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Significant GH deficiency after long-term cure by surgery in adult patients with Cushing’s disease

Chair of Endocrinology, Ospedale San Luca Istituto Auxologico Italiano IRCCS, University of Milan, via Spagnoletto 3, I-20149 Milan, Italy and ¹ Department of Endocrinology, Catholic University School of Medicine, Rome, Italy

(Correspondence should be addressed to F Cavagnini; Email: cavagnini{at}auxologico.it)

Objective: Impaired GH secretion usually accompanies Cushing’s syndrome and a variable proportion of patients reportedly fail to recover normal GH secretion after successful treatment. This wide variability is most probably due to differences in the treatment (i.e. surgery and/or radiotherapy), timing of patient re-evaluation after surgery and dynamic tests employed to challenge GH secretion, and hinders a precise assessment of risk of GH deficiency after cure. The aim of the present study is to evaluate GH secretory status after long-term cure of Cushing’s disease achieved by surgery alone.

Design and methods: We studied 34 patients (27 females and 7 males, age range 21–68 years) formerly affected by Cushing’s disease. Patients were studied 2–20 years (median 3.3 years) following remission of hypercortisolism; all patients underwent transsphenoidal surgery with the removal of an ACTH-secreting adenoma; repeat pituitary surgery for relapse was performed in two patients while bilateral adrenalectomy was necessary in two patients. In all subjects, the GH response to GHRH+arginine stimulation was evaluated. At the time of testing, 13 patients were still on steroid replacement therapy.

Results: In long-term surgical remission, 22 patients (65.0%) presented subnormal GH secretion; partial GH deficiency (GH peak <16.5 µg/l) was found in 11 patients and severe GH deficiency (GH peak <9 µg/l) in another 11. Male gender and length of hypercortisolism were risk factors for postsurgical GH deficiency.

Conclusions: This study demonstrates the presence of GH deficiency in a high percentage of patients with Cushing’s disease after long-term remission of hypercortisolism obtained by surgery alone. Male gender and length of hypercortisolism are the most significant predictors of postsurgical GH deficiency. This finding is significant as it highlights that even the most favourable therapeutical course, i.e. remission achieved by surgery alone, is accompanied by impaired GH secretion. Assessment of GH secretion is therefore recommended for all patients cured from Cushing’s disease, even if not submitted to radiotherapy. Studies on the clinical impact of GH deficiency and the use of GH replacement therapy seem warranted in patients cured from Cushing’s disease.