Abstract: Congenital hyperinsulinism (CH) is the most frequent cause of persistent hypoglycemia in the newborn. Octreotide, a long-acting somatostatin analogue (SSA), 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. Furthermore, some authors have emphasized that exocrine pancreatic insufficiency is a common but under-recognized adverse reaction in adults treated with octreotide. To our knowledge, no pediatric patient with somatostatin analogue-induced pancreatic exocrine insufficiency has been reported to date.
Objective: Our aim is to report the first case of an infant with CH and exocrine pancreatic insufficiency and secondary vitamin K deficiency, associated to Octreotide therapy.
Case report: A 7 month and 3 week old male with diazoxide unresponsive diffuse CH (heterozygous autosomal dominantly mutation in the ABCC8 gene; NM_000352.4:c.357del) was found with bruising of legs, back and forearms after two months of SSA treatment onset (8.9 µg/kg/day divided into 4 daily doses). In addition to intermittent capillary blood glucose measurement, Real-time subcutaneous continuous glucose monitoring was used for glycemic control (Guardian TM Sensor 3; Medtronic Diabetes, Northridge, CA, USA). Bruises and bleeding remnants were also observed at the puncture points of the sensor. Laboratory findings identified vitamin K deficiency as the cause of the cutaneous hemorrhagic syndrome with an abnormal coagulation values [prothrombin time 117.4 seconds - Reference range (RR) 11.5-15.3 seconds-; International Normalized Ratio 9.1 - RR 0.8-1.2 -; Activated Partial Thromboplastin Time 88.4 seconds - RR 35.0-46.0 seconds-; serum fibrinogen 340 mg/dl - RR 150-380 mg/dl-] and a decrease in all vitamin K-dependent proteins (Factor II: 4% -RR 70-120 %-; Factor VII: 10 % -RR 55-170 %-; Factor IX: 8 % -RR 60-150%- and Factor X: 3% -RR 70-120 %-). Coagulopathy was resolved with vitamin K treatment (5 mg/day intravenous; 3 days). The patient was discharged without incidents. Further investigations revealed association of steatorrhea, (fat fecal quantification: 18.8 -19 g fat/day -RR < 6 g/d-) and stool fecal elastase-1: 120 mcg/g -RR > 200 mcg/g-), both markers of malabsorption. Other causes (cystic fibrosis and bacterial overgrowth syndrome) were excluded.
Conclusion: We report the first pediatric case of exocrine pancreatic insufficiency and vitamin K deficiency associated to Octreotide therapy in congenital hyperinsulinism, emphasizing the potential adverse effects and clinical relevance of the exocrine pancreatic insufficiency associated to Octreotide treatment.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology