A surprising treatment response in a patient with rare isolated growth hormone deficiency, type IB

Abstract

Isolated Growth Hormone Deficiency (IGHD) is a rare cause of short stature, treated with the standard regimen of subcutaneous synthetic growth hormone (GH). Patients typically achieve a maximum height velocity in the first year of treatment, which then tapers shortly after treatment is stopped. We report a case of a 9-year-old male who presented with short stature (<3rd percentile for age and race). Basal hormone levels showed undetectable serum IGF1. Skeletal wrist age was consistent with chronologic age. Cranial MRI revealed no masses or lesions. Provocative arginine-GH stimulation testing demonstrated a peak GH level of 1.4 ng/mL. Confirmatory genetic testing revealed a rare autosomal recessive single-nucleotide polymorphism (SNP) with mutational frequency of 2%. GH supplementation was started and pursued for 2 years, producing dramatically increased height velocity. This velocity persisted linearly through adolescence, several years after treatment had been discontinued. Final adult height was >95th percentile for age and race. In conclusion, this is a case of primary hypopituitarism with differential diagnosis of IGHD vs Idiopathic Short Stature vs Constitutional Growth Delay. This case supports two objectives: Firstly, it highlights the importance of confirmatory genetic testing in patients with suspected, though diagnostically uncertain, IGHD. Secondly, it demonstrates a novel secondary growth pattern with implications for better understanding the tremendous variability of GH treatment response.

Learning points:

• GHD is a common cause of growth retardation, and IGHD is a specific subtype of GHD in which patients present solely with short stature.

• The standard treatment for IGHD is subcutaneous synthetic GH until mid-parental height is reached, with peak height velocity attained in the 1st year of treatment in the vast majority of patients.

• Genetic testing should be strongly considered in cases of diagnostic uncertainty prior to initiating treatment.

• Future investigations of GH treatment response that stratify by gene and specific mutation will help guide treatment decisions.

• Response to treatment in patients with IGHD is variable, with some patients demonstrating little to no response, while others are ‘super-responders.’