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Case Reports
. 2019 May 20;3(7):1383-1389.
doi: 10.1210/js.2019-00073. eCollection 2019 Jul 1.

Resistance to GHRH but Not to PTH in a 15-Year-Old Boy With Pseudohypoparathyroidism 1A

Martin Munteanu  1 , Cordula Kiewert  1 , Nora Matar  1   2 , Berthold P Hauffa  1 , Nicole Unger  3 , Olaf Hiort  4 , Susanne Thiele  4 , Karin Buiting  5 , Nuria C Bramswig  2   5 , Corinna Grasemann  1   2
Affiliations
Case Reports

Resistance to GHRH but Not to PTH in a 15-Year-Old Boy With Pseudohypoparathyroidism 1A

Martin Munteanu et al. J Endocr Soc. .

Abstract

Pseudohypoparathyroidism 1A (PHP1A) consists of signs of Albright hereditary osteodystrophy (AHO) and multiple, variable hormonal resistances. Elevated PTH levels are the biochemical hallmark of the disease. Short stature in PHP1A may be caused by a form of accelerated chondrocyte differentiation leading to premature growth plate closure, possibly in combination with GH deficiency in some patients. Treatment of short stature with recombinant growth hormone (rhGH) in pediatric patients may improve final height if started during childhood. The 10 11/12-year-old boy with clinical signs of AHO presented for evaluation of short stature [height standard deviation score (SDS) -2.72]. Clinically his mother was affected by AHO as well. A heterozygous mutation c.505G>A (p.E169K) in exon 6 of the GNAS gene confirmed a diagnosis of PHP1A in the boy. However, hormonal assessment was unremarkable except for low serum IGF-1 (SDS -2.67). On follow-up, GH deficiency due to GHRH resistance was suspected and confirmed by clonidine and arginine stimulation tests. Treatment with rhGH (0.035 mg/kg) for 2 years resulted in catch-up growth (height SDS -1.52). At age 15 years the PTH levels and bone age of the patient remain within the normal range. In patients with PHP1A, short stature is caused by the effects of Gs-α deficiency on the growth plate. However, resistance to GHRH and the resulting GH deficiency might also contribute. Recombinant GH treatment increases growth in these patients. Diagnostic workup for GH deficiency as a factor contributing to short stature is recommended even in the absence of other hormonal resistances.

Keywords: PHP1A; growth hormone; hormone resistence; short stature.

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Figures

Figure 1.
Figure 1.
X-ray of the left hand with brachydactyly of a patient with PHP1A. Left: 10 11/12 y (bone age according to Greulich and Pyle, 11 6/12 y). Right: 15 1/12 y (bone age according to Greulich and Pyle, 15 6/12 y). The standards of Greulich and Pyle may not be adequate to assess bone age in patients with PHP1A.
Figure 2.
Figure 2.
Height (upper chart) and height velocity (lower chart) from age 11 to 15 of the patient with PHP1A. Dots represent measured height (in cm), open squares indicate height corrected for bone age (according to Greulich and Pyle). The biochemical onset of puberty and the start of rhGH treatment are indicated in red.
See this image and copyright information in PMC

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