You are in: eMedicine Specialties >
Endocrinology > Pituitary Gland
Pituitary Microadenomas
Article Last Updated: Sep 21, 2007
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: David M Klachko, MBBCh, Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Missouri
David M Klachko is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Federation for Medical Research, Endocrine Society, Missouri State Medical Association, and Sigma Xi
Editors: Harris C Taylor, MD, Chief, Division of Endocrinology, Lutheran Medical Center of Cleveland; Clinical Professor, Department of Internal Medicine, Case Western University School Of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Yoram Shenker, MD, Chief of Endocrinology Section, VA Hospital of Madison, Interim Chief, Associate Professor, Department of Internal Medicine, Section of Endocrinology, Diabetes and Metabolism, University of Wisconsin at Madison; Mark Cooper, MD, Head, Vascular Division, Baker Medical Research Institute; Professor of Medicine, Monash University; George T Griffing, MD, Professor of Medicine, Director of General Internal Medicine, St Louis University
Author and Editor Disclosure
Synonyms and related keywords:
incidentalomas, prolactinomas, macroadenomas, secretory tumors, adrenocorticotrophic hormone, gonadotropin-secreting adenomas, ACTH, midline pituitary lesions, Rathke cleft cysts, amenorrhea, galactorrhea, mass effects, prolactin, hyperprolactinemia, hypogonadism, erectile dysfunction, decreased libido, hyperthyroidism, Cushing syndrome, acromegaly
Background
By definition, a microadenoma is a tumor less than 10 mm in diameter. Pituitary adenomas may secrete hormones, or they may be clinically inactive. Many pituitary lesions are discovered while investigating other neurologic problems; these are called incidentalomas.
Pathophysiology
Of the secretory tumors, the most common are prolactinomas. Other secretory tumors may secrete (1) adrenocorticotrophic hormone (ACTH), causing Cushing disease; (2) growth hormone, causing acromegaly; (3) gonadotropins with clinical presentations reflective of severity and sex; or, rarely, (4) thyroid-stimulating hormone (TSH), causing hyperthyroidism. Many secrete inactive alpha-subunits of the glycoprotein hormones. Most incidentalomas are inactive and are of no clinical consequence. As with adenomas in other endocrine glands, all these tumors probably derive from a local mutation, with loss of function of the genes controlling cell proliferation.
Frequency
United States
High-resolution MRI screening of a normal population has shown a 10% prevalence of pituitary lesions.
International
In studies with a total of 10,370 autopsies, the prevalence of pituitary microadenomas was 11%; however, in a Japanese series of 1000 autopsies, many of the midline pituitary lesions were Rathke cysts, not adenomas.
Mortality/Morbidity
Microadenomas do not cause directly attributable excess mortality. These tumors generally are too small to cause bony erosion or to put pressure on the optic chiasm. Any morbidity is caused by excessive hormone secretion.
Race
No race predilection exists.
Sex
Microadenomas may occur in either sex. Prolactinomas are diagnosed more frequently in women, possibly because of the more striking presenting features such as amenorrhea and/or galactorrhea. In men, the diagnosis of inactive adenomas is often delayed until they have become macroadenomas and cause mass effects.
Age
Microadenomas may occur at any age, but prevalence appears to increase with advancing age.
History
- Types of pituitary microadenomas
- Incidentalomas usually have no associated symptoms. They are ordinarily found in people who have radiologic studies for other reasons (eg, headaches). Unlike macroadenomas, incidentalomas are too small to cause pressure-related symptoms such as headache or visual field loss.
- Prolactinomas may be asymptomatic if prolactin levels are only slightly elevated. In women, hyperprolactinemia may cause galactorrhea, amenorrhea, or infertility. In men, hypogonadism, erectile dysfunction, and decreased libido may ensue. Gynecomastia may develop but galactorrhea is rare in men.
- ACTH-secreting adenomas cause Cushing disease.
- Growth hormone–secreting adenomas cause acromegaly.
- TSH-secreting adenomas are a very rare cause of hyperthyroidism.
- Gonadotropin-secreting adenomas have been reported. The frequency is unknown. Women may present with amenorrhea and a mismatch between estrogen and gonadotropin levels (eg, elevated gonadotropin levels despite normal or elevated levels estrogen levels without suppression of gonadotropins).
