Somatostatin analogs as a treatment for congenital hyperinsulinism

Congenital hyperinsulinism (CHI) is a functional disorder of insulin secretion. The long-term outcome of infants with CHI depends on the prevention of hypoglycemic episodes to avoid the high risk of permanent brain damage including psychomotor retardation, seizures, and learning disabilities. In its diffuse severe form, it is traditionally treated with near-total pancreatectomy. However, even after this procedure normoglycemia is not always achieved, and many patients develop diabetes mellitus at puberty. Human β-cells show a high expression of somatostatin receptors, particularly type 2 (SSTR2), and somatostatin directly suppresses insulin release. It was therefore hypothesized that somatostatin could be used as a therapeutic agent in CHI. This hypothesis was successfully tested as early as 1977, but clinical implementation was limited by the short half-life of native somatostatin. With the advent of the first somatostatin analog, octreotide, in the 1980's, a conservative approach to the treatment of CHI was developed, using octreotide administered subcutaneously by injection or through a pump, in combination with other medications (diazoxide, glucagon), as well as frequent or continuous feeding by means of a gastrostomy tube. Using this approach it is possible to achieve euglycemia, normal growth and good neurodevelopmental outcome, at least in some patients' groups. Potential side effects of treatment with somatostatin include cholelithiasis, impaired growth, and impaired thyroid function. However, the only side effect we usually encounter is asymptomatic cholelithiasis. Despite our success with the conservative approach, the treatment may pose a huge burden and be stressful for the patients and families. Recently, we and others reported successful treatment with the long -acting somatostatin analogs lanreotide acetate and octretide LAR, administered once-monthly, and resulting in simplification of daily care and improved quality of life.