Sirolimus-Induced Hepatitis in Two Patients with Hyperinsulinemic Hypoglycemia
Journal Title: Journal of Clinical Research in Pediatric Endocrinology - Year 2018, Vol 10, Issue 3
Abstract
Sirolimus has been reported to be effective in the treatment of the diffuse form of congenital hyperinsulinism (CHI), unresponsive to diazoxide and octreotide, without causing severe side effects. Two newborns with CHI due to homozygous ABCC8 gene mutations were started on sirolimus aged 21 and 17 days, due to lack of response to medical treatment. A good response to sirolimus was observed. At follow-up after ten and two months of treatment, liver enzymes were found to be increased [serum sirolimus level 1.4 ng/mL (normal range: 5-15), aspartate aminotransferase (AST): 298U/L, alanine aminotransferase (ALT): 302U/L and serum sirolimus level: 9.9 ng/mL, AST: 261U/L, ALT: 275U/L, respectively]. In Case 1, discontinuation of the drug resulted in normalization of liver enzymes within three days. Two days after normalization, sirolimus was restarted at a lower dose, which resulted in a repeated increase in transferases. In Case 2, a reduction of sirolimus dose caused normalization of liver enzymes within ten days. When the dose was increased, enzymes increased within three days. Sirolimus was discontinued in both cases. The rapid normalization of liver enzyme levels after sirolimus withdrawal or dose reduction; elevation of transaminases after restart or dose increase and rapid normalization after sirolimus withdrawal were findings strongly suggestive of sirolimus-induced hepatitis. To the best of our knowledge, this is the first report of sirolimus-induced hepatitis in CHI. Sirolimus is a promising drug for CHI patients who are unresponsive to medical treatment, but physicians should be vigilant for adverse effects on liver function.
Authors and Affiliations
Belma Haliloğlu, Heybet Tüzün, Sarah E. Flanagan, Muhittin Çelik, Avni Kaya, Sian Ellard, Mehmet Nuri Özbek
Under-recognized Hypoparathyroidism in Thalassemia
Objective: Symptomatic hypoparathyroidism [symptomatic hypocalcemia without elevated serum parathyroid hormone (PTH)] in patients with thalassemia is relatively rare. Asymptomatic mild hypocalcemia without elevated PTH,...
Congenital Hyperinsulinism and Evolution to Sulfonylurearesponsive Diabetes Later in Life due to a Novel Homozygous p.L171F ABCC8 Mutation
Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infants and children. Recessive inactivating mutations in the ABCC8 and KCNJ11 genes account for approximately 50% of all CHI cases....
Wrist Circumference and Frame Size Percentiles in 6-17-Year-Old Turkish Children and Adolescents in Kayseri
Objective: The aim of the current study was to provide wrist circumference (WrC) and body frame size (height/WrC) percentile values in Turkish children and adolescents aged 6-17 years. Methods: In this cross-sectional s...
Genetic and Clinical Characteristics of Patients with Vitamin D Dependent Rickets Type 1A
Objective: Vitamin D dependent rickets type 1A (VDDR1A) is an autosomal recessive disorder caused by mutations in the 1α-hydroxylase gene (CYB27B1). As it may be confused with nutritional rickets and hypophosphatemic ric...
Plasma Amino-Terminal Propeptide of C-Type Natriuretic Peptide Concentration in Normal-Weight and Obese Children
Objective: In studies on the relationship between amino-terminal propeptide of C-type natriuretic peptide (NT-proCNP) concentration and height velocity in children, CNP has been implicated as an emerging new growth marke...