Hypothalamic-pituitary dysfunction in Sturge-Weber syndrome: case report and review of the literature.

OBJECTIVES: Sturge-Weber syndrome (SWS) is a rare neurocutaneous disorder that is characterized by a segmental dermatomal facial port-wine stain birthmark and is frequently accompanied by ipsilateral brain and eye abnormalities. We present a case of a patient with SWS who exhibited hypogonadotropic hypogonadism, growth hormone (GH) deficiency, and central hypothyroidism at the age of 20 despite the absence of radiographic findings in the pituitary and hypothalamus. CASE PRESENTATION: A 20-year-old male with SWS with epilepsy and Klippel-Trenaunay syndrome presents with delayed pubertal development, short stature, and obesity. Upon further examination, he was found to have biochemical and clinical evidence of hypogonadism, hypothyroidism, and GH deficiency. A pituitary MRI displayed no abnormalities of the pituitary or hypothalamus. Treatment with testosterone cypionate and levothyroxine was initiated. Despite successful pubertal induction, IGF-1 levels have remained low and treatment with recombinant human growth hormone (rhGH) is now being considered for metabolic benefits. CONCLUSIONS: This case emphasizes the importance of endocrine evaluation and treatment of hormonal deficiencies in patients with SWS despite the absence of radiographic findings.

Retrospective study on long-term effects of hormone replacement therapy (HRT) and iron chelation therapy on glucose homeostasis and insulin secretion in female ß- thalassemia major (ß-TM) patients with acquired hypogonadotropic- hypogonadism (AHH).

BACKGROUND AND AIM: Hypogonadism and abnormalities of glucose homeostasis, resulting from iron-induced pituitary and pancreatic ß-cell dysfunction respectively, are the most frequently reported endocrine abnormalities in patients with ß-thalassemia major (ß-TM), also identified as transfusion-dependent thalassemia (TDT). STUDY DESIGN AND PATIENTS: The aim of the present retrospective study was to evaluate the long-term effects of hormone replacement therapy (HRT) on glucose metabolism and insulin secretion/sensitivity during 3-h oral glucose tolerance test (OGTT) in adolescent and young ß-TM women with acquired hypogonadototropic -hypogonadism (AHH).Twelve hypogonadal ß-TM females with AHH on HRT were followed for 8.26 ± 1.49 years. RESULTS: At baseline, 10 patients (83.3%) had normal OGTT, 1 patient presented with impaired glucose tolerance (IGT) and 1 patient had an isolated PG level of 165 mg/dL at 1-h during OGTT (H-NGT). At last evaluation, 7 patients (58.4 %) had normal OGTT, while 5 patients (41.6%) had abnormal OGTT. Reduced insulin sensitivity and impaired first-phase insulin secretion were also documented. Three of 4 ß-TM patients on treatment with estradiol hemihydrate MX 50 patches plus oral medroxyprogesterone acetate (MPA), associated with a very effective iron chelation therapy, maintained normal glucose tolerance from baseline to last evaluation. Significant adverse events due to HRT or additional endocrine complications were not documented in any cases during the follow-up. CONCLUSION: Deterioration of glycemia (dysglycemia) occurred in 45.4% (5/11) of thalassemic females on long-term HRT. Additional studies are needed to elucidate the validity of our preliminary observations.

Association between body mass index, metabolic syndrome and common urologic conditions: a cross-sectional study using a large multi-institutional database from the United States.

INTRODUCTION: The study aims to determine whether body mass index (BMI), metabolic syndrome (MS) or its individual components (primary hypertension, type 2 diabetes mellitus and dyslipidemias) are risk factors for common urological diseases. MATERIALS AND METHODS: Cross-sectional study with data collected on February 28, 2022 from the TriNetX Research Network. Patients were divided in cohorts according to their BMI, presence of MS (BMI > 30 kg/m2, type 2 diabetes mellitus, primary hypertension and disorders of lipoprotein metabolism) and its individual components and its association with common urological conditions was determined. For each analysis, odds ratio (OR) with 95% confidence intervals were calculated. Statistical significance was assessed at p < .05. RESULTS: BMI > 30 kg/m2 was associated with increased risk of lithiasis, kidney cancer, overactive bladder, male hypogonadism, benign prostatic hyperplasia, and erectile dysfunction (p < .05). On the contrary, BMI was inversely associated with ureteral, bladder and prostate cancer (p < .05). In all urological diseases, MS was the strongest risk factor, with prostate cancer (OR = 2.53) showing the weakest and male hypogonadism the strongest (OR = 13.00) associations. CONCLUSIONS: MS and its individual components were significant risk factors for common urological conditions. Hence holistic approaches with lifestyle modification might prevent common urological disease.Key messagesOverall, metabolic syndrome is the strongest risk factor for all the analysed urological diseases.Abnormally high body mass index can be a risk or protective factor depending on the threshold and urological disease that are being evaluated.Metabolic syndrome and increased BMI should be considered important factors associated to the prevalence of common urological diseases.

