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Objective: The main cause of death in patients with parathyroid carcinoma is parathyroid hormone (PTH)-induced hypercalcemia. To date, the management of hypercalcemia has been based on the use of bisphosphonates and calcimimetic agents. In recent reports, the use of denosumab has shown encouraging results in cases of refractory hypercalcemia of malignancy. Our objective is to present a case of successful management of resistant hypercalcemia due to parathyroid carcinoma with denosumab, to review similar cases from the literature, and to propose denosumab's use in the clinical management of PTH-induced refractory hypercalcemia., Methods: Presentation of a case report and review of the literature for cases of parathyroid carcinoma-mediated hypercalcemia successfully treated with denosumab., Results: A 71-year-old man with metastatic parathyroid carcinoma was referred to our department for uncontrolled hypercalcemia, resistant to treatment with bisphosphonates and cinacalcet. Treatment with denosumab (120 mg per month) in addition to cinacalcet (180 mg per day) resulted in normalization of calcium levels and maintenance within the normal range for an observation period of 11 months. Review of the literature revealed 4 case reports and a letter to the editor, all of which reported the successful treatment of resistant hypercalcemia associated with parathyroid carcinoma., Conclusion: Based on the above findings of the effectiveness of denosumab in controlling refractory hypercalcemia, its safety in renal failure and the fact that denosumab may reduce PTH-induced bone loss, we endorse its use in the management of hypercalcemia in patients with parathyroid carcinoma and perhaps other conditions with PTH-induced hypercalcemia.

Human survival has relied upon the ability to withstand starvation through energy storage, the capacity to fight off infection by a proinflammatory immune response, and the ability to cope with physical stressors by an adaptive stress response. Energy storage, mainly as glycogen in liver and triglycerides in adipose tissue, is regulated by the anabolic actions of insulin. On the other hand, mobilization of stored energy during infection, trauma or stress is served by the temporary inhibition of insulin action (insulin resistance) in target tissues by proinflammatory cytokines and stress hormones. In the current environment, high energy intake, low physical activity, and chronic stress favor the storage of surplus fat in adipose tissue depots that far exceeds their storage capacity and liporegulation. Lipid overload in central fat depots initiates an inflammatory response and adipocyte dysfunction with resultant low-grade systemic inflammation and lipid overflow to peripheral tissues. In turn, proinflammatory cytokines and non-oxidized lipid metabolites, accumulated in liver and muscle cells, activate the mechanism of insulin resistance as would occur in the case of infection or stress. The same factors together with the ensuing insulin resistance further contribute to pancreatic β-cell dysfunction and ultimately to type 2 diabetes and cardiovascular disease. The present review supports the hypothesis that insulin resistance evolved as a physiological adaptive mechanism in human survival and that the same mechanism is inappropriately activated on a chronic basis in the current environment, leading to the manifestations of the metabolic syndrome., (Copyright © 2013 Elsevier Inc. All rights reserved.)

PROP-1 gene mutations have been reported as a cause of combined pituitary hormone deficiency. Physical and hormonal phenotypes of affected individuals are variable. We report a 63-year-old female who presented with osteoporosis. She was short, did not enter puberty spontaneously and had primary amenorrhea. Biochemical evaluation revealed secondary hypothyroidism and mixed hyperlipidaemia, while dynamic testing of pituitary function was diagnostic of hypopituitarism. Bone density in the lumbar spine disclosed osteoporosis. DNA analysis showed that the patient was homozygote for the R73H mutation of the PROP-1 gene. The unfavourable long-term course of an untreated patient with PROP-1 gene mutation emphasizes the need for early aetiologic classification and proper management and follow-up of patients with short stature and/or disturbances of pubertal development.

Glucocorticoids are commonly used in the treatment of patients with thyroid disorders, in particular Graves' ophthalmopathy. Thyrotoxic hypokalemic periodic paralysis (TPP) is an infrequent but potentially serious condition characterised by recurrent episodes of weakness associated with hypokalemia. We describe the development of acute hypokalemic paralysis in a middle-aged Caucasian man with recently diagnosed thyrotoxicosis and severe, active Graves' opthalmopathy who developed progressive flaccid paralysis 12 hours following intravenous administration of methylprednisolone. Rechallenge with the same dose after the patient had been rendered euthyroid did not provoke TPP. Clinicians should exercise caution when administering high-dose glucocorticoids during thyrotoxicosis as there is a risk of provoking hypokalemic paralysis in susceptible patients.

