Paeds · endocrinology-diabetes-and-growth
Growth hormone deficiency and excess
Also known as Growth hormone deficiency · GHD · Growth hormone excess · Pituitary gigantism · Paediatric acromegaly · Somatotropin deficiency · Recombinant human growth hormone therapy · rhGH therapy · Idiopathic short stature · X-linked acrogigantism
A fellowship approach to disordered growth hormone action: recognise the short child with growth hormone deficiency (short stature crossing centiles, delayed bone age, neonatal hypoglycaemia and midline defects) and the overgrowing child with growth hormone excess (accelerating growth velocity, headache, visual field defect), confirm with IGF-1 and a stimulation test or an oral glucose load, and treat with recombinant growth hormone titrated to IGF-1 for deficiency and transsphenoidal surgery with somatostatin analogue or pegvisomant for excess.
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Target exams
Red flags
- A child whose height is crossing centiles downward on the growth chart, or whose height is below the third centile and distant from the mid-parental range — growth hormone deficiency or an underlying systemic cause must be excluded
- A neonate with persistent hypoglycaemia, micropenis, prolonged jaundice or a midline defect (cleft, single central incisor, septo-optic dysplasia) — congenital hypopituitarism and growth hormone deficiency
- A child whose growth velocity is above the 97th centile for age and sex, or is accelerating upward across centiles — pathological growth hormone excess until a normal variant of tall stature is confirmed
- An overgrowing child with headache, visual field defect, or a new pituitary mass — a somatotropinoma compressing the optic chiasm
- An adolescent with growth hormone deficiency who is stopping therapy at final height without being re-tested — untreated adult growth hormone deficiency impairs body composition and quality of life
- A child with Prader-Willi syndrome starting growth hormone therapy who develops new respiratory symptoms or sleep disturbance — upper-airway obstruction and sleep apnoea are life-threatening in this group
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Care settings
Clinical exam formats
Board mappings
- The child crossing centiles downward as a growth hormone deficiency clue
- Initial work-up of the short child including IGF-1 and bone age
- Principles of recombinant growth hormone therapy and monitoring
- Causes and classification of growth hormone deficiency and excess
- Interpretation of the GH stimulation test and the oral glucose suppression test
- Management of pituitary gigantism including surgery, somatostatin analogues and pegvisomant
- Recognising growth hormone deficiency in a short child and excess in an overgrowing child
- Building an rhGH monitoring plan including IGF-1, growth velocity and glucose
- Counselling on rhGH safety and the transition to adult care
- Long case of a child with growth hormone deficiency on rhGH therapy
- Short case of a child with overgrowth and a pituitary adenoma
- Growth assessment and the short child
- Investigation of disordered growth
- Endocrine causes of short and tall stature
- The GH-IGF-1 axis and the physiology of linear growth
- Diagnosis and management of growth hormone deficiency and excess
- Safety of recombinant growth hormone therapy
- Growth chart interpretation and the short-child work-up
- Communicating a growth hormone therapy plan to a family
- Growth hormone deficiency and the short child
- Pituitary gigantism and the overgrowing child
- Recombinant growth hormone indications and monitoring
- Growth hormone deficiency and excess
- Growth assessment and the interpretation of stimulation tests
- Multidisciplinary management of paediatric endocrine growth disorders
- Growth hormone deficiency and recombinant growth hormone therapy
- Pituitary overgrowth syndromes in children
- Transition of care from paediatric to adult endocrinology
The mark goes to the candidate who reasons along three axes at once. The first is the child in front of you and the growth chart: a trajectory crossing centiles, a height far from the mid-parental target, or a growth velocity that is abnormal for age and sex. The second is the axis physiology: pulsatile growth hormone from the somatotrophs acting through hepatic and local IGF-1, with IGF-1 in turn feeding back to suppress growth hormone release. The third is the whole child: a growth hormone deficiency that is often part of multiple pituitary hormone deficiency and a midline malformation, and a growth hormone excess that is often a pituitary adenoma with mass effect on the optic chiasm and the rest of the pituitary. Treatment is lifelong and multidisciplinary, and the transition from paediatric to adult endocrine care is a high-risk moment that the candidate must own. [1] [10]