Clomiphene citrate: A potential alternative for testosterone therapy in hypogonadal males.

BACKGROUND: Hypogonadism is a worldwide problem among men causing sexual, physical and mental problems. Testosterone therapy is the first-choice treatment for male hypogonadism, with several side effects, that is, subfertility. Clomiphene citrate (CC) is an alternative off-label therapy for a certain group of hypogonadal males, especially for those with an active or future child wish. There is scarce literature in usage of CC for men with hypogonadism. The aim of this retrospective study was to evaluate the effectiveness and safety of CC for hypogonadal males. METHODS: In this single-centre study, men treated with CC for hypogonadism were evaluated retrospectively. Primary outcome was hormonal evaluation including total testosterone (TT), free testosterone (FT), luteinizing hormone (LH) and follicle stimulating hormone (FSH). Secondary outcomes were hypogonadal symptoms, metabolic and lipid parameters, haemoglobin (Hb), haematocrit (Ht), prostate specific antigen (PSA), side effects, the effect of a trial without medication and potential predictors for biochemical and clinical response. RESULTS: In total, 153 hypogonadal men were treated with CC. Mean TT, FT, LH and FSH increased during treatment. TT increased from 9 to 16 nmol/L, with a biochemical increase in 89% of the patients. In patients who continued CC treatment, an increased level of TT persisted after 8 years of treatment. With CC treatment, 74% of the patients experienced hypogonadal symptom improvement. LH at the lower normal range before CC treatment was predictive for better TT response. During CC therapy, few side effects were reported and no clinical important changes in PSA, Hb and Ht were found. CONCLUSION: Clomiphene citrate is an effective therapy on short and long term, improving both clinical symptoms and biochemical markers of male hypogonadism with few side effects and good safety aspects.

A review of testosterone supplementation and cardiovascular risk.

Testosterone therapy is commonly utilized to treat hypogonadism. After diagnosis with morning serum testosterone level in patients with symptoms of hypogonadism, therapy has been shown to improve symptoms. Research focusing on cardiovascular risks associated with testosterone therapy has produced contradictory statements. We review trials that have investigated the impact of testosterone supplementation on heart failure, coronary artery disease, and myocardial ischemia.

Testosterone Deficiency as One of the Major Endocrine Disorders in Chronic Kidney Disease.

Reduced testosterone concentration is nowadays thought to be one of the main endocrine disorders in chronic kidney disease (CKD). It is caused by the dysfunction of the hypothalamic-pituitary-gonadal axis. The role of testosterone is multifactorial. Testosterone is responsible not only for reproductive processes, but it is a hormone which increases bone and muscle mass, improves lipid profile, insulin sensitivity, erythropoiesis, reduces blood pressure, and ameliorates mood and perception. The implications of hypogonadism in CKD are infertility and loss of libido, reduction of muscle mass and strength, disorders in bone mineralization, the development of sarcopenia and protein energy wasting (PEW), progression of atherosclerosis, increased visceral adiposity, insulin resistance, and anaemia. Reduced testosterone serum concentrations in CKD are associated with increased mortality rate. Testosterone supplementation improves sexual functions, reduces the level of inflammatory markers and blood pressure, stimulates muscle protein synthesis, improves insulin sensitivity and lipid profile, and increases muscle mass, bone mineral density, and haemoglobin concentration. It positively affects mood and well-being. The modes of testosterone supplementation are intramuscular injections, subcutaneous pellets, and percutaneous methods-patches and gels. Successful kidney transplantation may improve gonadal function and testosterone production, however, half of men with low testosterone concentrations before kidney transplantation do not restore hormonal function.

Late-Onset Hypogonadism in a Male Patient with Long COVID Diagnosed by Exclusion of ME/CFS.

