Predicting the Development of Orbitopathy in Graves Thyroidopathy Patients: The Potential Role of TSI Testing.

OBJECTIVE: To determine whether thyroid-stimulating immunoglobulin (TSI) testing can predict the risk of development of Graves orbitopathy in newly diagnosed Graves thyroidopathy patients. DESIGN: Retrospective cohort, from 2008 to 2013. SETTING: The Thyroid Referral Center at California Pacific Medical Center. PARTICIPANTS: A retrospective cohort of newly diagnosed Graves thyroidopathy patients from the California Pacific Medical Center Thyroid Referral Center. Patients were included if they had TSIs drawn at or near the time of diagnosis of Graves thyroidopathy. Patients were excluded from the study if they had a long-standing diagnosis of Graves thyroidopathy, orbitopathy at time of diagnosis, no TSIs drawn, or follow up of less than 6 months. MAIN OUTCOME MEASURES: Patients were followed for the development of orbitopathy as determined by their endocrinologists. Results were adjusted for family history, smoking status, age, radioiodine ablation treatment, and race. RESULTS: Thirty-three patients met inclusion criteria out of a screened population of 506 patients. Eight out of 33 patients (24%) developed orbitopathy. The mean time from diagnosis of Graves' thyroidopathy to development of orbitopathy was 11.6 months (median: 7.5 months, range: 1 to 20 months). The mean initial TSI value was 421.3 in those that developed orbitopathy compared to 245.9 in those who had at least 6 months of documented follow-up and did not develop orbitopathy (p = 0.04). Those in the top tercile of initial TSI values were 14 times as likely to develop orbitopathy (relative risk (RR) = 14.0, p = 0.02; multivariate adjusted RR = 13.08, p = 0.03). Family history, smoking status, age, radioiodine ablation, thyroid-stimulating hormone, and race were not statistically significant predictors. CONCLUSIONS: TSI level greater than 400 at time of presentation of Graves thyroidopathy may be a useful predictor of risk for development of orbitopathy. This information will help to identify patients likely to benefit from early referral to an ophthalmologist for possible preemptive therapy to prevent the development of orbitopathy. Prospective cohort studies are needed to definitively establish the metrics for TSI as a predictor of orbitopathy.

Keeping in touch. Cell phone use in people with schizophrenia disorders.

There is limited research exploring telephone intervention for psychiatric clients; no studies specific to cell phone use have been conducted. This pilot study examined the feasibility and acceptability of cell phone use in individuals with schizophrenia spectrum disorders (SSDs). Ten outpatients with SSDs were provided with previously activated cell phones for 5 months; trained nurses contacted participants weekly. Seven participants completed the 5-month follow-up period. A minority of participants reported difficulty retrieving messages and answering or charging their phone. These preliminary findings indicate the majority of individuals with SSDs are willing to use this method of communication and are able to do so with few problems. Possible barriers to the use of cell phones with this group include lifestyle factors and poor decision making. Future investigations should examine the use of cell phone access to foster personal safety, gain a sense of connectedness to others, and enhance quality of life.

Glucose sensor-augmented continuous subcutaneous insulin infusion in patients with diabetic gastroparesis: An open-label pilot prospective study.

Erratic blood glucose levels can be a cause and consequence of delayed gastric emptying in patients with diabetes. It is unknown if better glycemic control increases risks of hypoglycemia or improves hemoglobin A1c levels and gastrointestinal symptoms in diabetic gastroparesis. This study investigated the safety and potential efficacy of continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) in poorly controlled diabetes with gastroparesis. Forty-five type 1 or 2 patients with diabetes and gastroparesis and hemoglobin A1c >8% from the NIDDK Gastroparesis Consortium enrolled in a 24 week open-label pilot prospective study of CSII plus CGM. The primary safety outcome was combined numbers of mild, moderate, and severe hypoglycemic events at screening and 24 weeks treatment. Secondary outcomes included glycemic excursions on CGM, hemoglobin A1c, gastroparesis symptoms, quality-of-life, and liquid meal tolerance. Combined mild, moderate, and severe hypoglycemic events occurred similarly during the screening/run-in (1.9/week) versus treatment (2.2/week) phases with a relative risk of 1.18 (95% CI 0.85-1.64, P = 0.33). CGM time in hypoglycemia (<70 mg/dL) decreased from 3.9% to 1.8% (P<0.0001), time in euglycemia (70-180 mg/dL) increased from 44.0% to 52.0% (P = 0.02), time in severe hyperglycemia (>300 mg/dL) decreased from 14.2% to 7.0% (P = 0.005), and hemoglobin A1c decreased from 9.4±1.4% to 8.3±1.3% (P = 0.001) on CSII plus CGM. Symptom scores decreased from 29.3±7.1 to 21.9±10.2 with lower nausea/vomiting, fullness/early satiety, and bloating/distention scores (P≤0.001). Quality-of-life scores improved from 2.4±1.1 to 3.1±1.1 (P<0.0001) and volumes of liquid nutrient meals tolerated increased from 420±258 to 487±312 mL (P = 0.05) at 24 weeks. In conclusion, CSII plus CGM appeared to be safe with minimal risks of hypoglycemic events and associated improvements in glycemic control, gastroparesis symptoms, quality-of-life, and meal tolerance in patients with poorly controlled diabetes and gastroparesis. This study supports the safety, feasibility, and potential benefits of improving glycemic control in diabetic gastroparesis.

