ACTA ENDOCRINOLOGICA (BUC)

Purpose. Minimally invasive follicular thyroid carcinomas (MIFCs) are uncommon; literature offers limited guidance on their natural history and management. Starting January 2015 we measured circulating tumor cells (CTCs) in patients with MIFC (n=22) or benign thyroid tumors with follicular features (n=4). Methods. In a retrospective analysis, we assessed detectability of and serial changes in CTC, compared demographic/clinical differences between CTC-positive versus CTC-negative subgroups using Student’s t-test, and examined correlations between CTC status and serum thyroglobulin using Spearman’s test. CTCs were quantitated via immunomagnetic separation/microscopic inspection. Results. Thirteen patients (50%: 12/22 MIFC, 1/4 benign tumor) were initially CTC-positive; 3 remained CTC-positive in ≥1 subsequent measurement. CTC-positive patients had larger tumors and more frequent multifocality and vascular invasion versus CTC-negative patients (n=13). However, no tested variable differed significantly between the subgroups. After 17.2±10.5 months, neither subgroup showed evidence of disease. Significant correlation was absent (p ≥ 0.263) between CTC and Tg negativity (r = 0.243; n=13 evaluable) or initial CTC positivity and Tg positivity (r = -0.418; n=9 evaluable). Conclusions. In the studied settings, CTC measurement is feasible, has unclear clinical/outcome implications, but may provide different information versus thyroglobulin testing. Lengthier assessment is warranted in larger series.

Introduction. The recall rate in congenital hypothyroidism (CH) newborn screening programs depends on several factors such as primary screening strategy, sample collection guidelines, and cut-off. A recall rate of 0.05% is recommended but recall rates of 0.01-13% are reported worldwide. Objective. The aim of the study was to assess the recall rate in association with the age of the newborn at sample collection and with a lower cut-off. Design. This was a retrospective correlational study concerning TSH results in CH screening program. Subjects and methods. All newborns from a tertiary center in Targu Mures, Romania between 2013-2018 were included. Four groups were created and a correlation test between TSH median value and age in days was performed. The recall rate was calculated using three cut-off levels for 8182 TSH results performed in 2018. Results. 90% of the DBS were collected in days 3-5 after birth and 1/79 live births from this group had TSH above the lower cut-off used (10 mUI/L). 2% of the samples were collected in less than 48 hours after birth and 1/21 live birth from this group had TSH > 10 mUI/L. The recall rate in our center in 2018 was 0.08%, higher than the recommended rate of 0.05%. With the cut-off value recommended by the Health Ministry a 0.03% recall rate was obtained. Conclusions. Sample collection in less than 48 hours increases the recall rate in CH screening with TSH primary testing strategy. A lower cut-off raises the recall rate with a higher rate of false-positive cases (94.12%) but with 100% negative predictive value.

Context. Patients with radically treated differentiated thyroid carcinoma (DTC) undergo multiple episodes of iatrogenously-acquired hypothyroidism for the oncological follow-up. In some patients, this elevates high-sensitive C-reactive protein (hsCRP), a cardiovascular risk biomarker. Objective. We wanted to determine if there is any correlation between repeated hypothyroidism episodes, elevated hsCRP and an increased cardiovascular risk as stated through myocardial perfusion. Design. Between July 2014-January 2015, we analyzed serological levels of hsCRP for identifying our patients’ cardiovascular risk; we performed a myocardial perfusion scintigraphy to observe the alterations. Subjects and Methods. We included 27 patients (n=27), mean age of 52±10: CI (95%),14 female, all diseasefree after thyroidectomy, radioiodine ablation and chronic thyroid hormone treatment. We assigned the cardiovascular risk category for each patient according to hsCRP levels; all patients underwent a myocardial perfusion scintigraphy in order to determine the cardiac perfusion index (CPI). Results. hsCRP has been higher in > 65 years old male patients with more than 5 thyroid hormone withholdings. hsCRP is significantly associated with CPI (p=0.001). Spearman’s rank correlation indicates a strongly positive linear correlation between these two parameters (r=0.745). Conclusions. Repeated thyroid hormonal withdrawals in patients with DTC during the long-term follow-up elevated hsCRP at cardiovascular risk levels, having an impact on myocardial perfusion.

Alteration in nervous system function in patients with thyrotoxicosis is frequent. In rare cases, mental disturbances may be severe: maniac-depressive, schizoid or paranoid reaction. The pathophysiologic basis of these nervous system findings is not well understood. The first patient, being on treatment with benzodiazepine and Risperidone for mood deterioration, was admitted in Thyroid Unit 1 for clinical features suggesting addition, he developed auditory and visual hallucinations, bizarre behavior, disorganized speech, disorientation, poor attention and loss memory for recent events, having a good clinical response after addition of antithyroid drug therapy. The second case developed clinical features suggesting thyrotoxicosis, associated with visual and auditory hallucinations, marked psychomotor agitation and bizarre behavior. After an unsuccessful monotherapy (Risperidone), a good response of clinical features (including psychiatric symptoms) to combined therapy (Methimazole and Risperidone) was recorded. The diagnosis of Graves’ disease was based on clinical and laboratory data (suppressed serum TSH level, elevated serum FT3) and ophthalmological examination or positive anti - TPO antibodies. Both patients were successfully treated with combined therapy - Methimazole and Risperidone. Both case reports demonstrate the importance of performing thyroid function tests in patients with acute psychosis.

