerhill, Eleanor M; McCool, F Dennis

2009-01-01

Idiopathic diaphragm paralysis is probably more common and responsible for more morbidity than generally appreciated. Bell's palsy, or idiopathic paralysis of the seventh cranial nerve, may be seen as an analogous condition. The roles of zoster sine herpete and herpes simplex have increasingly been recognized in Bell's palsy, and there are some data to suggest that antiviral therapy is a useful adjunct to steroid therapy. Thus, we postulated that antiviral therapy might have a positive impact on the course of acute idiopathic diaphragm paralysis which is likely related to viral infection. Three consecutive patients with subacute onset of symptomatic idiopathic hemidiaphragm paralysis were empirically treated with valacyclovir, 1,000 mg twice daily for 1 week. Prior to therapy, diaphragmatic function was assessed via pulmonary function testing and two-dimensional B-mode ultrasound, with testing repeated 1 month later. Diaphragmatic function pre- and post-treatment was compared to that of a historical control group of 16 untreated patients. All three subjects demonstrated ultrasound recovery of diaphragm function 4-6 weeks following treatment with valacyclovir. This recovery was accompanied by improvements in maximum inspiratory pressure (PI(max)) and vital capacity (VC). In contrast, in the untreated cohort, diaphragm recovery occurred in only 11 subjects, taking an average of 14.9 +/- 6.1 months (mean +/- SD). The results of this small, preliminary study suggest that antiviral therapy with valacyclovir may be helpful in the treatment of idiopathic diaphragm paralysis induced by a viral infection.

Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis.

PubMed

Corona, Giovanni; Rastrelli, Giulia; Monami, Matteo; Saad, Farid; Luconi, Michaela; Lucchese, Marcello; Facchiano, Enrico; Sforza, Alessandra; Forti, Gianni; Mannucci, Edoardo; Maggi, Mario

2013-06-01

Few randomized clinical studies have evaluated the impact of diet and physical activity on testosterone levels in obese men with conflicting results. Conversely, studies on bariatric surgery in men generally have shown an increase in testosterone levels. The aim of this study is to perform a systematic review and meta-analysis of available trials on the effect of body weight loss on sex hormones levels. Meta-analysis. An extensive Medline search was performed including the following words: 'testosterone', 'diet', 'weight loss', 'bariatric surgery', and 'males'. The search was restricted to data from January 1, 1969 up to August 31, 2012. Out of 266 retrieved articles, 24 were included in the study. Of the latter, 22 evaluated the effect of diet or bariatric surgery, whereas two compared diet and bariatric surgery. Overall, both a low-calorie diet and bariatric surgery are associated with a significant (P<0.0001) increase in plasma sex hormone-binding globulin-bound and -unbound testosterone levels (total testosterone (TT)), with bariatric surgery being more effective in comparison with the low-calorie diet (TT increase: 8.73 (6.51-10.95) vs 2.87 (1.68-4.07) for bariatric surgery and the low-calorie diet, respectively; both P<0.0001 vs baseline). Androgen rise is greater in those patients who lose more weight as well as in younger, non-diabetic subjects with a greater degree of obesity. Body weight loss is also associated with a decrease in estradiol and an increase in gonadotropins levels. Multiple regression analysis shows that the degree of body weight loss is the best determinant of TT rise (B=2.50±0.98, P=0.029). These data show that weight loss is associated with an increase in both bound and unbound testosterone levels. The normalization of sex hormones induced by body weight loss is a possible mechanism contributing to the beneficial effects of surgery in morbid obesity.

[Physical therapy for idiopathic scoliosis].

PubMed

Steffan, K

2015-11-01

The objective is the description and summary of the current state of idiopathic scoliosis treatment with physical therapy based on new scientific knowledge and concluded from more than 15 years of experience as a leading physician in two well-known clinics specializing in the conservative treatment of scoliosis. Based on current scientific publications on physical therapy in scoliosis treatment and resulting from the considerable personal experience gained working with conservative treatment and consulting scoliosis patients (as inpatients and outpatients), the current methods of physical therapy have been compared and evaluated. Physical therapy according to Schroth and Vojta therapy are at present the most common and effective methods in the physical treatment of idiopathic scoliosis. These methods can be applied during inpatient or outpatient treatment or intensified in the practice of specialized therapists. As there are only a few scientific studies on this subject, the author's findings are based mainly on his own experiences of the conservative treatment of idiopathic scoliosis. Athough these experiences are the results of over 15 years of working in the field of therapy, and the Schroth method in combination with corrective bracing presents highly promising results, it would nevertheless be desirable to conduct detailed scientific studies to verify the effectiveness of conservative treatment.

Hypogonadism alters cecal and fecal microbiota in male mice.

PubMed

Harada, Naoki; Hanaoka, Ryo; Hanada, Kazuki; Izawa, Takeshi; Inui, Hiroshi; Yamaji, Ryoichi

2016-11-01

Low testosterone levels increase the risk for cardiovascular disease in men and lead to shorter life spans. Our recent study showed that androgen deprivation via castration altered fecal microbiota and exacerbated risk factors for cardiovascular disease, including obesity, impaired fasting glucose, excess hepatic triglyceride accumulation, and thigh muscle weight loss only in high-fat diet (HFD)-fed male mice. However, when mice were administered antibiotics that disrupted the gut microbiota, castration did not increase cardiovascular risks or decrease the ratio of dried feces to food intake. Here, we show that changes in cecal microbiota (e.g., an increased Firmicutes/Bacteroidetes ratio and number of Lactobacillus species) were consistent with changes in feces and that there was a decreased cecal content secondary to castration in HFD mice. Castration increased rectal body temperature and plasma adiponectin, irrespective of diet. Changes in the gut microbiome may provide novel insight into hypogonadism-induced cardiovascular diseases.

The pharmacotherapy of male hypogonadism besides androgens.

PubMed

Corona, Giovanni; Rastrelli, Giulia; Ratrelli, Giulia; Maggi, Mario

2015-02-01

Adulthood male hypogonadism (HG) is the most common form of HG. Although testosterone (T) replacement therapy (TRT) is the most common way of treating HG, other options are available depending on patient's needs and expectations. We analyze alternative options to TRT as a medical intervention in treating HG. Gonadotropin (Gn) therapy is the treatment of choice in men with secondary HG (sHG), who require fertility. Gonadotropin-releasing hormone therapy represents an alternative to Gn for inducing spermatogenesis in patients with sHG, however, its use is limited by the poor patient compliance and high cost. In obese HG men, lifestyle modifications and, in particular, weight loss should be the first step. Recent data suggest that antiestrogens represent a successful treatment for sHG. Other potential therapeutic options include the stimulation of hypothalamic activity (i.e., kisspeptin and neurokinin-B agonists). Conversely, the possibility of increasing Leydig cell steroid production, independently from Gn stimulation, seems unreliable. Understanding the nature of male HG and patient's needs are mandatory before choosing among treatment options. For primary HG only TRT is advisable, whereas for the secondary form several alternative possibilities can be offered.

Effects of testosterone replacement therapy on nocturia and quality of life in men with hypogonadism: a subanalysis of a previous prospective randomized controlled study in Japan.

PubMed

Shigehara, Kazuyoshi; Konaka, Hiroyuki; Koh, Eitetsu; Izumi, Koji; Kitagawa, Yasuhide; Mizokami, Atsushi; Nakashima, Takao; Shimamura, Masayoshi; Iwamoto, Teruaki; Namiki, Mikio

2015-01-01

We investigated the effects of testosterone replacement therapy (TRT) on nocturia and general health among men with hypogonadism and nocturia. From our previous EARTH study population, 64 patients with a clinical diagnosis of nocturia (two or more times per one night) and hypogonadism, comprising the TRT group (n = 31) and controls (n = 33), were included in this analysis. The TRT group was administered 250 mg of testosterone enanthate as an intramuscular injection every 4 weeks for 6 months. All patients responded to the following questionnaires: International Prostatic Symptoms Score (IPSS), Aging Male Symptoms (AMS) score and Short Form-36 health survey at baseline and 6-month visit. These categories were compared based on changes from baseline to the 6-month visit between TRT and control groups. At the 6-month visit, the TRT group had a significant decrease in IPSS question no. 7 and AMS question no. 4, whereas no significant changes were observed in the control group. Additionally, role limitation because of health program, vitality and mental health domains were significantly improved in the TRT group. Six-month TRT may improve nocturia, sleep conditions and quality of life among men with hypogonadism and nocturia.

[Vitrectomy for idiopathic and secondary preretinal macular membrane].

PubMed

Oficjalska-Młyńczak, Jolanta; Jamrozy-Witkowska, Agnieszka

2004-01-01

To evaluate the results of pars plana vitrectomy and membrane stripping for idiopathic and secondary preretinal macular membrane (PMM). Twenty one consecutive subjects (21 eyes) ranging in age from 40 to 78 (mean 66.9) with PMM underwent vitrectomy and membrane peeling. 17 cases had membranes that were considered idiopathic, and 4 cases were associated with other disorders: 3 occurred after successful retinal reattachment surgery, 1--after laserotherapy in the course of diabetic retinopathy. Visual acuity (VA), Amsler grid, and postoperative complications were assessed. The follow-up was 1 to 22 months, mean 5.7. Visual acuity improved postoperatively in 15 eyes (71.4%), at least two lines on the Snellen chart in 8 eyes (38.1%), entirely in patients with idiopathic PMM. It remained unchanged in 3 eyes (14.3%) and deteriorated in 3 eyes (14.3%). Eyes with transparent membrane showed greater visual improvement than opaque ones. The preoperative Amsler test was positive in 15 patients (71.4%), postoperatively--in 4 cases (19%). 2 idiopathic cases with VA of 0.7 showed postoperatively VA of 1.0. Complications included retinal detachment in 2 eyes (1 in idiopathic and 1 in secondary PMM), and development of nuclear sclerotic cataract in 2 eyes. At 6 months of follow-up, a residual membrane formation in 1 cases appeared. Macular pseudohole was observed in 1 eye with no impact on visual results. 1. Vitrectomy with membrane peeling for preretinal macular membrane provides improvement in visual acuity and reduces metamorphopsia 2. Thin, cellophane-like appearance of the membrane gives a better prognosis of visual function improvement.

Idiopathic hypersomnia: clinical features and response to treatment.

