Acromegaly

• Fred F. Ferri, M.D.

 Basic Information

Definition

Acromegaly occurs due to hypersecretion of growth hormone (GH) or increased amounts of insulin-like growth factor I (IGF-I). It is a chronic debilitating disease with an insidious onset.

Synonyms

Marie’s disease

ICD-10CM CODES
E22.0	Acromegaly and pituitary gigantism

Epidemiology & Demographics

Incidence

3 to 4 new cases per 1 million persons annually

Prevalence

50 to 60 cases per 1 million persons, with some estimates as high as 90 cases per 1 million persons

Predominant Sex

No sexual predominance

Mean Age at Diagnosis

Men: 40 yr; women: 45 yr

Risk Factors:

1. •

   Increased mortality rate, primarily from cardiovascular and respiratory causes

2. •

   Death in 50% of untreated patients by age 50 yr

3. •

   Increased prevalence of colon carcinoma and other malignancies (esophagus, stomach, melanoma, thyroid)

Physical Findings & Clinical Presentation

1. •

   Coarse features resulting from growth of soft tissue

2. •

   Coarse, oily skin

3. •

   Hands and feet that are spadelike, fleshy, and moist (Fig. E1)

   

4. •

   Prognathism, which can give an underbite

5. •

   Carpal tunnel syndrome

6. •

   Excessive sweating

7. •

   Arthralgias and severe osteoarthritis

8. •

   History of increased hat, glove, and/or shoe size. Epiphyseal growth plates require sex hormones to close; therefore, prior to puberty, these patients will develop excessive longitudinal growth and gigantism

9. •

   Hypertension

10. •

    Skin tags

11. •

    Muscle weakness and decreased exercise capacity

12. •

    Headache, often severe

13. •

    Diabetes mellitus

14. •

    Visual field defects

15. •

    Severe obstructive sleep apnea due to soft tissue swelling and macroglossia

16. •

    Cardiac abnormalities (cardiomyopathy, left ventricular hypertrophy, valvular heart disease, diastolic failure, arrhythmias)

Etiology

Cause is usually a pituitary adenoma affecting the anterior lobe. In rare cases, extrapituitary production of either GH or GH-releasing hormone (GHRH) can also lead to clinical manifestations.

Diagnosis

Differential Diagnosis

Ectopic production of GHRH from a carcinoid or other neuroendocrine tumor

Workup

1. 1.

   First screening test: measure serum IGF-I level.

   1. a.

      Direct measurement of the GH level is not as useful because it is secreted in a pulsatile fashion and a random level may be falsely normal

   2. b.

      Upper limits of a normal IGF-I level, depending on the assay: >380 ng/ml or 2.5 U/ml

2. 2.

   Failure to suppress serum GH to less than 2 ng/ml after 100 g oral glucose is considered conclusive.

   1. a.

      Patients may show suppression of GH (paradoxic response).

   2. b.

      Patients will not suppress GH to ≤2 ng/ml (typical response in patients with acromegaly).

   3. c.

      GHRH level >300 ng/ml is indicative of an ectopic source of GHRH such as from carcinoid tumors of the pancreas or lung.

Laboratory Tests

1. •

   Elevated IGF-I level

2. •

   Elevated serum phosphate

3. •

   Elevated urine calcium

Imaging Studies

1. •

   Imaging studies of choice: MRI of the pituitary and hypothalamus

2. •

   CT of the pituitary and hypothalamus sometimes used initially

Treatment

Surgery

1. •

   Treatment of choice: transsphenoidal microsurgical adenomectomy

2. •

   Surgical failure rate: approximately 13.3% for microadenomas (tumors <10 mm) and 11.1% for macroadenomas (tumors ≥10 mm confined to the sella)

3. •

   Preoperative IGF-I level: indicator of surgical outcome with higher levels associated with surgical failure

Radiotherapy

1. •

   Stereotactic radiosurgery (gamma knife) can be used to increase the chance of remission or cure.

2. •

   Radiotherapy is usually reserved for tumor recurrence or persistence after surgery in patients with resistance to or intolerance of medical treatment.

3. •

   Major complication: hypopituitarism, which may occur in up to 50% of patients; this complication is more likely in patients who had postoperative radiotherapy.

Medical Therapy

1. •

   Indicated when patients have not responded to surgical therapy (persistent elevation of IgF-1, abnormal glucose tolerance test), when surgery is contraindicated, and in patients waiting for the effects of radiotherapy to begin

2. •

   Somatostatin receptor ligands: octreotide, lanreotide

   1. 1.

      Important in the preoperative shrinkage of pituitary tumors and softening of adenomatous tissue.

   2. 2.

      Pegvisomant is a GH receptor antagonist that has shown promising results in the treatment of acromegaly. It is generally used in patients with resistance to or intolerance of somatostatin analogs. It should be used in patients who do not have central compressive symptoms and those with resistant diabetes.

   3. 3.

      Somatostatin agonist therapy has been shown to be effective as first-line medical therapy in reducing tumor volume. Dopamine receptor agonists (bromocriptine, cabergoline): can be used in addition to somatostatin receptor ligands.

Chronic Rx

Combination of bromocriptine and octreotide may be synergistic, allowing a lower combination dosage than either alone.

Disposition

1. •

   Patients receiving radiotherapy need long-term follow-up to monitor the potential development of hypopituitarism.

2. •

   Continuation of medical therapy should be based on the normalization of IGF-I levels.

Related Content

1. Pituitary Adenoma (Related Key Topic)

2. Acromegaly (Patient Information)