Prolactinomas: diagnosis and treatment

233

CME Review

www.expert-reviews.com ISSN 1744-6651© 2012 Expert Reviews Ltd10.1586/EEM.12.4

Farshad Nassiri1, Michael D Cusimano1, Bernd W Scheithauer2, Fabio Rotondo*3, Alessandra Fazio1, Luis V Syro4, Kalman Kovacs3 and Ricardo V Lloyd5

1Department of Surgery, Division of Neurosurgery, St Michael’s Hospital, University of Toronto, ON, Canada 2Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, MN, USA 3Department of Laboratory Medicine, Division of Pathology, 30 Bond Street, St Michael’s Hospital, Toronto, ON, M5B 1W8, Canada 4Department of Neurosurgery, Clinica Medellin & Hospital Pablo Tobon Uribe, Medellin, Colombia 5Department of Pathology & Laboratory Medicine, University of Wisconsin Hospital & Clinics, Madison, WI, USA *Author for correspondence: Tel.: +1 416 864 5851 Fax: +1 416 864 5648 [email protected]

Pituitary lactotrophs secrete prolactin. This process is enhanced by estrogen and inhibited by dopamine. Prolactinomas are benign neoplasms that rarely increase in size and are classified according to size as microadenomas (<10 mm diameter) or macroadenomas (>10 mm diameter). The clinical features of prolactinomas most commonly result from prolactin’s effect on the gonads and breast in women and from mass effect in men. This review details the clinical features and management of patients with prolactinomas.

Keywords: bromocriptine • cabergoline • hyperprolactinemia • pituitary • prolactinoma • treatment • tumor

Prolactinomas: diagnosis and treatmentExpert Rev. Endocrinol. Metab. 7(2), 233–241 (2012)

Learning objectivesUpon completion of this activity, participants should be able to:• Analyze clinical features of prolactinomas• Develop diagnostic processes to detect secondary hyperprolactinemia• Evaluate the clinical management of prolactinomas• Assess medical treatment options for prolactinomas

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Prolactinomas are benign neoplasms accounting for 40% of all pituitary tumors. Most prolactinomas are intrasellar and rarely increase in size [1]. In some cases, prolactinomas invade surround-ing structures (invasive extensions) and exceptionally they may metastasize to systemic organs. Prolactinomas consist of lacto-trophs that secrete excess prolactin (PRL) to varying degrees, resulting in hyperprolactinemia. Lactotroph secretion of PRL is enhanced by estrogen and inhibited by dopamine (DA). DA is synthesized by hypothalamic neurons and transported to the pituitary via portal vessels.

Prolactinomas can be classified as microadenomas (<10 mm diameter) or macroadenomas (>10 mm diameter). PRLs physio-logic role is to stimulate lactation but it also has secondary effects on gonadal function. The clinical features of hyperprolactinemia result from secondary effects of PRL on the gonads and differ in both men and women.

Clinical featuresNormal PRL levels in men and women are 20 and 25 µg/l, respec-tively. Excess PRL may lead to infertility and gonadal dysfunc-tion. The gonadal dysfunction is mediated by an interruption in the secretion of gonadotropin-releasing hormone, luteinizing hormone and follicle-stimulating hormone as well as the inter-ruption of gonadal steroidogenesis [2,3]. If the prolactinoma is large, compression of other pituitary cells may cause hypopitu-itarism. Neurologic symptoms – most often headaches and visual complaints – are also noticed with large tumors as they are able to compress the optic chiasm and invade structures of the skull base such as the cavernous sinus. There is a close correlation with tumor size and serum PRL levels [4] and as such, macroadenomas generally result in serum PRL levels greater than 250 µg/l [5].

Both males and females may develop reduced spinal bone min-eral density with chronic hyperprolactinemia due to the inhibitory effects of PRL on sex steroids. This reduction can be reversed after PRL normalization, though not always returned to normal values [6].

Men more commonly present with larger prolactinomas and neurologic symptoms. It is uncertain whether this discrepancy

in tumor size is due to either a diagnostic delay or biological difference in tumor aggressiveness; though the latter seems more likely [7]. Hyperprolactinemia in men often manifests as infertility, impotence and decreased libido [8].

Prolactinomas in women most often present as microadeno-mas. In premenopausal women, the most common symptoms of hyperprolactinemia are infertility and amenorrhea. Galactorrhea occurs in approximately 80% of women with prolactinomas. Postmenopausal women, like men, often do not present with these typical symptoms but rather of symptoms of mass effect and larger tumors.

