Early parathyroid hormone (PTH) level as a predictor of post-surgical hypoparathyroidism.

INTRODUCTION: Post-operative hypocalcemia and postoperative persistent hypoparathyroidism remain the most common complications after thyroidectomy. Many approaches have been developed to prevent them, but actually, a common protocol is not yet individuated. MATERIALS AND METHODS: We retrospectively analyzed the results of a prospectively collected database. We dosed PTH preoperatively and 4 h after surgery (PTH_4); calcium was evaluated preoperatively, on the first (I_POD) and on the second postoperative day (II_POD). Hypocalcemia was defined when calcium <8 mg/dl. PTH_4 and I_POD calcium serum levels are identified to predict postoperative hypocalcemia. RESULTS: Three hundred and forty-eight patients were enrolled, 37 patients resulted as hypocalcemic on I_POD and 41 on the II_POD. PTH_4 is related to I_POD (p < 0.001, r = 0.45) and II_POD (p < 0.001, r = 0.44) calcemia. PTH_4-cut-off predicting I_POD hypocalcemia was 10.50 pg/ml (sensitivity: 78.7%, specificity: 72.7%). A PTH_4 value of 11.5 pg/ml is able to predict hypocalcemia during II_POD (sensitivity: 76.5%, specificity: 69.2%). We set up a combined test to predict II_POD hypocalcemia, using PTH_4 and I_POD calcium (sensitivity: 77.8%, specificity: 89.9%). CONCLUSION: This research shows the association between PTH_4 and postoperative hypocalcemia. The PTH_4 cut-off to predict I_POD-hypocalcemia was 10.5 pg/ml. We analyzed the calcemia trend during the postoperative period and we realized a combined test using PTH_4 and I_POD-calcemia. This test improves the accuracy of the previous test. Further studies, in particular multicentric, with a larger sample are necessary to validate the combined model.

Erectile Dysfunction in Men with Chronic Obstructive Pulmonary Disease.

Erectile dysfunction (ED) seems to be a widespread sexual issue in men affected by chronic obstructive pulmonary disease (COPD). Multiple causes appear to be involved such as hormonal imbalance, smoking habit, chronic inflammation, endothelial dysfunction, chronic hypoxia, psychiatric disorders (depression and anxiety), and medications. ED can have a significant impact on COPD men and consequently on their quality of life, which is usually already compromised. Given this situation, however, pneumologists usually do not properly care for the sexuality of COPD patients especially because men can be reluctant to talk about their intimate issues. The aim of this narrative review is to briefly summarize the evidence emerging from literature and to provide a wide point of view about sexual dysfunction in COPD men.

Gonadal Failure and Infertility in Cancer Survivors: Clinical Management and Strategies for Prevention.

Modern advances in oncological treatments determined a significant improvement in survival rates for several malignancies. Nevertheless, survivorship and quality of life of cancer survivors may be negatively impaired by metabolic and endocrine side effects related to anticancer treatments, including alterations of pituitary-gonadal axis function. In fact, both medical (chemo- and radiotherapy) and surgical approaches may negatively impact on gonadal function, leading to transient or permanent hypogonadism and infertility. In view of these considerations, fertility preservation (FP) should be a primary concern in all oncological patients who may potentially achieve parenthood, irrespectively from their sex and pubertal status at treatment, and adequate counselling should be provided before undergoing gonadotoxic therapy or gonadectomy. Cryopreservation of gametes, when feasible, represents the mainstay for FP in postpubertal age, while procedures involving storage of tissue specimens or stem cells should still be considered as experimental. Given the complexity of both hormonal and psychological implications in this clinical setting, a multidisciplinary approach is advisable for optimal FP and for early diagnosis and treatment of hypogonadism.

Impact of Allogeneic Stem Cell Transplantation on Testicular and Sexual Function.

High-dose chemotherapy and radiotherapy, administered as a conditioning regimen before stem cell transplantation, are known to negatively impact testicular function and sexuality. However, to date, only a few studies have simultaneously analyzed the real prevalence of these complications in this clinical setting. Therefore, this study aimed to assess the prevalence of testicular dysfunction and sexual impairment in a cohort of males who underwent allogeneic stem cell transplantation in adulthood. This observational, cross-sectional, single-center study consecutively enrolled 105 subjects on outpatient follow-up. Testicular function and sexuality were evaluated through a hormonal profile (testosterone, follicle-stimulating hormone, luteinizing hormone, and inhibin B) and the IIEF-15 questionnaire, respectively. We found a higher prevalence of hypogonadism (21%), impaired spermatogenesis (87%), and erectile dysfunction (72%) compared with the general population. Chronic graft-versus-host disease, especially of moderate/severe grade, was associated with an increased risk of developing erectile dysfunction (odds ratio, 6.338). Moreover, a high proportion of patients presented with alterations in all domains of sexual function, even after complete clinical remission of hematologic disease. Our data confirm both testicular function and sexuality alterations as frequent complications after allogeneic stem cell transplantation. A multidisciplinary approach is advisable for early diagnosis and adequate treatment.

