GROWTH HORMONE DEFICIENCY

✓ Medically ReviewedDISEASEID: MDBT0283🚨 TRIAGE: URGENTICD-10: E23.0

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Definition

CLINICAL DEFINITION

Growth hormone deficiency (GHD) is a clinical syndrome defined by suboptimal secretion of growth hormone (GH) from the anterior pituitary, which may occur in isolation (isolated GHD) or in combination with other anterior and/or posterior pituitary hormone deficiencies (combined pituitary hormone deficiency). It may be congenital or acquired, sporadic or familial, and can present in childhood with growth failure or in adulthood with altered body composition, metabolic abnormalities, and impaired quality of life. Diagnosis is based on a combination of auxological, biochemical, neuroradiological, and clinical criteria, and provocative GH testing is often required except in defined circumstances where the diagnosis can be established without it.

IN PLAIN ENGLISH

Growth hormone deficiency means the body does not make enough growth hormone. In children, this can cause slow growth and short height. In adults, it can affect energy, muscle strength, body fat, and bone health.

COMMON MISCONCEPTION / WHAT IT DOES NOT MEAN

Growth hormone deficiency is NOT simply the presence of short stature. Most children with short stature do not have GHD; short stature is a common finding with many other causes, and the diagnosis requires biochemical and clinical evidence of insufficient GH secretion, not height alone.

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Word Breakdown

somatotropin

=somatotropin — the hormone that stimulates body growth (from Greek 'soma' — body, and 'trope' — a turning, referring to growth)

Literal Meaning: A deficiency of somatotropin (growth hormone)

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Abbreviations

GHD=Growth Hormone Deficiency — the overarching diagnostic term

GH=Growth Hormone — the pituitary hormone that is deficient

IGF-1=Insulin-like Growth Factor 1 — GH-dependent mediator used in screening

IGHD=Isolated Growth Hormone Deficiency — GHD without other pituitary hormone deficits

CPHD=Combined Pituitary Hormone Deficiency — deficiency of two or more pituitary hormones

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Synonyms & Variants

Somatotropin Deficiency›Pituitary Dwarfism›Hyposomatotropism›

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Category-Specific Context

As a Disease, growth hormone deficiency is a defined pathological condition with recognised diagnostic criteria. It spans a spectrum from isolated, idiopathic GH deficiency to combined pituitary hormone deficiency and acquired forms secondary to structural lesions, surgery, or irradiation. Severity is often described in terms of peak GH response to provocative testing and the number of additional pituitary hormone deficits.

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Clinical Context & Usage

CLINICAL SETTINGS

Paediatric Endocrinology ClinicAdult Endocrinology ClinicGeneral Paediatrics WardNeurosurgery/Neuro-oncology ClinicGeneral Medicine Ward

USAGE & DOCUMENTATION NOTES

In paediatric notes, GHD is typically documented as 'growth hormone deficiency (GHD)' with auxological data (height SDS, height velocity) and provocative test results. In adult practice, it is often recorded as 'adult growth hormone deficiency (AGHD)' or 'GHD secondary to [pituitary adenoma/irradiation]'. Referral letters frequently state the peak GH value on stimulation testing and whether other pituitary axes are affected. When the diagnosis is established without provocative testing under recognised criteria, the basis (e.g., structural hypothalamic–pituitary defect plus another pituitary hormone deficiency) is explicitly documented.

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Primary Causes & Pathophysiology

PATHOPHYSIOLOGY

Growth hormone (GH) is synthesized and secreted by somatotroph cells of the anterior pituitary under dual hypothalamic control: GH-releasing hormone (GHRH) stimulates secretion, while somatostatin inhibits it. GH exerts many of its growth-promoting effects indirectly through insulin-like growth factor 1 (IGF-1), produced mainly by the liver in response to GH. In GHD, disruption at any level of this hypothalamic–pituitary–somatotroph axis — developmental defects, genetic mutations, structural lesions, irradiation, or idiopathic dysfunction — leads to reduced GH secretion and consequently reduced IGF-1 production. The resulting deficiency of GH and IGF-1 impairs linear growth in children and contributes to altered body composition (reduced lean mass, increased visceral fat), reduced bone mineral density, dyslipidaemia, and impaired quality of life in both children and adults.

