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

Abstract

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 triglycerides) 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 mg/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 mg/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 mg/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 mg/l vs 20.1^2.4 mg/l vs 31.1^2.5 mg/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.European Journal of Endocrinology 154 659-666

Prevalence of GH deficiency in cured acromegalic patients: impact of different previous treatments

“…These results are in keeping with the held concept that RT may induce GHD in a quite high percentage of cured acromegalic patients (2-5), but for the first time states that also S alone may induce a deterioration of the residual GH secretion. In fact, to date, only scarce and contradictory data are available on the prevalence of GHD in only operated acromegalic patients (4,(7)(8)(9). In terms of possible prognostic factors, it seems that the presence of a macroadenoma and higher GH levels at the time of diagnosis together with the concomitant existence of other pituitary failures (in particular multiple deficiencies) might be the best candidates to predict GHD in the population of patients successfully treated for acromegaly.…”

“…Regarding acromegalic patients, it is known that RT may induce GHD in about 30-50% of treated patients (3)(4)(5) and radiosurgery in about 6% (6). On the contrary, few and contrasting studies conducted on small series of patients are present in the literature about the impact of transsphenoidal surgery (S) alone (4,(7)(8)(9). In a previous report, our group demonstrated that in a large series of acromegalic patients cured by neurosurgery alone, both GH and IGF-1 levels significantly decreased during a long-term follow-up, suggesting the occurrence of GHD at least in some of them (10).…”

GH deficiency in patients after cure of acromegaly by surgery alone

“…The result is that less attention is given to possible postoperative GH deficiency (GHD). Indeed, there have been few reports on GHD after radiotherapy for acromegaly (3)(4)(5)(6) and there have only been few and contradictory studies conducted on small numbers of patients of GHD after TSS alone (7)(8)(9)(10). Therefore, a large number of patients undergoing surgery who were later deemed cured by the recent stringent criteria for cure of acromegaly were studied to determine the characteristics of GH-deficient patients with prior acromegaly.…”

Ghrelin in Pathological Conditions

“…Treatment of acromegaly, which consists of administration of Growth Hormone Receptor (GHR) antagonists [62][63][64][65][66][67][68][69][70], somatostatin analogues (octreotide and lanreotide) [50,58,[71][72][73] or surgical treatment [50,57,58,74], results in diverse ghrelin levels. Treatment with octreotide has successfully suppressed previously elevated GH and IGF-1 levels [50, [71][72][73] and ghrelin secretion [45] in acromegalics.…”

“…Treatment with octreotide has successfully suppressed previously elevated GH and IGF-1 levels [50, [71][72][73] and ghrelin secretion [45] in acromegalics. Surgical transsphenoidal removal of a GH-secreting tumor has also been used in order to eliminate the cause of GH excess and is followed by an improvement of insulin sensitivity [50, 57,74]. Ghrelin levels have been reported to increase after successful transsphenoidal surgery followed by normalization of GH and IGF-1 [50, 57,58], suggesting a preoperative ghrelin suppression caused by GH/IGF-1 hypersecretion.…”