The Journal of Clinical Endocrinology & Metabolism Vol. 92, No. 8 2861-2865
Copyright © 2007 by The Endocrine Society
Long-Term Management of Prolactinomas
Janet A. Schlechte
University of Iowa, Iowa City, Iowa 52242
Address all correspondence and requests for reprints to: Janet A. Schlechte, M.D., Department of Internal Medicine, 157 MRF, University of Iowa Hospital, 200 Hawkins Drive, Iowa City, Iowa 52242. E-mail: janet-schlechte{at}uiowa.edu.
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Abstract
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Prolactinomas are a frequent cause of gonadal dysfunction and infertility, especially in young women. The regulation of prolactin secretion and the efficacy of dopamine agonists in the therapy of prolactinomas are well established. The current challenges in management of prolactinomas are related to follow-up after successful therapy. Issues and questions to be addressed in this approach to long-term management of prolactinomas include the frequency of radiographic monitoring, effect of pregnancy and menopause, safety of estrogen in women taking oral contraceptives, and the potential for discontinuation of dopamine agonist therapy.
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Case 1
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A 32-yr-old woman developed hyperprolactinemia, amenorrhea, and galactorrhea after the birth of her second child. Her serum prolactin was 95 µg/liter (normal is <25), a pituitary magnetic resonance imaging (MRI) scan showed a 6-mm adenoma, and she began treatment with cabergoline. For the last 2 yr she has taken 0.5 mg cabergoline weekly and has regular menses. Her prolactin now is 5 µg/liter, and she does not plan future pregnancies. She wants to know when to have another MRI and how long she needs to take cabergoline.
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Case 2
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While undergoing an evaluation for headaches, a 50-yr-old man had an MRI that showed a 25-mm pituitary mass with suprasellar extension. Laboratory testing revealed a serum prolactin of 1240 µg/liter, a normal free T4, and a total testosterone of 150 ng/dl (5.2 nmol/liter) (normal is 300–1200 ng/dl). After 3 months of therapy with cabergoline, his prolactin was 15 µg/liter and the tumor decreased in size to 4 mm. He has now taken 2 mg cabergoline weekly for 36 months and has no complaints. One month ago, his prolactin was 11 µg/liter and testosterone 320 ng/dl (11.1 nmol/liter), and an MRI showed a 4-mm intrasellar mass. He wants to know whether he should have pituitary surgery or how long he will need to take the dopamine agonist.
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Background
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Prolactinomas are the most common functioning pituitary tumor. Ninety percent are intrasellar adenomas that rarely increase in size. The rest are macroadenomas (>10 mm) that usually come to clinical attention because of local mass effects. In women, most prolactinomas are microadenomas (<10 mm), and hypersecretion of prolactin leads to amenorrhea, galactorrhea, and infertility. Men with prolactinomas frequently present with headache, visual loss, or neurological deficit but also have hypogonadism and infertility. Hyperprolactinemia may lead to bone loss in both men and women due to the inhibitory effect of prolactin on sex steroids (1).
The goals of therapy are to normalize prolactin, restore fertility, reduce tumor size, and ameliorate the symptoms of hypogonadism. In some cases, gonadal function normalizes even though serum prolactin remains elevated. In this situation, the clinical response is more important than the absolute level of prolactin. Pituitary surgery does not reliably lead to a cure, and a dopamine agonist is the preferred treatment for prolactinomas. Bromocriptine normalizes prolactin and decreases tumor size in 80–90% of patients with microadenomas and in 70% with large tumors (2). The selective D2 receptor agonist cabergoline is more effective and better tolerated than bromocriptine and is also effective in treatment of tumors resistant to other dopamine agonists (3, 4). The major shortcoming of therapy with both dopamine agonists is that cessation of therapy leads to recurrence of hyperprolactinemia and tumor reexpansion.
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Clinical Considerations
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Hormonal and radiographic monitoring
Normal prolactin levels in women are less than 25 µg/liter and less than 20 µg/liter in men. With macroadenomas, prolactin levels are generally more than 250 µg/liter and frequently exceed 1000 µg/liter when the tumor is invasive (1). In general, there is a close correlation between serum prolactin and tumor size, and it is rare for a prolactinoma to expand significantly without a marked increase in prolactin (5). The majority of prolactinomas are microadenomas and rarely increase in size over time. In a summary of 139 hyperprolactinemic women with tumors less than 10 mm followed longitudinally for over 8 yr, only 6.5% showed evidence of tumor expansion (5). Longitudinal studies have also shown resolution of hyperprolactinemia, amenorrhea, and galactorrhea without therapy in women with microadenomas (6, 7).