Physical
Any physical abnormalities are caused by excessive hormone secretion (eg, galactorrhea due to hyperprolactinemia, acromegaly due to excessive growth hormone, ACTH-mediated Cushing disease). Many microadenomas found incidentally on CT scan or MRI may be clinically inactive.
- Patients with prolactin-secreting adenomas may present with infertility, galactorrhea, amenorrhea, and loss of libido. Weight gain is frequent and may be reversed in some patients with normalization of prolactin levels.
- Growth hormone–secreting adenomas cause acromegaly with coarsening of facial features and soft tissue swelling of the hands and feet. Most patients complain of excessive perspiration and offensive body odor. Progressive bony proliferation occurs, and the mandible lengthens and thickens, resulting in an underbite.
- ACTH-secreting adenomas cause Cushing disease characterized by weight gain, primarily in the facial, nuchal, truncal, and girdle areas (ie, centripetal or "buffalo" obesity). Protein breakdown leads to thin, friable skin that bruises easily; breakdown may form wide striae and may cause muscle weakness, wasting, and osteopenia. In children, growth is arrested.
Causes
As with adenomas elsewhere, the likely cause of pituitary microadenomas is a local mutation leading to autonomous growth and/or secretion.
Acromegaly
Hyperprolactinemia
Hyperthyroidism
Other Problems to be Considered
Rathke cleft cyst
Thyroid hormone resistance
Lab Studies
- Current management strategies are controversial. In the absence of symptoms or signs suggesting excess of specific hormones, the most cost-effective strategy is simply measurement of the prolactin level.
- If clinical suspicion of Cushing syndrome, acromegaly, or other hormone excess exists, order appropriate tests. Some experts recommend a screening panel of prolactin and insulinlike growth factor-1 (IGF-1) or somatomedin-C and an overnight dexamethasone suppression test.
- Autonomous secretion by a tumor usually shows an inappropriate relationship between the level of the hormone secreted by the peripheral gland (thyroid, adrenal, gonadal) and the stimulating pituitary hormone (TSH, ACTH, gonadotropins). For example, a patient may be hyperthyroid without TSH suppression (must be differentiated from thyroid hormone resistance) or a patient with Cushing disease, who will have an elevated or "normal" ACTH level.
Imaging Studies
- MRI studies have shown sensitivity and specificity of about 90% for secretory tumors. Enhancement with gadolinium diethylenetriamine pentaacetic acid (DTPA) improves the detection rate. Sensitivity for detection of ACTH-secreting adenomas is much less (60-75%); diagnosis may require specialized tests such as petrosal sinus sampling.
- CT scans are not very specific.
- For secretory tumors, scintigraphy with [111In-DTPA-D-Phe]-octreotide can identify tumors with somatostatin receptors.
Other Tests
Other tests are dictated by the clinical picture of hormonal excess or, very rarely, hormonal deficiency. For larger functional microadenomas, especially those located in an area where upward pressure on the optic chiasma may exist, assessment of visual fields may be useful in monitoring therapy. Computer-assisted perimetry may be more sensitive than Goldman perimetry. In contrast to pituitary macroadenomas, microadenomas rarely cause any visual field defects.
Histologic Findings
If the tumor is removed surgically, immunohistochemical staining for secretory granules is advisable.
Staging
Staging is determined primarily by the size of the microadenoma.
Medical Care
- For prolactinomas, therapy with a dopaminergic drug is the treatment of choice (see Hyperprolactinemia). If bromocriptine is not tolerated orally, it may be given intravaginally.
- For other secretory tumors, particularly with Cushing syndrome or acromegaly, surgical removal by an expert pituitary surgeon usually is advisable. Radiation therapy employing a gamma knife unit may also be indicated. Inactive tumors are removed only if they enlarge.
Surgical Care
- For prolactin-secreting microadenomas, surgical removal is followed by recurrence in about 50% of patients. Therefore, medical therapy is preferred.
- Secretory tumors are best removed by the transsphenoidal approach. Postoperative conventional radiotherapy is not effective.
- Some centers have used gamma knife radiation for recurrent tumors.
Consultations
Endocrinologic consultation is advisable if clinical evidence of hormone secretion or deficiency exists.
Diet
No specific diet is necessary.
Activity
No restriction of activity is necessary.
