ACTA ENDOCRINOLOGICA (BUC)

Background. The loss of reproductive function is one of the mostimportant adverse effects of chemotherapy. Folic acid deficiency may be harmful in pregnancy. Hence, it is imperative to investigate if leucovorin (LCN), a folinic\r\nacid supplementation and withdrawal of MTX treatment facilitate maintenance of pregnancy in albino rats.\r\nAim. The aim of this study was to examine the role of leucovorin (LCN) and withdrawal of MTX treatment in the\r\nprotection of pregnancy at very early stage of pregnancy in MTX treated rats.\r\nAnimals and Methods. Rats with regular oestrous cycle were randomly divided into five groups (n=6) as follows: Control,\r\nMTXLD (low dose), MTXHD (high dose), MTXHD + LCN (leucovorin), and MTXHD + WD (withdrawal). Animals were treated intramuscularly (im) on days 1-5 of pregnancy. MTXHD treatment was withdrawn and female rats showing regular cycle were caged with male rats. Laparotomy was performed on day 8 of pregnancy to note the number of implantation sites. Rats were sacrificed on day 20.\r\nResults. MTX significantly reduced maternal weights, number of corpora lutea, and implantation sites. 100% foetal\r\nresorption was prevalent in MTX treated groups. LCN supplementation did not help maintain pregnancy. While approximately 45% foetal resorption was observed in\r\nwithdrawal group.

A 20-year-old woman was studied because of lack of spontaneous pubertal development and primary amenorrhea. At the moment of examination in the Medical Genetics Department she had normal height, sparse axillary and pubic hair, but breasts were well developed (she already had some estrogen therapy). She had normal but infantile external genitalia, normal vagina and small uterus. Laparoscopic investigation suggested the presence of gonadoblastoma in the dysgenetic gonads and histopathologic examination confirmed the diagnosis. The karyotype revealed a 46, XY chromosome constitution in lymphocytes, without structural defects of X or Y chromosomes. Because of the risk of malignancy, gonadectomy was performed.

It is known that antithyroid drugs have been associated with development of agranulocytosis or secondary autoimmune neutropenia. Aplastic anemia is an unusual but severe form of haematological complication after antithyroid drugs. We are presenting a case of a 34-year old woman diagnosed with Graves’ disease, based on ophthalmopathy, symptoms and signs of hyperthyroidism, a diffuse enlargement of the thyroid gland; TSH level= 0.17 mU/L, fT4= 28 pmol/L, T3= 4.92 nmol/L, thyroglobulin antibodies= 117 IU/mL. The patient developed, after six weeks of treatment with Carbimazole 60 mg daily, a moderate aplastic anemia (pancytopenia: haemoglobin level= 8.2 g/dL, granulocytes= 800/mmc, platelets= 40,000/mmc; hypocellular bone marrow with increased fat cells and lymphocytosis, plasmocytosis and mastocytosis, in the absence of neoplastic or infectious infiltrations, possibly with immune aetiology suggested by disturbance of CD4/CD8 and favourable response after immunosuppressive therapy). Therapy was represented by: stopping the administration of carbimazole, broad spectrum antibiotics, antiviral and antifungal prophylaxis,general and dental hygiene, high doses of methylprednisolone followed by Cyclosporin A 12 mg/kg/day, with favourable evolution. The serum T3 and T3/T4 ratio increased after the antithyroid drug regimen was stopped . After 3 months of therapy, the patient was in complete haematological response with haemoglobin value= 11.8g/dL, granulocytes= 2.200/mmc, platelets = 130,000/mmc and was submitted to subtotal thyroidectomy.

Background and Objectives. Levels of insulin-like growth factor-I are characteristically low in Laron syndrome which is a factor that has important roles on vascular health and development. Congenital insulin-like growth factor-I deficiency was reported to be associated with some vascular disorders. However, vasculitis diseases and Laron Syndrome association has not been reported in English literature up to date. Patient. We report the case of a two and a half years old Turkish girl, who was diagnosed as Laron syndrome when she was 12 months old. She presented with acute vasculitis lesions. Her physical examination and laboratory studies did not reveal a specific infectious agent or also an autoimmune disease was not detected. Her lesions disappeared during hospitalization without a complication. Conclusion. Since insulin-like growth factor-I reduces endothelial cell oxidative stress and maintains the structural integrity of vessels, some common mechanisms might be responsible for the occurrence of vasculitis in this patient with Laron syndome. The role of insulin-like growth factor-I and recombinant human insulin-like growth factor-I treatment choice in vasculitis diseases is a matter of investigation.

