ACTA ENDOCRINOLOGICA (BUC)

The objective of this review is to summarise what is known about mortality in ACTH dependent Cushing’s disease (CD). Specifically, mortality in other causes of Cushing’s\r\nsyndrome (CS) such as ectopic ACTH syndrome and adrenal adenomas is not considered because of the relative rarity of these causes of CS. Six papers addressed mortality of CD in relation to the background population.\r\nThe overall mortality in CD is increased 2-4 fold, but in patients that achieved early remission of hypercortisolaemia the standardised mortality ratio (SMR) is not different from that of the background population. Those in whom hypercortisolaemia was not controlled had a poor outcome (SMR 4-11), and died prematurely. Persistence of disease, older age at\r\ndiagnosis, and presence of hypertension appear as the main determinants of mortality. However, there are several caveats to these conclusions: 1. The number of patients studied is small and the number of deaths even smaller; 2. On average the patients were young (40yrs old) at diagnosis, their follow-up was 10 yrs, and by the age of 60 the expected number of deaths in the background population is going to be small so that differences in causes of death will be difficult to ascertain; 3. SMR of 1.5 -2.0 for patients in remission may not be statistically significant in the reported studies but could become so with larger numbers followed for a much longer time (30-40 yrs). Notwithstanding these caveats, it is encumbent on us as endocrinologists not only to treat the symptoms and complications of CD but also to ensure that patients are ‘cured’ of their hypercortisolism in order to maximise long-term survival.

A brief synopsis on the past three and a half decades of intracellular insulin research is given as it relates primarily to the human system. Thereby, a particular emphasis is placed on insulin binding and inactivation of the central tumor suppressor retinoblastoma protein (RB) and, moreover, on insulin degradation by the putative antioncoprotein insulin-degrading enzyme (IDE). Finally, the potential for (anticancer) therapeutics that target intracellular insulin is outlined.

Context. The effects of COVID-19 on the adrenocortical system and its hormones are not well known. Objectives. We studied serum cortisol, serum adrenocorticotropic hormone (ACTH), and their ratio in hospitalized non-critically ill COVID-19 patients. Design. A prospective case-control study. Methods. The study participants were divided into 2 groups. Group 1 consisted of 74 COVID-19 patients. The second group consisted of 33 healthy persons. Early admission above hormones levels was determined and compared between the study groups. Besides that, COVID-19 patients were grouped according to their Glasgow Coma Score (GCS), CURB-65 score, and intensive care unit (ICU) requirement, and further sub-analyses were performed. Results. There were no significant differences in the mean age or gender distribution in both groups. In the patients’ group, the serum ACTH concentration was lower than in the healthy group (p<0.05). On the other hand, the serum cortisol levels and cortisol/ACTH ratio of the patients’ group were significantly higher than of the healthy controls (p<0.05, all). Further analyses showed that, although serum cortisol and ACTH levels were not high, the cortisol/ACTH ratio was higher in COVID-19 patients with low GCS (<15) than patients with normal GCS (=15) (p<0.05). In COVID-19 in patients with different CURB-65 scores, the cortisol/ACTH ratio was significantly different (p<0.05), while serum cortisol and ACTH were not different in groups (p>0.05). Serum cortisol levels and cortisol/ACTH ratio were higher but ACTH level was lower in the ICU needed COVID-19 patients than in patients who do not need ICU (p<0.05). Conclusion. Our pilot study results showed that the cortisol/ACTH ratio would be more useful than serum cortisol and/or ACTH levels alone in evaluating the adrenocortical system of COVID-19 patients. Still, further detailed studies are needed to confirm these.

