Near-Normal Linear Growth in the Setting of Markedly Reduced Growth Hormone and IGF-1

Abstract

A 14.2-year-old prepubertal boy diagnosed with complete-type growth hormone deficiency and tertiary hypothyroidism, keeps growing in the height range between –1 and –2 SD. He has been treated with levothyroxine only. To understand the growth mechanism of this boy, we analyzed the serum growth hormone (GH) with a radioimmunoassay (RIA), serum GH bioactivity with Nb2 and erythroid progenitor cell bioassays, and growth hormone-binding protein (GHBP) with a ligand-mediated immunofunctional assay (LIFA). In addition, IGF-1 and free IGF-1 were analyzed by immunoradiometric assay (IRMA) and insulin-like growth factor-binding protein-3 (IGFBP-3) by Western immunoblot. Peak GH-RIA responses to insulin, arginine and GH-releasing factor, and nocturnal GH secretion, were low (0.5–2.3 ng/ml); bioactive GH was low (0.313 ng/ml), and GHBP was elevated (84 ng/ml). The serum levels of IGF-1 and free IGF-1 were continuously low, 17.1–39.3 and 0.17–0.26 ng/ml, respectively. Moreover, serum IGFBP-3 levels were low (1.68– 1.39 mg/l) and IGFBP-3 protease activity was negative. Prolactin and insulin were in the normal range. The result of the assay for growth-promoting activity showed that the patient’s serum stimulated normal erythroid progenitor cells twice as potently as did healthy thin adult control serum. These results suggest that GH and IGF-1 are not indispensable for maintaining physical growth in this boy. Thus, it appears that circulating GH and IGF-1 are not mandatory requirements for maintaining normal physical growth, and other, as yet uncharacterized, pathways or growth factors might be sufficiently compensatory under certain conditions.

Growth without growth hormone in combined pituitary hormone deficiency caused by pituitary stalk interruption syndrome

“…A few cases of normal growth without GH in patients with PSIS-induced CPHD, as in our patient, have been reported8). These patients, despite their marked reduced GH and IGF-I levels, were not obese, and their prolactin and insulin levels were within the normal ranges.…”

“…Similar reports on other suprasellar tumor surgeries5) have followed. Normal growth without GH was also reported in SOD6), empty sellar syndrome7), and PSIS8).…”

“…Free IGF-I was also within the normal range. Murashita et al8) stimulated erythroid progenitor cells with the serum of PSIS patients who showed near-normal growth despite CPHD, and reported that the experimental group showed a normal degree of serum growth-promoting activity when compared to the control group. However, the exact mechanism was not explained clearly.…”

Growth without growth hormone: growth pattern and final height of five patients with idiopathic combined pituitary hormone deficiency

“…Geffner et al . (1986) detected a potent growth factor in the serum of a child who grew without GH, and Murashita et al . (1999) found a normal degree of serum growth‐promoting activity in a patient who exhibited near‐normal growth without GH.…”

“…‘Growth without GH’ is uncommon in patients with idiopathic isolated GHD (IGHD) or CPHD (Geffner et al ., 1986;Murashita et al ., 1999). Accelerated linear height gain has been reported in many patients with panhypopituitarism and GHD following resection of craniopharyngiomas (Matson, 1964; Tiulpakov et al ., 1998; Pinto et al ., 2000; Pavlou et al ., 2001), or other suprasellar tumours (Finkelstein et al ., 1972), and in association with some intracranial anomalies, such as septo‐optic dysplasia (Petrykowski et al ., 1993; Bereket et al ., 1998; Hathout et al ., 1999), obesity (Vanderschueren‐Lodeweyckx, 1993).…”