Growth Hormone Response to Standard Provocative Stimuli and Combined Tests in Very Young Children with Prader-Willi Syndrome

Abstract

Background: In Prader-Willi syndrome (PWS) a reduced growth hormone (GH) response to several stimulators has been documented in many studies, but none have focused on very young children. We evaluated the pattern of GH secretion in very young PWS patients. Patients and Methods: Twenty-seven genetically confirmed PWS children (10 females, aged 0.4-5 years, mean: 2.2 ± 1.4 years) were included. All subjects underwent standard provocative tests (clonidine, CLO; and arginine, ARG) and one combined test [growth hormone-releasing hormone (GHRH) plus pyridostigmine (13 patients) or GHRH plus arginine (14 patients)]. Insulin-like growth factor-1 (IGF-1) levels were also measured. Results: While standard tests (CLO and ARG) showed low GH peak in 85.2 and 70.4% of the patients, respectively, the combined test was found to be normal in 85.2%. IGF-1 was low in 66.7% of patients. Out of 27 patients, 3 (11%) showed a normal GH peak with both standard tests (group A), 6 (22%) to one of the standard tests (group B) and 18 (67%) presented a low response to both standard tests (group C). Four subjects showed low response to both the combined and standard tests and reduced IGF-1. Conclusion: Our data suggest that very young PWS children seem to have impaired hypothalamic GHRH secretion with a normal GH pituitary reserve.

Prevalence of growth hormone (GH) deficiency in previously GH‐treated young adults with Prader‐Willi syndrome

“…Two studies in young children with PWS described a low GH peak after clonidine or arginine in 68%‐85% . One of these studies in 27 children with PWS also performed a combined test (GHRH‐arginine or GHRH‐pyridostigmine test), which showed a much lower prevalence of GHD (15%) than the clonidine and arginine tests .…”

Growth hormone secretion decreases with age in paediatric Prader‐Willi syndrome

“…15 In a recently published study, GH peak was low in 70-85% of children with PWS under 5 years of age based on standard GH stimulation tests. 16 In a slightly younger population, 4-37 months of age, only 55% were found to be GH deficient, based on a single GH stimulation test. 11 However, to our knowledge, our study is the first to focus on the developmental difference in the prevalence of GH deficiency using standard provocative tests and evaluate a cut-off age for biochemical GH deficiency in paediatric PWS.…”

The Relationship between Subnormal Peak-Stimulated Growth Hormone Levels and Auxological Characteristics in Obese Children

“…Pyridostigmine is a cholinergic agonist that acts similar to arginine to suppress somatostatin release by the hypothalamus. This enhances GH response to GHRH both in normal subjects, and in many instances of impaired GH secretion, including obesity (40). It is usually administered in conjunction with GHRH during GH stimulation testing.…”

“…Some investigators recommend that the diagnosis of GHD can only be made in an obese child in the presence of low height velocity, low IGF-I concentrations, and a subnormal peak GH response to standard stimulation that does not reverse with pyridostigmine administration. This additional testing with pyridostigmine is deemed necessary to prevent false-positive results because obese individuals are believed to have impaired hypothalamic secretion of GHRH, but possess a normal GH pituitary reserve (40). However, GHRH is no longer available in the United States, and the use of pyridostigmine is limited by its adverse effect profile as serious cholinergic side effects ranging from transient abdominal pain, muscle fasciculation, hypotension, and bradycardia have been reported in up to 23% of patients who received pyridostigmine during GHST (41).…”