Macroadenomas account for about 10% of prolactinomas and are more frequent in men. It has been postulated that the higher prevalence of large tumors in men is due to a delay in diagnosis, but this does not seem likely in light of the benign natural history of small tumors. In addition, autopsy studies do not show a preponderance of macroadenomas or a greater number of large tumors in men (8). The presence of histological markers of aggressiveness (Ki67 and proliferative cell nuclear antigen) in macroadenomas suggests greater proliferative activity, but the markers have limited predictive value. A molecular basis for enhanced aggressiveness of large tumors has not been clearly elucidated (9).
There is no consensus on how frequently to image the pituitary after therapy. For patients with microadenomas, I measure prolactin yearly and do not repeat an MRI unless there is a marked increase in prolactin (more than 250 µg/liter) or clinical signs of tumor expansion such as headaches or visual loss. Because macroadenomas possess a higher growth potential, more frequent radiographic monitoring is necessary. I repeat an MRI 2–3 yr after achievement of normal prolactin and reduction in tumor size to confirm tumor suppression and to ensure that prolactin levels are a reliable indicator of tumor size.
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The Effect of Pregnancy, Menopause, and Estrogen
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Pregnancy
During pregnancy, estrogen stimulates prolactin synthesis and induces lactotroph hyperplasia, which leads to pituitary enlargement. Prolactinomas also increase in size during pregnancy, but whether the tumor enlargement is clinically significant depends on the size of the tumor. Women with microadenomas and intrasellar macroadenomas have a less than 3% chance of symptomatic tumor enlargement during pregnancy compared with a more than 30% chance in women with macroadenomas (10). If macroadenomas are treated with radiation or surgery before conception, the risk of clinically significant tumor expansion falls from over 30% to less than 5% (10). Although breast stimulation stimulates prolactin release, there is no evidence that breastfeeding has an adverse effect on tumor growth (11).
When pregnancy is the treatment goal, bromocriptine is preferred over cabergoline because of its extensive safety record. Data on fetal exposure to bromocriptine has been reported in over 6000 pregnancies compared with about 350 with cabergoline (5, 12, 13). Administered during the first few weeks of gestation, bromocriptine is not associated with an increase in the rate of spontaneous abortions or congenital malformations (12) and should be discontinued as soon as pregnancy is confirmed. Women with microadenomas and intrasellar macroadenomas do not require serial MRI examinations or visual field testing during pregnancy but should be monitored each trimester for clinical signs of tumor expansion. Pregnant women with large tumors and those with extrasellar extension who have stopped bromocriptine are at risk for tumor growth, and formal visual field testing should be done each trimester. It is not necessary to measure serum prolactin throughout pregnancy because levels do not uniformly increase during gestation and do not correlate with tumor enlargement (10). A detailed discussion of management of prolactinomas during pregnancy is beyond the scope of this paper and is reviewed in Ref. 10 .
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Use of Oral Contraceptives
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The observation that prolactinomas frequently become apparent after pregnancy or after discontinuation of an oral contraceptive suggested that estrogen might play a role in the pathogenesis of prolactinomas. The finding that estrogen given to animals induced lactotroph hyperplasia and tumor formation led to concerns that estrogen administered to women with hyperprolactinemia would accelerate tumor growth (14). In reality, autopsies of patients treated with pharmacological doses of estrogen do not show an increased number of prolactinomas (15), and case control studies have not demonstrated an association between estrogen use and prolactinoma formation (16).
There are no long-term prospective trials demonstrating the safety of physiological doses of estrogen in women with prolactinomas. However, no evidence of tumor growth was seen in premenopausal women with microadenomas or women with idiopathic hyperprolactinemia treated with conjugated estrogen or oral contraceptives for 2–6 yr (14, 17, 18). Additional information supporting the safety of estrogen in women with prolactinomas is the observation that microprolactinomas rarely increase in size during pregnancy (10). There have been no trials examining the effect of estrogen on macroadenomas, and women with very large tumors and/or tumors with suprasellar extension should not be treated with estrogen.
