Big heart, small ring

Igor Kravets

doi:10.3949/ccjm.84a.16101

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Figure 1
Diagnostic and treatment algorithm for acromegaly.

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TABLE 1

Clinical manifestations of acromegaly

Neurologic symptoms due to pituitary tumor’s mass effect
Visual field deficits, headache, cranial nerve palsies

Musculoskeletal system
Increased thickness of soft tissue of hands and feet (enlarging size of gloves and shoes, rings becoming too small), prognathism, jaw malocclusion, arthropathy and osteoarthritis (affects up to 75% of patients and is a leading cause of morbidity and disability in patients with acromegaly), carpal tunnel syndrome (present in about 64% of patients on presentation), proximal myopathy, hypertrophy of frontal bones (frontal bossing)

Integumentary system
Oily texture, hyperhidrosis, skin tags, deep skin creases

Cardiovascular system
Biventricular hypertrophy, asymmetric septal hypertrophy, cardiomyopathy, congestive heart failure, diastolic heart failure, arrhythmias (up to 40% of patients develop conduction disorders), hypertension

Respiratory system
Obstructive sleep apnea

Gastrointestinal system
Colon polyps, colon cancer, macroglossia, hepatomegaly

Endocrine and metabolic system
Irregular menses, galactorrhea, decreased libido, erectile dysfunction, thyromegaly, diabetes mellitus, hypertriglyceridemia; in multiple endocrine neoplasia syndrome 1, acromegaly may be associated with primary hyperparathyroidism and pancreatic islet tumors.

Based on information from references 2 and 3.

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TABLE 2

Medical treatments for acromegaly

Medication	Dose	Normalization of IGF-1	Reduction of tumor size	Comments
Somatostatin receptor ligands (SRLs)
Octreotide	Starting dose 50 mg subcutaneously every 8 hours; can be increased every 2 weeks, usually up to 300 mg per day	30%–40%	Arrested growth or reduced tumor size in about 50%	Endocrine Society guidelines recommend use of either an SRL or pegvisomant as the initial adjuvant medical therapy. In patients with large tumors abutting the optic chiasm, an SRL is preferred as pegvisomant does not suppress tumor growth. An SRL is used as primary therapy in patients who cannot be cured by surgery, have extensive cavernous sinus invasion, have no chiasmal compression, or are poor surgical candidates.
Octreotide long-acting release	10–40 mg intramuscularly every 4 weeks	30%–40%	Arrested growth or reduced tumor size in about 50%
Lanreotide depot/autogel	60–120 mg deeply subcutaneous every 4 weeks	30%–40%	Arrested growth or reduced tumor size in about 50%
Pasireotide	40–60 mg intramuscularly every 28 days	About 35%	Arrested growth or reduced tumor size in about 50%	A novel SRL with enhanced binding to more somatostatin receptors than the other SRLs. Associated with hyperglycemia in 57% of patients (see Table 3).
Human GH receptor antagonist
Pegvisomant	10–40 mg subcutaneously daily	63%	Usually, no change, but tumor growth may occur in 3%–5% of patients	Can be combined with an SRL. IGF-1 but not GH should be used as a marker of efficacy. Improves glycemic control, useful when comorbid diabetes mellitus is present. Very expensive.
Dopamine agonist
Cabergoline	1–4 mg by mouth weekly	20%–30%	No change	Can be an initial adjuvant therapy in patients with modest elevations of IGF-1 and GH, with or without concomitant hyperprolactinemia, and with mild signs and symptoms of acromegaly. Can be used in combination with an SRL or pegvisomant. Therapeutic response tends to decrease with time.

GH = growth hormone; IGF-1= insulin-like growth factor 1
Based on information from references 14 and 15.

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TABLE 3

Side effects of drug therapy for acromegaly

Medication	Side effects	Comments
Octreotide Octreotide long-acting release Lanreotide depot/autogel	Common: abdominal cramps, flatulence and diarrhea; these symptoms usually subside with continued treatment; cholelithiasis and gallbladder sludge occur in approximately 25% of patients, usually without symptoms Less common: local skin irritation, pain at the injection site, reversible hair loss Glycemic control usually improves because these agents inhibit both insulin and glucagon as well as growth hormone secretion; rarely, glycemic control may worsen	Endocrine Society guidelines recommend against routine abdominal ultrasound for monitoring for cholelithiasis in patients receiving somatostatin receptor ligands (SRLs) because symptomatic gallbladder disease is infrequent.
Pasireotide	In contrast to other SRLs, pasireotide causes hyperglycemia in 57% of patients Other side effects are similar to those of the other SRLs
Pegvisomant	Elevated liver aminotransferases in 9% of patients Injection site reactions (local discomfort, reversible lipohypertrophy, or lipoatrophy) in 2.2% of patients	The Endocrine Society guidelines suggest monitoring liver function tests monthly for the first 6 months, and then every 6 months in patients receiving pegvisomant. Stop the drug if liver aminotransferase levels are elevated > 3 times the upper level of normal.
Cabergoline	Gastrointestinal upset, nasal congestion, fatigue, orthostasis, headache Cardiac valve abnormalities have occurred in patients with Parkinson disease on high doses of cabergoline (> 2 mg/week)	There is no consensus on frequency of cardiac valve monitoring in patients on cabergoline. If the dose exceeds 2 mg a week, consider obtaining a baseline echocardiogram and then serial echocardiograms; no specific recommendation currently exists.