If the tumor is secreting excess hormone (eg, prolactin, growth hormone, ACTH, gonadotropins, TSH [rarely]), initiate appropriate medical therapy as described in the articles on Acromegaly and Cushing disease. For the most common microadenoma, ie, prolactinomas, administer a dopaminergic drug such as bromocriptine or cabergoline (see Hyperprolactinemia).
Drug Category: Dopamine agonists
Directly stimulate postsynaptic dopamine receptors. The dopaminergic neurons in the tuberoinfundibular process modulate the secretion of prolactin from the anterior pituitary by secreting a prolactin inhibitory factor, believed to be dopamine.
| Drug Name | Bromocriptine (Parlodel) |
|---|
| Description | Semisynthetic, ergot alkaloid derivative; strong dopamine D2-receptor agonist; partial dopamine D1-receptor agonist. Inhibits prolactin secretion with no effect on other pituitary hormones. May be administered with food to minimize possibility of gastrointestinal irritation. |
|---|
| Adult Dose | 0.625-1.25 mg PO qd initially; gradually increase every few days to 2.5 mg PO bid/tid |
|---|
| Pediatric Dose | Not established |
|---|
| Contraindications | Documented hypersensitivity; ischemic heart disease; peripheral vascular disorders |
|---|
| Interactions | Toxicity may increase with ergot alkaloids; amitriptyline, butyrophenones, imipramine, methyldopa, phenothiazines, and reserpine may decrease effects |
|---|
| 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 renal or hepatic disease; discontinue if patient becomes pregnant as significant enlargement of the tumor is uncommon; if visual field impairment occurs, bromocriptine may be continued throughout the pregnancy; use is not approved by the FDA but several studies have shown it to be safe |
|---|
| Drug Name | Cabergoline (Dostinex) |
|---|
| Description | Long-acting dopamine receptor agonist with high affinity for D2 receptors. Prolactin secretion by anterior pituitary is primarily under hypothalamic inhibitory control exerted through dopamine. |
|---|
| Adult Dose | 0.25 mg PO twice weekly; not to exceed 1 mg twice weekly based on prolactin levels; discontinue if normal serum prolactin level is maintained for 6 mo |
|---|
| Pediatric Dose | Not established |
|---|
| Contraindications | Documented hypersensitivity; uncontrolled hypertension |
|---|
| Interactions | May increase effects of antihypertensive medications (adjust dose accordingly); dopamine antagonists may reduce effects of cabergoline |
|---|
| 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 because of relatively high incidence of stroke, seizures, hypertension; monitor prolactin levels monthly; caution in hepatic impairment |
|---|
Further Outpatient Care
Follow-up MRI scans can be performed at 6 and/or 12 months to assess progression. If the tumor enlarges, full endocrine testing and therapy are justified.
In/Out Patient Meds
If the tumor is secreting excess hormone, initiate appropriate medical therapy as described in the articles Hyperprolactinemia, Acromegaly, and Cushing disease.
Complications
- Complications are caused by enlargement of the tumor to a macroadenoma or by excessive hormone secretion.
- Inactive microadenomas rarely cause complications unless they are pressing on the pituitary stalk.
Prognosis
Prognosis depends on the hormonal activity of the adenoma. Most incidentalomas are inactive and do not cause morbidity, except morbidity related to excessive investigation.
Patient Education
Medical/Legal Pitfalls
Failure to monitor microadenoma for enlargement or excess hormone secretion can lead to subsequent preventable morbidity.
| Media file 1:
MRI showing a nonenhancing area in the pituitary consistent with a microadenoma in a patient with hyperprolactinemia. |
 |  View Full Size Image | |
Media type: MRI
|
- Aron DC, Howlett TA. Pituitary incidentalomas. Endocrinol Metab Clin North Am. Mar 2000;29(1):205-21. [Medline].
- Bailey RH, Aron DC. The diagnostic dilemma of incidentalomas. Working through uncertainty. Endocrinol Metab Clin North Am. Mar 2000;29(1):91-105. [Medline].
- Boni G, Ferdeghini M, Bellina CR, et al. [111In-DTPA-D-Phe]-octreotide scintigraphy in functioning and non-functioning pituitary adenomas. Q J Nucl Med. Dec 1995;39(4 Suppl 1):90-3. [Medline].
