ACTA ENDOCRINOLOGICA (BUC)

Context. Hepatitis C and diabetes represent important health problems globally. The new-onset diabetes after transplantation is a particular entity that appears due to the use of immunosuppression among transplanted patients. Objective. We aim to describe the clinical and biological aspects of severe hyperglycemia in a kidney transplant recipient undergoing Interferon-free therapy for chronic hepatitis C, discussing the interference of different factors with the glucose metabolism. Design. The occurrence of diabetes in a patient with history of renal transplantation and Interferon-free treated hepatitis C was studied from both clinical and paraclinical points of view. Subjects and methods. When presenting to the hospital, extensive blood tests were performed on the patient, revealing significant hyperglycemia and an elevated level of blood tacrolimus. Creatinine clearance was calculated. ECG presented T-wave alterations. Intensive insulin protocol was applied, the case being managed in a multidisciplinary approach. Results. Blood glucose and tacrolimus were slowly normalized, under therapy. The antiviral treatment was continued, with the achievement of sustained virologic response. Conclusions. Diabetes mellitus can have many causes, hepatitis C and transplantation both having an impact on glucose metabolism. The association of the three entities should be carefully managed, due to its enhancing effect on morbidity and mortality.

Background. The concept of NE differentiation in prostate carcinoma has two major aspects: prostate tumors with\r\nprimary NE differentiation and NE differentiation occurred during hormonal therapy for prostate adenocarcinoma, with\r\nthe extreme case of tumor dedifferentiation into a NE hormone resistant carcinoma.\r\nMaterial and method. The patient, 62 years old, with a history of poorly differentiated prostate adenocarcinoma,\r\nhormonally treated with the decrease and then constant maintenance of serum PSA level to 0.01 ng/mL was admitted in the hospital, 8 years after prostate tumor diagnosis, and 3 years after ceasing of hormone therapy, with multiple bone and liver metastases of unknown primary source.\r\nResults. The serum levels of CgA, NSE, CEA, CA19.9, serotonin were elevated. The histopathological examination\r\nof the needle biopsy fragment from a liver metastatic lesion revealed small cell neuroendocrine carcinoma. Despite the\r\nprompt chemotherapy, the disease has progressed, with the occurrence of brain metastases and the patient?s death\r\n6 months after detection of the metastatic disease.\r\nConclusions. The present case confirms the diagnostic difficulties in llymetastatic undifferentiated small cells\r\ntumors, and on the other hand, draws attention to the possibility of NE dedifferentiation as a result of hormone\r\ndeprivation in patients with prostate cancer.

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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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.

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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.

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. Insulin resistance is routinely measured by homeostasis model assessment of insulin resistance (HOMA-IR).Positron emission tomography of 18F-fluorodeoxyglucose combined with computed tomography (18F-FDG PET/CT) is a valuable assessment tool for patients with cancer or staging tumors. 18F-FDG PET/CT imaging can also be utilised to detect the metabolic activity of glucose in the adipose tissue, liver and muscles. The aim of this study was to determine insulin sensitivity in the liver, muscle visceral adipose and subcutaneous adipose tissue separately via18F-FDG PET/CT. Materials and method. Sixty three adult patients who underwent whole body 18F-FDG PET/CT scanning for clinical purposes (diagnosis or staging of cancer) between July and August of 2016 were included in the study. Patients were divided into two groups according to their BMI (Group 1: BMI<25kg/m2, Group 2: BMI>25kg/ m2). HOMA-IR,fasting glucose,insulin, triglycerides, total cholesterol, HDL levels were measured. We calculated SUV as the tissue activity of the ROI (MBq/g)/(injected dose [MBq]/ body weight [g]) on PET images and measured the maximum SUVs (SUVmax) of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT),liver and rectus muscle ROIs (2 cm). SUV corrected by blood glucose level (SUVgluc) was calculated as SUVmax×blood glucose level/100. Student-t test, Chi-square test and Pearson correlation test were used for statistical analysis. Results. Mean glucose,insulin,HOMA-IR levels of the group-2 were statistically higher than of group-1. Muscle SUVmax and liver SUVmax of group-1 were statistically higher than of group-2. Muscle SUVgluc of group-1 was statistically higher than of group-2. HOMA-IR was negatively correlated with both SUVmax(r=-0.340, p=0.01) and muscle SUVmax(r=-0.373, p=0.005) Conclusion. 18F-FDG PET/CT has shown that the muscle tissue maximum FDG uptake was lower in the insulin resistance group. Therefore, 18-FDG PET/CT could be a valuable tool for diagnosing insulin resistance.