Giovanna Motta

Neuroendocrine Alterations in Obese Patients with Sleep Apnea Syndrome

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.

Steroid myopathy: some unresolved issues.

Steroid myopathy is a non-inflammatory toxic myopathy that occurs as side effect of exogenous and endogenous glucocorticoid excess. The purpose of this review is to examine issues that limit our understanding of this myopathy with respect to nosology, etiopathogenesis, conditioning factors, and muscle fiber selectivity. We suggest that if more data were available on these issues, the understanding of steroid myopathy would be enhanced substantially, thus allowing an early detection of its occurrence (before the appearance of clinical or laboratory signs) and a proper treatment of the patients.

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.

Growth hormone/insulin-like growth factor-I axis in obstructive sleep apnea syndrome: An update

Obstructive sleep apnea syndrome (OSAS) is a serious, prevalent condition that has significant mortality and morbidity when untreated. It is strongly associated with obesity and is characterized by changes in the serum levels or secretory patterns of several hormones. In particular, obese patients with OSAS show a peculiar reduction of both spontaneous and stimulated GH secretion coupled with reduced IGF-I concentrations and impaired peripheral sensitivity to GH. These endocrine abnormalities are more marked than those observed in non-apneic obese subjects, and are likely to be due to the effects of hypoxia and sleep fragmentation on hormone secretory pattern. The GH/IGF-I axis activity disruption can be responsible, at least in part, for metabolic alterations, which are common in OSAS and increase the risk of cardiovascular events as well as mortality. Effective assessment and management of OSAS may correct endocrine changes, improve quality of life, and prevent associated morbidity or death.

Do muscle fiber conduction slowing and decreased levels of circulating muscle proteins represent sensitive markers of steroid myopathy? A pilot study in Cushing's disease

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 Cushings 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 Cushings 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.

Quantitative and qualitative adaptations of muscle fibers to glucocorticoids.

Introduction: The aim of this study was to understand the effects of short‐term glucocorticoid administration in healthy subjects. Methods: Five healthy men received dexamethasone (8 mg/day) for 7 days. Vastus lateralis muscle biopsy and knee extension torque measurement were performed before and after administration. A large number of individual muscle fibers were dissected from the biopsy samples (pre‐administration: n = 165, post‐administration: n = 177). Results: Maximal knee extension torque increased after administration (∼13%), whereas both type 1 and type 2A fibers had decreased cross‐sectional area (type 1: ∼11%, type 2A: ∼17%), myosin loss (type 1: ∼18%, type 2A: ∼32%), and loss of specific force (type 1: ∼24%, type 2A: ∼33%), which were preferential for fast fibers. Conclusion: Short‐term dexamethasone administration in healthy subjects elicits quantitative and qualitative adaptations of muscle fibers that precede (and may predict) the clinical appearance of myopathy in glucocorticoid‐treated subjects. Muscle Nerve 52: 631–639, 2015

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.

Genotype, phenotype and hormonal levels correlation in non-classical congenital adrenal hyperplasia

Non-classical congenital adrenal hyperplasia (NCAH) is a morbid condition sustained by the reduced function of one of the enzymes involved in the adrenal steroid biosynthesis pathway, mainly the 21-hydroxylase. Different degrees of enzyme activity impairment determine different clinical pictures, with childhood or post-pubertal onset. The aim of this study was to evaluate the relationship between genotype, phenotype, and adrenal hormonal levels in a group of 66 patients affected by NCAH attending outpatient pediatric or endocrinological Clinics. Our findings show that age at pubarche/menarche was significantly younger, height SD score) and Δ bone age-chronological age were significantly higher in patients with a more severe enzyme activity impairment, while cutaneous androgenization and menstrual irregularities in post-pubertal girls were not related to the grading of genotype.

Sociodemographic characteristics and traumatic experiences in an Italian transgender sample

ABSTRACT The aim of the present study is to define the sociodemographic and clinical characteristics of applicants for gender-affirming surgery at a single Italian institute, officially accredited as the referral unit for gender dysphoria in the Piedmont region. The study population comprised 196 transgender patients (136 trans females and 60 trans males) who met the criteria for gender dysphoria (GD; DSM-5 American Psychiatric Association, 2013). The subjects were asked to supply detailed information about general demographic characteristics, personal relationships, and traumatic events. Our data showed that participants who had experienced traumatic events sought assistance at an older age, had a lower level of education and a higher rate of unemployment, and had taken cross-sex hormonal therapy without a doctors prescription at a higher frequency than those without experience of traumatic events. In order to better understand the role of trauma in the lives of transgender people, further research is needed in order to expand on our findings and make the proper adjustments to psychological treatment to improve patients’ well-being.

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. Todays 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.