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Relationship between the Morphological Evaluation of the Pituitary and the Growth Hormone (GH) Response to GH-Releasing Hormone Plus Arginine in Children and Adults with Congenital Hypopituitarism¹

Departments of Pediatrics (M.M., B.S., S.B., M.R.), Biometry-Scientific Direction (C.T.), and Servizio Analisi Chimico Cliniche (M.A.), IRCCS Policlinico S. Matteo, University of Pavia, I-27100 Pavia; and Division of Endocrinology, Department of Internal Medicine, University of Turin (G.A., E.G.), 10126 Turin, Italy

Address all correspondence and requests for reprints to: Mohamad Maghnie, M.D., Ph.D., Department of Pediatrics, IRCCS Policlinico S. Matteo, Viale Golgi 2, I-27100 Pavia, Italy. E-mail: maghnie{at}smatteo pv.it.

The relationship between the hypothalamus-pituitary morphology and the somatotroph responsiveness to maximal provocative tests exploring the GH releasable pool is still unclear. We evaluated the GH-releasing effect of GHRH plus arginine (GHRH plus Arg) in 36 patients with congenital GH deficiency (GHD) according to their pituitary magnetic resonance imaging findings, consisting of anterior pituitary hypoplasia, stalk agenesis (neural and or vascular component), and posterior pituitary ectopia. Seventeen children (12 boys and 5 girls, aged 1–5.2 yr) were evaluated at the time of diagnosis of GHD (mean age, 3.6 ± 1.4 yr), and 19 adults (13 males and 6 females, aged 15.9–28.6 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 hormone deficiency (MPHD) whereas 7 adults had isolated GHD, and 12 had MPHD. A residual vascular component of the pituitary stalk was visualized in 7 children and 7 adults with isolated GHD, whereas magnetic resonance imaging showed complete pituitary stalk agenesis (both vascular and neural components) in 10 children and 10 adults, including 16 with MPHD (6 children) and 4 children with isolated GHD. In the children, the median peak GH response to GHRH plus Arg (7.6 µg/L; range, 2.4–40.2 µg/L) was significantly higher than that in the adults (1.8 µg/L; range, 0.8–37.4 µg/L; P = 0.0039); it was also significantly higher in the isolated GHD patients (18 µg/L; range, 3.3–40.2 µg/L) than in those with MPHD (1.9 µg/L; range, 0.8–7.6 µg/L; P = 0.00004). In the patients with residual vascular component of the pituitary stalk the median peak GH responses to GHRH plus Arg (19.1 µg/L; range, 1.6–40.2 µg/L) was significantly higher than that in patients with complete pituitary stalk agenesis (2.2 µg/L; range, 0.8–8.8 µg/L; P = 0.00005). There was a trend toward a decrease with age in peak GH response to GHRH plus Arg. Mean serum insulin-like growth factor I (IGF-I) levels were 36 ± 7.1 µg/L in the children and 63.5 ± 22.6 µg/L in the adults (P = 0.0001). The mean IGF-I level did not differ between the children with (35.7 ± 4.8 µg/L) and those without (36.3 ± 8.7 µg/L) the pituitary stalk; it was much higher in the adults with residual vascular pituitary stalk (81.1 ± 17.7 µg/L) than in those with complete pituitary stalk agenesis (47.7 ± 12.5 µg/L; P = 0.0002). The IGF-I level was 36.1 ± 6.7 µg/L in the isolated GHD children and 36 ± 8.6 µg/L in those with MPHD; levels were 82.1 ± 19.4 and 52.7 ± 16.8 µg/L respectively, in the adults (P = 0.003).

In this study we have confirmed that the partial integrity of the hypothalamic pituitary connections is essential for GHRH plus Arg to express its GH-releasing activity and have shown that this provocative test is able to stimulate GH secretion to a greater extent in those patients with GHD, but with a residual vascular component of the pituitary stalk. This test is reliable in the diagnosis of congenital hypopituitarism in both children and adults when associated with complete pituitary stalk agenesis and MPHD. In younger children with congenital GHD but less severe impairment of the pituitary stalk the GH response to GHRH plus Arg may be within the normal range; deterioration of pituitary GH reserve with a GH response of less than 10 µg/L after 20 yr of age makes this test very sensitive in the diagnosis of adult GHD.

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