ACTA ENDOCRINOLOGICA (BUC)

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. Thyroidectomy is becoming an ambulatory surgical procedure. By predicting hypocalcemia,duration of hospital stay might decline. We tried to determine whether measuring parathormone two hours after total thyroidectomy predicts hypocalcemia. Objective. We aimed to design a protocol for early prediction of hypocalcemia by defining PTH measurement time and cut-off value of our center. Design. One hundred and six patients undergoing total thyroidectomy between November 2017 and October 2018 were prospectively studied. Methods. Pregnant women, patients with renal failure, parathyroid disease, previous neck operation and thyroid malignancy requiring neck dissection were excluded from the study. Parathormone (PTH) and calcium measurement was done preoperatively and in the postoperative second hour. Results. Group 1 consisted of 75 normocalcemic patients while group 2 had 31 hypocalcemic patients. Mean age was 45±13.1 (age range: 18-76). Female/male ratio was 82/24. While with a 8.36 pg/mL postoperative second hour PTH, hypocalcemia can be predicted with a 51.5% sensitivity and 90.7% specificity while with a PTH decline of 40.8% hypocalcemia can be diagnosed with a 83.9% sensitivity and 52% specificity. Conclusion. Postoperative second hour PTH and PTH percentage decline can predict postoperative hypocalcemia in total thyroidectomies. Preoperative Dualenergy X-ray absorptiometry (DXA) was not found useful in hypocalcemia prediction.

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.

Background. Multiple endocrine neoplasia type 2B (MEN 2B) is a rare hereditary syndrome caused mainly by Met918Thr germline RET mutation and characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), and typical phenotypic features. MEN 2B cases previously reported in the literature have variable clinical course. Objectives. We aimed to discuss the characteristics of four MEN 2B cases with unusual presentations,clinical course and review the recent clinical data on MEN2B Results. All patients had de novo M918T mutation and no family history. The mean age of patients was 38.2 years (27-56). Two patients had typical phenotypic features of MEN 2B; the other two patients had no striking phenotypic features. First detected MEN 2B component was MTC in two, intestinal ganglioneuromatosis in one, and PHEO in one of the cases. Bilateral PHEO was detected in all four cases. Conclusions. MEN 2B is a complex syndrome characterized by wide phenotypic variability and different clinical outcomes. To diagnose sporadic MEN 2B cases, genetic testing should be performed in all cases with suspicious clinical features. Although early diagnosis is the main factor that increases life expectancy, some MEN 2B patients with late diagnosis may exhibit a mild clinical course and better prognosis than expected, with effective treatment.

Aim: We have undertaken an attempt to compare the application efficacy of the proliferative activity markers in the differential diagnosis of thyroid H?rthle cell tumors using the PCNA and Ki-67 labeling and AgNOR visualization techniques.\r\nMaterials and methods: The present work is a retrospective analysis of proliferative potential in 40 H?rthle cell tumors, on paraffin blocks: 10 H?rthle cell carcinomas (HCC), 16 H?rthle cell adenomas (HCA) and 14 hyperplastic nodules with H?rthle cell metaplasia (HCM). The evaluation of the mean number of nucleolar organizer regions (NORs) per nucleus and the proliferative index (PI-the percentage of PCNA and Ki-67 positive cells) was performed using staining silver impregnation method and antibodies against PCNA (clone PC 10) and Ki-67 (clone MIB-1) in LSAB detection Kit and visualization with DAB (diaminobenzidine). U-Mann-Whitney test was used for statistical analysis. The difference was considered significant for p<0.05.\r\nResults: The values of PI-PCNA, PI-Ki-67 as well as the mean AgNOR counts in nuclei were: 25.5, 12.8, and 5.0 in HCC; 7.6, 4.9, and 3.1 in HCA and respectively 5.1, 4.0 and 2.3 in HCM. Statistically significant differences were found in all the proliferative\r\nactivity markers between malignant and benign tumors: HCM: HCC (p<0.0001) and HCC: HCA (p<0.001). Indifferently of the examined markers and the method of quantification of the reaction, we did not found significant differences between hyperplastic nodules with H?rthle cell metaplasia and oncocytic adenomas (p< 0.07).\r\nConclusions: PI-PCNA, PI Ki-67 and mean AgNOR/ nucleus, used as markers for the appreciation of proliferative activity of oncocytic thyroid tumors (classified as adenomas, carcinomas and hyperplastic nodules with H?rthle cells), reflect differences between the studied thyroid lesions. Our results indicate the utility of these parameters in the differentiation of the benign oncocytic tumors from the malignant ones.