When fertility is not an issue in women with microprolactinomas, treatment of hypogonadal symptoms with an oral contraceptive is less expensive and has fewer side effects than treatment with a dopamine agonist. Treatment with estrogen may, however, induce or worsen preexisting galactorrhea. Oral contraceptives may lead to a mild increase in serum prolactin, and prolactin levels should be monitored yearly. It is not necessary to repeat an MRI in a woman taking estrogen unless the prolactin rises unexpectedly and exceeds 250 µg/liter (1).
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Beneficial Effects of Pregnancy and Menopause
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Despite the tumor expansion and pituitary growth that occurs during gestation, observational studies have shown that pregnancy has a favorable effect on the natural history of preexisting prolactinomas. Prolactin levels are lower after delivery than before conception and complete remission of hyperprolactinemia has been reported in 17–37% of women after pregnancy (19, 20). Changes in tumor vasculature resulting in pituitary necrosis, microinfarction, or hemorrhage have been suggested as potential mechanisms to explain how pregnancy might lead to normalization of prolactin (21).
Based on declining estrogen levels that accompany the cessation of menses, it is not surprising that menopause appears to have a beneficial effect on the natural history of hyperprolactinemia. In a retrospective analysis, Karunakaran et al. (22) showed that 45% of hyperprolactinemic patients who passed through menopause normalized serum prolactin compared with 7% of controls. A prospective analysis will be necessary to confirm potential beneficial effects of pregnancy and menopause on remission of hyperprolactinemia and to determine whether either factor is a predictor of remission.
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Can Therapy with Dopamine Agonists Be Discontinued?
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The major shortcoming of all dopamine agonists is that interruption of therapy leads to recurrence of hyperprolactinemia and tumor regrowth. In addition, the drugs are expensive, side effects are not infrequent, and compliance can be problematic. The observation that long-term therapy leads to perivascular fibrosis and cytocidal effects on pituitary tissue (23) suggested that bromocriptine might lead to permanent normoprolactinemia. The first studies to assess the effect of dopamine agonist withdrawal showed rapid recurrence of hyperprolactinemia in over 95% of patients treated for 24 months (24, 25). Although normoprolactinemia was not maintained, postwithdrawal prolactin levels remained lower than pretreatment levels (24, 25).
Table 1
summarizes the results of 13 studies involving 853 patients who were withdrawn from dopamine agonist therapy between 1983 and 2006 (24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36). Drawing conclusions is difficult because few of the studies were prospective, radiographic monitoring included computed tomography and MRI examinations, some studies included micro- and macroadenomas, some used bromocriptine, others used cabergoline, and some used both drugs or other dopamine agonists. In addition, many of the patients had undergone transsphenoidal surgery or had received radiation therapy before drug withdrawal. The duration of therapy ranged from 12–84 months, and the length of observation after drug withdrawal was 12–60 months. The percentage of subjects achieving a period of normoprolactinemia ranged from 7–69% (mean 29%). Tumor regrowth was noted in only two individuals (26, 29). Extending therapy with bromocriptine from 12 to 24 months in one study doubled the rate of remission (26).
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TABLE 1. Summary of the results of 13 studies involving 853 patients who were withdrawn from dopamine agonist therapy between 1983 and 2006
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In a comprehensive prospective study, Colao et al. (34) treated patients with micro- and macroadenomas with cabergoline (1 mg/wk) for 48 and 42 months, respectively. Before drug withdrawal, the cabergoline was tapered to 0.5 mg/wk, and the drug was withdrawn if 1) prolactin levels were normal, 2) an MRI showed no tumor or tumor reduction of at least 50%, 3) the tumor was more than 5 mm from the optic chiasm, and 4) there was no cavernous sinus invasion. From 2–5 yr after cabergoline withdrawal, prolactin was normal in 69% of patients with microadenomas and 64% with macroadenomas, and no tumor regrowth was observed. In both micro- and macroadenomas, prolactin levels at the time of recurrence were significantly lower than at diagnosis. Of those who developed recurrent hyperprolactinemia, 50% recurred during the first year after drug withdrawal, 33% during the second year, and 11% during the third year. Sex, age, menopause, and pregnancy were not significantly associated with recurrence of hyperprolactinemia. Although the rate of recurrence was higher among patients who had evidence of a tumor on MRI at the time of drug withdrawal, 59% with remnant microadenomas and 23% with remnant macroadenomas had normal prolactin after cabergoline was withdrawn.
