MECHANISMS IN ENDOCRINOLOGY: Metabolic syndrome through the female life cycle

The normal function of the female reproductive system is closely linked to energy homeostasis with the ultimate scope of fertility and human race perpetuation through the centuries. During a woman's lifetime there are normal events such as puberty, pregnancy and menopause which are related to alterations in energy homeostasis and gonadal steroids levels followed by increase of body fat and insulin resistance, important components of metabolic syndrome (MetS). Pathological conditions such as premature adrenarche, polycystic ovary syndrome and gestational diabetes also present with shifts in gonadal steroid levels and reduced insulin sensitivity. The aim of this review is to discuss these conditions, both normal and pathological, analyzing the changes or abnormalities in ovarian function that coexist with metabolic abnormalities which resemble MetS in relationship with environmental, genetic and epigenetic factors

Biological therapies for premature ovarian insufficiency: what is the evidence?

Premature Ovarian Insufficiency (POI) is a multi-factorial disorder that affects women of reproductive age. The condition is characterized by the loss of ovarian function before the age of 40 years and several factors have been identified to be implicated in its pathogenesis. Remarkably though, at least 50% of women have remaining follicles in their ovaries after the development of ovarian insufficiency. Population data show that approximately up to 3.7% of women worldwide suffer from POI and subsequent infertility. Currently, the treatment of POI-related infertility involves oocyte donation. However, many women with POI desire to conceive with their own ova. Therefore, experimental biological therapies, such as Platelet-Rich Plasma (PRP), Exosomes (exos) therapy, In vitro Activation (IVA), Stem Cell therapy, MicroRNAs and Mitochondrial Targeting Therapies are experimental treatment strategies that focus on activating oogenesis and folliculogenesis, by upregulating natural biochemical pathways (neo-folliculogenesis) and improving ovarian microenvironment. This mini-review aims at identifying the main advantages of these approaches and exploring whether they can underpin existing assisted reproductive technologies

Favorable Effect of Anti-TNF Therapy on Insulin Sensitivity in Nonobese, Nondiabetic Patients with Inflammatory Bowel Disease

Background. The aim of this study was to investigate the effect of anti-TNF therapy on glucose and lipid metabolism in nondiabetic, nonobese patients with inflammatory bowel disease (IBD). Patients and Methods. We studied 44 patients with IBD, without a known history of diabetes. Three of the patients were diagnosed with overt diabetes and were excluded. Eighteen of the remaining patients (9 M/9 F, 33.6 ± 8.8 years) were on anti-TNF therapy for longer than 1 year, while 23 patients (16 M/7 F, 38.7 ± 12.5 years) were treated with aminosalicylates (AMSs). Twelve of the patients from the second group were then treated with anti-TNF and reassessed 6 months later. Fasting glucose, insulin, c-peptide, HbA1c, lipid, CRP, and fibrinogen levels were determined, and HOMA-IR index was calculated in all patients. Results. Patients from the two therapy groups were matched for age and BMI and were not obese. We did not find any differences between patients from the two therapy groups regarding fasting glucose, c-peptide, HbA1c, total cholesterol, HDL, LDL, triglycerides, CRP, and HOMA-IR index. In patients who were treated for 6 months with anti-TNF, a statistically significant decrease in insulin (before 15.5 ± 5.9 versus after 9.9 ± 2.9 μIU/ml, p=0.042) and c-peptide (before 2.4 ± 1 versus after 1.3 ± 0.4 ng/ml, p=0.030) levels as well as the HOMA-IR index (before 4.2 ± 1.9 versus after 2.2 ± 0.9, p=0.045) was observed, without any changes in weight, BMI, glucose, HbA1c, lipid, CRP, and fibrinogen levels. Conclusion. Anti-TNF therapy exerts a favorable effect on insulin sensitivity, while it has no effect on lipid levels in nondiabetic, nonobese patients with inflammatory bowel disease

Cardiac tamponade in a patient with autoimmune polyglandular syndrome type 2

We describe a case of a 40-year-old woman who was admitted to the intensive care unit with a rapid onset of dyspnea and orthopnea. She presented progressive weakness, weight loss and secondary amenorrhea during last year, while intermittent fever was present for the last two months. Initial biochemical evaluation showed anemia, hyponatremia and increased C-reactive protein levels. Clinical and echocardiographic evaluation revealed cardiac tamponade, which was treated with pericardiocentesis. Pleural fluid samples were negative for malignancy, tuberculosis or bacterial infection. Hormonal and serologic evaluation led to the diagnosis of autoimmune polyglandular syndrome (APS) type 2 (including primary adrenal insufficiency and autoimmune thyroiditis), possibly coexisting with systemic lupus erythematosus. After symptomatic rheumatologic treatment followed by replacement therapy with hydrocortisone and fludrocortisone, the patient fully recovered. In patients with the combination of polyserositis, cardiac tamponade and persistent hyponatremia, possible coexistence of rheumatologic and autoimmune endocrine disease, mainly adrenal insufficiency, should be considered. Early diagnosis and non-invasive treatment can be life-saving

