Relationship between the morphological evaluation of the pituitary and thegrowth hormone (GH) response to GH-releasing hormone plus arginine in children and adults with congenital hypopituitarism

The relationship between the hypothalamus-pituitary morphology and the soma totroph responsiveness to maximal provocative tests exploring the GH releas able pool is still unclear. We evaluated the GH-releasing effect of GHRH pl us arginine (GHRH plus Arg) in 36 patients with congenital GH deficiency (G HD) according to their pituitary magnetic resonance imaging findings, consi sting of anterior pituitary hypoplasia, stalk agenesis (neural and or vascu lar component), and posterior pituitary ectopia. Seventeen children (12 boy s and 5 girls, aged 1-5.2 yr) were evaluated at the time of diagnosis of GH D (mean age, 3.6 +/- 1.4 yr), and 19 adults (13 males and 6 females, aged 1 5.9-28.6 yr) with childhood-onset GHD were reevaluated after completion of GH treatment (at least 6 months of withdrawal) at a mean age of 20.5 +/- 3. 5 yr. Eleven children had isolated GHD. and 6 had multiple pituitary hormon e deficiency (MPHD) whereas 7 adults had isolated GHD, and 12 had MPHD. A r esidual vascular component of the pituitary stalk was visualized in 7 child ren and 7 adults with isolated GHD, whereas magnetic resonance imaging show ed complete pituitary stalk agenesis (both vascular and neural components) in 10 children and 10 adults, including 16 with MPHD (6 children) and 4 chi ldren with isolated GHD. In the children, the median peak GH response to GH RH plus Arg (7.6 mug/L; range, 2.4-40.2 mug/L) was significantly higher tha n that in the adults (1.8 mug/L; range, 0.8-37.4 mug/L; P = 0.0039); it was also significantly higher in the isolated GHD patients (18 mug/L; range, 3 .3-40.2 mug/L) than in those with MPHD (1.9 mug/L: range, 0.8-7.6 mug/L; P = 0.00004). In the patients with residual vascular component of the pituita ry stalk the median peak GH responses to GHRH plus Arg (19.1 mug/L; range, 1.6-40.2 mug/L) was significantly higher than that in patients with complet e pituitary stalk agenesis(2.2 mug/L; range, 0.8-8.8 mug/L; P = 0.00005). T here was a trend toward a decrease with age in peak GH response to GHRH plu s Arg. Mean serum insulin-like growth factor I(IGF-I) levels were 36 +/- 7. 1 mug/L in the children and 63.5 +/- 22.6 mug/L in the adults (P = 0.0001). The mean IGF-I level did not differ between the children with (35.7 +/- 4. 8 mug/L) and those without (36.3 +/- 8.7 mug/L) the pituitary stalk; it was much higher in the adults with residual vascular pituitary stalk (81.1 +/- 17.7 mug/L) than in those with complete pituitary stalk agenesis (47.7 +/- 12.5 mug/L; P = 0.0002). The IGF-I level was 36.1 +/- 6.7 mug/L in the iso lated GHD children and 36 +/- 8.6 mug/L in those with MPHD: levels were 82. 1 +/- 19.4 and 52.7 +/- 16.8 mug/L respectively, in the adults (P = 0.003). In this study we have confirmed that the partial integrity of the hypothala mic pituitary connections is essential for GHRH plus Arg to express its GH- releasing activity and have shown that this provocative test is able to sti mulate GH secretion to a greater extent in those patients with GHD, but wit h a residual vascular component of the pituitary stalk. This test is reliab le in the diagnosis of congenital hypopituitarism in both children and adul ts when associated with complete pituitary stalk agenesis and MPHD. In youn ger children with congenital GHD but less severe impairment of the pituitar y stalk the GH response to GHRH plus Arg may be within the normal range; de terioration of pituitary GH reserve with a GH response of less than 10 mug/ L after 20 yr of age makes this test very sensitive in the diagnosis of adu lt GHD.