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For further information, see CMDT Part 26-03: Acromegaly & Gigantism

Key Features

Essentials of Diagnosis

  • Pituitary 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)


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 ...

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