Anaplastic thyroid carcinoma (ATC) is the most aggressive type of thyroid\r\ndedifferentiation. Rarely, ATC associates rhabdoid characteristics and only few cases have been\r\npresented to date. We present a case of a thyroid papillary carcinoma which shifted to an\r\naggressive anaplastic form with rhabdoid dedifferentiation and concomitant leukemic reaction\r\nwith eosinophilia. A 76 years old man with a long standing history of a thyroid nodule, noticed\r\nwithin months a rapid growth of the nodule associating marked compression phenomena with\r\nleft deviation of the trachea and esophagus and mild dysphonia. Palliative surgery was\r\nperformed, but the evolution was unfortunate with further health deterioration (fatigue, dyspnea,\r\ndysphagia, loss of appetite and weight loss). Laboratory tests proved leukocytosis with\r\nneutrophilia and left deviation of leukocytes formula, with major eosinophilia. The pathology\r\nshowed a thyroid papillary carcinoma with anaplastic changes. By immunohistochemistry,\r\nit was confirmed the thyroid origin of the tumor (thyreoglobulin positive areas) but also the\r\nepithelial nature of the undifferentiated areas (positive areas for cytokeratin and epithelial\r\nmembrane antigen). Moreover, in the anaplastic areas, rhabdoid differentiation was\r\nidentified by positive coloration against vimentin, protein S100 and desmin. The tumor was\r\naggressive by its anaplastic transformation, confirmed by a high proliferation index (Ki67:\r\n40% positive). The computed tomography was concordant with the phenotype predicted by\r\nhistological description showing a malignant thyroid tumor, invading cervical and mediastinal\r\nareas with secondary lung disseminations. Unfortunately, the outcome was fatal even though\r\nadditional treatment methods have been tried: radiotherapy and chemotherapy. The\r\nparticularities of this case reside in the very rare dedifferentiation of a papillary thyroid\r\ncarcinoma towards an anaplastic thyroid carcinoma harboring the rhabdoid phenotype and\r\nalso its association with eosinophilia.

Aims: To assess if amiodarone maintains its antiarrhythmic efficacy in the presence of amiodarone-induced hyperthyroidism (AIT) and to identify the tri-iodothyronine (T3) threshold for atrial fibrillation in patients with AIT versus common hyperthyroidism.\r\nPatients and methods. Study group A consists in 49 patients (25 M/24 F) with AIT (220.83 ? 71.33 mg/day along 2.36 ? 2.25 years) and severe cardiopathies (9 valvulopathies, 40 ischaemic, dilatative and hypertensive cardiomyopathies), aged 57.87?12.63 years. Control group B consists in 51 hypothyroid (B1) or euthyroid patients (B2) treated with amiodarone (222.55 ? 68.78 mg/day along 2.67 ? 1.84 years) and also in 100 patients (23M/77F) with overt hyperthyroidism (B3), without major heart diseases, aged 52.74?12.85 years; TSH, total T3, total T4, free T4 were measured by radioimmunoassay. All were clinically, ECG and echocardiography evaluated.\r\nResults. Prevalence of arrhythmias recurrence was 59.2% (29/49 patients) in group A, significantly higher than in each control subgroups B: B1- 28% (7/25), B2- 15.45% (4/26) and B3- 20% (20/100), P< 0.001. Patients from study group A with AIT and T3 levels >250 ng/dL developed significantly more frequent atrial fibrillation (p= 0.04). However, in control group B3 with common hyperthyroidism, no T3 threshold for arrhythmias could be identified. Overall, there were no significant differences in total T3 levels with respect to the presence of atrial fibrillation in both study group A and subgroup B3 with common hyperthyroidism (p=ns).\r\nConclusion. Amiodarone antiarrhythmic efficacy is surpassed in AIT by the increased arrhythmic susceptibility of damaged myocardial tissue to minimally increased thyroid hormones levels. A tri-iodothyronine level > 250 ng/dL superimposed on preexistent proarrhythmic substrate in amiodarone-induced hyperthyroidism should be avoided.