After the acute phase of COVID-19, some patients have been reported to have persistent symptoms including general fatigue. We have established a COVID-19 aftercare clinic (CAC) to provide care for an increasing number of these patients. Here, we report the case of a 36-year-old man who developed post-COVID fatigue after acute infection with SARS-CoV-2. In the acute phase of COVID-19, the patient's fever resolved within four days; however, general fatigue persisted for three months, and he visited our CAC 99 days after the initial infection. Examination revealed a high Aging Male's Symptoms (AMS) score of 44 and low free testosterone (FT) level of 5.5 pg/mL, which meet the Japanese criteria of late-onset hypogonadism (LOH) syndrome. Imaging studies revealed an atrophic pituitary in addition to fatty liver and low bone mineral density. Anterior pituitary function tests showed a low follicle-stimulating hormonelevel and delayed reaction of luteinizing hormone (LH) after gonadotropin-releasing hormone (GnRH) stimulation, indicating the possibility of hypothalamic hypogonadism in addition to primary hypogonadism seen in patients with post-COVID-19 conditions. After the initiation of Japanese traditional medicine (Kampo medicine: hochuekkito followed by juzentaihoto), the patient's symptoms as well as his AMS score and serum FT level were noticeably improved. Furthermore, follow-up tests of GnRH stimulation revealed improvements in LH responsiveness. Although many patients have been reported to meet the criteria of ME/CFS such as our case, we emphasize the possibility of other underlying pathologies including LOH syndrome. In conclusion, LOH syndrome should be considered a cause of general fatigue in patients with post-COVID-19 conditions and herbal treatment might be effective for long COVID symptoms due to LOH (264 words).

Functional hypogonadism among patients with obesity, diabetes, and metabolic syndrome.

Testosterone deficiency, defined as low total testosterone combined with physical, cognitive, and sexual signs and/or symptoms, is a common finding in adult men. Functional hypogonadism (FH) is defined as borderline low testosterone (T) secondary to aging and/or comorbid conditions such as diabetes, obesity, and/or metabolic syndrome. The relationship between FH and metabolic disorders is multifactorial and bidirectional, and associated with a disruption of the hypothalamic-pituitary-gonadal axis. Resolution of FH requires the correct diagnosis and treatment of the underlying condition(s) with lifestyle modifications considered first-line therapy. Normalization of T levels through dietary modifications such as caloric restriction and restructuring of macronutrients have recently been explored. Exercise and sleep quality have been associated with T levels, and patients should be encouraged to practice resistance training and sleep seven to nine hours per night. Supplementation with vitamin D and Trigonella foenum-graecum may also be considered when optimizing T levels. Ultimately, treatment of FH requires a multidisciplinary approach and personalized patient care.

Leptin and inflammatory factors play a synergistic role in the regulation of reproduction in male mice through hypothalamic kisspeptin-mediated energy balance.

BACKGROUND: Energy balance is closely related to reproductive function, wherein hypothalamic kisspeptin mediates regulation of the energy balance. However, the central mechanism of kisspeptin in the regulation of male reproductive function under different energy balance states is unclear. Here, high-fat diet (HFD) and exercise were used to change the energy balance to explore the role of leptin and inflammation in the regulation of kisspeptin and the hypothalamic-pituitary-testis (HPT) axis. METHODS: Four-week-old male C57BL/6 J mice were randomly assigned to a normal control group (n = 16) or an HFD (n = 49) group. After 10 weeks of HFD feeding, obese mice were randomly divided into obesity control (n = 16), obesity moderate-load exercise (n = 16), or obesity high-load exercise (n = 17) groups. The obesity moderate-load exercise and obesity high-load exercise groups performed exercise (swimming) for 120 min/day and 120 min × 2 times/day (6 h interval), 5 days/week for 8 weeks, respectively. RESULTS: Compared to the mice in the normal group, in obese mice, the mRNA and protein expression of the leptin receptor, kiss, interleukin-10 (IL-10), and gonadotropin-releasing hormone (GnRH) decreased in the hypothalamus; serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels and sperm quality decreased; and serum leptin, estradiol, and tumor necrosis factor-α (TNF-α) levels and sperm apoptosis increased. Moderate- and high-load exercise effectively reduced body fat and serum leptin levels but had the opposite effects on the hypothalamus and serum IL-10 and TNF-α levels. Moderate-load exercise had anti-inflammatory effects accompanied by increased mRNA and protein expression of kiss and GnRH in the hypothalamus and increased serum FSH, LH, and testosterone levels and improved sperm quality. High-load exercise also promoted inflammation, with no significant effect on the mRNA and protein expression of kiss and GnRH in the hypothalamus, serum sex hormone level, or sperm quality. Moderate-load exercise improved leptin resistance and inflammation and reduced the inhibition of kisspeptin and the HPT axis in obese mice. The inflammatory response induced by high-load exercise may counteract the positive effect of improving leptin resistance on kisspeptin and HPT. CONCLUSION: During changes in energy balance, leptin and inflammation jointly regulate kisspeptin expression on the HPT axis.

