ACTA ENDOCRINOLOGICA (BUC)

Genome Wide Association Studies (GWAS) are excellent opportunities to define culprit genes in complex disorders such as the polycystic ovary syndrome (PCOS). PCOS is a prevalent disorder characterized by anovulation, hyperandrogenism and polycystic ovaries, which benefitted from several GWASs in Asians and Europeans revealing more than 20 potential culprit genes near associated single nucleotide variations (SNV). Translation of these findings into the clinical practice raises difficulties since positive hits are surrogate SNVs linked with causative mutations by linkage disequilibrium (LD). Studies in Mediterranean populations (e.g. Southern Europe and North Africa) raise supplementary problems because of a different LD-pattern, which may disrupt the link with causative mutations. Our experience in MEDIGENE program between Tunisia and France enforces the necessity of genetic anthropology studies before translating GWAS data. Tunisians are a heterogeneous population with ancestral Berbers, European, Arab and Sub-Saharan African components while South Europeans display a high level of genetic diversity, partially explained by gene flow from North Africa. Human diversity studies require sampling from Middle East and North Africa (MENA) region that will help to understand genetic factors in complex diseases.

Background. Thyroid nodules are common; however, the association of two or more different tumors in the thyroid gland is unusual. We present a first case with the association of three histological types of thryroid tumors. To the best of our knowledge, this association has not been reported in the literature before. We aim here to highlight the possible coexistence of many lesions in the thyroid gland and to discuss treatment options. Case presentation. We report the case of a female patient who presented with a multinodular goiter. The final pathology after total thyroidectomy found the association of a multifocal papillary thyroid microcarcinoma arising within a Hurthle cells adenoma in a lobe and a noninvasive follicular thyroid neoplasm with papillary nuclear features in the other lobe. Due to the very low risk of recurrence, the patient was not treated with radioactive iodine. Conclusions. Many controversies remain about the management of Hurthle cells tumors and many variants of papillary thyroid carcinoma. Although the management of our case did not change, more studies are necessary to analyze the evolution of patients with multiple thyroid neoplasms. When discussing therapeutic options, the advantages and disadvantages should be considered case by case based on disease staging.

The prerequisite for developing methods for type 1 diabetes mellitus prevention is to know its pathogenic mechanisms. The aim of this work was to characterize a group of children with type 1 diabetes mellitus regarding pancreatic antibody positivity and fasting C peptide concentrations. The study group enrolled 117 children, 61 boys (52.1%), mean age 12.7?3.1 years. Islet cell antibodies, glutamic acid decarboxylase antibodies (GADA), IA-2 antibodies (IA-2A) and fasting C peptide were measured. Sensitivity for GADA and IA-2A tests was 85% and 75%, respectively. Specificity for the tests was 87.1% and 98%, respectively. The threshold for pancreatic antibody positivity was considered the 97.5th percentile, and normal values for fasting C peptide were between the 5th and 95th percentiles from a control group (n=73), matched for age and gender. Thirty-nine patients (33.3%) were positive for 1 antibody, 10 (8.6%) were positive for 2 and 2 (1.7%) were positive for all 3 antibodies. The positivity for pancreatic antibodies and for islet cell antibodies was significantly lower in patients with diabetes duration>2 years, compared with the rest: 32% vs. 52.2% (p=0.03) and 6% vs. 20.9% (p=0.03), respectively. Mean fasting C peptide and the percentage of patients with normal C peptide decreased significantly one year after the diagnosis of diabetes: 0.20?0.40 ng/ml vs. 0.44?0.57 ng/ml (p=0.03) and 9.5% vs. 27.3% (p=0.02), respectively. In conclusion, in children with type 1 diabetes mellitus, pancreatic autoimmunity is more intense in the first two years of the disease and insulin secretion decreases one year after the diagnosis.

Introduction. Graves’ disease (GD) and concomitant thyroid nodules can be found in up to 44% of all cases, of which up to 17% are determined as malignant tumors. Medullary thyroid carcinoma (MTC) seems to be found extremely rarely, which causes belated diagnosis. Case presentation. A 50-year-old man was diagnosed with GD. Neck ultrasound revealed suspicious thyroid nodule, a fine needle aspiration biopsy was performed, and it revealed microfollicular hyperplasia, Bethesda IV. The patient was operated on and the histological examination confirmed MTC. Genetic testing revealed the sporadic form of MTC. Six weeks after the initial surgery, elevated tumor markers confirmed the persistence of the disease. The patient underwent a pyramidal lobe removal with a unilateral central compartment lymph node dissection. Histological analysis confirmed typical changes of MTC and a spread of the disease. 2 months after the lymphadenectomy, tumor markers and imaging examination revealed suspicious lymph nodes; this discovery was followed by a bilateral lymph nodes dissection and persistence of MTC confirmation. Conclusion. An early detection of sporadic MTC with concomitant GD is challenging. We want to emphasize the benefits of calcitonin (Ctn) measurement in the blood sample and a Ctn immunocytochemistry detection in the case of an autoimmune thyroid disease and suspicious thyroid nodule before the radical treatment, despite the lack of universal recommendations for routine Ctn measurement, in order to reach an earlier diagnosis of the cancer, and to perform a more radical surgical treatment.

