Endocrine Abstracts (2006) 11 P135

The effects of lanreotide administration vs unilateral adrenalectomy on disease activity in gip-dependent cushing’s syndrome

M Robaczyk, B Krzyzanowska-Swiniarska, G Kulig & K Pilarska

Pomeranian Medical Academy (PAM), Department of Endocrinology, Hypertension and Metabolic Diseases, Szczecin, Poland.

GIP-dependent Cushing’s syndrome (CS) is caused by ectopic expression in adrenal cortex of gastric inhibitory peptide (GIP) receptors coupled to steroidogenesis, which leads to postprandial increases of cortisol (food-dependent CS). In a few cases a transient effect of short-acting octreotide on cortisol levels has been shown, but bilateral adrenalectomy is still thought to be a definitive treatment.

We report on a case of a 45-year old woman with bilateral macronodular adrenal hyperplasia and clinically apparent CS, chronically treated for several years with aminogluthetimide (A). After we had observed that pre-treatment with octreotide s.c. prevents an increase in cortisol levels during OGTT, we administered a single dose (30 mg i.m.) of long-acting lanreotide (Ipsen Biotech) after 4 weeks’ withdrawal of A. Plasma pre- and postprandial levels (90 min.) of intact GIP and cortisol (6-point profile), as well as blood glucose and urinary free cortisol (UFC) were measured on day 0, 2 and 8. Intact GIP levels expectedly reflected normal fasting and postprandial values (range 6–55 pmol/l) and were correlated with the corresponding cortisol levels (r=0.59, P=0.004) on day 0. Mean cortisol levels were moderately suppressed on day 2 (60.4±12.7 vs. 43.7±10.2 μg/dl; P<0.01), but rose again on day 8 (49.8±10.4 μg/dl), which was accompanied by a significant suppression of postprandial GIP increases. However, lanreotide induced recurrent postprandial hyperglycaemia (up to 11.1 mmol/l) and failed to control clinical symptoms (hypertension, leg oedema). Unilateral adrenalectomy performed 6 months later did not influence pre- and postprandial intact GIP levels, but in turn normalised UFC during the first 4 weeks postoperatively (50.0–55.7 μg/24 hrs). After 6 weeks UFC increased again to supra-normal values, which necessitated continuation of treatment with A.

Conclusion: Although pathophysiologically justified, a single lanreotide administration in GIP-CS does not seem to effectively control hypercortisolism and it may worsen glucose metabolism. Short-term results of unilateral adrenalectomy are more convincing, but its curative effect may be transient.

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