Clinical approachThe diagnosis of a prolactinoma requires endocrinological find-ings of hyperprolactinemia and radiographic evidence of a pitu-itary adenoma. Recent Endocrine Society clinical practice guide-lines recommend using a single measurement of serum PRL to establish hyperprolactinemia as long as the sample was obtained without excessive venipunture stress [9]. Causes of hyperprolac-tinemia other than a prolactinoma must also be ruled out. Other large sellar or parasellar masses, brain trauma and hypothalamic damage may result in hyperprolactinemia either by impairment of hypothalamic DA production or transport. Hypophysitis may also cause hyperprolactinemia. Generally, such causes will rarely result in serum PRL levels greater than 150 µg/l [5].

Many drugs are able to cause hyperprolactinemia by antagoniz-ing DA receptors or impairing DA delivery to the portal vessels. An exhaustive list of medications that may cause hyperprola-tinemia is not within the scope of this review and can be found elsewhere [10]. Some of these pharmacological agents include metoclopramide, risperidone, domperidone and verapamil. In general, medication-induced hyperprolactinemia rarely results in serum PRL levels greater than 100 µg/l [5].

Patients with primary hypothyroidism may develop mild hyperprolactinemia [11]. It is thought that this is brought about by increased synthesis or sensitivity to hypothalamic thyrotropin-releasing hormone that can stimulate pituitary lactotroph cells, although the actual mechanism is still unknown [12,13]. Chronic

Financial & competing interests disclosure (cont.)Authors

Farshad Nassiri, HBSc, Department of Surgery, Division of Neurosurgery, St Michael’s Hospital, University of Toronto, ON, CanadaDisclosure: Farshad Nassiri, HBSc, has disclosed no relevant financial relationships.Michael D. Cusimano, MD, PhD, Department of Surgery, Division of Neurosurgery, St Michael’s Hospital, University of Toronto, ON, CanadaDisclosure: Michael D. Cusimano MD, PhD, has disclosed no relevant financial relationships.Bernd W. Scheithauer, MD, PhD, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USADisclosure: Bernd W. Scheithauer, MD, PhD, has disclosed no relevant financial relationships.Fabio Rotondo, BRT, BSc, Department of Laboratory Medicine, Division of Pathology, St Michael’s Hospital, Toronto, ON, CanadaDisclosure: Fabio Rotondo BRT, BSc, has disclosed no relevant financial relationships.Alessandra Fazio, HBSc, Department of Surgery, Division of Neurosurgery, St Michael’s Hospital, University of Toronto, ON, CanadaDisclosure: Alessandra Fazio, HBSc, has disclosed no relevant financial relationships.Luis V. Syro MD, Department of Neurosurgery, Clinica Medellin and Hospital Pablo Tobon Uribe, Medellin, ColombiaDisclosure: Luis V. Syro MD, has disclosed no relevant financial relationships.Kalman Kovacs, MD, PhD, Department of Laboratory Medicine, Division of Pathology, St Michael’s Hospital, Toronto, ON, CanadaDisclosure: Kalman Kovacs, MD, PhD, has disclosed no relevant financial relationships.Ricardo V. Lloyd, MD, PhD, Department of Pathology and Laboratory Medicine, University of Wisconsin Hospital and Clinics, Madison, WI, USADisclosure: Ricardo V. Lloyd MD, PhD, has disclosed no relevant financial relationships.

Nassiri, Cusimano, Scheithauer et al.

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renal failure and liver disease may result in mild hyperprolac-tinemia due to decreased clearance [14,15]. During pregnancy, estrogen from the placenta stimulates PRL synthesis and raises PRL levels approximately tenfold compared with normal values [16,17]. When all causes of hyper prolactinemia have been ruled out, the diagnosis of idiopathic hyperprolactinemia can be considered. However, some of these patients may have microprolactinomas that are too small to be recognized radiographically which may appear at a later follow-up [18].

Therefore, secondary causes of hyperprolactinemia can be ruled out with a careful history, physical examination, routine biochemistry for liver and renal function, pregnancy test and TSH levels. If a patient is known to be taking a drug that can induce hyperprolactinemia, then withdrawal for 72 h or alternative drugs should be sought if safe and feasible [9,10,19]. Discontinuation of an antipsychotic medication should always be carried out after consulting the patient’s physician.

