ACTA ENDOCRINOLOGICA (BUC)

Context. The prevalence of both heart failure and vitamin D deficiency increases with age and is associated with poor outcome in the elderly. Objectives. We aimed to investigate the relationship between all-cause mortality and vitamin D deficiency in elderly patients with chronic heart failure. Design. It is a retrospective, observational crosssectional study. Median follow-up time was 497 days. Subjects and Methods. 302 patients aged ≥65 years heart failure patients was categorized into tertiles based on the 25-hydroxy-vitamin D levels. Clinical and laboratory parameters were evaluated according to tertiles. Hospitalization rates and overall survival were compared between tertiles. Independent predictors of all cause mortality were defined. Results. Patients with low vitamin D tertile were mostly women (p=0.001), and had a worse NYHA functional class (p=0.005). During follow-up, deaths were more frequent in the first tertile (p = 0.001). All-cause mortality increased significantly with decreasing vitamin D tertiles (from third tertile 7.9%, to 11.9%, to 26%; log rank test p=0.003). No significant difference was observed at the composite endpoint of mortality or HF hospitalizations (P=0.451). Multivariate analysis supported that low vitamin D concentration was an independent predictor of all causes of mortality (HR 0.93; 95% CI 0.89-0.97; p=0.004). Conclusions. Low vitamin D levels were independent predictors of all-cause mortality in the elderly population with chronic heart failure.

Introduction. Primary bilateral macronodular adrenal hyperplasia (PBMAH) is one of the uncommon causes of endogenous Cushing’s syndrome (CS). Pheochromocytoma (PCC) is another adrenal tumor which is derived from neural crest arising in the adrenal medulla. Here we are reporting a case with recurrent overt CS due to PBMAH, 2 years after unilateral adrenalectomy, concomitant with recently developed PCC. Case Presentation. A 43-year-old woman was admitted to our clinic with a 30 kg weight gain, proximal muscle weakness, menstrual irregularity, easy bruising and excessive hair growth on face and body.The lab results were compatible with a diagnosis of solely ACTH-independent CS. Screening showed bilateral macronodular lesions and she underwent right adrenalectomy. Postoperatively, she had lost weight and her well-being had improved; 2 years later, she developed CS and paroxysmal hypertension. The left adrenal gland was laparoscopically removed. Histopatologically, the lesion was reported as a typical PCC and macronodularmicronodular hyperplasia of the adrenal tissue surrounding that lesion. Conclusions. Pheochromocytoma with synchronous ACTH-independent CS originating from the same adrenal gland is very rare. To the best of our knowledge,our case is the first one describing the coexistence of overt ACTHindependent CS due to PBMAH and metachronous PCC. The importance of detailed re-evaluation of patients with recurrent ACTH-independent CS is highlighted here.

Background. Pheochromocytoma, the great masquerader, can have a varied spectrum of clinical manifestations. It can often cause a diagnostic challenge despite the availability of modern investigation modalities. Case. We present the case of a 38-year-old male who presented with uncontrolled hypertension for the past 10 years and heart failure for one year. The diagnosis of pheochromocytoma was missed in the initial setting, leading to a biopsy of the retroperitoneal mass. Fortunately, the patient survived the procedure. Subsequently, with the involvement of a multi-disciplinary team, he was optimized for surgery under strict cardiac monitoring. After the complete excision of the tumour, he showed significant improvement not only in his clinical symptoms but also in his cardiac status. Conclusions. This case emphasizes the age-old medical phrase of ‘Primum non nocere or first, do no harm’. Any invasive procedure in a pheochromocytoma can lead to a massive release of catecholamines causing a hypertensive crisis, pulmonary oedema, and even cardiac arrest. Any young patient presenting with hypertension or heart failure should be investigated for secondary causes. Cardiomyopathy due to pheochromocytoma is because of catecholamine overload and usually reverses or improves after curative surgery.

Context. Immunoassays are vulnerable to occasional analytical errors despite their sensitivity and specificity. Adrenocorticotropic hormone (ACTH) is among hormones which are vulnerable to assay interference. Objective. In this case report, we aimed to present a case of ACTH interference in a patient with subclinical hypercortisolism. Case report. We present a case of subclinical hypercortisolism with unexpectedly elevated levels of ACTH in whom interference was shown by different biochemical methods. It is important for the clinician to keep in mind the possibility of interference when clinical and laboratory results are discordant. The communication between the clinician and laboratory staff is important while interpreting results. This case report shows that ACTH interference should be considered in patients with subclinical hypercortisolism who have unexpectedly high levels of adrenocorticotropic hormone.

