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J Endocr Soc. 2019 Feb 7;3(4):699-713. doi: 10.1210/js.2018-00417. eCollection 2019 Apr 1.

Sirolimus: Efficacy and Complications in Children With Hyperinsulinemic Hypoglycemia: A 5-Year Follow-Up Study.

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Endocrinology Department, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
Section of Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme, University College London Great Ormond Street Hospital Institute of Child Health, London, United Kingdom.
Histopathology Department, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, United Kingdom.



Sirolimus, a mammalian target of rapamycin inhibitor, has been used in congenital hyperinsulinism (CHI) unresponsive to diazoxide and octreotide. Reported response to sirolimus is variable, with high incidence of adverse effects. To the best of our knowledge, we report the largest group of CHI patients treated with sirolimus followed for the longest period to date.


Retrospective study of CHI patients treated with sirolimus in a tertiary service and review of the 15 publications reporting CHI patients treated with mammalian target of rapamycin inhibitors. Comparison was made between the findings of this study with those previously published.


Twenty-two CHI patients treated with sirolimus were included in this study. Twenty showed partial response, one showed complete response, and one was unresponsive. Five of the partially/fully responsive patients had compound heterozygous ABCC8 mutations and five had heterozygous ABCC8 mutations. A total of 86.4% (19/22) developed complications, with infection being the most frequent (17/22), of which 11 were of bacterial etiology, followed by persistent diarrhea (3/22) and hyperglycemia (2/22). Seventeen patients stopped sirolimus: 13 from infections; 2 from hyperglycemia; and 2 from alternative treatment (lanreotide) response. Compared with data previously published, our study identified a higher number of partially sirolimus-responsive CHI cases, although the high rate of complications while on this medication limited its potential usefulness.


Sirolimus candidates must be carefully selected given its frequent and potentially life-threatening side effects. Its use as a short-term, last-resort therapy until normoglycemia is achieved with other agents such as lanreotide could avoid pancreatectomy. Further studies evaluating the use of sirolimus in patients with CHI are required.


ABCC8 gene; hyperinsulinemic hypoglycemia; mTOR inhibitors; side effects; sirolimus

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