One should also be aware of the ‘hook effect’ and macropro-lactin when analyzing serum PRL levels. The hook effect occurs when serum PRL is exceptionally high, such as in the case of a giant prolactinoma. The high PRL results in antibody satu-ration during immunoradiometric assay leading to apparently low PRL results. Serial dilutions help in eliminating this artifact in measurement and should be requested routinely in patients with large pituitary masses [20]. Macroprolactin is a complex of PRL with an IgG antibody that leads to decreased clearance and pseudo-hyperprolactinemia. Size exclusion chromatography, or more often polyethylene glycol precipitation, can confirm macroprolactinemia [21].

After excluding secondary causes of hyperprolactinemia and PRL measurement artifacts, a gadolinium-enhanced MRI of the sella should be performed. It is important to note that a normal MRI does not rule out a microadenoma [22], and that a positive MRI with hyperprolactinemia is not definitively diagnostic of a prolactinoma, as any sellar mass compressing the pituitary stalk may result in hyperprolactinemia. Confirmation of a prolacti-noma can be obtained with pathology or by treating the patient with medication and obtaining serial PRL and imaging assess-ments. If both serum PRL normalize and the tumor shrinks substantially, then the diagnosis of a prolactinoma is confirmed. Should serum PRL normalize but the tumor size remain stable, this confirms the diagnosis of a pituitary adenoma other than pro-lactinoma. Should serum PRL and tumor size remain unchanged after medication, then the diagnosis of a resistant prolactinoma is indicated [23].

ManagementAll patients with macroadenoma and many patients with micro-prolactinoma require treatment. In all patients the goal of treat-ment is to restore gonadal function but with macroprolactino-mas reducing tumor size and inhibiting tumor growth are also important. Premenopausal women with normal menstruation and postmenopausal women without bothersome galactorrhea or mass effects do not need to be actively treated, but should have serum PRL and imaging monitored to watch for tumor growth.

Medical therapyDA agonists such as bromocriptine or cabergoline are the first-line treatment approach in prolactinomas as they have been shown to effectively normalize PRL levels and reduce tumor volume irre-spective of tumor size [24–26]. DA agonists work by binding the G-protein coupled lactotroph D

2 receptors resulting in involution

of the endoplasmic reticulum and Golgi apparatus, and therefore, tumor shrinkage [27,28]. DA may also induce apoptosis in early phases of treatment [29]. DA binding to lactotroph D

2 receptors

also inhibits PRL release. Bromocriptine therapy is started at a dose of 0.625 mg daily

for the first week, and is then increased by 1.25 mg weekly until PRL levels normalize. Doses that exceed 7.5 mg daily are rarely required [30]. Cabergoline treatment is started at 0.5 mg weekly and the dosage is increased monthly until PRL levels normalize [26]. Pergolide mesylate, a previously US FDA-approved treat-ment for Parkinson’s disease and quinagolide, a selective D

2 recep-

tor agonist that is an approved treatment for prolactinomas in Europe, are also possible DA agonists but their use is limited and they will not be thoroughly discussed in this review.

Several studies have shown that cabergoline is a well-tolerated agent and comparisons with bromocriptine show that cabergo-line is superior in normalizing PRL levels and reducing tumor volume [26,31–34]. The use of cabergoline during pregnancy has been shown to be safe, but the number of pregnancies studied is limited [35]. If value is placed on the reversal of hypogonadism, then cabergoline is considered the gold standard DA agonist [9]. However, if value is based on cost and effects during pregnancy, then bromocriptine therapy should be considered given that it is off patent and less expensive and it is safe to use during pregnancy [9,36–38]. Despite the effectiveness of these drugs, some patients are intolerant at therapeutic doses and some do not respond at therapeutic levels or higher. Such patients are considered to be DA resistant [39]. The mechanism of resistance seems to be mediated by a decreased number of D

2 receptors without a decreased affin-

ity for DA agonists, and an altered signal transduction mecha-nism [40,41]. It is possible that resistance is due to decreased drug absorbance, but this seems unlikely [42,43]. There have also been reports of the development of DA resistance after gonadotrophin replacement [44–46].

In resistant patients, treatment options include switching DA agonists, increasing DA agonist dosage beyond convention and surgery and/or radiotherapy.