Fracture risk assessment in an Italian group of transgender women after gender-confirming surgery.

INTRODUCTION: Bone health is a critical issue in transgender women (TW) health care. Conflicting results have been reported on bone status after gender-confirming surgery (GCS). No recent data in Italian TW are available. MATERIALS AND METHODS: The aim of this cross-sectional study was to evaluate fracture risk, lumbar spine BMD and 25OH vitamin D (25OHD) levels in a population of TW on estrogen replacement therapy (ERT) after GCS. We retrospectively analyzed a group of 57 TW, aged 45.3 ± 11.3 years, referred to our Gender Dysphoria Clinic, at least 2 years after GCS. Anthropometric parameters, patient compliance to ERT, biochemical and hormonal assessment, lumbar spine BMD and fracture risk were evaluated. RESULTS: Prevalence of low bone mass (Z-score ≤ -2) was 40% according to the natal gender. In this group, 17ß-estradiol levels were significantly lower (median 21 pg/ml [25th-75th percentile 10.6-48.5] vs 63 pg/ml [38.5-99.5]; p < 0.001) and a higher prevalence of low compliance to ERT was recorded (83% vs 29%; p < 0.0001) compared to those with higher bone mass. An intermediate-high fracture risk was found in 14% of the sample. A high percentage (93%) of hypovitaminosis D was present. CONCLUSIONS: TW on ERT have a high prevalence of low bone mass, significantly associated with low estradiol levels and low compliance to ERT. A high prevalence of hypovitaminosis D was highlighted. Considering that one out of seven TW showed an intermediate-high 10-year fracture risk, such risk assessment may be considered to prevent and manage osteoporosis in this clinical setting.

Management of GH treatment in adult GH deficiency.

Growth hormone (GH) replacement therapy in adults with GH deficiency is still a challenge for the clinical endocrinologist and its implementation has still numerous difficulties and uncertainties. The decision to treat GH deficient adults requires a thoughtful and individualized evaluation of risks and benefits. Benefits have been found in body composition, bone health, cardiovascular risk factors, and quality of life. However, evidences for a reduction in cardiovascular events and mortality are still lacking, and treatment costs remain high. It is advisable to start treatment with low doses of GH, the goals being an appropriate clinical response, an avoidance of side effects, and IGF-I levels in the age-adjusted reference range. Although treatment appears to be overall safe, certain areas continue to require long-term surveillance, such as risks of glucose intolerance, pituitary/hypothalamic tumor recurrence, and cancer.

Endocrine Autoimmunity in Down's Syndrome.

Since the mid 1900s, a significant increase of infectious, hematological, and autoimmune diseases has been reported in patients with Down's syndrome (DS), independent of sex, age, family history, and exposure to other risk factors, suggesting an intrinsic alteration of the immune system. Several in vitro and in vivo studies have demonstrated alterations of both cellular and humoral immunological response mainly, although not exclusively, secondary to alterations of the expression of autoimmune regulator gene (located on chromosome 21), leading to thymic structural and functional impairments. Autoimmune thyroid disorders (i.e. Hashimoto's thyroiditis and Graves' disease) and type 1 diabetes mellitus are the most common autoimmune endocrine disorders associated with DS, and present with some peculiar features. The underlying etiopathogenic mechanisms and clinical significance of some mild laboratory alterations are still poorly understood. For these aspects, together with the associated multiple comorbidities and intellectual impairment - that make DS patients dependent on care givers - and in the absence of definite guidelines, disease management is very challenging and should be patient-tailored.

Ghrelin Actions on Somatotropic and Gonadotropic Function in Humans.

