AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Background

Prolactinoma is the most common hormone-secreting pituitary tumor. Based on size, a prolactinoma can be classified as a microprolactinoma (<10 mm diameter) or macroprolactinoma (>10 mm diameter).

Pathophysiology

Tumor formation is due to neoplastic transformation of anterior pituitary lactotrophs, resulting in excess synthesis and secretion of prolactin (PRL).

Physiologically, PRL, a polypeptide hormone consisting of 199 amino acids, is regulated by hypothalamic factors. These include prolactin-releasing factors (PRFs) and prolactin-inhibitory factors (PIFs).

Dopamine (DA) is the principal PIF, and thyrotropin-releasing hormone (TRH), vasoactive intestinal peptide, and peptide histidine methionine are the putative PRFs. The physiologic role of these PRFs is not established. A delicate balance between the PRFs and PIFs normally keeps the serum PRL level within a physiological range. Moreover, the interplay of various neurohormonal factors results in a pulsatile secretion of PRL from the pituitary.

Prolactinoma is one of the several causes of pathologic hyperprolactinemia (see Other Problems to be Considered).

Frequency

United States

The exact frequency with which prolactinomas occur in the general population is not clearly established. In nonselected surgical series, this tumor accounts for approximately 25-30% of all pituitary adenomas. Some growth hormone (GH)–producing tumors also co-secrete PRL. Microprolactinomas are much more common than macroprolactinomas.

Sex

Of women with prolactinomas, 90% present with microprolactinomas. Of men with prolactinomas, as many as 60% present with macroprolactinomas. This may due, in part, to the fact that men with this tumor present much later for clinical evaluation of complaints of hypogonadism compared to women with this tumor who often present earlier for clinical evaluation of amenorrhea.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

History

Prolactinomas can cause symptoms secondary to the hormonal effects of excess PRL and to the space-occupying effects of the tumor itself.

• Effects of sustained hyperprolactinemia
• • Clinical features vary with the age and sex of the patient and with the duration and degree of hyperprolactinemia.

  • Reproductive-aged females can present with menstrual disturbance and/or infertility. The usual types of menstrual aberrations in these women are oligomenorrhea, amenorrhea, or irregular menstrual cycles. Occasionally, if the prolactinoma occurs in a person of younger age, delayed menarche can result.

  • Galactorrhea can be spontaneous or expressive (only upon squeezing of the nipples). Galactorrhea is observed in up to 30-80% of these women and can be quite distressing for the patient.

  • Other features of hypoestrogenism include vaginal dryness, dyspareunia, and a decline in bone mineral density (ie, osteopenia or osteoporosis).

  • Men with prolactinoma have one or more features of hypogonadism, which may include decreased libido, erectile dysfunction, or infertility. Gynecomastia is very unusual in these men. Galactorrhea is much less common in men compared to women, and demonstrating galactorrhea in men may require vigorous breast manipulation.

  • If a prolactinoma develops prepubertally, hyperprolactinemia may result in a female body habitus and small testicles.

  • If the prolactinoma is large enough to compress the surrounding normal hormone-secreting pituitary cells, it may result in deficiencies of one or more hormones (eg, thyroid-stimulating hormone [TSH], GH, adrenocorticotropic hormone).

• Space-occupying effects of prolactinoma
• • Space-occupying effects correlate with the size of the tumor. Larger tumors are frequently associated with headache secondary to stretching of the pain-sensitive structures around the pituitary gland.

  • Encroachment of surrounding tissues may result in visual problems in the form of field defects, ranging from bitemporal hemianopsia (from compression of the optic chiasm), which is common, to total loss of vision and ophthalmoplegia (from compression of cranial nerves III, IV, or VI).

  • Postmenopausal women and elderly men frequently present only with the space-occupying effects of the tumor.

Physical

• Focus the physical examination in women on assessing for galactorrhea and identifying clinical signs of estrogen deficiency.
• In men, examine testicular size and consistency and the pattern of hair on the body. Also assess for the rare occurrence of gynecomastia, galactorrhea, or both.
• In both male and female patients, assess visual acuity and visual fields (by confrontation method) and perform a cranial nerve examination at the bedside to help determine if any mass effect has occurred from the tumor.