Objective. To study papillary thyroid microcarcinomas (PTMCs) detected incidentally/non-incidentally, especially those with suggestive signs for progression into clinically overt forms.\r\nMaterial and methods. In the first part of study 102 microcarcinomas diagnosed between 1988-2008 were investigated. In the second part we included all the 311 patients thyroidectomized for different thyroid diseases in surgical clinics from T?rgu Mures in 2007.\r\nResults. During 1988-2008 the frequency of PTMCs increased progressively, achieving a peak in 2007 (46.5% of 58 PTCs). In 2007 from the 311 thyroidectomies 27 microcarcinomas were diagnosed, the majority (70.3%) being incidentalomas. In incidental and non-incidental PTMC groups the rate of microcarcinomas with potential progression into overt carcinomas was 21% and 50%, respectively. Only non-incidental forms with signs of progression were treated by total thyroidectomy in every case, while microincidentalomas\r\njust in about half of cases, although all must be treated the same way.\r\nConclusions. After the Chernobyl nuclear accident and use of modern diagnostic methods (ultrasound and FNA) the frequency of PTCs has increased progressively and\r\nsignificantly, including that of microcarcinomas diagnosed mostly incidentally. We must pay attention for PTMCs, because in our casuistry 29.6% harbored suggestive signs\r\n(multifocality, extrathyroidal extension, regional lymph node metastases) for progression.

Objective. Opium is a narcotic drug that is commonly abused. The prescription of pharmaceutical derivatives of opium is limited due to their possible harmful effects on the body’s metabolism and tolerability by patients. The aim of the present study was to evaluate the effects of chronic opium consumption on some sexual and thyroid hormones in diabetic and non-diabetic male and female rats. Material and Methods. This experimental study was conducted on 56 Wistar rats. The animals were divided into diabetic addicted (DA), diabetic non-addicted (DNA), non-diabetic addicted (NDA) and non-diabetic non-addicted (NDNA) groups of male and female rats. Peripheral blood samples were collected to measure the thyroid and sex hormone levels. Student’s t-test was used to compare the mean values of the hormones between two groups. Results. T3 serum level in male addicted groups significantly increased in comparison with non-addicted ones in both diabetic and non-diabetic groups. The testosterone level of male rats decreased due to the consumption of opium while it was significantly increased in diabetic and NDNA female rats in comparison with non-addicts. In DNA female animals, the mean level of 17-hydroxyprogesterone increased significantly compared with non-diabetic groups, however, it decreased in addicted females (diabetic and non-diabetic) in comparison with non-addicts. The level of DHEA-S increased significantly in diabetic and NDA male rats as compared with the non-addicted group. Conclusion. Opium affects the endocrine system in a sex-dependent manner, and opium could have different effects in diabetic and non-diabetic conditions.

Background. Relative adrenal insufficiency (RAI) is the inadequate production of cortisol due to dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis during a severe illness. We evaluated the HPA axis and RAI in a tertiary pediatric intensive care unit (PICU). Methods. A total of 100 PICU patients were included in this prospective cohort study. Basal serum levels of adrenocorticotropic hormone (ACTH), cortisol values were compared with those in the control group. A low-dose ACTH stimulation test was performed in patients with basal cortisol levels below 18 μg/dL. Results. The basal cortisol levels of the PICU patients were significantly higher than those of the control group (P < 0.05). All tested patients (n= 24) had delta cortisol levels > 9 μg/dL and a peak cortisol response > 18 μg/dL. Basal cortisol levels were positively correlated with Pediatric Risk of Mortality (PRISM) III scores (P < 0.05; r = 0.363). The basal or stimulated cortisol levels of the patients who received glucocorticoid treatment were higher than the cut-off levels. Conclusions. High basal or stimulated cortisol levels are indicative of disease severity in the acute phase of stress. Patients with very high cortisol levels should be particularly carefully monitored because of the high mortality risk.

