eMedicine Specialties > Endocrinology > Pituitary Gland
Pituitary Macroadenomas: Treatment & Medication
Updated: Aug 3, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
The goal of treatment is complete cure. When this is not attainable, reducing tumor mass, restoring hormone function, and restoring normal vision are attempted using medications, surgery, and radiation. Pituitary macroadenomas often require surgical intervention for cure. The exceptions to this rule are the macroprolactinomas, which usually have an excellent response to medical therapy. The tumor size may be diminished but often does not disappear completely. Medical treatment can play a role in reducing tumor size, controlling hormonal excess, or correcting hormonal deficiency.
- Prolactin-secreting macroadenomas respond to dopaminergic agonists. The most frequently employed medications include bromocriptine, cabergoline, and, previously, pergolide. Quinagolide is an alternative with fewer adverse effects than bromocriptine. Prolactin-secreting macroadenomas are so responsive to medical therapy that surgery and radiation often are not used in treatment. Hyperprolactinemia from other lesions interfering with the hypothalamic-pituitary communication also responds to medical therapy.
- Pergolide was withdrawn from the US market March 29, 2007, because of heart valve damage resulting in cardiac valve regurgitation. It is important not to stop pergolide abruptly. Health care professionals should assess patients' need for dopamine agonist (DA) therapy and consider alternative treatment. If continued treatment with a DA is needed, another DA should be substituted for pergolide. For more information, see FDA MedWatch Product Safety Alert and Medscape Alerts: Pergolide Withdrawn From US Market.
- Growth hormone-secreting tumors should be treated surgically, often followed by radiation therapy. That acromegaly can be treated with surgery alone is very unlikely. However, debulking the tumor is very important. Radiation therapy results in 50% reduction in growth hormone levels within 2 years, followed by an additional 25% in the following 2 years. Thereafter, the growth hormone levels decline more slowly. Therefore, the lower the postoperative growth hormone level, the higher the chance of remission after radiation therapy. Medical treatment is used after surgery to suppress growth hormone secretion, awaiting the occurrence of the effects of radiotherapy. Octreotide is the treatment of choice. A long-acting formulation administered monthly is now available.
- Somatostatin must be administered as a continuous infusion, while shorter-acting octreotide is administered tid-qid. Growth hormone receptor antagonists have been another addition to the treatment of acromegaly. Dopamine agonists also may be used but are not as effective as octreotide (approximately 30% of somatotropinomas respond).
- Corticotropin-secreting pituitary tumors are treated using surgery and radiation therapy (however, they are rather radioresistant). Medical therapy is reserved for patients whose therapy fails, those who decline other therapy, and those who cannot be treated otherwise. Medical therapy is divided into centrally acting agents that reduce corticotropin release and peripherally acting agents that reduce cortisol secretion or block cortisol action. Centrally acting medications (unfortunately effective in very rare occasions only) include bromocriptine, valproic acid, and cyproheptadine. Peripherally acting agents include ketoconazole, mitotane, and metyrapone. Use of such medications should be in combination with radiotherapy.
- Gonadotropin-secreting macroadenomas are treated surgically, followed by radiation. Medical therapy is reserved for those patients who decline definitive treatment. Bromocriptine or octreotide may be used. LH-releasing hormone antagonists may decrease hormone levels but do not affect the tumor size.
- Nonsecretory macroadenomas are treated surgically.1 If surgery is contraindicated, octreotide or bromocriptine may be tried; however, the results are often disappointing.
- Thyrotropin-secreting tumors are treated surgically, followed by radiation therapy. Octreotide is quite effective in such tumors and can be used as adjuvant therapy.
- Traditional radiotherapy using external beam radiation is used to complement surgery in inoperable cases or in patients declining surgery. The major drawbacks include delayed onset of action and high incidence of panhypopituitarism.
- Radiosurgery using a Gamma knife employs a computer-assisted stereotactic mapping followed by several discrete radiation treatment fields to the tumor. This allows targeting maximal radiation to the tumor while minimizing radiation to the surrounding tissues. Incidence of hypopituitarism is less. However, long-term studies are not available yet.
