Spontaneous Resolution of Congenital Hyperinsulinism With Octreotide Therapy

AbstractBackgroundCongenital hyperinsulinism (CH) is the most frequent cause of persistent hypoglycemia in the newborn. Octreotide, a long-acting somatostatin receptor analog (SSRA), is a second line treatment for diazoxide unresponsive CH patients. Although it has been found to be a safe and effective treatment, long-term benefits and side effects, have not been thoroughly evaluated.Case presentationSome authors have indicated that exocrine pancreatic insufficiency (EPI) is a common but under-recognized adverse reaction in adults treated with octreotide. However, no pediatric patient with SSRA-induced EPI has been reported to date. Here we report a case of an infant with diazoxide unresponsive, diffuse CH, caused by a heterozygous pathogenic paternally inherited mutation in the ABCC8 gene (NM_000352.4:c.357del), that developed exocrine pancreatic insufficiency and secondary vitamin K deficiency associated to chronic octreotide therapy.ConclusionsWe point out the atypical clinical onset with a cutaneous hemorrhagic syndrome, emphasizing the clinical relevance of this potential side effect.

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Congenital Hyperinsulinism due to a Compound Heterozygous ABCC8 Mutation with Spontaneous Resolution at Eight Weeks

Hormone Research in Paediatrics ◽

10.1159/000284394 ◽

2010 ◽

Vol 73 (4) ◽

pp. 287-292 ◽

Cited By ~ 11

Author(s):

Anitha Kumaran ◽

Ritika R. Kapoor ◽

Sarah E. Flanagan ◽

Sian Ellard ◽

Khalid Hussain

Keyword(s):

Spontaneous Resolution ◽

Compound Heterozygous ◽

Congenital Hyperinsulinism

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Long-Term Follow-Up of Children With Congenital Hyperinsulinism on Octreotide Therapy

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2014-1866 ◽

2014 ◽

Vol 99 (10) ◽

pp. 3660-3667 ◽

Cited By ~ 30

Author(s):

Huseyin Demirbilek ◽

Pratik Shah ◽

Ved Bhushan Arya ◽

Louise Hinchey ◽

Sarah E. Flanagan ◽

...

Keyword(s):

Congenital Hyperinsulinism ◽

Long Term Follow Up ◽

Octreotide Therapy

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Clinical characteristics and phenotype–genotype analysis in Turkish patients with congenital hyperinsulinism; predominance of recessive KATP channel mutations

Acta Endocrinologica ◽

10.1530/eje-14-0045 ◽

2014 ◽

Vol 170 (6) ◽

pp. 885-892 ◽

Cited By ~ 7

Author(s):

Huseyin Demirbilek ◽

Ved Bhushan Arya ◽

Mehmet Nuri Ozbek ◽

Aysehan Akinci ◽

Murat Dogan ◽

...

Keyword(s):

Birth Weight ◽

Clinical Characteristics ◽

Genetic Diagnosis ◽

Pathogenic Mutation ◽

Early Age ◽

Congenital Hyperinsulinism ◽

Hyperinsulinaemic Hypoglycaemia ◽

Genotype Information ◽

Octreotide Therapy ◽

Turkish Patients

ObjectiveCongenital hyperinsulinism (CHI) is the commonest cause of hyperinsulinaemic hypoglycaemia in the neonatal, infancy and childhood periods. Its clinical presentation, histology and underlying molecular biology are extremely heterogeneous. The aim of this study was to describe the clinical characteristics, analyse the genotype–phenotype correlations and describe the treatment outcome of Turkish CHI patients.Design and methodsA total of 35 patients with CHI were retrospectively recruited from four large paediatric endocrine centres in Turkey. Detailed clinical, biochemical and genotype information was collected.ResultsDiazoxide unresponsiveness was observed in nearly half of the patients (n=17; 48.5%). Among diazoxide-unresponsive patients, mutations in ABCC8/KCNJ11 were identified in 16 (94%) patients. Among diazoxide-responsive patients (n=18), mutations were identified in two patients (11%). Genotype–phenotype correlation revealed that mutations in ABCC8/KCNJ11 were associated with an increased birth weight and early age of presentation. Five patients had p.L1171fs (c.3512del) ABCC8 mutations, suggestive of a founder effect. The rate of detection of a pathogenic mutation was higher in consanguineous families compared with non-consanguineous families (87.5 vs 21%; P<0.0001).Among the diazoxide-unresponsive group, ten patients were medically managed with octreotide therapy and carbohydrate-rich feeds and six patients underwent subtotal pancreatectomy. There was a high incidence of developmental delay and cerebral palsy among diazoxide-unresponsive patients.ConclusionsThis is the largest study to report genotype–phenotype correlations among Turkish patients with CHI. Mutations in ABCC8 and KCNJ11 are the commonest causes of CHI in Turkish patients (48.6%). There is a higher likelihood of genetic diagnosis in patients with early age of presentation, higher birth weight and from consanguineous pedigrees.

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Clinical Efficacy Evaluation of Sirolimus in Congenital Hyperinsulinism

International Journal of Endocrinology ◽

10.1155/2020/7250406 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Somayyeh Hashemian ◽

Reza Jafarzadeh Esfehani ◽

Siroos Karimdadi ◽

Rahim Vakili ◽

Daniel Zamanfar ◽

...

Keyword(s):

Genetic Disorder ◽

Mammalian Target Of Rapamycin ◽

Gene Mutations ◽

Therapeutic Effects ◽

Congenital Hyperinsulinism ◽

Efficacy Evaluation ◽

Abcc8 Gene ◽

Octreotide Therapy ◽

One Year

Background. Congenital hyperinsulinism (CHI) is a rare and life-threatening genetic disorder. Sirolimus as a mammalian target of rapamycin inhibitor may be helpful in patients with CHI who do not respond well to other treatments including diazoxide and octreotide. However, the safety and efficacy of this therapy are still unclear. This study aimed to evaluate the potential therapeutic effects of sirolimus in CHI patients with mutations in the ABCC8 and KCNJ11 genes. Methods. During the period of this follow-up study, every child with a confirmed diagnosis of unresponsive CHI underwent genetic evaluation. Among those who had positive genetic testing, six families agreed to participate in this study. The participants were evaluated for ABCC8, KCNJ11, or HNF4α gene mutations by polymerase chain reaction (PCR) sequencing. The participants who were unresponsive to diazoxide and octreotide therapy received 0.5 mg/m2/d of sirolimus, and the dose was gradually increased until a serum concentration of 5–15 ng/ml was achieved. Then, the participants were followed up for any possible complications. Results. Among the study participants, only one neonate was completely free of hypoglycemia after one year of follow-up, whereas three others experienced a partial reduction in hypoglycemic episodes over six months. One neonate underwent pancreatectomy despite receiving sirolimus. The oldest participant with a mutation in the ABCC8 gene responded well to sirolimus therapy after surgery and remained asymptomatic for 18 months. Conclusion. This study suggested that sirolimus therapy needs further evaluation to determine which patients will benefit the most. The genetic basis of CHI may have possible implications for determining the patient’s response.

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