Luteinizing hormone and insulin resistance in menopausal patients with adrenal incidentalomas: The cause-effect relationship?

OBJECTIVE: A high prevalence of insulin resistance (IR) has proven to manifest in patients with adrenal incidentalomas (AI). It has been demonstrated that an increase in IR is related to the size of tumourous masses; additionally, luteinizing hormone (LH)-dependent adrenal pathologies are well documented in patients with LH-responsive adrenal tumours occurring under conditions of physiologically elevated LH. We hypothesized that an association between LH and insulin might play a role in adrenal tumourigenesis and steroidogenesis. DESIGN: The aim of our study was to investigate the association between LH and IR; adrenal tumour size (ATS) and IR; LH and cortisol after the 1 mg overnight dexamethasone test (1 mg DST); and ATS and 1 mg DST cortisol in AI patients. This was a case-control study conducted in the Clinic for Endocrinology, Diabetes and Metabolic Diseases in Belgrade, Serbia. The total study group consisted of 105 menopausal women: 75 AI patients [27 with nonfunctional AI (NAI) and 48 with (possible) autonomous cortisol secretion ((P)ACS)] and 30 age-, BMI-, LH- and menopause duration-matched healthy control (HC) women. To estimate IR, we used homeostasis model assessment (HOMA-IR). RESULTS: Luteinizing hormone and ATS are in a significant positive correlation with HOMA-IR and 1 mg DST cortisol in menopausal patients with AI and (P)ACS. CONCLUSIONS: Our data point to a possible cause-effect relationship between LH and insulin in patients with AI and (P)ACS adding to the body of evidence of their involvement in adrenal tumourigenesis and steroidogenesis.

Obstructive Sleep Apnea Is Associated With Low Testosterone Levels in Severely Obese Men.

Background: Disrupted sleep affects cardio-metabolic and reproductive health. Obstructive sleep apnea syndrome represents a major complication of obesity and has been associated with gonadal axis activity changes and lower serum testosterone concentration in men. However, there is no consistent opinion on the effect of obstructive sleep apnea on testosterone levels in men. Objective: The aim of this study was to determine the influence of obstructive sleep apnea on total and free testosterone levels in severely obese men. Materials and methods: The study included 104 severely obese (Body Mass Index (BMI) ≥ 35 kg/m2) men, aged 20 to 60, who underwent anthropometric, blood pressure, fasting plasma glucose, lipid profile, and sex hormone measurements. All participants were subjected to polysomnography. According to apnea-hypopnea index (AHI) patients were divided into 3 groups: <15 (n = 20), 15 - 29.9 (n = 17) and ≥ 30 (n = 67). Results: There was a significant difference between AHI groups in age (29.1 ± 7.2, 43.2 ± 13.2, 45.2 ± 10.2 years; p < 0.001), BMI (42.8 ± 5.9, 43.2 ± 5.9, 47.1 ± 7.8 kg/m2; p = 0.023), the prevalence of metabolic syndrome (MetS) (55%, 82.4%, 83.6%, p = 0.017), continuous metabolic syndrome score (siMS) (4.01 ± 1.21, 3.42 ± 0.80, 3.94 ± 1.81, 4.20 ± 1.07; p = 0.038), total testosterone (TT) (16.6 ± 6.1, 15.2 ± 5.3, 11.3 ± 4.44 nmol/l; p < 0.001) and free testosterone (FT) levels (440.4 ± 160.8, 389.6 ± 162.5, 294.5 ± 107.0 pmol/l; p < 0.001). TT level was in a significant negative correlation with AHI, oxygen desaturation index (ODI), BMI, MetS and siMS. Also, FT was in a significant negative correlation with AHI, ODI, BMI, age, MetS and siMS. The multiple regression analysis revealed that both AHI and ODI were in significant correlation with TT and FT after adjustment for age, BMI, siMS score and MetS components. Conclusion: Obstructive sleep apnea is associated with low TT and FT levels in severely obese men.

Approach to the Patient with Subclinical Cushing's Syndrome.

A growing number of patients with adrenal incidentalomas and subclinical Cushing's syndrome (SCS) led to an increasing number of different guidelines, and diagnostic and treatment recommendations. Excess cortisol secretion in patients with SCS is associated with several comorbidities, such as hypertension, dyslipidemia, type 2 diabetes mellitus, and obesity, which in the long-term increase mortality of these patients. Subtle cortisol secretion affects bone health, quality of life and causes depression, but due to the unapparent clinical features, patients with SCS are often at risk between over and under treatment. This narrative review aimed to summarize the latest recommendations on the approach to the patient with subclinical Cushing's syndrome.

Ghrelin and the enteroinsular axis in healthy men.