PubMed

Ali, Mohsin; Auger, R Robert; Slocumb, Nancy L; Morgenthaler, Timothy I

2009-12-15

A recent American Academy of Sleep Medicine publication identified a need for research regarding idiopathic hypersomnia. We describe various clinical and polysomnographic features of patients with idiopathic hypersomnia, with an emphasis on response to pharmacotherapy. A retrospective review of our database initially identified 997 patients, utilizing "idiopathic hypersomnia", "hypersomnia NOS", and "primary hypersomnia" as keywords. The charts of eligible patients were examined in detail, and data were abstracted and analyzed. Response to treatment was graded utilizing an internally developed scale. Eighty-five patients were ultimately identified (65% female). Median (interquartile range) ages of onset and diagnosis were 19.6 (15.5) and 33.7 (15.5), respectively. During a median follow-up duration of 2.4 (4.7) years, 65% of patients demonstrated a "complete response" to pharmacotherapy as assessed by the authors' grading schema. Methylphenidate was most commonly used as a first-line agent prior to December 1998, but subsequently, modafinil became the most common first drug. At the last recorded follow-up visit, 92% of patients were on monotherapy, with greater representation of methylphenidate versus modafinil (51% vs. 32%). Among these patients, methylphenidate produced a higher percentage of "complete" or "partial" responses than modafinil, although statistical significance was not reached (38/40 [95%] vs. 22/25 [88%], respectively, p = 0.291). The majority of patients with idiopathic hypersomnia respond well to treatment. Methylphenidate is chosen more often than modafinil as final monotherapy in the treatment of idiopathic hypersomnia, despite the fact that it is less commonly used initially. Further prospective comparisons of medications should be explored.

Effects of testosterone undecanoate replacement and withdrawal on cardio-metabolic, hormonal and body composition outcomes in severely obese hypogonadal men: a pilot study.

PubMed

Francomano, D; Bruzziches, R; Barbaro, G; Lenzi, A; Aversa, A

2014-04-01

Modifications of cardiovascular and metabolic parameters during testosterone (T) replacement and withdrawal have never been investigated in severely obese hypogonadal men. Twenty-four severely obese (mean BMI 42; mean age 54.5) hypogonadal men (mean T = 245 ± 52 ng/dL) were enrolled in an observational, parallel-arm, open-label, 54-week study of hypocaloric diet plus physical activity (DPE; n = 12) or DPE plus T injections (DPE + T; n = 12), followed by 24 weeks of DPE alone. Primary endpoints were variations from baseline of cardiovascular (cardiac performance, blood pressure, endothelial function, carotid intima-media thickness, CIMT; epicardial fat thickness, EF) and body composition (fat/lean mass) parameters. Secondary endpoints were variations from baseline of hormonal (T and GH) and metabolic (oral glucose tolerance test, lipids, fibrinogen) parameters. At 54 weeks, DPE + T showed improvements in EF, ejection fraction, diastolic function, CIMT and endothelial function (p < 0.01 vs. controls). Also, hormonal (T, p < 0.0001; GH, p < 0.01), metabolic (HOMA, p < 0.01; microalbuminuria, p < 0.01), lipid (total cholesterol, p < 0.05) and inflammatory (fibrinogen, p < 0.05) parameters improved. After 24 weeks from T withdrawal, all cardiac and hormonal parameters returned to baseline, while fat but not lean mass and blood pressure ameliorations were maintained. An inverse relationship either between EF vs. endothelial function and EF vs. T levels was found (r (2) = -0.46, p < 0.001 and r (2) = -0.56, p < 0.0005, respectively) while direct relationship between T vs. endothelial function occurred (r (2) = 0.43, p < 0.005) in DPE + T. A 33 % dropout rate was reported in DPE without serious adverse events. In middle-aged hypogonadal obese men, 1-year T treatment was safe and improved cardio-metabolic and hormonal parameters. We firstly demonstrated that T withdrawal determines a return back to hypogonadism within 6 months, with loss of cardiovascular and some body

Downregulation of leptin receptor and kisspeptin/GPR54 in the murine hypothalamus contributes to male hypogonadism caused by high-fat diet-induced obesity.

PubMed

Zhai, Lingling; Zhao, Jian; Zhu, Yiming; Liu, Qiannan; Niu, Wenhua; Liu, Chengyin; Wang, Yi

2018-06-13

Obesity may lead to male hypogonadism, the underlying mechanism of which remains unclear. In the present study, we established a murine model of male hypogonadism caused by high-fat diet-induced obesity to verify the following hypotheses: 1) an increased leptin level may be related to decreased secretion of GnRH in obese males, and 2) repression of kisspeptin/GPR54 in the hypothalamus, which is associated with increased leptin levels, may account for the decreased secretion of GnRH and be involved in secondary hypogonadism (SH) in obese males. Male mice were fed high-fat diet for 19 weeks and divided by body weight gain into diet-induced obesity (DIO) and diet-induced obesity resistant (DIO-R) group. The effect of obesity on the reproductive organs in male mice was observed by measuring sperm count and spermatozoid motility, relative to testis and epididymis weight, testosterone levels, and pathologic changes. Leptin, testosterone, estrogen, and LH in serum were detected by ELISA method. Leptin receptor (Ob-R), Kiss1, GPR54, and GnRH mRNA were measured by real-time PCR in the hypothalamus. Expression of kisspeptin and Ob-R protein was determined by Western blotting. Expression of GnRH and GPR54 protein was determined by immunohistochemical analysis. We found that diet-induced obesity decreased spermatozoid motility, testis and epididymis relative coefficients, and plasma testosterone and luteinizing hormone levels. An increased number and volume of lipid droplets in Leydig cells were observed in the DIO group compared to the control group. Significantly, higher serum leptin levels were found in the DIO and DIO-R groups. The DIO and DIO-R groups showed significant downregulation of the GnRH, Kiss1, GPR54, and Ob-R genes. We also found decreased levels of GnRH, kisspeptin, GPR54, and Ob-R protein in the DIO and DIO-R groups. These lines of evidence suggest that downregulation of Ob-R and kisspeptin/GPR54 in the murine hypothalamus may contribute to male hypogonadism

Idiopathic inflammatory myopathies overlapping with systemic diseases

PubMed Central

Lepreux, Sébastien; Hainfellner, Johannes A.; Vital, Anne

2018-01-01

A muscle biopsy is currently requested to assess the diagnosis of an idiopathic inflammatory myopathy overlapping with a systemic disease. During the past few years, the classification of inflammatory myopathy subtypes has been revisited progressively on the basis of correlations between clinical phenotypes, autoantibodies and histological data. Several syndromic entities are now more clearly defined, and the aim of the present review is to clarify the contribution of muscle biopsy in a setting of idiopathic inflammatory myopathies overlapping with systemic diseases. PMID:29154752

Obesity is a significant susceptibility factor for idiopathic AA amyloidosis.

PubMed

Blank, Norbert; Hegenbart, Ute; Dietrich, Sascha; Brune, Maik; Beimler, Jörg; Röcken, Christoph; Müller-Tidow, Carsten; Lorenz, Hanns-Martin; Schönland, Stefan O

2018-03-01

To investigate obesity as susceptibility factor in patients with idiopathic AA amyloidosis. Clinical, biochemical and genetic data were obtained from 146 patients with AA amyloidosis. Control groups comprised 40 patients with long-standing inflammatory diseases without AA amyloidosis and 56 controls without any inflammatory disease. Patients with AA amyloidosis had either familial Mediterranean fever (FMF) or long-standing rheumatic diseases as underlying inflammatory disease (n = 111, median age 46 years). However, in a significant proportion of patients with AA amyloidosis no primary disease was identified (idiopathic AA; n = 37, median age 60 years). Patients with idiopathic AA amyloidosis were more obese and older than patients with AA amyloidosis secondary to FMF or rheumatic diseases. Serum leptin levels correlated with the body mass index (BMI) in all types of AA amyloidosis. Elevated leptin levels of more than 30 µg/l were detected in 18% of FMF/rheumatic + AA amyloidosis and in 40% of patients with idiopathic AA amyloidosis (p = .018). Finally, the SAA1 polymorphism was confirmed as a susceptibility factor for AA amyloidosis irrespective of the type of the disease. Obesity, age and the SAA1 polymorphism are susceptibility factors for idiopathic AA amyloidosis. Recent advances in treatment of FMF and rheumatic disorders will decrease the incidence of AA amyloidosis due to these diseases. Idiopathic AA, however, might be an emerging problem in the ageing and increasingly obese population.

Placental villous hypermaturation is associated with idiopathic preterm birth

PubMed Central

Morgan, Terry K.; Tolosa, Jorge E.; Mele, Lisa; Wapner, Ronald J.; Spong, Catherine Y.; Sorokin, Yoram; Dudley, Donald J.; Peaceman, Alan M.; Mercer, Brian M.; Thorp, John M.; O’Sullivan, Mary Jo; Ramin, Susan M.; Rouse, Dwight J.; Sibai, Baha

2014-01-01

Objective Pregnancy complications such as intra-amniotic infection, preeclampsia, and fetal intrauterine growth restriction (IUGR) account for most cases of preterm birth (PTB), but many spontaneous PTB cases do not have a clear etiology. We hypothesize that placental insufficiency may be a potential cause of idiopathic PTB. Methods Secondary analysis of 82 placental samples from women with PTB obtained from a multicenter trial of repeat versus single antenatal corticosteroids. Samples were centrally reviewed by a single placental pathologist masked to clinical outcomes. The histopathologic criterion for infection was the presence of acute chorioamnionitis defined as neutrophils marginating into the chorionic plate. Placental villous hypermaturation (PVH) was defined as a predominance of terminal villi (similar to term placenta) with extensive syncytial knotting. Idiopathic PTB comprised a group without another known etiology such as preeclampsia, IUGR or infection. Results Acute chorioamnionitis was observed in 33/82 (40%) cases. Other known causes of PTB were reported in 18/82 (22%). The remaining 31/82 (38%) were idiopathic. The frequency of PVH in idiopathic PTB (26/31=84%) was similar to cases with IUGR or preeclampsia (16/ 18=89%), but significantly more common than PVH in the group with acute chorioamnionitis (10/33=30%) (p<0.001). Conclusions PVH, which is a histologic marker of relative placental insufficiency, is a common finding in idiopathic PTB. PMID:23130816

Allelic variation of the FRMD7 gene in congenital idiopathic nystagmus.