MANAGEMENT OF ENDOCRINE DISEASE: Rationale and current evidence for testosterone therapy in the management of obesity and its complications.

Overt hypogonadism in men adversely affects body composition and metabolic health, which generally improve upon testosterone (TS) therapy. As obese men often display lower serum TS levels, in particular when they present with the metabolic syndrome (MetS) or type 2 diabetes (T2DM), there have been claims that androgen therapy prevents or reverses obesity and improves metabolic health. This has contributed to the increase in TS prescriptions during the past two decades. In this narrative review, based on findings from larger observational studies and randomized controlled intervention trials, we evaluate whether low TS predicts or predisposes to obesity and its metabolic consequences, and whether obese men with low TS are truly hypogonadal. We further describe the mechanisms underlying the bi-directional relationships of TS levels with obesity and metabolic health, and finally assess the evidence for TS therapy in men with obesity, MetS and/or T2DM, considering efficacy, safety concerns and possible alternative approaches. It is concluded that low serum sex hormone-binding globulin and total TS levels are highly prevalent in obese men, but that only those with low free TS levels and signs or symptoms of hypogonadism should be considered androgen deficient. These alterations are reversible upon weight loss. Whether low TS is a biomarker rather than a true risk factor for metabolic disturbances remains unclear. Considering the limited number of sound TS therapy trials have shown beneficial effects, the modest amplitude of these effects, and unresolved safety issues, one cannot in the present state-of-the-art advocate TS therapy to prevent or reverse obesity-associated metabolic disturbances. Instead, the focus should remain on lifestyle measures and management of obesity-related consequences.

Potential Cardiovascular and Metabolic Beneficial Effects of ω-3 PUFA in Male Obesity Secondary Hypogonadism Syndrome.

Long-chain ω-3 polyunsaturated fatty acids (PUFAs) are fundamental biocomponents of lipids and cell membranes. They are involved in the maintenance of cellular homeostasis and they are able to exert anti-inflammatory and cardioprotective actions. Thanks to their potential beneficial effects on the cardiovascular system, metabolic axis and body composition, we have examined their action in subjects affected by male obesity secondary hypogonadism (MOSH) syndrome. MOSH syndrome is characterized by the presence of obesity associated with the alteration of sexual and metabolic functions. Therefore, this review article aims to analyze scientific literature regarding the possible benefits of ω-3 PUFA administration in subjects affected by MOSH syndrome. We conclude that there are strong evidences supporting ω-3 PUFA administration and/or supplementation for the treatment and management of MOSH patients.

Adverse Effects of Common Sports and Recreational Activities on Male Reproduction.

CONTEXT: Male factor infertility plays a significant role in infertility. Many factors have been associated with male infertility; however, the link between many sports and recreational factors and male reproduction remains poorly characterized. OBJECTIVE: To evaluate the current literature regarding the impact of many common sports and recreational factors on male reproduction. EVIDENCE ACQUISITION: A comprehensive PubMed and Embase search for relevant articles published between 1970 and 2017 was performed by combining the following search terms: male, sports (including individual sports), traumatic brain injury, sauna, hot tub, fertility, erectile dysfunction, varicocele, environment, cell phone, and laptop computer. EVIDENCE SYNTHESIS: Hypogonadism and erectile dysfunction can be associated with sports with high rates of head injuries, such as American football. Although early reports linked other sports, such as bicycling, to erectile dysfunction, subsequent studies isolated these associations to sports cycling rather than recreational cycling. Certain sports (football, basketball, handball, and volleyball) were linked to increasing prevalence and severity of varicocele, offering a potential link to male infertility. In addition, recreational activities such as sauna, hot tubs, Jacuzzis, heated car seats, and laptop use were associated with high testicular temperature, which can impair spermatogenesis. Radio frequency electromagnetic waves from cell phones and laptops have also been shown to have deleterious effects on sperm viability and motility. CONCLUSIONS: Many common sports and daily activities represent potential sources of male infertility. Clinicians should be aware of these associations in explaining idiopathic infertility in males. PATIENT SUMMARY: Male infertility is an often overlooked component of a couple's inability to conceive. We outline many common and often overlooked sports and recreational exposures that have been associated with male infertility.

