Male and Female Hypogonadisms: Etiological, Metabolic and Osteodensitometric Aspects

Introduction: Studies showed a high prevalence of metabolic abnormalities including dyslipidemia, type 2 diabetes in cases of low testosterone in men and which are associated with increased cardiovascular risk. Hypogonadism represents the second cause of endocrine osteoporosis. Objectives: The objectives of our work were: to determine the main causes of hypogonadism in women and men;to assess the frequency of metabolic and osteosdensitometric abnormalities in the hypogonadal population. Patients and methods: A retrospective descriptive study was carried out over 7 years on 120 patients, hospitalized in the Endocrinology department of the Hassan II University Hospital of Fez-Morocco for hypogonadism. The patients selected were those who had symptoms of hypogonadism confirmed in men by: low total testosterone for Tanner stage in adolescents, ng/ml or lower limit of normal for adults;in women, hypoestrogenia 30 pg/l. Gonadotropin dosage, karyotype, pelvic or testicular ultrasound and pituitary MRI, for etiological diagnosis, were performed. Bone densitometry was performed for bone impact and lipid profile for metabolic profile. Results: Out of 120 patients, there were 77 women and 43 men. The average age was 31.51 years. In men, the main causes were central hypogonadism in 67.4% and primary testicular failure in 32.6%. In women, central hypogonadism was also the most common cause noted in 63.7% and premature ovarian failure was observed in 36.4%. HypoHDL was significantly more frequent p (0.005) in women, osteopenia and osteoporosis were significantly more frequent in women than in men p (0.046). Conclusion: Central causes represent the most common etiology of hypogonadism in both sexes;abnormalities of bone mineralization and metabolic disorders were predominant in women.

Hypergonadotrophic Hypogonadism with Cerebellar Ataxia in a Twenty-Six-Year-Old Female: A Case Report

Gordon Holmes Syndrome is a rare inherited disease characterized by both neurological and reproductive signs and symptoms. Most patients develop neurologic challenges in early adulthood and cerebellar ataxia occurs as the disease progresses. In the majority of patients, hypogonadism is hypogonadotropic but rarely hypergonadotropic. We report a case of a 26-year-old female in Nigeria, with hypergonadotropic hypogonadism and cerebellar atrophy from a non-consanguineous marriage and no family history.

Management of male obesity-related secondary hypogonadism:A clinical update

The global obesity pandemic has resulted in a rise in the prevalence of male obesity-related secondary hypogonadism(MOSH)with emerging evidence on the role of testosterone therapy.We aim to provide an updated and practical approach towards its management.We did a comprehensive literature search across MEDLINE(via PubMed),Scopus,and Google Scholar databases using the keywords“MOSH”OR“Obesity-related hypogonadism”OR“Testosterone replacement therapy”OR“Selective estrogen receptor modulator”OR“SERM”OR“Guidelines on male hypogonadism”as well as a manual search of references within the articles.A narrative review based on available evidence,recommendations and their practical implications was done.Although weight loss is the ideal therapeutic strategy for patients with MOSH,achievement of significant weight reduction is usually difficult with lifestyle changes alone in real-world practice.Therefore,androgen administration is often necessary in the management of hypogonadism in patients with MOSH which also improves many other comorbidities related to obesity.However,there is conflicting evidence for the appropriate use of testosterone replacement therapy(TRT),and it can also be associated with complications.This evidence-based review updates the available evidence including the very recently published results of the TRAVERSE trial and provides comprehensive clinical practice pearls for the management of patients with MOSH.Before starting testosterone replacement in functional hypogonadism of obesity,it would be desirable to initiate lifestyle modification to ensure weight reduction.TRT should be coupled with the management of other comorbidities related to obesity in MOSH patients.Balancing the risks and benefits of TRT should be considered in every patient before and during longterm management.

Late-onset hypogonadism： current concepts and controversies of pathogenesis, diagnosis and treatment