PubMed

Self, James E; Shawkat, Fatima; Malpas, Crispin T; Thomas, N Simon; Harris, Christopher M; Hodgkins, Peter R; Chen, Xiaoli; Trump, Dorothy; Lotery, Andrew J

2007-09-01

To perform a genotype-phenotype correlation study in an X-linked congenital idiopathic nystagmus pedigree (pedigree 1) and to assess the allelic variance of the FRMD7 gene in congenital idiopathic nystagmus. Subjects from pedigree 1 underwent detailed clinical examination including nystagmology. Screening of FRMD7 was undertaken in pedigree 1 and in 37 other congenital idiopathic nystagmus probands and controls. Direct sequencing confirmed sequence changes. X-inactivation studies were performed in pedigree 1. The nystagmus phenotype was extremely variable in pedigree 1. We identified 2 FRMD7 mutations. However, 80% of X-linked families and 96% of simplex cases showed no mutations. X-inactivation studies demonstrated no clear causal link between skewing and variable penetrance. We confirm profound phenotypic variation in X-linked congenital idiopathic nystagmus pedigrees. We demonstrate that other congenital nystagmus genes exist besides FRMD7. We show that the role of X inactivation in variable penetrance is unclear in congenital idiopathic nystagmus. Clinical Relevance We demonstrate that phenotypic variation of nystagmus occurs in families with FRMD7 mutations. While FRMD7 mutations may be found in some cases of X-linked congenital idiopathic nystagmus, the diagnostic yield is low. X-inactivation assays are unhelpful as a test for carrier status for this disease.

Association between cholesterol gallstones and testosterone replacement therapy in a patient with primary hypogonadism.

PubMed

Squarza, S; Rossi, U G; Torcia, P; Cariati, M

A 16-year-old boy had a past medical history of primary hypogonadism, due to bilateral anorchia. He presented with gallstones located in the gallbladder and a mild dilatation of the intrahepatic biliary tree. The histology study reported cholesterol gallstones. The patient had been treated with testosterone replacement therapy since infancy. We suggest a possible correlation between testosterone replacement therapy and the presence of cholesterol gallstones. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Study on Treatment with Respect to Idiopathic Scoliosis

NASA Astrophysics Data System (ADS)

Takeuchi, Kenzen; Azegami, Hideyuki; Murachi, Shunji; Kitoh, Junzoh; Ishida, Yoshito; Kawakami, Noriaki; Makino, Mitsunori

A hypothesis that the thoracic idiopathic scoliosis is buckling phenomenon of the fourth mode induced by the growth of thoracic vertebral bodies was presented in the previous work by the authors using numerical simulations with finite element model of the spine. If the hypothesis is acceptable, sensitivity function with respect to the critical growth of thoracic vertebrae on the maximization problem of buckling load with the fourth buckling mode gives us useful information to improve and develop treatments for the idiopathic scoliosis. The numerical results analyzed by the finite element method demonstrated that the sensitivity function is high at the articular capsules of the intervertebral joints, the intervertebral disks, the costotransverse joints and the constovertebral joints around the apex of the curvature in the case of the thoracic idiopathic scoliosis.

Idiopathic orbital inflammatory disease successfully treated with rituximab.

PubMed

Schafranski, Marcelo Derbli

2009-02-01

We report a case of a 66-year-old Caucasian female with a diagnosis of idiopathic orbital inflammatory disease (OID) refractory to azathioprine therapy. The coexistence of diabetes mellitus represented a relative contraindication to chronic prednisone use. After two infusions of rituximab, a chimeric anti-CD20+ antibody, ophthalmic signs and symptoms remarkably improved. To our knowledge, this is the first case of idiopathic OID successfully treated with rituximab.

Pathogenesis, Newly Recognized Etiologies, and Management of Idiopathic Anaphylaxis

PubMed Central

Kuhlen, James L.; Virkud, Yamini V.

2018-01-01

Idiopathic anaphylaxis (IA) is a life-threatening allergic disease and the most common diagnosis given to patients following an anaphylactic event. The inability of the healthcare provider and the patient to identify the trigger for anaphylaxis makes standard allergen avoidance measures ineffectual. IA is diagnosed after other causes of anaphylaxis have been excluded. Mast cell activation syndromes (MCAS), mastocytosis, IgE to galactose-alpha-1,3-galactose (α-gal), and certain medications have recently been recognized as causes of anaphylaxis that were previously labeled idiopathic. This review will describe the epidemiology and proposed theories of pathogenesis for IA, its diagnostic approach, its clinical management, and examine newly recognized disorders that were previously labeled as idiopathic anaphylaxis. PMID:25725228

Waist circumference is superior to weight and BMI in predicting sexual symptoms, voiding symptoms and psychosomatic symptoms in men with hypogonadism and erectile dysfunction.

PubMed

Yassin, A A; Nettleship, J E; Salman, M; Almehmadi, Y

2017-05-01

Waist circumference is considered a useful predictor of obesity-associated cardiovascular risk, but its use as an indicator of sexual health status and quality of life (QoL) in hypogonadal men is unknown. We investigated whether three measurements of obesity, weight, body mass index and waist circumference, correlate with the International Index of Erectile Function-5 (IIEF-5), the Aging Males' Symptoms (AMS) and the International Prostate Symptom Score (IPSS) questionnaires. A total of 261 patients were enrolled in a prospective study on hypogonadism treatment with intramuscular long-acting testosterone undecanoate. Patients with total testosterone ≤3.5 ng ml -1 were enrolled, and baseline demographic data were recorded. Patient's response to IIEF, IPSS and AMS standardised questionnaires was recorded to evaluate health-related QoL. The mean length of treatment and follow-up was 4.7 years (max 6 years). ANOVA regression analysis showed that waist circumference was significantly inversely proportional to IIEF-5 and directly proportional to AMS and IPSS. Weight was inversely proportional to IIEF and directly proportional to IPSS but not associated with AMS. BMI had no proportionality to measurements of sexual function and quality of life. These results suggest that among weight, BMI and waist circumference, the latter is the best predictor of health-related QoL in men with hypogonadism. © 2016 Blackwell Verlag GmbH.

Serum levels of enclomiphene and zuclomiphene in men with hypogonadism on long-term clomiphene citrate treatment.

PubMed

Helo, Sevann; Mahon, Joseph; Ellen, Joseph; Wiehle, Ron; Fontenot, Gregory; Hsu, Kuang; Feustel, Paul; Welliver, Charles; McCullough, Andrew

2017-01-01

To determine the relative concentrations of enclomiphene (ENC) and zuclomiphene (ZUC) isomers in men with hypogonadism on long-term clomiphene citrate (CC) therapy, and to determine whether patient age, body mass index (BMI) or duration of therapy were predictive of relative concentrations of ENC and ZUC. Men already receiving CC 25 mg daily therapy for secondary hypogonadism for a minimum of 6 weeks were recruited to have their ENC and ZUC levels assessed. Total testosterone, free testosterone, oestradiol, follicle stimulating hormone (FSH), and luteinizing hormone (LH) before initiation of and while on CC therapy were recorded for all patients. Patient demographics including age, BMI and medical comorbidites were recorded. Serum samples were obtained at the time of enrolment to determine ENC and ZUC concentrations. A total of 15 men were enrolled in the period from June 2015 to August 2015. The median (range) patient age was 36 (22-70) years, BMI 32.0 (21.1-40.3) kg/m 2 and duration of treatment 25.9 (1.7-86.6) months. Baseline median total testosterone, oestradiol and LH levels were 205.0 ng/dL, 17.0 pg/mL and 4.0 mlU/mL, respectively. The post-treatment median total testosterone, oestradiol and LH level increased to 488.0 ng/dL, 34.0 pg/mL and 6.1 mIU/mL, respectively (all P<0.001). The median ENC and ZUC concentrations were 2.2 and 44.0 ng/mL, respectively. After at least 6 weeks of CC therapy, the median ZUC: ENC serum concentration ratio was 20:1. On linear regression analysis. patient age, BMI, duration of treatment and serum testosterone levels were not predictive of ENC or ZUC concentrations. Long-term CC therapy resulted in a significant alteration of ENC and ZUC concentrations, with ZUC as the predominant isomer. Given the vastly different biochemical and toxicological properties of ENC and ZUC, this study supports the need for the development of a pure selective oestrogen receptor antagonist for the treatment of men with hypogonadism. © 2016 The

Short-term Assessment of HSCT Effects on the Hypothalamus-Pituitary Axis in Pediatric Thalassemic Patients.

PubMed

Hamidieh, Amir Ali; Mohseni, Fariba; Behfar, Maryam; Hamidi, Zohreh; Alimoghaddam, Kamran; Pajouhi, Mohamad; Larijani, Bagher; Mohajeri-Tehrani, Mohammad-Reza; Ghavamzadeh, Ardeshir

2018-02-01

Beta thalassemia major (BTM) and its treatment by hematopoietic stem cell transplantation (HSCT) may have deleterious effects on the endocrine systems. We assessed endocrine complications of HSCT in pediatric patients for 3 months. In 20 (6 female) pediatric major thalassemic patients (mean age of 10.8 ± 3.9 years old), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), T4, T3, thyroid-stimulating hormone (TSH), IGF-1, testosterone (in males) or estradiol (in females) were measured as a batch at the Endocrinology and Metabolism Research Center (EMRC) of Tehran University of Medical Sciences (TUMS) laboratories before HSCT and 1 and 3 months afterwards. The cosyntropin test for all and the clonidine test for short stature patients was conducted before HSCT. Before HSCT, delayed puberty and hypogonadotropic hypogonadism was found in 10% and 20% of patients, respectively. GH deficiency, low IGF1 and short stature was found in 25%, 55% and 40% of patients, respectively. Hypocortisolism, hypothyroidism and panhypopituitarism was found in 15%, 10% and 15% of patients, respectively. Prevalence of hypogonadotropic hypogonadism, low IGF1, hypothyroidism and panhypopituitarism was found in 20%, 40%, 10% and 10% of patients after 3 months, respectively (delayed puberty and short stature prevalence do not change after 3 months). HSCT caused lower T3 and estradiol and higher TSH. Corticosteroid users (15) had higher GH and lower T3 and testosterone or estradiol. Ferritin had a significant (negative) correlation with (before) prolactin and a significant correlation with T3 and T4 after HSCT. Age and acute graft-versus-host disease (GVHD) had no significant effect. Considering the small sample size and short duration of the study, it is difficult to reach any conclusion however it seems HSCT does not appear to have an overall positive or negative effect on prevalence of pituitary- hypothalamus axis disorders in pediatric thalassemic patients in 3 months. �

MR venography in idiopathic intracranial hypertension: unappreciated and misunderstood

PubMed Central

Higgins, J; Gillard, J; Owler, B; Harkness, K; Pickard, J

2004-01-01

Background: Venous sinus disease must be excluded before diagnosing idiopathic intracranial hypertension but is found only rarely in typical cases. Magnetic resonance venography (MRV) is the technique of choice for investigating this, and provides images that are diagnostic and easy to interpret. However, recent work using more invasive techniques has documented pressure gradients and stenoses in the lateral venous sinuses in many cases of idiopathic intracranial hypertension. Objective: To examine the reason for this discrepancy and to establish whether there are characteristic appearances on MRV in idiopathic intracranial hypertension that are routinely overlooked in clinical practice. Methods: MRVs from 20 patients with idiopathic intracranial hypertension were reviewed, unblinded, by two neuroradiologists, and their appearances rated for focal narrowings and signal gaps. A control group of 40 asymptomatic volunteers, matched for age and sex with the patient group, was recruited prospectively for MRV, and their scans rated in the same way. Results: The lateral sinuses presented a range of appearances with quite different distributions in the two groups (p<0.001). Bilateral lateral sinus flow gaps were seen in 13 of 20 patients with idiopathic intracranial hypertension and in none of 40 controls. Conclusions: A historical failure to use normal healthy controls to establish the boundaries between imaging artefact, normal anatomical variant, and disease means that the pathological significance of the different appearances of the lateral sinuses on MRV has not so far been appreciated. PMID:15026510

Management of hypogonadism in adolescent girls and adult women with Prader-Willi syndrome.

