Premature Adrenarche and its Association with Cardiovascular Risk in Females

Early activation of the adrenal zona reticularis, leading to adrenal androgen secretion, mainly dehydroepiandrosterone sulfate (DHEAS), is called premature adrenarche (PA). The fact that adrenal hyperandrogenism in females has been linked to a cluster of cardiovascular (CV) risk factors, even in prepubertal children, warrants investigation. Controversial results have been obtained in this field, probably due to genetic, constitutional, and environmental factors or differences in the characteristics of participants. In an attempt to understand, in depth, the impact of PA as a potential activator of CV risk, we critically present available data stratified according to pubertal status. It seems that prepubertally, CV risk is increased in these girls, but is somewhat attenuated during their second decade of life. Furthermore, different entities associated with PA, such as polycystic ovary syndrome, non-classical congenital adrenal hyperplasia, heterozygosity of CYP21A2 mutations, and the impact of DHEAS on CV risk, are reviewed. At present, firm and definitive conclusions cannot be drawn. However, it may be speculated that girls with a history of PA display a hyperandrogenic hormonal milieu that may lead to increased CV risk. Accordingly, appropriate long-term follow-up and early intervention employing a patient-oriented approach are recommended.

POLY CYSTIC OVARIAN SYNDROME: AN UPDATED REVIEW

Polycystic ovarian syndrome(PCOS) is the most common endocrine and inflammatory disorder in women associated with oligo-anovulatory infertility and cardiometabolic disorder. Insulin plays a vital role in PCOS; it is also responsible for regulating the action of ovarian and liver metabolic enzymes and also involved in the production of Androgens. The hyperandrogenism prevalence nearly (70-80%). In PCOS, the target tissue is controlled by sex hormone-binding globulin(SHBG) because this is a type of protein produced by hepatic and tightly bind with testosterone and as well as dihydrotestosterone (DHT) and estradiol.[3] Currently study reported, associated with rs6259 polymorphism with link SHBG level and PCOS in most Indian women, nearly 3-5%. The PCOS cases associated with isolated functional adrenal hyperandrogenism and the remaining case of PCOS maybe lack clinical evidence of steroids secretory dysfunction. Most of the females are obese in PCOS; the treatment approaches of PCOS are towards improving insulin tolerance reduce the level of androgen and maintain the normal menstrual cycle and regulate proper fertility. Nonpharmacological approaches are also helpful, like proper exercise, weight management, and maintain healthy diets. The etiology is still unclear, not clear, and has no cure. Some studies reported dysregulation of the gut microbiome and played the crucial role played in Pathogenesis in PCOS.

Utilisation of gonadotrophin-releasing hormone (GnRH) analogue to differentiate ovarian from adrenal hyperandrogenism in postmenopausal women

Summary Postmenopausal hyperandrogenism is a relatively rare diagnosis resulting from excess androgen production from the adrenals or ovaries. The exclusion of malignant causes is a priority. Laboratory tests and imaging are utilised to help differentiate the source of excess androgens. We report two cases of postmenopausal hyperandrogenism in women aged 75 and 67 years. Both cases presented with clinical features suggestive of hyperandrogenism which had developed gradually over the previous 2 years. Laboratory investigations confirmed a significant elevation in their serum testosterone levels. In both cases, imaging did not reveal any abnormality of the adrenals or ovaries. To help differentiate an adrenal vs ovarian source a single-dose GnRH analogue was given with measurement of testosterone and gonadotrophin levels pre and post. The reduction in gonadotrophins achieved by the GnRH analogue resulted in suppression of testosterone levels which suggested an ovarian source. Both patients proceeded to bilateral oophorectomy. Histology revealed a benign hilus cell tumour in one case and a benign Leydig cell tumour in the other. Learning points: A key part of the work-up of postmenopausal hyperandrogenism is to differentiate between an adrenal or an ovarian source of excess androgens; Imaging may not identify small ovarian tumours or hyperthecosis and may also identify incidental adrenal masses which are non-functioning; Current guidelines suggest ovarian and adrenal venous sampling when imaging is inconclusive but this requires technical expertise and has a high failure rate; GnRH analogue use can successfully confirm ovarian source and should be considered as a diagnostic tool in this setting.

