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Significance of "Abnormal" Nadir Growth Hormone Levels after Oral Glucose in Postoperative Patients with Acromegaly in Remission with Normal Insulin-Like Growth Factor-I Levels

Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032; and Department of Neurosurgery, Mount Sinai Medical Center, New York, New York 10029

Address all correspondence and requests for reprints to: Pamela U. Freda, M.D., Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032. E-mail: puf1{at}columbia.edu.

Our initial study in postoperative patients with acromegaly identified a group of patients in remission, as defined by normal IGF-I levels, but who had a subtle abnormality of GH suppression after oral glucose. To investigate the significance of this abnormality, we have undertaken further detailed testing of GH secretion and a longitudinal follow-up of some of these patients.

Of the 110 postoperative patients with acromegaly evaluated by oral glucose tolerance test, 76 were in remission (i.e. normal IGF-I level), and of these subjects with acromegaly in remission, 50 had normal nadir GH (<0.14 µg/ml) (group I), and 26 had abnormal nadir GH (>0.14 µg/ml) (group II). Fourteen subjects in remission, seven from remission group I and seven from remission group II, underwent additional testing consisting of both hourly GH sampling over 8 h and, on a separate day, arginine stimulation testing. The mean of hourly GH was higher in group II (0.47 ± 0.04 µg/liter) than in group I (0.19 ± 0.07 µg/liter; P = 0.002). GH response to arginine was greater in group II than in group I (P < 0.01). Of those patients in remission from the initial cohort studied, 49 (30 subjects from group I and 19 from group II) underwent serial longitudinal oral glucose tolerance testing every 1–2 yr over a 1- to 6.5-yr period (mean follow-up, 3.2 yr). The initial pattern of GH suppression persisted in most patients. IGF-I levels remained normal in all patients in group II, but five subjects from group II developed an elevated IGF-I level and, thus, a biochemical recurrence. The rate of disease recurrence was greater in group II than in group I (P = 0.003).

We have found that some postoperative subjects with acromegaly in remission with normal IGF-I levels have persistently abnormal nadir GH levels after oral glucose that may be accompanied by other evidence of greater GH secretion than postoperative patients with normal GH suppression. This abnormal pattern of GH suppression may be associated with increased risk of disease recurrence in some patients.

This work was supported by National Institutes of Health Grants K08 DK02561 and R03 DK60475 (to P.U.F.) and RR00645 to the Columbia University GCRC, and by Novartis International AG.

Results of this work were presented in part at the 84th Annual Meeting of The Endocrine Society, San Francisco, CA, 2002.

Abbreviations: BMI, Body mass index; IRMA, immunoradiometric assay; OGTT, oral glucose tolerance test.

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