Growth hormone secretion elicited by GHRH, GHRP‐6 or GHRH plus GHRP‐6 in patients with microprolactinoma and macroprolactinoma before and after bromocriptine therapy
Authors: Popovic  , Simic  , Ilic  , Micic  , Damjanovic  , Djurovic  , Obradovic  , Dieguez  , Casanueva  
Published: March 2003

OBJECTIVE

Growth hormone‐releasing peptides (GHRPs) are potent GH releasers which act at both pituitary and hypothalamic levels through specific G‐protein coupled receptors, recently cloned. A synergistic effect from the simultaneous administration of GHRH + GHRP‐6 on GH release is observed in normal subjects, while it is absent in patients with hypothalamo‐pituitary disconnection. We studied the effects of GHRH, GHRP‐6 and both secretagogues on GH release in patients harbouring pituitary tumours that may be reduced in size by medical treatment.

DESIGN

Analysis of peak GH response to GHRH, GHRP‐6 and GHRH plus GHRP‐6 in patients with micro‐ and macroprolactinomas. Integrated GH response over 2 hours calculated as AUG‐GH mU/l × 120 min. Analysis of delta PRL above the basal level in response to the same GH releasers.

PATIENTS

Eleven patients with macroprolactinomas aged 41.2 ± 4.8 years (range 24–75), nine patients with microprolactinomas aged 31.5 ± 3.4 (range 22–53) and 13 healthy subjects aged 42.1 ± 4.7 years (range 22–64) were studied. Prolactinoma patients were then treated with bromocriptine (15–20 mg orally) for 6–24 months. Tests were repeated when there was evidence of tumour shrinkage and normalized plasma prolactin concentrations.

RESULTS

Peak GH response before treatment in macroprolactinoma patients was 4.9 ± 0.9 mu/l after GHRH, 8 ± 4 mU/l after GHRP‐6 and 18 ± 5 mU/l after GHRH + GHRP‐6. Synergism was absent. AUC were 390 ± 90; 500 ± 100 and 1100 ± 300 mU/l × 120 min respectively. These values were all significantly different (P < 0.05) from normal subjects and patients with microprolactinomas with peak GH 16.8 ± 0.9 mU/l after GHRH; 43 ± 6 mU/l after GHRP‐6 and 130 ± 10 mU/l after GHRH + GHRP‐6. AUC‐GH was 1200 ± 400 after GHRH, 2200 ± 400 after GHRP‐6 and 9000 ± 1000 mU/l × 120 min after GHRH + GHRP‐6. As in normal subjects, synergism was preserved in patients with microprolactinoma (P > 0.05). After treatment with bromocriptine peak GH in patients with macroprolactinoma was 8 ± 4 mU/l after GHRH, 22 ± 5 mU/l after GHRP‐6 and 70 ± 20 mU/l after GHRH + GHRP‐6. AUC‐GH was 800 ± 300, 1100 ± 300 and 3500 ± 800 mU/l × 120 min, respectively. The response of GH after GHRP‐6 and GHRH + GHRP‐6 improved significantly (P < 0.05) in treated patients with macroprolactinoma. There was no significant change in GH response in microprolactinoma patients after treatment with bromocriptine. Peak GH after GHRH was 30 ± 20 mU/l, after GHRP‐6 it was 75 ± 8 mU/l and after GHRH + GHRP‐6 it was 200 ± 30 mU/l. AUC‐GH was 1500 ± 700 after GHRH, 4500 ± 500 after GHRP‐6 and 15 100 ± 600 mU/l × 120 min. Delta prolactin after GHRP‐6 did not change before and after bromocriptine treatment in patients with macroprolactinoma or microprolactinoma.

CONCLUSION:

GH release after GHRP‐6 or GHRH + GHRP‐6 is fully preserved in patients with microprolactinomas and does not differ before and after treatment with bromocriptine. Patients with macroprolactinoma have blunted responses of GH after GHRH and GHRP‐6 and synergism is severely compromised. GH responsiveness to and synergistic interaction between GHRH and GHRP‐6 recovers after shrinkage of macroprolactinoma with bromocriptine. Prolactin release stimulated by intravenous administration of GHRP‐6 in healthy subjects was not seen in patients with micro‐ or macroprolactinomas.