Introduction. We aimed to investigate Cardiotrophin-1 (CT-1) levels along with other markers of cardiovascular disease and the association of androgen levels with these parameters in both lean and overweight or obese PCOS patients. Material and Methods. The study included 90 overweight or obese PCOS patients with metabolic syndrome (MS) and 80 lean PCOS patients without MS. The control group consisted of 140 healthy females. Anthropometric measurements, plasma glucose, insulin, lipid and hormone profile, homocysteine, hs-CRP, CT-1 levels and carotid-IMT were evaluated in all study subjects. Results. Fasting insulin, HOMA values were significantly higher in obese PCOS patients. Total testosteron levels were higher in both PCOS groups with respect to both controls. Serum homocysteine, hs-CRP, CT-1 and carotid- IMT values were significantly higher in both PCOS groups compared to controls (p=0.001, pCIMT: 0.005). CT-1 was positively correlated with insulin, HOMA, total testosterone, homocysteine, hs-CRP and carotid IMT. After multiple regression analysis, CT-1 was significantly positively correlated with total testosterone, hs-CRP and carotid IMT. Conclusions. CT-1 was associated with other cardiovascular risk markers and its use as a cardiovascular risk marker might be suggested. Cardiovascular risk was increased even in lean PCOS patients without MS and it might be associated with elevated androgen levels.

Background. Postoperative hypocalcemia after thyroid surgery has a high prevalence ( 16-55% in different series). Incidental parathyroidectomy (IP) is a less discussed complication of thyroidectomy with consequences not properly defined. The aim of our study was to find incidence, risk factors and how to prevent IP. Methods. Extensive search of English literature publications via PubMed was performed and 73 papers from 1980 to 2017 were analysed using the GRADE system/classification, quality of evidence was classified as “strong” when the result is highly unlikely to change existing recommendation and “weak” when opposite. Results. Incidence of IP is 3.7-24.9%, while prevalence of permanent hypoparathyroidism is less frequent 6-12%. Direct relation between IP and hypoparathyroidism/ hypocalcemia remains controversial. Female patients, ectopic parathyroids, small thyroids, Graves’, malignancy, redo surgeries and total thyroidectomy favour IP. Routine visualization of parathyroids, new hemostatic devices, magnifying instruments and fluorescence can prevent incidental removal of parathyroids. Incidence of IP during videoassisted or robotic thyroidectomies was similar to open procedures. High volume, experienced and younger surgeons have lower complication rates (including hypoparathyroidism). Conclusions. Incidental parathyroidectomy is more frequent than we might have expected. It should be avoided and parathyroid glands should be kept in situ. Majority of studies are retrospective (low degree of evidence according to previous mentioned GRADE classification) and further meta-analysis or randomized control studies are welcome in order to define the impact of incidental removal of parathyroids on postoperative outcome.

Context. We report the use of subcutaneous somatostatin injection three times a day to decrease hypercortisolism in a patient who had Cushing’s syndrome induced by bronchial carcinoid tumour progressive pneumonia due to immune suppression. Subject and Method. A 46-yearold man with 7-month history of DM type-2, hypertension and cerebrovasculardisease, vertebral compression-fracture was admitted to our clinic. Physical examination was consistent with Cushing’s syndrome. Laboratory results revealed hyperglycemia (143 mg/dL; reference range, <100 mg/dL) and hypokalemia (2.29 mEq/L; reference range, 3.5-5.1 mEq/L). His morning serum cortisol was 40 μg/dL (reference range 6.7- 22.6 μg/dL), urine cortisol-excretion was 2245 μg/24 hours (reference range 58-403 μg/24 hours), after 1 mg dexamethasonesuppression test serum cortisol was 28 μg/dL (6.7-22.6 μg/dL) and ACTH 354 pg/mL (reference range 7.9-66 pg/mL). Adrenal CT and hypophyseal MRI were normal. An ectopic source was searched for Cushing’s syndrome. Chest CT scan of the right lung showed 12x9 mm nodule. High fever cough occurred on the followp. Chest radiograph revealed diffuse pneumonic infiltration. Despite 3-drug antibiotic combination therapy, infection did not improve. Subcutaneous injection of octreotide 3x100 μ/g was initiated to decrease hypercortisolism. The infection improved rapidly after the therapy. The morning serum cortisol, urine cortisol-excretion, ACTH was at the upper normal range (77.1 pg/mL, reference range 7.9-66 pg/mL) on 10th day of treatment. The patient was a consulted for surgery and the nodule was excised. The pathology was consistent carcinoid tumor. Conclusion. Subcutaneous octreotide treatment may be helpful to gain time for exploring the focus in ectopic cushing’s syndrome and to control the serious infections due to hypercortisolism.