Treatment of hypoglycemia using combined glucocorticoid and recombinant human growth hormone in a patient with a metastatic non-islet cell tumor hypoglycemia

Abstract

Background: Non-islet cell tumor hypoglycemia(NICTH) is a rare cause of recurrent hypoglycemia. It has been associated with the tumoral overproduction of high-molecular-weight insulin-like growth factor (IGF)-2 ("big IGF-2"). Big IGF-2 suppresses growth hormone (GH) biosynthesis and impairs the storage of IGFs by suppressing the formation of the GH-dependent ternary complexes containing IGF, IGF binding protein 3 (IGFBP-3), and acid-labile subunit (ALS). Thus, big IGF-2 exerts hypoglycemic activity. The only effective treatment of NICTH is surgery. However, in inoperable patients with NICTH, treatment of hypoglycemia may require high doses of glucocorticoid (30-60 mg/d [0.5-1.0 mg/kg x d]) or recombinant human GH (rhGH) (2.6-12.0 mg/d [0.043-0.20 mg/kg x d]).

Objective: We hypothesized that the association of low doses of glucocorticoid and rhGH could be an effective therapy for hypoglycemia in inoperable patients with NICTH.

Methods: A 3-phase treatment regimen was conducted in an inoperable 67-year-old woman with NICTH. Decreasing dosages of prednisone (from 30 to 10 mg/d [from 0.50 to 0.15 mg/kg x d]), followed by decreasing doses of rhGH (from 2.6 to 1.3 mg/d [from 0.043 to 0.016 mg/kg x d]), and then a combination of the lowest doses of each, were tested. Glucose, insulin, and IGF monitoring were performed at each of the 3 treatment phases.

Results: Fasting plasma glucose (FPG) level was normalized and the IGF-1 concentration was increased with high-dose prednisone monotherapy (30 mg/d [0.50 mg/kg x d]) or rhGH (2.6 mg/d [0.043 mg/kg x d]). Prednisone monotherapy partially suppressed big IGF-2 secretion, and rhGH monotherapy acted on IGFBP-3 and ALS concentrations. FPG level was normalized with combined low-dose prednisone and rhGH, and this combination was more effective than high-dose monotherapy with either drug in reestablishing the IGF system. No adverse effects (AEs) were found.

Conclusions: In this patient with inoperable NICTH, the combination of low doses of prednisone and rhGH was a successful long-term therapy for hypoglycemia, with no AEs. This therapy could be proposed for use in patients with inoperable NICTH.