Congenital hyperinsulinism and panhypopituitarism: a rare combination

Author:

Patel Foram1ORCID,Darling Ginger2,Torky Ahmed3ORCID

Affiliation:

1. Department of Pediatrics, Southern Illinois University, Springfield, Illinois, USA

2. Department of Pediatrics, Division of Neonatology, Southern Illinois University, Springfield, Illinois, USA

3. Department of Pediatrics, Division of Pediatric Endocrinology and Diabetes, Southern Illinois University, Springfield, Illinois, USA

Abstract

Summary Neonatal hypoglycemia is a serious condition that can have a major impact on the growing neonatal brain. The differential diagnosis of neonatal hypoglycemia is broad and includes hyperinsulinism as well as panhypopituitarism. The FOXA2 gene has been involved in the development of the pancreas as well as the pituitary gland. Six cases have been reported thus far with FOXA2 mutations presenting with variable degrees of hypopituitarism, and only two patients had permanent hyperinsulinism; other cases have been reported with microdeletions in 20p11, the location that encompasses FOXA2, and those patients presented with a wider phenotype. A full-term female infant presented with severe hypoglycemia. Critical sampling showed an insulin of 1 mIU/mL, suppressed beta-hydroxybutyric acids, and suppressed free fatty acids. Blood glucose responded to glucagon administration. Growth hormone (GH) stimulation test later showed undetectable GH in all samples, and cortisol failed to respond appropriately to stimulation. Gonadotropins were undetectable at 1 month of life, and MRI showed ectopic posterior pituitary, interrupted stalk, hypoplastic anterior pituitary, cavum septum pellucidum, and diminutive appearance of optic nerves. Whole-exome sequencing revealed a likely pathogenic de novo c.604 T>C, p.Tyr202His FOXA2 mutation. We expand the known phenotype on FOXA2 mutations and report a likely pathogenic, novel mutation associated with hyperinsulinism and panhypopituitarism. Learning points FOXA2 has been shown to play an important role in the neuroectodermal and endodermal development. FOXA2 mutation may lead to the rare combination of hyperinsulinism and panhypopituitarism. Patients reported so far all responded well to diazoxide. Dysmorphology may be subtle, and liver functions should be monitored.

Publisher

Bioscientifica

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

Reference8 articles.

1. Recommendations from the pediatric Endocrine Society for evaluation and management of persistent hypoglycemia in neonates, infants, and children;Thornton,2015

2. Novel FOXA2 mutation causes Hyperinsulinism, Hypopituitarism with Craniofacial and Endoderm-derived organ abnormalities;Giri,2017

3. Congenital hyperinsulinism and hypopituitarism attributable to a mutation in FOXA2;Vajravelu,2018

4. Heterozygous deletion of FOXA2 segregates with disease in a family with heterotaxy, panhypopituitarism, and biliary atresia;Tsai,2015

5. Dysgenesis and dysfunction of the pancreas and pituitary due to FOXA2 gene defects;Kaygusuz,2021

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