ACTA ENDOCRINOLOGICA (BUC)

Introduction. The functions of CD36 membrane receptor include removal of oxidized low-density lipoproteins from\r\nplasma. The aim of our study was to search association between the IVS3-6 C allele and hypercholesterolemia in overweight children.\r\nMaterial and Methods. The study groups comprised 55 Caucasian children with (33) and without hypercholesterolemia (22). Amplicons of exon 4 including\r\nfragments of introns 3 and 4 were studied using denaturing high-performance liquid chromatography (DHPLC).\r\nResults. Polymorphism detected by DHPLC was single nucleotide substitution in intron 3 (IVS3-6 T/C - rs3173798). The IVS3-6 T/C polymorphism is located in the\r\nregion encoding the oxidized LDL binding domain, at a conserved splice site. Total serum cholesterol concentrations were significantly lower in the IVS3-6 TC\r\nheterozygotes than in the TT patients. Furthermore we found tendency (p=0.06) to lower LDL-cholesterol level in IVS3-6 TC heterozygotes than in wild-type homozygotes.\r\nConclusion. The results of our preliminary study suggest that the IVS3-6 C allele of CD36 rs3173798 polymorphism\r\nmay be associated with lower serum total and LDL-cholesterol in overweight children diagnosed with hypercholesterolemia.

Calciphylaxis, also known as calcific uremic arteriolopathy (CUA), is usually observed in women and it is a serious complication of hyperparathyroidism secondary to chronic renal failure. CUA is characterized by ischemic tissue loss secondary to progressive vascular degeneration. Although it is rare, it may end up with sepsis and organ failure and can be fatal. Its pathogenesis is not fully understood, but it is thought that it occurs secondary to increased calcification activators such as oxidized LDL, TNF- α, calcitriol, fibronectin, collagen-I, and TGF-1α. The most effective treatment is managing underlying pathology and decreasing serum calcium and phosphorus levels. In this report, we aimed to present an end stage renal failure case with coexisting hyperparathyroidism, hyperthyroidism and calciphylaxis in whom cutaneous manifestations were healed 6 months after parathyroidectomy.

Purpose. About 30% of patients with liver cirrhosis have diabetes. Postprandial hyperglycemia is more problematic than fasting hyperglycemia when managing diabetic patients with cirrhosis. Nateglinide decreases in the mealtime plasma glucose levels. The present study aims to determine\r\nwhether nateglinide is suitable for the management of diabetic patients with liver cirrhosis.\r\nMethods. This was a retrospective analysis of the cirrhotic patients who were treated at CNUH between Jan 2003 and Dec\r\n2009. A total of 81 Child-Pugh Class A or B patients who had been treated with insulin (I, n=27) or nateglinide (N, n=27) for at least 12 months were included in the study, while 27 cirrhotic patients without diabetes (C, n=27) were included as a control group. We compared the efficacy of treatment and the safety between the groups.\r\nResults. The basal mean HbA1c level was higher in the insulin treatment group than that in the nateglinide treatment group. The mean HbA1c was lowered in thepatients treated with insulin (9.36 ? 1.71% → 7.69?1.52%, p=0.026), but this was not changed in the patients treated with\r\nnateglinide (8.01?2.37 % → 7.78?2.11%, p=0.692) after 12 months treatment. There was no change in the Child-Pugh score in all the groups.\r\nConclusion. In case of mild hyperglycemia, nateglinide may be used for glycemic control in diabetic patients with\r\ncirrhosis as an insulin substitute without worsening the state of liver cirrhosis.

Isolated sarcoidosis of the hypothalamic-pituitary system is a very rare form of neurosarcoidosis. A high index of suspicion is required for diagnosis and the choice of therapy embodies another challenge due to lack of standardized protocols. Glucocorticoids are the mainstay of initial treatment, whereas the second and third-line therapy include immunomodulators and cytotoxic drugs, in addition to monoclonal antibodies. This report presents an unusual case of panhypopituitarism in a 32-year-old previously healthy male patient due to isolated hypothalamo-pituitary sarcoidosis confirmed histologically, refractory to pulsedose glucocorticoids and then successfully treated by methotrexate. Based on our report, in patients requiring additional therapy usage of the methotrexate as the second line agent should be considered, however the time frame and the dosing schedule of methotrexate are still unknown and deserve further investigation.