PRIMARY CAUSES

Idiopathic isolated growth hormone deficiency

The most common paediatric form; the underlying cause is not identifiable in most cases, but the result is suboptimal GH secretion from the somatotroph cells without an evident structural or genetic lesion.

Congenital hypothalamic–pituitary malformations (e.g., ectopic posterior pituitary, pituitary hypoplasia, abnormal pituitary stalk)

Developmental disruption of the hypothalamic–pituitary axis reduces the number or function of somatotroph cells and/or impair GHRH delivery to the anterior pituitary.

Genetic mutations affecting GH synthesis, secretion, or pituitary development (e.g., GH1, GHRHR, PROP1, POU1F1)

Monogenic defects impair somatotroph differentiation, GH gene expression, or GHRH signalling, leading to isolated or combined pituitary hormone deficiency.

Pituitary or hypothalamic tumours (e.g., craniopharyngioma, pituitary adenoma)

Mass effect compresses normal somatotroph cells or the pituitary stalk, reducing GH secretion; tumours may also cause hypopituitarism through raised intrasellar pressure.

Cranial irradiation or surgery involving the hypothalamic–pituitary region

Radiation and surgical damage to somatotroph cells or hypothalamic GHRH neurons reduce GH secretory capacity; the effect may be delayed and progressive.

Traumatic brain injury

Traumatic damage to the hypothalamic–pituitary axis can cause acute or delayed hypopituitarism, including GHD, through vascular or direct parenchymal injury.

Infiltrative, infectious, or inflammatory hypothalamic–pituitary disease (e.g., Langerhans cell histiocytosis, sarcoidosis, meningitis)

Inflammatory or infiltrative processes damage somatotroph cells or hypothalamic regulatory centres, impairing GH secretion.

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Drug-Induced Causes

💊 Glucocorticoids (e.g., prednisolone, dexamethasone) ↗

Mechanism: Supraphysiological glucocorticoid exposure suppresses hypothalamic GHRH gene expression and reduces GH secretion, and may also impair GH action at peripheral tissues.

→ Use the lowest effective glucocorticoid dose; in children receiving long-term glucocorticoids, monitor growth and consider endocrine assessment if growth failure occurs.

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Epidemiology

Prevalence:Paediatric GHD is uncommon; systematic review estimates range from approximately 1 in 1,107 to 1 in 8,646 children and adolescents, with reported incidences of about 1 in 28,800 to 1 in 46,700 per year in European studies. Congenital GHD incidence is estimated at 1 in 3,500 to 10,000 live births. Adult-onset GHD is most often secondary to pituitary tumours or their treatment.

Age Group:GHD can present at any age. Congenital forms typically present in infancy or early childhood with growth failure; idiopathic isolated GHD is commonly diagnosed in mid-childhood (median age around 8–9 years in reported series). Adult-onset GHD usually results from acquired hypothalamic–pituitary disease or its treatment and is most often diagnosed in adults with a history of pituitary tumour, surgery, or irradiation.

Sex Predilection:Male

Geographic Distribution:No consistent, established global geographic or ethnic variation in the prevalence of congenital GHD has been demonstrated; reported estimates are predominantly from European studies and may not be globally representative. Adult GHD distribution largely reflects the epidemiology of pituitary and hypothalamic disease and access to cranial irradiation.

Red Flags & Triage ★

TRIAGE LEVEL

🚨 URGENT

DO NOT MISS — LIFE-THREATENING PRESENTATIONS

A child with growth failure and signs of raised intracranial pressure or visual field defects — consider a hypothalamic–pituitary tumour (e.g., craniopharyngioma) and arrange urgent neuroimaging.
An infant with hypoglycaemia, micropenis, or prolonged jaundice — consider congenital hypopituitarism with multiple pituitary hormone deficiencies, which requires urgent endocrine assessment and treatment of adrenal insufficiency if present.
An adult with a history of pituitary tumour or cranial irradiation who develops fatigue, hypotension, or electrolyte disturbance — consider unrecognised ACTH or TSH deficiency alongside GHD, because adrenal insufficiency can be life-threatening.