PubMed

Eldar-Geva, Talia; Hirsch, Harry J; Pollak, Yehuda; Benarroch, Fortu; Gross-Tsur, Varda

2013-12-01

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by an insatiable appetite, dysmorphic features, cognitive and behavioral difficulties, and hypogonadism. The heterogeneous reproductive hormone profiles indicate that some PWS women may have symptoms of hypoestrogenism, while others may potentially be fertile. We describe our experience in the assessment and treatment of hypogonadism in adolescents and adult females with PWS. The study population consisted of 20 PWS females, age ≥16 years (27.3 ± 7.9 years), followed in our clinic (12 deletion, 7 uniparental disomy, 1 imprinting-center defect). General physical examination, pubertal assessment, body mass index (BMI), gynecological examination, ultrasonography, bone densitometry, and hormonal profiles [FSH, LH, inhibin B, estradiol, prolactin, and TSH] were performed. The relevant assessed factors were: FSH and inhibin B, menstrual cycles (oligo/amenorrhea or irregular bleeding), ultrasound findings (endometrial thickness, uterine/ovarian abnormalities), BMI, bone densitometry, and patient/caregivers attitude. We classified seven women with inhibin B >20 ng/ml as potentially fertile. Following the assessment of the above factors, we recommended the individual-specific treatment; contraceptive pills, intra-uterine device, estrogen/progesterone replacement, and cyclic progesterone, in 3, 1, 4, and 1 patients, respectively. Four patients did not follow our recommendations due to poor compliance or family refusal. We recommended contraception pills for one 26-year-old woman with inhibin B and FSH levels 53 ng/ml and 6.4 IU/L; however, she refused treatment, conceived spontaneously and had an abortion. Guidelines for hormonal replacement therapy in PWS need to be tailored individually depending on physical development, hormonal profiles, bone density, and emotional and social needs of each PWS adolescent and adult. © 2013 Wiley Periodicals, Inc.

Idiopathic scrotal calcinosis.

PubMed

Celik, Orcun; Ipekci, Tumay; Kazimoglu, Hatem

2013-12-01

Idiopathic scrotal calcinosis is a rare scrotal benign disease. Its distinct features are painless, non-pruritic, semi-soft palpable calcific transdermal nodules. We report a 42-year-old-man with asymptomatic multiple calcified scrotal skin nodules for 10 years. Under spinal anesthesia, the affected scrotal skin was excised and the nodules removed. We aim to explain the etiology, pathophysiology, diagnosis, and treatment modalities of this rare disease.

A procedure to detect abnormal sensorimotor control in adolescents with idiopathic scoliosis.

PubMed

Pialasse, Jean-Philippe; Mercier, Pierre; Descarreaux, Martin; Simoneau, Martin

2017-09-01

This work identifies, among adolescents with idiopathic scoliosis, those demonstrating impaired sensorimotor control through a classification procedure comparing the amplitude of their vestibular-evoked postural responses. The sensorimotor control of healthy adolescents (n=17) and adolescents with idiopathic scoliosis (n=52) with either mild (Cobb angle≥15° and ≤30°) or severe (Cobb angle >30°) spine deformation was assessed through galvanic vestibular stimulation. A classification procedure sorted out adolescents with idiopathic scoliosis whether the amplitude of their vestibular-evoked postural response was dissimilar or similar to controls. Compared to controls, galvanic vestibular stimulation evoked larger postural response in adolescents with idiopathic scoliosis. Nonetheless, the classification procedure revealed that only 42.5% of all patients showed impaired sensorimotor control. Consequently, identifying patients with sensorimotor control impairment would allow to apply personalized treatments, help clinicians to establish prognosis and hopefully improve the condition of patients with adolescent idiopathic scoliosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Idiopathic hemifacial spasm responsive to zonisamide: a case report.

PubMed

Siniscalchi, Antonio; Gallelli, Luca; Palleria, Caterina; De Sarro, Giovambattista

2009-01-01

We describe a patient with idiopathic hemifacial spasm (HFS) that was responsive to zonisamide treatment. A 65-year-old woman presented with a 4-year history of left-sided HFS developing gradually, starting from the upper facial muscles. After several analyses, the diagnosis of idiopathic HFS was made, and the clonazepam treatment (0.5 mg every 8 hours) was started, without a complete remission of symptoms. Therefore, zonisamide (150 mg twice a day for a 6-week period) was added, with a complete resolution. The rechallenge with zonisamide after its dechallenge confirmed its effectiveness. During follow-up, the patient remained symptom-free, with no adverse drug reactions. We suggest that zonisamide could represent a useful therapeutic option in the treatment of idiopathic HFS.

[Secondary male hypogonadism induced by sellar space-occupying lesion: Clinical analysis of 22 cases].

PubMed

Lu, Hong-Lei; Wang, Tao; Xu, Hao; Chen, Li-Ping; Rao, Ke; Yang, Jun; Yuan, Hui-Xing; Liu, Ji-Hong

2016-08-01

To analyze the clinical characteristics of secondary male hypogonadism induced by sellar space-occupying lesion, explore its pathogenesis, and improve its diagnosis and treatment. We retrospectively analyzed the clinical data about 22 cases of secondary male hypogonadism induced by sellar space-occupying lesion, reviewed related literature, and investigated the clinical manifestation, etiological factors, and treatment methods of the disease. Hypogonadism developed in 10 of the patients before surgery and radiotherapy (group A) and in the other 12 after it (group B). The patients received endocrine therapy with Andriol (n=7) or hCG (n=15). The average diameter of the sellar space-occupying lesions was significantly longer in group A than in B (［2.35±0.71］ vs ［1.83±0.36］ cm, P<0.05) and the incidence rate of prolactinomas was markedly higher in the former than in the latter group (60% vs 0, P<0.01). The levels of lutein hormone (LH), follicle stimulating hormone (FSH) and testosterone (T) were remarkably decreased in group B after surgery and radiotherapy (P<0.01). Compared with the parameters obtained before endocrine therapy, all the patients showed significant increases after intervention with Andriol or hCG in the T level (［0.78±0.40］ vs ［2.71±0.70］ ng/ml with Andriol; ［0.93±0.44］ vs ［3.07±0.67］ ng/ml with hCG) and IIEF-5 score (5.00±2.61 vs 14.50±3.62 with Andriol; 5.36±1.82 vs 15.07±3.27 with hCG) (all P<0.01). The testis volume increased and pubic hair began to grow in those with hypoevolutism. The patients treated with hCG showed a significantly increased testis volume (P<0.01) and sperm was detected in 7 of them, whose baseline testis volume was markedly larger than those that failed to produce sperm (［11.5±2.3］ vs ［7.5±2.3］ ml, P<0.01). Those treated with Andriol exhibited no significant difference in the testis volume before and after intervention and produced no sperm, either. Hypothyroidism might be attributed

Idiopathic central diabetes Insipidus.

PubMed

Grace, Mary; Balachandran, Venu; Menon, Sooraj

2011-10-01

Idiopathic central diabetes insipidus (CDI) is a rare disorder characterized clinically by polyuria and polydipsia, and an abnormal urinary concentration without any identified etiology. We report a case of central diabetes insipidus in a 60-year-old lady in the absence of secondary causes like trauma, infection, and infiltrative disorders of brain.

Idiopathic thoracic transdural intravertebral spinal cord herniation

PubMed Central

Turel, Mazda K; Wewel, Joshua T; Kerolus, Mena G; O'Toole, John E

2017-01-01

Idiopathic spinal cord herniation is a rare and often missed cause of thoracic myelopathy. The clinical presentation and radiological appearance is inconsistent and commonly confused with a dorsal arachnoid cyst and often is a misdiagnosed entity. While ventral spinal cord herniation through a dural defect has been previously described, intravertebral herniation is a distinct entity and extremely rare. We present the case of a 70-year old man with idiopathic thoracic transdural intravertebral spinal cord herniation and discuss the clinico-radiological presentation, pathophysiology and operative management along with a review the literature of this unusual entity. PMID:29021685

Multiple idiopathic external apical root resorption: report of four cases.

PubMed

Cholia, S S; Wilson, P H R; Makdissi, J

2005-07-01

Multiple idiopathic external root resorption is an unusual condition that may present in a cervical or an apical form. In this article, we review the published literature relating to multiple idiopathic external apical root resorption and present four clinical cases. We consider the aetiology of this condition and discuss the various treatment options.

Orthodontic treatment in patient with idiopathic root resorption: a case report.

PubMed

Rey, Diego; Smit, Rosana Martínez; Gamboa, Liliana

2015-01-01

Multiple idiopathic external root resorption is a rare pathological condition usually detected as an incidental radiographic finding. External root resorption of permanent teeth is a multifactorial process related to several local and systemic factors. If an etiological factor cannot be identified for root resorption, the term "idiopathic" is applied. This report presents a case of multiple idiopathic apical root resorption. The condition was found in a young female patient seeking orthodontic treatment due to malocclusion. This kind of resorption starts apically and progresses coronally, causing a gradual shortening and rounding of the remaining root. Patients with this condition are not the ideal candidates for orthodontic treatment; however, the aim of this report is to describe an unusual case of idiopathic root resorption involving the entire dentition, and to present the orthodontic treatment of this patient. It describes the progress and completion of orthodontic therapy with satisfactory end results.

Prolonged Hypogonadism in Males Following Withdrawal from Anabolic-Androgenic Steroids: an Underrecognized Problem

PubMed Central

Kanayama, Gen; Hudson, James I.; DeLuca, James; Isaacs, Stephanie; Baggish, Aaron; Weiner, Rory; Bhasin, Shalender; Pope, Harrison G.