Although suppressed serum testosterone （T） is common in ageing men, only a small proportion of them develop the genuine syndrome of low T associated with diffuse sexual （e.g., erectile dysfunction）, physical （e.g. loss of vigor and frailty） and psychological （e.g., depression） symptoms. This syndrome carries many names, including male menopause or climacterium, andropause and partial androgen deficiency of the ageing male （PADAM）. Late-onset hypogonadism （LOH） describes it best and is therefore generally preferred. The decrease of T in LOH is often marginal, and hypogonadism can be either due to primary testicular failure （low T, high luteinizing hormone （LH）） or secondary to a hypothalamic-pituitary failure （low T, low or inappropriately normal LH）. The latter form is more common and it is usually associated with overweight/obesity or chronic diseases （e.g., type 2 diabetes mellitus, the metabolic syndrome, cardiovascular and chronic obstructive pulmonary disease, and frailty）. A problem with the diagnosis of LOH is that often the symptoms （in 20%-40% of unselected men） and low circulating T （in 20% of men 〉70 years of age） do not coincide in the same individual. The European Male Ageing Study （EMAS） has recently defined the strict diagnostic criteria for LOH to include the simultaneous presence of reproducibly low serum T （total T 〈11 nmol 1-1 and free T 〈220 pmol 1-1） and three sexual symptoms （erectile dysfunction, and reduced frequency of sexual thoughts and morning erections）. By these criteria, only 2% of 40- to 80-year-old men have LOH. In particular obesity, but also impaired general health, are more common causes of low T than chronological age per se. Evidence-based information whether, and how, LOH should be treated is sparse. The most logical approach is lifestyle modification, weight reduction and good treatment of comorbid diseases. T replacement is widely used for the treatment, but evidence-based information about its real benefits and short- and long-term risks, is not yet available. In this review, we will summarize the current conceets and controversies in the Dathogenesis, diagnosis and treatment of LOH.

Survey for late-onset hypogonadism among old anti middle-aged males in Shanghai communities

This study sought to investigate late-onset hypogonadism （LOH） in old and middle-aged males in Shanghai communities, using symptom score evaluation systems and measurements of sex hormone levels. One thousand cases of males aged 40-70 years were investigated. The aging male symptoms （AMS） scale and androgen deficiency in aging males （ADAM） questionnaire were used at the beginning of the investigation, followed by measurement of the sex hormone-related factors （total testosterone （TT）, free testosterone （fT）, sex hormone-binding globulin （SHBG） and bioavailability of testosterone （Bio-T））. There were 977 valid questionnaires. The LOH-positive rates shown by AMS and ADAM were 59.88% and 84.65%, respectively; values increased with the age of the patients. There were 946 results related to sex hormone measurements, which showed the following results： TT was not related to aging （P〉O.05）; levels of SHBG increased with age; and fT and Bio-T decreased with age. There was a significant difference in fT between LOH-positive and LOH-negative patients, as shown by the ADAM. In summary, TT levels were not related to aging, even though SHBG did increase while fT and Bio-T decreased with aging. Clinically, the diagnosis of LOH cannot be based on serum TT level.

New understandings of the genetic basis of isolated diopathic central hypogonadism

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 ~s 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 （nlCH）, 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.

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

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.

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

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.

Molecular analysis of KAL-1 in a series of Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism patients from Northwestern China

We conducted an analysis of the Kallmann syndrome 1 （KAL-1） genotype in 17 patients with Kallmann syndrome （KS）, 9 patients with normosmic idiopathic hypogonadotropic hypogonadism （nlHH） and 20 age-matched normal men in Northwestern China. To do this, we used multiplex PCR analysis with exon-flanking primers and automated sequencing techniques with peripheral blood DNA samples. Intragenic deletions were found at the KAL-1 locus in two KS patients. One case with an atrial septal defect exhibited an intragenic deletion of exon 6. Another KS patient with cryptorchidism had intragenic deletions of exons 5 and 6. For the nlHH patients, no abnormalities were observed in the exonic and flanking sequences of KAL-1. This report describes two intragenic deletions of KAL-1 in two KS patients and suggests that KAL-1 deletion might be more prevalent in KS patients with other congenital organ abnormalities than those described previously in other series from Northwestern China.

The role of hypogonadism in Klinefelter Syndrome

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 beth 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.

Hypogonadism and erectile dysfunction： an overview

In humans androgen decline is presented as a clinical picture which includes decreased sexual interest, diminished erectile capasity, delayed or absent orgasms and reduced sexual pleasure. Additionally, changes in mood, diminished well being, fatigue, depression and irritability are also associated with androgen insufficiency. The critical role of androgens on the development, growth, and maintanence of the penis has been widely accepted. Although, the exact effect of androgens on erectile physiology still remains undetermined, recent experimental studies have broaden our understanding about the relationship between androgens and erectile function. Preclinical studies showed that androgen deprivation leads to penile tissue atrophy and alterations in the nerve structures of the penis. Furthermore, androgen deprivation caused to accumulation of fat containing cells and decreased protein expression of endothelial and neuronal nitric oxide synthases （eNOS and nNOS）, and phosphodiesterase type-5 （PDE-5）, which play crucial role in normal erectile physiology. On the light of the recent literature, we aimed to present the direct effect of androgens on the structures, development and maintanence of penile tissue and erectile physiology as well. Furhermore, according to the clinical studies we conclude the aetiology, pathophysiology, prevalance, diagnosis and treatment options of hypogonadism in aging men.

