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Ghrelin test for the assessment of GH status in successfully treated patients with acromegaly

¹ Institutes of Endocrinology, Diabetes and Metabolism and ² Neurosurgery, University Clinical Centre, Dr Subotic 13, 11000 Belgrade, Serbia, ³ Laboratory Consilium, Belgrade, Serbia and Montenegro, ⁴ Department of Physiology, Faculty of Medicine and ⁵ Complejo Hospitalario, Endocrine Section, Santiago de Compostela University, Santiago de Compostela, Spain

(Correspondence should be addressed to V Popovic; Email: popver{at}Eunet.Yu)

Objective: Posttreatment assessment of disease activity and definition of cure of acromegaly, using measurement of GH secretion, remains problematic. Furthermore, with our efforts to achieve tight biochemical control of the disease it is foreseeable that a proportion of patients may be rendered GH deficient, thus requiring testing for GH deficiency. The aim of our study was to evaluate residual GH secretion in cured patients with acromegaly.

Design and methods: At baseline, circulating GH, IGF-I, IGFBP-3, leptin and lipid (cholesterol and tri-glycerides) levels were measured in 33 acromegalic patients nine years after treatment with surgery of whom 6 were additionally irradiated. Two tests were performed: the GH suppression test - oral glucose tolerance test (OGTT) and the GH provocation test - ghrelin test (1 µg/kg i.v. bolus) and the results were compared with 11 age- and sex-matched control subjects.

Results: According to the consensus criteria (normal IGF-I levels and post-OGTT GH nadir <1 µg/l), 21 treated acromegalic patients were cured, 6 had discordant IGF-I and GH nadir values during OGTT, while 6 had persistent acromegaly. After the GH provocative test with ghrelin (cut-off for severe GH deficiency is GH <3 µg/l), we detected 9 severely GH deficient patients (GHD) among 21 cured acromegalic patients. Mean GH peak (±S.E.M.) response to the ghrelin test in GHD acromegalics was significantly lower compared with acromegalics with sufficient GH secretory capacity and control subjects (1.2 ± 0.2 µg/l vs 20.1 ± 2.4 µg/l vs 31.1 ± 2.5 µg/l respectively, P<0.0001). Mean IGF-I and IGFBP-3 levels were not different between GHD and GH-sufficient cured acromegalics. Leptin levels and body mass index (BMI) were significantly higher in GHD male acromegalics compared with GH-sufficient male acromegalics. GHD female acromegalics tended to have higher BMIs while leptin levels were not different.

Conclusions: The assessment of residual GH secretory capacity by the GH provocation test is necessary in the long-term follow-up of successfully treated acromegalics since a large proportion of these patients are rendered GH deficient.