Ghrelin, a 28 amino-acid octanoylated peptide predominantly produced by the stomach, was discovered to be the natural ligand of the type 1a GH secretagogue receptor (GHS-R1a). It was thus considered as a natural GHS additional to GHRH, although later on ghrelin has mostly been considered a major orexigenic factor. The GH-releasing action of ghrelin takes place both directly on pituitary cells and through modulation of GHRH from the hypothalamus; some functional antisomatostatin action has also been shown. However, ghrelin is much more than a natural GH secretagogue. In fact, it also modulates lactotroph and corticotroph secretion in humans as well as in animals and plays a relevant role in the modulation of the hypothalamic-pituitary-gonadal function. Several studies have indicated that ghrelin plays an inhibitory effect on gonadotropin pulsatility, is involved in the regulation of puberty onset in animals, and may regulate spermatogenesis, follicular development and ovarian cell functions in humans. In this chapter ghrelin actions on the GH/IGF-I and the gonadal axes will be revised. The potential therapeutic role of ghrelin as a treatment of catabolic conditions will also be discussed.

Gonadal Imaging in Endocrine Disorders.

Ultrasound (US) is the most widely available method of diagnostic imaging for the evaluation and characterization of gonadal lesions and is usually the method of choice because of its high accuracy, low cost and wide availability. Today's high-resolution images allow for a confident diagnosis of many scrotal and adnexal lesions, with high sensitivity and specificity. Magnetic resonance imaging (MRI) is reliable in the detection of gonadal lesions in males, allowing the differentiation into testicular or nontesticular lesions, and their characterization. It is also an accurate and cost-effective diagnostic adjunct in those patients with solid scrotal lesions for whom the findings of clinical and US evaluations are inconclusive. In females, MRI is recommended as a second-line investigation for the characterization of complex adnexal masses that are indeterminate on US. In this review, gonadal pathologies related with the steroidogenic and gametogenic function of the testes and ovaries will be discussed. The main imaging features of benign and malignant lesions will also be presented.

Effects of oncological treatments on semen quality in patients with testicular neoplasia or lymphoproliferative disorders.

Pretherapy sperm cryopreservation in young men is currently included in good clinical practice guidelines for cancer patients. The aim of this paper is to outline the effects of different oncological treatments on semen quality in patients with testicular neoplasia or lymphoproliferative disorders, based on an 8-year experience of the Cryopreservation Centre of a large public hospital. Two hundred and sixty-one patients with testicular neoplasia and 219 patients with lymphoproliferative disorders who underwent chemotherapy and/or radiotherapy and pretherapy semen cryopreservation were evaluated. Sperm and hormonal parameters (follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, inhibin B levels) were assessed prior to and 6, 12, 18, 24 and 36 months after the end of cancer treatment. At the time of sperm collection, baseline FSH level and sperm concentration were impaired to a greater extent in patients with malignant testicular neoplasias than in patients with lymphoproliferative disorders. Toxic effects on spermatogenesis were still evident at 6 and 12 months after the end of cancer therapies, while an improvement of seminal parameters was observed after 18 months. In conclusion, an overall increase in sperm concentration was recorded about 18 months after the end of cancer treatments in the majority of patients, even if it was not possible to predict the evolution of each single case 'a priori'. For this reason, pretherapy semen cryopreservation should be considered in all young cancer patients.

Metabolic and cardiovascular outcomes in a group of adult patients with Turner's syndrome under hormonal replacement therapy.

OBJECTIVE: Turner's syndrome (TS) is a rare genetic disorder caused by complete or partial X chromosome monosomy in a phenotypic female, and it is associated with increased morbidity and mortality for cardiovascular diseases, impaired glucose tolerance, and dyslipidemia. SUBJECTS AND METHODS: In 30 adult TS patients under chronic hormonal replacement therapy (HRT), 17ß-estradiol (E(2)), body mass index (BMI), waist circumference, fasting glucose and insulin, homeostatic model assessment (HOMA) index, serum lipids, oral glucose tolerance test (OGTT), 24 h ambulatory blood pressure monitoring (ABPM), and intima-media thickness (IMT) were evaluated and compared with those in 30 age- and sex-matched controls (CS). RESULTS: No difference was found between TS and CS in E(2) and BMI, whereas waist circumference was higher (P<0.05) in TS (77.7±2.5 cm) than in CS (69.8±1.0 cm). Fasting glucose in TS and in CS was similar, whereas fasting insulin, HOMA index, and 2 h glucose after OGTT were higher (P<0.0005) in TS (13.2±0.8 mUI/l, 2.5±0.2, and 108.9±5.5 mg/dl respectively) than in CS (9.1±0.5 mUI/l, 1.8±0.1, and 94.5 ± 3.8 mg/dl respectively). Total cholesterol was higher (P<0.05) in TS (199.4 ± 6.6 mg/dl) than in CS (173.9±4.6 mg/dl), whereas no significant differences in high-density lipoprotein, low-density lipoprotein, and triglycerides were found between the two groups. In 13% of TS, ABPM showed arterial hypertension, whereas IMT was <0.9 mm in all TS and CS. A negative correlation between insulin levels, HOMA index, or 2 h glucose after OGTT and E(2) was present in TS. CONCLUSIONS: Our results indicate that adult patients with TS under HRT are connoted by higher frequency of central obesity, insulin resistance, hypercholesterolemia, and hypertension.

