THU182 Widening The Spectrum Of ABCC8-related Disease: Insulin-mediated Pseudoacromegaly
Authors: Roza Machado Iza Franklin , Mendonca Berenice Bilharinho , Latronico Ana Claudia , Nishi Mirian Yumie , Gomes Larissa Garcia 
Published: October 2023

Disclosure: I.F. Machado: None. B.B. Mendonca: None. A. Latronico: None. M.Y. Nishi: None. L.G. Gomes: None.

Introduction: Insulin-mediated pseudoacromegaly is a rare condition characterized by acromegaloid phenotype without excessive GH secretion in the context of severe hyperinsulinemia. Case report: A 10.5 years old girl with tall stature, obesity, acanthosis nigricans, neurosensorial hearing deficiency and acromegaloid features was referred for clinical investigation. She was born of non-consanguineous parents, full-term, with normal birth weight and stature. She had no history of neonatal hypoglycemia or in infancy. At six years of age, she presented marked accelerated growth velocity and weight gain resulting in bilateral slipped femoral epiphysis. She developed thelarche at 7 years old, and was treated with gonadotropin releasing hormone agonist (GnRHa) from 8-10.5 years. Hearing deficiency was diagnosed at 7 years of age. Her family history was remarkable for paternal sudden cardiac death at age 35. At physical examination, she had an acromegaloid facial appearance with a prominent forehead and jaw, large hands and feet, and severe acanthosis nigricans in neck and axillae. Her weight and height were 99.5 kgs (Z 8.8) and 170 cm (Z 4.6), respectively; target height was 1.66 m (Z 0,72) and BMI was 34.4 (Z 3.5). Her breast and pubic hair development were Tanner stage IV. Laboratory exams showed normal IGF-1 and random GH levels. There was an abnormal response of GH (2.63 ng/mL) following an oral glucose tolerance test (OGTT), considered as false positive in the context of obesity and puberty. Her brain magnetic resonance was normal. She had a hemoglobin glycated of 6.1% and very high basal insulin levels of 98 µUI/mL with a normal glucose value of 81 mg/dL and OGTT-120 minutes insulin levels &gt; 1000 µUI/mL with glucose of 113 mg/dL. Exome sequencing analysis showed a heterozygous missense ABCC8 variant c.622G&gt;A p.(Glu208Lys), located in an exonic hotspot, and allele frequency absent from gnomAD databases. The ACMG classified this variant as pathogenic. Pseudoacromegaly, a heterogeneous condition, is caused by multiple genetic and pathophysiological backgrounds. In insulin-mediated pseudoacromegaly, the defects are mainly associated with postreceptor insulin signaling and action. We described a new type of hyperinsulinemic pseudoacromegaly caused by a mutation in the ABCC8 gene, which encodes the sulfonylurea receptor, a member of the K(ATP) channel superfamily. This gene is associated with congenital hyperinsulinemia causing hypoglycemia, generally when in homozygous state. This clinical report illustrates a new phenotype associated with ABCC8 mutation, and identifies a new genetic cause of hyperinsulinemic pseudoacromegaly. Conclusion: We described a patient with insulin-mediated pseudoacromegaly associated with neurosensorial hearing deficiency caused by a dominant variant in the ABCC8 gene, defining a new genetic cause of this intriguing disorder.

Presentation: Thursday, June 15, 2023