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Other Problems to be Considered

If women have primary or secondary amenorrhea, consider other possible causes of primary or secondary amenorrhea in the differential. If patients (men or women) present with infertility, consider all other causes of infertility in the differential.

If a patient has an elevated PRL level, other causes of hyperprolactinemia must be sought. These include (1) drugs (eg, phenothiazines, haloperidol, metoclopramide, methyldopa, reserpine, verapamil, tricyclic antidepressants, chronic opiate abuse, cocaine); (2) pituitary or hypothalamic causes (eg, GH-secreting adenoma, nonfunctioning adenoma, pituitary stalk compression, empty sella syndrome, craniopharyngioma, meningioma, dysgerminoma, lymphocytic hypophysitis, other granulomatous conditions causing pituitary stalk distortion, prior radiation to the area); (3) pregnancy, primary hypothyroidism, chronic renal failure, cirrhosis, or adrenal insufficiency; (4) chest wall lesions, breast stimulation, or spinal cord lesions; and (5) idiopathic causes.

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Lab Studies

• Hormone testing
• • Serum PRL: Measure serum PRL levels on one or more occasions, especially if the elevation is modest. Do not measure the PRL level directly after performing a breast examination because the breast examination may cause a physiological PRL elevation.
  
  
  
  • Urine pregnancy test: Always consider the possibility of pregnancy in reproductive-aged females because this is the most common cause of secondary amenorrhea in this group.
  
  
  
  • Serum TSH: Measure TSH levels to exclude the possibility of an elevated PRL level occurring secondary to an elevated TRH level. TRH is one of the PRFs. If the TSH level is elevated, confirm the finding by measuring the free thyroxine level.
     
• Measurement of other pituitary hormones
• • In a male presenting with symptoms of hypogonadism, measure serum testosterone or bioavailable testosterone levels.
  
  
  
  • In a patient with a history suggestive of adrenal insufficiency, measure basal and cosyntropin-stimulated cortisol levels.
  
  
  
  • In a person with features consistent with acromegaly, measure serum insulinlike growth factor-1 levels.
     
• Exclude other possible systemic causes for hyperprolactinemia, such as chronic renal failure or cirrhosis, using appropriate laboratory tests as warranted.

Imaging Studies

• After performing biochemical testing, order a magnetic resonance imaging (MRI) scan of the pituitary hypothalamic area (with gadolinium enhancement) or CT scan of the region (with contrast) to determine if a mass lesion is present.
  • MRI is better for soft tissue delineation and identification of a small lesion. CT scan is better for identification of any bone distortion or destruction. Special attention is given to the size of the tumor and its encroachment on surrounding structures (eg, optic chiasm, other cranial nerves) and resulting effects (eg, bony destruction).
  
  
  
  • Good correlation exists between the size of the prolactinoma and the degree of elevation of the serum PRL. A serum PRL value of 200 ng/mL or greater, in the presence of a macroadenoma (>10 mm), is virtually diagnostic of prolactinoma. However, if the serum PRL value is less than 200 ng/mL in the presence of a large pituitary mass lesion, this is more suggestive of secondary hyperprolactinemia secondary to stalk compression by the lesion or to an artifact in the lab method used to measure prolactin called the hook effect. Immunoassays used to measure PRL such as immunoradiometric assay (IRMA), enzyme immunoassay (EIA), and immunochemiluminometric assay (ICMA) employ a "sandwich" (2 antibody) technique. When PRL level is markedly elevated, the excess antigen (PRL) is washed off in the liquid phase of the sandwich assay and thereby results in gross underestimation of antigen levels in the specimen. When this is suspected, serial dilutions of the serum sample will reveal the actual hormone level.
  
  
  
  • Repeat scans are obtained postoperatively and during follow-up examinations thereafter, or they are obtained after medical treatment to help determine if the tumor has progressed or regressed. The frequency with which repeat imaging scans are performed is individualized to the patient being treated.

Other Tests

• Formal visual-field (VF) testing by an ophthalmologist is performed when the tumor is large and is in close vicinity of the optic chiasm prior to any therapy. The same testing is repeated after treatment is begun to monitor the patient's response to treatment.

Procedures

• If a pituitary/hypothalamic lesion other than prolactinoma is considered, such as lymphocytic hypophysitis or a granulomatous condition, biopsy of the lesion by a neurosurgeon is indicated.

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Medical Care

Treatment is indicated if mass effects from the tumor, significant effects from hyperprolactinemia, or both are present.

Although the natural history of prolactinomas is unclear, most microprolactinomas (up to 95%) do not progress to macroadenomas, as determined after a 4- to 6-year observation period. Hence, if a patient with a microprolactinoma has minimal symptoms, the patient can be monitored closely with serial estimations of serum PRL levels combined with imaging studies at yearly intervals. However, if a patient with a microprolactinoma has significant effects from the hyperprolactinemia, treatment is indicated.

Any patient with macroprolactinoma needs treatment because the tumor has already shown a propensity to grow.

• Medical treatment
  
  
  • Bromocriptine (BEC) is generally considered to be the agent of choice in the treatment of prolactinoma because of its long track record and safety. As a DA agonist, it decreases the synthesis and secretion of PRL. It also decreases the rate of tumor cell division and growth of individual cells.
  
  
  • Typically, BEC is administered at an initial dose of 1.25 mg nightly with food and gradually increased to 2.5 mg bid in 1-2 weeks, as tolerated. Doses larger than 7.5 mg/d are seldom needed except in the treatment of macroadenomas.
  
  
  • Common adverse effects include nausea, nasal stuffiness, and dizziness associated with orthostatic hypotension. Others include vasospasm in the peripheral circulation and exacerbation or unmasking of depression and psychosis.
  
  
  • In patients intolerant to even small doses of BEC, one alternative is to administer the same daily dose intravaginally once a day, which has almost equal efficacy.
  
  
  • Normalization of PRL levels occurs in 85-90% of all patients with prolactinomas.
  
  
  • In microprolactinomas, PRL levels return to normal within days to a few weeks of starting treatment in almost all patients who can tolerate appropriate doses of BEC. If PRL levels normalize, gonadal function also typically has a near-total recovery. Menses return to normal within a few months. Sometimes, pregnancy can occur before resumption of menstruation; therefore, the couple must be advised to use barrier methods of contraception until normal menses have returned.
  
  
  • In macroprolactinomas, BEC treatment results in some reduction of tumor size in up to 80-85% of the patients. Significant VF improvements have been noted as early as 1-3 days, and significant changes on imaging findings occur as soon as 2 weeks after starting treatment.
  
  
  • In contrast to patients with microadenomas, resolution of hyperprolactinemia is often incomplete in patients with macroadenomas. However, the extent of reduction in tumor size is not well correlated with the changes in serum PRL levels. Nevertheless, reductions in PRL levels always precede tumor shrinkage, and those who do not show a drop in PRL do not have any tumor shrinkage.
  
  
  • A reduction in tumor size is often accompanied by improvement in pituitary function. Examples include improvement in serum testosterone levels and an increase in sperm counts.
  
  
  • Once normalization of PRL levels is achieved and sustained, the dose of BEC is gradually tapered to approximately 2.5 mg/d. If PRL levels and tumor size are stable on the above dose, consider tapering BEC to the lowest dose possible. The patient should be evaluated periodically with monitoring of symptoms, PRL levels, and radiological changes.
  
  


• Other medical treatments available for patients who do not respond to BEC or those who cannot tolerate BEC
  
  
  • Cabergoline, a long-acting nonergot DA agonist, was recently made available in the United States and is usually better tolerated than BEC. Efficacy profiles are somewhat superior to those of BEC. It offers the convenience of twice-a-week administration, with a usual starting dose of 0.25 mg biweekly to a maximum dose of 1 mg biweekly. Some studies have shown efficacy even with once-a-week dosing. Cabergoline appears to be more effective in lowering prolactin levels and restoring ovulation. Up to 70% of patients who do not respond to BEC respond to cabergoline. The only problem is cost. Side effects are somewhat fewer than with BEC and include headache, nausea, postural hypotension, and fatigue.
  
  
  • Quinagolide, a nonergot DA agonist with a long duration of action, is not yet available for use in the United States. It can be administered once daily. Efficacy and tolerance are comparable to that of BEC.
  