Fanconi's syndrome in HIV+ adults: report of three cases and literature review.

UNLABELLED: We diagnosed Fanconi's syndrome (phosphate depletion and dysfunction of the renal tubules) in three HIV(+) patients. This was temporally related to their HIV treatment. Physicians caring for patients with HIV should recognize the association of this rare syndrome with antiretroviral medications and monitor their patients carefully. INTRODUCTION: Fanconi's syndrome is caused by increased excretion of phosphate, glucose, amino acids, and other intermediary metabolites, and can result in osteomalacia. MATERIALS AND METHODS: We diagnosed this syndrome in three HIV(+) patients. RESULTS: The first was a 43-year-old woman referred for multiple painful stress fractures. She demonstrated hypophosphatemia, metabolic acidosis, phosphaturia, glucosuria, and generalized aminoaciduria. These abnormalities resolved with oral phosphate replacement and discontinuation of the antiretroviral medication tenofovir. The second patient was a 39-year-old man with hypophosphatemia and bone pain. His symptoms improved with discontinuation of adefovir and supplementation of phosphate, potassium, and calcitriol. The third patient was a 48-year-old man who presented with symptomatic tetany caused by hypocalcemia (total serum calcium of 6.5 mg/dl [8.5-10.5 mg/dl]). Nine months before presentation, he had been treated with cidofovir for retinitis caused by cytomegalovirus. With calcium, phosphate, potassium, and calcitriol therapy, his laboratory abnormalities improved substantially, although he continues to require daily electrolyte replacement. CONCLUSIONS: Each patient demonstrated generalized renal tubular dysfunction temporally related to treatment with antiretroviral drugs. The mechanism responsible for these abnormalities is not known; however, physicians caring for patients with HIV disease should recognize the association of Fanconi's syndrome with antiretroviral medications and monitor susceptible patients to prevent potential skeletal and neuromuscular complications.

Inadvertent sulfonylurea overdosage and hypoglycemia in an elderly woman: failure of serum hypoglycemia screening.

We report a case of an 82 year-old woman who had two episodes of documented hypoglycemia. Initial laboratory testing revealed hyperinsulinemia and a negative serum sulfonylurea screen. While these data suggested the presence of an insulinoma, further evaluation of the case revealed inadvertent ingestion of glimepiride, a sulfonylurea not included in the standard serum sulfonylurea screen.

Histopathological analysis of renal cystic epithelia in the Pkd2WS25/- mouse model of ADPKD.

It has been proposed that autosomal dominant polycystic kidney disease (ADPKD)affected renal epithelial cells undergo a phenotypic transition from a highly differentiated absorptive state to a much less differentiated secretory state during cystogenesis and that this transition is accompanied by loss of epithelial cell polarity and mistargeting of specific membrane proteins. We conducted a detailed evaluation of this hypothesis in the Pkd2WS25/- mouse model of ADPKD. Ultrastructural analysis of Pkd2WS25/- cysts by electron microscopy confirmed that cystic epithelial cells progressively dedifferentiate with cyst enlargement. Immunocytochemical analysis of both early- and late-stage cysts with antibodies directed against Na+-K+-ATPase, Ksp-cadherin, and E-cadherin failed to detect evidence of altered cyst cell polarity. Na+-K+-ATPase and Ksp-cadherin were expressed exclusively on the basolateral membranes (BLM) of epithelial cells in all early cysts. Expression levels of both Na+-K+-ATPase and Ksp-cadherin decreased progressively with the degree of cyst cell dedifferentiation, but neither protein was ever mislocalized. Highly dedifferentiated cysts did not express immunodetectable levels of either Na+-K+-ATPase or Ksp-cadherin. E-cadherin was expressed prominently on the BLM of all cysts. Cysts were subsequently stained with an antibody directed against the secretory isoform of the Na+-K+-Cl- cotransporter NKCC1. NKCC1 expression was detected on the BLM of advanced cysts only. Our data are consistent with a model of progressive cystic epithelial cell dedifferentiation in which fluid accumulation in late-stage cysts is mediated by transepithelial secretion of chloride rather than secretion of sodium by apical Na+-K+-ATPase.