Biswas et al. (35) retrospectively analyzed 89 subjects with microadenomas treated with cabergoline (0.5–3.0 mg weekly) or bromocriptine (2.5–10 mg daily) for a mean duration of 3.1 yr. Previously treated patients were excluded, the drugs were withdrawn without tapering, and the subjects were observed for at least 12 months after discontinuation of the dopamine agonist. Thirty-six percent achieved remission after at least 1 yr of surveillance, and 84% of these subjects remained in remission for more than 24 months. Of those who developed recurrent hyperprolactinemia, 81% recurred within 12 months of discontinuation of therapy, and the mean time to recurrence was 9.6 months. There was no difference in remission rates between subjects treated with cabergoline and bromocriptine. Pretreatment prolactin was the only factor significantly associated with relapse. The difference between the remission rates in the Biswas (36%) and Colao (69%) studies is likely due to the fact that the latter study excluded patients who were pregnant, had failed to normalize prolactin, or had tumor nonshrinkage.
These data can be used to formulate recommendations for drug withdrawal. Patients with microadenomas and those with macroadenomas and negative MRI scans after treatment are good candidates for drug withdrawal. Because tumor enlargement is uncommon in small tumors, it is not necessary to obtain a prewithdrawal MRI in a patient with microadenoma, and the drug can be stopped without a taper. In patients with macroadenomas and negative MRI scans, the drug should be slowly tapered before withdrawal. During the first year after drug withdrawal, prolactin levels and clinical symptoms should be assessed at 3-month intervals because recurrence rates are highest in the 12 months after withdrawal (34, 35). Because increases in prolactin generally precede tumor growth, repeating an MRI is not necessary unless hyperprolactinemia recurs. Although recurrence is more likely in the presence of a tumor remnant, some of these patients will maintain normal prolactin levels after drug withdrawal (34). These patients will, however, require very careful follow-up because their risk of tumor regrowth over time may be increased. Although a patient with a macroadenoma may not achieve normoprolactinemia, tumor suppression and normal prolactin may be attainable at lower doses over time (37).
It is not clear whether a dopamine agonist exerts a direct antitumor effect or whether the normoprolactinemia that occurs after withdrawal is a manifestation of the natural history of the disorder. Tumor disappearance does occur in patients with microadenomas without therapy, but it is more difficult to attribute remission of a macroadenoma to spontaneous tumor disappearance. The possibility that lifelong therapy for prolactinomas may be unnecessary is intriguing, but it should be noted that the patients with macroadenomas studied thus far represent a subset of patients with large tumors, and the findings should not be generalized to all patients with large prolactinomas. The importance of long-term follow-up studies cannot be overemphasized.
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Is There a Role for Surgery in Long-Term Management of Prolactinomas?
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Dopamine agonists are the preferred therapy for prolactinomas because of the risk of recurrent hyperprolactinemia that accompanies transsphenoidal surgery. Success rates after surgical treatment of microadenomas range from 73–90% and 30–50% for macroadenomas (38, 39). With an experienced surgeon, success rates over 90% can be achieved in carefully selected young patients with small tumors and prolactin levels less than 200 µg/liter (38, 39). It has been proposed that it may be more economical to operate on patients with a high likelihood of surgical cure rather than relying on long-term dopamine agonist therapy (40). However, persistence of normoprolactinemia after withdrawal of cabergoline discussed above, even in macroadenomas, weakens this economic argument. Although infrequently used, transsphenoidal surgery is an option in individuals who cannot tolerate a dopamine agonist or in whom the drug is ineffective, but dopamine agonists remain the first line of therapy.
Whether therapy with a dopamine agonist exerts a negative effect on surgical outcome remains controversial. Landolt and Osterwalder (23) noted that patients treated with bromocriptine before surgery were significantly less likely to normalize prolactin due to perivascular and tumor fibrosis. In contrast, other analyses have noted improved outcomes when patients were treated with bromocriptine before surgery (41).
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Safety of Dopamine Agonists
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All of the dopamine agonists have side effects, and patients may note nausea, vomiting, dry mouth, dyspepsia, or dizziness at the initiation of therapy. Used in doses of 2.5–10 mg daily (bromocriptine) and 0.25–2 mg weekly (cabergoline), long-term adverse effects have not been reported in patients with prolactinomas. In contrast, pleural thickening, parenchymal lung disease, and serosal fibrosis have been reported in patients with Parkinson’s disease receiving chronic therapy with bromocriptine, cabergoline, and pergolide (42, 43).