Vitamin D is essential in efficient absorption of calcium and normal mineralization of bone. Severe vitamin D deficiency produces impairment of bone mineralization and osteomalacia. Less severe vitamin D deficiency, called vitamin D insufficiency or inadequacy, causes secondary hyperparathyroidism, increased bone turnover and bone loss. The aims of our study were: the evaluation of vitamin D status and its seasonal variation in postmenopausal women with osteoporosis, from Romania; we studied also the relationship between vitamin D and parathyroid hormone serum concentrations in order to establish the threshold level of vitamin D which determines secondary hyperparathyroidism. The study was performed on 834 postmenopausal (natural or surgical) women who attended the National Osteoporosis Center and were diagnosed with osteoporosis using dual absorptiometry with X ray (DEXA). None was receiving vitamin D supplementation and they were not taking drugs affecting bone and mineral metabolism and were not suffering from such diseases. Estimation of vitamin D and parathyroid hormone status was made by determining 25-hydroxyvitamin D (25OHD) and PTH-intact (PTH) serum concentrations from a single blood sample using immuno-enzyme methods. The results were compared using Student? t test for unpaired values and linear regression to establish the correlation. All data were expressed as mean value ? standard deviation and a value of p<0.05 was considered as statistically significant. In a previous study we reported for premenopausal normal women the mean value for 25OHD at 26.58?10ng/ml. At the same time, we defined the vitamin D deficiency as the levels below 12 ng/mL, and the insufficiency of vitamin D (vitamin D inadequacy) as the values between 12 and 26.58 ng/mL. The mean serum 25OHD concentration for our study group was 20.04?144.22 mg/mL. We defined arbitrary values (using data from international studies) for 25OHD serum levels to estimate the prevalence of vitamin D deficiency and vitamin D inadequacy in our study group. In 834 postmenopausal women with osteoporosis, living in Romania, without vitamin D supplementation or pharmacological therapy to treat or prevent osteoporosis, the prevalence of vitamin D deficiency was 32.2% and the prevalence of vitamin D inadequacy was 42.3%. Seasonal variation of 25OHD was found statistically significant (p<0.05), with lower values at the end of winter. Statistical tests applied to results have shown a significant negative correlation between PTH and 25OHD serum levels (p<0.001) and established the cut-off concentration for 25OHD which determine secondary hyperparathyroidism at 20 ng/mL. Our data underscore the need for adequate vitamin D supplementation in women with osteoporosis.

Background. Exposure to methotrexate (MTX) causes infertility in young women treated for non-neoplastic\r\ndiseases. Leucovorin an antidote to MTX is used to prevent its side effects. Reproductive tract cells are fast proliferating like cancer cells. Hence, MTX may cause deleterious effect on these cells.\r\nAim. Explore MTX effect on biochemical markers and the protective role of leucovorin in the accessory reproductive\r\norgans viz; oviduct, uterus, cervix and vagina.\r\nAnimals and Methods. Rats with regular oestrous cycle were randomly divided into five groups (n=6) as follows:\r\nControl, MTX LD (low dose), MTX HD (high dose), MTXHD+LCN (leucovorin, LCN), and MTXHD+WD (withdrawal): 20 days withdrawal. Animals were treated once per day intramuscularly (im) for 20 days. Rats were sacrificed on day 21. MTXHD treatment was withdrawn for additional 20\r\ndays and animals sacrificed on day 41. Oviducts, uterus, cervix and vagina were used for biochemical markers analysis.\r\nResults. MTX treatment decreased RNA, DNA and protein concentrations. Such similar effects were also observed in\r\nG6PD, LDH and ALP activities. Leucovorin and withdrawal of treatment partially recovered MTX effects. Uniquely, this study signifies MTX action on nucleic acids and protein levels and also G6PD, LDH and ALP activities in oviducts, uterus, cervix and vagina.

Introduction. Hypoparathyroidism is a rare endocrine disorder, leading to complications affecting the kidneys, the eyes, the cerebrum (Fahr’s syndrome, epilepsy, parkinsonism, cognitive impairment), and the heart. Case report. We present the case of a 24-year old male that presented to our clinic for generalized tonicclonic seizures increasing in frequency for the last year or so. Furthermore, he was diagnosed with subcapsular cataract of both eyes and had intraocular lens implant surgery 12 years ago. CT scan performed at admission showed calcium deposits on the dentate nuclei, basal ganglia, thalamus, cerebellum and bilateral subcortical fronto-parietal white matter compatible with Fahr’s disease. The results of the laboratory tests were normal except for hypocalcemia, hyperphosphoremia and low intact parathormone (iPTH). The patient was diagnosed with primary hypoparathyroidism which led to Fahr’s syndrome. The patient was prescribed oral medication including calcium carbonate, calcidiol, magnesium orotate and levetiracetam. The follow-up after three months revealed a seizure free status and normalization of magnesium, calcium, and phosphorus levels. Conclusion. Fahr’s syndrome can be a cause of epileptic seizures and should be considered in the clinical approach to an epileptic patient, especially in children, teenagers, and young adults.

Context. The objectives of treatment of thyroid carcinoma include hormonal suppression, radioiodine ablation and follow-up with serum thyroglobulin (Tg). Tg levels should not be measured before six weeks postthyroidectomy. Objective. To describe the behaviour of early postoperative Tg in patients who underwent total thyroidectomy and its ability to predict the serum Tg levels after suppression. Design. This is a retrospective cohort study. Subjects and methods. Adult patients who underwent total thyroidectomy with at least two postoperative measurements of serum Tg, negative TgAb and concomitant serum TSH values were included. Tg, TgAb and TSH level measurements were completed two weeks postoperatively and during the follow-up period. Results. Twenty-nine patients fulfilled all criteria. The median serum Tg level at two weeks after surgery was 3.8 ug/L (0.3 -300) with a serum TSH level of 69.9 mU/L; 11-227. At the two-week measurement, 16 (55%) patients had serum Tg levels lower than 5 ug/L and 4 patients had levels between 5-10 μg/L. Conclusions. Postoperative early serum Tg could be an alternative to values measured six months after surgery and could be used as a predictive tool to make earlier therapeutic decisions.

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.