Acromegaly & Gigantism

KEY FEATURES

Essentials of Diagnosis

• Pituitary neuroendocrine tumor with oversecretion of growth hormone (GH)

• Gigantism: begins pre-puberty before closure of epiphyses

• Acromegaly: occurs post-puberty with excessive growth of hands, feet, jaw, and internal organs

• 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 from the liver and other tissues

• Acromegaly is nearly always caused by a pituitary adenoma

• About 70% are macroadenomas (≥ 1 cm) when diagnosed

• May be locally invasive, especially into the cavernous sinus, but < 1% are malignant

• 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

• Acromegaly is rarely caused by ectopic secretion of GH-releasing hormone or GH secreted by a neuroendocrine tumor or lymphoma

• Manifestations usually present insidiously; median time to diagnosis after symptom onset is 10 years

Demographics

• Acromegaly: yearly incidence of ∼10 cases per million

CLINICAL FINDINGS

Symptoms and Signs

• Gigantism and tall stature if oversecretion of GH occurs in youth (before closure of epiphyses); afterward, acromegaly

• Acromegaly

  • Head and neck

    • Facial features coarsen

    • Hat size increases, tooth spacing widens

    • Mandible becomes more prominent

    • Macroglossia and hypertrophy of pharyngeal and laryngeal tissue; may cause snoring and obstructive sleep apnea

    • Deep, coarse voice

    • 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

  • Insulin resistance is usually present and frequently causes diabetes mellitus (30%)

  • 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

  • Pregnant women 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

• Normal adolescence: serum IGF-1 is elevated and GH may not suppress

• 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

  • Medications (oral estrogens, β-blockers, clonidine)

  • Pregnancy

    • GH is produced by the placenta

    • Commercial GH assays may not distinguish between pituitary and placental GH