A recent report of cardiac valve regurgitation in patients with Parkinson’s disease treated with pergolide and cabergoline has raised new concerns about long-term safety of dopamine agonists (44). A population-based study of patients with Parkinson’ disease treated with pergolide and cabergoline showed similar findings (45). The risk of valvular regurgitation appears to be greatest in patients who receive at least 3 mg cabergoline daily, and this dose is 10–20 times higher than that used for usual treatment of macroadenomas. Patients who have demonstrated resistance to a dopamine agonist and who require very high daily doses (46) should have an echocardiogram. In addition, because the risk of valvular disease in patients receiving long-term, low-dose dopamine agonist therapy is unknown, endocrinologists should discuss with each patient the potential risks of therapy and decide on the need for an echocardiogram on an individual basis. In all cases, treatment with any dopamine agonist should use the lowest dose and shortest duration possible.
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Returning to the Patients
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Case 1
Because she had a microadenoma and fertility was not an issue when the diagnosis was made, she could have been treated with an oral contraceptive instead of a dopamine agonist. The cabergoline can be discontinued without a taper. Her prolactin and clinical symptoms should be monitored every 3 months during the first year. If she is amenorrheic after withdrawal of the cabergoline, an oral contraceptive can be used to prevent bone loss and treat symptoms of hypogonadism. While taking estrogen, her prolactin level should be monitored yearly. Another MRI is not necessary unless she develops clinical signs of tumor expansion or a marked (>250 µg/liter) increase in serum prolactin.
Case 2
This man is also a candidate for dopamine agonist withdrawal. The cabergoline should be tapered slowly, and his prolactin levels and clinical symptoms should be monitored every 3 months in the first year after drug withdrawal. If normoprolactinemia is not maintained, cabergoline should be reinstituted at the lowest dose capable of maintaining normoprolactinemia. He is not a candidate for transsphenoidal surgery because the procedure is not likely to provide a cure.
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Conclusions
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Dopamine agonists are the mainstay for therapy of prolactinomas. Some patients with micro- and macroadenomas may have normalization of prolactin, resolution of symptoms, and no tumor regrowth after drug withdrawal. Prospective analyses are necessary to define the optimal duration of therapy and predictors of remission and to elucidate whether the apparent remission represents an antitumor effect of the dopamine agonist or the natural history of prolactinomas.
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Footnotes
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Disclosure Statement: The author has nothing to disclose.
Abbreviation: MRI, Magnetic resonance imaging.
Received April 13, 2007.
Accepted May 23, 2007.
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References
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- Schlechte JA 2003 Prolactinoma. N Engl J Med 349:2035–2041[Free Full Text]
- Molitch ME, Elton RL, Blackwell RE, Caldwell B, Change RJ, Jaffe R, Joplin G, Robbins RJ, Tyson J, Thorner MO 1985 Bromocriptine as primary therapy for prolactin-secreting macroadenomas: results of a prospective multicenter study. J Clin Endocrinol Metab 60:698–705[Abstract/Free Full Text]
- Webster J, Piscitelli G, Polli A, Ferrari CI, Ismail I, Scanlon MR 1994 A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. N Engl J Med 331:904–909[Abstract/Free Full Text]