Only a few subacute thyroiditis (SAT) cases secondary to hypocortisolemia developed after successfully treating Cushing's disease (CD) have been reported. In this report, we present an SAT case, which developed immediately after discontinuation of steroid treatment for hypocortisolemia after the successful treatment of CD. A 54-year-old female patient who had recently been diagnosed with type 2 diabetes mellitus was admitted to our center with complaints of proximal myopathy and obesity. Serum cortisol did not suppress adequately after the 1 mg dexamethasone suppression test. Pituitary MRI of the patient with increased basal plasma ACTH level revealed a 6 x 5 mm right-sided adenoma. After successful surgical treatment, the patient was given ten months of steroid therapy due to a suppressed corticotroph axis. Shortly after the steroid treatment was discontinued, the patient was admitted with neck pain, fever, and thyrotoxicosis. The patient was diagnosed with SAT, and methylprednisolone treatment was started again. The underlying pathophysiological mechanisms in SAT cases that develop after the treatment of CD can only be speculated. One possible mechanism could be that the glucocorticoid deficiency develops after effective treatment of hypercortisolism alters the immunological responses or generates self-reactive cells and prepares an appropriate environment for the thyrolytic process.

Context. Noninvasive encapsulated anaplastic thyroid carcinomas (NE-ATCs) have been described in few case reports, and consistently associated with favorable outcome compared to the classical ATCs. Objective. Our aim is to remark a rare histological finding in ATCs, encapsulation, which has been associated with a favorable outcome. Design. We have documented a rare case of an NE-ATC with its clinical, pathological, and molecular features. We also provided a thorough discussion of all the encapsulated ATCs reported in the literature. Subjects and Methods. A 50-year-old woman with an unremarkable medical history, who presented with a thyroid nodule, and diagnosed as “follicular lesion of undetermined significance” by fine needle aspiration biopsy. The patient was lost to follow-up for six years and revisited upon her neck disturbances and underwent total thyroidectomy. Results. Sections of the right lobe revealed a grossly encapsulated nodular lesion, measuring 75x55x55 mm. Histologically, the tumor consisted of both carcinomatous and sarcomatous components supported by immunohistochemical stains. Necrosis and atypical mitotic figures were evident. Capsular and/or vascular invasion was not identified. There were no BRAF codon 600, KRAS, NRAS mutations and RET/PTC rearrangement. During three-month follow-up, the patient was free of disease without adjuvant therapy. Conclusion. Encapsulated ATCs tend to follow a favorable clinical course and may deserve conservative treatment approaches.

Context. Vitamin D is a steroid hormone that acts by binding to the vitamin D receptor (VDR) found in many tissues. According to the long-term mechanism, vitamin D causes the proliferation and differentiation of muscle cells by gene transcription. Objective. We aimed to evaluate the relationship between muscle strength and serum vitamin D levels in elderly men. Design. Cross-sectional study. Subjects and Methods. Male patients over age 50 were included in the study. Study population was divided into 2 groups with handgrip strength according to body mass index, either as subjects with weak or with normal handgrip strength test (HGST). Vitamin D levels and other variables compared between weak and normal groups. Results. Vitamin D level of weak and normal groups were 7.5 (3-19.9) μg/L, and 11.6 (11.6-34.9) μg/L, which means significant reduced vitamin D levels in weakness group (p=0.01). Vitamin D levels were significantly correlated with HGST levels (r:0.362, p=0.001). Vitamin D levels were found to be an independent predictor of weakness according to HGST in logistic regression analysis (OR: 0.453, 95% Cl:0.138-0.769, p=0.05). Conclusions. Low vitamin D level is an independent risk factor for muscle weakness in men aged more than 50 years. Therefore, vitamin D levels should be screened and early replacement should be initiated for the sake of improvement of muscle strength in elderly subjects that vulnerable for frailty.

