ACTA ENDOCRINOLOGICA (BUC)

Thyroid cancer, the most frequent endocrine malignancy, is in most patients a treatable disease, with excellent outcome and cure rate. However, a few patients present with rapidly progressive metastatic differentiated thyroid cancer which loses the radioiodine uptake capacity. These rare cases are prone to a rapid evolution and poor prognosis. Medullary thyroid cancer is a neuroendocrine tumor occurring sporadically or as part of endocrine tumor syndromes, genetic tests being part of standard clinical evaluation. Current knowledge of tumor biology in thyroid cancer allowed development of a new class of drugs, thyrosine kinase inhibitors (TKI). Their use in clinical trials allowed the development of more specific drugs, increasingly effective and with less adverse reactions, interfering with multiple thyrosine kinase enzymes. Improvement of the progression free survival, decrease of tumor volume and tumor markers, as well as patients with stable disease on TKI are strong arguments for including patients in clinical trials. Currently, only four TKI are approved by FDA: sorafenib and lenvatinib for DTC; vandetanib and cabozantinib for MTC. In this paper we present this new class of drugs used in the treatment of aggressive thyroid cancer.

-

Diabetic ketoacidosis (DKA) is a common medical emergency situation. In rare cases, glycemic changes associated with the menstrual cycle may create a predisposing factor for DKA. In the absence of facilitating factors that may cause DKA, catamenial DKA should be considered. In the patients with catamenial DKA, increasing the insulin dose 1-2 days before menstruation may prevent the development of hyperglycemia or DKA associated with menstrual cycle. In this study, we present a 21-year-old female with type 1 diabetes mellitus (DM) that recurrently applied to our hospital due to DKA a few days prior to menstrual bleeding.

-

Background. The involvement of IGF 1 in renal pathophysiology has been studied in many details in type 1 diabetes but the role of IGF 1 in early nephropathy in patients with type 2 diabetes is less well characteristic. Objective. To determine whether serum IGF1 and GFBP-1 levels were different between patients with and without diabetic nephropathy and also to investigate the association between them and insulin resistance. Subjects and methods. Insulin resistance (HOMA-IR), IGF 1 and IGFBP-1 were measured in 20 type 2 diabetic patients with nephropathy, 20 type 2 diabetic patients without nephropathy and 15 control subjects. Results. Serum IGF 1 in diabetic nephropathy (333.3 +/-16.44 ng/mL) was significantly higher than in both diabetic patients without nephropathy (133.16 +/- 3.43 ng/mL) and in control subjects (174.33+/-6.23) (P <0.001). A significant negative correlation was observed between IGF 1 and HOMA, (r = -0.72) in diabetic patients without nephropathy and a positive correlation in diabetic nephropathy patients (r = 0.49). Conclusion. High IGF 1 and insulin levels in diabetic nephropathy patients in addition to the significant positive association between IGF 1 and HOMA suggest that both IGF 1 and insulin resistance may play major role in early renal changes in type 2 diabetes.

Long lasting hypocalcemia, hyperphosphatemia, low calcitriol and high fibroblast growth factor 23 could result in progressive parathyroid gland hyperplasia with high, uncontrolled, parathormone production, e.g. severe secondary hyperparathyroidism (sHPT), in 10% of dialysis patients. Parathyroidectomy (PTX) could be a solution, but has inherent (low) surgical risks and although dramatically decreases parathormone levels, could induce hypoparathyroidism (50-66%) and low turnover bone disease. Moreover, the rate of recurrences is 15-20% at 10 years. Total and subtotal PTX with autografting are equally safe and effective with similar recurrences rates. Calcimimetics are efficient drugs, but with limited effectiveness in sHPT, as only 25% of patients responded to cinacalcet. In the USA, they are more cost-effective than PTX only in patients with >2 years expected dialysis duration. As there are not randomized studies to compare surgical to medical therapy, the strength of evidence allows only for suggestions in guidelines. In countries like Romania, where dialysis vintage is high because of the low transplantation rate and calcimimetics are costly, PTX seems a better solution when parathyroid glands are large (diameter >1cm or\r\ntotal mass >500mg), parathormone levels >800pg/mL, in patients who are not candidates for renal transplantation or are anticipated to stay >2 years on dialysis.

-

Background. Antineutrophil cytoplasmic antibodies (ANCA) positivity is usually determined in vasculitis of medium and large arteries. In literature, data related to the prevalence of ANCA positivity and the development of antibodies after antithyroid therapy in Graves’ disease are quite rare. Aim. To investigate the titers of myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA in Graves’ patients treated with propylthiouracil (PTU) and to determine the factors that may contribute to ANCA positivity. Subjects and Methods. Fifty-two Graves’ patients treated with propylthiouracil (PTU) were included into the study. The control group consisted of 37 healthy subjects. MPO-ANCA and PR3-ANCA titers were measured in both groups. Results. Mean titer of PR3-ANCA in Graves’ group was significantly higher than in controls (p=0.025), but no significant difference was found in the titer of MPOANCA between two groups (p=0.060). A positive correlation was observed between PR3-ANCA titer, and anti-thyroid peroxidase antibody and anti-thyroglobulin antibody levels in Graves’ patients (p=0.001, r=0.447 and p=0.030, r=0.310, respectively). PR3-ANCA titer in anti-thyroglobulin antibody positive patients was higher than those with negative antibody (p=0.018). A positive correlation was detected between the duration of treatment and PR3-ANCA titer (p=0.024, r=0.314). Both MPO-ANCA and PR3-ANCA were positive in two Graves’ patients, while only MPO-ANCA was positive in two patients. No signs of vasculitis in ANCA positive patients were observed. Conclusion. Propylthiouracil (PTU) may cause ANCA positivity, but no vasculitis may develop in most of the cases. A correlation was determined between PR3- ANCA titer, and thyroid autoantibodies and the duration of treatment.