- Colao A, Di Sarno A, Sarnacchiaro S, Ferone D, DiRenzo G, Merola B, Annunziato L, Lombardi G 1997 Prolactinomas resistant to standard dopamine agonists respond to chronic cabergoline treatment. J Clin Endocrinol Metab 82:876–883[Abstract/Free Full Text]
- Gillam MP, Molitch ME, Lombardi G, Colao A 2006 Advances in the treatment of prolactinomas. Endocr Rev 27:485–534[Abstract/Free Full Text]
- Schlechte J, Dolan K, Sherman B, Chaplet F, Luciano A 1989 The natural history of untreated hyperprolactinemia: a prospective analysis. J Clin Endocrinol Metab 68:412–418[Abstract/Free Full Text]
- Weiss MH, Teal J, Gott P, Wycoff R, Yadley R, Apuzzo ML, Giannotta SL, Kletzky O, March C 1983 Natural history of microprolactinomas: six-year follow-up. Neurosurgery 12:180–183[Medline]
- Sano T, Kovacs KT, Scheithauer BW, Young Jr WF 1993 Aging and the human pituitary gland. Mayo Clin Proc 68:971
- Delgrange E, Trouillas J, Maiter D, Donckier J, Tourniaire J 1997 Sex-related difference in the growth of prolactinomas: a clinical and proliferation marker study. J Clin Endocrinol Metab 82:2102–2107[Abstract/Free Full Text]
- Molitch ME 1985 Pregnancy and the hyperprolactinemic woman. N Engl J Med 312:1365–1370
- Holmgren U, Hagenfeldt K, Werner S 1986 Women with prolactinomas: effect of pregnancy and lactation on serum prolactin and on tumour growth. Acta Endocrinol (Copenh) 111:452–459[Abstract/Free Full Text]
- Krupp P, Monka C1987 Bromocriptine in pregnancy: safety aspects. Klin Wochenschr 65:823–827
- Robert E, Musatti L, Piscitelli G, Ferrari CI 1996 Pregnancy outcome after treatment with the ergot derivative, cabergoline. Reprod Toxicol 10:333–337[CrossRef][Medline]
- Corenblum B, Donovan L 1993 The safety of physiological estrogen plus progestin replacement therapy with oral contraceptive therapy in women with pathological hyperprolactinemia. Fertil Steril 59:671–673[Medline]
- Scheithauer BW, Kovacs KT, Randall RV, Ryan N 1992 Effects of estrogen on the human pituitary: a clinicopathologic study. Mayo Clin Proc 64:1077–1084
- Pituitary Adenoma Study Group 1983 Pituitary adenomas and oral contraceptives: a multicenter case-control study. Fertil Steril 39:753–760[Medline]
- Fathy UM, Foster PA, Torode HW, Hartog M, Hull MG 1992 The effect of combined estrogen/progesterone treatment in women with hyperprolactinemic amenorrhea. Gynecol Endocrinol 6:183–188[Medline]
- Testra G, Vegetti W, Motta T, Alagna F, Bianchedi D, Carlucci C, Bianchi M, Parazzini F, Crosignani PG 1998 Two year treatment with oral contraceptives in hyperprolactinemic patients. Contraception 58:69–73[CrossRef][Medline]
- Jeffcoate WJ, Pound N, Sturrock ND, Lambourne J 1996 Long-term follow-up of patients with hyperprolactinaemia. Clin Endocrinol (Oxf) 45:299–303[CrossRef][Medline]
- Crosignani PG, Mattei AM, Scarduelli C, Cavioni V, Boracchi P 1989 Is pregnancy the best treatment for hyperprolactinaemia? Hum Reprod 4:910–912[Abstract/Free Full Text]
- Freeman R, Wezenter B, Silverstein M, Kuo D, Weiss KL, Kantrowitz AB, Schubart UK 1992 Pregnancy-associated subacute hemorrhage into a prolactinoma resulting in diabetes insipidus. Fertil Steril 58:427–429[Medline]
- Karunakaran S, Page RC, Wass JA 2001 The effect of menopause on prolactin levels in patients with hyperprolactinaemia. Clin Endocrinol (Oxf) 54:295–300[CrossRef][Medline]
- Landolt AM, Osterwalder V 1984 Perivascular fibrosis in prolactinomas: is it increased by bromocriptine? J Clin Endocrinol Metab 58:1179–1183[Abstract/Free Full Text]
- Johnston DG, Kendall-Taylor P, Watson M, Hall K, Patrick D, Cook DB 1984 Effect of dopamine agonist withdrawal after long-term therapy in prolactinomas. Lancet 2:187–192[Medline]
- Zarate A, Canales ES, Cano C, Pilonieta CJ 1983 Follow-up of patients with prolactinomas after discontinuation of long-term therapy with bromocriptine. Acta Endocrinol (Copenh) 104:139–142[Abstract/Free Full Text]
