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.

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Thyroid tumors are the most frequently reported endocrine malignancies. However thyroid collision tumors are rare pathological findings, representing less than 1% of thyroid cancers. In our case, a 50-year-old female patient presented with a complaint of neck swelling. During the exams, nodules were identified in both thyroid lobes. Pathologic analysis of a fine-needle aspiration biopsy(FNA) has been obtained from a 60×50 mm hypoechoic nodule raised suspicion of oncocytic carcinoma(OC). Another FNA was performed on a 17×11 mm hypoechoic solid nodule, revealing features of medullary thyroid carcinoma (MTC). Preoperative whole-body scans indicated no evidence of metastases. The patient subsequently underwent total thyroidectomy and central lymph node dissection. Pathological examination revealed OC, MTC, papillary microcarcinoma (PTMC), simultaneous metastasis of MTC and papillary thyroid carcinoma (PTC) to the same lymph node. The patient's calcitonin level was normalized postoperatively and I-131 ablation therapy was administered to the patient in the ATA high risk category. The patient was monitored under levothyroxine suppression. The simultaneous occurrence of OC, MTC and PTMC of the thyroid gland along with metastases of PTC and MTC in the same lymph node are reported in this case. To the best of our knowledge, this association had not been previously reported in the literature.

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Familial hypercholesterolemia (FH) is a genetic disease with autosomal dominant transmission, characterised by high blood cholesterol levels. The evolution of this disease leads to primary atherosclerosis and cardiovascular disease. Patients with HF develop atherosclerosis by the age of 20 and usually do not survive past the age of 30. We present the case and oro-dental aspects of a preschooler that was diagnosed at the age of 4 with FH, compound heterozygote (mutation/genotype1 LDLR: C20IX, exon 4; mutation/ genotype2 LDLR: G571E, exon 12) and the experience of our clinic in the management of this patient that received offlabel treatment with statins. When diagnosed, his cholesterol level was 932 mg/dL and his LDL-cholesterol level was 792 mg/dL. Treatment with rosuvastatin and ezetimibe was prescribed. Both substances (rosuvastatin and ezetimibe) are not approved for children under the age of 6 in Europe. Taking into considerations the diagnosis and prognosis for unfavorable evolution, treatment with statins was started at the age of 5 years.

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.

Hyperinsulinism/hyperammonemia (HI/HA) syndrome is caused by activating mutations in GLUD1 gene, and causes fasting as well as protein sensitive symptomatic hypoglycemia, in addition to persistently elevated plasma ammonia levels. First-line treatment is diazoxide, and most patients respond well to this agent, however side effects may be observed. The most frequent side effect of diazoxide is fluid retention and hypertrichosis, while hyperuricemia and hematologic side effects are observed less often. Herein, we report a case who had a heterozygous mutation of GLUD1 gene and who developed diazoxide related neutropenia 8 years after the start of treatment. On follow-up, leucopenia and mild neutropenia persisted and the treatment was changed to somatostatin analogues. However, she developed persistent severe symptomatic hypoglycemia and required diazoxide retreatment. A lower dose of diazoxide (6 mg/kg/day) successfully controlled hypoglycemia and cell counts increased even though they were not normalized. Neutropenia in current case presented after a long period of time of diazoxide use and this period is the longest defined in the literature. Long-term endocrine and hematologic follow-up of this patient up to 18 years old will also be presented.

Triple A syndrome is an autosomal recessive inherited multisystem disorder that was first described in 1978. Triple A syndrome has a high genotypic and phenotypic heterogeneity and has been linked with mutations in the AAAS gene, which has been identified on chromosome 12q13. A 14 years old male patient applied to outpatient clinic complaining of weakness and darkening of skin color since 4 months. On physical examination hyperpigmentation was observed on both the skin and mucosa. The morning cortisol level was 1.8 μg/dL and ACTH was >1250 ng/L. Schirmer test showed absence of tears. In the patient’s esophagoscopy, mucosal paleness and stenosis of the cardia were observed. Molecular genetic analysis of AAAS gene confirmed the diagnosis of triple A syndrome caused by homozygous mutation: c.1368_1372delGCTCA (p.Gln456HisfsTer38). This variant is considered to be a possible pathogenic because it causes a frame shift that changes the protein structure. As a result of the genetic analysis of the patient’s parents, the AAAS gene was detected as heterozygous in both parents for the c.1368_1372delGCTCA mutation. To the best of our knowledge, this is the first report of homozygous mutation: c.1368_1372delGCTCA (p.Gln456HisfsTer38).