Erectile function and late-onset hypogonadism symptoms related to lower urinary tract symptom severity in elderly men

The aim of this study was to evaluate the relationship between lower urinary tract symptoms （LUTSs）, erectile dysfunction （ED） and symptomatic late-onset hypogonadism （SLOH） in ageing men in the Aegean region of Turkey. Five hundred consecutive patients 〉40 years old who had been in a steady sexual relationship for the past 6 months and were admitted to one of six urology clinics were included in the study. Serum prostate-specific antigen and testosterone levels and urinary flow rates were measured. All patients filled out the International Prostate Symptom Score and Quality of Life （IPSS-QoL）, International Index of Erectile Function （IIEF） and Aging Males＇ Symptoms （AMS） scale forms. Of the patients, 23.9% had mild LUTSs, 53.3% had moderate LUTSs and 22.8% had severe LUTSs. The total testosterone level did not differ between groups. Additionally, 69.6% had ED. The presence of impotence increased with increasing LUTS severity. Symptomatic late-onset hypogonadism （AMS 〉27） was observed in 71.2% of the patients. The prevalence of severe hypogonadism symptoms increased with the IPSS scores. A correlation analysis revealed that all three questionnaire scores were significantly correlated. In conclusion, LUTS severity is an age-independent risk factor for ED and SLOH. LUTS severity and SLOH symptoms appear to have a strong link that requires etiological and biological clarification in future studies.

Stem cell therapy for the treatment of Leydig cell dysfunction in primary hypogonadism

The production of testosterone occurs within the Leydig cells of the testes. When production fails at this level from either congenital, acquired, or systemic disorders,the result is primary hypogonadism. While numerous testosterone formulations have been developed, none are yet fully capable of replicating the physiological patterns of testosterone secretion. Multiple stem cell therapies to restore androgenic function of the testes are under investigation. Leydig cells derived from bone marrow, adipose tissue, umbilical cord, and the testes have shown promise for future therapy for primary hypogonadism. In particular, the discovery and utilization of a group of progenitor stem cells within the testes, known as stem Leydig cells(SLCs), has led not only to a better understanding of testicular development, but of treatment as well. When combining this with an understanding of the mechanisms that lead to Leydig cell dysfunction, researchers and physicians will be able to develop stem cell therapies that target the specific step in the steroidogenic process that is deficient. The current preclinical studies highlight the complex nature of regenerating this steroidogenic process and the problems remain unresolved. In summary, there appears to be two current directions for stem cell therapy in male primary hypogonadism. The first method involves differentiating adult Leydig cells from stem cells of various origins from bone marrow, adipose, or embryonic sources. The second method involves isolating, identifying, and transplanting stem Leydig cells into testicular tissue. Theoretically, in-vivo re-activation of SLCs in men with primary hypogonadism due to age would be another alternative method to treat hypogonadism while eliminating the need for transplantation.

Surveys of serum reproductive hormone levels and the prevalence rates of late onset of hypogonadism in Chinese aging males

