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Jelmer M van Lieshout, Christiaan F Mooij, A. S Paul van Trotsenburg, and Nitash Zwaveling-Soonawala

Objective: Comparison of studies on remission rates in pediatric Graves’ disease is complicated by lack of uniformity in treatment protocols, remission definition, and follow-up duration. We performed a systematic review on remission rates in pediatric Graves’ disease and attempted to create uniformity by recalculating remission rates based on an intention-to-treat analysis.

Methods: PubMed and Embase were searched in August 2020 for studies on patients with Graves’ disease (i) 2 to 18 years of age, (ii) initially treated with methimazole or carbimazole for at least 18 months, (iii) with a follow-up duration of at least one year after cessation of methimazole or carbimazole. All reported remission rates were recalculated using an intention-to-treat analysis.

Results: Of 1,890 articles, 29 articles consisting of 24 patient cohorts, were included with a total of 3,057 patients (82.6% female). Methimazole or carbimazole was initially prescribed in 2,864 patients (93.7%). Recalculation based on intention-to-treat analysis resulted in an overall remission rate of 28.8% (829/2,880). Pooled remission rates based on treatment duration were 23.7%, 31.0%, 43.7%, and 75% after respectively 1.5-2.5 years, 2.5-5 years, 5-6 years (two studies), and 9 years (single study) treatment duration. Occurrence of adverse events was 419 in 2,377 patients (17.6%), with major side effects in 25 patients (1.1%).

Conclusions: Using a standardized calculation the overall remission rate in methimazole treated pediatric GD is 28.8%. A few small studies indicate that longer treatment increases the remission rate. However, evidence is limited and further research is necessary to investigate the efficacy of longer treatment durations.

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Jeanne Margot Kroese, Christiaan F Mooij, Marinette van der Graaf, Ad R M M Hermus, and Cees J Tack

Context

Patients with congenital adrenal hyperplasia (CAH) are chronically treated with supraphysiological doses of glucocorticoids, which are known to induce insulin resistance. Thiazolidinediones might reverse this effect and improve insulin sensitivity.

Objectives

To assess insulin sensitivity in CAH patients and the effect of pioglitazone treatment on insulin sensitivity in CAH patients. Secondary objectives were the effects of treatment with pioglitazone on blood pressure, body fat distribution, lipid, and steroid profiles.

Design

Randomized placebo controlled crossover trial.

Participants

Twelve CAH patients and 12 body mass and age-matched control subjects.

Intervention

Sixteen-week treatment with pioglitazone (45 mg/day) or placebo.

Main outcome measure

Insulin sensitivity measured by euglycemic clamp and oral glucose tolerance test. Further measures were 24-h blood pressure profiles, body fat distribution measured by magnetic resonance imaging, dual energy x-ray absorptiometry (DEXA) and bioimpedance procedures, liver fat by magnetic resonance spectroscopy, lipid, and steroid profiles.

Results

CAH patients were insulin resistant compared with healthy controls. Treatment with pioglitazone significantly improved insulin sensitivity in CAH patients (glucose infusion rate (GIR) from 28.5±11.6 to 38.9±11.0 μmol/kg per min, P=0.000, GIR in controls 46.2±23.4 μmol/kg per min, P<0.05 versus CAH). Treatment with pioglitazone decreased blood pressure (systolic: 124.0±13.6 vs 127.0±14.9 mmHg, P<0.001, diastolic: 72.8±11.5 vs 77.4±12.6 mmHg, P<0.001). No changes in body fat distribution, lipid, and steroid profiles were observed.

Conclusions

CAH patients are insulin resistant compared with matched control subjects. Treatment with pioglitazone improves insulin sensitivity and decreases blood pressure in CAH patients.