Thyrotoxicosis crisis is a major emergency due to the brutal occurrence and\r\nexacerbation of untreated or inadequately treated hyperthyroidism. It has uncharacteristic\r\nsigns all of which require immediate treatment. Thyroid hormones may directly influence\r\nmyocardial oxygen supply and demand and cause a critical imbalance resulting in angina\r\npectoris and myocardial infarction. We present a case patient with a fatal myocardial\r\ninfarction (MI) secondary to thyrotoxicosis. The patient presented classical coronary risk\r\nfactors and unknown hyperthyroidism, which was taken into consideration as a possible\r\ncause of the acute coronary syndrome. Although he was under anti - ischemic agents and\r\ndespite normal coronary arteries he developed MI and cardiogenic shock and died due to\r\nthyroid storm aggravated by iodine contrast and catecholamine agents.

Context. Exenatide is a Glucagon-like Peptide-1 receptor agonist, which is widely used for type 2 diabetes mellitus (T2DM). Limited and conflicting results are present about the effect of exenatide on the thyroid gland. Objective. The aim of this study was to evaluate the effect of exenatide treatment on structural and functional features of the thyroid gland in patients with T2DM. Design. The study was a prospective study, performed between 2015 and 2017. The laboratory values and thyroid ultrasonography features were compared before and after exenatide treatment. Subjects and Methods. The study included 39 obese diabetic patients. After inclusion to the study exenatide was started and patients were followed up for 6 months. Total thyroid volume, thyroid function tests, serum carcinoembryonic antigen (CEA) and calcitonin levels, the size and appearance of thyroid nodules were compared between baseline and after 6 months of treatment. Results. Exenatide at a dose of 5μg bid was started, increased to 10 μg bid after 4 weeks. We found a statistically significant decrease in thyroid volume (p=0.043) and serum thyroid stimulating hormone (TSH) levels (p=0.007), whereas serum ATPO. ATGl, fT4, fT3, CEA and calcitonin levels did no change with 6 months of exenatide treatment. There were no significant differences in the size and appearance of the thyroid nodules with treatment. The thyroid volume decrease was not correlated with TSH, body mass index and HbA1c reduction. Conclusion. Exenatide treatment for 6 months decreased serum TSH levels and thyroid volume, but had no effect on thyroid nodules and serum CEA and calcitonin levels.

Objective. This study aimed to evaluate the utility of C-peptide levels in the differentiation of monogenic forms of diabetes from type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in clinical practice. Subjects and Methods. A total of 104 patients aged >16 who visited the Dicle University’s Faculty of Medicine between April 2011 and December 2020 and were diagnosed with monogenic diabetes by genetic analysis or with T1DM and T2DM were randomly selected for retrospective evaluation. The C-peptide levels of these patients at the time of diagnosis of diabetes were compared. Results. Of the 104 patients, 24 (23%) were diagnosed with maturity-onset diabetes of the young (MODY), 40 (38.5%) with T1DM, and 40 (38.5%) with T2DM. Median C-peptide levels (ng/mL) (interquartile range) were 1.78 (1.24–2.88) in MODY group, 0.86 (0.34– 1.22) in T1DM group, and 2.38 (1.58–4.27) in T2DM group. Conclusions. There was a difference in C-peptide levels between MODY and T1DM groups but not between MODY and T2DM groups. As per clinical evaluations, although C-peptide levels of patients with MODY are similar to those of patients with T2DM patients, the possibility of C-peptide levels being similar to those required for T1DM diagnosis should also be considered.

