Acromegaly & Gigantism

Key Features

Essentials of Diagnosis

• Pituitary neuroendocrine tumor

• Acromegaly: excessive growth of hands, feet, jaw, and internal organs

• Gigantism if growth hormone (GH) excess before closure of epiphyses; acromegaly if after closure

• Amenorrhea, hypertension, headaches, visual field loss, weakness

• Soft, doughy, sweaty handshake

• Elevated serum insulin-like growth factor 1 (IGF-1)

• Serum GH not suppressed following oral glucose

General Considerations

• GH exerts much of its effects by stimulating release of IGF-1

• Nearly always caused by pituitary adenoma, usually macroadenomas (> 1 cm); may be locally invasive but < 1% are malignant

• GH-secreting pituitary tumors usually cause hypogonadism by cosecretion of prolactin or direct pressure on pituitary

• Usually sporadic, rarely familial with < 3% being due to multiple endocrine neoplasia (MEN) types 1 or 4

• Rarely, acromegaly may be seen in McCune-Albright syndrome and Carney complex

• Occasionally caused by ectopic secretion of GH-releasing hormone or GH secreted by lymphoma, hypothalamic tumor, bronchial carcinoid, or pancreatic tumor

Clinical Findings

Symptoms and Signs

• Tall stature

• Head and neck

  • Facial features coarsen

  • Hat size increases, tooth spacing widens

  • Mandible becomes more prominent

  • Macroglossia and hypertrophy of pharyngeal and laryngeal tissue

    • Deep, coarse voice

    • May cause obstructive sleep apnea

  • Goiter may be noted

• Hands

  • Enlarged

  • Fingers widen and rings no longer fit

  • Carpal tunnel syndrome is common

• Feet grow, particularly as change in shoe width

• Hypertension (50%) and cardiomegaly

• Weight gain

• Arthralgias, degenerative arthritis, and spinal stenosis may occur

• Colon polyps common

• Skin

  • Hyperhidrosis

  • Thickening

  • Cystic acne

  • Skin tags

  • Acanthosis nigricans

• Symptoms of hypopituitarism

  • Hypogonadism: decreased libido, erectile dysfunction, irregular menses or amenorrhea common

  • Women who become pregnant have an increased risk of gestational diabetes mellitus and hypertension

  • Secondary hypothyroidism sometimes occurs, hypoadrenalism is unusual

  • Headaches and temporal hemianopia

Differential Diagnosis

• Familial tall stature, coarse features, or large hands and feet

• Physiologic growth spurt

• Pseudoacromegaly (acromegaly features, insulin resistance)

• Inactive ("burned-out") acromegaly (spontaneous remission due to pituitary adenoma infarction)

• Myxedema

• Isolated prognathism (jaw protrusion)

• Aromatase deficiency or estrogen receptor deficiency causing tall stature

• Other causes of increased GH level

  • Exercise or eating prior to test

  • Acute illness or agitation

  • Liver failure or kidney disease

  • Malnourishment

  • Diabetes mellitus

  • Drugs (estrogens, β-blockers, clonidine)

Diagnosis

Laboratory Tests

• Assay for the following

  • Serum GH

  • IGF-1 (usually over five times normal in acromegalic patients)

  • PRL (cosecreted by many GH-secreting tumors)

  • Glucose (diabetes mellitus is common in acromegaly)

  • Liver enzymes and serum creatinine or urea nitrogen (liver failure or kidney disease can misleadingly elevate GH)

  • Serum calcium (to exclude hyperparathyroidism)

  • Serum inorganic phosphorus (frequently elevated)

  • Serum free T₄

  • TSH (secondary hypothyroidism is common in acromegaly; primary hypothyroidism may increase PRL)

• Acromegaly is excluded if any serum GH is < 1 mcg/L; however, ...