Effects of cetrorelix, a GnRH-receptor antagonist, on gonadal axis in women with functional hypothalamic amenorrhea.

BACKGROUND: Gonadotropin Releasing Hormone (GnRH) antagonists (GnRHa) suppress gonadotropin and sex-steroid secretion. In normal women, acute GnRHa administration induces inhibitory effect on pituitary-gonadal axis, followed by Luteinizing Hormone (LH) rebound. Functional hypothalamic amenorrhea (HA) is characterised by impaired gonadotropin secretion and hypogonadism secondary to blunted GnRH pulsatility. METHODS: We studied the effects of a GnRHa, cetrorelix (CTX 3.0 mg), in six women with HA (age 30.7 ± 3.2 years; BMI 21.5 ± 1.7 kg/m(2)) and six control subjects (CS, 28.2 ± 0.6 years; 22.6 ± 0.9 kg/m(2)) on LH, Follicle-Stimulating Hormone (FSH) and oestradiol levels over 4 h (08.00-12.00 am) before, +24 h and +96 h after CTX; LH, FSH, and oestradiol were also evaluated at +6, +8, +12, +48, +72 h after CTX. RESULTS: CS: CTX reduced (p < 0.05) LH, FSH, and oestradiol (nadir at +12 h, +24 h, and +24 h); LH rebounded at +96 h, FSH and oestradiol recovered at +48 h and +72 h. The 4-h evaluation showed LH and FSH reduction (p < 0.05) at +24 h, with LH rebound at +96 h. HA: CTX reduced (p < 0.05) LH, FSH, and oestradiol, (nadir at +24 h, +48 h, and +48 h, recovery at +48 h, +72 h, and +96 h). The 4-h evaluation showed gonadotropin reduction (p < 0.05) 24 h after CTX, without any rebound effect. CONCLUSIONS: One single CTX dose still modulates gonadotropin secretion in HA. Its 'paradoxical' stimulatory effect on gonadotropins needs to be verified after prolonged administration.

Ghrelin and anterior pituitary function.

Ghrelin, a 28-amino-acid octanoylated peptide predominantly produced by the stomach, was discovered to be the natural ligand of the type 1a GH secretagogue receptor. Thus, it was considered as a natural GH secretagogue (GHS) additional to GHRH, although later on ghrelin has mostly been considered a major orexigenic factor. The GH-releasing action of ghrelin takes place both directly on pituitary cells and through modulation of GHRH from the hypothalamus; some functional anti-somatostatin action has also been shown. However, even at the neuroendocrine level, ghrelin is much more than a natural GHS. In fact, it significantly stimulates prolactin secretion in humans, independent of both gender and age and probably involving a direct action on somatomammotroph cells. Above all, ghrelin and synthetic GHS possess an acute stimulatory effect on the activity of the hypothalamus-pituitary-adrenal axis in humans, which is, at least, similar to that of the opioid antagonist naloxone, arginine vasopressin and even corticotropin-releasing hormone. Also, ghrelin plays a relevant role in the modulation of the hypothalamic-pituitary-gonadal function, with a predominantly CNS-mediated inhibitory effect upon the gonadotropin pulsatility both in animals and in humans.

Tall stature without growth hormone: four male patients with aromatase deficiency.

