eMedicine Specialties > Endocrinology > Pituitary Gland
Acromegaly: Treatment & Medication
Updated: Feb 13, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
The goal of treatment is amelioration of symptoms caused by the local effects of the tumor, excess GH/IGF-I production, or both.
Because elevated GH/IGF-I concentration is associated with increased mortality rates, try to decrease/normalize their concentration. Most experts define cure, or adequate control, as a glucose-suppressed GH concentration of less than 2 ng/mL by radioimmunoassay (RIA) (1 mcg/L by IRMA) and normalization of the serum IGF-I concentration.
No single modality of treatment consistently achieves the above levels. A multimodality approach usually requires surgery as the first line of treatment, followed by medical therapy for residual disease. Radiation treatment is generally reserved for refractory cases.
- Somatostatin and dopamine analogues and GH receptor antagonists are the mainstays of medical treatment and are generally used after failure of primary surgery to induce complete remission.
- Bromocriptine is a dopamine agonist with limited effectiveness in the treatment of acromegaly. It can reduce the circulating GH level to less than 5 ng/mL in only 20% of patients and can normalize the IGF-I concentration in 10% of patients. Shrinkage in tumor size is also observed in fewer than 20% of patients. Cabergoline, another dopamine agonist, fares somewhat better with response rates of 46%.
- Tumors that cosecrete prolactin have a better response rate to dopamine agonists. The response to these agents is often detected by a trial of the drug in suitable patients.
- Somatostatin is a natural inhibitor of GH secretion. Because of its very short half-life, long-acting analogues have been developed. The long-acting analogue can be administered once per month but is extremely expensive (>$12,000/y in 1999).
- Octreotide is the most extensively studied and used somatostatin analogue.
- It primarily binds to the somatostatin receptor subtypes II and V and inhibits GH secretion.
- Treatment with octreotide reduces GH concentration to less than 5 ng/mL in 65% of patients and to less than 2 ng/mL in 40% of patients; it normalizes concentration IGF-I in 60% of patients.
- Tumor shrinkage is observed in 20-50% of patients.
- Pegvisomant, a GH receptor antagonist normalizes IGF-I levels in 90-100% of patients. As expected from its mechanism of action, GH levels increase during treatment and no decrease in tumor size is seen. A minority of patients may experience an increase in tumor size; whether this is due to natural history of the disease or an effect of treatment is unclear. Periodic imaging studies are advised in patients on this medication.
- Radiation treatment takes to reduce/normalize GH/IGF-I levels. About 60% of patients have a GH concentration of less than 5 ng/mL 10 years after radiotherapy. A similar percentage of patients develop panhypopituitarism as a result of treatment. Because of the disappointing results and adverse effects, radiotherapy is used as an adjuvant for large invasive tumors and when surgery is contraindicated. Some studies suggest that radiation is associated with the development of secondary tumors.
Surgical Care
- Even though surgery might not cure a significant number of patients, it is employed as first-line therapy. Patients with residual disease can then be offered adjuvant treatment.
- Transsphenoidal hypophysectomy has the dual advantage of rapidly improving symptoms caused by mass effect of the tumor and significantly reducing or normalizing GH/IGF-I concentrations.
- Remission depends on the initial size of the tumor, the GH level, and the skill of the neurosurgeon.
- A remission rate of 80-85% can be expected for microadenomas and 50-65% for macroadenomas.
- The postoperative GH concentration may predict remission rates. According to the results of one study, a postoperative GH concentration of less than 3 ng/dL was associated with a 90% remission rate, which declined to 5% in patients with postoperative GH concentration greater than 5 ng/dL.
Medication
After transsphenoidal surgery, somatostatin analogues are generally the first line of treatment, followed by GH receptor antagonist or dopamine agonists.
Somatostatin analogues
Used to reduce blood levels of GH and IGF-I in patients who have an inadequate response to surgery. Their role as the primary treatment modality is being evaluated.
Octreotide (Sandostatin)
Acts primarily on somatostatin receptor subtypes II and V. Inhibits GH secretion and has a multitude of other endocrine and nonendocrine effects, including inhibition of glucagon, VIP, and GI peptides. Periodically monitor GH/IGF-I concentrations to assess response.