Iodine deficiency in a geographical area can be quantified, not only by urinary iodine\r\nexcretion, but also through the incidence of elevated TSH levels measured in newborns. We\r\nmeasured the TSH level in 3015 newborns, in a partial screening realized in Mures County\r\nduring the years 2001–2006. The law for the universal salt iodization with increased KIO3\r\nlevel (34 ? 8.5 mg/kg) was adopted in Romania in 2002, and implemented in practice\r\nstarting with December 2003. We compared TSH levels of 2,454 children born in the years\r\n2001-2003, before the universal salt iodization, with those of 561 children born in 2004-\r\n2006 after the implementation of the law of universal salt iodization. An elevated TSH\r\nlevels (over 10 mUI/L, according to the WHO criteria) was revealed in 8.23 %( 199/2,454)\r\nnewborns during 2001-2003, as compared to 9.62% (54/561) subjects born during 2004-\r\n2006 (p=NS). Based on both criteria and results, Mures County is a region with a\r\nmoderately mild iodine deficiency. However, the mean value of TSH levels (over 12\r\nmUI/L) obtained during 2001-2003, (19.81 ? 2.63 mUI/L, X ? SD, n= 145) significantly\r\ndecreased in the second period (15.63 ?7.35 mUI/L, n=34) (p= 0.02), i.e. a medium decrease\r\nwith 4.18 mUI/L. While the moderate increase of TSH levels (10-12 mUI/L) is an indicator\r\nof iodine deficiency, higher concentrations (>20 mUI/L) usually indicate the coexistence of\r\na hypothyroidism due to the low iodine supply. We observed an important decrease of the\r\nhypothyroidism induced by iodine deficiency: when during the first period its incidence was\r\n2.49%, in the second one it decreased to 1.46% (p=ns). In conclusion, after increasing the\r\niodine-content by universal salt iodization, the incidence of elevated TSH level (and the\r\ncorresponding hypothyroidism) did not decrease in newborns, but the mean value of higher\r\nthan normal TSH presented a statistically significant decrease, reflecting the improvement\r\nin iodine supplementation.

Background. Paget Disease (PD) is usually asymptomatic and discovered incidentally, it is known that it is exhibited low to high grade increased F-18 FDG uptake. Aim. In this study, we investigated the distinguishability of FDG PET/CT in incidental PD cases from other bone diseases and at different stages of the disease. Patients and Methods. In this cross-sectional, descriptive study, “Paget” identification associated with PET/ CT reports was found in 69 of 18,119 studies (~3.8%). Of the 45 patients (33 males and 12 females) eligible for inclusion in the study, 35.6% had monostotic and 64.4% had polyostotic disease (p>0.5). There was no statistically significant difference in biochemical parameters between groups. Results. According to the radiological appearance of the patients, 36 were in the mixed stage and 9 were in the blastic stage. Only the difference in ALP and creatinine values between the groups was statistically significant. SUVmax, SUVmean and HU values were found to be statistically significantly higher in pagetoid bones compared to control bone lesions. For SUVmax for PD bone lesion we found the 2.55 cutoff point with a sensitivity of 91% and a specificity of 84%. Conclusion. The specific radiological appearance of bone lesions and the evaluation of metabolic activity compared to normal bone seem to help differentiate PD from other lesions. Prospective studies are needed in the differentiation of FDG's disease stage and treatment response evaluation. The ability to differentiate between benign and malignant FDG avid bone lesions in oncological patients’ enables appropriate patient management, including avoiding unnecessary additional invasive procedures such as bone biopsy.

Background. Skull metastasis has not been reported from mixed medullary follicular thyroid carcinoma (MMFTC). Objective. To present a patient with expansile lytic skull metastasis. Case report. A 61 year lady is presented with goiter for 7 years and 8 cm diameter painful swelling over frontal bone for 18 months, aspiration from which revealed sheets and clusters of polygonal cells, similar to aspiration from hypoechoic nodule in right thyroid lobe. Serum calcitonin (569pg/mL) and carcinoembryonic antigen (11.2ng/mL) were elevated. Histopathology of 3.8×3.1cm nodule in thyroidectomy specimen revealed irregular islands of small polygonal tumor cells with extracellular amyloid deposits (suggesting medullary thyroid carcinoma (MTC)), intermingled with thyroid follicular cells showing capsular and vascular invasion (follicular thyroid carcinoma (FTC)). Immunohistochemistry of the thyroid tumor was negative for calcitonin and for thyroglobulin. Post-operative serum calcitonin and stimulated thyroglobulin were respectively 97 pg/mL and 11.5 ng/mL. I131 whole body scan revealed intense uptake in region of the skull metastasis with small uptake in thyroid bed. She received 150 mCi of I131with resolution of pain, heaviness, throbbing, reduction in swelling size, and lack of disease progression. Conclusions. Skull metastasis was the presenting feature of MMFTC which improved with I131 therapy. Patients with lytic skull metastasis should be evaluated for occult thyroid malignancy.