2015-01-01

Aims To assess the frequency and severity of hypogonadal symptoms in male long-term anabolic-androgenic steroid (AAS) misusers who have discontinued AAS use. Design Cross-sectional, naturalistic. Setting Outpatient facility. Participants Twenty-four male former long-term AAS users and 36 non-AAS-using weightlifters, recruited by advertisement in Massachusetts, USA. Five of the former users were currently receiving treatment with physiologic testosterone replacement, leaving 19 untreated users for the numerical comparisons below. Measurements The Structured Clinical Interview for DSM-IV, questions regarding history of AAS use, physical examination, serum hormone determinations, and the International Index of Erectile Function (IIEF). Findings Compared with the 36 non-AAS-using weightlifters, the 19 untreated former AAS users displayed significantly smaller testicular volumes (estimated difference [95% confidence interval (CI)]: 2.3 [0.1, 4.5] ml; p = 0.042) and lower serum testosterone levels (estimated difference: 131 [25, 227] dL; p = 0.009), with five users showing testosterone levels below 200 ng/dL despite abstinence from AAS for 3–26 months. Untreated former users also displayed significantly lower scores on the IIEF Sexual Desire subscale (estimated difference: 2.4 [1.3, 3.5] points on a 10-point scale; p < 0.001). In the overall group of 24 treated plus untreated former users, 7 (29%) had experienced major depressive episodes during AAS withdrawal; 4 of these had not experienced major depressive episodes at any other time. Two men (8%) had failed to regain normal libidinal or erectile function despite adequate replacement testosterone treatment. Conclusions Among long-term anabolic-androgenic steroid misusers, anabolic-androgenic steroid-withdrawal hypogonadism appears to be common, frequently prolonged, and associated with substantial morbidity. PMID:25598171

Disease of the year: juvenile idiopathic arthritis--differential diagnosis.

PubMed

Hu-Torres, Sandra; Foster, C Stephen

2014-02-01

The purpose of this review is to comprehensively explain the differential diagnosis of juvenile idiopathic arthritis-associated uveitis. Web-based literature review. Main diagnostic decisions are made through a thorough anterior segment exam and a comprehensive exploration of past medical and family history. High clinical suspicion of other uveitic entities occurring in children is necessary and must be excluded by the practitioner before immediate diagnosis of juvenile idiopathic arthritis is made.

[Osteoporosis fracture in a male patient secondary to hypogonadism due to androgen deprivation treatment for prostate cancer].

PubMed

Verdú Solans, J; Roig Grau, I; Almirall Banqué, C

2014-01-01

A 84 year-old patient, in therapy with androgen deprivation during the last 5 years due a prostate cancer, is presented with a osteoporotic fracture of the first lumbar vertebra. The pivotal role of the primary care physician, in the prevention of the osteoporosis secondary to the hypogonadism in these patients, is highlighted. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

[Coincidence of juvenile idiopathic arthritis and multiple sclerosis: case report].

PubMed

Puszczewicz, Mariusz J; Tuchocka-Piotrowska, Aleksandra; Majewski, Dominik; Kołczewska, Aleksandra

2006-01-01

Juvenile idiopathic arthritis is a systemic pathology of connective tissue characterized by a chronic inflammatory process with an autoimmune background whereas multiple sclerosis is a demyelination disease with an important role of immune disorders in its pathogenesis. The etiology in both cases remains unknown. The coincidence of juvenile idiopathic arthritis and multiple sclerosis was described a just a few patients. We now report on a 31-year-old woman with juvenile idiopathic arthritis and multiple sclerosis. In the present case, the main problem was to find the right proper medication for a very, aggressive course of multiple sclerosis and for arthritis. Treatment with interferon-beta and methylprednisolone led to remission with just minor side-effects.

Evidence for human leukocyte antigen-related susceptibility in idiopathic childhood ischemic stroke.

PubMed

Zou, Li-Ping; Guo, Yu-Hong; Fang, Fang; Jin, Hong; Wu, Hu-Sheng; Mix, Eilhard

2002-01-01

Stroke in children is a relatively uncommon condition and frequently associated with other diseases like cardiopathies, sickle cell disease and chronic smoking. In contrast to stroke in adults, it is rarely caused by atherosclerosis, hypertension or diabetes mellitus. Childhood stroke of unknown causes is called idiopathic stroke. The etiology of idiopathic stroke is unknown. However, several so-called idiopathic diseases develop on the basis of a genetic predisposition. As an approach to investigate this possibility in idiopathic childhood ischemic stroke, we studied the relationship between clinical and immunogenetic features in this disease. We demonstrate that the gene frequencies and relative risk of HLA-B51 were markedly increased in our patients compared with controls (p < 0.001). Thirteen of seventeen HLA-B51-positive patients had had a preceding respiratory infection, which was a higher proportion than in the control group (p < 0.05). In the patient group, the alleles HLA-DRB1*0802, -DRAI*0401 and -DQBI*0402 were also significantly increased, defining the haplotype DRB1*0802-DRA1*0401-DQB1*0402 as a high-risk haplotype for idiopathic childhood ischemic stroke. Transient viral or bacterial infections, which involve vasculitis and vascular occlusion in the brain, can trigger idiopathic childhood ischemic stroke on the basis of an genetic predisposition. Copyright 2002 S. Karger AG, Basel

Milia-like idiopathic calcinosis cutis in a child with Down syndrome.

PubMed

Kumar, Piyush; Savant, Sushil S; Nimisha, Esther; Das, Anupam; Debbarman, Panchami

2016-05-15

Idiopathic calcinosis cutis refers to progressive deposition of crystals of calcium phosphate in the skin and other areas of the body, in the absence of any inciting factor. Idiopathic calcinosis cutis may sometimes take the form of small, milia-like lesions. Most commonly, such milia like lesions are seen in the setting of Down syndrome. Herein, we report a 5-year-old girl with multiple asymptomatic discrete milia-like firm papules distributed over the face and extremities. A diagnosis of milia-like idiopathic calcinosis cutis associated with Down Syndrome was provisionally made and was confirmed by histopathology and karyotyping.

Bayesian comparative effectiveness study of four consensus treatment plans for initial management of systemic juvenile idiopathic arthritis: FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST).

PubMed

Nigrovic, Peter A; Beukelman, Timothy; Tomlinson, George; Feldman, Brian M; Schanberg, Laura E; Kimura, Yukiko

2018-06-01

Systemic juvenile idiopathic arthritis is a rare febrile arthritis of childhood characterized by a potentially severe course, including prolonged glucocorticoid exposure, growth failure, destructive arthritis, and life-threatening macrophage activation syndrome. Early cytokine-blocking biologic therapy may improve long-term outcomes, although some systemic juvenile idiopathic arthritis patients respond well to non-biologic treatment, leaving optimal management undefined. Consequently, treatment of new-onset systemic juvenile idiopathic arthritis by expert clinicians varies widely. To describe a pragmatic, observational comparative effectiveness study that takes advantage of diversity in the management of a rare disease: FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST), comparing non-biologic and biologic consensus treatment plans for new-onset systemic juvenile idiopathic arthritis within the 60-center Childhood Arthritis and Rheumatology Research Alliance Registry (CARRA). FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST) is a multicenter, prospective, non-randomized study that compares four Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus treatment plans for new-onset systemic juvenile idiopathic arthritis: (1) glucocorticoids alone, (2) methotrexate, (3) interleukin-1 blockade, and (4) interleukin-6 blockade. Patients consenting to participation in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry are started on one of four Consensus Treatment Plans at the discretion of the treating physician. The outcome of primary interest is clinically inactive disease off glucocorticoids at 9 months, comparing non-biologic (Consensus Treatment Plans 1 + 2) versus biologic (Consensus Treatment Plans 3 + 4) strategies. Bayesian analytic methods will be employed to evaluate response rates, using propensity scoring to balance treatment groups for potential

Hypogonadal Men with Higher Body Mass Index have Higher Bone Density and Better Bone Quality but Reduced Muscle Density.

PubMed

Aguirre, Lina E; Colleluori, Georgia; Dorin, Richard; Robbins, David; Chen, Rui; Jiang, Bryan; Qualls, Clifford; Villareal, Dennis T; Armamento-Villareal, Reina

2017-12-01

Although hypogonadism is a risk factor for bone loss and fractures, the different etiopathophysiology and hormonal profile of classical and obesity-induced hypogonadism may lead to differences in musculoskeletal profile. This is a cross-sectional study of hypogonadal men between 40 and 74 years old. Our outcomes include: areal bone mineral density (aBMD) and body composition by dual-energy X-ray absorptiometry; volumetric BMD (vBMD) and soft tissue composition of the tibia by peripheral quantitative computed tomography. Fracture risk assessment tool (FRAX) scores were evaluated. Testosterone, estradiol, luteinizing hormone, follicle stimulating hormone, sex hormone-binding globulin, C-telopeptide, osteocalcin, and sclerostin were measured. We divided the population into subgroups of BMI: group 1: BMI < 30; group 2: BMI ≥30 to <35 and group 3: BMI ≥ 35 kg/m 2 . One-hundred five men were enrolled. Spine and hip aBMD, and total and trabecular vBMD at the 4% tibia significantly increased with increasing BMI. Cortical thickness (330.7 ± 53.2, 343.3 ± 35.4, and 358.7 ± 38.2 mm, p = 0.04; groups 1, 2 and 3, respectively) and cortical area (5.3 ± 0.7, 5.5 ± 0.6, and 5.7 ± 0.6 mm, p = 0.01; groups 1, 2 and 3, respectively) at 38% tibia increased with increasing BMI. While absolute lean mass increased with increasing BMI, % lean mass and muscle density (70.2 ± 5.0, 71.3 ± 6.4, and 67.1 ± 5.1 mg/cm 3 ; groups 1, 2 and 3, respectively) were lowest in group 3. Although severely obese hypogondal men have better BMD and bone quality, they have reduced muscle density, the significance of which remains to be determined.

Idiopathic hypertrophic pachymeningitis presenting with occipital neuralgia.

PubMed

Auboire, Laurent; Boutemy, Jonathan; Constans, Jean Marc; Le Gallou, Thomas; Busson, Philippe; Bienvenu, Boris

2015-03-01

Although occipital neuralgia is usually caused by degenerative arthropathy, nearly 20 other aetiologies may lead to this condition. We present the first case report of hypertrophic pachymeningitis revealed by isolated occipital neuralgia. Idiopathic hypertrophic pachymeningitis is a plausible cause of occipital neuralgia and may present without cranial-nerve palsy. There is no consensus on the treatment for idiopathic hypertrophic pachymeningitis, but the usual approach is to start corticotherapy and then to add immunosuppressants. When occipital neuralgia is not clinically isolated or when a first-line treatment fails, another disease diagnosis should be considered. However, the cost effectiveness of extended investigations needs to be considered.

