ACTA ENDOCRINOLOGICA (BUC)

Anaplastic thyroid cancer (ATC) is a highly uncommon (less than 2% of thyroid malignancies) and aggressive type of cancer, with aggressive behavior and, therefore, exhibiting poor prognosis. ATC tumors are automatically labeled as stage IV disease regardless of standard criteria such as tumor burden or metastasis. ATC tumors require a diversified treatment approach that includes surgical resection, followed by a complete an aggressive combination of radiation and chemotherapy and/or palliative care. Despite best efforts, 1-year overall survival of patients is 20% to 40% with nearly universal mortality rate. Consequently, novel approaches (targeted therapy, immunotherapy) have been studied, alone or in combination, to improve the dire prognosis of these patients. BRAF V600E mutation is the most common genetic mutation found in ATC. We report the case of a 57-year-old man diagnosed with stage IVc (undifferentiated) ATC with hepatic and osseous metastases. The molecular analysis of the tumor revealed a V600E BRAF-mutation. The patient was treated with Dabrafenib and Trametinib, and achieved remission 5 weeks after starting the treatment. Subsequently, he had a thyroidectomy, and pembrolizumab was added to the two tyrosine kinase inhibitors. 9 months later he is still in remission. This case illustrates the importance of obtaining molecular information in anaplastic thyroid cancer and the urgent need of studies investigating the combination of tyrosine kinase inhibitors and check-point inhibitors in patients with V600E BRAF- mutations.

Objective. Antithyroid drugs, surgical excision, and radiation therapy with 131I are the common treatment modalities thyrotoxicosis. The medical treatment of\r\nthyrotoxicosis has approximately 0.35% serious complications which consist of agranulocytosis, liver necrosis and failure. Therapeutic plasma exchange is an effective\r\npreoperative preparation method in thyrotoxicosis patients who are candidates for surgery and unable to manage an euthyroid state with medical treatment.\r\nPatients and Methods. This study was constructed between 2002-2009 in 9 patients who were resistant or had complications with medical treatment of thyrotoxicosis. The\r\ntherapeutic plasma exchange procedures were performed with discontinuous flow cell separator devices.\r\nResults. Seven patients were females and 2 patients were males. The mean age was 51.22 years (32-78 years). The mean duration of the disease was 35.4 months (3-120 months). The patients underwent 3.3 (2-6 sessions) session of therapeutic plasma exchange before surgery. The mean volume of\r\nplasma exchange was 10549 mL (7150-18372 mL). The plasma is exchanged with %10 albumin and/or fresh frozen plasma. The\r\ncomplication rate was 22% during therapeutic plasma exchange. Four patients underwent near total thyroidectomy and five patients underwent total thyroidectomy. The mortality rate was zero. Neck hematoma causing acute\r\nrespiratory compromise and requiring urgent evacuation developed in one patient.\r\nConclusions. Total plasma exchange is an effective and safe procedure in preoperative preparation of the patients with thyrotoxicosis who were resistant or complicated with\r\nantithyroid drug in which a high level of concern and steady supervision is mandatory to prevent life threatening preoperative and postoperative complications.

Context. Osteonecrosis (ON) is bone death caused by inadequate blood supply and its optimal management remains uncertain. Objective. We describe the outcomes of BP (pamidronate) treatment in our patients. Design. Data regarding clinical, laboratory, magnetic resonance imaging (MRI) studies, and bone mineral density measurements (BMD) were recorded before and one year after treatment (reevaluation). The severity of the clinical picture was assessed using the criteria of the common terminology criteria for adverse events (CTCAE). Subjects and Methods. There were four female patients (patient 1, acute lymphoblastic leukemia; patient 2, immune thrombocytopenic purpura; patients 3 and 4, systemic lupus erythematosus) .All of them had been treated with high-dose prednisolone. Clinical picture of all patients were consistent with grade 3 according to CTCAE(: severe symptoms, limiting self-care ). Results. ON lesions were multifocal in the lower limbs in all of them and none of them had any fractures. All of them had been treated with high-dose glucocorticoid. Patients were treated with pamidronate (1 mg/kg/day, with maximum dose of 60 mg/day, for two days, quarterly). At the time of re-evaluation(one year after treatment), the lesions were stable on MRI, and their clinical condition was consistent with grade 1 according to CTCAE(asymptomatic). No side effects related to the use of bisphosphonates were observed except for increased BMD (SD score of 2.9) in one of the patients. Conclusions. Pamidronate may be an effective treatment for the improvement of functional impairment and pain among patients with severe osteonecrosis (ON) lesions.

