A Very Rare Case of Diabetes Mellitus Occurring in a Patient With Hyperinsulinism Hyperammonemia Syndrome.

Background/Objective: To illustrate an unusual case of type 2 diabetes mellitus (T2DM) developing many years after the diagnosis of hyperinsulinism hyperammonemia (HI/HA) syndrome. Case Report: This article reports about a 36-year-old female with a history of congenital hyperinsulinism due to HI/HA syndrome, which was diagnosed in infancy. The patient presented with hypoglycemia and seizures as an infant and was treated with diazoxide and a low-protein diet for many years with reduction in her hypoglycemic events. She subsequently developed T2DM >30 years later. Genetic analysis was positive for a glutamate dehydrogenase 1 gene (GLUD1) alteration. She was treated with metformin and a glucagon-like peptide 1 agonist, with significant improvement in her blood glucose control and weight loss. Discussion: HI/HA syndrome is a rare genetic syndrome that manifests in childhood with signs and symptoms of hypoglycemia and neurologic symptoms. This is the first case reported in the literature of a patient with HI/HA syndrome due to a GLUD1 alteration who developed T2DM much later in life. Patients with this disorder usually have recurrent hypoglycemia and require long-term medical therapy or very occasionally may have a resolution. She had class 3 obesity and evidence of insulin resistance, which likely contributed to her risk of diabetes. Conclusion: This is a rare case of T2DM presenting in a patient with HI/HA syndrome. This should be considered a possible outcome in patients with this disorder, especially in the presence of obesity.

Bilateral Adrenal Myelolipomas in a Female Patient With Undiagnosed Non-classic Congenital Adrenal Hyperplasia.

Non-classic congenital adrenal hyperplasia (CAH) usually presents later in life with signs of androgen excess but may also be diagnosed after the detection of an incidental adrenal myelolipoma. This is a patient with previously undiagnosed CAH who presented to the emergency department with chest discomfort and palpitations. A computed tomography (CT) scan of the chest done to rule out pulmonary embolism showed bilateral large adrenal myelolipomas. She also had evidence of marked hirsutism on examination, which prompted further workup, and her laboratory data was in keeping with CAH. Further management was unable to be pursued due to the patient's poor compliance, and she was subsequently lost to follow-up. Chronic exposure of the adrenal glands to high adrenocorticotropic hormone (ACTH) levels increases the risk of developing myelolipomas. CAH needs to be considered as a diagnosis in the evaluation of incidental adrenal myelolipomas.

Recurrent Neuroendocrine Tumor of the Cervix Presenting With Ectopic Cushing's Syndrome.

Neuroendocrine carcinomas (NEC) of the cervix are a rare disease entity and account for only 1-2% of cervical carcinomas. The small-cell variant is the most common, with a worse prognosis and a higher rate of lymphatic and hematogenous metastases when compared with other subtypes of NEC. The diagnosis is usually made when the extra-pelvic disease is already apparent. Cushing's syndrome due to adrenocorticotropic hormone (ACTH)-secreting tumors of the cervix is exceedingly rare. To date, there have been no reported cases in the literature of Cushing's syndrome induced by the recurrence of metastases years after the initial diagnosis. This is a case of recurrent small-cell neuroendocrine carcinoma of the cervix presenting with Cushing's syndrome five years after her original diagnosis. We present here the workup, management, and follow-up of this patient, including multisystemic, coordinated medical care.

Methimazole-Induced Pleural Effusion in the Setting of Graves' Disease.