OBJECTIVE: Ghrelin, a potent stimulator of GH secretion, also acts as an orexigenic hormone. Plasma ghrelin levels rise before meals with postprandial reduction, suggesting that circulating levels of enteroinsular hormones might influence ghrelin secretion. AIM: The aim of this study was to evaluate the effects of ghrelin on enteroinsular hormones in healthy men. DESIGN: Three tests were performed on 3 different days in 6 healthy men: On the first day, saline was infused from 0-120 minutes followed by a ghrelin bolus (1 microg/kg) administration (Test 1); on the second experimental day, GHRH was administered at 0 min, and a ghrelin bolus was given at 120 min (Test 2); on the third experimental day, GHRP-6 was administered at 0 min, followed by a ghrelin bolus at 120 min (Test 3). Plasma glucose, insulin, proinsulin, C-Peptide Glucagone Like Peptide one (GLP-1) determined at 0, 15, 30, 60, 90, and 120 min of the test period. RESULTS: There was a significant increase in AUC glucose (526.41+/-22.91 mmol . ml(-1) . min vs. 566.37+/-15.64 mmol . ml(-1) . min; p<0.05) and AUC insulin (756.25+/-107.56 mU . ml(-1) . min vs. 981.62+/-180.32 mU . ml(-1) . min; p<0.05) and a significant decrease in AUC GLP-1 (2346.87+/-874.28 pmol . ml(-1) . min vs. 1769.5+/-784 pmol . ml(-1) . min; p<0.05) after ghrelin administration in Test 1 compared to Test 3. There was a mild but non-significant increase in AUC for insulin, proinsulin, and C-Peptide and a mild reduction in AUC GLP-1 after every ghrelin administration. CONCLUSION: There was no evidence of a direct effect of ghrelin administration on enteroinsular hormone levels in this study. However, ghrelin may potentiate the glucose-insulin stimulatory effects of GHRP-6. More studies should be carried out for further evaluation of ghrelin-enteroinsular hormones interplay.

Growth hormone response to GHRH + GHRP-6 in type 2 diabetes during euglycemic and hyperglycemic clamp.

The aim of this study was to investigate the effect of two different glucose levels on GH response to the combined administration of GHRH+GHRP-6 in patients with type 2 diabetes. GH response to i.v. bolus of GHRH+GHRP-6 (100 mcg, each) was measured in 12 male patients with type 2 diabetes (mean age: 53.9+/-1.59 years; BMI: 25.58+/-0.39 kg/m(2); mean HbA(1c): 8.7+/-0.42%), during a euglycemic (mean glucose: 4.92+/-0.08 mmol) hyperinsulinemic clamp (insulin infusion rate of 100 mU/kg/h) and a hyperglycemic clamp (mean glucose: 12.19+/-0.11 mmol/l). There was no difference in basal GH levels between the hyperglycemic and euglycemic clamps (2.9+/-0.99 mU/l versus 1.48+/-0.44 mU/l; P>0.05). Peak GH response to GHRH+GHRP-6 during the hyperglycemic clamp was lower than in the englycemic clamp (112.45+/-14.45 mU/l versus 151.06+/-16.87 mU/l; P<0.05). Area under the GH curve was lower in the hyperglycemic than in the euglycemic clamp (6974.49+/-1001.95 mU/l/min versus 9560.75+/-1140.65 mU/l/min; P<0.05). It is concluded that hyperglycemia significantly reduces GH response to combined administration of GHRH+GHRP-6 in normal weight patients with type 2 diabetes. It is suggested that ambient glucose levels should be taken into account during interpretation of GH response to combined administration of GHRH+GHRP-6 in patients with type 2 diabetes.

Ectopic calcitonin secretion in a woman with large cell neuroendocrine lung carcinoma.

OBJECTIVE: Serum calcitonin (CT) is a sensitive but not specific marker for medullary thyroid carcinoma (MTC). There are a large number of conditions that may elevate CT levels. CASE REPORT: Herein we present the case of a 47-year old woman with Hashimoto thyroiditis, goiter, cervical lymphadenopathy and high CT and CEA levels. After surgical extirpation of the lymph node neuroendocrine cancer metastasis was suspected. Computed tomography of the chest showed a tumor mass on the right lung. Bronchoscopy was performed and pathological and immunohistochemical analysis revealed large cell neuroendocrine lung cancer (LCNEC). After chemotherapy, significant reduction of tumor mass was achieved with a moderate decrease in CT levels in parallel. CONCLUSIONS: We present a female with LCNEC, a condition which is usually observed in older men (7(th) decade) and is not associated with CT secretion. Hashimoto thyroiditis is associated with increased incidence of different types of cancers (e.g. thyroid, colon). No reports at present exist on the incidence of lung cancers in patients with thyroid disease.

Low leptin level in an obese hyperandrogenic woman--potential marker for androgen-secreting tumor.

