Insulin resistant diabetes mellitus in SHORT syndrome: case report and literature review.
Endocr J
; 68(1): 111-117, 2021 Jan 28.
Article
em En
| MEDLINE
| ID: mdl-32879144
ABSTRACT
SHORT syndrome is a rare developmental disorder frequently associated with growth failure and insulin resistant diabetes mellitus (IRDM). Since GH has a diabetogenic effect, GH therapy has been regarded as a contraindication. We observed a Brazilian girl with SHORT syndrome who received GH therapy from 4 6/12 years of age for SGA short stature. GH dosage was increased from 0.23 to 0.36 mg/kg/week, but statural response to GH therapy remained poor. Her blood HbA1c level, though it remained 5.5-6.0% in childhood, began to elevate with puberty and increased to 9.2% at 10 6/12 years of age, despite the discontinuation of GH therapy at 9 11/12 years of age. Laboratory studies indicated antibody-negative IRDM. She was treated with metformin and canagliflozin (a sodium glucose co-transporter 2 (SGLT2) inhibitor), which ameliorated overt diurnal hyperglycemia and mild nocturnal hypoglycemia and reduced her blood HbA1c around 7%. Whole exome sequencing revealed a de novo heterozygous pathogenic variant (c.1945C>Tp.(Arg649Trp)) in PIK3R1 known as the sole causative gene for SHORT syndrome. Subsequent literature review for patients with molecularly confirmed SHORT syndrome revealed the development of IRDM in 10 of 15 GH-untreated patients aged ≥12 years but in none of three GH-treated and six GH-untreated patients aged ≤10 years. These findings imply a critical role of pubertal development and/or advanced age rather than GH therapy in the development of IRDM, and a usefulness of SGLT2 inhibitor in the treatment of IRDM.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
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Diabetes Mellitus
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Transtornos do Crescimento
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Hipercalcemia
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Doenças Metabólicas
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Nefrocalcinose
Tipo de estudo:
Diagnostic_studies
Limite:
Child
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Female
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Humans
País como assunto:
America do sul
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Brasil
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article