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.

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Background. Phosphaturic mesenchymal tumor (PMT) is a recently described concept\r\nunifying the mesenchymal tumor associated with oncogenic osteomalacia. Most of the cases of\r\nPMT occur in the extremities and appendicular skeleton. PMT occurring in the paranasal\r\nsinuses is extremely rare with only a few cases reported in the available literature.\r\nCase. A 51-year-old man presented with a long history of bone pains. Biochemical\r\nand radiologic investigations, including skeletal survey showed features of osteomalacia.\r\nPositron emission tomography (PET) scan showed a small tumor in the left nasal cavity,\r\nethmoid and sphenoid sinuses. Histopathological examination of the excised tumor showed\r\nfeatures of a phosphaturic mesenchymal tumor- mixed connective tissue variant. Excision\r\nof the tumor was associated with marked improvement in the biochemical parameters and\r\nremarkable clinical relief.\r\nConclusion. Phosphaturic mesenchymal tumor is a rare cause of osteomalacia and is\r\nusually associated with small tumors, which escape detection for long periods. Its occurrence in\r\nthe paranasal sinuses needs to be kept in mind and evaluated to allow for timely detection of the\r\ntumor with subsequent surgical excision and clinico-biochemical relief.

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We describe clinical features of women with extremely low bone density, and investigate secondary causes of osteoporosis. Our hypothesis was that this population would be enriched in identifiable causes of osteoporosis. We performed a retrospective review of medical records of all women seen at our university over 4 years with T-score on bone densitometry at/below -4 at any site. Historical and fracture details were abstracted. We considered a thorough work up to include Vitamin D, PTH, CBC, chemistry panel, cortisol, transglutaminase, myeloma screen, tryptase and 24-hour urine calcium. Results. 137 women were identified with T-score at/below -4. Percent identified as Asian was 26% (higher than local prevalence of 8%). Average BMI was 21.6 kg/ m2. Clearly identifiable causes of osteoporosis were noted in 57% (inflammatory disorder, glucocorticoid or antacid exposure, prolonged immobilization and alcoholism were most prevalent). Of the remainder, full work up was performed only in 8%. Endocrine consultation and white race predicted thoroughness of secondary work-up. Conclusion. Fragility fractures, leanness and Asian race were common in women with very low T-score. However, few new causes were identified. Underlying etiology was either immediately evident or inadequately studied, especially in minorities.

Denosumab,a monoclonal IgG2 antibody, is used as neoadjuvant therapy for giant cell bone tumors, particularly in inoperable or metastatic cases. It targets the receptor activator of nuclear factor kappa-β ligand (RANKL), which is overexpressed in tumor stromal cells. However, denosumab treatment can lead to side effects such as hypocalcemia during treatment and rarely but malignant hypercalcemia after discontinuation. The unpredictable onset time and persistent course of hypercalcemia attacks increase the duration of hospitalization and the risk of complications. Case. A 9-year-old girl with a giant cell bone tumor was treated with denosumab for diffuse tumor recurrence. Severe hypercalcemia occurred four months after completing therapy. Evaluation suggested "rebound-linked" hypercalcemia following denosumab discontinuation. IV bisphosphonate treatment normalized calcium levels initially, but hypercalcemia recurred, requiring repeated IV bisphosphonate administration. Oral alendronate was used weekly to prevent further attacks, resulting in stable calcium levels during follow-up. Results. Rebound hypercalcemia, as an unpredictable recurrent episode at any time, is a potential complication of denosumab cessation, and requires close monitoring post-treatment. Children may be at higher risk due to their rapid bone cycle. In long-term follow-up, IV and oral bisphosphonates can be used effectively in the management of especially life-threatening recurrent attacks.

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.

Objective. We aimed to reach a diagnosis for patients with pituitary failure (PF) with more detailed multifaceted examination, to obtain new gains in this way and to apply this experience to our future patients. Patients and Method. The study included 72 patients with pituitary failure diagnosis. Patients were divided into two groups of 32 female patients with Sheehan syndrome (SS) and 40 non-Sheehan syndrome patients (20 female and 20 male). Results. The mean age of the 32 patients with Sheehan syndrome was 56.1±11.7 years with mean disease duration 20.3±8.3 years and mean age at disease onset 34.3±7.6 years. For the 40 non-SS pituitary failure patients mean age was 46.5±16.6 years, mean disease duration was 4.7±5.1 years and mean age at disease onset was 41.8±18.2 years. The prolactin response (PRL) on the TRH test was found to be significantly lower in SS patients compared to non-SS patients(p<0.05). Both patient groups had low basal pituitary hormones, with mean PRL level in SS patients 4.9±4.0 ng/mL which was significantly low compared to non-SS patients with 36.8±84.7 ng/mL(p=0.022). Conclusion. Pituitary failure patients may present with a broad range of clinical symptoms and findings. Early diagnosis and timely replacement treatment have vital importance for SS patients.