GH secretion in a cohort of children with pseudohypoparathyroidism type Ia

Abstract

Pseudohypoparathyroidism type Ia (PHP-Ia) is characterized by Albright's hereditary osteodistrophy (AHO) and resistance to hormones that act via the alpha subunit of the Gs protein (Gsalpha) protein, ie PTH, TSH, FSH/LH, and, as recently described in limited series, GHRH. However, the current lack of data on GHRH secretion, obesity and short stature included in the AHO phenotype hampers interpretation of GH secretory status and its effects on these subjects. We evaluated GH secretion after GHRH plus arginine (Arg) stimulus, IGF-I levels and anthropometric features in an exclusively pediatric population of 10 PHP-Ia subjects. Of our PHP-Ia children, 5 out of 10 (50%) showed impaired GH responsiveness to the provocative test, with a lower prevalence than the 75-100% previously reported. A negative correlation (p=0.024) was found between GH secretion and body mass index (BMI), whereas no correlation emerged between GH and IGF-I values (p=0.948). Height and growth velocity did not significantly differ between GH-deficient and GH-sufficient subjects. In the 5 GH-deficient patients, GHRH resistance could arguably be responsible for hormonal impairment; however, 3 of them were obese, showing normal stature and IGF-I levels: the increased BMI in these subjects could influence GH secretion and its effects. In conclusion, GH deficiency is frequent among PHP-Ia children and its prevalence is variable, two factors indicating that GH secretory testing should be part of the routine management of this patient group. It could be argued that GHRH resistance is the pathogenetic mechanism in most patients, but further studies on GHRH secretion are needed to define which values can be considered as raised. Lastly, because BMI has been indicated as a major determinant of evoked adult GH response to provocative testing, GH levels related to increased BMI also in childhood could be helpful in defining GH assessment in obese or overweight PHP-Ia children.

Genetic and epigenetic alterations in the GNAS locus and clinical consequences in Pseudohypoparathyroidism: Italian common healthcare pathways adoption

“…Although multiple hormone resistances were classically described in PHP-Ia patients [1], their relative low prevalence in our series could in part be explained by the very young age of most subjects, but it also might reflect that neither the historically reported hormonal derangements (involving vasopressin, prolactin, ACTH, CRF, calcitonin and glucagon [31–33]) nor the newly recognized ones (including insulin, leptin and αMSH [5]) are initially investigated and routinely included in the follow-up program. Likewise for rGHRH, reported as a common finding in PHP-Ia subjects, the GH secretory testing should be part of the initial management [22, 34].…”

From pseudohypoparathyroidism to inactivating PTH/PTHrP signalling disorder (iPPSD), a novel classification proposed by the EuroPHP network

“…Resistance to growth hormonereleasing hormone (GHRH), leading to growth hormone deficiency, is the most frequent additional resistance found in PHP1A, affecting as many as 60% of patients (97,98,99). Calcitonin resistance has been described without clinical features in patients affected with PHP1A (27).…”

Role of hormones and neurosteroids in epileptogenesis

“…Steroid hormones play a key role in the neuroendocrine control of neuronal excitability and seizure susceptibility ( Table 2 ; Herzog, 2002; Reddy, 2003a, 2010; Verrotti et al, 2007). Steroid hormones are synthesized and secreted from ovarian, gonadal, and adrenal sources.…”