Increasing hypothalamic nucleobindin 2 levels and decreasing hypothalamic inflammation in obese male mice via diet and exercise alleviate obesity-associated hypogonadism.

To explore the role of nesfatin-1 in regulating male reproductive function during energy balance variation, we employed an obese mouse model which was first induced by a high-fat diet (HFD) and followed by interventions of a normal diet (ND) and/or moderate exercise, and then serum reproductive hormones of male mice, hypothalamic nucleobindin 2 (NUCB2)/nesfatin-1, inflammatory factors, and gonadotropin-releasing hormone (GnRH) levels were tested. Our findings showed that both serum nesfatin-1, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) levels and hypothalamic NUCB2/nesfatin-1 and Gnrh mRNA levels were reduced, whereas, the mRNA and protein levels of hypothalamic tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, inhibitor kappa B kinase ß (IKKß), and nuclear factor (NF)-κB were increased in obese male mice. Diet, exercise, and diet combined with exercise interventions reversed the decreases in serum nesfatin-1, FSH, LH, and T levels; increased hypothalamic NUCB2/nesfatin-1 and Gnrh mRNA levels; and reduced hypothalamic TNF-α, IL-1ß, IKKß, and NF-κB levels. These changes were accompanied by reduced adiposity, and these effects were more obvious in the diet combined with exercise group. Overall, our findings suggested that the hypogonadotropic hypogonadism associated with obesity may be induced by reduced hypothalamic NUCB2/nesfatin-1 levels, which attenuated the stimulatory effect on GnRH directly or indirectly by suppressing its anti-inflammatory effect in the brain. Diet and/or exercise interventions were able to alleviate the hypogonadotropic hypogonadism associated with obesity, potentially by increasing hypothalamic NUCB2/nesfatin-1 levels.

Addressing the Unintentional Consequences of Cancer Therapy With Novel Integrative Therapeutics.

There are 15.5 million cancer survivors in the United States because of, in part, improvements in therapy. As a result, there will be an increased burden of long- and late-term complications of cancer care, such as metabolic alterations. These metabolic changes will include alterations in bone resorption, obesity, hypercholesterolemia, and diabetes mellitus. The majority of cancer treatment-related toxicities have focused on endocrine therapy; however, chemotherapy and supportive medications, such as steroids, contribute to the development of these disorders. Because of the chronicity of these metabolic changes and their impact on morbidity, cancer risk, and outcomes as well other negative effects, including musculoskeletal pain and vasomotor symptoms, alternative strategies must be developed. These strategies should include nonpharmacologic approaches. Here, we summarize metabolic changes secondary to cancer care and integrative approaches to help alleviate therapy-associated toxicities.

Iron overload directly affecting the ovaries in a patient with Diamond-Blackfan anaemia: a case report.

Iron is a 'one-way' element and the primary point of regulation of body iron stores is at the level of intestinal iron absorption. Repeated blood transfusions for congenital anaemias bypass this regulatory checkpoint and inevitably lead to iron overload in the long-term. Iron overload causes multi-organ dysfunction of the heart, liver, pancreas and joints. It also causes reproductive toxicity primarily through its damaging effect on the anterior pituitary leading to hypogonadotrophic hypogonadism. Another less understood mechanism of reproductive toxicity is direct gonadal damage of excess free iron. In this article, we present the case of a 24-year-old woman with Diamond-Blackfan anaemia who presented to our unit seeking fertility assistance. The evaluation revealed a combination of hypogonadotrophic hypogonadism and reduced ovarian reserve along with evidence of severe iron overload. A literature search along with input from clinical experts has allowed us to counsel the patient to help her make an informed choice. A multi-disciplinary approach which would include initial optimization of pre-conceptional health with aggressive iron chelation therapy and subsequent ovulation induction with gonadotrophins has been planned, failing which, egg donation may be the only viable alternative.

Does long-term androgen deficiency lead to metabolic syndrome in middle-aged rats?