Sublingual testosterone replacement improves muscle mass and strength, decreases bone resorption, and increases bone formation markers in hypogonadal men--a clinical research center study.

PubMed

Wang, C; Eyre, D R; Clark, R; Kleinberg, D; Newman, C; Iranmanesh, A; Veldhuis, J; Dudley, R E; Berman, N; Davidson, T; Barstow, T J; Sinow, R; Alexander, G; Swerdloff, R S

1996-10-01

To study the effects of androgen replacement therapy on muscle mass and strength and bone turnover markers in hypogonadal men, we administered sublingual testosterone (T) cyclodextrin (SLT; 5 mg, three times daily) to 67 hypogonadal men (baseline serum T, < 8.4 nmol/L) recruited from 4 centers in the U.S.: Torrance (n = 34), Durham (n = 12), New York (n = 9), and Salem (n = 12). Subjects who had received prior T therapy were withdrawn from injections for at least 6 weeks and from oral therapy for 4 weeks. Body composition, muscle strength, and serum and urinary bone turnover markers were measured before and after 6 months of SLT. We have shown previously that this regimen for 60 days will maintain adequate serum T levels and restore sexual function. Total body (P = 0.0104) and lean body mass (P = 0.007) increased with SLT treatment in the 34 subjects in whom body composition was assessed. There was no significant change in total body fat or percent fat. The increase in lean body mass was mainly in the legs; the right leg lean mass increased from 8.9 +/- 0.3 kg at 0 months to 9.2 +/- 0.3 kg at 6 months (P = 0.0008). This increase in leg lean mass was associated with increased leg muscle strength, assessed by leg press (0 months, 139.0 +/- 4.0 kg; 6 months, 147.7 +/- 4.2 kg; P = 0.0038). SLT replacement in hypogonadal men led to small, but significant, decreases in serum Ca (P = 0.0029) and the urinary calcium/creatinine ratio (P = 0.0066), which were associated with increases in serum PTH (P = 0.0001). At baseline, the urinary type I collagen-cross linked N-telopeptides/creatinine ratio [75.6 +/- 7.9 nmol bone collagen equivalents (BCE/mmol] was twice the normal adult male mean (41.0 +/- 3.6 nmol BCE/mmol) and was significantly decreased in response to SLT treatment at 6 months (68.2 +/- 7.7 nmol BCE/mmol; P = 0.0304) without significant changes in urinary creatinine. Serum skeletal alkaline phosphatase did not change. In addition, SLT replacement caused significant

From bad to worse: when lung cancer complicates idiopathic pulmonary fibrosis.

PubMed

Strock, Stephen B; Alder, Jonathan K; Kass, Daniel J

2018-04-01

Patients with idiopathic pulmonary fibrosis have a significantly increased risk for the development of lung cancer. The morbidity and mortality of this disease combination are substantial, and, unfortunately, there are currently few data to help guide clinicians in its diagnosis and treatment. In a recent issue of this journal, Hwang et al presented one of the first studies to evaluate lung cancer in patients with idiopathic pulmonary fibrosis at the molecular level. They demonstrate variants in regulators of the cell cycle, which are known to be important in malignant transformation and may also be important in the pathogenesis of idiopathic pulmonary fibrosis. Further understanding of the pathogenic overlap between lung cancer and idiopathic pulmonary fibrosis could help point the direction to specific diagnostic modalities and targeted treatment of both conditions in the future. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Genetics Home Reference: idiopathic pulmonary fibrosis

MedlinePlus

... structures at the ends of chromosomes known as telomeres . It is not well understood how defects in ... Collard HR, Wolters PJ, Garcia CK. Effect of telomere length on survival in patients with idiopathic pulmonary ...

Radiographic and MRI characteristics of lumbar disseminated idiopathic spinal hyperostosis and spondylosis deformans in dogs.

PubMed

Togni, A; Kranenburg, H J C; Morgan, J P; Steffen, F

2014-07-01

To evaluate clinical signs, describe lesions and differences in the magnetic resonance imaging appearance of spinal new bone formations classified as disseminated idiopathic spinal hyperostosis and/or spondylosis deformans on radiographs and compare degeneration status of the intervertebral discs using the Pfirrmann scale. Retrospective analysis of 18 dogs presented with spinal disorders using information from radiographic and magnetic resonance imaging examinations. All dogs were found to be affected with both disseminated idiopathic spinal hyperostosis and spondylosis deformans. Neurological signs due to foraminal stenosis associated with disseminated idiopathic spinal hyperostosis were found in two dogs. Spondylosis deformans was associated with foraminal stenosis and/or disc protrusion in 15 cases. The Pfirrmann score on magnetic resonance imaging was significantly higher in spondylosis deformans compared with disseminated idiopathic spinal hyperostosis and signal intensity of new bone due to disseminated idiopathic spinal hyperostosis was significantly higher compared to spondylosis deformans. Differences between disseminated idiopathic spinal hyperostosis and spondylosis deformans found on magnetic resonance imaging contribute to an increased differentiation between the two entities. Clinically relevant lesions in association with disseminated idiopathic spinal hyperostosis were rare compared to those seen with spondylosis deformans. © 2014 British Small Animal Veterinary Association.

Giant scrotal elephantiasis: an idiopathic case.

PubMed

Dianzani, C; Gaspardini, F; Persichetti, P; Brunetti, B; Pizzuti, A; Margiotti, K; Degener, A M

2010-01-01

Scrotal elephantiasis is very rare disease in industrialized countries, where it is mainly due to surgery, irradiation or malignancies. It can be defined as idiopathic only when the possible congenital, infectious and compressive causes are excluded. We report a case of massive scrotal lymphoedema in an adult Caucasian patient, in Italy. He presented an extremely voluminous scrotal mass measuring 50 x 47 x 13 cm (weight 18 kg), which extended below his knees, invalidating all his daily activities. The patient was hospitalized in order to undergo to surgical treatment. Although genetic causes were searched and the possible role of infectious agents and compressive factors was evaluated, no etiology was ascertained. Histopathologic examination showed non-specific chronic inflammation, confirming the diagnosis of idiopathic elephantiasis. One year after surgical treatment, the patient is healthy without recurrence signs.

Idiopathic hypersomnia: a report of three adolescent-onset cases in a two-generation family.

PubMed

Janácková, Sona; Motte, Jacques; Bakchine, Serge; Sforza, Emilia

2011-04-01

Idiopathic hypersomnia is an uncommon sleep disorder characterized by prolonged sleep time and excessive daytime sleepiness without cataplexy. This study concerned a case of familial occurrence. The proband expressed an idiopathic hypersomnia with long sleep time at the age of 12 years. Clinical interview and ad libitum polysomnographic study did not reveal any symptoms of narcolepsy or other sleep disorders. Family history revealed that a 20-year-old sister had experienced symptoms of hypersomnia from the age of 16 and their mother had been diagnosed with idiopathic hypersomnia previously. The diagnosis of idiopathic hypersomnia with long sleep time was confirmed in the sister by clinical interview and ad libitum polysomnography. Human leukocyte antigen (HLA) did not reveal the DQB1-0602 phenotype in the proband and relatives. This report confirms the hypothesis of a genetic predisposition in idiopathic hypersomnia.

Screening for Adolescent Idiopathic Scoliosis: US Preventive Services Task Force Recommendation Statement.

PubMed

Grossman, David C; Curry, Susan J; Owens, Douglas K; Barry, Michael J; Davidson, Karina W; Doubeni, Chyke A; Epling, John W; Kemper, Alex R; Krist, Alex H; Kurth, Ann E; Landefeld, C Seth; Mangione, Carol M; Phipps, Maureen G; Silverstein, Michael; Simon, Melissa A; Tseng, Chien-Wen

2018-01-09

Adolescent idiopathic scoliosis, a lateral curvature of the spine of unknown cause with a Cobb angle of at least 10°, occurs in children and adolescents aged 10 to 18 years. Idiopathic scoliosis is the most common form and usually worsens during adolescence before skeletal maturity. Severe spinal curvature may be associated with adverse long-term health outcomes (eg, pulmonary disorders, disability, back pain, psychological effects, cosmetic issues, and reduced quality of life). Early identification and effective treatment of mild scoliosis could slow or stop curvature progression before skeletal maturity, thereby improving long-term outcomes in adulthood. To update the 2004 US Preventive Services Task Force (USPSTF) recommendation on screening for idiopathic scoliosis in asymptomatic adolescents. The USPSTF reviewed the evidence on the benefits and harms of screening for and treatment of adolescent idiopathic scoliosis. The USPSTF found no direct evidence on screening for adolescent idiopathic scoliosis and health outcomes and no evidence on the harms of screening. The USPSTF found inadequate evidence on treatment with exercise and surgery. It found adequate evidence that treatment with bracing may slow curvature progression in adolescents with mild or moderate curvature severity (Cobb angle <40° to 50°); however, evidence on the association between reduction in spinal curvature in adolescence and long-term health outcomes in adulthood is inadequate. The USPSTF found inadequate evidence on the harms of treatment. Therefore, the USPSTF concludes that the current evidence is insufficient and that the balance of benefits and harms of screening for adolescent idiopathic scoliosis cannot be determined. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for adolescent idiopathic scoliosis in children and adolescents aged 10 to 18 years. (I statement).

Electronic protocol of respiratory physical therapy in patients with idiopathic adolescent scoliosis.

PubMed

Cano, Danila Vieira Baldini; Malafaia, Osvaldo; Alves, Vera Lúcia dos Santos; Avanzi, Osmar; Pinto, José Simão de Paula

2011-01-01

To create a clinical database of respiratory function in patients with adolescent idiopathic scoliosis; computerize and store this clinical data through the use of a software; incorporate this electronic protocol to the SINPE© (Integrated Electronic Protocols System) and analyze a pilot project with interpretation of results. From the literature review a computerized data bank of clinical data of postural deviations was set up (master protocol). Upon completion of the master protocol a specific protocol of respiratory function in patients with adolescent idiopathic scoliosis was designed and a pilot project was conducted to collect and analyze data from ten patients. It was possible to create the master protocol of postural deviations and the specific protocol of respiratory function in patients with adolescent idiopathic scoliosis. The data collected in the pilot project was processed by the SINPE ANALYZER©, generating charts and statistics. The establishment of the clinical database of adolescent idiopathic scoliosis was possible. Computerization and storage of clinical data using the software were viable. The electronic protocol of adolescent idiopathic scoliosis could be incorporated into the SINPE© and its use in the pilot project was successful.

Periprosthetic Tissue Loss in Patients With Idiopathic Vitreous Inflammation After the Boston Keratoprosthesis.

