ACTA ENDOCRINOLOGICA (BUC)

Background. ROHHADNET syndrome is a pleiotropic disorder defined by rapid onset of obesity, hypothalamic-pituitary endocrine dysfunctions, alveolar hypoventilation and hypothalamic autonomic dysregulation and neural tumors. Case presentation. We report the case of a 5.8-year-old female patient with rapid onset of obesity and growth arrest, hypercortisolism, hyperprolactinemia, low IGF1, severe hypernatremia (with no signs of diabetes insipidus) and chronic hyperchloremic metabolic acidosis. Additional symptoms included sleep apnea and two episodes of cardiopulmonary arrest after mild sedation. Brain MRI, chest and abdominal enhanced CT scans were all negative. As no tumors were revealed at the time of diagnosis, ROHHAD syndrome was suspected. Treatment with potassium bicarbonate was initiated in an attempt to control both the severe hypernatremia and chronic hyperchloremic metabolic acidosis. Patient developed dilated cardiomyopathy and kaliopenic nephropathy. Conclusion. The presence of dilated cardiomyopathy is in keeping with only one other reported case, while the severe hypernatremia joined by hyperchloremic metabolic acidosis seen in our patient has not been presented previously. Although it is a very rare medical condition, ROHHAD syndrome has to be considered in the differential diagnosis of any case with rapid onset obesity associated with hypothalamic-pituitary endocrine dysfunctions, and alveolar hypoventilation.

Aim. To explore the effects and underlying mechanisms of pioglitazone (pio) on insulin sensitivity in insulin-resistant KKAy mice. Methods. Sixteen eight-week-old male KKAy mice were randomly assigned to two groups based on body weight: an insulin resistance model group and a pioglitazone treatment group (hereafter referred to as the pio-group). Eight male C57BL/6J mice were used as an insulin resistance control group. Mice in all three groups were fed an AIN-93G diet, and pio was added to the diet in the pio-group. After twelve weeks of treatment, blood glucose, serum insulin, glucose tolerance, and insulin tolerance were measured. ELISA was used to determine adiponectin and leptin in serum. A real time PCR assay was used to detect the mRNA of adiponectin and leptin in epididymal adipose tissue. A Western blot assay was used to analyze protein expression and/ or phosphorylation levels of peroxisome proliferator activated receptor γ (PPARγ), insulin receptor substrate 1 (IRS1), and protein kinase B (PKB/AKT) in the liver and epididymal adipose tissue.Results. The results showed that Pio treatment may effectively reduce levels of blood glucose and serum insulin, improve insulin tolerance and glucose tolerance, increase serum adiponectin, decrease serum leptin, and enhance mRNA expression of adiponectin in epididymal adipose tissue. Furthermore, with pio treatment, protein expression of PPARγ and phosphorylation levels of IRS1 and AKT were increased in the liver and epididymal adipose tissue. Conclusion. These results suggested that Pio intervention may ameliorate insulin resistance and improve insulin sensitivity in KKAy mice, which may be due to an increase of PPARγ and further activation of the insulin signaling transduction pathway (IRS1 and AKT) in the liver and epididymal adipose tissue of KKAy mice.

Background. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancers. Antibodies directed against programmed cell death receptor 1 (PD-1) interrupt the ability of the cancerous cell to depress the immune system. Methods and results. We report three patients who developed different endocrine abnormalities after treatment with nivolumab, a monoclonal antibody directed against PD-1. First, we report a 76-year-old male presenting with generalized fat loss after treatment with nivolumab which predominantly affected his face and trunk. Second, we described the development of thyroiditis that presented with thyrotoxicosis and the expression of thyroid-stimulating hormone receptor antibodies (TRAb). Finally, we observed the emergence of adrenal insufficiency due to hypophysitis in another case. Conclusion. Although immune checkpoint inhibitors are an effective anticancer treatment modality, adverse effects are evident that can affect the endocrine system. These adverse events may relate to different endocrine systems that include the thyroid and pituitary glands. Also, acquired generalized lipodystrophy should be suspected in patients developing unusual fat loss after treatment with ICIs.

