A Case Series of Patients With Central Hypothyroidism From Oxcarbazepine Therapy.

Many medications can impact thyroid function. Antiseizure medications have been shown to disrupt thyroid function in adults, but information is limited about how antiseizure medications may affect thyroid function in children. Oxcarbazepine is an analog of carbamazepine designed to minimize effects from the hepatic P450 metabolic enzymes. We have found that in the pediatric population, serum free thyroxine is reduced and thyroid-stimulating hormone concentrations are unchanged in patients taking oxcarbazepine with the mechanism thus being central hypothyroidism.

PDE5 inhibition alleviates functional muscle ischemia in boys with Duchenne muscular dystrophy.

OBJECTIVE: To determine whether phosphodiesterase type 5 (PDE5) inhibition can alleviate exercise-induced skeletal muscle ischemia in boys with Duchenne muscular dystrophy (DMD). METHODS: In 10 boys with DMD and 10 healthy age-matched male controls, we assessed exercise-induced attenuation of reflex sympathetic vasoconstriction, i.e., functional sympatholysis, a protective mechanism that matches oxygen delivery to metabolic demand. Reflex vasoconstriction was induced by simulated orthostatic stress, measured as the decrease in forearm muscle oxygenation with near-infrared spectroscopy, and performed when the forearm muscles were rested or lightly exercised with rhythmic handgrip exercise. Then, the patients underwent an open-label, dose-escalation, crossover trial with single oral doses of tadalafil or sildenafil. RESULTS: The major new findings are 2-fold: first, sympatholysis is impaired in boys with DMD-producing functional muscle ischemia-despite contemporary background therapy with corticosteroids alone or in combination with cardioprotective medication. Second, PDE5 inhibition with standard clinical doses of either tadalafil or sildenafil alleviates this ischemia in a dose-dependent manner. Furthermore, PDE5 inhibition also normalizes the exercise-induced increase in skeletal muscle blood flow (measured by Doppler ultrasound), which is markedly blunted in boys with DMD. CONCLUSIONS: These data provide in-human proof of concept for PDE5 inhibition as a putative new therapeutic strategy for DMD. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in patients with DMD, PDE5 inhibition restores functional sympatholysis.