The effects of finasteride on insulin resistance and of metformin on hyperandrogenism in patients with polycystic ovary syndrome (PCOS) are not clear. This study therefore compared the effects of finasteride, metformin, and finasteride plus metformin treatments on hormone levels, insulin resistance, and hirsutism score in women with PCOS. Fifty-two patients with PCOS were randomly assigned to receive finasteride 5 mg/day, metformin 1700 mg/day or finasteride plus metformin for 12 months. Body mass index (BMI), Ferriman Gallway score (FGS), serum concentrations of estradiol, sex hormone-binding globulin, free testosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, and homeostasis model assessment of insulin resistance (HOMA-IR) index and areas under the curve (AUC) for insulin and glucose were evaluated before and after 12 months of treatment. Reductions in FGS, free testosterone, DHEAS, androstenedione, HOMA-IR, AUCinsulin, and AUC-glucose were significant within each group, whereas BMI and estradiol were not. Comparisons of changes in parameters in the 3 groups did not clearly show the superiority of any treatment modality. The treatment with finasteride alone significantly reduced both androgen levels and parameters of insulin resistance. In addition, metformin alone was effective, and not inferior to finasteride, in the treatment of hyperandrogenism.

Background. Secreting different adipocytokines, adipose tissue plays an important role in health and disease. Upon omega-3 consumption, changes in the secretion of adipose tissue and its effects on glycemic profile are a controversial subject at the present time. Objectives. We evaluated the effects of eicosapentaenoic acid (EPA) alone and in combination with vitamin E on adiponectin and serum glycemic indices in type II Diabetes patients. Design. This double-blind clinical trial divided all patients randomly into four balanced permuted blocks of EPA, Vitamin E, EPA and vitamin E and placebo (Corn oil). Subjects and Methods. 127 patients with type II diabetes living in Kashan in 2008, 35-50 years old, and 25≤BMI ≤30 were enrolled. ELISA, Glucose Oxidase, spectrophotometry, and Radioimmunoassay methods were used for measurement of serum adiponectin, Fasting Blood Glucose (FBG), HbA1C, and Insulin, respectively. Results. Serum adiponectin increased significantly after EPA consumption in EPA and EPA+E groups. Moreover, FBG, HbA1c, serum insulin and Homeostasis Model HOMA-IR decreased significantly after EPA consumption in the two previously mentioned groups. Conclusions. This study showed that EPA supplementation affects the secretion of adipose tissue, improves the FBS as well as HbA1c values and significantly decreases fasting serum insulin and insulin resistance.

Background. Bilateral adrenal hemorrhage is a serious condition that can result in adrenal insufficiency, shock, acute adrenal crisis, and mortality if it is not managed with adequate treatment. We report a rare case of idiopathic bilateral adrenal hemorrhage. C ase presentation. A 50-year-old woman visited our hospital with complaints of right upper abdominal pain. A computed tomography (CT) revealed unilateral left adrenal gland hemorrhage. However, the results of rapid adrenocorticotropic hormone (ACTH) stimulation test and adrenomedullary hormone function test were normal. Since the patient did not show signs of adrenal insufficiency, corticosteroid therapy was postponed and only supportive management therapy was started. After 1 week, a followup CT showed a previously unseen adrenal hemorrhage on the right adrenal gland, but the rapid ACTH stimulation test result was normal. One year later, no hemorrhagic signs were observed on the follow-up CT. Conclusion. In most cases of idiopathic bilateral adrenal hemorrhage, patients are treated with steroid replacement therapy due to adrenal insufficiency. In some other cases, patients are treated with steroids despite the absence of adrenal insufficiency. Here we reported a very rare case of idiopathic bilateral adrenal hemorrhage sequentially to emphasize that before initiation of adrenal hormone replacement therapy, it is important to determine whether adrenal insufficiency is present. If there is no evidence of adrenal insufficiency, adrenal replacement therapy should be postponed until the presence of adrenal insufficiency is confirmed.

Endogenous hyperinsulinemia was found in a 38-yearold female patient with recurrent neuroglycopenic symptoms (the glucose level was 25 mg/dL, insulin 43.9 μ/mL, C-peptide 5.54 ng/mL). No lesion was found on imaging tests including enhanced computed tomography (CT) methods performed with a preliminary diagnosis of insulinoma. A suspicious hyperperfusion was present in the pancreatic tail on the perfusion CT examination performed after obtaining approval. The selective arterial calcium stimulation test (SACST) result was consistent with a diffuse disease in the body and tail. The patient underwent partial (75%) pancreatectomy and is now followed up as a diabetes patient on intensive insulin treatment at the postoperative 38th month. The most common cause of endogenous hyperglycemia in hypoglycemia patients is insulinoma. The noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS) is rarely seen in the adult age group. Although invasive, SACST seems to be the most suitable test to differentiate diffuse or multiple disease from insulinoma and to guide the surgery when advanced radiological imaging methods are inadequate to detect the presence of insulinoma. Regarding perfusion CT, it would be more appropriate to wait for comparative data to be put forward in a more consistent manner. When no response can be obtained to medical treatment in NIPHS, partial/total pancreatectomy is the most appropriate treatment option as it enables recovery from the hypoglycemic episodes despite leading to a significant condition like diabetes.