- Moriondo P, Travaglini P, Nissim M, Conti A, Faglia G 1985 Bromocriptine treatment of microprolactinomas: evidence of stable prolactin decrease after drug withdrawal. J Clin Endocrinol Metab 60:764–772[Abstract/Free Full Text]
- Wang C, Lam KS, MA JT, Chan T, Liu MY, Yeung RT 1987 Long-term treatment of hyperprolactinaemia with bromocriptine: effect of drug withdrawal. Clin Endocrinol (Oxf) 27:363–371[Medline]
- Rasmussen C, Bergh T, Wide L 1987 Prolactin secretion and menstrual function after long-term bromocriptine treatment. Fertil Steril 48:550–554[Medline]
- Van’t Verlaat JW, Croughs RJ 1991 Withdrawal of bromocriptine after long-term therapy for macroadenomas; effect on plasma prolactin and tumour size. Clin Endocrinol (Oxf) 34:175–178[Medline]
- Ferrari C, Paracchi A, Mattei A, de Vincentiis S, D’Alberton A, Crosignani P 1992 Cabergoline in long-term therapy of hyperprolactinemic disorders. Acta Endocrinol (Copenh) 126:489–494[Abstract/Free Full Text]
- Muratori M, Arosio M, Gambina G, Biella O, Faglia G 1997 Use of cabergoline in the long-term treatment of hyperprolactinaemic and acromegalic patients. J Endocrinol Invest 20:537–546[Medline]
- Cannavo S, Curto L, Squadrito S, Almoto B, Vieni A, Trimarchi F 1999 Cabergoline: a first-choice treatment in patients with previously untreated prolactin-secreting pituitary adenomas. J Endocrinol Invest 22:354–359[Medline]
- Passos VQ, Souza JJ, Musolino NR, Bronstein MD 2002 Long-term follow-up of prolactinomas: normoprolactinemia after bromocriptine withdrawal. J Clin Endocrinol Metab 87:3578–3582[Abstract/Free Full Text]
- Colao A, Di Sarno A, Cappabianca P, De Somma C, Pivonello R, Lombardi G 2003 Withdrawal of long-term carbergoline therapy for tumoral and nontumoral hyperprolactinemia. N Engl J Med 349:2023–2033[Abstract/Free Full Text]
- Biswas M, Smith J, Jadon D, McEwan P, Rees DA, Evans LM, Scanlon MF, Davies JS 2005 Long-term remission following withdrawal of dopamine agonist therapy in subjects with microprolactinomas. Clin Endocrinol (Oxf) 63:26–31[CrossRef][Medline]
- Guitelman M 2006 Long-term follow-up of prolactimomas: should dopamine agonist treatment be life-long? Front Horm Res 35:88–101[Medline]
- Liuzzi A, Dallabonzana D, Oppizzi G, Verde GG, Cozzi R, Chiodini P, Luccarelli G 1985 Low doses of dopamine agonists in the long-term treatment of macroprolactinomas. N Engl J Med 313:656–659[Abstract]
- Jane Jr JA, Laws Jr ER 2001 The surgical management of pituitary adenomas in a series of 2093 patients. J Am Coll Surg 193:651–659[Medline]
- Nomikos P, Buchfelder M, Fahlbusch R 2001 Current management of prolactinomas. J Neurooncol 54:139–150[CrossRef][Medline]
- Couldwell WT, Rovit RL, Weiss MH 2003 Role of surgery in the treatment of microprolactinomas. Neurosurg Clin North Am 14:89–92, vii[CrossRef][Medline]
- Thompson JA, Davies DL, McLaren EH, Teasdale GM 1994 Ten year follow-up of microprolactinoma treated by transsphenoidal surgery. BMJ 309:409–410[Medline]
- Tintner R, Manian P, Gauthier P, Jankovic J 2005 Pleuropulmonary fibrosis after long-term pergolide for Parkinson disease. Arch Neurol 62:1290–1295[Abstract/Free Full Text]
- McElvaney NG, Wilcox PG, Churg A, Fleetham JA 1988 Pleuropulmonary disease during bromocriptine treatment of Parkinson’s disease. Arch Intern Med 148:2231–2236[Abstract/Free Full Text]
- Zanettini R, Antonini A, Gatto G, Gentile R, Tesei S, Pezzoli G 2007 Valvular heart disease and the use of dopamine agonists for Parkinson’s disease. N Engl J Med 356:39–46[Abstract/Free Full Text]
- Schade R, Andersohn F, Suissa S, Haverkamp W, Garbe E 2007 Dopamine agonists and the risk of cardiac valve regurgitation. N Engl J Med 356:29–38[Abstract/Free Full Text]
- Gillam MP, Middler S, Freed DJ, Molitch ME 2002 The novel use of very high doses of cabergoline and a combination of testosterone and an aromatase inhibitor in the treatment of giant prolactinoma. J Clin Endocrinol Metab 87:4447–4451[Abstract/Free Full Text]
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Abstract
Case 1