CONTEXT: From preliminary observations, GH-IGF-I seems to be compromised in men with aromatase deficiency. The GH deficiency (GHD) coexists paradoxically with tall stature, raising the question whether or not a true GHD is part of this rare syndrome. OBJECTIVE: To evaluate the GH secretion in aromatase-deficient men, their GH response to the GHRH plus arginine (GHRH-ARG) test was compared with that of normal subjects. The effect of estrogen replacement treatment on the GH-IGF-I axis in aromatase-deficient men was evaluated before and during therapy. DESIGN AND SETTING: A case-control study was conducted. PATIENTS: Four adult men with aromatase deficiency were compared with 12 normal subjects. MAIN OUTCOME MEASURES: We measured the GH response to GHRH-ARG in aromatase-deficient men (at baseline and during estrogen treatment) and in normal subjects. Basal serum IGF-I was measured in both patients and controls. RESULTS: The response of GH to GHRH-ARG was severely impaired in men with aromatase deficiency and resulted in significantly lower (P < 0.001) levels than in normal subjects. Although normal, serum IGF-I levels were also significantly lower (P < 0.001) than in normal subjects. Both GH peak and IGF-I concentrations were not modified by estrogen therapy in men with aromatase deficiency. CONCLUSIONS: In aromatase-deficient men, GH response to potent provocative stimuli is impaired and is not restored by exogenous estrogens. Furthermore, a tall stature may be reached, notwithstanding the coexistence of GHD, if a prolonged time for growth is available due to a delay in bone maturation, and other growth factors different from GH (mainly insulin) promote growth.

A novel mutation in the human aromatase gene: insights on the relationship among serum estradiol, longitudinal growth and bone mineral density in an adult man under estrogen replacement treatment.

OBJECTIVE: Here we report on a new case of human aromatase deficiency in a man of 26 years of age and present the results of five year follow-up during trandermal estradiol (tE2) substitution, focusing on bone growth and mineralization. The lack of patient's compliance to tE2 treatment, resulting in low but detectable serum estradiol levels, provides helpful information about the physiological estradiol needed in serum to guarantee a complete bone maturation and mineralization. DESIGN: Clinical case report study. METHODS: Genetic, biochemical and hormonal evaluations and the study of bone health were performed before and during estrogen treatment. RESULTS: Eunuchoid body proportions, unfused epiphyses, tall stature, osteopenia, increase fasting insulin, mild astenozoospermia and a history of right cryptorchidism were present. Baseline serum FSH was slightly above the normal range and estradiol was undetectable. Genetic analysis revealed a pattern of compound heterozygosity due to 23 bp deletion in exon IV and a point mutation in the first nucleotide of intron IX of the CYP19A1 gene, respectively. The closure of epiphyseal cartilage, the normalization of bone BMD and bone turnover markers, and the improvement of insulin levels were reached during tE2 only when serum estradiol raised above 73 pmol/L. Sperm parameters and overweight did not improve with substitutive therapy. CONCLUSIONS: This new case of aromatase deficiency underlines the role of estrogen on skeletal maturation, BMD, metabolic abnormalities and gonadal axis. It provides evidence on the need not only of a continuous estrogen replacement, but also of ensuring adequate estradiol levels in serum in order to ensure a complete bone maturation and mineralization and to prevent the worsening of body skeletal proportions. The comprehension of this physiological aspect has relevant clinical significance especially for the development of new therapeutic strategies useful to treat growth disorders by targeting serum estradiol in men.

Acylated ghrelin inhibits spontaneous luteinizing hormone pulsatility and responsiveness to naloxone but not that to gonadotropin-releasing hormone in young men: evidence for a central inhibitory action of ghrelin on the gonadal axis.

CONTEXT: Recent evidence suggests that ghrelin exerts a negative modulation on the gonadal axis. Ghrelin was reported to suppress LH secretion in both animal and human models. Moreover, acylated ghrelin (AG) also decreases the LH responsiveness to GnRH in vitro. OBJECTIVE: The objective of the study was to evaluate the effects of AG infusion on spontaneous and stimulated gonadotropin secretion. DESIGN, PARTICIPANTS, AND INTERVENTION: In seven young healthy male volunteers (age mean +/- sem 26.4 +/- 2.6 yr), we evaluated LH and FSH levels every 15 min during: 1) iv isotonic saline infusion; 2) iv saline followed by AG; LH and FSH response to GnRH (100 microg iv as a bolus), 3) alone and 4) during AG infusion; LH and FSH response to naloxone (0.1 mg/kg iv as a slow bolus), 5) alone and 6) during AG infusion. RESULTS: Significant LH but not FSH pulses were recorded in all subjects under saline infusion. AG infusion inhibited LH levels [area under the curve((240-480)): 415.8 +/- 69.7 mIU/ml.min during AG vs. 744.6 +/- 120.0 mIU/ml.min during saline, P < 0.02] and abolished LH pulsatility. No change in FSH secretion was recorded. The LH and FSH responses to GnRH during saline were not affected by AG administration. However, AG inhibited the LH response to naloxone [area under the curve ((120-210)): 229.9 +/- 39.3 mIU/ml.min during AG vs. 401.1 +/- 44.6 mIU/ml.min during saline, P < 0.01]. FSH levels were not modified by naloxone alone or in combination with AG. CONCLUSIONS: AG inhibits both spontaneous LH pulsatility and the LH response to naloxone. Because AG does not affect the LH response to GnRH, these findings indicate that the ghrelin system mediates central inhibition of the gonadal axis.