Arteriovenous malformations of adrenal gland are extremely rare. We report a case of an adrenal arteriovenous malformation, mimicking an adrenal tumor in preoperative imaging. A 48-year-old woman presented to our clinic with abdominal pain. A 9x7 cm right adrenal tumor was detected. Based on the imaging findings, adrenal adenoma was suspected. However, clinical symptoms and endocrine abnormalities were absent, the lesion was thought to be non-functional. Laparoscopic right adrenalectomy was performed. Pathologically, this was diagnosed as an adrenal arteriovenous malformation. To the best of our knowledge, this is the first reported case of an adrenal arteriovenous malformation in the current literature.

Background and aims. There are numerous intrinsic and extrinsic factors associated with the pathophysiology of rosacea, including immune dysregulation. The aim of this study is to determine the relationship between rosacea and thyroid autoimmunity. Methods. Seventy-two patients with rosacea and 62 rosacea-free control subjects were included in the study. Serum free triiodothyronine (fT3), free thyroxine (fT4), thyrotropin releasing hormone (TSH), antithyroidperoxidase antibody (ATPO), antithyroglobulin (anti-Tg), prolactin, dehydroepiandrosterone sulfate (DHEAS), basal cortisol, serum CRP concentrations and erythrocyte sedimentation rate were measured. Results. The number of the cases with high levels of CRP, anti-M and prolactin in rosacea group were significantly higher than the controls (p<0.05), there was no significant difference according to other parameters in both groups (p>0.05). There was no significant difference according to the presence of a thyroid disease in both groups (p>0.05). The decrease in the CRP parameter in patients with the disease duration of 1-5 years was found to be statistically significant (βCRP=-0.251, pCRP<0.05). There was no statistically significant difference according to disease severity or disease duration (p>0.05). Conclusions. Rosacea may be associated with high thyroid autoantibodies, prolactin and CRP levels, in which immune-endocrine interactions are important.

Background. Weight loss associated with long-term lifestyle changes has significant beneficial effects on metabolic syndrome (MetS) features on obese patients; unfortunately, the weight recidivism rate is high and the weight fluctuations could increase the cardiovascular and metabolic risk. On the other hand, there are many data about the endocrine role of adipose tissue. Objective. Taking into account the imbalance between pro-inflammatory and anti-inflammatory cytokines secreted by adipose tissue on obese patients, this study assessed the effects of one month-long supervised lifestyle change (SLC) program without weight loss on the MetS-associated inflammatory status. Methods. The study included 29 obese adults with MetS. The SLC program included supervised moderate physical activities and diet for one month. The levels of adipocytokines, lipids and inflammatory markers were analyzed before and after one month SLC program, and 2 months later at follow-up. Results. At follow-up, the leptin, vascular endothelial growth factor (VEGF), and hsCRP levels decreased, whereas the interleukin-4 (IL-4) and high-density lipoprotein (HDL) cholesterol levels increased from their baseline levels. So, an SLC program, even in the absence of weight loss, could have an extended antiinflammatory effect by decreasing the proinflammatory adipocytokines. Conclusion. Our data furthermore emphasize the importance of the adipocytokines gender-related variation for a more personalized evaluation protocol on obese patients.

Diabetes is one of the most prevalent chronic disorders, associating numerous somatic and behavioral modifications. Oxytocin has been widely studied for its involvement in social behavior and psychiatric disorders. This pilot study presents a series of 3 patients with type 1 diabetes and diabetic neuropathy in which the values of plasma oxytocin, neurotensin, β-endorphins, α-MSH, substance P and orexin A were measured in comparison to 3 healthy controls with matching ages. In the diabetic patients group, there was a strong negative correlation between the value of plasma glucose and oxytocin (r=-0.99, p=0.04), respectively neurotensin (r=- 0.99, p=0.03). These values did not correlate in the control group. The results suggest that oxytocin, in conjunction with neurotensin, could be investigated as a potential early detection marker of diabetic neuropathy and, to our knowledge, this is the first report focusing on plasma oxytocin levels in patients with diabetic neuropathy.

Objective. Hyperkalemia is one of the most common acute life-threatening metabolic emergencies. Alterations in serum potassium (K+) levels can have dramatic effects on\r\ncardiac cell conduction and may lead to electrocardiographic (ECG) changes. But in some\r\npatients ECG changes do not accompany serum K+ abnormalities. Severe hyperkalemia secondary to Addison Disease (AD) is rare.\r\nCase. A 40-year-old woman with AD was admitted to emergency service with generalized pain. The patient?s serum K+ level was found to be at the highest level that can be detected in our laboratory (>10.0 mmol/L, normal 3.5-4.5 mmol/L) and repeated serum K+ confirmed the previous result. Results of repeated ECGs have revealed a normal sinus rhythm. Our case is particularly interesting because it demonstrates an Addison patient that has an extremely high level of K+ (>10 mmol/L) without any accompanying ECG changes.\r\nConclusion. Our case confirms that diagnostic ECG changes do not always accompany severe hyperkalemia. Therefore, clinicians should be careful that ECG may look\r\nnormal in the presence of severe hyperkalemia.