Growth Hormone Deficiency & Excess for USMLE 2

Already subscribed? Log in »

Growth Hormone Deficiency & Excess for the USMLE Step 2 Exam

Growth Hormone Deficiency (GHD)

Congenital Causes:
Genetic mutations affecting GH production or release (e.g., GH1 gene mutation).
Congenital malformations of the hypothalamus or pituitary (e.g., septo-optic dysplasia).
Acquired Causes:
Pituitary Tumors: Compression of somatotroph cells.
Trauma: Head injury causing hypothalamic or pituitary damage.
Radiation Therapy: Used for brain or head and neck cancers, which can impair GH production.
Infiltrative Diseases: Sarcoidosis, Langerhans cell histiocytosis affecting pituitary function.

Adults:
Decreased Muscle Mass and Strength: Loss of lean body mass.
Increased Fat Mass: Predominantly in the abdomen, leading to central obesity.
Osteoporosis: Decreased bone mineral density and increased risk of fractures.
Cardiovascular Risk: Increased risk of dyslipidemia, atherosclerosis, and cardiovascular disease.

Stimulation Tests:
Insulin Tolerance Test (ITT): A gold standard test where GH secretion is stimulated by hypoglycemia.
Arginine or Glucagon Stimulation Tests: Alternative tests to evaluate GH reserve.
Low IGF-1 Levels: Supportive of GH deficiency.
MRI: To assess pituitary structure and rule out tumors or structural abnormalities.

Recombinant GH Therapy: Used in both children and adults to promote growth (in children) and improve body composition and quality of life (in adults).
Monitoring: Regular assessments of IGF-1 levels and monitoring for side effects like edema, joint pain, and insulin resistance.

Growth Hormone Excess (Acromegaly and Gigantism)

Pituitary Adenoma: The most common cause, typically a benign somatotroph adenoma that secretes excess GH.
Ectopic GHRH Production: Rarely, tumors (e.g., bronchial carcinoid) may secrete GHRH, stimulating excess GH production.

Acromegaly (Adults):
Skeletal Changes: Enlargement of the hands, feet, jaw, and frontal bones.
Soft Tissue Overgrowth: Thickened skin, macroglossia, and organomegaly.
Cardiovascular Complications: Hypertension, left ventricular hypertrophy, and increased risk of heart failure.
Metabolic Abnormalities: Insulin resistance and hyperglycemia; some patients develop diabetes mellitus.
Respiratory Issues: Obstructive sleep apnea due to enlarged soft tissues of the airway.

Gigantism (Children):
Excessive Linear Growth: Rapid growth before the closure of epiphyseal plates, leading to very tall stature.

Elevated IGF-1: A key marker of chronic GH excess.
Oral Glucose Tolerance Test (OGTT): GH levels fail to suppress after glucose ingestion.
Pituitary MRI: Used to detect pituitary adenomas or other masses.

Transsphenoidal Surgery: First-line treatment for pituitary adenomas to remove the tumor and normalize GH secretion.
Medical Therapy:
Somatostatin Analogs: Octreotide and lanreotide inhibit GH secretion.
GH Receptor Antagonists: Pegvisomant blocks GH action and reduces IGF-1 levels.
Dopamine Agonists: Cabergoline or bromocriptine may reduce GH secretion in some patients.
Radiation Therapy: Considered if surgery and medications fail to control GH levels.

Key Points

Causes include congenital genetic mutations, pituitary tumors, trauma, or radiation.
Presents in children as growth retardation and in adults as muscle loss, central obesity, and cardiovascular risk.
Diagnosis relies on GH stimulation tests (e.g., ITT) and low IGF-1 levels.
Treatment includes recombinant GH therapy to improve growth and body composition.

Most commonly caused by a pituitary adenoma, leading to acromegaly in adults or gigantism in children.
Symptoms include skeletal overgrowth, metabolic disturbances, and cardiovascular complications.
Diagnosis is based on elevated IGF-1 levels and failure of GH suppression in an OGTT.
Treatment includes surgery, somatostatin analogs, and GH receptor antagonists.