Depression: another cortisol-related comorbidity in patients with adrenal incidentalomas and (possible) autonomous cortisol secretion.

PURPOSE: Hypercortisolism is associated with a high prevalence of depression and impaired health-related quality of life (QoL). According to the available literature, studies examining the depression risk in patients with adrenal incidentalomas (AI), nonfunctioning and the ones with (possible) autonomous cortisol secretion ((P)ACS) are scarce. The aim of this observational, case-control study was to screen patients with nonfunctioning adrenal incidentalomas (NAI) and the ones with (P)ACS for depression and to assess their QoL. METHODS: The total studied group consisted of 92 subjects-26 with NAI, 34 with (P)ACS and 32 age-matched healthy controls (HC). To screen for depression, we used the Beck Depression Inventory-II (BDI-II) and to assess the QoL, we used the Short-Form 36 Health Survey (SF-36). RESULTS: Patients with (P)ACS had significantly higher BDI-II scores and substantially lower QoL than patients with NAI or HC. Midnight cortisol level was the most significant predictor of BDI-II and SF-36 score. The receiver operating characteristic curve analysis demonstrated that a midnight cortisol value of 86.95 nmol/l had a high sensitivity (82.8%) and high specificity (80%) for detection of mild depression in patients with (P)ACS. CONCLUSION: Screening for depression and QoL assessment should become an integral part of clinical evaluation in patients with (P)ACS.

Microsatellite variation of ESR1, ESR2, and AR in Serbian women with primary ovarian insufficiency.

OBJECTIVE: This study aimed to investigate the potential role of microsatellite polymorphisms of the estrogen receptor alpha gene (ESR1) TA repeat, estrogen receptor beta gene (ESR2) CA repeat, and androgen receptor gene (AR) CAG and GGN repeats among Serbian women with primary ovarian insufficiency (POI). These microsatellites have been reported to be associated with POI in different racial/ethnic populations. METHODS: A cohort of 196 POI cases matched with 544 fertile controls was recruited by the Institute for Endocrinology, Diabetes and Metabolic Disorders of Serbia between 2007 and 2010. DNA was extracted from saliva. The four microsatellites were genotyped using a PCR-based assay to determine the repeat lengths. RESULTS: POI patients carried shorter repeat lengths of ESR2 (CA)n than controls (P = 0.034), but the difference was small. ESR1 (TA)n was on the borderline of statistical differences between groups (P = 0.059). AR (CAG)n and (GGN)n showed no association with POI. CONCLUSIONS: We cautiously conclude that microsatellite polymorphisms of gonadal steroid receptor genes might contribute to the genetic basis of POI in Serbian women, but a larger-scale study and family-based studies are warranted to validate our findings even though the sample size in this study is larger than any previously published in this field.

ACTH and cortisol responses to ghrelin and desmopressin in patients with Cushing's disease and adrenal enlargement.

BACKGROUND: Overexpression of ghrelin and vasopressin (V3) receptors demonstrated on corticotrophe adenomas accounts for exaggerated ACTH and cortisol responses to ghrelin and desmopressin (DDAVP) in patients with Cushing's disease (CD). AIM: In this study we have compared ACTH and cortisol responsiveness to DDAVP and ghrelin in CD patients with and without adrenal enlargement. SUBJECTS AND METHODS: Ghrelin and DDAVP tests were performed in 15 patients with CD (7 with and 8 without signs of adrenal enlargement) with CRH test in 8 patients. In 7 age and sex-matched healthy subjects, ghrelin test was performed. Plasma ACTH and serum cortisol concentrations were measured after ghrelin, DDAVP and CRH. Growth hormone was measured after stimulation with ghrelin. RESULTS: Significantly higher baseline and peak ACTH and cortisol concentrations after ghrelin were observed in all patients with CD compared to healthy control subjects. Patients with CD and adrenal enlargement had significantly lower baseline and peak ACTH concentrations after stimulation with ghrelin compared to CD patients without adrenal enlargement, while cortisol levels at baseline and after ghrelin administration were similar. Three out of seven patients with CD and adrenal enlargement did not respond to DDAVP while they responded well to CRH and ghrelin. CONCLUSION: Patients with CD and adrenal enlargement pose special diagnostic problems. They may have lower baseline ACTH levels and may not respond to DDAVP while they respond to ghrelin and CRH. Despite increased endogenous cortisol levels in CD, cortisol responses to ghrelin and CRH are preserved in patients with CD and adrenal enlargement.

