gigantism

Gigantism is a rare condition caused by chronic excess growth hormone (GH) secretion beginning in childhood, while the growth plates (epiphyses) are still open. The result is excessive linear growth and overgrowth of bone and soft tissues, often accompanied by metabolic and organ hypertrophy.

Most cases are due to a GH-secreting pituitary adenoma (somatotroph adenoma). Less common causes include X-linked acrogigantism due to duplication of the GPR101 gene and pituitary hyperplasia. The elevated GH stimulates production of insulin-like growth factor 1 (IGF-1), mainly in the liver, which mediates many growth-promoting effects.

Clinically, individuals present with rapidly increasing height, enlarged hands and feet, prominent facial features, and tongue enlargement. Headaches and visual field deficits from pituitary enlargement are possible. Sleep apnea, joint pain, and delayed puberty may occur. Metabolic sequelae include insulin resistance and diabetes; cardiovascular complications can develop over time.

Diagnosis involves measuring elevated serum IGF-1 for age, and demonstrating failure of GH to suppress during an oral glucose tolerance test, followed by MRI to identify a pituitary lesion. Evaluation for comorbidities and, when appropriate, genetic testing are common. It is distinguished from acromegaly, which results when GH excess occurs after the growth plates have closed.

Treatment aims to normalize GH/IGF-1 levels and manage complications. First-line therapy is surgical resection of the pituitary adenoma via transsphenoidal surgery. Medical options include somatostatin analogues (e.g., octreotide, lanreotide), GH receptor antagonists (pegvisomant), and, in some cases, dopamine agonists. Radiotherapy may be used for residual disease. Prognosis improves with early treatment; untreated gigantism carries risks such as cardiomyopathy, hypertension, diabetes, and reduced life expectancy.