Objective:To investigate the change patterns of reproductive hormones in serum of aging males and the difference among male age brackets and the prevalence rates of late onset of hypogonadism(LOH) in males in Chinese middle and aging males. Methods:Subjects included 1,498 men aged 40 to 69 from a county,and the serum reproductive hormones of 434 subjects were measured and calculated.In addition,the prevalence rates of LOH were analyzed by cut-off point of total testosterone(TT) and free testosterone(cFT),and screening scales(a questionnaire of androgen deficiency in the aging males(ADAM) and a scale of aging males’ symptoms(AMS)).TT,cFT,bio-available testosterone (Bio-T),luteinizing hormone(LH),sex hormone binding globulin(SHBG),testosterone secretion index(TSI), free testosterone index(FTD,the positive rates of LOH screening,androgen deficiency rates and the clinical prevalence rates of LOH were measured or calculated. Results:The serum TT levels did not change significantly with male aging while serum LH and SHBG levels gradually increased,but cFT,Bio-T,TSI and FTI levels gradually decreased with male aging.There was very significant difference in other six parameters of reproductive hormones(P<0.01),except for serum TT among the four age brackets(P>0.05).There was no correlation between serum TT levels and aging,LH levels(P>0.05). However,there was significantly a positive correlation between serum LH,SHBG and age(P<0.01),while there were negative correlation between cFT,Bio-T,TSI,FTI and age,LH levels(P<0.01).Moreover,SHBG level was positively correlated with LH level(P<0.01). Utilizing the Questionnaire of ADAM and AMS to screen subjects aged 40 to 69 years,mean positive rates of LOH screening were 80.77%and 32.34%respectively.Mean androgen deficiency rates were 14.02%and 43.69% by using TT and cFT cut-off point.In addition,mean LOH clinical prevalence rates of subjects on positive questionnaire results were 37.85%and 15.42%. Conclusion:The serum TT levels did not change significantly with male aging while serum LH,SHBG,cFT, Bio-T,TSI and FTI levels had the gradient change with aging.On the basis of Chinese population,however,the positive rate of LOH screening,androgen deficiency rate and clinical prevalence rate of LOH were obviously higher than that those of the other foreign studies.

Treatment of hypogonadotropic male hypogonadism: Case-based scenarios

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 effcacy 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 thatexogenous 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.

Bulbocavernosus muscle area as a novel marker for hypogonadism

Objective:Late-onset hypogonadism,or androgen deficiency in the aging male,is a significant cause of morbidity in older men.Many men in the low normal or equivocal range for low testosterone level exhibit signs and symptoms of hypogonadism.Serum testosterone is an imperfect maker for hypogonadism as symptoms vary greatly within the low to low normal range in addition to variations among testosterone assays.Perineal ultrasound can be effectively used to examine the bulbocavernosus muscle(BCM),an androgenized tissue that may be impacted by androgen receptor activity.Methods:This study was a retrospective analysis of men who underwent perineal ultrasound for hypogonadism.The ultrasound data were used to calculate the area of the BCM and correlate it with indices of hypogonadismin symptomatic men including free and total testosterone and dual-energy X-ray absorptiometry(DEXA).Results:The results demonstrate that there is a significant correlation between total and free testosterone and BCM area in hypogonadal patients.Comparison between BCM area and total testosterone showed R^2=0.061 and p=0.0187 and comparison between BCM area and free testosterone showed R^2=0.0957 and p=0.0034.In addition,low BCM was also correlated with DEXA results showing osteoporosis and osteopenia(R^2=0.2239,p=0.0027).Conclusion:There has been recent controversy over the safety of testosterone replacement therapy.This might be particularly important in men with hypogonadal symptoms but a low normal testosterone level.Our study investigated the use of perineal ultrasound to measure BCM as a surrogate marker for poor androgenized men presenting with hypogonadism.

Idiopathic Hypogonadotropic Hypogonadism— An Update on the Aetiopathogenesis, Management of IHH in Both Males and Females—An Exhaustive Review

Methods: Asystematic literature search was performed using PUBMED for all English articles up to April 2014. Although this review mainly focuses on published human studies, it also draws attention to where future research should be directed based on animal studies. Results: Besides the 9 known mutations widely quoted for KS namely KAL1, Fibroblast growth factor 8 (FGF8), fibroblast growth factor receptor 1 (FGFR1), prokineticin 2 (PROK2), PROK receptor 2 (PROKR2), WDR11, heparin sulfate-6-O-Transferase (HS6T1), chromodomain helicase DNA binding protein 7 (CHD7) and semaphorin 3A (SEMA 3A), additional mutations in “FGF8 synexpression” group e.g., FGF 17, ILRD, DUSP 6, SPRY4 and FLRT3 have been shown to be involved in CHH, mostly KS besides SEMA 7A. Although traditionally division has been based on anosmic/normosnic criteria, further genes found to cause so called nIHH like Gonadotropin releasing hormone receptor (GNRHR). KISS1, TAC3, TACR3 have also been found to be associated with hyposmia on detailed testing on UPSIT and MRI for olfactory structures revealed absent OB. Further detailed examination of transcription factor genes have revealed involvement of HESX1, TSHZ1, AXL, SOX10 with a strong overlap of in transcription factors in development of septooptic dysplasia (SOD), combined pituitary hormone deficiency (CHPD) and KS. Treatment with rFSH/-hCG gives almost similar results to pulsatile GnRH therapy and should be based on cost factor, availability and in occasional cases specific treatment like kisspeptin therapy. Conclusions: Contrary to the traditional thinking, one shoud reconsider classifying cases of IHH simply on basis of anosmia/normosmia. Deafness calls for looking for mutations in Sox 10/CHD7/ILRD7 considering 38% association of former. Therapy should be individualized based on availability of pulsatile GnRH, cost factor and in recalcitrant cases kp therapy may be of use with kp mutations and NKB mutations.