Until recently, bromocriptine was considered the gold-standard treatment for prolactinomas. Up to 85% of patients resistant to bromocriptine and quinagolide could obtain normal PRL levels after switching to cabergoline [47]. Therefore, it is recommended that patients who were started on bromocriptine and who are resistant switch to cabergoline prior to attempting surgical inter-vention. Although doses of 2 mg/week exceed recommended package levels for cabergoline, some patients may require up to 3 mg/day for normalization of PRL levels [48]. Levels of caber-goline may be continuously raised, irrespective of tumor size, as long as there is caution used to avoid adverse reactions and that the increased doses continue to provide therapeutic benefit [49].

Prolactinomas: diagnosis & treatment


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There are some reports indicating that cabergoline use may result in cardiac valve damage, but it seems that this is only the case in extremely high doses of cabergoline that is not necessary in the treatment of prolactinomas [50]. It has been suggested that reports of cabergoline-induced cardiac valve disease may be a result of echocardiographer operator bias [51].

Surgical & radiation therapyWhen medical therapy proves ineffective and when the tumor is operable, trans-sphenoidal surgery is a good option [52]. A review of 50 surgical series showed that 75% of microadenomas and 34% of macroadenomas achieved normal PRL levels after surgery; recurrence rate for both micro- and macro-adenomas after 1 year was 20% [4]. Microprolactinomas and macrop-rolactinomas confined to the sella, have a higher chance of remission after surgery [53]. Unfortunately, the invasiveness and complexity of giant prolactinomas makes a surgical approach an unlikely candidate for a cure, although endoscopic approaches may improve the outlook for these difficult lesions [30,54–56]. With macroprolactinomas, the aim of the surgery is often to reduce neurologic symptoms associated with optic and cerebral compression [55]. In rare instances of pituitary apoplexy during drug therapy, immediate surgical intervention may be required. Although surgery is reserved for intolerant or resistant prolac-tinomas, it may be used as a reasonable primary therapeutic strategy with an experienced neurosurgeon if the patient wishes to do so [53].

Radiation therapy is often reserved as a final therapeutic option for tumor shrinkage. Conventional fractionated radiotherapy results in reduced PRL levels in approximately 25% of patients. It can be associated with hypopituitarism, rarely stroke and develop-ment of a second tumor [57]. In medically and surgically refractory patients, Gamma knife radiosurgery resulted in PRL normaliza-tion in 26% of patients at 24.5 months follow-up [58]. Gamma knife radiosurgery is limited to well-defined tumors smaller than 3 cm that are a minimum of 3 mm away from the optic apparatus. In patients with recurrent, invasive prolactinoma and prolactinoma carcinomas with low O-6-methylguanine-DNA methyltransferase (MGMT) staining, temozolomide therapy can be used as a successful therapeutic agent [59–62]. Temozolomide therapy has even reduced tumor volume and normalized PRL levels in a resistant macroprolactinoma suggesting a possible role for temozolomide in resistant prolactinomas [61]. The number of cycles of treatment necessary to determine efficacy has not yet been determined, although three cycles has been suggested as sufficient [62].

Treatment & fertilityIn women who desire fertility, bromocriptine is the primary therapeutic agent. It is important to note that fertility can be restored immediately with DA agonists, and so the use of mechanical contraception is advised. In microprolactinomas, the risk of tumor expansion during pregnancy is low and there-fore DA agonist therapy can be stopped as soon as pregnancy is confirmed to limit the exposure to the fetus [63]. Given the

30% chance of tumor expansion in macroprolactinomas dur-ing pregnancy, it is advised that conception be planned after PRL levels have normalized and tumor volumes have reduced significantly in females [64]. Women with macroprolactinomas have the option of stopping DA therapy when pregnancy is confirmed, or continuing with DA therapy during pregnancy. In pregnant patients who stop therapy and develop symptoms of mass effect, an MRI without gadolinium should be ordered and DA therapy should be re-instituted if there is significant tumor growth. Surgery during pregnancy is potentially dan-gerous for mothers and fetuses and should remain a last resort [65]. Last, it is important for women wishing to breastfeed to stop DA therapy so that milk production is not impaired and to prevent excess DA in the breast milk.

In patients who do not desire fertility, cabergoline is advised as the first pharmacological agent given its superiority to bromocrip-tine. In women with microprolactinomas who do not desire fertil-ity, hypogondal features can be treated with estrogen replacement in the form of oral contraceptives. Although estrogen enhances PRL release, estrogen therapy given to patients with microprolac-tinomas does not cause tumor growth [66,67]. Given the growth potential of macroprolactinomas, estrogen replacement therapy is not recommended even when fertility is not desired.

