Pseudopseudohypoparathyroidism associated with idiopathic Growth Hormone deficiency. Role of treatment with biosynthetic Growth Hormone

Abstract

A case is presented of a prepubertal girl with the characteristic somatic features of Albright's hereditary osteodystrophy, including severe short stature, cataracts and shortening of all metacarpals and metatarsals and of the second middle hand phalanges, whose diagnosis of pseudopseudohypoparathyroidism (PPHP) was confirmed by laboratory evaluation (normocalcemia, normophosphatemia, normal levels of circulating PTH and normal response to exogenous PTH). Since an isolated idiopathic GH deficiency has been diagnosed at the age of 9.7 yr, by an abnormal GH response to standard provocation tests, a poor spontaneous nocturnal GH secretion and a blunted response to GHRH test, our patient was treated with biosynthetic GH during a 3.5-year period. Although a good improvement of growth velocity was obtained when comparing pretreatment height velocity (4 cm/yr) with growth velocity evaluated during GH treatment (6.6, 6.2 and 5.9 cm/yr in the first, the second and the third year of therapy, respectively), bone age advanced more rapidly than chronological age, so that it is uncertain whether the growth acceleration promoted by GH administration really improved final height, which remained below the third centile. Our patient is the first described case of PPHP associated with idiopathic GH deficiency, and the second report of long-term GH treatment in a subject with PPHP. Further observations are necessary to define the frequency and significance of GH deficiency and the role of GH replacement therapy in pseudohypoparathyroidism- and PPHP-associated short stature.

Evidence of hormone resistance in a pseudo-pseudohypoparathyroidism patient with a novel paternal mutation in GNAS

“…The blunted response in these tests could partly reflect resistance to GHRH, which is also an unexpected finding, as GHRH resistance is typically found in PHP-Ia patients due, presumably, to the predominant maternal expression of Gsα in the anterior pituitary combined with maternal loss-of-function GNAS mutations [2–4]. However, a PPHP case has previously been reported to have growth hormone deficiency and a blunted response to GHRH stimulation [20]. It thus appears that, at least in some cases, paternal Gsα mutations lead to GHRH resistance.…”

Case Report: A Paternal 20q13.2-q13.32 Deletion Patient With Growth Retardation Improved by Growth Hormone

“…As for GH treatment in PPHP patient, R Manfredi et al repoted a female PPHP patient, who received a 3-yr-6 months GH treatment. As a result, a significant improvement of growth velocity was obtained, while the height SDS failed to improve (-3.30 pretreatment (10 years old); -3.14(11 years old), -3.36(12 years old) and -3.59 (13 years old) after the first, the second and the third year of treatment, respectively) ( Manfredi et al, 1993 ). As for our patient, although he failed to return to normal height with GH treatment, his height SD changed more in the first 2 years (5–7 years old) than that in those reports ( Figure 2A ).…”

Genetic Characterization of Growth Hormone Deficiency and Resistance

“…Occasional reports have mentioned variable degrees of GH insufficiency or normal GH secretion in pseudohypoparathyroidism, [93][94][95][96][97][98][99][100] but a systematic investigation has not been performed. There is a clear need to define the GH status of a large number of patients as it appears that the degree of GH insufficiency is variable.…”