Background. Patients with Down&#8217;s syndrome have an increased prevalence of\r\nautoimmune thyroid diseases.\r\nAim. The purpose of this study was to assess the prevalence of thyroid dysfunction in\r\nchildren with Down&#8217;s syndrome (DS) and to find the best screening and management strategy\r\nin this group of patients.\r\nMethods. A total of 63 DS patients aged between 5 days and 18 years from our University\r\nHospital, were recruited. In all patients, serum free T4, and TSH were measured, the presence\r\nof congenital anomalies and specific clinical findings were assessed. Karyotype was performed\r\nin each case.\r\nResults. Sixty patients showed total 21 trisomy. Mosaicism was present in other 2 cases\r\n(3.17%) and only one girl had 47,XXder(14;21)(q10;q10)+21.\r\nHigh TSH level was seen in 24 out of 63 cases (38 %) of which 1 (1.5%) had congenital\r\nmixedema while the other 23 had a high TSH level. According to TSH levels, these 23 patients\r\nwere divided into two groups: the first group with TSH between 6-10 microUI/mL (17 patients-\r\n27%), and the second with TSH>11 microUI/mL (6 patients - 9.5%). Thyroid ultrasound was\r\nalso performed and antibodies to thyroid peroxidase, anti-TPO, were measured, when TSH\r\nlevel was high. In all cases thyroid ultrasound showed a normal located thyroid gland. In the\r\ngroup of patients with TSH level above 11 microUI/mL, two had congenital heart disease, but\r\nnone of them had gastrointestinal disease.\r\nHyperthyroidism was not observed in any of the cases.\r\nConclusions. Children with DS have high prevalence of thyroid dysfunction and\r\nbiochemical screening of this is essential. Subtle thyroid abnormalities were the most common\r\nfinding in DS.

Fetal goitre is found in about 1 in 5,000 births, usually in association with maternal Graves’ disease, due to transplacental passage of high levels of thyroid stimulating antibodies or of anti-thyroid drugs. A goitre can cause complications attributable to its size and to the associated thyroid dysfunction. Fetal ultrasound examination allows easy recognition of the goitre but is not reliable in distinguishing between fetal hypo- and hyperthyroidism. Assessment of the maternal condition and, in some cases, cordocentesis provide adequate diagnosis of the fetal thyroid function. First-line treatment consists of adjusting the dose of maternal anti-thyroid drugs. Delivery is aimed at term. In cases with large goitres, caesarean-section is indicated.

Context. Scarce data on dietary habits in Eastern European countries is available and reports investigated individual food items and not dietary patterns in these populations Objective. To identify dietary patterns and to explore their association with obesity in a sample from Romanian population. Design. Cross-sectional. Subjects and Methods. This was an analysis of data collected from 1398 adult participants in ORO study. Data on lifestyle, eating habits and food frequency consumption were collected. Results. By principal component analysis we identified 3 dietary patterns explaining 31.4% of the diet variation: High meat/High fat pattern, Western pattern and Prudent pattern. High meat/High fat pattern was associated with male gender, lower educational level, living in a rural, smoking and a higher probability for the presence of obesity (OR 1.2 [95%CI: 1.1-1.4]). Western pattern was associated with younger age, a higher level of physical activity and smoking. Prudent pattern was associated with older age, female gender, a higher level of physical activity, not smoking status and a lower probability for the presence of obesity (OR 0.8 [95%CI: 0.7-0.9]). Conclusions. This study provides for the first-time information on the association between dietary patterns in adults from an Eastern European country and the presence of obesity.