Introduction: Prolactinomas may grow during pregnancy. Dopamine agonists (DA) prevent tumor growth, but usually suppress prolactin (PRL) both in mother and fetus. Possible long-term consequences on fetal development remain unknown.\r\nAim: to assess whether DA treatment throughout pregnancy in a dosage able to maintain physiological gestational serum levels of prolactin (PRL) still prevents prolactinoma growth.\r\nPatients and methods: We evaluated 68 pregnancies in 49 women with prolactinoma (PRM) and 46 pregnancies in healthy women as controls. Thirty-three pregnancies were recorded in 27 women treated throughout pregnancy with bromocriptine (BRC) (n = 25) or cabergoline (CAB) (n = 2) divided in 2 groups: group A (22 pregnancies in 18 patients) had suppressed serum PRL (below the 5th percentile of the control group Z during the last trimester); group B (11 pregnancies in 10 patients) had physiological serum PRL levels. Other 26 pregnancies in 21 patients were incompletely evaluated and included only in the pregnancy outcome and cure rate analysis. Treated patients were compared with the control group Y 8 women with PRM who discontinued DA after pregnancy induction (9 pregnancies) and a control group Z of 46 healthy pregnant women, randomly selected from two departments of Obstetrics. Patients with multiple pregnancies were recorded in each corresponding study group.\r\nResults: In the control group Y, tumor size showed an increase in 2 (intrasellar macroPRM) out of 8 cases (25%). DA treatment throughout gestation in 27 women with PRM prevented the growth in all cases and induced a shrinkage of more than 30% of tumor mass in 8/14 macroPRM (57.1%), i.e., in 4/7 (57.1%) of macroPRM with physiological serum PRL levels during pregnancy, and in 5/8 (62.5%) of macroPRM with suppressed PRL levels (p = NS) (1 patient had pregnancies in both groups). Low dose DA (BRC 2.5 ? 5 mg/day or CAB 0.5 mg/week) maintains physiological PRL levels in 6/12 (50%) macroPRM, but suppressed PRL in 80% of microPRM. Cure was recorded in 6/49 (12.2%) of patients. Two patients with PRM-induced neuroophthalmic syndrome were successfully treated with DA throughout 1 and respectively 3 pregnancies.\r\nConclusions: Some women with prolactinomas showed a tumour size increase if they were not treated with dopamine agonists throughout pregnancy. Maintaining physiological serum PRL levels during pregnancy (frequently with low doses of DA) prevented tumor growth, avoiding a PRL suppression that may have subtle influence on long-term foetal development.

Introduction. Pituitary adenomas (PA) are the third most common intracranial tumors, with an incidence rate of 10-15%. More than half are invasive, infiltrating adjacent structures. The primary objective of this project was to determine whether MGMT expression is associated with the invasiveness of PA. Material and Method. All patients who underwent surgical decompression consecutively between 2007- 2012 were included. All data were obtained from the case records. Formalin-fixed paraffin-embedded (FFPE) tissue specimens were stained with hematoxylin and eosin (HE) and then examined via light microscope. Paraffin blocks that lacked necrosis and hemorrhage were chosen for histologic examination. In addition to an immunoprofile battery that consisted of Ki-67 and p53, MGMT, S-100 and Pan-CK were evaluated as well. Results. The subjects included 25 women and 15 men. The mean age was 48.9 ± 14.5 years. Of these, 63% of cases involved the invasion of adjacent structures. Of the PA, 17 (42%) were non-functioning pituitary adenomas (NFPA). There was a statistically significant relationship between the invasiveness and Ki-67, p53, MGMT expression, and prolactinoma. Gonodotropinomas were mostly non-invasive. FPAs presented invasive features more frequently than NFPAs. Pan-CK was positive in GH-secreting adenomas but negative in FSH- and LH-secreting adenomas. Conclusion. Ki-67 and p53 in lower expression level can be used for evaluating invasiveness but not for recurrence. MGMT expression can be a useful IHC indicator for invasiveness. However, Pan-CK cannot be used for invasiveness or aggressiveness.