Chronic transfusion regimen and chelating therapy has dramatically improved the life expectancy of thalassemic patients. The aim of this study was to assess the prevalence of endocrine disturbances in patients with beta-thalassemia major. Subjects were 64 patients with a mean age of 19.45 ? 6.82 years found in haematological care at the National Institute of Transfusional Haematology. All the patients were evaluated clinically and biologically. LH, FSH, estradiol, testosterone, TSH, free T4, insulin were measured by chemiluminescence; mean ferritin value was used to assess iron overload. Fifty one patients (79.68%) -27 male and 24 female in our group were at pubertal or adult age. Eleven boys (40.74%) had delayed puberty, 10 (37%) arrested puberty and 4 (14.8%) had reached complete sexual maturation. In the female group, 6 (25%) had delayed puberty, 4 (16.66%) arrested puberty and 14 (58.32%) reached full sexual development. Half of both the male and female patients with complete sexual maturation had hypogonadotropic hypogonadism at the evaluation moment. Moreover, 34 (53.12%) of our patients had pathological short stature, 11 (17.18%) primary hypothyroidism, 5 (7.8%) hypoparathyroidism, 3 (4.68%) diabetes mellitus and 6 (9.37%) insulin resistance. We found a significantly higher mean ferritin value in patients with endocrine disturbances of any type compared to subjects without endocrinopathies. In conclusion, our data showed that hypogonadism and short stature were the most frequently found endocrine disturbances. Early form of hypogonadism had a major clinical impact on sexual development and final height. These results suggest that early endocrine evaluation and treatment are necessary in order to improve the quality of life of these patients.

Aim. Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) become an important tool in oncology by combining the metabolic information from 18F-FDG PET with the morphological information of CT. The main objective of this study was to assess the diagnostic value of PET/CT in patients with differentiated thyroid carcinoma (DTC). Material and Methods. We analyzed 173 PET/CT scans of patients with DTC presenting elevated thyroglobulin (Tg) levels, negative Tg-antibodies levels, negative Iodine-131 whole-body scanning (I-131 WBS) and without any signs of clinical or other imaging technique for tumor recurrence/metastases. Results. PET/CT scans were positive in 38% of cases (65/173). The sensitivity, specificity, positive predictive values and the accuracy of PET/CT imaging were 88.09%, 98.6%, 93.1% respectively 96.53%. After the PET/CT scan 29 patients underwent surgery, 24 of them continued radio-iodine therapy, 5 patients initiated tyrosine kinase inhibitors treatment and external radiotherapy. Conclusion. 18F-FDG PET/CT is a valuable imaging technique which has the capability of identifying those cases of thyroid recurrence/metastases with elevated Tg levels and negative I-131 WBS. The treatment strategy was changed in 89.2% cases of positive PET/CT scans which shows us that 18F-FDG PET/CT imaging should be integrated into the follow-up programs for DTC patients.

Aim: to evaluate the impact of hyperthyroidism on glycemic control among patients with diabetes mellitus (DM).\r\nResearch design and methods: This retrospective study included patients with hyperthyroidism and DM admitted in Endocrinology, Nutrition Diseases and Diabetes Department of Elias University Emergency Hospital. We evaluated 37 patients (35 women/ 2 men), with a mean age of 54.7?15.3 years and duration of diabetes 8.1?7.49 years; 20 patients with Graves diseases (54%), 10 with toxic multinodular goiter (27%), 5 with autonomous hyperfunctioning adenoma (13%) and 2 with amiodarone induced hyperthyroidism (5.4%). Clinical data were recorded for all our patients, as well as thyroid ultrasound exploration, laboratory analyses (glycosylated hemoglobin, free thyroxine FT4, triiodothyronine T3, thyroid stimulating hormone TSH).\r\nResults: Diabetes control was achieved with: insulin in 23 (62%) patients, antidiabetic oral agents in 9 (24%) and solely diet in 5 patients (13.5%). Hyperthyroid patients had a mean value of glycosylated hemoglobin of 9.3%?2.4% (poor glycemic control) versus 7.2%?1.6% after the treatment of hyperthyroidism. Among insulin-treated patients, the average need of insulin in hyperthyroid status was 0.72 u/kg versus 0.55 u/kg when the patients became euthyroid (p<0.01). We found a significant association between type 1 diabetes mellitus and Graves&#8217; disease compared to toxic multinodular goiter (80% vs 50%, p<0.01).\r\nConclusions: The presence of hyperthyroidism aggravates glycemic control of the patients with diabetes mellitus and increases insulin need in insulin-treated patients. Once the thyroid function was stable, the insulin need decreased significantly (p<0.01). Hyperthyroidism should be radically treated to obtain a good glycemic control. Type 1 diabetes is significantly associated to Graves&#8217;s disease by an autoimmune mechanism.

There are no new national growth references for the Romanian population and the current recommendations for short stature evaluation is the use of the Swiss growth charts developed based on a longitudinal study. The aim of the present paper is to present the new synthetic growth references for Romanian children. Material and methods. We used local Romanian data from 9 studies with information on height and weight obtained between 1999 and 2016. Based on their plausibility and methodology six studies were selected for generating the National Synthetic Growth References for Romanian Children based on the specific methodology described previously. The selected studies included 8407 subjects measured in schools/kindergartens. Age is reported in years covering a range from 3-18 years. Height and weight were measured at a precision of 0.1 cm and 0.1 kg. All children were measured at normal temperature, in light clothes, without footwear. Results. We present the charts and tables with the common centiles for height, weight and body mass index for boys and girls. Conclusion. We suggest synthetic growth references based upon recent growth data from 6 different Romanian regions as new National Growth Charts for Romanian children.