Paget's disease of bone is a focal skeletal disorder characterized by the formation of structurally abnormal bone, skeletal deformities, and other complications leading to bone pain and significant disability. It can involve one or more areas in a single bone (monostotic) or multiple bones (polyostotic). Most of the time the disease is asymptomatic and the diagnosis is made incidentally by increased levels of bone metabolism markers, especially alkaline phosphatase and is confirmed by specific findings in radiographs and radionuclide bone scan. In this report, we describe the case of a 65-year-old female with clinical and radiological findings of active Paget's disease of bone, but with absence of abnormal biochemical markers. The patient was given a dose of 5 mg zoledronic acid intravenously with significant clinical improvement within the next 6 months. The present case not only shows that Paget's disease of bone can occur in the setting of normal markers of bone metabolism but also that, in such cases, the response to treatment can be monitored by improvement in the clinical picture or by correct evaluation of the imaging findings.

Cardiovascular disease in patients with congenital hypopituitarism is not rare; however, there is a lack of reports referring to cardiac interventions in such patients. We present a 76-year-old man with complete pituitary hormone deficiency, who presented with recurrent events of unstable angina. He had a significant stenosis of the left anterior descending artery and he underwent off-pump coronary artery bypass. Our aim is to present the successful management of this patient with congenital hypopituitarism who underwent cardiac surgery and to review the relevant literature.

Hot flush is one of the most commonly reported symptoms during menopause; however, it is not experienced by all menopausal women, for reasons that remain unclear. In this review, we present current evidence that link hot flushes with cardiovascular disease, suggesting that the persistence of hot flushes many years after the menopause may represent a marker of an underlying disorder that increases the risk for cardiovascular disease.

Objective: Fas is a cell-surface receptor responsible for induction of apoptosis in human thyrocytes upon interaction with Fas Ligand. Fas protein expression on thyroid cells and Fas-mediated apoptosis is decreased in multinodular goiter (MNG) resulting in thyroid cell proliferation. The soluble form of Fas (sFas) produced by alternative mRNA splicing may inhibit Fas-Fas Ligand binding and apoptosis. The aim of this study was to examine whether sFas is differentially expressed in multinodular goiter (MNG), which is associated with decreased Fas-mediated apoptosis., Method: We determined serum sFas levels using enzyme-linked immunosorbent assay (ELISA) in 42 patients with MNG and 23 normal controls., Results: Serum sFas levels were increased in patients with MNG (7.47 +/- 2.55 ng/ml) compared to normal controls (2.26 +/- 0.9 ng/ml). Levels of sFas were not significantly correlated with age, sex or clinical parameters, such as serum levels of FT4 or TSH., Discussion: Increased sFas in MNG may indicate increased expression of alternatively spliced Fas mRNA variant and decreased expression of cell-surface Fas protein, and may enhance thyroid cell proliferation by protecting thyroid cells from Fas-mediated apoptosis.

Hypolipidaemias can be either primary due to several genetic defects altering the serum concentration of lipoproteins, or secondary resulting from various disorders such as liver disease, malabsorption, malnutrition, malignancy, hyperthyroidism and immunoglobulin disorders. We present a review of the current knowledge regarding the various causes of hypolipidaemias. Our aim is to emphasize on the different mechanisms, apart from deranged liver synthetic function, that are responsible for unusually low levels of cholesterol and on the disorders that need to be considered during the investigation of hypolipidaemia.

Fine needle aspiration biopsy (FNAB)-based cytology is an accurate preoperative diagnostic method for the evaluation of thyroid nodules. Despite its high specificity and sensitivity, the results are non-diagnostic in a significant number of cases, commonly due to inadequacy of the samples or the presence of undetermined cellular morphology. Overlap-ping cytologic features among follicular-derived lesions are the most common causes of cyto-histopathologic discordances. The management of thyroid nodules with a non-diagnostic FNAB remains controversial. The significant probability of malignancy imposes either the repeat of the procedure or direct surgery. Recent studies have demonstrated the important role of molecular-based techniques such as RT-PCR in the diagnosis of thyroid lesions. Follicular cells obtained from the remaining material within the needle can be used for RNA extraction and then for RT-PCR amplification of specific mRNAs that are expressed in benign or malignant thyroid nodules. Furthermore, FNAB-RT-PCR in combination with molecular scanning techniques or direct sequencing provides a valuable screening tool for mutations. The present review highlights the applications of FNAB-RT-PCR method in the identification of new diagnostic molecular markers. The parallel molecular and cytological analysis of FNABs may contribute to a more accurate diagnosis and, thus, to a more specific clinical management of thyroid nodules.