Context and objective. Somatostatin analogues and cinacalcet have been suggested to have some role in managing hypophosphatemia. This report highlights challenges in managing surgically incurable tumor induced osteomalacia (TIO) with somatostatin analogues and cinacalcet. Patient and methods. A twenty-two year old patient with severe osteomalacia was diagnosed to have TIO due to left hemipelvis tumor (June 2013). Partial surgical removal of tumor (due to its proximity to neurovascular bundles), led to transient remission for 6 weeks. Clinical worsening in spite of maximum tolerable phosphate and calcitriol dose led to trial of octreotide. Acute improvement in phosphate following subcutaneous octreotide 100 mcg was the basis for use of long acting depot octreotide, which was associated with maximal improvement for 4 months, followed by reduced efficacy. Repeated MRI revealed an increase in residual tumor size. Reevaluation revealed very a high parathyroid hormone. Cinacalcet titrated to 90 mg/day induced hypoparathyroidism, improved hypophosphatemia but caused symptomatic hypocalcemia. Cinacalcet at lower doses (30mg/day), though well tolerated, was less effective in improving hypophosphatemia. There was a near 10-fold reduction (2406 to 246RU/ml) in C-terminal FGF-23 levels with cinacalcet. Reduction in phosphate and calcitriol requirements with cinacalcet may contribute to decreased FGF-23. There was no decrease in tumor size. Conclusion. Octreotide and cinacalcet are effective in controlling hypophosphatemia over short periods. Progressive nature of TIO leading to an increased disease severity, tachyphylaxis may explain decreased efficacy of octreotide, higher cinacalcet requirement, poor tolerability, thus limiting their role in long-term management of TIO.

Resistant Graves’ disease in pregnancy is a rare entity. The clinical situation poses immense difficulty to the treating endocrinologist and obstetrician in optimizing maternal and fetal heath. No guidelines till date are available to manage resistant Grave’s disease in pregnancy. We hereby present a case series on resistant Grave’s in pregnancy and our institute experience in managing this rare and challenging clinical entity. Definitive management is total thyroidectomy in second trimester. Higher doses of ATDs and betablockers may have its fetopathic effects. Use of immunosuppressive agents are not advised in pregnancy to suppress the TRAb titre. Steroid therapy may be used as an adjuvant to permissible doses of anti-thyroid medications to curb the thyrotoxicosis in pregnancy. An alternate fetal friendly ATD is not available to add on to existing ATDs. TRAb estimation in maternal blood is mandatory. Mothers need frequent monitoring of cardiac status and need to avoid factors that can cause cardiac decompensation. Fetal surveillance includes growth monitoring and biophysical profile at nearby intervals, helps to ascertain the effects of excess thyroid hormones, TRAb and anti-thyroid drugs. Immediate neonatal cord blood screening for thyroid abnormalities is necessary. Maternal and fetal management in such a clinical situation is multidisciplinary.

Intrasellar plasmacytoma is a rare pituitary tumor, which originates from monoclonal plasma cells in a single lesion. Knowledge of its features comes from case reports only. Here, we present an interesting case of a 77-year-old woman with a presumptive diagnosis of nonfunctioning pituitary adenoma, as based on both clinical and radiological examinations. Following endoscopic endonasal transsphenoidal surgery, the definitive diagnosis of intrasellar plasmacytoma was made by immunohistochemical analysis of the sellar mass. Intrasellar plasmacytoma is rare, but it should be evaluated in the differential diagnosis of a pituitary mass due to its different therapeutic approach and prognosis, since it can frequently progress to multiple myeloma.

Evans syndrome is a rare combination of autoimmune hemolytic anemia and immune thrombocytopenia. Evans syndrome in cases of Graves’ disease is extremely rare. The coexistence of these autoimmune diseases suggests that they may share a common pathogenic pathway. The case here presented is of a 36-year old female patient who was admitted for anemia and thrombocytopenia and was diagnosed with Evans syndrome associated with Graves’ disease, and was then treated with methimazole and methylprednisolone (MPSL). During follow-up, MPSL was discontinued gradually over the course of two months. Interestingly, while Evans syndrome is characterized by frequent relapses, this patient has been in remission of Evans syndrome for approximately 1 year without MPSL therapy. The remission of Evans syndrome associated with Graves’ disease in the absence of immunosuppressive therapy suggests that these 2 diseases have a common pathogenetic mechanism.

Medullary thyroid carcinoma is a neuroendocrine tumour of the parafollicular C cells of the thyroid gland. It is an aggressive tumor that can be cured only by complete resection of the thyroid tumour and any local and regional metastases. Thus, the discovery of novel diagnostic and prognostic markers is very important for early diagnosis and correct management, in order for the survival rates to rise. New research has emphasized the potential role of various genes, serum and immunohistochemical markers, as well as potential targets for therapeutic agents. The calcium stimulated calcitonin test has been recently reintroduced in clinical practice, and current medullary thyroid carcinoma guidelines encourage laboratories to set their own criteria defining reference ranges for elevated serum basal and stimulated calcitonin levels.

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