Cancerous leptomeningitis and familial congenital hypopituitarism.

People are at higher risk of cancer as they get older or have a strong family history of cancer. The potential influence of environmental and behavioral factors remains poorly understood. Earlier population and case control studies reported that upper quartile of circulating IGF-I is associated with a higher risk of developing cancer suggesting possible involvement of the growth hormone (GH)/IGF system in initiation or progression of cancer. Since GH therapy increases IGF-1 levels, there have been concerns that GH therapy in hypopituitarism might increase the risk of cancer. We report a 42-year-old female patient who presented with subacute onset of symptoms of meningitis and with the absence of fever which resulted in death 70 days after the onset of symptoms. The patient together with her younger brother was diagnosed at the age of 5 years with familial congenital hypopituitarism, due to homozygous mutation c.150delA in PROP1 gene. Due to evolving hypopituitarism, she was replaced with thyroxine (from age 5), hydrocortisone (from age 13), GH (from age 13 until 17), and sex steroids in adolescence and adulthood. Her consanguineous family has a prominent history of malignant diseases. Six close relatives had malignant disease including her late maternal aunt with breast cancer. BRCA 1 and BRCA 2 mutational analysis in the patient's mother was negative. Histology after autopsy disclosed advanced ovarian cancer with multiple metastases to the brain, leptomeninges, lungs, heart, and adrenals. Low circulating IGF-1 did not seem to protect this patient from cancer initiation and progression in the context of strong family history of malignancies.

Effects of alternate fasting or very low calorie diet and low calorie diet on metabolic syndrome in severely obese patients.

BACKGROUND AND AIM: Weight loss improves the metabolic syndrome (MetS) features and related clinical abnormalities in obese subjects. The aim of this study was to assess the effects of a non-surgical therapeutic program on the MetS in severely obese patients. PATIENTS AND METHODS: Sixty-four extremely obese patients were involved in the therapeutic program, which consisted of two alternating phases: the three-week therapeutic fasting or semi-fasting in hospital conditions and the low calorie diet with dosed physical activity in outpatient conditions. At the baseline we measured: anthropometric parameters, blood pressure and lipid profile. Subjects underwent an oral glucose tolerance test and insulin resistance/sensitivity was evaluated by the homeostasis model assessment and the oral glucose insulin sensitivity. After weight reduction by at least 10%, all mentioned assessments were repeated. RESULTS: None of the patients had significant adverse effects. Forty-one patients aged 43.0±11.5 years completed the study. The mean weight loss was 27 kg or 18% of the initial weight (p<0.01), which was followed by a significant decrease of the insulin resistance, the overall prevalence of MetS (32%) and all MetS parameters, without the significant change in high-density lipoprotein. This weight loss pogram substantially improves the MetS in extremely obese patients. CONCLUSION: The tailored alternating either fasting or semi- fasting should be considered as an optional approach to manage extreme obesity and related metabolic abnormality.

Sandflies (Diptera: Psychodidae) in the Bar area of Montenegro (Yugoslavia).

The species and ecology of sandflies present in the coastal district of Bar, which lies in Montenegro, an endemic focus of visceral leishmaniasis (VL), were investigated in 1996-1999. A mean of 10 cases of VL and a greater number of viral infections (some of which are attributed to pathogens transmitted by sandflies) are diagnosed each year in this district. Phlebotomus papatasi, P. perfiliewi, P. tobbi, P. neglectus and Sergentomyia minuta were collected, P. perfiliewi being recorded for the first time in Montenegro. The ecology and distribution of each of these five species are described and their role, if any, in the transmission of Leishmania to humans is discussed.