Methimazole is a thionamide drug that inhibits the synthesis of thyroid hormones by blocking the oxidation of iodine in the thyroid gland. We report a case of methimazole-induced recurrent pleural effusion. A 67-year-old female with recently diagnosed Graves' disease on methimazole 20mg daily was admitted with dyspnea and new onset atrial fibrillation with rapid ventricular rate. Chest X-ray revealed a unilateral right pleural effusion, which was consistent with a transudate on thoracocentesis. She was managed as a case of congestive heart failure and methimazole dose was increased to 30 mg daily. She was readmitted twice with recurrent right pleural effusion. The fluid revealed an exudative process on repeat thoracocentesis. CT scan of the chest with contrast showed mediastinal lymphadenopathy and a diffuse ground glass process involving the right lower lobe suggestive of pneumonitis. Bronchoalveolar lavage showed neutrophil predominant fluid, and cytology and adenosine deaminase were negative. Patient also had an endobronchial ultrasound guided biopsy of the lymph nodes (EBUS). She was treated empirically with steroids 40 mg for 10 days and the methimazole was also discontinued. The antinuclear antibodies (ANA) came back positive with a speckled pattern; antineutrophil cytoplasmic antibody (c-ANCA) and antimyeloperoxidase were also positive. The effusion resolved but recurred on rechallenge with methimazole. She was referred for urgent thyroidectomy. The patient's repeat chest X-ray showed complete resolution of the pleural effusion after stopping the methimazole. Few weeks later, repeat ANCA and antimyeloperoxidase antibody were both negative. Our case report highlights the importance of the recognition of a rare side effect of methimazole. Timely diagnosis would ensure that appropriate treatment is given.

Role of adipokines and inflammatory markers in postmenopausal hypertension.

BACKGROUND: The role of inflammatory markers and adipokines contributing to the development of postmenopausal hypertension, has not been established. The aim of our study was to assess the complex association between blood pressure, obesity, menopausal status, adipokines and inflammatory mediators in postmenopausal women. METHODS: We recruited 38 women seen at our Endocrinology Clinic and collected anthropometric measures and blood pressure and obtained serum samples for inflammatory markers and adipokine levels. Out of 38 women, 23 (60%) were postmenopausal. RESULTS: In the pre-menopausal and postmenopausal women, there were no significant differences in measured adipokines and inflammatory markers based on hypertensive status. When obesity was eliminated, significantly higher levels of EGF, IL-8, MCP1 and TNF-α and lower levels of IL-1α and IL-3 were observed in the postmenopausal group (P<0.05). Women with higher waist-to-hip ratio (WHR) had a significant trend towards lower adiponectin levels as compared to those with lower WHR (P=0.014 and P=0.04, respectively). CONCLUSIONS: There was a significant difference in pro-inflammatory markers in non-obese, pre- and post-menopausal women. These higher inflammatory markers might play a role in the development of post-menopausal hypertension.

Improving Rural Bone Health and Minimizing Fracture Risk in West Virginia: Validation of the World Health Organization FRAX Assessment Tool as a Phone Survey for Osteoporosis Detection.

West Virginia ranks second nationally in population ≥ 65 years old placing our state at greater risk for osteoporosis and fracture. The gold standard for detecting osteoporosis is dual X-ray absorptiometry (DXA), yet over half of West Virginia's counties do not have this machine. Due to access barriers, a validated phone-administered fracture prediction tool would be beneficial for osteoporosis screening. The World Health Organization's FRAX fracture prediction tool was administered as a phone survey to 45 patients; these results were compared to DXA bone mineral density determination. Results confirmed that the FRAX phone survey is as reliable as DXA in detecting osteoporosis or clinically significant osteopenia: 92% positive predictive value, 100% negative predictive value, 100% sensitivity and 91% specificity when compared to the gold standard. These promising results allow for the development of telephone-based protocols to improve osteoporosis detection, referral and treatment especially in areas with health care access barriers.

Protective Effects of Cerium Oxide Nanoparticles on MC3T3-E1 Osteoblastic Cells Exposed to X-Ray Irradiation.

