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

• Published in: Clinical therapeutics Vol. 27; no. 2; pp. 246 - 251
• Main Authors: BOURCIGAUX, Nathalie, ARNAULT-OUARY, Gwenaëlle, CHRISTO, Rémy, PERIN, Laurence, CHARBONNEL, Bernard, LE BOUC, Yves
• Format: Journal Article
• Language: English
• Published: Belle Mead, NJ Excerpta Medica 01.02.2005
• Subjects: Aged; Biological and medical sciences; Blood Glucose - drug effects; Drug Therapy, Combination; Female; Fibroma - pathology; Glucocorticoids - administration & dosage; Glucocorticoids - therapeutic use; Human Growth Hormone - administration & dosage; Human Growth Hormone - therapeutic use; Humans; Hypoglycemia - drug therapy; Hypoglycemia - etiology; Insulin - blood; Insulin-Like Growth Factor Binding Protein 3 - metabolism; Insulin-Like Growth Factor I - metabolism; Liver Neoplasms - complications; Liver Neoplasms - secondary; Medical sciences; Pharmacology. Drug treatments; Pleural Neoplasms - pathology; Prednisone - administration & dosage; Prednisone - therapeutic use; Recombinant Proteins - administration & dosage; Recombinant Proteins - therapeutic use; Human; Langerhans islet; Somatotropin hormone; Metabolic diseases; Malignant tumor; Metastasis; Hypoglycemia; Insulin like growth factor 2; Glucocorticoid; Somatropin; Treatment; Adenohypophyseal hormone; Neurohypophyseal hormone; Advanced stage; big IGF-2; non-islet cell tumor hypoglycemia; Tumor cell; Endocrine pancreas
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2005.02.004

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