- Cannavo S, De Natale R, Curto L, et al. Effectiveness of computer-assisted perimetry in the follow-up of patients with pituitary microadenoma responsive to medical treatment. Clin Endocrinol (Oxf). Aug 1992;37(2):157-61. [Medline].
- De Rosa M, Zarrilli S, Di Sarno A, et al. Hyperprolactinemia in men: clinical and biochemical features and response to treatment. Endocrine. Feb-Mar 2003;20(1-2):75-82. [Medline].
- Karam K, Sayegh R, Saadeh G, Saba M. Gonadotropin secreting pituitary microadenoma. J Med Liban. 1992;40(1):31-5. [Medline].
- King JT, Justice AC, Aron DC. Management of incidental pituitary microadenomas: a cost-effectiveness analysis. J Clin Endocrinol Metab. Nov 1997;82(11):3625-32. [Medline].
- Losa M, Mortini P, Barzaghi R, et al. Surgical treatment of prolactin-secreting pituitary adenomas: early results and long-term outcome. J Clin Endocrinol Metab. Jul 2002;87(7):3180-6. [Medline].
- Maruyama T, Masuda H, Uchida H, Nagashima T, Yoshimura Y. Follicle stimulating hormone-secreting pituitary microadenoma with fluctuating levels of ovarian hyperstimulation. Obstet Gynecol. May 2005;105(5 Pt 2):1215-8. [Medline].
- Minniti G, Jaffrain-Rea ML, Esposito V, et al. Evolving criteria for post-operative biochemical remission of acromegaly: can we achieve a definitive cure? An audit of surgical results on a large series and a review of the literature. Endocr Relat Cancer. Dec 2003;10(4):611-9. [Medline].
- Molitch ME. Management of prolactinomas during pregnancy. J Reprod Med. Dec 1999;44(12 Suppl):1121-6. [Medline].
- Oruckaptan HH, Senmevsim O, Ozcan OE, Ozgen T. Pituitary adenomas: results of 684 surgically treated patients and review of the literature. Surg Neurol. Mar 2000;53(3):211-9. [Medline].
- Park YG, Chang JW, Kim EY, Chung SS. Gamma knife surgery in pituitary microadenomas. Yonsei Med J. Jun 1996;37(3):165-73. [Medline].
- Shimon I, Ram Z, Cohen ZR, Hadani M. Transsphenoidal surgery for Cushing''s disease: endocrinological follow-up monitoring of 82 patients. Neurosurgery. Jul 2002;51(1):57-61; discussion 61-2. [Medline].
- Simard MF. Pituitary tumor endocrinopathies and their endocrine evaluation. Neurosurg Clin N Am. Jan 2003;14(1):41-54, vi. [Medline].
- Teramoto A, Hirakawa K, Sanno N, Osamura Y. Incidental pituitary lesions in 1,000 unselected autopsy specimens. Radiology. Oct 1994;193(1):161-4. [Medline].
- Tripathi S, Ammini AC, Bhatia R, et al. Cushing's disease: pituitary imaging. Australas Radiol. Aug 1994;38(3):183-6. [Medline].
- Verhelst J, Abs R, Maiter D, et al. Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients. J Clin Endocrinol Metab. Jul 1999;84(7):2518-22. [Medline].
- Xu RK, Wu XM, Di AK, et al. Pituitary prolactin-secreting tumor formation: recent developments. Biol Signals Recept. Jan-Feb 2000;9(1):1-20. [Medline].
- de Herder WW, Uitterlinden P, Pieterman H, et al. Pituitary tumour localization in patients with Cushing's disease by magnetic resonance imaging. Is there a place for petrosal sinus sampling?. Clin Endocrinol (Oxf). Jan 1994;40(1):87-92. [Medline].
- Galluzzi F, Salti R, et al. Reversible weight gain and prolactin levels--long-term follow-up in childhood. J Pediatric Endocrinology. Sep 2005;18(9(:921-4. [Medline].
- Ricci G, Giolo E, Nucera G et al. Pregnancy in hyperprolactinemic infertile women treated with vaginal bromocripptine: report of two cases and review of the literature. Gynecologic and Obstetric Investigation. 2001;51(4):266-70. [Medline].
Pituitary Microadenomas excerpt Article Last Updated: Sep 21, 2007
|