Overview & Definition
Growth hormone deficiency is the state in which the anterior pituitary somatotrophs fail to secrete enough growth hormone to sustain normal linear growth and metabolic homeostasis, producing short stature with a delayed bone age and, in early and severe forms, fasting hypoglycaemia and central adiposity. Growth hormone excess is the sustained over-secretion of growth hormone, almost always from a pituitary somatotropinoma, producing pathological linear growth while the growth plates are open — pituitary gigantism — and acral overgrowth with soft-tissue swelling and visceromegaly once the plates fuse, the paediatric counterpart of adult acromegaly. Both sit at the centre of the somatotrope axis, the neuroendocrine loop that runs from the hypothalamus through the pituitary and liver to the growth plate. [1] [10]
The axis is built around insulin-like growth factor 1. Growth hormone releasing hormone from hypothalamic neurones stimulates the somatotrophs to release growth hormone in pulsatile fashion, peaking at night and rising through puberty under the influence of sex steroids. Growth hormone acts on the liver to generate circulating (endocrine) IGF-1 and on cartilage and other tissues to generate local (paracrine) IGF-1, and IGF-1 then drives chondrocyte proliferation and linear growth at the growth plate while feeding back negatively on the hypothalamus and pituitary to restrain further growth hormone release. Insulin-like growth factor binding protein 3 is the principal carrier of IGF-1 in the circulation and is co-regulated by growth hormone, so a low IGF-1 with a low IGFBP-3 is the biochemical signature of growth hormone deficiency. [1] [3]
References12ShowHide
- [1]Collett-Solberg PF, Ambler G, Backeljauw PF, Bidlingmaier M, Biller BMK, Boguszewski MCS, et al. Diagnosis, genetics, and therapy of short stature in children: a Growth Hormone Research Society international perspective. Horm Res Paediatr, 2019.PMID 31514194
- [2]Grimberg A, DiVall SA, Polychronakos C, Allen DB, Cohen LE, Quintos JB, et al. Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency. Horm Res Paediatr, 2016.PMID 27884013
- [3]Murray PG, Dattani MT, Clayton PE. Controversies in the diagnosis and management of growth hormone deficiency in childhood and adolescence. Arch Dis Child, 2016.PMID 26153506
- [4]Sävendahl L, Maes M, Albertsson-Wikland K, et al. Long-term mortality and causes of death in isolated GHD, ISS, and SGA patients treated with recombinant growth hormone during childhood in Belgium, The Netherlands, and Sweden: preliminary report of 3 countries participating in the EU SAGhE study. J Clin Endocrinol Metab, 2012.PMID 22238393
- [5]Guzzetti C, Ibba A, Pilia S, Beltrami N, Loche S. Cut-off limits of the peak GH response to stimulation tests for the diagnosis of GH deficiency in children and adolescents: study in patients with organic GHD. Eur J Endocrinol, 2016.PMID 27147639
- [6]Lee PA, Chernausek SD, Hokken-Koelega AC, Czernichow P; International Small for Gestational Age Advisory Board. International Small for Gestational Age Advisory Board consensus development conference statement: management of short children born small for gestational age, April 24-October 1, 2001. Pediatrics, 2003.PMID 12777538
- [7]Houk CP, Lee PA. Early diagnosis and treatment referral of children born small for gestational age without catch-up growth are critical for optimal growth outcomes. Int J Pediatr Endocrinol, 2012.PMID 22559301
- [8]Aversa T, Li Pomi A, Pepe G, et al. Growth hormone treatment to final height in Turner syndrome: systematic review. Clin Ther, 2024.PMID 38151406
- [9]Fillion M, Deal C, Van Vliet G. Retrospective study of the potential benefits and adverse events during growth hormone treatment in children with Prader-Willi syndrome. J Pediatr, 2009.PMID 18814886
- [10]Korbonits M, Blair JC, Boguslawska A, et al. Consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: Part 2, specific diseases. Nat Rev Endocrinol, 2024.PMID 38336898
- [11]Joshi K, Daly AF, Beckers A, et al. Resistant paediatric somatotropinomas due to AIP mutations: role of pegvisomant. Horm Res Paediatr, 2018.PMID 29953972
- [12]Daly AF, Beckers A The genetic pathophysiology and clinical management of the TADopathy, X-linked acrogigantism. Endocr Rev, 2024.PMID 38696651