FRI598 Evolving Growth Hormone Deficiency: A Proof Of Concept

Disclosure: S. Chimatapu: None. S. Sethuram: None. J. Samuels: None. M. Savage: None. R. Rapaport: None. Introduction: Most cases of growth hormone deficiency (GHD) in pediatric patients are idiopathic, isolated and acquired. All acquired conditions commence with a period during which the diagnosis maybe unapparent. We document here evidence for evolution of GHD in a group of adolescent males who tested sufficient on initial GH stimulation test (GST) but tested deficient upon reevaluation. The rationale for repeat GST was ongoing growth failure. Hypothesis: We hypothesize that GHD in some individuals evolves with time and can be diagnosed by repeat testing (EGHD). We also postulate that their response to GH therapy is similar to other patients with GHD. Methods: We performed an IRB-approved retrospective chart review of children who presented for short stature (height less < 2SD for mean or < 2SD for mid-parental height) to pediatric endocrinology at Kravis Children’s Hospital at Mount Sinai, New York and who had 2 GST. GST were performed using two different stimuli (arginine and glucagon) and highly sensitive assay serum GH measurements were processed by the same laboratory, Esoterix. No patient had obesity, chronic illnesses, or any genetic conditions affecting growth. Data were collected from electronic medical records and analyzed using SPSS v28.0 once at least half the population studied reached adult height. We defined adult height as bone age ≥ 16 years and growth velocity ≤ 2 cm/year. Results: Of 42 charts analyzed, all male, 25 had EGHD. Their average GH peak on initial GST was 15.48 ± 4.92 ng/ml, mean age 10.07 ± 2.65 years, mean height -1.68 ± 0.56 SD , IGF-1 -1.00 ± 0.88 SD. After 2.23 ± 1.22 years, at 12.04 ± 2.41years, height decreased to -1.82 ± 0.63 SD and IGF-1 was -1.08 ± 0.84 SD. At repeat GST, GH peak was 7.59 ± 2.12 ng/mL and 28% were in puberty. All patients had MRI before starting GH therapy; 40% had small anterior pituitary glands. 12 males who reached adult height had a height of -1.88 ± 0.64 SD, IGF-1 of -1.15 ± 0.81 SD, with 42% pubertal and peak GH of 7.33 ± 2.47 ng/mL at repeat GST. They had a mean height gain of 1.83 ± 0.56 SD(p<0.005), with an adult height of 0.09 ± 0.70 SD after 4.64 ± 1.4years of treatment. They were 2.10 ± 4.20 cm taller than their mid-parental target heights. Discussion/Conclusions: We provide proof of concept for the diagnosis of EGHD. The diagnosis could be established by repeat GST in children with ongoing growth deceleration despite pubertal progression and a non-diagnostic initial GST. Our patients who reached adult height had a height gain consistent with that reported by KIGS for patients with growth hormone deficiency (1.7SD; Cutfield,1999) and indeed better than patients with ISS (0.7SD; Maghnie,2022). Presentation: Friday, June 16, 2023