Androgens, Male Hypogonadism and Traumatic Brain Injury

Traumatic brain injury (TBI) is a worldwide public health problem. Populations with a growing number of vehicles are experiencing many traumas and accidents. The highest-risk group is young men. Significant advances in neurosurgery and intensive therapy have resulted in increased survival rates of TBI patients. These higher survival rates, in turn, have led to an increasingly higher number of patients with neurological, cognitive, clinical, and social problems. This lack of knowledge about TBI has been called by some “the silent epidemic”. In recent years, studies of patients with moderate and severe TBI are increasing. Glasgow Coma Scale ≤ 8 and abnormal pupils at admission are used to determine the prognosis of patients with moderate or severe TBI. Several biomarkers such as interleukins, thiobarbituric acid reactive species, and some hormones have been studied in an effort to aid prognosis. Testosterone plays a key role in men. Thus, an understanding of androgens in TBI is essential to follow these survivors of head trauma. This review will discuss the epidemiology of TBI, its association with male hypogonadism, and possible treatments.

Hyperhidrosis of Central Hypogonadism Leading to Diagnosis of Shapiro Syndrome: Temperature Dysregulation, Hypothermia and Agenesis of the Corpus Callosum

Background: Central or hypothalamic hypogonadism as an initial manifestation of Shapiro Syndrome has not been described in the literature. Herein, we report first case in which initial presentation of central hypogonadism led to a confirmed diagnosis of Shapiro Syndrome during a casual evaluation of hypothalamic pituitary anatomy with MRI of brain. Case presentation: 53 year old Caucasian man was documented to manifest Central or hypogonadotropic hypogonadism following evaluation of excessive sweating episodes, lack of libido and erectile dysfunction for a duration of several years. Brain MRI performed for assessment of the etiology documented no pituitary abnormality. Instead agenesis of Corpus Callosum was noted. The subject had been hospitalized on many occasions at this and several other medical centers with hypothermia or hyperthermia without a documentation of a definite cause. Therefore, the diagnosis of Shapiro Syndrome was made. Conclusion: This report is the first documentation of subject manifesting central, more likely to be hypothalamic rather than hypogonadotropic hypogonadism in conjunction with Shapiro Syndrome.

Prevalence of Hypogonadotropic Hypogonadism in Type 2 Diabetes Male Patients

Background: Erectile dysfunction is common in patients with diabetes mellitus. In addition, reduced testosterone itself is considered as a risk factor for diabetes;therefore hypogonadism was studied in diabetes. Objective: This study was done to determine the prevalence of hypo- and hypergonadotropic hypogonadism in the type 2 diabetes male patients in Mashhad in north-east of Iran. Methods: This study was done on type 2 diabetic men aged 40 - 60 years in the endocrine clinic, Endocrinology Research Center, Mashhad University of Medical Sciences, Iran. Fasting blood samples were collected at 8 am for measurement of fasting blood sugar (FBS), HbA1C, total serum testosterone, FSH, Sex Hormone Binding Globulin (SHBG), LH, prolactin, thyroxin-stimulating hormone (TSH), and immediately was sent to laboratory. Results: Out of total 96 type 2 diabetic males (mean age of 51.4 ± 11.26 years, range of 40 - 60 years), 11 (12.94%) patients were excluded because of inadequate samples, insufficient information and fulfillment of the exclusion criteria of the study. Hypogonadism based on Testosterone, Calculated free testosterone (CFT), and boiavailable testosterone (BT) were observed in 10 (11.8%), 31 (36.6%), and 30 (35.3%) of the patients, respectively. Libido was decreased in 55 (64.7%) of the patients. Based on the obtained SHBG values there were 7 (8.2%), 52 (61.2%), and 26 (30.6%) cases of low, normal and high values, respectively. According to TSH observed values there were 6 (7.1%) patients and 1 case of sub-clinical hypothyroidism and hyperthyroidism, respectively, and the rest 78 (91.8%) cases were euthyroid. Prolactin level was normal in all cases. Conclusion: Hypogonadotropic hypogonadism is common in type 2 diabetic men, and whether its treatment is useful for erectile dysfunction or not, needed additional investigation.