Hyperandrogenism in postmenopausal women is due to ovarian hyperthecosis or an androgen-secreting ovarian/adrenal tumor. Making the correct diagnosis might be complicated due to the possible existence of an adrenal neoplasm secreting testosterone only, ectopic ovarian tissue or ectopic luteinizing hormone/human chorionic gonadotropin receptors in the adrenals, as well as the relatively low sensitivity of imaging techniques (computed tomography, magnetic resonance imaging) and vein catheterization for this type of pathology. We present the case of an obese postmenopausal woman with metabolic syndrome, hyperandrogenism (high testosterone levels, suppressed gonadotropins), adrenal macronodular hyperplasia and Leydig-cell ovarian tumor. At presentation she had low leptin levels despite high body fat content. After a catheter study left adrenalectomy was carried out but hyperandrogenism persisted. Then, bilateral oophorectomy with hysterectomy was performed and a small Leydig-cell tumor was found in the left ovary. Postoperatively, testosterone and gonadotropin levels were normal (postmenopausal) and leptin level became elevated without change in body mass index or body fat content. In conclusion, we speculate that low leptin levels in obese hyperandrogenic women might be a marker for androgen-secreting tumors.

Pitfalls in diagnosing a small cystic insulinoma: a case report.

Insulinoma is a rare pancreatic endocrine tumour and is typically sporadic and solitary. Over 90% of all insulinomas are benign. Cystic insulinomas are also rare. It is not difficult to determine the site of such neoplasm, as cystic insulinomas are usually 4-10 cm in diameter. We present the case of a patient with a histologically confirmed cystic insulinoma diagnosed after approximately 10 years of hypoglycaemia symptoms. This case is unique because of the small size (2.2 cm) of the tumour. Endoscopic ultrasound (EUS) was useful for localizing this tumour.

[Use of continuous subcutaneous insulin infusion by a portable insulin pump during pregnancy in women with type 1 diabetes mellitus].

BACKGROUND/AIM: Diabetes mellitus is associated with an increased risk for neonatal morbidity and mortality. One of the most important goals in treating pregnancies complicated with diabetes is keeping glucose level within the normal range, especially in the first trimester. A portable insulin pump for continuous subcutaneous insulin infusion (CSII) represents the best form of therapy for patients with type 1 diabetes mellitus during pregnancy. The aim of our study was to evaluate the effects of therapy with a portable insulin pump for continuous subcutaneous insulin infusion during the first trimester of pregnancy on the quality of glycoregulation and pregnancy outcome in women with type 1 diabetes mellitus. METHODS: A total of 17 newly diagnosed pregnant women with type 1 diabetes mellitus were treated with CSII therapy for three months. The parameters of glycoregulation (hemoglobin A, glycosylated--HbAlc, mean blood glucose value in daily profiles--MBG, daily requirement for insulin--IJ/kg BM), lipid levels, blood preassure and renal function were estimated before and after the therapy. These parameters were correlated with parameters of pregnancy outcome: fetal weight, APGAR score, duration of pregnancy. RESULTS: There was a significant improvement in HbA1c (8.94 +/- 1.62 vs. 6.90 +/- 1.22 %,p < 0.05), MBG (9.23 +/- 2.22 vs. 6.41 +/- 1.72 mmol/l, p < 0.01), and daily requirement for insulin (0.66 +/- 0.22 vs. 0.55 +/- 0.13 IJ/kg BM, p < 0.05) during the CSII therapy. There were significant correlations between fetal weight and HbAlc (r = -0.60, p < 0.05), triglyceride levels (r = -0.63, p < 0.01), and the number of pregnancies (r = -0.62, p < 0.01), as well as between APGAR score and MBG (r = -0.52, p < 0.05) and cholesterol levels (r = -0.65, p < 0,01) before a portable insulin pump was applicated. CONCLUSIONS: There was a significant improvement in the quality of glycoregulation during CSII therapy in the pregnant women with type 1 diabetes mellitus. The quality of glycoregulation in the moment of conception was the important factor for pregnancy outcome.

Hypopituitarism as a late complication of hemorrhagic fever.

We report three patients who developed hypopituitarism as a late complication of hemorrhagic fever with renal syndrome (HFRS). Their past history, physical examination, and endocrine investigation confirmed hypopituitarism. Magnetic resonance imaging of the pituitary revealed atrophic pituitary gland with an empty sella. Hemorrhagic fever is endemic in certain regions of the Balkans, and this preliminary report suggests the importance of investigating the endocrine status in every patient who survived HFRS.

Age and body mass related changes of cardiovascular risk factors in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is considered a metabolic disorder closely related to obesity, insulin resistance (IR), hyperinsulinemia and unfavorable lipid profile, all increasing the risk for the occurrence of cardiovascular diseases. The aim of this study was to assess age and body mass index (BMI) related changes of cardiovascular risk factors in 90 women with PCOS. The cut-off age point was 30 years and for BMI 27.8 kg/m2. In all patients systolic and diastolic blood pressure (BP), metabolic parameters comprising values of glucose and insulin during oral glucose tolerance test (OGTT), and basal lipid values were determined. Significant increase in blood pressure (BP) indices, basal insulin values and insulin resistance (IR) assessed by HOMA model were observed with aging and the increase of BMI, while the parameters of glucose metabolism, total cholesterol and triglycerides were significantly elevated only with aging. However, the correlation between the indices of arterial blood pressure, and lipid and glucose metabolism parameters occurred only in patients over 30 years of age, pointing to the causative relation and the consequent deterioration of IR and lipid profile with aging, influencing cardiovascular function in women with PCOS.