BACKGROUND/AIMS: Exposure to ionizing radiation can result in bone damage, including decreased osteocyte number and suppressed osteoblastic activity. However, molecular mechanisms remain to be elucidated, and effective prevention strategies are still limited. This study was to investigate whether cerium oxide nanoparticles (CeO2 NP) can protect MC3T3-E1 osteoblast-like cells from damaging effects of X-ray irradiation, and to study the underpinning mechanism(s). METHODS: MC3T3-E1, a osteoblast-like cell line, was exposed to X-ray irradiation and treated with different concentration of CeO2 nanoparticles. The micronucleus frequency was counted under a fluorescence microscope. Cell viability was evaluated using MTT assay. The effects of irradiation and CeO2 nanoparticles on alkaline phosphatase activity and MC3T3-E1 mineralization were further assayed. RESULTS: We found that the ratio of micronuclei to binuclei was dose-dependently increased with X-ray irradiation (from 2 to 6 Gy), but diminished with the increased concentration of CeO2 NP treatment (from 50 to 100 nM). Exposure to X-rays (6 Gy) decreased cell viability, differentiation and the mineralization, but CeO2 NP treatment (100 nM) attenuated the deteriorative effects of irradiation. Both intracellular reactive oxygen species (ROS) production and extracellular H2O2 concentration were increased after X-ray irradiation, but reduced following CeO2 NP treatment. Similar to irradiation, exposure to H2O2 (10 µM) elevated the frequency of micronuclei and diminished cell viability and mineralization, while these changes were ameliorated following CeO2 NP treatment. CONCLUSIONS: Taken together, our findings suggest that CeO2 nanoparticles exhibit astonishing protective effects on irradiation-induced osteoradionecrosis in MC3T3-E1 cells, and the protective effects appear to be mediated, at least partially, by reducing oxidative stress.

Gene expression classifier for the diagnosis of indeterminate thyroid nodules: a meta-analysis.

Prior studies demonstrate that a novel genomic test, the gene expression classifier (GEC), could identify a benign gene expression signature in those nodules with indeterminate cytology with a negative predictive value of greater than 95 %. Examine the performance of the AFIRMA gene expression classifier in predicting benign and malignant nodules in patients with cytologically indeterminate nodules. MEDLINE and EMBASE search for studies meeting eligibility criteria between January 1, 2005, and August 30, 2015. A total of 58 studies identified. After excluding duplicates, case reports, reviews, commentary, insufficient data, a total of seven studies selected for analysis. We combined individual patient data from seven studies that examined the GEC test for indeterminate thyroid nodules. The reference standard for determination of benign or malignant nodules was the histopathology of the thyroidectomy specimen. A QUADAS-2 report for all studies included in the final analysis was tabulated for risk of bias and applicability. The pooled sensitivity of the GEC was 95.7 % (95 % CI 92.2-97.9, I (2) value 45.4 %, p = 0.09), and the pooled specificity was 30.5 % (95 % CI 26.0-35.3, I (2) value 92.1 %, p < 0.01). Overall, the diagnostic odds ratio was 7.9 (95 % CI 4.1-15.1). Patients with benign GEC were not followed long enough to ascertain the actual false-negative rates of the index test. Our meta-analysis revealed a high pooled sensitivity and a low specificity for the AFIRMA-GEC test for indeterminate thyroid nodules. This makes it an excellent tool to rule out malignancy.

Metabolic syndrome-induced tubulointerstitial injury: role of oxidative stress and preventive effects of acetaminophen.

The prevalence of metabolic syndrome persistently increases and affects over 30% of U.S. adults. To study how metabolic syndrome may induce tubulointerstitial injury and whether acetaminophen has renal-protective properties, 4-week-old obese Zucker rats were randomly assigned into three groups, control (OC), vehicle dimethyl sulfoxide (OV), and acetaminophen treatment (30 mg/kg/day for 26 weeks), and lean Zucker rats served as healthy controls. Significant tubulointerstitial injuries were observed in both OC and OV animals, evidenced by increased tubular cell death, tubular atrophy/dilation, inflammatory cell infiltration, and fibrosis. These tubulointerstitial alterations were significantly reduced by treatment with a chronic but low dose of acetaminophen, which acted to diminish NADPH oxidase isoforms Nox2 and Nox4 and decrease tubulointerstitial oxidative stress (reduced tissue superoxide and macromolecular oxidation). Decreased oxidative stress by acetaminophen was paralleled by the reduction of tubular proapoptotic signaling (diminished Bax/Bcl-2 ratio and caspase 3 activation) and the alleviation of tubular epithelial-to-mesenchymal transition (decreased transforming growth factor ß, connective tissue growth factor, α-smooth muscle actin, and laminin). These data suggest that increased oxidative stress plays a critical role in mediating metabolic syndrome-induced tubulointerstitial injury and provide the first evidence suggesting that acetaminophen may be of therapeutic benefit for the prevention of tubulointerstitial injury.