Adult
Initial: 50 mcg SC tid; can increase to 500 mcg tid; doses of 300-600 mcg/d or higher seldom result in additional benefit
Pediatric
Not established
May reduce effects of cyclosporine; patients on insulin, oral hypoglycemics, beta-blockers, and calcium channel blockers may need dosage adjustments
Documented hypersensitivity
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Adverse effects are primarily related to altered GI motility and include nausea, abdominal pain, diarrhea, and increased incidence of gallstones and biliary sludge; because of alteration in counterregulatory hormones (eg, insulin, glucagon, GH), hypoglycemia or hyperglycemia can occur; bradycardia, cardiac conduction abnormalities, and arrhythmias have been reported; because of inhibition of thyrotropin secretion, hypothyroidism can also occur; exercise caution in patients with renal impairment; cholelithiasis can occur
Octreotide LAR (Sandostatin LAR)
Long-acting somatostatin analogue is administered every 4 wk. Similar improvements occur in GH/IGF-I concentration compared to octreotide but are associated with fewer adverse effects. A trial of short-acting somatostatin analogue is necessary to confirm the patient's ability to tolerate the compound.
Adult
10-30 mg IM q28d
Pediatric
Not established
May reduce effects of cyclosporine; patients on insulin, oral hypoglycemics, beta-blockers, and calcium channel blockers may need dosage adjustments
Documented hypersensitivity
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Adverse effects are primarily related to altered GI motility and include nausea, abdominal pain, diarrhea, and increased incidence of gallstones and biliary sludge; because of alteration in counterregulatory hormones (eg, insulin, glucagon, GH), hypoglycemia or hyperglycemia can occur; bradycardia, cardiac conduction abnormalities, and arrhythmias have been reported; because of inhibition of thyrotropin secretion, hypothyroidism can also occur; exercise caution in patients with renal impairment; cholelithiasis can occur
Lanreotide (Somatuline Depot)
Indicated for long-term treatment of acromegaly in patients who experience inadequate response to other therapies. Octapeptide analogue of natural somatostatin. Inhibits a variety of endocrine, neuroendocrine, exocrine, and paracrine functions. Elicits high affinity for human somatostatin receptors 2, 3, and 5. Inhibits basal secretion of motilin, gastric inhibitory peptide, and pancreatic polypeptide. Markedly inhibits meal-induced increases in superior mesenteric artery blood flow and portal venous blood flow. Also significantly decreases prostaglandin E1 – stimulated jejunal secretion of water, sodium, potassium, and chloride. Reduces prolactin levels in acromegalic patients when treated long term.
Adult
90 mg SC q4wk for 3 mo initially; adjust dose according to growth hormone (GH) and/or insulinlike growth factor-1 (IGF-1) levels; dosage range is 60-120 mg q4wk
Moderate to severe renal or hepatic impairment: 60 mg SC q4wk for 3 mo initially, then adjust dose according to GH and/or IGF-1 levels
Note: Administer by deep SC injection in superior external quadrant of buttock; alternate injection sites
Pediatric
Not established
Gastrointestinal effects may decrease intestinal absorption of coadministered drugs; may decrease cyclosporine bioavailability; may cause additive effects to other drugs that decrease heart rate (eg, beta blockers) or drugs that increase or decrease blood glucose levels
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Common adverse effects include diarrhea, abdominal pain, and nausea; less common adverse effects include constipation, gallstones, dermatitis, hyperglycemia, and hypoglycemia; rare instances of acute pancreatitis and slight decreases in thyroid function have been reported; cardiovascular effects (ie, bradycardia, myocardial infarction, hypertension, ventricular tachycardia) have also been reported; may initially cause redness, itching, and induration at injection site
Dopamine agonists
Usually added to somatostatin analogues if complete remission has not been achieved. Have modest effects if used as a single agent.
Bromocriptine (Parlodel)
Acts on central dopamine receptors. More effective in tumors that co-secrete prolactin. Dose used to treat acromegaly is usually much higher than that used for hyperprolactinemia.
Adult
Initial: 1.25 mg PO qhs; increase gradually
Maintenance: 20-30 mg PO qd in divided doses
Safety not demonstrated at >100 mg/d
Pediatric
Not established
Amitriptyline, butyrophenones, imipramine, methyldopa, phenothiazines, reserpine; toxicity may increase with ergot alkaloids; may decrease bromocriptine effects
Documented hypersensitivity, ischemic heart disease, peripheral vascular disorders
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Adverse effects include nausea, vomiting, headaches, nasal congestion, orthostatic hypotension, and digital vasospasm; patients tend to develop tolerance to adverse effects; caution in renal or hepatic disease
Growth hormone antagonists
Blocks GH binding to receptors, resulting in decreased IGF-1, IGFBP-3, and acid-labile subunit.