URGENT EVALUATION TRIGGERS

Hypoglycaemia in a neonate or young infant that is not readily explained by hyperinsulinism, especially if accompanied by micropenis or cholestatic jaundice.
Headache with visual field loss, papilloedema, or cranial nerve palsy in a child with growth failure — concerning for a hypothalamic–pituitary mass.
New-onset hypotension, hyponatraemia, or collapse in a patient with known hypopituitarism or a pituitary lesion — possible adrenal crisis requiring immediate glucocorticoid therapy.

Contraindications & Precautions

CONTRAINDICATIONS

Active malignancy — GH and IGF-1 have mitogenic potential
so GH replacement is generally contraindicated in patients with active neoplasia unless specifically directed by the treating oncology team.
Acute critical illness (e.g.
sepsis
acute respiratory failure
post-cardiac surgery) — GH therapy should not be initiated or continued in the acute critical care setting because of increased mortality observed in trials of high-dose GH in critically ill patients.
Diabetic retinopathy — proliferative or severe non-proliferative diabetic retinopathy is a relative contraindication; GH/IGF-1 may worsen retinopathy
and ophthalmological assessment is required before treatment.

SPECIAL PRECAUTIONS

Monitor for intracranial hypertension (papilloedema
headache
visual changes)
slipped capital femoral epiphysis
and scoliosis progression in children receiving GH; assess at each visit.
Reassess the adrenal and thyroid axes after starting GH in patients at risk of multiple pituitary hormone deficiencies
because GH replacement can unmask or worsen adrenal insufficiency and hypothyroidism.
Titrate GH dose to age-appropriate IGF-1 levels and clinical response rather than using a fixed dose
and reduce the dose if IGF-1 rises above the normal range.
In adults with GHD
assess cardiovascular risk factors and bone density at baseline and during follow-up.

Complications

DOWNSTREAM CLINICAL COMPLICATIONS

Reduced bone mineral density and increased fracture risk (GH and IGF-1 deficiency impair bone remodelling and peak bone mass accrual)
Adverse body composition — increased visceral adiposity and reduced lean mass (GH deficiency shifts substrate metabolism toward fat storage and reduces muscle protein synthesis)
Dyslipidaemia and increased cardiovascular risk (GH deficiency is associated with elevated LDL cholesterol
triglycerides
and reduced HDL cholesterol)
Impaired quality of life and psychological disturbance (adults with GHD report reduced energy
impaired well-being
and poorer cognitive function)
Short stature and psychosocial burden in childhood (if untreated or diagnosed late)
Hypoglycaemia in neonates and young children with congenital hypopituitarism (GH is counter-regulatory and its deficiency reduces hepatic glucose output)

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Confused With (LASA & DDx) ★

CLINICAL DIFFERENTIAL DIAGNOSES (DDx)

Constitutional delay of growth and puberty

Key Distinguishing Feature: Delayed bone age and pubertal development with eventual spontaneous catch-up growth; GH provocative testing is usually normal, and sex steroid priming may be needed before testing to avoid misclassification.

Familial short stature

Key Distinguishing Feature: Height consistent with mid-parental target height, normal growth velocity, and normal IGF-1 and GH stimulation results.

GH insensitivity (e.g., Laron syndrome)

Key Distinguishing Feature: Low IGF-1 and IGFBP-3 with elevated or normal GH on stimulation; IGF-1 generation test may help distinguish GH resistance from GH deficiency.

Primary hypothyroidism

Key Distinguishing Feature: Low free T4 and elevated TSH; hypothyroidism can impair growth and should be treated before interpreting GH axis testing.

Chronic systemic disease (e.g., coeliac disease, inflammatory bowel disease, chronic kidney disease)

Key Distinguishing Feature: Evidence of the underlying systemic illness, often with growth failure but without a specific GH secretory defect; treating the primary condition improves growth.

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Clinical Pearls

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GHD is a biochemical diagnosis, not a height-based one. A child with short stature and a normal growth velocity is unlikely to have GHD; the combination of poor growth velocity and a low IGF-1 for age should prompt endocrine referral.

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IGF-1 is a screening test, not a stand-alone diagnostic test. In adults, up to 20% of those with documented GHD can have a normal IGF-1, so provocative testing is required when clinical suspicion remains.

