Renato Pasquali

Obesity is an emerging condition, with a prevalence of ~20%. Although the simple measurement of BMI is likely a simplistic approach to obesity, BMI is easily calculated, and there are currently no data showing that more sophisticated methods are more useful to guide the endocrine work-up in obesity. An increased BMI leads to a number of hormonal changes. Additionally, concomitant hormonal diseases can be present in obesity and have to be properly diagnosed – which in turn might be more difficult due to alterations caused by body fatness itself. The present European Society of Endocrinology Clinical Guideline on the Endocrine Work-up in Obesity acknowledges the increased prevalence of many endocrine conditions in obesity. It is recommended to test all patients with obesity for thyroid function, given the high prevalence of hypothyroidism in obesity. For hypercortisolism, male hypogonadism and female gonadal dysfunction, hormonal testing is only recommended if case of clinical suspicion of an underlying endocrine disorder. The guideline underlines that weight loss in obesity should be emphasized as key to restoration of hormonal imbalances and that treatment and that the effect of treating endocrine disorders on weight loss is only modest.

Androgen excess is often associated with obesity states, at any age of life, because of changes in the pattern of secretion or metabolism of androgens and in their actions at the level of target tissues, particularly the adipose tissue. Androgen excess plays an important role in favouring the expansion of visceral fat, which characterize so-called visceral obesity. Moreover, there is evidence that the combination of androgen excess and obesity may favour the development of metabolic disorders, such as the metabolic syndrome and type 2 diabetes. In obese adolescent girls, androgen excess may also suggest the potential development of the polycystic ovary syndrome (PCOS). A new hypothesis, based on long-term lifestyle intervention programs or bariatric surgery, supports the concept that a “PCOS secondary to obesity” may exist, as confirmed by the complete resolution of all features defining PCOS after considerable weight loss. Obesity can also develop after long-term exposure to chronic stress, which is characterized by increased activity of the hypothalamic-pituitary-adrenal axis and the sympathetic system combined with higher than normal androgen production rates in women. This increasingly observed condition, often underestimated, should be considered more carefully, not only in mature women but also in girls during adolescence. The presence of a hyperandrogenic state can also be detected in menopausal women, as a consequence of the rearrangement of the sex hormone balance which, in turn, may play some role in determining the development of both visceral adiposity and even obesity and, consequently, metabolic disorders. Undoubtedly, the recognition of the potential negative effects of androgen excess in obese women may open new therapeutic perspectives aimed at achieving a sustained weight loss and its maintenance for as long as possible.

New perspectives on the role of anti-Müllerian hormone (AMH) in women

Branched-chained amino acids (BCAA) are essential dietary components for humans and can act as potential biomarkers for diabetes development. To efficiently estimate dietary intake, we developed a BCAA database for 1331 food items found in the French Centre d’Information sur la Qualité des Aliments (CIQUAL) food table by compiling BCAA content from international tables, published measurements, or by food similarity as well as by calculating 267 items from Greek, Turkish, Romanian, and Moroccan mixed dishes. The database embedded in MEDIPAD software capable of registering 24 h of dietary recalls (24HDR) with clinical and genetic data was evaluated based on archived 24HDR of the Saint Pierre Institute (France) from 2957 subjects, which indicated a BCAA content up to 4.2 g/100 g of food and differences among normal weight and obese subjects across BCAA quartiles. We also evaluated the database of 119 interviews of Romanians, Turkish and Albanians in Greece (27–65 years) during the MEDIGENE program, which indicated mean BCAA intake of 13.84 and 12.91 g/day in males and females, respectively, comparable to other studies. The MEDIPAD is user-friendly, multilingual, and secure software and with the BCAA database is suitable for conducting nutritional assessment in the Mediterranean area with particular facilities for food administration.

Introduction: Cardiovascular morbidity is more prevalent in primary aldosteronism (PA) than in essential hypertension. Preclinical studies have shown a possible association between ascending aorta dilatation and PA, probably mediated by the mineralocorticoid receptor. Patients and methods: A total of 84 patients attending the Endocrinology Unit of the S. Orsola-Malpighi University Hospital of Bologna, (Italy) were evaluated. Thirty-nine patients had a diagnosis of PA. The control group (NS) consisted of 45 hypertensive patients with an adrenal adenoma or hyperplasia, in whom primary aldosteronism, hypercortisolism and pheocromocytoma were appropriately excluded. All patients underwent transthoracic echocardiographic assessment at baseline. Ten PA patients underwent adrenalectomy due to unilateral adrenal disease, whereas the remaining 29 PA subjects were treated with a mineralocorticoid receptor antagonist. The aortic root was measured on each echocardiographic assessment. PA patients underwent a further echocardiographic evaluation during follow-up. Results: PA and NS groups were homogeneous as to age and body surface area. The aortic root was significantly higher at baseline in PA group as compared with NS group (34.9±5.3 mm vs 32.2±3.9 mm, PP=0.47). In the medically treated PA group, the aortic root measured 34.6±4.7 mm at baseline and 35.1±4.8 mm at follow-up (P=0.94). Also, percentage variation did not show statistical significance in either group. Conclusion: PA patients showed larger aortic roots as compared with a homogeneous hypertensive population. Our preliminary follow-up data suggest that treatment of primary aldosteronism might not reverse vascular damage, thus suggesting a pathogenesis of irreversible vascular fibrosis induced by aldosterone excess.