Surgical Care
Pituitary macroadenomas often require surgical extirpation for cure. Transsphenoidal surgery is the approach of choice.2,3 Only about 1% of patients require a transcranial approach. Compared with remission rates of 90% in microadenomas, macroadenomas with significant extrasellar extension have remission rates of 15-37% when treated with surgery alone. Radiation therapy and medical treatment often complement surgery.4
In a study of 13 patients, Elhateer et al reported on the effectiveness of fractionated stereotactic radiation therapy (FSRT) in the treatment of macroadenomas.5 In 12 of the patients, FSRT was employed following tumor resection, while in 1 patient, it served as primary treatment. All but 4 of the patients had nonfunctional macroadenomas. After a follow-up period of 6-60 months (median, 24 months), the investigators found that local control in the patients was 100% and that 1 patient had a clinical complete response.
According to the authors, the results indicated that FSRT is an effective means of tumor control in patients with pituitary macroadenoma and that it is associated with a low rate of radiation-related morbidity. (No patients were found to have radiation-induced optic neuropathy or radiation-related endocrine dysfunction.) The authors stated, however, that because the study contained so few patients with functioning tumors, they could not judge the hormonal response of macroadenomas to FSRT.
Consultations
When a pituitary macroadenoma is diagnosed, consultations with an endocrinologist, neurosurgeon, neuroradiologist, and neurophthalmologist should be considered.
Medication
Medications are used to control excess hormone secretion or to replace deficient hormones.
Dopaminergic agents
These agents directly stimulate postsynaptic dopamine receptors. The dopaminergic neurons in the tuberoinfundibular process modulate the secretion of hormones from the anterior pituitary by secreting an inhibitory factor, believed to be dopamine.
Bromocriptine (Parlodel)
Dopamine agonist used to normalize serum prolactin levels. Semisynthetic, ergot alkaloid derivative. Strong dopamine D2-receptor agonist. Partial dopamine D1-receptor agonist. FDA approved as an adjunct to levodopa/carbidopa but less effective than other dopamine agonists.
Might relieve akinesia, rigidity, and tremor associated with Parkinson disease. Stimulates dopamine receptors in the corpus striatum. Approximately 28% absorbed from the GI tract and metabolized in the liver. Approximate elimination half-life is 50 h, with 85% excreted in feces and 3-6% eliminated in the urine.
Initiate at low dosage and slowly increase dosage to individualize therapy. Assess dosage titration q2wk. Gradually reduce dose in 2.5-mg decrements if severe adverse reactions occur.
Adult
5-15 mg PO qd administered in most cases bid or tid; safety not demonstrated at >100 mg/d; initiate at low dosage, slowly increase dosage to individualize therapy; assess dosage titration q2wk
Gradually reduce dose in 2.5-mg decrements if severe adverse reactions occur
Pediatric
Not established
Ergot alkaloids might increase toxicity; effects may be decreased by amitriptyline, butyrophenones, imipramine, methyldopa, phenothiazines, and reserpine
Documented hypersensitivity; ischemic heart disease; peripheral vascular disorders; uncontrolled hypertension; ergot sensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal or hepatic disease, seizures, orthostatic hypotension, and elderly patients
Cabergoline (Dostinex)
Dopamine agonist used to normalize serum prolactin levels. Long-acting dopamine receptor agonist with high affinity for D2 receptors. Prolactin secretion by anterior pituitary is under hypothalamic inhibitory control exerted through dopamine.
Adult
0.25-1 mg PO twice qwk
Pediatric
Not established
Might increase effects of antihypertensive medications (adjust dose accordingly); dopamine antagonists might reduce effects of cabergoline
Documented hypersensitivity; uncontrolled hypertension; ergot alkaloid sensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution when patient is taking antihypertensives; do not use to inhibit physiologic lactation due to relatively high incidence of stroke, seizures, and hypertension; monitor prolactin levels monthly; caution in hepatic impairment
Pergolide (Permax)
Pergolide was withdrawn from the US market March 29, 2007. Potent dopamine receptor agonist at both D1 and D2 receptor sites. Approximately 10-1000 times more potent than bromocriptine on a mg-per-mg basis. Inhibits secretion of prolactin. Causes a transient rise in serum concentrations of growth hormone and decrease in serum concentrations of LH.
