Acromegaly resident survival guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Tayyaba Ali, M.D.[2]

Synonyms and keywords:Somatotroph adenoma; Growth hormone excess; Growth hormone secreting pituitary adenoma

Overview

Acromegaly is the clinical syndrome that results from excessive secretion of growth hormone (GH). Its annual incidence is six to eight per million people. The mean age at diagnosis is 40 to 45 years. The most common cause of acromegaly is a somatotroph (GH-secreting) adenoma of the anterior pituitary. Life-threatening causes include conditions that may result in death or permanent disability within 24 hours if left untreated. There is no life-threatening cause of acromegaly. However, if left untreated, 30% of patients with acromegaly may progress to develop cardiovascular manifestations, pulmonary dysfunction, and cerebral complications. These comorbidities will increase the mortality rate.

Causes

Life Threatening Causes

Life-threatening causes include conditions that may result in death or permanent disability within 24 hours if left untreated. There is no life-threatening cause of acromegaly. However, if left untreated, 30% of patients with acromegaly may progress to develop cardiovascular manifestations, pulmonary dysfunction, and cerebral complications. These comorbidities will increase the mortality rate.

Common Causes

• Primary Growth hormone (GH) excess
  • GH-cell adenoma
  • Mixed GH-cell and PRL-cell adenoma
  • Mammosomatotroph-cell adenoma
  • Plurihormonal adenoma
  • GH-cell carcinoma
• Familial syndromes
  • Multiple endocrine neoplasia type 1 (GH-cell adenoma)
  • Familial acromegaly
  • McCune-Albright syndrome (rarely adenoma)
  • Carney's syndrome
• GH excess (ectopic or iatrogenic)
  • Pancreatic islet-cell tumor
  • Lymphoma
  • Iatrogenic
• GHRH excess
  • Central ectopic (<1 percent)
    • Hypothalamic hamartoma, choristoma, ganglioneuroma
  • Peripheral ectopic (1 percent)
    • Bronchial carcinoid, pancreatic islet-cell tumor, small cell lung cancer, adrenal adenoma, medullary thyroid carcinoma, pheochromocytoma

Diagnosis

The approach to diagnosis of Acromegaly is based on a step-wise testing strategy. Below is an algorithm summarising the identification and laboratory diagnosis of Acromegaly.

Characterize the symptoms: ❑ Headaches ❑ Enlargement of the hands (change in ring or glove size) and feet (change in shoe size) ❑ Lethargy ❑ Hyperhidrosis (excessive sweating) ❑ Paraesthesia ❑ Fatigue ❑ Jaw pain ❑ Body odor ❑ Blood in the stool ❑ Sleep apnea ❑ Weight gain ❑ In males: ❑ Sexual dysfunction ❑ Loss of libido ❑ Gynecomastia ❑ In females: ❑ Amenorrhea ❑ Galactorrhea

Examine the patient: ❑ HEENT Changes in facial appearance (large bones of the face, large jaw and tongue, widely spaced teeth) Visual disturbance Hoarseness of voice Enlargement of thyroid gland ❑ Musculoskeletal exam: Joint pain Limited joint movement Swelling of the bony areas around a joint Carpal tunnel syndrome ❑ Neurological exam: Decreased muscle strength and power (Muscle weakness) Kyphoscoliosis Cranial nerves palsy ❑ Cardiovascular exam: High blood pressure ❑ Skin exam: Thickening of the skin Skin tags Acne Acanthosis nigricans Hyperhidrosis

Measure Insulin like growth factor-1 (IGF-1) levels

Normal

Equivocal

Elevated

Active acromegaly ruled out

Oral glucose tolerance test (OGTT) with growth hormone (GH) levels

Acromegaly confirmed in a patient with typical clinical manifestations

Growth hormone (GH) suppressed

Inadequate suppression

Active acromegaly ruled out

Order pituitary MRI

Normal

Mass or empty sella

Chest and abdominal CT, Growth hormone-releasing hormone (GHRH) measurement

GH-secreting pituitary adenoma

Extra-pituitary acromegaly

This algorithm developed and modified according to Endocrine Society (ES): Clinical practice guideline on acromegaly.

Treatment

Shown below is an algorithm summarizing the treatment of Acromegaly according the the Endocrine Society (ES): Clinical practice guideline on acromegaly.

Acromegaly

Transphenoidal surgery ❑ Complete resection ❑ Tumors that are unresectable, a surgical debulking procedure may be performed followed by medical therapy

Yes

Patient is not a surgical candidate ❑ Patient preference ❑ High risk due to medical comorbidities ❑ Unresectable tumors

Are the following criteria met postoperatively? ❑ Morning serum GH the day after surgery <1ng/ml ❑ 12 weeks postoperative: Normal serum IGF-1 (for age and gender) No evidence of residual tumor on pituitary MRI

Yes

No

Remission ❑ Monitor with annual IGF-1

Is there residual tumor that appears resectable and readily accessible (eg, not invading the cavernous sinus)?

Perform MRI for clinical or biochemical evidence of recurrence

Medical therapy ❑ Somatostatin analogs: Preferred regimen (1): Octreotide 50 mcg q8hr subcutaneous as initial dose and 100 mcg q8hr as effective dose. Preferred regimen (2): Lanreotide 90 mg q4week for 3 months every 4 weeks subcutaneous. Preferred regimen (3): Pasireotide 40 mg q4wk intramuscular. ❑ Dopamine agonists: Preferred regimen (1): Cabergoline 0.25 mg 2x/week orally. Preferred regimen (2): Bromocriptine 1.25-2.5 mg qDay orally. ❑ GH receptor antagonist: Preferred regimen (1): Pegvisomant 10 mg qDay subcutaneous.

Failure of medical therapy

Radiation therapy ❑ Stereotactic radiotherapy is most common method

This algorithm developed and modified according to Endocrine Society (ES): Clinical practice guideline on acromegaly.

Do's

• IGF-1 should be measured in patients without the typical manifestations of acromegaly, but who have several of these associated conditions: sleep apnea syndrome, type 2 diabetes mellitus, debilitating arthritis, carpal tunnel syndrome, hyperhidrosis, and hypertension.

Don'ts

• The content in this section is in bullet points.

References

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