We studied the incidence, risk factors, presentation, treatment and prognosis of calcific uremic arteriolopathy (CUA) in 140 of our hemodialysis patients. Methods. Patients with CUA in the past 3 years have been compared to controls in a cross-sectional survey of 140 hemodialysis patients. Results. Prevalence of CUA was 6/140 (4.28%); common presentation was ulcerated acral necrosis. Age, sex ratio, BMI, prevalence of diabetes were similar in case (n=6) and control (n=134) patients. CUA patients had higher serum calcium (9.58?1.25 mg/dL vs. 8.50?1.03 mg/dL, p=0.01), calcium-phosphate product (71.06?19.67 mg2/dL2 vs. 58.73?17.20 mg2/dL2, p=0.01) and parathormone levels (1854?1407 pg/mL vs. 654?776 pg/mL, p=0.0002). Differences in ingestion of calcium, active vitamin D and non-calcium containing phosphate binders in the year prior to the assessment were not significant. CUA patients had higher CRP values in the 6 preceding months than non CUA patients (6.61?9.68 mg/dL vs. 1.97?4.20 mg/dL, p=0.01); logistic regression disclosed CRP as the only predictive factor for CUA (p=0.03). 4 (66%) of the CUA patients died due to sepsis, as compared to 3(2.23%) of the control group (p=0.001). 2 of 3 parathyroidectomised patients survived. In conclusion, this is, to our knowledge, the first series of CUA reported from Eastern Europe. In our center acral, ulcerated forms of CUA in patients with severe hyperparathyroidism are predominant.

Context and objective. In this study, we aimed to investigate how moderate physical activity improves the bone ultrastructural parameters in rats with glucocorticoidinduced secondary osteoporosis. Animals and Methods. Research has been carried out on Wistar female rats. Secondary osteoporosis was induced through daily i.m.1.5 mg/kgbw methylprednisolone, over a period of 30 days. A group of rats with induced secondary osteoporosis were subjected to physical activity (swimming) for one hour/day for 30 days. Rats were sacrificed 24 hours after the last administration and femoral bones were used for electron microscopy analysis. Results. The ultrastructural findings obtained from the rats with osteoporosis showed varying degrees of alteration in all cellular components. A moderate physical effort led to the overall maintenance of the normal ultrastructure of the cells and connective components, protecting the lamellar structure of the compact bone from the deleterious effects of glucocorticoid. The shape and components of osteocytes were also preserved and the accumulation of lipids in the bone marrow diminished. Conclusions. Physical exercise has been shown to have a protective role by lowering the development of structural alterations specific to osteoporosis. Therefore, moderate physical exercises are recommended for improving the structure of the bone mass affected by glucocorticoid treatment.

The appearance and normal development of the anterior pituitary gland requires several signalling molecules and specific transcription factors. Gene mutations of these\r\npituitary transcription factors may lead to different degrees of combined pituitary hormone deficiency (CPHD) associated or not with morphological changes of the hypothalamicpituitary region. We present the first Romanian case of progressive CPHD in two brothers from a consanguineous family. Clinical, hormonal and MRI follow-up were performed during 20 years. Growth hormone deficiency was certified at the age of 5, respectively 3 years, followed by gonadotropin deficiency diagnosed at the age of 21, respectively 19 years, and by central hypothyroidism diagnosed at the age of 23, respectively 21 years.\r\nSubstitutive treatment rhGH was commenced, followed by testosterone and later thyroxin, in adequate doses. Adrenal function was normal during the follow-up. MRI revealed\r\nanterior pituitary hypoplasia in both siblings, with a partially empty sella in the younger brother and a thick midline septum in the sphenoid sinus in both siblings, which was not described in previous reports. The progressive CPHD suggested a PROP 1 deficiency, which was confirmed by genetic analysis. The c.301-302delAG homozygous mutation in the PROP 1 gene was identified, resulting in a complete loss of promoter binding and\r\ntranscriptional activation of the mutant protein.

