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

Obstructive sleep apnea syndrome (OSAS) is a serious, prevalent condition that has significant morbidity and mortality when untreated. It is strongly associated with obesity and is characterized by changes in the serum levels or secretory patterns of several hormones. Obese patients with OSAS show a reduction of both spontaneous and stimulated growth hormone (GH) secretion coupled to reduced insulin-like growth factor-I (IGF-I) concentrations and impaired peripheral sensitivity to GH. Hypoxemia and chronic sleep fragmentation could affect the sleep-entrained prolactin (PRL) rhythm. A disrupted Hypothalamus-Pituitary-Adrenal (HPA) axis activity has been described in OSAS. Some derangement in Thyroid-Stimulating Hormone (TSH) secretion has been demonstrated by some authors, whereas a normal thyroid activity has been described by others. Changes of gonadal axis are common in patients with OSAS, who frequently show a hypogonadotropic hypogonadism. Altogether, hormonal abnormalities may be considered as adaptive changes which indicate how a local upper airway dysfunction induces systemic consequences. The understanding of the complex interactions between hormones and OSAS may allow a multi-disciplinary approach to obese patients with this disturbance and lead to an effective management that improves quality of life and prevents associated morbidity or death.

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.

Objective: Glucocorticoids are known to decrease protein synthesis and conduction velocity of muscle fibers. However, the degree of impairment of muscle protein synthesis and conduction slowing in patients with Cushing's disease remains poorly characterized. Our objective was to investigate whether and to what extent chronic endogenous hypercortisolism could decrease the circulating levels of muscle proteins and modify myoelectric indexes of sarcolemmal excitability and fatigability.Design: A total of ten patients with Cushing's disease and 30 healthy controls matched for age, sex, and body mass index were compared.Methods: Blood sampling and electrophysiological tests on vastus lateralis, vastus medialis, and tibialis anterior muscles were performed.Results: Serum creatine kinase (CK) and plasma myoglobin were significantly lower in patients with respect to controls (P<0.001 and P<0.05 respectively): the mean relative difference between patients and controls was 48.9% for CK and 21.4% for myoglobin. Muscle fiber conduction velocity (MFCV) and myoelectric manifestations of fatigue were significantly decreased in all muscles of the patients with respect to controls. The mean relative difference in MFCV between patients and controls was 26.0% for vastus lateralis, 22.9% for vastus medialis, and 11.6% for tibialis anterior. These differences contrasted with the paucity of signs suggestive of myopathy that were obtained by needle electromyography in the patients.Conclusions: Slowing of muscle fiber conduction and decreased levels of circulating muscle proteins are sensitive markers of impaired muscle function, which are suitable for use in combination with clinical assessment and standard electrodiagnostic tests for accurate identification and follow-up of myopathic patients.