Evidence from clinical observational studies and animal experiments suggests that hypogonadism is associated with the metabolic syndrome. In most of the experiments, androgen deficiency is induced by gonadectomy in the adulthood and relatively short-term effects of hypogonadism on metabolic parameters are usually observed. The purpose of this study was to evaluate the metabolic effects of long-term androgen deficiency starting before puberty in middle-aged male rats. The components of the metabolic syndrome were examined in male, female and gonadectomized male rats at the age of 18months. Sex differences were observed in plasma testosterone, cholesterol, high-density lipoproteins and also in body weight and in glycemia dynamics during oral glucose tolerance test. Gonadectomy and long-term hypogonadism did not affect most of the analyzed metabolic parameters such as blood pressure, glycemia, plasma insulin and uric acid. The only exception was the significantly higher liver enzymes in plasma and triacylglycerol in liver found in gonadectomized males. Except low-density lipoprotein, neither treatment of middle-aged males and females with letrozole, nor supplementation of estradiol as the metabolite of testosterone in gonadectomized male rats changed any of the observed metabolic parameters. Our results suggest that long-term hypogonadism started before puberty does not induce metabolic syndrome in middle-aged male rats, but may affect the liver. Sex differences in metabolic parameters in middle-aged rats are not mediated by testosterone. Whether hypogonadism predispose to metabolic syndrome in combination with other risk factors needs further clarification.

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

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.

Treatment of osteoporosis secondary to hypogonadism in prostate cancer patients: a prospective randomized multicenter international study with denosumab vs. alendronate.

BACKGROUND: Osteoporosis is a complication of androgen deprivation therapy (ADT) in men with prostate carcinoma. This is a multicenter, randomized, double-blind prospective study on use of denosumab versus alendronate in the therapy of secondary osteoporosis related to ADT. METHODS: A total of 234 patients with diagnosis of osteoporosis underwent ADT for prostate cancer were enrolled. Patients were randomly assigned 1:1 to receive denosumab 60 mg subcutaneously every 6 months or alendronate (70 mg/week) for 2 years. All patient received supplemental vitamin D (600 IU/day) and supplemental calcium to maintain a calcium intake of 1200 mg per day. Effectiveness of therapy in both groups (denosumab group and alendronate group) was assessed by changes in bone turnover markers (BTMs), bone mineral density, fracture incidence, Visual Analogue Scale score for back pain, and Short Form-8 health survey score for health-related quality of life. RESULTS: In the denosumab study group, level of BTMs for bone formation were significantly increased from baseline at all time points during the study (P<0.001); in the alendronate study group level of BTMs for bone formation were increased too (P>0.05). Mean changes in BMD at final follow-up differed significantly between two groups. BMD changes at the lumbar spine at 24 months were 5.6% with denosumab vs. -1.1% with alendronate (P<0.001). CONCLUSIONS: Denosumab and alendronate showed similar clinical efficacy in the therapy of ADT-related osteoporosis in men with prostate carcinoma; both drugs provided significant improvements in back pain and general health conditions. Denosumab showed significant increase of BTMs and BMD than alendronate with lower rate of new vertebral fractures.

Rapid height growth after liver transplantation in adulthood.

Glycogen storage disease Ib is a rare, inherited metabolic disorder caused by glucose-6-phosphatase translocase deficiency. Its main symptoms are hypoglycemia, hyperlipidemia, neutropenia, hepatomegaly, liver adenomas and short stature. The exact mechanism of short stature in this disease is unclear, the most feasible possibility is that it is caused by impairment of growth-hormone and insulin-like growth factor I axis. Here we report the case of a patient who showed typical symptoms of glycogen storage disease Ib since his infancy, his height being under 1 percentile since then. Later-developed hypothyroidism and hypogonadism have also contributed to his short stature. Hypothyroidism was treated but sexual steroid substitution was not started because of an increased risk of hepatic adenomas. Because he developed hepatic adenoma at the age of 23, he had to undergo orthotopic liver transplantation. At the time of the transplantation his height was 128cm. The transplantation was followed by rapid height growth; our patient's height reached 160.3cm 62months after transplantation. We observed that while his IGF-I level increased, his GH level remained unchanged. During the post-transplantation period we ensured adequate calcium and vitamin D supplementation, leaving hormonal substitution unchanged. According to our knowledge, this is the first report of a rapid height growth as big as 32cm, of an individual over the age of 20, not related to endocrine treatment but liver transplantation.

Vanishing testes syndrome-related osteoporosis and high cardio-metabolic risk in an adult male with long term untreated hypergonadotropic hypogonadism.

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.