Background. The prevention of type 2 diabetes has great clinical importance. Many pharmacologic and nonpharmacologic\r\nmethods are used to prevent type 2 DM. Metformin reduces the risk of developing diabetes in insulin resistant subjects. Oxidative stress plays pivotal roles in the pathogenesis and complications of diabetes mellitus. Paraoxonase 1 has\r\nantioxidant capacity.\r\nObjective. This study was planned to assess the effects of metformin and life style changes on paraoxonase activity and\r\noxidative stress markers in premenopausal, obese, insulin resistant women.\r\nDesign.Open-pilot clinical study.\r\nSubjects and methods. Thirty-two insulin resistant, premenopausal, obese women were enrolled into this clinical\r\nstudy. These women were treated by diet + exercise + metformin (1700 mg/d) for 6-month interval. All anthropometric characteristics, serum fasting and\r\npostprandial glucose, fasting insulin, paraoxonase, arylesterase, and malondialdehyde (MDA) levels and lipid\r\nsub-fractions were measured at the commencement and the finish of the study. Homeostasis model assessment (HOMAIR)\r\nwas used to estimate insulin resistance.\r\nResults. Significantly reduced body weight, body mass index, waist circumference measurements, HOMA-IR and serum fasting\r\ninsulin, postprandial glucose, triglyceride, MDA levels and paraoxonase/high density lipoprotein cholesterol (HDL-C) ratio were observed at the end of the study compared\r\nwith initial evaluations. Conversely, there were considerable increases in serum arylesterase and HDL-C levels following the treatment. Nevertheless, the increase in serum PON-1 level was statistically insignificant.\r\nArylesterase was inversely correlated with TC, LDL-C levels and HOMA-IR.\r\nConclusions. Metformin treatment with intensive life-style modification may be appropriate management in premenopausal,\r\nobese, insulin resistant women who have increased propensity for the development of type 2 diabetes, although long-term,\r\ncontrolled studies are needed for evaluation in greater detail.

Context. Despite the developments in strategies related to the iodization of salt, iodine deficiency is still a serious problem, particularly among pregnant women in certain regions of Turkey. Objective. We aimed to re-evaluate the efficiency of iodine prophylaxis in pregnant women and adults 13 years after iodized dietary salt became mandatory in Istanbul. Subjects and Methods. This study was performed with pregnant women (n = 200) and adults (n = 200, 100 nonpregnant women and 100 men). The participants were questioned about the iodization status of the salt they used. Urinary iodine concentration (UIC) was measured using the Sandell-Kolthoff method. Goiter size and UIC were determined according to Pan American Health Organization and World Health Organization recommendations, respectively. Results. Ratio of iodized table salt use was 91% in both groups. Although the median UICs were 162.5μg/L (95% CI = 162.5–186.1) in pregnant women and 167μg/L (95% CI = 153.7–172.7) in adults, 43% of pregnant women had a UIC < 150μg/L, and 23% of adults had a UIC < 100μg/L. The prevalence of goiter was significantly higher in pregnant women than that in adults (50% and 32%, respectively), but a small goiter was found in all cases. Conclusion. Iodine prophylaxis in Istanbul is sufficient and has progressed. However, iodine deficiency remains a problem for a considerable proportion of pregnant women, despite more than one decade of successful salt iodization in Istanbul Province. Iodine-containing preparations should be considered to supplement iodized salt for pregnant women.

Background. Thyroid nodules stiffness may predict thyroid malignancy. Objectives. The purpose of the study was to investigate the diagnostic value, interobserver agreement and reliability of real time ultrasound elastography (USE) when assessing solid thyroid nodules. Design. A prospective, observational study in a tertiary center. Subjects and Methods. In 49 patients scheduled for thyroidectomy, a senior radiologist and two radiologists in training independently assessed 81 solid thyroid nodules with USE using a 6600 Hitachi machine. Pathology results were used as a reference standard. Nodule stiffness was evaluated using the Asteria scoring system. The diagnostic ability of the elastography scores for the assessment of the thyroid solid nodules was evaluated using AUROC (area under the receiver operating characteristic curve) analysis. The Cohen’s kappa (k) values were used for interobserver agreement evaluation and interclass correlation coefficient (ICC) was used as a measure of reliability. Results. Pathology results revealed 20 papillary carcinomas and 61 benign nodules. The elastography identification of malignant nodules by the senior radiologist was performed with an AUROC of 0.84 [95% Confidence interval (CI) 0.74-0.91], with Sensitivity= 100%, and Specificity= 68.85%. When performed by ultrasound operators in training, the diagnostic performance slightly decreased. With no statistically significant difference between the diagnostic performance of the three readers, USE demonstrated good inter-observer agreement and good reliability (ICC= 0.81). Conclusion. USE may be an accurate tool of assessment for solid thyroid nodules, identifying with high sensitivity the malignant ones, particularly micronodules. USE is reproducible and reliable when used both by experienced operators and medical professionals in training.