Growth Hormone Deficiency & Excess for USMLE 3
Growth Hormone Deficiency & Excess for the USMLE Step 3 Exam
Growth Hormone Deficiency (GHD)
- Etiology
- Congenital:
- Genetic mutations affecting GH production (e.g., GH1 gene mutations).
- Congenital pituitary or hypothalamic malformations (e.g., septo-optic dysplasia).
- Acquired:
- Pituitary Adenomas: Tumors that compress the somatotroph cells or disrupt the hypothalamic-pituitary axis.
- Trauma or Surgery: Injury to the pituitary region.
- Radiation Therapy: Common after treatment for brain or head and neck cancers.
- Infiltrative Diseases: Sarcoidosis, tuberculosis, or Langerhans cell histiocytosis that damage pituitary function.
- Clinical Features
- Children:
- Short Stature: Decreased growth velocity and failure to meet expected growth milestones.
- Delayed Puberty: Late onset of sexual development.
- Adults:
- Reduced Lean Body Mass: Loss of muscle mass, increased fat mass, and central obesity.
- Osteoporosis: Decreased bone mineral density with increased fracture risk.
- Increased Cardiovascular Risk: Dyslipidemia, increased risk of atherosclerosis, and reduced cardiac output.
- Diagnosis
- GH Stimulation Tests:
- Insulin Tolerance Test (ITT): GH levels should rise in response to hypoglycemia.
- Arginine or Glucagon Stimulation Test: Alternative tests used to assess GH reserve.
- Low IGF-1 Levels: A marker of GH deficiency, as IGF-1 reflects GH activity.
- MRI of the Pituitary: To evaluate for tumors or structural abnormalities.
- Treatment
- Recombinant GH Therapy: Indicated for both children and adults.
- In children, it promotes normal growth and development.
- In adults, it improves muscle mass, decreases fat, and enhances quality of life.
- Monitoring: Regular follow-up for dose adjustments, monitoring IGF-1 levels, and managing side effects like joint pain and insulin resistance.
Growth Hormone Excess (Acromegaly and Gigantism)
- Etiology
- Pituitary Adenoma: The most common cause of GH excess, resulting in unregulated secretion of GH from a somatotroph adenoma.
- Ectopic GHRH Production: Rarely, extrapituitary tumors (e.g., bronchial carcinoid) can produce GHRH, leading to increased GH secretion.
- Clinical Features
- Acromegaly (Adults):
- Skeletal Overgrowth: Enlarged hands, feet, and facial bones (prominent jaw and forehead).
- Soft Tissue Overgrowth: Thickened skin, enlarged tongue (macroglossia), and organomegaly.
- Cardiovascular Disease: Hypertension, left ventricular hypertrophy, and increased risk of heart failure.
- Metabolic Effects: Insulin resistance and hyperglycemia, increasing the risk of diabetes mellitus.
- Sleep Apnea: Due to airway obstruction from enlarged soft tissues.
- Gigantism (Children):
- Excessive Height: Rapid linear growth before the closure of epiphyseal plates.
- Diagnosis
- Elevated IGF-1 Levels: IGF-1 reflects the activity of GH and is typically elevated in GH excess.
- Oral Glucose Tolerance Test (OGTT): GH levels fail to suppress following oral glucose administration in patients with acromegaly.
- MRI of the Pituitary Gland: Essential for identifying pituitary adenomas.
- Treatment
- Transsphenoidal Surgery: The primary treatment for pituitary adenomas, aiming to reduce tumor mass and normalize GH levels.
- Medical Therapy:
- Somatostatin Analogs: Octreotide and lanreotide inhibit GH secretion.
- GH Receptor Antagonists: Pegvisomant blocks GH receptors, reducing IGF-1 levels.
- Dopamine Agonists: Cabergoline and bromocriptine can suppress GH secretion in some cases.
- Radiation Therapy: Used as adjunctive therapy when surgery and medications fail to control GH excess.
Key Points
- Growth Hormone Deficiency (GHD):
- Causes include congenital mutations, pituitary tumors, trauma, and radiation.
- Presents with short stature in children and decreased muscle mass, obesity, and cardiovascular risks in adults.
- Diagnosis includes GH stimulation tests and low IGF-1 levels.
- Treatment involves recombinant GH therapy with regular monitoring.
- Growth Hormone Excess:
- Typically caused by a pituitary adenoma, leading to acromegaly in adults and gigantism in children.
- Symptoms include skeletal and soft tissue overgrowth, cardiovascular complications, and insulin resistance.
- Diagnosis is based on elevated IGF-1 levels and failure of GH suppression in an OGTT.
- Treatment involves surgery, somatostatin analogs, GH receptor antagonists, and radiation if needed.