ACTA ENDOCRINOLOGICA (BUC)

Tuberous sclerosis complex (TSC) is an inherited neurocutaneous disease characterized by multiple hamartomas in multiple organs. However, there is limited evidence about neuroendocrine tumors (NETs) in patients with TSC, and routine screening of NETs is not recommended in the guidelines. Insulinomas are also an extremely rare disease. According to our knowledge, we presented the 10th TSC patient diagnosed with insulinoma in the literature. Thirty-two years old male patient diagnosed with TSC at the age of 27 due to typical skin findings, renal angiomyolipoma, history of infantile seizures, and cranial involvement was referred to our clinic. The main symptoms of the patient were palpitations, diaphoresis, confusion, and symptoms were improved after consuming sugary foods. Seventy-two hours fasting test was performed, and a low glucose level at 41 mg/dl, a high insülin level at 21.65 μIU/mL, and a high C-peptide level at 7.04 ng/mL were found at the 8th hour. In addition, a 12x7 mm lesion in the pancreatic tail was detected in abdominal imaging. Ga-68 PET-CT (gallium-68 positron emission tomographycomputed tomography) detected an increased uptake of Ga-68 in the pancreatic tail. The patient underwent distal pancreatectomy, and pathological evaluation was consistent with an insulinoma. The patient’s symptoms improved postoperatively. Since in nearly all TSC cases, as in our case, neuropsychiatric abnormalities, such as epilepsy, are one of the main disease manifestations, and these symptoms may be confused with the clinical manifestations of hypoglycemia in insulinoma. Therefore, patients with newly developed neurological symptoms and behavioral defects should be evaluated in terms of insulinoma.

This editorial discusses the context of thediscovery of GNRH 1 as a cause of congenital hypogonadotropic hypogonadism published last year by Bouligand et al in the New England Journal of Medicine

Introduction. Ganglioneuromas are rare, benign tumors that arise from the neural crest tissue and are usually asymptomatic and discovered accidentally. GN have good prognosis with surgical removal and the standard treatment for such lesions is laparoscopic adrenalectomy. Case report. We report the case of a 13 year old patient who presented to our hospital with abdominal pain. The ultrasound and the CT scan confirmed the presence of a well-defined mass situated in the right renal space. Taking into account the size of the tumor, its position and the fact that CT scan showed no local signs of invasion, the decision was taken to perform a laparoscopic removal of the right adrenal mass. After dividing the main adrenal vein and while dissecting the adrenal gland, we noticed an intraoperative bleeding due to the fact that one of the clips used to ligate the vein had slipped. Because we were unable to control the intraoperative bleeding we decided to convert to open surgery. The histopathological result showed that the adrenal lesion was a ganglioneuroma. Conclusion. While the role of minimal invasive adrenalectomy in patients with larger lesion is still controversial, advantages such as reduced hospital stay and postoperative morbidity, lower rate of complications, have resulted in the laparoscopic approach for adrenal pathology becoming the choice procedure in the removal of adrenal lesion.

Morris Syndrome is a pathological condition which needs a special approach regarding both diagnosis and treatment\r\nbecause of its rarity. While the diagnosis is based on karyotype test, the treatment should follow the idea of harmless and cosmetic benefits as well as complete gonads removal. This paper is presenting the usefulness and advantages of minimally invasive surgery as a feasible treatment for such a disease. A retrospective study was performed for two patients with Morris Syndrome, admitted to\r\nthe ?CI Parhon? National Institute of Endocrinology, Bucharest, Romania, followed-up for 4 - 16 years, and operated to the Department of Surgery, Emergency\r\nHospital, Bucharest, Romania. Patients with primary amenorrhea have been clinically observed and three patients\r\nwith 46, XY karyotype have been identified as Morris Syndrome cases needing surgical removal of the intraperitoneal gonads because of the risk of malignant transformation. A minimally invasive surgical technique has\r\nbeen chosen for proper treatment: the anterior transperitoneal laparoscopic approach. The surgery was adapted to every case, in according with preoperative imagistic diagnosis of the intraperitoneal testes\r\n(localization, dimensions, adjacent organs involvement, surgical access). No postoperative complications were noticed and specimens' pathology confirmed the final\r\ndiagnosis. Cosmetic benefits were achieved for every young patient as well as rapid postoperative recovery (discharge after 48 hours). The authors concluded that Morris Syndrome patients could benefit from the laparoscopic surgery which is a feasible, safe and proper treatment for such cases.

Adipocytokines involved in inflammation and the acute phase responders have been found to be increased in the metabolic syndrome (MS). The aim of the study was to compare the ‘normal’ weight women’s fibrinogen, hsCRP, adiponectin, TNF-α, vascular cell adhesion molecule (VCAM) with obese patients with MS, and to evaluate the association between fibrinogen, hsCRP, adiponectin, TNF-α, VCAM and insulin resistance. The study included 52 obese women who met the criteria for MS defined as in 2001, the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) ATP III and 24 normal women. Serum concentrations of glucose (FBG), triglyceride, total and HDL-Cholesterol were determined by enzymatic procedures, serum insulin was measured by chemiluminescence, plasma levels of adiponectin, TNF-α and VCAM by Elisa, hsCRP by immunoturbimetric assay and fibrinogen by coagulation method. Measurements of insulin resistance were obtained using the homeostasis model assessment. Mean plasma levels of adiponectin, TNF-α, VCAM, fibrinogen and hsCRP were found 6.11±2.39 mg/ml, 3.10±3.30 pg/ml, 14.21±4.00 ng/ml, 375.49±49.67 mg/dl, 0.33±0.10 mg/dl in the obese with MS; 6.20±2.48 mg/ml, 3.01±1.68 pg/ml, 12.63±2.54 ng/ml, 304.06±49.52 mg/dl, 0.30±0.19 mg/dl in the normal women, respectively. Mean fasting insulin level and HOMA-IR were measured 13.80±6.32 mU/ml and 3.69±1.90 mU/ml, respectively in obese with MS. In normal women, fasting insulin level and HOMA-IR were measured 8.30±3.08 mU/ml and 1.49±0.37, respectively. Mean levels of adiponectin were positively correlated with mean TNF-α levels in the obese with MS (r=0.472, p=0.001). VCAM was negatively correlated with TNF-α levels (r=-0.301, p=0.038) in the obese with MS. This study demonstrated that TNF-α showed a positive association with adiponectin and a negative association with VCAM in the obese women with MS.

