Growth hormone response to growth hormone-releasing hormone varies with the hypothalamic-pituitary abnormalities

Abstract

We determined growth hormone (GH) and insulin-like growth factor I (IGF-I) levels after a 3 h infusion of escalating doses of growth hormone-releasing hormone (GHRH(1-29)) followed by a bolus injection in hypopituitary patients with marked differences in pituitary features at magnetic resonance imaging (MRI) in order to evaluate further the contribution of MRI in the definition of pituitary GH reserve in GH-deficient patients. Twenty-nine patients (mean age 14.5 +/- 4.0 years) were studied. Group I comprised 13 patients: seven with isolated GH deficiency (IGHD) (group Ia) and six with multiple pituitary hormone deficiency (MPHD) (group Ib) who had anterior pituitary hypoplasia, unidentified pituitary stalk and ectopic posterior pituitary at MRI, Group II consisted of eight patients with IGHD and small anterior pituitary/empty sella, while in group III eight had IGHD and normal morphology of the pituitary gland. Growth hormone and IGF-I levels were measured during saline infusion at 08.30-09.00 h, as well as after infusion of GHRH (1-29) at escalating doses for 3h: 0.2 micrograms/kg at 09.00-10.00 h, 0.4 micrograms/kg at 10.00-11.00 h, 0.6 micrograms/kg at 11.00-12.00 h and an intravenous bolus of 2 micrograms/ kg at 12.00 h. In the group I patients, the peak GH response to GHRH(1-29) was delayed (135-180 min) and extremely low (median 2mU/l). In group II it was delayed (135-180 min), high (median 34.8 mU/l) and persistent (median 37.4 mU/l at 185-210 min). In group III the peak response was high (median 30.8 mU/l) and relatively early (75-120 min) but it declined rapidly (median 14.4 mU/l at 185-210 min). In one group I patient, GH response increased to 34.6 mU/l. The mean basal value of IGF-I levels was significantly lower in group I (0.23 +/- 0.05 U/ml) than in groups II (0.39 +/- 0.13U/ ml, p < 0.01) and III (1.54 +/- 0.46 U/ml, p < 0.001) and did not vary significantly during the GHRH(1-29) infusion. The present study demonstrates that the impaired GH response to 3 h of continuous infusion of escalating doses of GHRH(1-29) was strikingly indicative for pituitary stalk abnormality, strengthening the case for use of GHRH in the differential diagnosis of GH deficiency. The low GH response, more severe in MPHD patients, might be dependent on the residual somatotrope cells, while the better response (34.6 mU/l) in the group Ia patients might suggest that prolonged GHRH infusion could help in evaluating the amount of residual GH pituitary tissue. Pituitary GH reserve, given the GH response to GHRH infusion in GH-deficient patients with small anterior pituitary/empty sella, seems to be maintained.

Growth Hormone (GH) Deficiency (GHD) of Childhood Onset: Reassessment of GH Status and Evaluation of the Predictive Criteria for Permanent GHD in Young Adults

“…Our findings suggest that the severity of GHD is related not only to the number of pituitary hormone deficits, but also to the MRI findings. In this regard, we have previously shown that the GH response to a GHRH infusion in patients with pituitary stalk agenesis and ectopic posterior pituitary lobe was low regardless of whether they had IGHD or MPHD (22). We observed a significant correlation between the GH peak after provocative tests and serum IGF-I and IGFBP-3 concentrations as well as between IGF-I and IGFBP-3 at retesting.…”

GH response to ghrelin in subjects with congenital GH deficiency: evidence that ghrelin action requires hypothalamic–pituitary connections

“…We are aware that the absence of pituitary stalk is associated with pituitary somatotrope hypoplasia, likely as the result of a defective GHRH stimulation. Nonetheless, testing with GHRH or GHRH plus arginine has shown various degrees of GH-releasing capabilities in these patients indicating the presence of functionally preserved somatotropes (14,21).…”

“…Use of this imaging technique after contrast medium administration in GHD patients has permitted the identification of residual vascular components of the pituitary stalk with significantly higher accuracy than with standard MRI (20). Interestingly, a GH response to GHRH and to GHRH plus arginine has been demonstrated in the great majority of GHD patients with a residual vascular connection, as opposed to a lack of response in patients with absent pituitary stalk (21,14). In other words, the GH responses to GHRH and to GHRH plus arginine were negatively correlated with the degree of pituitary stalk impairment as assessed by MRI.…”

Posterior pituitary (PP) evaluation in patients with anterior pituitary defect associated with ectopic PP and septo-optic dysplasia

“…Several studies have shown abnormal PP function, ranging from reduced vasopressin release after osmotic challenge, hypodipsia, or polydipsia (6) to persistent nocturnal enuresis or symptomatic CDI, in both familial (7) and sporadic cases of hypopituitarism associated with either isolated GH deficiency (IGHD) or multiple pituitary hormone deficiencies (MPHD) (6,8,9). Other studies which focused on the assessment of anterior pituitary function in patients with EPP have never reported water and electrolyte disturbances or CDI in these patient populations (1,2,(10)(11)(12)(13)(14)(15).…”