DA agonist withdrawalInitial studies on DA agonist withdrawal showed a quick recur-rence of hyperprolactinemia [68,69]. However, necrotic changes and fibrosis have been observed in prolactinomas treated with bromocriptine, suggesting the possibility of DA agonist with-drawal [70]. Recent studies provide evidence for the possibility of DA agonist withdrawal and remission of hyperprolactinemia. Two to five years after cabergoline withdrawal, 67% of patients with prolactinomas remained in remission [71]. In patients treated with either bromocriptine or cabergoline, 36% remained in remission after agonist withdrawal at 1 year follow-up [72]. The indications for withdrawal vary according to size. Given the little growth potential for microprolactinomas, DA therapy may be withdrawn after normalization of PRL and tapering is not necessary [72,73]. Patients with macroadenomas who have achieved normal PRL levels and have no evidence of a tumor on MRI may withdraw DA therapy after tapering. All patients should have PRL levels closely monitored for a minimum of 1 year after withdrawal given that remission rates are highest 1 year after withdrawal [71,72].

Expert commentary & five-year viewMonumental progress has been made from the laboratory to the clinic regarding PRL-producing pituitary tumors during the last few decades. Previously, morphologic methods did not exist to diagnose pituitary tumors correctly. Prognostic indica-tors and medical therapy were also not available. Patients with PRL-producing pituitary tumors were treated only by surgery or irradiation. Currently, based on immunohistochemistry and elec-tron microscopy we can properly diagnose and classify pituitary tumors. Medical treatment using DA agonists is very effective



ReviewCME

Key issues

• Lactotroph secretion of prolactin is enhanced by estrogen and inhibited by dopamine. Dopamine is synthesized by hypothalamic neurons and transported to the pituitary via portal vessels.

• Prolactinomas are tumors that secrete prolactin. Prolactinomas can be classified as microadenomas (<10 mm diameter) or macroadenomas (>10 mm diameter).

• Diagnosis of a prolactinoma is often achieved with a single elevated serum prolactin level and gadolinium-enhanced MRI of the sellar.

• Dopamine agonists should be used as initial treatment for prolactinomas. Cabergoline has shown to be superior to bromocriptine in terms of tumor shrinkage and normalizing prolactin levels. Unless fertility is desired, cabergoline should be used as the initial dopamine agonist.

• In resistant prolactinomas, surgical therapy is considered a good alternative. Radiation therapy is reserved as a final option. Gamma knife radiosurgery can be offered to select patients. Temozolomide therapy has been used in few patients with prolactin carcinomas with good success. A few studies have suggested a possible role for temozolomide in resistant prolactinomas.

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in many cases. In these patients, surgery and/or irradiation are not necessary. Biomarkers can predict prognosis with acceptable accuracy. The discovery of temozolomide made it possible to use this drug in the treatment of aggressive, atypical pituitary adenomas and pituitary carcinomas. Unfortunately, not every patient is responsive to this drug. Therapies targeting local and endocrine symptoms are of great importance given their effects on patient quality of life. Well-designed clinical trials with clearly defined efficacy criteria will be critical in accelerating the use of such agents.

There are still several major problems. Treatment of aggressive, atypical adenomas and carcinomas is still a major challenge. The introduction of molecular/genetic methods will open new avenues. The goal is not only to predict prognosis, to inhibit tumor growth and to completely destroy the tumor cells, but to prevent develop-ment of the tumor. Further investigation should offer the possibil-ity of generating novel targets that could overcome issues of drug resistance, improve therapeutic efficacy, make tumor treatment more successful and perhaps even curative while averting systemic toxicity. These aims require much more work in developing new drugs, discovering the biologic behavior of tumors and providing a better understanding of pituitary tumor pathogenesis.

ConclusionProlactinomas can be microadenomas or microadenomas and cause hyperprolactinemia. Diagnosis is established based on endocrinological evidence of elevated PRL and radiographic evidence of a pituitary tumor and exclusion of secondary causes of hyperprolactinemia. Initial therapy for prolactinomas is DA therapy. Bromocriptine is the preferred pharmacological agent if fertility is desired. Cabergoline has been shown to be superior to bromocriptine, and can be used in cases of bromocriptine-resistant prolactinomas or when fertility is not a treatment goal. Estrogen replacement therapy may also be used when fertility is not desired with women.

