Paradoxical Growth Hormone Response to an Oral Glucose Load Not always Acromegaly!

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 88-129-Acromegaly & Prolactinoma
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-125
Subramanian Kannan*1, Georgiana Alina Dobri1, Leann Olansky2 and Charles Faiman2
1Cleveland Clinic Foundation, Cleveland, OH, 2Cleveland Clinic, Cleveland, OH
Background: The normal response of growth hormone (GH) to oral glucose (OGTT) is an initial suppression reaching a nadir within 2 hours followed by a stimulatory rebound after 2 hours. Paradoxical elevation of GH has been reported in patients with acromegaly (1-4). However the literature with currently available GH assays is sparse. 

Hypothesis: We studied the paradoxical response of GH to oral glucose loading in patients with and without acromegaly in order to assess its utility in confirming the diagnosis. 

Methodology: Retrospective chart review of GH suppression tests by oral glucose performed from 2000 to 2012 at the Cleveland Clinic. Acromegaly was excluded based on normal IGF-1or GH nadir <0.4 ng/ml or tumor negative for GH stain. Patients with an inconclusive work up or on medical therapy for acromegaly were excluded. Patients were considered to have a paradoxical GH response if their post-glucose GH levels were higher than the corresponding basal GH level within the first 2 hours without a preceding nadir and an absolute post-glucose GH value was > 1ng/ml.

Results: Of the 104 patients studied, 40 (38%) had acromegaly and of the 8 (7.6%) patients who had a paradoxical GH response, 6 patients had acromegaly but 2 did not. In these 2, 1F & 1M, BMI was 20 and 53 kg/m2 respectively. In the morbidly obese patient, IGF-1 was elevated at 365 ng/ml (Z score = 3.2) at the time of the OGTT. Basal GH level was 0.15 ng/ml, peak GH level at 60 min was 4.74 and reached a nadir of 0.38 ng/ml at the end of 2 hours. On follow up in 6 months a repeat IGF-1 level was 246 ng/ml (Z score = 1.3), MRI of the pituitary was normal and a repeat OGTT showed a GH nadir of 0.09 ng/ml at 60 minutes followed by a rise to 7.38 at 90 minutes. In the other patient the IGF-1 level was 443 ng/ml (normal <267), basal GH was 0.15 ng/ml and the peak GH level at 60 minutes was 1.71 and reached a nadir to 0.12 ng/ml at the end of 2 hours. Pituitary MRI was normal. In the acromegaly group (3M, 3F) with the paradoxical response, median (range) basal GH and IGF-1 levels was 2.35 (0.9-30) ng/ml and 484 (327-1030) ng/ml respectively. There was a statistical trend for a paradoxical GH response to occur more frequently in acromegaly patients compared to non-acromegaly patients (P 0.052).

Conclusion: A paradoxical GH response to oral glucose load cannot be used by itself to confirm the diagnosis of acromegaly. The paradoxical GH rise was not reproducible in the non-acromegaly patients.

1. Grottoli S, Procopio M, Maccario M, Zini M, Oleandri SE, Tassone F, et al. In obesity, glucose load loses its early inhibitory, but maintains its late stimulatory, effect on somatotrope secretion. J Clin Endocrinol Metab. 1997 Jul;82(7):2261-5. 2. Grecu EO, Walter RM,Jr, Gold EM. Paradoxical release of growth hormone during oral glucose tolerance test in patients with abnormal glucose tolerance. Metabolism. 1983 Feb;32(2):134-7. 3. Iranmanesh A, Lawson D, Veldhuis JD. Distinct metabolic surrogates predict basal and rebound GH secretion after glucose ingestion in men. J Clin Endocrinol Metab. 2012 Jun;97(6):2172-9. 4. Reichlin S: Growth and the hypothalamus. Endocrinology 1960;67:760-773.

Nothing to Disclose: SK, GAD, LO, CF

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