Ghrelin and prostate cancer.

Ghrelin, a 28-amino acid octanoylated peptide predominantly produced by the stomach, has been discovered to be a natural ligand of the type 1a growth hormone secretagogue receptor (GHSR1a). Ghrelin has recently attracted the interest as a new GH-releasing and orexigenic factor. However, ghrelin exerts several other activities, including regulation of tissue growth and development and control of neoplastic cell proliferation. Several endocrine and nonendocrine cancer cells (pituitary adenomas; gastroenteropancreatic and pulmonary carcinoids; colorectal neoplasms, thyroid tumors; lung, breast, and pancreatic carcinomas) as well as their related cell lines have been shown able to express ghrelin both at mRNA and at protein level. Many of the above-listed tumors express GHSR1a and/or alternative GHS receptor subtypes such as the type 1b GHSR, a truncated isoform of GHSR1a, and binding sites able to recognize ghrelin independently of its acylation. Evidence that ghrelin and multiple ghrelin/GHS receptors are coexpressed in cancer cell lines and tumoral tissues from organs, such as the breast, that do not express these receptors in physiological conditions suggests that the ghrelin system is likely to play an important autocrine/paracrine role in some cancers. This chapter highlights the evidence for the expression of ghrelin and its receptors in one of the most frequent human malignancies, the prostate cancer, and information regarding their potential functional role in related cell lines.

Endocrine and metabolic responses to extreme altitude and physical exercise in climbers.

CONTEXT: Chronic hypoxia induces complex metabolic and endocrine adaptations. High-altitude (HA) exposure is a physiological model of hypoxia. OBJECTIVE: To further investigate the endocrine and metabolic responses to extreme HA. METHODS: We studied nine male elite climbers at sea level and at 5200 m after climbing Mt. Everest. RESULTS: After 7 weeks at HA, body weight was reduced (P<0.05); regarding endocrine variables we observed: a) an increase of 2-h mean GH concentration (P<0.05) as well as of total IGF-I and IGF binding protein-3 levels (P<0.05 for both); b) a prolactin increase (P<0.05) coupled with testosterone decrease (P<0.01) and progesterone increase (P<0.05) without any change in estradiol levels: c) no change in cortisol, ACTH, and dehydroepiandrosterone sulfate (DHEAS) levels; d) an increase in free thyroxine (P<0.05) and free tri-iodothyronine (T(3)) decrease (P<0.05) but no change in TSH levels; e) a plasma glucose decrease (P<0.05) without any change in insulin levels; f) an increase in mean free fatty acid levels (P<0.05); g) despite body weight loss, leptin levels showed non-significant trend toward decrease, while ghrelin levels did not change at all. CONCLUSIONS: The results of the present study in a unique experimental human model of maximal exposure to altitude and physical exercise demonstrate that extreme HA and strenuous physical exercise are coupled with specific endocrine adaptations. These include increased activity of the GH/IGF-I axis and a low T(3) syndrome but no change in ghrelin and leptin that was expected taking into account body weight decrease. These findings would contribute to better understanding human endocrine and metabolic physiology in hypoxic conditions.

Klinefelter's syndrome.

Klinefelter's syndrome is the most common genetic cause of human male infertility, but many cases remain undiagnosed because of substantial variation in clinical presentation and insufficient professional awareness of the syndrome itself. Early recognition and hormonal treatment of the disorder can substantially improve quality of life and prevent serious consequences. Testosterone replacement corrects symptoms of androgen deficiency but has no positive effect on infertility. However, nowadays patients with Klinefelter's syndrome, including the non-mosaic type, need no longer be considered irrevocably infertile, because intracytoplasmic sperm injection offers an opportunity for procreation even when there are no spermatozoa in the ejaculate. In a substantial number of azoospermic patients, spermatozoa can be extracted from testicular biopsy samples, and pregnancies and livebirths have been achieved. The frequency of sex chromosomal hyperploidy and autosomal aneuploidies is higher in spermatozoa from patients with Klinefelter's syndrome than in those from normal men. Thus, chromosomal errors might in some cases be transmitted to the offspring of men with this syndrome. The genetic implications of the fertilisation procedures, including pretransfer or prenatal genetic assessment, must be explained to patients and their partners.