Pegvisomant (Somavert)
Recombinant DNA analog of human growth hormone (GH) that is structurally altered to act as a GH receptor antagonist. Selectively binds to growth hormone (GH) receptors on cell surfaces, thereby blocking endogenous GH binding. This action interferes with GH signal transduction, resulting in decreased insulinlike growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), and acid-labile subunit (ALS).
Adult
Loading dose: 40 mg SC
Maintenance dose: 10 mg SC qd initially; may increase or decrease q4-6wk by 5-mg increments as determined by IGF-I levels; not to exceed 30 mg/d
Pediatric
Not established
May increase insulin or oral hypoglycemic effect; patients receiving opioid analgesics may require higher pegvisomant doses
Documented hypersensitivity
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
The vial stopper contains latex; may increase tumor size; may improve insulin sensitivity; may elevate liver test findings
More on Acromegaly |
| Overview: Acromegaly |
| Differential Diagnoses & Workup: Acromegaly |
 Treatment & Medication: Acromegaly |
| Follow-up: Acromegaly |
| References |
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References
Asa SL. The pathology of pituitary tumors. Endocrinol Metab Clin North Am. 28(1):13-43, v-vi. [Medline].
Bates AS, Van't Hoff W, Jones JM, et al. An audit of outcome of treatment in acromegaly. Q J Med. May 1993;86(5):293-9. [Medline].
Ezzat S. Acromegaly. Endocrinol Metab Clin North Am. Dec 1997;26(4):703-23. [Medline].
Feenstra J, de Herder WW, ten Have SM, et al. Combined therapy with somatostatin analogues and weekly pegvisomant in active acromegaly. Lancet. May 7-13 2005;365(9471):1644-6. [Medline].
Freda PU. Current concepts in the biochemical assessment of the patient with acromegaly. Growth Horm IGF Res. Aug 2003;13(4):171-84. [Medline].
Freda PU, Wardlaw SL, Post KD. Long-term endocrinological follow-up evaluation in 115 patients who underwent transsphenoidal surgery for acromegaly. J Neurosurg. Sep 1998;89(3):353-8. [Medline].
Gagel RF, McCutcheon IE. Images in clinical medicine. Pituitary gigantism. N Engl J Med. Feb 18 1999;340(7):524. [Medline].
McCutcheon IE. Management of individual tumor syndromes. Pituitary neoplasia. Endocrinol Metab Clin North Am. Mar 1994;23(1):37-51. [Medline].
Melmed S, Ho K, Klibanski A, et al. Clinical review 75: Recent advances in pathogenesis, diagnosis, and management of acromegaly. J Clin Endocrinol Metab. Dec 1995;80(12):3395-402. [Medline].
Melmed S, Jackson I, Kleinberg D, Klibanski A. Current treatment guidelines for acromegaly. J Clin Endocrinol Metab. Aug 1998;83(8):2646-52. [Medline].
Newman CB. Medical therapy for acromegaly. Endocrinol Metab Clin North Am. Mar 1999;28(1):171-90. [Medline].
Newman CB, Melmed S, George A, et al. Octreotide as primary therapy for acromegaly. J Clin Endocrinol Metab. Sep 1998;83(9):3034-40. [Medline].
Paisley AN, Trainer PJ. Medical treatment in acromegaly. Curr Opin Pharmacol. Dec 2003;3(6):672-7. [Medline].
Rajasoorya C, Holdaway IM, Wrightson P, et al. Determinants of clinical outcome and survival in acromegaly. Clin Endocrinol (Oxf). Jul 1994;41(1):95-102. [Medline].
Spada A, Vallar L. G-protein oncogenes in acromegaly. Horm Res. 1992;38(1-2):90-3. [Medline].
Thorner M, Vance ML, Laws E. The anterior pituitary. In: Wilson JD, ed. Williams Textbook of Endocrinology. 9th ed. Philadelphia, Pa: Saunders; 1998:249-340.
Trainer PJ, Drake WM, Katznelson L, et al. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med. Apr 20 2000;342(16):1171-7. [Medline].
Further Reading
Keywords
growth hormone, GH, somatotroph tumor, growth hormone-releasing hormone, GHRH, insulinlike growth factor-I, IGF-I, somatomedin C, SM-C, guanosine triphosphate, GTP, glycogen synthetase phosphatase, GSP, acral overgrowth, macrognathia, visceral overgrowth, macroglossia, panhypopituitarism, somatic hypertrophy, hypertrophic arthropathy, kyphosis, hyperhidrosis, visceral hypersomia, multinodular goiter, colon polyposis, pseudoacromegaly, transsphenoidal hypophysectomy, somatostatin analogues, dopamine agonists, immunoradiometric assay, IRMA