PubMed

Grassi, Christina M; Cruzat, Andrea; Taniguchi, Elise V; Crnej, Alja; Colby, Kathryn A; Dohlman, Claes H; Chodosh, James

2015-11-01

Idiopathic vitritis is a poorly understood complication after Boston keratoprosthesis surgery with unclear etiology. We sought to determine whether an association exists between periprosthetic corneal tissue loss and the development of idiopathic vitritis in keratoprosthesis recipients. Thirteen Boston type I keratoprosthesis recipient eyes with a history of idiopathic vitritis and 34 type I keratoprosthesis recipient eyes with no history of idiopathic vitritis underwent anterior segment optical coherence tomography (AS-OCT) at a median time postoperatively of 2.4 years versus 1.9 years (range, 0.5-14.2 vs. 0.1-13.6 years), respectively. Areas of corneal graft tissue loss ("gaps") around the keratoprosthesis stem were identified and analyzed by 2 masked observers. The difference in the presence, number, and size of gaps was compared between cases and controls. A periprosthetic gap was identified more commonly in idiopathic vitritis cases than in controls on AS-OCT (11/13, 86% vs. 11/34, 33.3%, P < 0.001). The number of gaps between cases and controls was also significantly different (2.6 ± 1.6 vs. 0.5 ± 0.8, P < 0.001), but not the estimated gap area (0.056 ± 0.049 mm² vs. 0.039 ± 0.025 mm², P = 0.22). A significantly higher proportion of keratoprosthesis recipient eyes with idiopathic vitritis had corneal tissue loss around the keratoprosthesis stem than did controls. Tissue loss could serve as an entry point for debris or bacterial components, triggering idiopathic vitritis. Our study underscores the utility of AS-OCT imaging in the postoperative management of keratoprosthesis patients.

Debate: idiopathic short stature should be treated with growth hormone.

PubMed

Ambler, Geoffrey R; Fairchild, Jan; Wilkinson, Dominic J C

2013-03-01

In this paper we outline the case for and against the treatment of idiopathic short stature with growth hormone. Drs Ambler and Fairchild argue that many of those with 'idiopathic' short stature are not 'short, normal children' and will ultimately receive molecular diagnoses. They also argue that there is a subset of children who suffer negative psychosocial consequences of their stature for whom growth hormone therapy is effective. Growth hormone has a very good safety record and is likely to be as cost-effective in idiopathic short-stature as in some other conditions that are currently funded. Dr Wilkinson counters that short stature is not associated with physical or psychological illness, and that there is no evidence that growth hormone improves psychological or physical wellbeing. Moreover, growth hormone for idiopathic short stature represents a form of enhancement rather than treatment, and is not a fair use of resources. Socially mediated disadvantage should be treated by attention to prejudice and not by hormone treatment. © 2012 The Authors. Journal of Paediatrics and Child Health © 2012 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Pelvic confined idiopathic retroperitoneal fibrosis mimicking a large tumor.

PubMed

Salemis, N S; Tsiambas, E; Tsohataridis, E

2009-01-01

Idiopathic retroperitoneal fibrosis (IRF) entirely confined to the pelvic cavity is an extremely rare clinical entity. Herein, is described the case of a 36- year old male who presented with clinical and imaging manifestations of a large pelvic tumor. Exploratory laparotomy revealed a large mass in the right pelvis originating from the retroperitoneal space, displacing the right iliac vessels, the right ureter and the urinary bladder completely to the left. A laborious resection of the mass measuring 14 x 10cm was performed. Histopathological examination and detailed immunohistochemistry analysis were suggestive of idiopathic retroperitoneal fibrosis with no evidence of malignancy. This is a very rare case regarding localization and clinical presentation of idiopathic retroperitoneal fibrosis. We conclude that IRF should be included in the differential diagnosis of patients presenting with a pelvic mass even if there is no involvement of the typical para aortic area.

Locomotor skills and balance strategies in adolescents idiopathic scoliosis.

PubMed

Mallau, Sophie; Bollini, Gérard; Jouve, Jean-Luc; Assaiante, Christine

2007-01-01

Locomotor balance control assessment was performed to study the effect of idiopathic scoliosis on head-trunk coordination in 17 patients with adolescent idiopathic scoliosis (AIS) and 16 control subjects. The aim of this study was to explore the functional effects of structural spinal deformations like idiopathic scoliosis on the balance strategies used during locomotion. Up to now, the repercussion of the idiopathic scoliosis on head-trunk coordination and balance strategies during locomotion is relatively unknown. Seventeen patients with AIS (mean age 14 years 3 months, 10 degrees < Cobb angle > 30 degrees) and 16 control subjects (mean age 14 years 1 month) were tested during various locomotor tasks: walking on the ground, walking on a line, and walking on a beam. Balance control was examined in terms of rotation about the vertical axis (yaw) and on a frontal plane (roll). Kinematics of foot, pelvis, trunk, shoulder, and head rotations were measured with an automatic optical TV image processor in order to calculate angular dispersions and segmental stabilizations. Decreasing the walking speed is the main adaptive strategy used in response to balance problems in control subjects as well as patients with AIS. However, patients with AIS performed walking tasks more slowly than normal subjects (around 15%). Moreover, the pelvic stabilization is preserved, despite the structural changes affecting the spine. Lastly, the biomechanical defect resulting from idiopathic scoliosis mainly affects the yaw head stabilization during locomotion. Patients with AIS show substantial similarities with control subjects in adaptive strategies relative to locomotor velocity as well as balance control based on segmental stabilization. In contrast, the loss of the yaw head stabilization strategies, mainly based on the use of vestibular information, probably reflects the presence of vestibular deficits in the patients with AIS.

Fluid Distribution Pattern in Adult-Onset Congenital, Idiopathic, and Secondary Normal-Pressure Hydrocephalus: Implications for Clinical Care.

PubMed

Yamada, Shigeki; Ishikawa, Masatsune; Yamamoto, Kazuo

2017-01-01

In spite of growing evidence of idiopathic normal-pressure hydrocephalus (NPH), a viewpoint about clinical care for idiopathic NPH is still controversial. A continuous divergence of viewpoints might be due to confusing classifications of idiopathic and adult-onset congenital NPH. To elucidate the classification of NPH, we propose that adult-onset congenital NPH should be explicitly distinguished from idiopathic and secondary NPH. On the basis of conventional CT scan or MRI, idiopathic NPH was defined as narrow sulci at the high convexity in concurrent with enlargement of the ventricles, basal cistern and Sylvian fissure, whereas adult-onset congenital NPH was defined as huge ventricles without high-convexity tightness. We compared clinical characteristics and cerebrospinal fluid distribution among 85 patients diagnosed with idiopathic NPH, 17 patients with secondary NPH, and 7 patients with adult-onset congenital NPH. All patients underwent 3-T MRI examinations and tap-tests. The volumes of ventricles and subarachnoid spaces were measured using a 3D workstation based on T2-weighted 3D sequences. The mean intracranial volume for the patients with adult-onset congenital NPH was almost 100 mL larger than the volumes for patients with idiopathic and secondary NPH. Compared with the patients with idiopathic or secondary NPH, patients with adult-onset congenital NPH exhibited larger ventricles but normal sized subarachnoid spaces. The mean volume ratio of the high-convexity subarachnoid space was significantly less in idiopathic NPH than in adult-onset congenital NPH, whereas the mean volume ratio of the basal cistern and Sylvian fissure in idiopathic NPH was >2 times larger than that in adult-onset congenital NPH. The symptoms of gait disturbance, cognitive impairment, and urinary incontinence in patients with adult-onset congenital NPH tended to progress more slowly compared to their progress in patients with idiopathic NPH. Cerebrospinal fluid distributions and

Idiopathic pulmonary fibrosis: evolving concepts.

PubMed

Ryu, Jay H; Moua, Teng; Daniels, Craig E; Hartman, Thomas E; Yi, Eunhee S; Utz, James P; Limper, Andrew H

2014-08-01

Idiopathic pulmonary fibrosis (IPF) occurs predominantly in middle-aged and older adults and accounts for 20% to 30% of interstitial lung diseases. It is usually progressive, resulting in respiratory failure and death. Diagnostic criteria for IPF have evolved over the years, and IPF is currently defined as a disease characterized by the histopathologic pattern of usual interstitial pneumonia occurring in the absence of an identifiable cause of lung injury. Understanding of the pathogenesis of IPF has shifted away from chronic inflammation and toward dysregulated fibroproliferative repair in response to alveolar epithelial injury. Idiopathic pulmonary fibrosis is likely a heterogeneous disorder caused by various interactions between genetic components and environmental exposures. High-resolution computed tomography can be diagnostic in the presence of typical findings such as bilateral reticular opacities associated with traction bronchiectasis/bronchiolectasis in a predominantly basal and subpleural distribution, along with subpleural honeycombing. In other circumstances, a surgical lung biopsy may be needed. The clinical course of IPF can be unpredictable and may be punctuated by acute deteriorations (acute exacerbation). Although progress continues in unraveling the mechanisms of IPF, effective therapy has remained elusive. Thus, clinicians and patients need to reach informed decisions regarding management options including lung transplant. The findings in this review were based on a literature search of PubMed using the search terms idiopathic pulmonary fibrosis and usual interstitial pneumonia, limited to human studies in the English language published from January 1, 2000, through December 31, 2013, and supplemented by key references published before the year 2000. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

[Physiopathology of idiopathic hypersomnia. Current studies and new orientations].

PubMed

Billiard, M; Rondouin, G; Espa, F; Dauvilliers, Y; Besset, A

2001-11-01

In 1976 Bedrich Roth coined the term "idiopathic hypersomnia" and described two forms of the disease, one monosymptomatic, manifested only by excessive daytime sleepiness, and one polysymptomatic, characterized by excessive daytime sleepiness, nocturnal sleep of abnormally long duration and signs of "sleep drunkenness" on awakening. In comparison with that of narcolepsy, the pathophysiology of idiopathic hypersomnia remains poorly known. There are two main reasons for that: the absence of clinical and polysomnographic criteria pathognomonic or at least characteristic of the condition, as the cataplexies and the sleep onset REM periods of narcolepsy, and also the absence of a natural animal model comparable with the canine model of narcolepsy. The first investigations have stressed the frequent familial pattern of idiopathic hypersomnia. Later on biochemical assays have been performed in the CSF with results in favour of a dysfunction of noradrenergic systems. In the light of the two process model of sleep regulation in which sleep propensity is determined by a homeostatic process S and a circadian process C and of the later three-process model of regulation in which sleepiness/alertness are simulated by the combined action of a homeostatic process, a circadian process and sleep inertia, we suggest that idiopathic hypersomnia is not a pathological entity in itself, but rather the consequence of chronic sleep deprivation in very long sleepers.