Adult
0.05 mg PO for first 2 d initially; increase gradually by 0.1 or 0.15 mg/d q3d over next 12 days of therapy followed by increments of 0.25 mg/d q3d until optimal therapeutic dosage achieved
Pediatric
Not established
Dopamine antagonists such as neuroleptics, phenothiazines, butyrophenones, thioxanthenes, or metoclopramide may diminish effectiveness of pergolide, a dopamine agonist; because pergolide mesylate is more than 90% bound to plasma proteins, exercise caution if pergolide is coadministered with other drugs known to affect protein binding
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
May cause valvular heart disease (yearly echocardiograms recommended for patients on chronic therapy); inhibits secretion of prolactin; causes transient rise in serum concentrations of growth hormone and decrease in serum concentrations of luteinizing hormone; adverse effects include nausea, hypotension, hallucinations, and somnolence; use caution in patients who have been treated for cardiac dysrhythmias; may cause or exacerbate preexisting states of confusion and hallucinations or dyskinesia
Growth hormone receptor antagonists
Used for the treatment of acromegaly.
Pegvisomant (Somavert)
Genetically engineered growth hormone receptor antagonist used to treat acromegaly. Useful in patients not responding to somatostatin analogues. May be used concurrently with somatostatin analogues after surgery and radiation.
Adult
10-20 mg IM qd
Pediatric
Not established
None reported
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
Caution in hepatic insufficiency; improves diabetes mellitus control
Somatostatin analogues
Used to control symptoms resulting from excess hormone secretion.
Octreotide (Sandostatin)
Somatostatin analogue used to normalize growth hormone levels. Acts primarily on somatostatin receptor subtypes II and V. Inhibits growth hormone secretion and has multiple other endocrine and nonendocrine effects, including inhibition of glucagon, VIP, and GI peptides.
Adult
50-200 mcg SC q8h
Administration can be by continuous SC infusion via a pump or a long-acting formulation administered IM every mo
Pediatric
Not established
Might reduce effect of cyclosporine; patients on insulin, oral hypoglycemics, beta-blockers, and calcium channel blockers might require dosage adjustments
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adverse effects primarily are related to altered GI motility and include nausea, abdominal pain, diarrhea, and increased incidence of gallstones and biliary sludge; because of alteration in counter-regulatory hormones (eg, insulin, glucagon, growth hormone) hypocalcemia or hyperglycemia can be observed; bradycardia, cardiac conduction abnormalities, and arrhythmias have been reported; due to inhibition of TSH secretion, hypothyroidism also can occur; exercise caution in patients with renal impairment; cholelithiasis might occur
More on Pituitary Macroadenomas |
| Overview: Pituitary Macroadenomas |
| Differential Diagnoses & Workup: Pituitary Macroadenomas |
 Treatment & Medication: Pituitary Macroadenomas |
| Follow-up: Pituitary Macroadenomas |
| References |
| Further Reading |
| « Previous Page | Next Page » |
References
Greenman Y, Stern N. How should a nonfunctioning pituitary macroadenoma be monitored after debulking surgery?. Clin Endocrinol (Oxf). Jun 2009;70(6):829-32. [Medline].
Wu JS, Shou XF, Yao CJ, et al. Transsphenoidal pituitary macroadenomas resection guided by PoleStar N20 low-field intraoperative magnetic resonance imaging: comparison with early postoperative high-field magnetic resonance imaging. Neurosurgery. Jul 2009;65(1):63-70; discussion 70-1. [Medline].
