Development of an objective tool for the diagnosis of myxedema coma

Myxedema coma, a rare entity, with a reported 25%–65% mortality had no objective criteria for making the diagnosis when we began our study. We developed an objective screening tool for myxedema coma to more easily identify patients and examine the best treatment method in future prospective studies to reduce the mortality of this entity. We conducted a retrospective chart review to find all patients aged ≥18 years admitted with myxedema coma from January 1, 2005 through June 13, 2010 at Indiana University Health Methodist Hospital. On the basis of both our retrospective chart review and on literature accounts, we identified 6 criteria to diagnose myxedema coma. We identified 10 patients initially diagnosed with myxedema coma and established a control group consisting of 13 patients identified with altered mental status and increased thyroid-stimulating hormone (TSH) levels. The 6 variables we created for the screening tool were heart rate, temperature, Glasgow coma scale, TSH, free thyroxine, and precipitating factors. The screening tool has a sensitivity and specificity of about 80%. We ran a logistic regression model using the 10 study patients and 13 controls with the 6 variables. No variables alone significantly contributed to the model. However, the overall model was highly significant (P = 0.012), providing strong support for a scoring system that uses these variables simultaneously. This screening tool enables physicians to rapidly diagnose myxedema coma to expedite treatment. A more refined diagnostic tool may be used in future clinical studies designed to determine the optimal treatment

Hypothyroidism Prolongs Hospitalization Following Surgery

Objective: Each year 45 million surgical procedures are performed in the United States, and a significant number of these are performed on hypothyroid patients. Little guidance is available to determine the postoperative risk to these subjects. We hypothesized that new surgical techniques and modern anesthesia would lead to no differences in outcome between hypothyroid patients and euthyroid controls. Methods: We queried surgical databases in our health system for patients who underwent an operative procedure between January 1, 2010 and December 31, 2015 with a TSH > 10 mcU/mL or a FT4 < 0.6 ng/dL. Identified patients were matched to euthyroid controls selected for age, sex, surgical procedure, and search interval. Predicted length of hospital stay (LOS) was determined using the American College of Surgeons National Surgical Quality Improvement Program surgical risk calculator. Results: We identified 29 hypothyroid patients. The LOS was significantly longer for the hypothyroid patients compared to the predicted LOS (14.4 vs 6.7 days, P < 0.001). The LOS in the matched controls was not significantly different than their predicted LOS (9.6 vs 7.1 days, P = 0.11). Other complications were not different between the hypothyroid and control patients. Conclusions: In contrast to our initial hypothesis, hypothyroidism is associated with a 2-fold longer LOS following surgery. Hypothyroidism continues to place patients at increased surgical risk

Relacorilant, a Selective Glucocorticoid Receptor Modulator in Development for the Treatment of Patients With Cushing Syndrome, Does Not Cause Prolongation of the Cardiac QT Interval

Objective: To assess the effect of relacorilant, a selective glucocorticoid receptor modulator under investigation for the treatment of patients with endogenous hypercortisolism (Cushing syndrome [CS]), on the heart rate–corrected QT interval (QTc). Methods: Three clinical studies of relacorilant were included: (1) a first-in-human, randomized, placebo-controlled, ascending-dose (up to 500 mg of relacorilant) study in healthy volunteers; (2) a phase 1 placebo- and positive-controlled thorough QTc (TQT) study of 400 and 800 mg of relacorilant in healthy volunteers; and (3) a phase 2, open-label study of up to 400 mg of relacorilant administered daily for up to 16 weeks in patients with CS. Electrocardiogram recordings were taken, and QTc change from baseline (ΔQTc) was calculated. The association of plasma relacorilant concentration with the effect on QTc in healthy volunteers was assessed using linear mixed-effects modeling. Results: Across all studies, no notable changes in the electrocardiogram parameters were observed. At all time points and with all doses of relacorilant, including supratherapeutic doses, ΔQTc was small, generally negative, and, in the placebo-controlled studies, similar to placebo. In the TQT study, placebo-corrected ΔQTc with relacorilant was small and negative, whereas placebo-corrected ΔQTc with moxifloxacin positive control showed rapid QTc prolongation. These results constituted a negative TQT study. The model-estimated slopes of the concentration-QTc relationship were slightly negative, excluding an association of relacorilant with prolonged QTc. Conclusion: At all doses studied, relacorilant consistently demonstrated a lack of QTc prolongation in healthy volunteers and patients with CS, including in the TQT study. Ongoing phase 3 studies will help further establish the overall benefit-risk profile of relacorilant.</p

Triiodo-l-thyronine Rapidly Stimulates Alveolar Fluid Clearance in Normal and Hyperoxia-injured Lungs

Rationale: Edema fluid resorption is critical for gas exchange and requires active epithelial ion transport by Na,K-ATPase and other ion transport proteins