ACTA ENDOCRINOLOGICA (BUC)

Aim. To evaluate the malignancy rates of Atypia of undetermined significance /follicular lesion of undetermined significance (AUS/FLUS) cases in the light of clinical and sonographic features. Material and Methods. The percentage of AUS/ FLUS cases, second fine needle aspiration cytology (FNAC) results, cyto-histopathological correlations and risk of malignancy were analyzed. Results. 113 out of 1461 thyroid FNAC samples (7.7%) were diagnosed as AUS/FLUS and included in the study. Seventy three out of 113 cases (64.6 %) underwent repeat biopsies or surgery. From 45 cases repeat biopsies were taken and 28 had thyroidectomy or lobectomy. There was a significant relation between nodule size and underwent surgery or repeat FNAC (p=0.036). Malignancy rate was 24.6% for cases which had any managements. The malignancy rates were higher in AUS/FLUS cases with cytological atypia (28.8%). After surgery the most common malignancy was papillary thyroid carcinoma, followed by follicular carcinoma. Conclusion. The risk of malignancy of AUS/ FLUS cases is quite high because of the heterogeneity of the group. The sub-classification of this category according to cytological or/and architecture atypia may be more useful in predicting malignancy risk. Further larger studies with ancillary techniques including molecular analysis may be more useful in determining the malignancy risk and appropriate management of this heterogeneous category.

A 63-years old patient with severe thyrotoxicosis with cachexia and high frequency atrial fibrillation showed an inadequate secretion of TSH. A pituitary macroadenoma was revealed by computed tomography. Acute octreotide administration decreased serum TSH\r\nfrom 2.48 mU/mL to 0.06 mU/mL and T3 from 3.1 ng/mL to normal values (0.93 ng/mL) in 3 days; at the same time serum T4 remained unchanged (raised).The response to octreotide supported the diagnosis of TSH-secreting adenoma. T3 suppression test is no longer useful at present for diagnosis.Administration of long- acting somatostatin analogues (lanreotide) together with antithyroid drugs (ATD) was initially necessary. However, after removal of pituitary tumor the clinical symptoms (including atrial fibrillation) disappeared.ATD administration was no longer necessary, nor was octreotide or lanreotide. Immunohistochemistry certified that the pituitary tumor was a pure thyrotropinoma (without plurihormonal expression). Complete cure of severe thyrotoxicosis due to a TSH-secreting pituitary adenoma by pituitary surgery is possible. Thyroidectomy is not indicated.

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.

Background. Patients with Down’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’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.

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.

Context. Graves' disease is the most prevalent cause of hyperthyroidism worldwide. Adiponectin, the most abundant adipokine, plays a significant role in a cluster of prevalent diseases connected to metabolic disorders. Objective. Although the association between adiponectin and Graves' disease has been studied, the existing data is inconsistent. Therefore, we conducted this systematic review and meta-analysis to evaluate the relationship between adiponectin levels and Graves' disease. Methods. We performed a systematic electronic search on PubMed, EMBASE, Scopus and Cochrane Library using predefined keywords. We used the NHLBI quality assessment tools to assess the included studies. Results. There were 11 studies involving 781 subjects included in our qualitative synthesis, while 6 studies were included in our quantitative synthesis. We observed significantly increased adiponectin levels in Graves' disease patients compared to controls (MD 2.983 [95% CI 0.138– 5.828]) and hypothyroidism patients (MD 3.389 [95% CI 1.332–5.446]). Nevertheless, no significant MD was observed when comparing Graves' disease patients with and without Graves' ophthalmopathy (MD -27.124 [95% CI -88.893 – 34.645]). Conclusions. Adiponectin levels were significantly higher in patients with Graves' disease compared to controls and hypothyroidism patients. However, patients with and without Graves' ophthalmopathy did not present a significant mean difference in adiponectin levels.

Abstract Introduction. Turner syndrome, a genetic disorder with an exclusively feminine phenotype, is caused by complete or partial X monosomy in some or all cells. Although the condition is usually diagnosed after birth, now, it is possible to detect the syndrome prenatally. Case reports. We present two cases of Turner syndrome diagnosed during the first trimester of pregnancy. The condition was suspected because of several ultrasound signs and was confirmed in both cases after an invasive prenatal technique. In one case, the fluorescent in situ hybridization technique was applied. In the other case, the chromosomal anomaly was detected using the G banding technique. Threedimensional ultrasound and HDlive technology were extremely useful in helping the patients to better understand the fetal pathology and accept an invasive procedure as a final step in establishing the diagnosis. Conclusion. These cases demonstrate the importance of using ultrasound as a screening method to detect suspected cases of Turner syndrome, however, the disorder needs to be confirmed with chromosomal analysis after performing an invasive prenatal technique.

