Growth Dysfunction

Overview – Growth Dysfunction

Growth dysfunction refers to abnormal patterns of growth, typically caused by disturbances in the endocrine regulation of the growth hormone (GH) axis. These disorders can present as excessive growth (e.g. gigantism or acromegaly) or impaired growth (e.g. pituitary dwarfism). Growth dysfunction can result from a wide range of causes, including pituitary or hypothalamic pathology, receptor resistance, or downstream signalling defects. Understanding the underlying aetiology is crucial for diagnosis and targeted therapy. This page explores both hyper- and hypo-growth hormone conditions, including their clinical features and treatment.

Definition

Growth dysfunction is a disturbance in the normal growth trajectory of a person due to endocrine imbalances—typically involving growth hormone, IGF-1, or their regulatory pathways.

Aetiology

Hypergrowth Disorders

• Excess GH or growth factor production
  • Gigantism: GH excess before epiphyseal plate closure (childhood).
  • Acromegaly: GH excess after epiphyseal closure (adulthood).
• Non-GH causes
  • Precocious puberty.

Hypogrowth Disorders

• GH Deficiency
  • Primary GH Deficiency:
    • Hypothalamic defect.
    • Pituitary defect.
  • Secondary GH Deficiency:
    • Tumours, trauma, or infiltrative disease.
    • Psychosocial deprivation.
• Bio-inactive GH: Normal GH secretion but receptor inactivation.
• GH Insensitivity:
  • Primary:
    • GH receptor defect.
    • IGF synthesis defect.
    • IGF receptor or signalling defect.
  • Secondary:
    • GH-inhibiting antibodies.
    • Chronic disease: malnutrition, uraemia, diabetes.
    • Hormonal deficiencies (e.g. hypothyroidism).

Morphology / Pathophysiology

• GH Deficiency: ↓ IGF-1 production → ↓ chondrocyte proliferation → impaired bone growth.
• GH Excess: ↑ IGF-1 → excessive soft tissue and bone growth. In adults, bone thickening predominates over lengthening due to closed epiphyseal plates.

Clinical Features

GH Deficiency

• Short stature with normal body proportions.
• Delayed puberty.
• Associated signs of pituitary hormone deficiency:
  • Polyuria, excessive thirst, craniofacial anomalies.

GH Excess (Gigantism/Acromegaly)

• Enlarged hands, feet, facial features.
• Jaw and supraorbital ridge prominence.
• Skin thickening, carpal tunnel syndrome.
• Compressive symptoms from pituitary adenoma (e.g. headache, visual field loss).

Investigations

• GH Deficiency
  • GH levels, IGF-1 levels.
  • MRI brain.
  • X-ray: bone age assessment.
• GH Excess
  • Elevated IGF-1.
  • Lack of GH suppression on glucose tolerance test.
  • MRI: pituitary adenoma.

Management

• GH Deficiency
  • Synthetic GH (Somatropin) therapy.
  • Hormone replacement for coexisting deficiencies.
• GH Excess (Acromegaly/Gigantism)
  • Trans-sphenoidal surgery (pituitary adenoma).
  • Somatostatin analogues.
  • Pegvisomant (GH receptor antagonist) in refractory cases.
• Other Treatment Principles
  • IGF-I supplementation in IGF deficiency.
  • Multidisciplinary approach in syndromic or systemic causes.

Complications

• Untreated GH Deficiency:
  • Psychosocial issues.
  • Metabolic syndrome risk in adults.
• GH Excess:
  • Cardiovascular disease: cardiomyopathy, hypertension.
  • Renal failure.
  • Diabetes mellitus.
  • Increased malignancy risk.
  • Osteoarthritis and skeletal deformities.

Differential Diagnosis

• Constitutional short stature.
• Familial tall stature.
• Chronic systemic illness.
• Skeletal dysplasia.
• Hypothyroidism.
• Turner syndrome.
• Precocious puberty (for hypergrowth presentations).

Summary – Growth Dysfunction

Growth dysfunction results from abnormalities in the growth hormone axis, leading to either impaired or excessive somatic growth. Common causes include GH deficiency, receptor resistance, or GH-secreting pituitary adenomas. Early diagnosis and appropriate hormonal therapies can significantly improve outcomes. For a broader context, see our Endocrine Overview page.