  
  • Pergolide, a drug approved for the treatment of Parkinson disease, is a DA agonist with a long duration of action. Daily doses of 50-150 mcg are nearly as effective as treatment with BEC. Tolerance is comparable to that with BEC. Some patients who do not respond to BEC tend to respond to pergolide and vice versa. Rare cases of valvular heart disease have been reported in users of pergolide much like the lesions noted with use of fenfluramine or in patients with carcinoid tumors. The use of pergolide is therefore not generally recommended in patients with prolactinoma for this reason.
  
  
  • 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 abruptly stop pergolide. 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.
  
  


• Withdrawal of medical therapy: In some patients with prolactinoma who have adequately responded to medical treatment, withdrawing medical treatment after about 24 months of treatment may be possible. Even though no clear predictive criteria for such successful withdrawal exist, it appears that recurrence of hyperprolactinemia was generally lower in patients with microadenomas than in those with macroadenomas. Hyperprolactinemia recurred more likely in those with tumor remnant on pituitary MRI compared with those without a remnant. In very large adenomas, regrowth of tumor is often seen after withdrawal of medical treatment. In any case, if medical treatment is withdrawn, close clinical, biochemical, and radiologic monitoring is warranted to look for evidence of tumor recurrence.


• Radiation treatment
  
  
  • Radiation treatment (XRT) has a limited role in the treatment of prolactinomas. Following conventional XRT, PRL levels normalize in only approximately 25% of patients. The major complication of this treatment is hypopituitarism, which occurs in up to 12.5-80% of patients. The other complications include optic nerve damage and neurologic dysfunction (see Complications).
  
  
  • Because of the excellent results with medical treatment, with or without surgery, XRT is seldom used. XRT is considered only in select cases, ie, with rapid tumor regrowth despite medical and surgical treatment.
  
  


• Pregnancy and prolactinoma
  
  
  • During pregnancy, a physiologic doubling in the volume of normal pituitary gland occurs. Moreover, prolactin levels increase by 10-fold during this period.
  
  
  • When a woman with prolactinoma presents with infertility and is proceeding with medical treatment for hyperprolactinemia, mechanical (barrier) methods of contraception is advised, until menstrual cycles resume for the first few cycles, so that accurate dating of pregnancy can be performed. BEC is the preferred medical treatment in this situation because of its long safety record. BEC can be discontinued after the first skipped period. This is to prevent unwanted fetal exposure to BEC despite its safety record. However, to date, increased rates of spontaneous abortion, ectopic pregnancy, or teratogenic effects have not been reported with BEC therapy.
  
  
  • Most women with microprolactinomas do not show significant increases in tumor size during pregnancy. Rates of tumor progression of 1-5% have been reported in such women. In contrast, those women with macroadenomas show significant tumor enlargement, up to 15-35%, during gestation secondary to the hormonal stimulation of lactotrophs.
  
  
  • The treatment of pregnant women with prolactinomas must be tailored to the individual patient. In those with microadenomas and in the subgroup of women with intrasellar macroadenomas without significant suprasellar or parasellar extension, BEC can usually be safely discontinued upon conception, and the patient can be monitored clinically for symptoms of tumor enlargement. Periodic monitoring of PRL levels and VFs is not usually required in such women.
  
  
  • In those women with larger macroadenomas, a definitive individualized plan is made only after thorough discussions with the patient. Options include (1) discontinuation of BEC at conception and careful monitoring of PRL levels and VFs, with or without MRI scan evidence of tumor enlargement; (2) prepregnancy transsphenoidal surgery with debulking of the tumor, ie, with the resultant risk of complications (see Complications); and (3) continuation of BEC throughout gestation, with the theoretical risk to the fetus.

Surgical Care

Transsphenoidal pituitary adenomectomy is the preferred surgical treatment in patients with microprolactinoma and most patients with macroprolactinoma. A transcranial approach is used only in patients with large extrapituitary extension. A transcranial pituitary tumor resection is more hazardous, ie, associated with higher mortality and morbidity rates.

A combination of surgery followed by postoperative medical treatment with BEC or one of the other agents is used in patients with incomplete resolution of elevated PRL levels or in those with residual tumors seen on follow-up imaging studies.

In surgical series of patients with microadenomas, normalization of PRL levels is reported in approximately 70-75% of patients. Recurrence rates of approximately 17% are reported. This surgery is associated with low mortality and morbidity rates (approximately 0.3% and 0.4%, respectively).