Published data sustain the involvement of diet on pathogenesis of immune-mediated diseases.\r\nAim. To determine if the high fat diet (HFD), in the absence of obesity, could modulate the altered pulmonary arteries\r\nreactivity associated to allergic lung diseases.\r\nMaterials and Methods. Obese resistant rats were divided into 2 groups: standard chow diet and HFD. Randomly chosen rats from both groups were sensitized against ovalbumin. The histological aspect and reactivity of pulmonary arteries were comparatively assessed. Taking into account the involvement of adipokines on obesity associated vascular reactivity alteration we also studied the vasomotor effects of few adipokines on pulmonary vessels.\r\nResults. Lung histological examination revealed that HFD aggravated the remodelling of pulmonary arteries and\r\ninflammation of lung parenchyma. The HFD amplified the phenylephrine - induced contractions. Angiotensinogen amplified and apelin inhibited the Phe contractile effects on sensitized HFD fed rats.\r\nConclusion.These effects could be at least mediated, by both the alteration of adipokines vasomotor effects and\r\ninflammation associated to pulmonary allergic disease.

49, XXXXY karyotype syndrome has an incidence of between 1/85 000 and 1/100 000 live births. Typical clinical features include hypogonadism, mental retardation with severe learning difficulties, craniofacial and skeletal abnormalities, but also congenital heart disease. We report on a 4 year-old boy diagnosed with severe generalized hypotonia during his first year of life. Behavioural and cognitive profiles of the case are presented. MRI shows apart from global volume loss and atrophy, scattered punctate foci of T2 signal hyperintensity in the white matter. Endocrine investigations revealed impaired GH concentration during clonidine test, low IGF-1 concentration and cryptorchidism. Long term follow-up of patients with polysomy X by a team of specialists in pediatric neurology, endocrinology and cardiology is mandatory.

Context. Although, many studies have been made on the clinical course of autoimmune thyroiditis, this study focused on women and the factors effecting the natural course such as Selenium. Objective. The study aimed to determine Hashimoto’s thyroiditis (HT) clinical course in adults and the factors that could affect it. Design. The study was in a retrospective manner between 2010-2018. Subjects and Methods. 101 patients with HT were followed for 60.7±32.7 months. Biochemical and ultrasonographic data were collected. We investigated whether the age at diagnosis, family history, smoking habits, levothyroxine replacement therapy, and serum selenium (Se) levels influenced the disease course. Results. No relationship was observed between age and thyroid functions, thyroid volumes (TV), and autoantibody (Ab) levels at diagnosis. Ab levels were irrelevant with TV, echogenicity, and nodularity at diagnosis. However, initial TSH levels were significantly associated with anti-TPO levels (p=0.028, r=0.218). In the untreated group, thyroid functions seemed to be stable. TV decreased significantly in both treated and untreated patients (p<0.001). The decrease in TV was significantly higher in the treatment group (p=0.002). In euthyroid and subclinical hypothyroid patients, levothyroxine therapy did not affect the decrease in TV. Ab levels remained stable in untreated patients, but anti-TPO levels significantly decreased in treated patients (p<0.001). Smoking seemed to increase only anti-Tg levels (p=0.009). Family history was not associated with any of the studied parameters. Serum Se level was negatively correlated only with thyroid echostructure and only in treated patients. TV showed a “Gaussian distribution” in all patients at the diagnosis and at the end, independent of levothyroxine treatment. Conclusions. Most euthyroid patients remained euthyroid during five years of follow-up. The decrease in TV was significantly prominent with LT4 treatment. Importantly, TV followed a normal distribution instead of the bimodal distribution that is classically described.

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Background. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancers. Antibodies directed against programmed cell death receptor 1 (PD-1) interrupt the ability of the cancerous cell to depress the immune system. Methods and results. We report three patients who developed different endocrine abnormalities after treatment with nivolumab, a monoclonal antibody directed against PD-1. First, we report a 76-year-old male presenting with generalized fat loss after treatment with nivolumab which predominantly affected his face and trunk. Second, we described the development of thyroiditis that presented with thyrotoxicosis and the expression of thyroid-stimulating hormone receptor antibodies (TRAb). Finally, we observed the emergence of adrenal insufficiency due to hypophysitis in another case. Conclusion. Although immune checkpoint inhibitors are an effective anticancer treatment modality, adverse effects are evident that can affect the endocrine system. These adverse events may relate to different endocrine systems that include the thyroid and pituitary glands. Also, acquired generalized lipodystrophy should be suspected in patients developing unusual fat loss after treatment with ICIs.