An unusual circulating steroid profile in a virilized postmenopausal woman

Background: Virilism is a female disorder in which secondary male sexual characteristics develop, caused by an excessive adrenal or ovarian androgen secretion. Case presentation: Here, we report an unusual case of an ovarian steroid cell tumor, not otherwise specified (NOS), in a 68-year-old female who presented with androgenic alopecia, clitoromegaly and an increased muscle mass. Laboratory investigations revealed both ovarian and adrenal hyperandrogenism with an elevation of androgen precursors mimicking congenital adrenal hyperplasia. A left adnexal mass was confirmed by imaging techniques. A laparoscopic bilateral salpingo-oophorectomy was performed and histopathology confirmed the diagnosis of an ovarian steroid cell tumor NOS. After surgical intervention, circulating androgen levels and their precursors returned to normal values in the postmenopausal woman. Conclusions: A detailed anamnesis and physical examination are key to the correct diagnosis in a woman with hyperandrogenism independent of her circulating androgen profile.

Adrenal hyperandrogenism does not deteriorate insulin resistance and lipid profile in women with PCOS

Objective The aim of this study was to investigate the impact of adrenal hyperandrogenism on insulin resistance and lipid profile in women with polycystic ovary syndrome (PCOS). Patients and methods We studied 372 women with PCOS according to the NIH criteria. 232 age- and BMI-matched women served as controls in order to define adrenal hyperandrogenism (DHEA-S >95th percentile). Then, patients with PCOS were classified into two groups: with adrenal hyperandrogenism (PCOS-AH, n = 108) and without adrenal hyperandrogenism (PCOS-NAH, n = 264). Anthropometric measurements were recorded. Fasting plasma glucose, insulin, lipid profile, sex hormone-binding globulin (SHBG) and androgen (TT, Δ4A, DHEA-S) concentrations were assessed. Free androgen index (FAI) and homeostatic model assessment-insulin resistance (HOMA-IR) index were calculated. Results Women with PCOS-AH were younger than PCOS-NAH (P < 0.001), but did not differ in the degree and type of obesity. No differences were found in HOMA-IR, total cholesterol, HDL-c, LDL-c and triglyceride concentrations (in all comparisons, P > 0.05). These metabolic parameters did not differ between the two groups even after correction for age. Women with PCOS-AH had lower SHBG (29.2 ± 13.8 vs 32.4 ± 11.8 nmol/L, P = 0.025) and higher TT (1.0 ± 0.2 vs 0.8 ± 0.4 ng/mL, P = 0.05) and Δ4A (3.9 ± 1.2 vs 3.4 ± 1.0 ng/mL, P = 0.007) concentrations, as well as FAI (14.1 ± 8.0 vs 10.2 ± 5.0, P < 0.001). These results were confirmed by a multiple regression analysis model in which adrenal hyperandrogenism was negatively associated with age (P < 0.001) and SHBG concentrations (P = 0.02), but not with any metabolic parameter. Conclusions Women with PCOS and adrenal hyperandrogenism do not exhibit any deterioration in insulin resistance and lipid profile despite the higher degree of total androgens.

Programming of the Hypothalamus-Pituitary-Adrenal Axis by Very Preterm Birth

Background: Many very preterm (i.e., <32 weeks of gestation) newborns fail to mount an adequate adrenocortical response to stress or illness, termed relative adrenal insufficiency. Conversely, later in life these infants show features of increased glucocorticoid bioactivity, such as abdominal adiposity, insulin resistance, raised blood pressure, shorter stature and internalizing problem behavior. Summary: Studies suggested that very preterm newborns have impairments along multiple levels of the hypothalamus-pituitary-adrenal (HPA) axis. Among the impairment were defects in: (1) the pituitary responsiveness to exogenous corticotropin-releasing hormone, (2) 11β-hydroxylase activity, and (3) the interconversion between cortisol and inert cortisone. There is some evidence suggesting that later in life these infants have an increased basal secretion rate of cortisol and adrenal hyperandrogenism. However, the response to acute (psychosocial) stress was blunted rather than enhanced in them. The mechanisms explaining this switch in HPA axis activity are complex and not yet fully understood. Key Messages: Very preterm newborns have several impairments along the HPA axis that could impede an adequate adrenocortical response to stress or illness. Later in life, these infants are predisposed to increased HPA axis activity, which could partially explain their phenotype.