Background: Germline aryl hydrocarbon receptor-interacting protein (AIP) mutations are found in familial isolated pituitary adenoma syndrome (FIPA) families and in a small number of sporadic pituitary adenoma (PA) patients. Although the tumorigenic mechanisms of AIP mutations are unclear, truncating mutations are considered pathogenic, but missense mutations are difficult to evaluate. p.R16H (c.47G>A) is a controversial AIP variant of unknown significance. Aim: To describe a new PA case associated with AIP p.R16H. Patients and methods: One AIP p.R16H non-functioning pituitary adenoma (NFPA) case identified by mutation sequencing screening of sporadic PA patients; 108 controls were screened for p.R16H. Results: The 38 yrs. old male NFPA patient had no family history of PA and harboured a heterozygous p.R16H variant. The proband and two brothers presented severe intellectual disability. Severe visual impairment was the initial symptom and clinical, biochemical and imaging examination demonstrated a large NFPA invading the right cavernous sinus. After transsphenoidal debulking, the remaining tumor continued growth. One of proband’s sisters was negative for p.R16H. Among controls, we identified one heterozygous p.R16H carrier, presenting a thyroid follicular neoplasm. Loss of heterozygosity analysis of the pituitary and thyroid tumors was not performed. Conclusions: We report two new occurrences of AIP p.R16H, associated with a NFPA and with a thyroid tumor. The NFPA patient was young and presented an invasive macroadenoma, features typical of AIP-mutated patients. Because the association between p.R16H and PAs has not been conclusively established, further research of p.R16H is warranted, in view of its implications for AIP genetic testing.

Context. Rapidly progressive precocious puberty (RPPP) is a rare condition in Turner syndrome (TS), with no consensus on treatment and follow-up. Only 12 cases have been reported so far. Objective. We aimed to evaluate the effects of the GnRH analog (GnRHa) on growth and anti-mullerian hormone (AMH) levels in TS and RPPP. Design. The clinical and laboratory data was recorded at baseline and after treatment. Subjects and methods. An 8.1-year old girl with a karyotype of 45, X/46, XX presented with breast development at Tanner stage-2. Breast development advanced to Tanner stage-3 at the age of 8.7 years. Growth velocity (GV) was 8 cm/year. Bone age was 11 years with a predicted adult height of 152 cm. Luteinizing hormone (LH) was 1.69mIU/mL and estradiol was 33pg/mL, confirming the central puberty. AMH level was 6.33ng/mL. The sizes of ovaries and uterus were compatible with the pubertal stage, with an endometrial thickness of 5 mm. GnRHa was started for RPPP. Results. After three months, GV declined to 0 cm/3 months and AMH level to 50% of the baseline. Growth hormone (GH) treatment was started for insufficient growth. GV improved with GH treatment, as well as a far more decreased AMH level. Conclusion. GV usually declines before puberty in patients with TS, even if the mid-parental height is tall. RPPP should be considered if GV is increased. Excessive suppression of growth may be prevented with GH treatment. GnRHa treatment also plays a role in reducing AMH levels in patients with TS.

Introduction. Vitamin D (VD) deficiency is highly prevalent worldwide. Aim. To assess the prevalence of hypovitaminosis D in HIV-positive Romanian patients compared to controls. Methods. Serum 25OHD concentration was measured in HIV-infected patients and a control sample, matched by age, sex and menopausal status. The 25OHD status was defined as: deficiency < 20 ng/mL (severe deficiency <10 ng/mL), insufficiency 20-30 ng/mL, normal >30 ng/mL. Results. We evaluated 118 HIV-positive patients (72 males, 46 females), aged 36.9±12.2 years. 98.14% of them were on complex antiviral regimens. The B/C hepatitis coinfection rate was 9.3%. The control sample consisted of 119 subjects, (74 males, 45 women). The median and interquartile range for serum 25OHD concentration in patients was 17.6 (9.7, 26.9) ng/mL and 23.7 (18.4, 27.5) ng/mL in controls (p=0.001). Only 15.96% of HIV-positive cases and 12.71% of controls had normal VD status. The percentage of cases with severe VD deficiency was significantly higher in HIV positive cases (23.52%) compared to HIV-negative controls (4.2%, p=0.001). Conclusions. Hypovitaminosis D was identified in 84.04% of HIV-infected patients, but the serum 25OHD concentration was not associated with specific HIV-related factors in our sample. Clinical guidelines regarding VD status determination and supplementation in HIV patients are needed.