PCSK1 Mutations and Human Endocrinopathies: From Obesity to Gastrointestinal Disorders.

PubMed

Stijnen, Pieter; Ramos-Molina, Bruno; O'Rahilly, Stephen; Creemers, John W M

2016-08-01

Prohormone convertase 1/3, encoded by the PCSK1 gene, is a serine endoprotease that is involved in the processing of a variety of proneuropeptides and prohormones. Humans who are homozygous or compound heterozygous for loss-of-function mutations in PCSK1 exhibit a variable and pleiotropic syndrome consisting of some or all of the following: obesity, malabsorptive diarrhea, hypogonadotropic hypogonadism, altered thyroid and adrenal function, and impaired regulation of plasma glucose levels in association with elevated circulating proinsulin-to-insulin ratio. Recently, more common variants in the PCSK1 gene have been found to be associated with alterations in body mass index, increased circulating proinsulin levels, and defects in glucose homeostasis. This review provides an overview of the endocrinopathies and other disorders observed in prohormone convertase 1/3-deficient patients, discusses the possible biochemical basis for these manifestations of the disease, and proposes a model whereby certain missense mutations in PCSK1 may result in proteins with a dominant negative action.

De morseir syndrome presenting as ambiguous genitalia.

PubMed

Thukral, Anubhav; Chitra, S; Chakraborty, Partho P; Roy, Ajitesh; Goswami, Soumik; Bhattacharjee, Rana; Dutta, Deep; Maisnam, Indira; Ghosh, Sujoy; Mukherjee, Satinath; Chowdhury, Subhankar

2012-12-01

A 10-year-old boy presented with genital ambiguity, poor linear growth, and delayed milestones. The aim and to highlight that although rare but congenital, hypogonadotropic hypogonadism may rarely present as ambiguity. The patient was found to have bilateral cryptorchidism with proximal penile hypospadias, microphallus with a proportionate dwarfism with mildly delayed bone age, and karyotype 46XY. Euthyroid with normal steroid axis, growth hormone insufficient as suggested by auxology, low IGF1, and poor response to clonidine stimulation. MRI brain shows hypoplastic corpus callosum, hypoplastic anterior pituitary, and ectopic posterior pituitary bright spot. The patient underwent laparoscopic removal of right intrabdominal testis and orchidoplexy was performed on the left one. Testicular biopsy revealed no malignancy and growth hormone replacement was initiated. The patient awaits definitive repair of hypospadias. As a provisional diagnosis of combined growth hormone and gonadotropin deficiency, most probable diagnosis is septo-optic dysplasia or de moseir syndrome leading to genital ambiguity.

Restoration and maintenance of spermatogenesis by HCG therapy in patients with hypothalamo-hypophyseal damage.

PubMed

Levalle, O; Bokser, L; Pacenza, N; Aszenmil, G; Fiszlejder, L; Chervin, A; Guitelman, A

1984-01-01

Both gonadotropins are necessary to induce spermatogenesis in man and to recover hypophysectomized males. The patients who suffer from tumoral or traumatic hypothalamo-hypophyseal lesion use to have low endogenous gonadotropins (opposite to hypophysectomized patients), which can produce a minor involution of spermatogenesis. Three patients with postpubertal hypogonadotropic hypogonadism and oligozoospermia were studied. Two of them were operated on for chromophobous adenoma of pituitary, and the other patient had traumatic hypothalamo-hypophyseal lesion. The three patients were treated with 5000 IU HCG/week, associated with testosterone enanthate, in two cases and with bromocryptine in the remaining one. All the patients had normalized spermiogram, but when HCG was interrupted, the sperm count regressed to pretreatment levels in spite of the maintenance of treatment with testosterone or bromocryptine. Minimal amounts of FSH together the testosterone supplied by Leydig cell under the HCG stimulus, are able to recover and maintain the spermatogenesis in these patients.

Prevalence of hypothalamo pituitary dysfunction in patients of traumatic brain injury.

PubMed

Hari Kumar, K V S; Swamy, M N; Khan, M A

2016-01-01

Traumatic brain injury (TBI) is common in young soldiers of armed forces leading to significant morbidity and mortality. We studied the prevalence of hypopituitarism following TBI and its association with trauma severity. We conducted a 12-month prospective study of 56 TBI patients for the presence of hormonal dysfunction. Hormonal parameters were estimated during the early phase (0-10 days posttraumatically) and after 6 and 12 months. Dynamic testing was done when required, and the results were analyzed by appropriate statistical methods. Hormonal dysfunction was seen in 39 of the 56 (70%) patients at initial assessment. Persisting pituitary deficiencies are seen in 7 and 8 patients at the end of 6 months and 12 months, respectively. Hypogonadotropic hypogonadism, hypothyroidism, and growth hormone deficiency are the most common diagnoses. Initial severe TBI and plurihormonal involvement predicted the long-term hypopituitarism. Early hypopituitarism was common in severe TBI, but recovers in majority. Evaluation for the occult pituitary dysfunction is required during the rehabilitation of TBI patients.

[Hepatomegaly due to glycogen storage disease and type 1 diabetes mellitus].

PubMed

Flotats Bastardas, M; Miserachs Barba, M; Ricart Cumeras, A; Clemente León, M; Gussinyer Canadell, M; Yeste Fernández, D; Albisu Aparicio, María A; Carrascosa Lezcano, A

2007-08-01

Patients with type 1 diabetes and poor metabolic control can develop hepatomegaly due to intrahepatic glycogen deposition. If these patients also have elevated liver enzymes, dyslipidemia, cushingoid features and delayed growth or sexual maturation, Mauriac syndrome can be diagnosed. This disorder is common and reversible with optimization of insulin therapy. We report three adolescents with type 1 diabetes and a long-standing history of poor glycemic control, who developed hepatomegaly, elevated liver enzymes and dyslipidemia with preserved liver function. One of these patients also had delayed growth and another had hypogonadotropic hypogonadism. Liver ultrasound showed changes suggestive of glycogenosis. In all three patients, optimization of insulin therapy achieved good glycemic control and reversed the manifestations within 2 weeks. The etiology of Mauriac syndrome is controversial since both prolonged hyperglycemia and hyperinsulinization produce glycogen accumulation in the liver. Hypercortisolism (due to ketosis or hypoglycemia) contributes to glycogen storage and also causes growth and sexual maturation delay.

A rare de novo interstitial duplication of 15q15.3q21.2 in a boy with severe short stature, hypogonadism, global developmental delay and intellectual disability.

PubMed

Yuan, Haiming; Meng, Zhe; Zhang, Lina; Luo, Xiangyang; Liu, Liping; Chen, Mengfan; Li, Xinwei; Zhao, Weiwei; Liang, Liyang

2016-01-01

Interstitial duplications distal to 15q13 are very rare. Here, we reported a 14-year-old boy with severe short stature, delayed bone age, hypogonadism, global developmental delay and intellectual disability. His had distinctive facial features including macrocephaly, broad forehead, deep-set and widely spaced eyes, broad nose bridge, shallow philtrum and thick lips. A de novo 6.4 Mb interstitial duplication of 15q15.3q21.2 was detected by chromosomal microarray analysis. We compared our patient's clinical phenotypes with those of several individuals with overlapping duplications and several candidate genes responsible for the phenotypes were identified as well. The results suggest a novel contiguous gene duplication syndrome characterized with shared features including short stature, hypogonadism, global developmental delay and other congenital anomalies.

Interventional Radiologic Treatment for Idiopathic Portal Hypertension

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hirota, Shozo; Ichikawa, Satoshi; Matsumoto, Shinichi

1999-07-15

Purpose: To evaluate the usefulness of interventional radiological treatment for idiopathic portal hypertension. Methods: Between 1995 and 1998, we performed an interventional radiological treatment in five patients with idiopathic portal hypertension, four of whom had refused surgery and one of whom had undergone surgery. Three patients with gastroesophageal varices (GEV) were treated by partial splenic embolization (PSE), one patient with esophageal varices (EV) and massive ascites by transjugular intrahepatic portosytemic shunt (TIPS) and PSE, and one patient with GEV by percutaneous transhepatic obliteration (PTO). Midterm results were analyzed in terms of the effect on esophageal and/or gastric varices. Results: Inmore » one woman with severe GEV who underwent three sessions of PSE, there was endoscopic confirmation that the GEV had disappeared. In one man his EV shrunk markedly after two sessions of PSE. In two patients slight reduction of the EV was obtained with one application of PSE combined with endoscopic variceal ligation therapy. PTO for GV in one patient resulted in good control of the varices. All patients have survived for 16-42 months since the first interventional treatment, and varices are well controlled. Conclusion: Interventional radiological treatment is effective for patients with idiopathic portal hypertension, whether or not they have undergone surgery.« less

Influence of the hypothalamic-pituitary-adrenal axis dysregulation on the metabolic profile of patients affected by diabetes mellitus-associated late onset hypogonadism.

PubMed

Tirabassi, G; Chelli, F M; Ciommi, M; Lenzi, A; Balercia, G

2016-01-01

Functional hypercortisolism (FH) is generated by clinical states able to chronically activate the hypothalamic-pituitary-adrenal (HPA) axis [e.g. diabetes mellitus (DM)]. No study has evaluated FH influence in worsening the metabolic profile of male patients affected by DM-associated hypogonadism. In this retrospective work, we assess the possible association between HPA axis-dysregulation and cardiovascular risk factors in men simultaneously affected by DM and late-onset hypogonadism (LOH). Fourteen DM and LOH subjects affected by FH (Hypercort-DM-LOH) and fourteen DM and LOH subjects who were not suffering from FH (Normocort-DM-LOH) were retrospectively considered. Clinical, hormonal and metabolic parameters were retrieved. All metabolic parameters, except for systolic blood pressure, were significantly worse in Hypercort-DM-LOH than in Normocort-DM-LOH. After adjustment for body mass index, waist and total testosterone, Hypercort-DM-LOH subjects showed significantly worse metabolic parameters than Normocort-DM-LOH ones. In Normocort-DM-LOH, no significant correlation between general/hormonal parameters and metabolic variables was present. In Hypercort-DM-LOH, positive and significant correlations of cortisol area under the curve (AUC) after corticotropin releasing hormone with glycemia, triglycerides and blood pressure were evident; on the other hand, negative and significant correlation was present between cortisol AUC and high density lipoprotein (HDL) cholesterol. The associations of AUC cortisol with glycemia, HDL cholesterol and diastolic blood pressure (DBP) were further confirmed at quantile regression after adjustment for therapy. FH may determine a worsening of the metabolic profile in DM-associated hypogonadism. Copyright © 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by