Surgery is reserved for patients who fail medical therapy. Patients on DA therapy may withdraw treatment after normal-ization of PRL levels, and negative MRIs in the case of macro-prolactinomas. Patients choosing to withdraw DA therapy should have PRL levels and imaging closely monitored for the possibility of recurrence.

AcknowledgementsWe are grateful to the Jarislowsky and Lloyd Carr-Harris Foundations for their generous support.



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45 Pasqualini C, Bojda F, Kerdelhue B. Direct effect of estradiol on the number of dopamine receptors in the anterior pituitary of ovariectomized rats. Endocrinology 119(6), 2484–2489 (1986).

46 Prior JC, Cox TA, Fairholm D, Kostashuk E, Nugent R. Testosterone-related exacerbation of a prolactin-producing macroadenoma: possible role for estrogen. J. Clin. Endocrinol. Metab. 64(2), 391–394 (1987).

47 Colao A, Di Sarno A, Sarnacchiaro F et al. Prolactinomas resistant to standard dopamine agonists respond to chronic cabergoline treatment. J. Clin. Endocrinol. Metab. 82(3), 876–883 (1997).

48 Gillam MP, Middler S, Freed DJ, Molitch ME. The novel use of very high doses of cabergoline and a combination of testosterone and an aromatase inhibitor in the treatment of a giant prolactinoma. J. Clin. Endocrinol. Metab. 87(10), 4447–4451 (2002).

49 Ono M, Miki N, Kawamata T et al. Prospective study of high-dose cabergoline treatment of prolactinomas in 150 patients. J. Clin. Endocrinol. Metab. 93(12), 4721–4727 (2008).

50 Kars M, Pereira AM, Bax JJ, Romijn JA. Cabergoline and cardiac valve disease in prolactinoma patients: additional studies



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54 Hofle G, Gasser R, Mohsenipour I, Finkenstedt G. Surgery combined with dopamine agonists versus dopamine agonists alone in long-term treatment of macroprolactinoma: a retrospective study. Exp. Clin. Endocrinol. Diabetes 106(3), 211–216 (1998).

55 Shrivastava RK, Arginteanu MS, King WA, Post KD. Giant prolactinomas: clinical management and long-term follow up. J. Neurosurg. 97(2), 299–306 (2002).

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Prolactinomas: diagnosis and treatment

Activity EvaluationWhere 1 is strongly disagree and 5 is strongly agree

1 2 3 4 5

1. The activity supported the learning objectives.

2. The material was organized clearly for learning to occur.

3. The content learned from this activity will impact my practice.

4. The activity was presented objectively and free of commercial bias.

1. Your patient is a 37-year-old woman whose last menses was 6 months ago. A urine pregnancy test is negative.You consider whether this patient might have a prolactinoma. Which of the following is characteristic of clinical features of prolactinoma?

£ A There is no correlation between tumor size and serum prolactin levels

£ B There is no gender difference in terms of clinical presentation with large prolactinomas

£ C In premenopausal women, the most common symptoms of prolactinoma are infertility and amenorrhea

£ D The general course of prolactinomas is increasingly larger growth

3. The patient’s head MRI demonstrates a 9-mm pituitary microadenoma. What should you consider as a management option for this patient’s tumor?

£ A If menses return to normal and no other symptoms are present, treatment may be unnecessary

£ B Tissue samples are necessary prior to initiating medical therapy

£ C Radiation therapy is now considered first-line therapy for prolactinomas

£ D Cabergoline is preferred if the patient wants to become pregnant

2. The patient’s serum prolactin level is elevated at 90 µg/l. Which of the following interventions would be most appropriate in the search for a secondary cause of hyperprolactinemia?

£ A Measuring a serum 21-hydroxylase level

£ B Measuring a serum growth hormone level

£ C Withdrawal of medications that might promote hyperprolactinemia for 72 hours

£ D Measuring a serum adrenocorticotropic hormone level



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4. Which of the following statements regarding the medical management of prolactinomas is most accurate?

£ A Dopamine agonists can reduce serum prolactin levels but not tumor size

£ B Bromocriptine is similar to cabergoline in normalizing prolactin levels

£ C No dose titration is necessary in using dopamine agonists

£ D Patients who do not respond to bromocriptine should receive cabergoline


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Prolactinomas: diagnosis and treatment