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

Abstract

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 ACTHsecreting 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 GHRHCarginine 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 mg/l) was found in 11 patients and severe GH deficiency (GH peak !9 mg/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.

Metabolic comorbidities in Cushing's syndrome

“…GHD is present in adult CD patients after long-term remission even if treated only with transsphenoidal neurosurgery. Male gender and the duration of disease were the most relevant predictors of GH/IGF1 axis disturbances after cure of CD (150).…”

Gender-dependent changes in haematological parameters in patients with Cushing's disease before and after remission

“…In keeping, erythropoiesis may be impaired in patients with GH deficiency (27) and haemoglobin levels, reticulocyte counts and erythropoietin concentrations increase on replacement therapy with rhGH (28,29). Patients with Cushing's disease are notably GH deficient (30, 31) and we had previously reported that defects in the GH-IGF1 axis are more persistent in men in remission after transsphenoidal surgery (15), possibly again connected to persistent hypogonadism. In fact, all male patients tested for GH deficiency after surgery were GH deficient compared with only 2/3 of women in remission.…”

Somatostatin and somatostatin receptors in Cushing's disease

“…Cushing's syndrome, in a significant percentage of patients even after long-term remission of hypercortisolism obtained by surgery alone [64]. In this respect, the potent suppression of circulating GH and IGF-I levels by SOM230 [65] should be taken into account as well, in particular in patients who are already significantly catabolic.…”