ACTA ENDOCRINOLOGICA (BUC)

Context. Epilepsy and osteoporosis are closely related. The detrimental effect on bone by older generation of antiepileptic drugs (AEDs) is well known, but newer AEDs can also cause a decline in bone health. Objective. To provide a review on the impact of AEDs on bone mineral density, fractures and bone turnover markers and to analyze the effect of bone active treatments in epileptic patients. Methods. Medline (PubMed) and EMBASE were searched for studies about AEDs and bone health. The PRISMA statement was used. Results. Chronic use of AEDs is associated with alterations in bone metabolism, low bone mineral density values, and increased risk of fractures. These effects appear to be more associated to the use of enzyme-inducing AEDs. Supplements with vitamin D and bone active treatments may have benefits in terms of bone mineral density gain and of mortality risk. More studies are required to determine the impact of non-enzyme-inducing AEDs on bone health and to gather useful information about the management of osteoporosis therapy in epileptic patients. Conclusion. Chronic AED use has a significant impact on bone health; it is therefore necessary to evaluate in such individuals the claim to vitamin D and calcium supplements and bone active treatments.

Adrenoleukodystrophy (ALD) is a hereditary metabolic disease X-linked (Xq28) with autosomal recessive traits, secondary to a mutation in the ABCD1 gene. The case of a boy aged 7 years and 10 months admitted for vision disturbances, muscle weakness, balance disturbances and spastic paraparesis is presented. Seventeen months prior to this admission, the child was diagnosed with acute adrenal insufficiency and was still on replacement therapy with dexamethasone and fludrocortisone. While on therapy the child presented several relapses that required treatment correction. MRI revealed cerebral atrophy lesions, which, together with the laboratory findings and clinical symptoms, conducted the diagnosis of ALD. This diagnosis was also supported by the pathogenic mutation detected in the ACBD1 gene identified in the pacient and patient?s mother and sister. The child died 8 months after the onset of neurological signs. Childhood ALD is classified as classical ALD form, the most frequent, affecting only boys aged 4 to 10 years. Family screening obliged by the identification of the homozygotes is helpful for the early therapy of heterozygotes, genetic counseling and disease prevention. The prognosis is still poor, the available treatment being hormone substitution therapy and psychological support.

Background. The aim of this experimental study was to examine the effect of erythropoietin (Epo) on rat model and particularly in an ischemia-reperfusion (IR) protocol. The beneficial effect or non-effectiveness of that molecule were studied haematologically using blood mean corpuscular hemoglobin levels (MCH). Materials and methods. Forty rats of mean weight 247.7 g were used in the study. MCH levels were measured at these time points: on 60 min after reperfusion (groups A and C), and on 120 min after reperfusion (groups B and D). C and D groups were administered by Epo. Results. Epo administration nonsignificantly increased the MCH levels by 0.19 pg [-0.34 pg - 0.72 pg] (P= 0.4762). This finding was in accordance with the results of paired t-test (P= 0.3827). Reperfusion time non-significantly increased the MCH levels by 0.02 pg [-0.51 pg - 0.55 pg] (P= 0.9404), also in accordance with paired t-test (P= 0.9049). However, Epo administration and reperfusion time together produced a nonsignificant combined effect in decreasing the MCH levels by 0.13 pg [-0.18 pg - 0.45 pg] (P= 0.4087). Conclusion. Results of this study indicate that Epo administration, even in short-term prospect of 2 hours reperfusion, starts reversing ischemic damages. These results are also reinforced by predicted MCH values adjusted for weight. However, the significant effect needs more than 2 hours in order to appear.

No inheritance of early-onset female-related type 2 diabetes was reported within Chinese families. In this study, we aim to describe the inheritance pattern of type 2 diabetes in a 3-generation family and identify the gene responsible for type 2 diabetes. Genome-wide multipoint parametric linkage analysis revealed a maximum multipoint logarithm of odds (lod) score of 2.1 for a locus being associated with type 2 diabetes in this family on chromosome 20p11.2-12 between 23.5~30.8cM. Type 2 diabetes may be transmitted as an autosomal dominant trait with a high female-related penetrance in this family. Here we describe the first genetic locus for type 2 diabetes at chromosome 20p11.2-12. This region contains 8 known or predicted genes (PLCB1, PLCB4, LAMP5, PAK7, ANKEF1, SNAP25, SLX4IP, and JAG1). Gene SNAP25 which linked to energy or glucose homeostasis associated phenotypes may play a role in the development of type 2 diabetes in this family.

