Diagnosis and Treatment > Investigation > GH stimulation

You are looking at 1 - 3 of 3 items

George Stoyle Department of Paediatric Endocrinology, Royal Manchester Children’s Hospital, Manchester, UK
Manchester Medical School, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK

Search for other papers by George Stoyle in
Google Scholar
PubMed
Close
,
Siddharth Banka Manchester Centre for Genomic Medicine, Division of Evolution & Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
Manchester Centre for Genomic Medicine, St Mary’s Hospital, Manchester University, NHS Foundation Trust, Health Innovation Manchester, Manchester, UK

Search for other papers by Siddharth Banka in
Google Scholar
PubMed
Close
,
Claire Langley Manchester Centre for Genomic Medicine, St Mary’s Hospital, Manchester University, NHS Foundation Trust, Health Innovation Manchester, Manchester, UK

Search for other papers by Claire Langley in
Google Scholar
PubMed
Close
,
Elizabeth A Jones Manchester Centre for Genomic Medicine, Division of Evolution & Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
Manchester Centre for Genomic Medicine, St Mary’s Hospital, Manchester University, NHS Foundation Trust, Health Innovation Manchester, Manchester, UK

Search for other papers by Elizabeth A Jones in
Google Scholar
PubMed
Close
, and
Indraneel Banerjee Department of Paediatric Endocrinology, Royal Manchester Children’s Hospital, Manchester, UK

Search for other papers by Indraneel Banerjee in
Google Scholar
PubMed
Close

Summary

Wiedemann–Steiner Syndrome (WSS) is a rare condition characterised by short stature, hypertrichosis of the elbow, intellectual disability and characteristic facial dysmorphism due to heterozygous loss of function mutations in KMT2A, a gene encoding a histone 3 lysine 4 methyltransferase. Children with WSS are often short and until recently, it had been assumed that short stature is an intrinsic part of the syndrome. GHD has recently been reported as part of the phenotypic spectrum of WSS. We describe the case of an 8-year-old boy with a novel heterozygous variant in KMT2A and features consistent with a diagnosis of WSS who also had growth hormone deficiency (GHD). GHD was diagnosed on dynamic function testing for growth hormone (GH) secretion, low insulin-like growth factor I (IGF-I) levels and pituitary-specific MRI demonstrating anterior pituitary hypoplasia and an ectopic posterior pituitary. Treatment with GH improved height performance with growth trajectory being normalised to the parental height range. Our case highlights the need for GH testing in children with WSS and short stature as treatment with GH improves growth trajectory.

Learning points:

  • Growth hormone deficiency might be part of the phenotypic spectrum of Wiedemann–Steiner Syndrome (WSS).

  • Investigation of pituitary function should be undertaken in children with WSS and short stature. A pituitary MR scan should be considered if there is biochemical evidence of growth hormone deficiency (GHD).

  • Recombinant human growth hormone treatment should be considered for treatment of GHD.

Open access
Jia Xuan Siew Paediatric Medicine, KK Women’s and Children’s Hospital, Singapore, Singapore

Search for other papers by Jia Xuan Siew in
Google Scholar
PubMed
Close
and
Fabian Yap Paediatric Endocrinology, KK Women’s and Children’s Hospital, Singapore, Singapore

Search for other papers by Fabian Yap in
Google Scholar
PubMed
Close

Summary

Growth anomaly is a prominent feature in Wolf-Hirschhorn syndrome (WHS), a rare congenital disorder caused by variable deletion of chromosome 4p. While growth charts have been developed for WHS patients 0–4 years of age and growth data available for Japanese WHS patients 0–17 years, information on pubertal growth and final height among WHS children remain lacking. Growth hormone (GH) therapy has been reported in two GH-sufficient children with WHS, allowing for pre-puberty catch up growth; however, pubertal growth and final height information was also unavailable. We describe the complete growth journey of a GH-sufficient girl with WHS from birth until final height (FH), in relation to her mid parental height (MPH) and target range (TR). Her growth trajectory and pubertal changes during childhood, when she was treated with growth hormone (GH) from 3 years 8 months old till 6 months post-menarche at age 11 years was fully detailed.

Learning points:

  • Pubertal growth characteristics and FH information in WHS is lacking.

  • While pre-pubertal growth may be improved by GH, GH therapy may not translate to improvement in FH in WHS patients.

  • Longitudinal growth, puberty and FH data of more WHS patients may improve the understanding of growth in its various phases (infancy/childhood/puberty).

Open access
Jordan Yardain Amar Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA

Search for other papers by Jordan Yardain Amar in
Google Scholar
PubMed
Close
,
Kimberly Borden David Geffen School of Medicine at UCLA, Los Angeles, California, USA

Search for other papers by Kimberly Borden in
Google Scholar
PubMed
Close
,
Elizabeth Watson Sidney Kimmel College of Medicine at Thomas Jefferson University, Philadelphia, Pennsylvania, USA

Search for other papers by Elizabeth Watson in
Google Scholar
PubMed
Close
, and
Talin Arslanian Mattel Children’s Hospital, University of California, Los Angeles, California, USA

Search for other papers by Talin Arslanian in
Google Scholar
PubMed
Close

Summary

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.’

Open access