Fomekong E, Maiter D, Grandin C, et al. Outcome of transsphenoidal surgery for Cushing's disease: a high remission rate in ACTH-secreting macroadenomas. Clin Neurol Neurosurg. Jun 2009;111(5):442-9. [Medline].
Paek SH, Downes MB, Bednarz G, Keane WM, Werner-Wasik M, Curran WJ Jr, et al. Integration of surgery with fractionated stereotactic radiotherapy for treatment of nonfunctioning pituitary macroadenomas. Int J Radiat Oncol Biol Phys. Mar 1 2005;61(3):795-808. [Medline].
Elhateer H, Muanza T, Roberge D, et al. Fractionated stereotactic radiotherapy in the treatment of pituitary macroadenomas. Curr Oncol. Dec 2008;15(6):286-92. [Medline]. [Full Text].
Hwang YC, Chung JH, Min YK, et al. Comparisons between macroadenomas and microadenomas in Cushing's disease: characteristics of hormone secretion and clinical outcomes. J Korean Med Sci. Feb 2009;24(1):46-51. [Medline]. [Full Text].
Bardin CW. Anterior pituitary disease. In: Current Therapy in Endocrinology and Metabolism. 6th ed. St. Louis, Mo: Mosby Year Book; 1997:33-8.
Becker KL, Bilezikian JP, Bremner WJ. Adenohypophysis. In: Principles and Practice of Endocrinology and Metabolism. 2nd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1995:207-37.
Biller BM, Molitch ME, Vance ML, Cannistraro KB, Davis KR, Simons JA, et al. Treatment of prolactin-secreting macroadenomas with the once-weekly dopamine agonist cabergoline. J Clin Endocrinol Metab. Jun 1996;81(6):2338-43. [Medline].
Diez JJ, Iglesias P. Current management of acromegaly. Expert Opin Pharmacother. Jul 2000;1(5):991-1006. [Medline].
Manieri C, Di Bisceglie C, Razzore P, et al. Gonadotroph cell pituitary adenomas in males. Panminerva Med. Dec 2000;42(4):237-40. [Medline].
Martin CH, Schwartz R, Jolesz F, et al. Transsphenoidal resection of pituitary adenomas in an intraoperative MRI unit. Pituitary. Aug 1999;2(2):155-62. [Medline].
Mulinda JR, Hasinski S, Rose LI. Successful therapy for a mixed thyrotropin-and prolactin-secreting pituitary macroadenoma with cabergoline. Endocr Pract. Mar-Apr 1999;5(2):76-9. [Medline].
Takahashi T, Miki Y, Takahashi JA, et al. Ectopic posterior pituitary high signal in preoperative and postoperative macroadenomas: dynamic MR imaging. Eur J Radiol. Jul 2005;55(1):84-91. [Medline].
Wilson JD, Foster DW. Pituitary disorders. In: Williams Textbook of Endocrinology. 8th ed. Philadelphia, Pa: W.B. Saunders, Co; 1992:260-95.
Further Reading
Clinical guidelines:
American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of acromegaly. American Association of Clinical Endocrinologists - Medical Specialty Society
American College of Endocrinology - Medical Specialty Society. 2004 May/June. 13 pages. NGC:003789
Stereotactic radiosurgery for patients with pituitary adenomas. IRSA - Professional Association. 2004 Apr. 12 pages. NGC:003598
Clinical trials:
Characterization of Receptors in Non-Functioning Pituitary Macroadenomas
Lanreotide as Primary Treatment for Acromegalic Patients With Pituitary Gland Macroadenoma
Prevalence of Pituitary Incidentaloma in Relatives of Patients With Pituitary Adenoma
Keywords
pituitary macroadenoma, pituitary, pituitary gland, tumor pituitary, pituitary adenoma, prolactinoma, microadenoma, tumor pituitary gland, pituitary hormone, pituitary hormones, pituitary tumor, pituitary tumors, pituitary macroadenomas, hypophyseal adenoma, multiple endocrine neoplasia type 1, MEN 1, acromegaly, McCune-Albright syndrome, epithelial pituitary cells
