Growth hormone deficiency (GHD) is a rare paediatric disorder, affecting 1:4000-1:10,000 people globally.1
Anatomy and physiology
Growth hormone (GH) is produced by the anterior pituitary gland in response to GH-releasing hormone (GHRH) from the hypothalamus (Figure 1). Binding of GH to its receptors causes the liver to produce insulin-like growth factor 1 (IGF1). IGF1 then mediates growth-promoting functions of GH.
Capillary blood glucose (DM may cause short stature)
Relevant laboratory investigations in the context of suspected GHD, include:
Plasma cortisol level
Coeliac (TTG) antibodies5
Serum IGF1: low in GHD, hypothyroidism, malnutrition and chronic diseases
GH provocation test – GH level measured after clonidine or arginine is administered which stimulates GH secretion
Random GH (neonates only)
Levels of other pituitary hormones (e.g. prolactin, gonadotropin, ACTH)2,4
Relevant image studies in the context of suspected GHD, include:
Wrist X-ray – to determine bone age and compare to chronological age
MRI brain – pituitary gland pathology must be ruled out in all patients with GHD2,4
The mainstay of medical management is GH replacement with regular monitoring:
SC recombinant human GH before bed (mimics normal GH secretion)
The dose should be altered based on growth response and serum IGF1
Treatment is continued until the final height or fusion of growth plates is achieved
Height increase during the first year of treatment is used to predict treatment response2,8
Early GH replacement is associated with a better growth response and prognosis.
If there is widespread pituitary dysfunction, additional pituitary hormone replacement may be necessary:
Levothyroxine for hypothyroidism
Corticosteroids for ACTH deficiency
Oestrogen or testosterone for gonadotrophin deficiency
In certain causes of GHD, surgical management may be considered:
Urgent neurosurgical opinion if CNS tumour is found on imaging.2
Management may include a surgical biopsy with or without resection.9
The following referrals may be considered in the management of GHD:
Ophthalmology referral if eye abnormalities or visual disturbance
Social services referral if abuse-related – psychosocial GHD is reversible and does not respond well to GH replacement2
If GHD is untreated, the following complications may occur:
Ongoing short stature and failure to meet the expected adult height
Coronary artery disease
Type 2 diabetes mellitus
Poor quality of life – low libido, lethargy, social isolation2
There are also several adverse effects associated with GH replacement:
Headaches and idiopathic intracranial hypertension
Slipped capital femoral epiphysis
Exacerbation of pre-existing scoliosis8
Patients are routinely monitored for these complications following initiation of treatment. These issues may be related to the rapid growth associated with GH replacement. If complications occur, GH therapy may be stopped and restarted at a reduced dose.
GHD is a rare condition, usually associated with short stature.
Risk factors include family history and additional pituitary hormone deficiencies.
There is no gold standard test for GHD- diagnosis is dependent on clinical findings and investigations.
GHD is primarily managed by GH replacement unless there is an underlying pathology warranting surgical treatment.
The prognosis of GHD is good if hormone replacement therapy is initiated early.
Stanley T. Diagnosis of Growth Hormone Deficiency in Childhood. Published in 2013. [LINK]
BMJ Best Practice. Growth Hormone Deficiency in Children. Published in 2020. [LINK]
Witkowska-Sidek E and Ruminska M et al. The associations between the growth hormone/insulin-like growth factor-1 axis, adiponectin, resistin and metabolic profile in children with growth hormone deficiency before and during growth hormone treatment. Published in 2018. [LINK]
Chinoy A and Murray P. Diagnosis of growth hormone deficiency in the paediatric and transitional age. Published in 2016. [LINK]
National Organization for Rare Disorders (NORD). Growth Hormone Deficiency. Published in 2016 [LINK]
Fideleff H. Burden of Growth Hormone Deficiency and Excess in Children. Published in 2016 [LINK]
Davis T. Examination: the child with short stature. Published in 2014. [LINK]
Rogol A and Richmond E. UpToDate: Treatment of growth hormone deficiency in children. Published in 2019. [LINK]
Chamberlain M and Silbergeld D. BMJ Best Practice: Published in 2018. [LINK]