Smith-Lemli-Opitz syndrome is an autosomal recessive disorder caused by mutations of 3-hydroxysterol –7reductase gene (DHCR7) which maps to 11q12-13 and was the first discovered defect in cholesterol biosynthesis resulting in a congenital dysmorphology syndrome. We present the case of a 46,XY newborn with ambiguous genitalia and multiple congenital anomalies (atrial septal defect, ventricular septal defect, syndactyly of the second and third toe, cleft palate, webbed neck, small fontanels, mesomelia, simian palmar crease, micrognathia, wide nasal bridge with anteverted nostrils, low set ears). Hormonal assessment performed at twelve days revealed a decreased testosterone level (0.03 ng/mL), a high estradiol level (448.8 pg/mL), normal LH (2.8UI/mL), DHEAS (86.61?g/dL), progesterone (1.34ng/mL) and 17 hydroxyprogesterone (1.08ng/mL) levels. Cholesterol was low (44mg/dL) confirming the diagnostic of Smith-Lemli-Opitz syndrome.

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.

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.

Objective: Co-existence of Cushing disease and Rathke?s Cleft Cyst (RCC) has been reported in a few cases in the literature so far. We herein describe a rare condition of Cushing disease that might originate from epithelium of RCC. \r\nCase: A 48-year-old woman was admitted to the hospital with complaints of headache, weakness, and weight gain. The patient underwent endoscopic transsphenoidal surgery due to Cushing Disease. Histopathological examination revealed cyst contents and walls compatible with RCC, and normal adenohypophysis and neurohypophysis tissues. Immunhistochemical staining with ACTH, GH, and prolactin were positive on the epithelium of the cyst. \r\nConclusion: In our case Cushing disease might be associated with hormonal activity derived from cyst wall of RCC or disappearance of a small microadenoma during surgical or pathological processing. According to recent data, origin of this lesion and histogenetic link between RCC with Cushing disease could not be explained.

Context. As we progress into the COVID-19 pandemic, it has become apparent that this infection is associated with a multitude of systemic effects, some involving the thyroid gland. The thyroid is also frequently affected in the HCV chronic infection. Objective. The objective of this study is to determine the effects of COVID-19 infection on the presence and severity of thyroid disorders associated with chronic HCV infection, at short and mid-term follow-up. Design. We prospectively evaluated patients with documented HCV- associated thyroid disease (with sustained virologic response after antiviral therapy). Subjects and Methods. The study group consisted of 42 patients with HCV- associated thyroid disease, diagnosed with COVID -19 infection between April and October 2020. We determined serum values of thyroidstimulating hormone, freeT3, free T4, anti-thyroglobulin antibodies and anti-thyroid peroxidase antibodies at one and three months after resolution of infection and compared them to the baseline characteristics of the patient. We also evaluated the changes in thyroid substitution treatments or antithyroid drugs. Results. At baseline, out of the 42 patients, 5 presented hypothyroidism under levothyroxine substitution therapy, while 2 presented hyperthyroidism under methimazole therapy; 37 patients had positive antithyroid antibodies. At one month follow-up, we note an increase in serum values of antibodies, with a decrease in TSH, freeT3 and freeT4 levels, correlated with the severity of COVID-19 infection. Two patients required discontinuation of levothyroxine. At 3 months follow-up, lower levels of antithyroid antibodies were recorded, with an increase in TSH levels. No medication doses were adjusted at this time. Conclusion. Among the systemic effects of COVID-19, the impact of thyroid dysfunction should not be underestimated, especially in the presence of pre-existing conditions, such as HCV infection.

Thyroid tumors are the most frequently reported endocrine malignancies. However thyroid collision tumors are rare pathological findings, representing less than 1% of thyroid cancers. In our case, a 50-year-old female patient presented with a complaint of neck swelling. During the exams, nodules were identified in both thyroid lobes. Pathologic analysis of a fine-needle aspiration biopsy(FNA) has been obtained from a 60×50 mm hypoechoic nodule raised suspicion of oncocytic carcinoma(OC). Another FNA was performed on a 17×11 mm hypoechoic solid nodule, revealing features of medullary thyroid carcinoma (MTC). Preoperative whole-body scans indicated no evidence of metastases. The patient subsequently underwent total thyroidectomy and central lymph node dissection. Pathological examination revealed OC, MTC, papillary microcarcinoma (PTMC), simultaneous metastasis of MTC and papillary thyroid carcinoma (PTC) to the same lymph node. The patient's calcitonin level was normalized postoperatively and I-131 ablation therapy was administered to the patient in the ATA high risk category. The patient was monitored under levothyroxine suppression. The simultaneous occurrence of OC, MTC and PTMC of the thyroid gland along with metastases of PTC and MTC in the same lymph node are reported in this case. To the best of our knowledge, this association had not been previously reported in the literature.