Hypokalemia: a clinical update

Hypokalemia is a common electrolyte disturbance, especially in hospitalized patients. It can have various causes, including endocrine ones. Sometimes, hypokalemia requires urgent medical attention. The aim of this review is to present updated information regarding: (1) the definition and prevalence of hypokalemia, (2) the physiology of potassium homeostasis, (3) the various causes leading to hypokalemia, (4) the diagnostic steps for the assessment of hypokalemia and (5) the appropriate treatment of hypokalemia depending on the cause. Practical algorithms for the optimal diagnostic, treatment and follow-up strategy are presented, while an individualized approach is emphasized

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 0.05). 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

MENSTRUAL DISORDERS AND ANDROGEN-RELATED TRAITS IN YOUNG WOMEN WITH TYPE 1 DIABETES MELLITUS: A CLINICAL STUDY

Objective: To investigate possible causes of menstrual disorders and androgen-related traits in young women with type 1 diabetes mellitus (T1DM). Methods: Fifty-three women with T1DM (duration 8.0 +/- 5.6 years), 41 women with (polycystic ovary syndrome) PCOS, and 51 controls matched for age (19.4 +/- 4.3 years vs. 21.2 +/- 2.7 years vs. 20.8 +/- 3.1 years; P&gt;.05) and body mass index (BMI) (22.2 +/- 2.7 kg/m(2) vs. 21.9 +/- 2.0 kg/m(2) vs. 21.4 +/- 1.9 kg/m(2); P&gt;.05) were prospectively recruited. Results: Two women (3.8%) in the T1DM group had not experienced menarche (at 15.5 and 16.6 years); of the rest, 2.3.5% had oligomenorrhea, 32.1% hirsutism, and 45.3% had acne. The age at menarche was delayed in the T1DM group compared to controls (12.7 +/- 1.3 vs. 12.0 +/- 1.0 years; P = .004), while no difference was observed with the polycystic ovary syndrome (PCOS) group (12.4 +/- 1.2 years). There were no differences in total testosterone (0.43 +/- 0.14 ng/mL vs. 039 +/- 0.14 ng/mL; P&gt;.05), dehydroepi- androsterone sulfate (DHEA-S) (269 +/- 112 mu g/dL vs. 238 +/- 106 mu g/dt,; P&gt;.05) or Delta 4-androstenedione (2.4 +/- 1.3 ng/mL vs. 1.9 +/- 0.5 ng/mL; P&gt;.05) concentrations between T1DM and controls. However, patients with T1DM had lower sex hormone binding globulin (SHBG) concentrations than controls (61 +/- 17 nmol/L, vs. 83 +/- 18.1 nmol/L; P = .001), which were even lower in the PCOS group (39.5 +/- 12.9 nmol/L; P = .001 compared with T1DM). The free androgen index (FAI) was higher in the PCOS group compared with both other groups (T1DM vs. PCOS vs. controls: 2.53 +/- 0.54 vs. 7.88 +/- 1.21 vs. 1.6 +/- 0.68; P&lt;.001). FAI was higher in patients with T1DM compared to controls as well (P = .038). There was no difference in DHEA-S concentrations between T1DM and PCOS patients (269 +/- 112 mu g/dt, vs. 297 +/- 100 mu g/dL; P&gt;.05). Conclusion: Menstrual disorders and androgen-related traits in young women with T1DM may be attributed to an increase in androgen bioavailability due to decreased SHBG concentrations

Use of thyroid hormones in hypothyroid and euthyroid patients: a 2020 THESIS questionnaire survey of members of the Hellenic Endocrine Society

Purpose To investigate current practices of specialists in the use of thyroid hormone preparations in Greece as part of an ongoing international survey, namely THESIS-Treatment of Hypothyroidism in Europe by Specialists: an International Survey. Methods An electronic link leading to an anonymized questionnaire was sent to all (n = 837) members of the Hellenic Endocrine Society. Results In total, 501 respondents participated in the survey, though only part of the questionnaire was filled in by some participants. A total of 88.2% were endocrinologists and 57.9% worked in private practice. Levothyroxine (LT4) was the first-line choice (98.6%) for the treatment of hypothyroid patients. In total, 70.2% preferred LT4 soft-gel capsules for patients reporting intolerance to various foods. Soft-gel capsules were the preferred LT4 formulation for patients on generic LT4 and with unexplained poor biochemical control of hypothyroidism (66.3%) or inability to take LT4 fasted and separate from food/drink (68.3%). It was found that 48.4% would never use combined LT4 + LT3. However, 25% would use combination therapy for a short period in patients recovering from protracted hypothyroidism or in patients with normal serum TSH but persistent symptoms. Concerning euthyroid individuals, 31.9% considered treatment with thyroid hormones in infertile females with positive thyroid antibodies and 24.4% in patients with growing goiter. Selenium or iodine supplementation was used occasionally, mostly in patients with coexisting autoimmune thyroiditis. Conclusions LT4 tablets are the treatment of choice for hypothyroidism in Greece. Several conditions may lead to various other practices, some of which deviate from current evidence-based guidelines and need more scrutiny