GH deficiency in patients irradiated for acromegaly: significance of GH stimulatory tests in relation to the 24 h GH secretion

Abstract

Background: Radiotherapy for pituitary adenomas frequently leads to GH deficiency (GHD). The characteristics of GH secretion in GHD induced by postoperative radiotherapy for acromegaly are not known. Hypothesis: In the long term, stimulated and spontaneous GH release is not different between patients with GHD treated by postoperative radiotherapy for acromegaly or for other pituitary adenomas. Design/subjects: We compared the characteristics of basal and stimulated GH secretion in patients with GHD, who had previously received adjunct radiotherapy after surgery for GH-producing adenomas (nZ10) vs for other pituitary adenomas (nZ10). All patients had a maximal GH concentration by insulin tolerance test (ITT) of 3 mg/l or less, compatible with severe GHD. Mean time after radiation was 17 and 18.7 years, respectively. Stimulated GH release was also evaluated by infusion of growth hormone-releasing hormone (GHRH), GHRH-arginine and arginine, and spontaneous GH by 10 min blood sampling for 24 h. Pulse analyses were performed by Cluster and approximate entropy. Outcomes: There were no differences between both patient groups in stimulated GH concentrations in any test. Spontaneous GH secretion was not different between both patient groups, including basal GH release, pulsatility and regularity. Pulsatile secretion was lost in two acromegalic and three nonacromegalic patients. Insulin-like growth factor-I (IGF-I) was below K2 S.D. score in nine patients in each group. Conclusion: Acromegalic patients treated by surgery and postoperative radiotherapy with an impaired response to the ITT do not differ, in the long term, in GH secretory characteristics from patients treated similarly for other pituitary tumors with an impaired response to the ITT. The ITT (or the GHRHarginine test) is therefore reliable in establishing the diagnosis of GHD in patients treated for acromegaly by surgery and radiotherapy.

GH deficiency in patients after cure of acromegaly by surgery alone

“…Little is known about the effects of GH replacement therapy in those who develop GHD after cure of acromegaly and reported data have been contradictory (5,20,22,23). van der Klaauw et al (23) recently concluded that the beneficial effects of GH replacement in patients with GHD during treatment of acromegaly are limited.…”

“…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.…”

Gamma knife stereotactic radiosurgery for acromegaly

“…As the cure criteria for acromegaly have become stricter, the space between cure on one side and GH deficiency (37,38) on the other has become narrow. Although subgroup analysis of the data presented by Holdaway et al (39) show that the presence of hypopituitarism in acromegaly patients does not have any significant influence on survival, increased mortality has been associated with hypopituitarism in general (40).…”

Cardiac manifestations of GH deficiency after treatment for acromegaly: a comparison to patients with biochemical remission and controls

“…Treatment of acromegaly, however, can result in GHD in some patients, especially after previous radiotherapy (5). Several parameters of cardiac morphology and function were altered in our patients with GHD after acromegaly.…”

“…However, surgical treatment of GH excess followed by radiotherapy can result in GH deficiency (GHD) (5) and GHD per se is also associated with cardiomyopathy. Cardiac manifestations of GHD include a decrease in LV mass and LV ejection fraction (LVEF) (6)(7)(8)(9)(10)(11)(12), which is correlated to the severity of GHD (8).…”