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Provocative GH testing must be interpreted in context. Sex steroid priming improves diagnostic accuracy in prepubertal children, and the cut-off for a ‘pass’ depends on the stimulus, the assay, and the clinical scenario.

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In congenital hypopituitarism, GH deficiency is often accompanied by other pituitary hormone deficiencies. Adrenal insufficiency must be treated before or alongside GH replacement because GH can unmask or worsen cortisol deficiency.

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Not all childhood-onset GHD persists into adulthood. Reassessment of the GH–IGF-1 axis after completion of growth and puberty is necessary to determine who requires long-term adult GH replacement.

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Example Usage & SOAP

CLINICAL SENTENCE

"‘Growth hormone deficiency was diagnosed in a 7-year-old boy with height −2.8 SDS, height velocity <4 cm/year, peak GH 4.2 ng/mL on arginine stimulation, and a low IGF-1 for age; MRI showed a hypoplastic anterior pituitary with an ectopic posterior pituitary.’"

IN A SOAP NOTE

S: Parent reports the child has been growing slowly for 2 years and is the shortest in his class. O: Height 106 cm (−2.9 SDS), height velocity 3.5 cm/year, bone age 4 years (chronological age 7 years), IGF-1 45 ng/mL (low for age), peak GH 3.8 ng/mL on glucagon stimulation. A: Growth hormone deficiency, likely congenital, with no other pituitary hormone deficits on baseline testing. P: Initiate recombinant human GH at 0.16–0.24 mg/kg/week subcutaneously; monitor IGF-1, growth velocity, and for adverse effects; arrange follow-up in 3–6 months.

DIFFERENTIAL DIAGNOSIS CONTEXT

Differential diagnosis for a child with short stature and poor growth: (1) Growth hormone deficiency — low IGF-1, peak GH <10 ng/mL on provocative testing, and often a structural pituitary abnormality on MRI. (2) Constitutional delay of growth and puberty — delayed bone age, family history of late puberty, and eventual spontaneous catch-up; GH testing is usually normal. (3) GH insensitivity — low IGF-1 with elevated GH on stimulation, suggesting a post-receptor defect. (4) Primary hypothyroidism — low free T4 and elevated TSH; growth failure improves with levothyroxine. (5) Chronic systemic disease — evidence of coeliac disease, inflammatory bowel disease, or chronic kidney disease, with growth failure resolving when the underlying condition is treated.

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Prognosis

SHORT-TERM OUTCOME

With appropriate GH replacement, children with GHD can achieve catch-up growth; short-term height velocity typically improves within the first year of treatment. In adults, GH replacement improves body composition, exercise capacity, and quality of life over months, but the response is variable and depends on the underlying cause and other hormone deficiencies.

LONG-TERM PROGNOSIS

Early diagnosis and sustained GH treatment in childhood usually allow attainment of a normal or near-normal adult height. Some patients with childhood-onset GHD have persistent deficiency and require continued GH therapy into adulthood; others may recover. Adults with untreated GHD have increased long-term cardiovascular and skeletal morbidity. Prognosis in acquired GHD depends on the underlying lesion and the adequacy of replacement of all deficient pituitary hormones.

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References & Coding

ICD-10 DIAGNOSTIC CODE

E23.0

LITERATURE CITATIONS & GUIDELINES

[1]Pediatric Endocrine Society. Guidelines on growth disorders and their treatment. Drug and Therapeutics Committee and Ethics Committee of the Pediatric Endocrine Society. 2024.

[2]Mameli C, Guadagni L, Orso M, et al. Epidemiology of growth hormone deficiency in children and adolescents: a systematic review. Endocrine. 2024;85:91–98. doi:10.1007/s12020-024-03778-4.

[3]Aversa LS, Cuboni D, Grottoli S, Ghigo E, Gasco V. A 2024 update on growth hormone deficiency syndrome in adults: from guidelines to real life. J Clin Med. 2024;13(20):6079. doi:10.3390/jcm13206079.

[4]Yuen KCJ, Biller BMK, Radovick S, et al. American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of growth hormone deficiency in adults and patients transitioning from pediatric to adult care. Endocr Pract. 2019;25(11):1191-1232. doi:10.4158/GL-2019-0405.

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