Recent data from a tertiary center indicate an initial cure rate of approximately 90% and a recurrence rate of 16% for microprolactinomas. However, results vary with the experience of the neurosurgeon and the duration of follow-up. Complications include hypopituitarism, bleeding, cerebrospinal fluid rhinorrhea, and diabetes insipidus (see Complications).

In patients with macroprolactinomas, normalization of the PRL level occurs initially in approximately 30% of patients and the recurrence rate is approximately 15-20%. Mortality and morbidity rates are less than 1% and 6%, respectively.

• Indications for surgery
  
  
  • Women who have a microadenoma, desire pregnancy, and cannot tolerate BEC should undergo surgical treatment.
  
  
  
  • Patients who do not wish to take BEC or one of the other drugs long-term should be considered for surgical treatment.
  
  
  
  • Patients who do not respond to medical treatment or those who show progression after an initial response to medical treatment should receive surgical treatment.

Consultations

Neurosurgeon

MEDICATION

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

The drugs effective in the treatment of hyperprolactinemia are DA agonists. DA is the primary physiological inhibitor of PRL secretion; however, DA is not used for treatment because it does not cross the blood-brain barrier. Therefore, drugs that mimic the action of DA on the lactotrophs are used in the medical management of prolactinoma.

Drug Category: Dopamine agonists

Salutary effects on inhibition of PRL synthesis and secretion. These agents are also effective for reducing tumor size.

Drug Name	Cabergoline (Dostinex)
Description	Recently made available in the United States for use in prolactinoma. Long-acting DA agonist with similar efficacy and adverse effects to BEC.
Adult Dose	0.25-1 mg PO twice weekly
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; severe hypertension
Interactions	May increase effects of antihypertensive medications (adjust dose accordingly); DA agonists may reduce effects
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in toxemia of pregnancy, liver or renal disease, cardiovascular disease, psychiatric disorders, or patients taking hypertensives; do not use to inhibit physiologic lactation because of a relatively high incidence of stroke, seizures, and hypertension; monitor PRL levels monthly; caution in hepatic impairment

Drug Name	Pergolide (Permax)
Description	Pergolide withdrawn from US market. Potent DA-receptor agonist at both D1 and D2 receptor sites. Approximately 10-1000 times more potent than BEC on a mg-per-mg basis. Inhibits secretion of PRL; causes a transient rise in serum concentrations of GH and decreases serum concentrations of luteinizing hormone.
Adult Dose	0.25-0.6 mg/d PO qd
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	DA antagonists (eg, neuroleptics phenothiazines, butyrophenones, thioxanthenes, metoclopramide) may diminish effectiveness of pergolide, a DA agonist; because pergolide mesylate is more than 90% bound to plasma proteins, exercise caution if coadministered with other drugs known to affect protein binding
Pregnancy	B - Usually safe but benefits must outweigh the risks.
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

Drug Name	Quinagolide (CV 205-502)
Description	Specific DA-receptor (type 2) agonist with a relatively long duration of action. Not available in the United States.
Adult Dose	0.05-0.1 mg/d PO for microprolactinoma; up to 0.5 mg/d for macroprolactinoma
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy
Precautions	Cardiovascular disease, preeclamptic toxemia, renal or hepatic insufficiency, psychiatric disorders

FOLLOW-UP

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Complications

• Complications of untreated prolactinoma
  
  
  • Mass effects of the tumor may cause VF defects (and blindness), cranial nerve palsies, hydrocephalus, apoplexy (from hemorrhage/infarction into the tumor), and hypopituitarism (from compression of surrounding pituitary cells).
  
  
  
  • The effects of prolonged untreated hyperprolactinemia can include hypergonadism, infertility, and osteoporosis.
     
• Complications of the treatment of prolactinoma
  
  
  • No long-term complications have been reported with medical treatment.
  
  
  
  • Adverse effects of treatment are discussed Medical Care and Medication. 
     
• Complications of pituitary surgery
  
  
  • The mortality rate for transsphenoidal surgery is 0.27% for microadenomas and 0.86% for macroadenomas. The rate is higher for patients undergoing transcranial surgery and in those patients who have been previously been treated with other modalities (~2.5%).
  