Introduction: Clinical and laboratory hyperandrogenisms indistinctly contribute to PCOS diagnosis; however, they differ in hormonal and metabolic correlates and require proper therapeutic strategies. Circulating biomarkers of hirsutism were not identified so far, with elevated testosterone being observed only in half of hirsute patients. Reasons for such inconsistencies possibly relies in previously used immunoassays, nowadays recognized as not adequate because of poor reliability and limited steroid panel. The present study aimed at defining the circulating steroid fingerprint that specifically distinguishes hirsutism by LC-MS/MS profiling of a broad steroid panel. Methods: Sixteen serum steroids were determined in 352 patients (age 14–49 years) in follicular phase. The independent effect of ovarian dysfunction (OD; oligo-amenorrhea and/or PCO morphology), hyperandrogenemia (testosterone≥1.56 nmol/L and/or androstenedione≥5.72 nmol/L) and hirsutism (modified-Ferriman-Gallway score≥8) on circulating steroids was valued. Moreover, hirsute (n=74) vs not-hirsute (n=47) women were compared within patients showing both OD and hyperandrogenemia. Results: OD directly associated with LH (P=0.048) and LH/FSH (PPP=0.002), 17OHprogesterone/progesterone (PP=0.004), androstenedione/dehydroepiandrosterone (PP=0.026), dehydroepiandrosterone (P=0.029), dehydroepiandrosterone-sulfate (P=0.034) and 11deoxycortisol/17OHprogesterone (P=0.003). Hyperandrogenemia positively associated with mFG-score (P=0.012), ACTH, LH and LH/FSH (all PP=0.025) and HOMA-IR (P=0.045). Hyperandrogenemia positively associated with 17OHpregnenolone, progesterone, dehydroepiandrosterone, 17OHprogesterone, estrone (all PP=0.004), dihydrotestosterone (P=0.009), corticosterone, 11deoxycortisol, cortisol (all PP=0.009), 17OHprogesterone/progesterone (PP=0.014), and negatively with dehydroepiandrosterone-sulfate/dehydroepiandrosterone, testosterone/androstenedione, estrone/androstenedione, estradiol/testosterone, dihydrotestosterone/testosterone and cortisol/11deoxycortisol (all PP=0.014) and inversely with HDL (P=0.041). Hirsutism also associated with lowering progesterone (P=0.007) and 17OHprogesterone (P=0.003) and increasing androstenedione/17OHprogesterone (PP=0.021). Compared with not-hirsute, hirsute women with OD and hyperandrogenemia exhibited higher BMI (P=0.002) and dehydroepiandrosterone/17OHpregnenolone (P=0.011), and lower SHBG (P=0.001), 17OHprogesterone (P=0.030), testosterone (P=0.004), androstenedione/dehydroepiandrosterone (P=0.024) and testosterone/androstenedione (P=0.039). Conclusions: Androstenedione excess in OD apparently originates by gonads, as indicated by imbalanced gonadotropin, low progesterone, increased 17hydroxylase activity and reduced adrenal secretion. Hyperandrogenemia is featured by insulin resistance, combined ovarian and adrenal hypersecretion of the overall steroid profile, and reduced precursors’ conversion in downstream active steroids. Hirsutism is characterized by obesity and dyslipidemia, by low 17OHprogesterone and, in the PCOS context, by mild hypertestosteronemia and reduced SHBG, overall suggesting that this phenotype could result by increased free-androgens at the pilosebaceous unit.

Polycystic ovary syndrome (PCOS) is a common disorder in women in their reproductive years and is characterized by androgen excess, ovulatory dysfunction, and polycystic ovarian morphology. It is also associated with several metabolic abnormalities, particularly insulin resistance and obesity, which play an important role in the pathophysiology of PCOS and, in particular, negatively influence ovarian function and fertility. This review article summarizes the available treatment for women with PCOS. Specifically, current and potentially new therapies are discussed.

There is a growing debate on the opportunity of improving the understanding in the diagnosis and management of polycystic ovary syndrome (PCOS).