Growth hormone status following treatment for Cushing's syndrome
Authors: Hughes  , Lissett  , Shalet  
Published: March 2003

OBJECTIVEBoth pituitary surgery and radiotherapy for Cushing's disease can lead to growth hormone (GH) deficiency. Studies to date have, however, described the incidence of impaired GH secretion and not the incidence of severe GH deficiency following treatment of Cushing's disease. Furthermore, following cure of Cushing's disease and resolution of hypercortisolaemia, recovery of GH secretory status is seen, thus creating uncertainty as to the persistence of any documented GH deficiency. This study has two aims; to determine the incidence of severe persistent GH deficiency following treatment of Cushing's disease and to assess the time scale of any recovery of GH secretory status following surgical cure of Cushing's disease.DESIGN AND PATIENTSThe case notes of 37 patients either cured or in clinical and biochemical remission following treatment for Cushing's syndrome were reviewed to determine the incidence of severe GH deficiency. Of 34 patients with Cushing's disease, 20 were treated by pituitary surgery, and 14 with radiotherapy. Three patients with adrenal adenomas underwent unilateral adrenalectomy.MEASUREMENTSGH secretory status was assessed by provocative testing using an insulin tolerance test (ITT, 85% of all tests), glucagon stimulation test (GST) or arginine stimulation test (AST).RESULTSThirty‐six percent (5/14) of radiotherapy treated patients demonstrated severe GH deficiency at a mean time of 99 months following remission. Fifty‐nine percent (10/17) of surgically treated patients assessed in the two years following remission demonstrated severe GH deficiency, whilst only 22% (2/9) of patients assessed beyond two years following remission demonstrated severe GH deficiency. This latter cohort is biased, with patients in whom severe GH deficiency had been demonstrated on earlier tests being over‐represented. It is more accurate to estimate the incidence of persistent severe GH deficiency following surgically induced remission of Cushing's disease by incorporating data from patients in whom original testing demonstrated adequate GH reserve. Collating such data, 13% (2/15) of patients had persistent severe GH deficiency. Across all time periods five surgically treated patients demonstrated recovery of GH secretory status over a median time course of 19 months.In the surgically treated cohort, seven (35%) patients had anterior pituitary hormone deficits other than GH deficiency: 14% (2/14) of patients with normal GH secretory status at the last assessment, 83% (5/6) of patients with severe GHD at the last assessment. Of the 5 patients who demonstrated recovery of GH secretory status 40% (2) had additional anterior pituitary hormone deficits.Within the radiotherapy treated cohort 14% (2/14) of patients demonstrated additional anterior pituitary hormone deficits: 11% (1/9) of patients with normal GH secretory status and 20% (1/5) of patients with severe GH deficiency.None of the patients with adrenal adenomas treated by unilateral adrenalectomy demonstrated any abnormality of GH secretory statusCONCLUSIONSThe incidence of severe persistent GH deficiency following surgically induced or radiotherapy induced remission of Cushing's disease is lower than has been suggested by previous studies, although these latter studies have assessed GH insufficiency and not severe GH deficiency. In the presence of additional pituitary hormone deficits severe GHD is common and is likely to be persistent. Recovery of GH secretory status is seen in a high proportion of patients reassessed, at a median time of 19 months following surgically induced remission of Cushing's disease. Thus, we recommend that definitive assessment of GH secretory status is delayed for at least two years following surgical cure of Cushing's disease. This has important implications for patients in whom GH replacement therapy is being considered.