  
  
  • Morbidity includes cerebrospinal fluid rhinorrhea, diabetes insipidus (transient or permanent), meningitis, stroke, visual disturbances, and hypopituitarism (cumulative incidence rate of 2% for microadenomas and up to 14% for macroadenomas).
     
• Complications of radiation treatment
  
  
  • The major complication is hypopituitarism. It occurs in 33-70% of patients; incidence increases with the length of follow-up.
  
  
  
  • Other less common complications include damage to optic nerve/chiasm, seizures, vascular injury, and CNS malignancy.

Prognosis

• Patients with microprolactinoma generally have an excellent prognosis. In up to 95% of patients, these tumors do not enlarge over a 4- to 6-year follow-up period. These patients generally do well for extended periods on suppressive therapy with DA agonists.
• Macroprolactinomas have a tendency to grow with time and require aggressive treatment to prevent complications. The rate of growth varies with the individual and cannot be reliably predicted. Careful monitoring of clinical signs and symptoms coupled with serial measurements of serum PRL levels and pituitary imaging remain the cornerstones of follow-up for these patients (ie, to detect any major change in the behavior of these tumors).

Patient Education

• The symptoms of prolactinoma should be explained to the patient, and patients should be advised to report any new or worsening symptom.
• Reproductive-aged females should be encouraged to practice barrier methods of contraception while on BEC (or similar agents), until menstrual cycles normalize. This facilitates accurate timing of any conception that may ensue and allows the physician to withhold BEC treatment upon conception.
• For excellent patient education resources, visit eMedicine's Women's Health Center and Pregnancy and Reproduction Center. Also, see eMedicine's patient education articles Amenorrhea, Birth Control Overview, and Birth Control FAQs.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

• Carter JN, Tyson JE, Tolis G, et al. Prolactin-screening tumors and hypogonadism in 22 men. N Engl J Med. Oct 19 1978;299(16):847-52. [Medline].
• Foyouzi N, Frisbaek Y, Norwitz ER. Pituitary gland and pregnancy. Obstet Gynecol Clin North Am. Dec 2004;31(4):873-92, xi. [Medline].
• Frantz AG. Endocrine diagnosis of prolactin-secreting pituitary tumors. In: Black PM, Zervas NT, Ridgway EC, Martin JB, eds. Secretory Tumors of the Pituitary Gland. 1st ed. New York, NY: Raven Press; 1984:. 45-53.
• Frieze TW, Mong DP, Koops MK. "Hook effect" in prolactinomas: case report and review of literature. Endocr Pract. Jul-Aug 2002;8(4):296-303. [Medline].
• Honbo KS, van Herle AJ, Kellett KA. Serum prolactin levels in untreated primary hypothyroidism. Am J Med. May 1978;64(5):782-7. [Medline].
• Molitch ME. Prolactinoma. In: Melmed S, ed. The Pituitary. Boston, Mass: Blackwell Scientific; 1995:. 443-7.
• Raymond JP, Goldstein E, Konopka P, et al. Follow-up of children born of bromocriptine-treated mothers. Horm Res. 1985;22(3):239-46. [Medline].
• Rivera JL, Lal S, Ettigi P, et al. Effect of acute and chronic neuroleptic therapy on serum prolactin levels in men and women of different age groups. Clin Endocrinol (Oxf). May 1976;5(3):273-82. [Medline].
• Schlechte J, Dolan K, Sherman B, et al. The natural history of untreated hyperprolactinemia: a prospective analysis. J Clin Endocrinol Metab. Feb 1989;68(2):412-8. [Medline].
• Schlechte JA. Clinical practice. Prolactinoma. N Engl J Med. Nov 20 2003;349(21):2035-41. [Medline].
• Serri O. Progress in the management of hyperprolactinemia. N Engl J Med. Oct 6 1994;331(14):942-4. [Medline].
• Tyrrell JB, Lamborn KR, Hannegan LT, et al. Transsphenoidal microsurgical therapy of prolactinomas: initial outcomes and long-term results. Neurosurgery. Feb 1999;44(2):254-61; discussion 261-3. [Medline].
• Webster J, Piscitelli G, Polli A, et al. A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. Cabergoline Comparative Study Group. N Engl J Med. Oct 6 1994;331(14):904-9. [Medline].

Article Last Updated: May 12, 2006