Prolactinoma

Updated: Nov 15, 2017
  • Author: Venkatesh Babu Segu, MD, MBBS, DM; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Overview

Practice Essentials

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

Workup

Laboratory studies include the following:

  • Serum prolactin (PRL)
  • Serum pregnancy test
  • Serum thyroid-stimulating hormone (TSH)
  • Serum testosterone or bioavailable testosterone: In males presenting with symptoms of hypogonadism
  • Basal and cosyntropin-stimulated cortisol: In patients with a history suggestive of adrenal insufficiency
  • Serum insulinlike growth factor-1: In persons with features consistent with acromegaly

After performing biochemical testing, order a magnetic resonance imaging (MRI) scan of the pituitary hypothalamic area (with gadolinium enhancement) or a computed tomography (CT) scan of the region (with contrast) to determine if a mass lesion is present.

Management

Treatment is indicated if mass effects from the tumor and/or significant effects from hyperprolactinemia are present. [1]  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 dopamine (DA) agonist, it decreases the synthesis and secretion of PRL. [2] It also decreases the rate of tumor cell division and the growth of individual cells.

Other medical treatments for prolactinomas are available for patients who do not respond to BEC or for those who cannot tolerate the drug. A long-acting, nonergot DA agonist, cabergoline is available in the United States.

In those patients with DA agonist–resistant prolactinomas (DARPs) having persistent hyperprolactinemia despite surgical debulking, with or without radiotherapy, temozolomide, a chemotherapeutic alkylating agent, has been recommended. [3]

Transsphenoidal pituitary adenomectomy is the preferred surgical treatment in patients with microprolactinoma and in most patients with macroprolactinoma. [4] 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 and in persons with residual tumors seen on follow-up imaging studies.

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Pathophysiology

Tumor formation is due to neoplastic transformation of anterior pituitary lactotrophs, resulting in excess synthesis and secretion of prolactin (PRL). Linkage to aryl hydrocarbon-interacting protein gene (AIP) mutation has been identified in some families with prolactinoma and in childhood-onset pituitary adenomas. [5]

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 physiologic 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). [1, 6, 7, 8, 9]

A retrospective study by Peng et al of 102 patients found that growth hormone deficiency and hypogonadism were the most frequent types of pituitary hormone dysfunction in adult males with prolactinomas, with hypocortisolism occurring less often. [10] This observation should come as no surprise, since prolactinomas in men are often larger (macroprolactinomas) and are thus likely to cause tissue compression, in contrast to prolactinomas in women, which are often small (microprolactinomas) at the time of initial diagnosis.

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Epidemiology

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 cosecrete PRL. Microprolactinomas are much more common than macroprolactinomas.

International

In a study of 81,449 inhabitants of Banbury, Oxfordshire, in the United Kingdom, Fernandez et al determined the incidence of pituitary adenomas there to be 77.6 cases per 100,000 population, with the majority of cases (57%, or 44.4 persons per 100,000 population) being prolactinomas. [11] It was also determined that prolactinomas accounted for most pituitary adenomas in persons up to age 60 years, the incidence being 75% of pituitary adenomas occurring in persons up to age 20 years, and 61% of pituitary adenomas in persons between the ages of 20 and 60 years. Moreover, prolactinomas accounted for 76% of pituitary adenomas in females, although in males, the majority of pituitary adenomas (57%) were nonfunctioning lesions.

The incidences of nonprolactinoma pituitary adenomas were as follows: nonfunctioning pituitary adenomas, 28%; adenomas associated with acromegaly, 11%; corticotroph adenomas, 2%; and adenomas of unknown functional status, 2%.

Sex

Among patients with prolactinomas, as many as 60% of the males present with macroprolactinomas, while 90% of the females present with microprolactinomas. This may partially be due to the fact that the male patients often present much later (for clinical evaluation of hypogonadism) than do the female patients (for clinical evaluation of amenorrhea). [12]

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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 growth rate varies with the individual and cannot be reliably predicted. Careful monitoring of clinical signs and symptoms, coupled with pituitary imaging and with serial measurements of serum PRL levels (ie, to detect any major change in tumor behavior), remain the cornerstones of follow-up for these patients. [13] .

A study by Sala et al indicated that in patients with prolactinomas undergoing cabergoline treatment, the prolactinoma recurrence rate does not decline even if therapy is continued for over 3 years prior to withdrawal. In the study, 74 patients with a prolactinoma were separated into three groups, including those treated with cabergoline for 3 years, those treated for 3-5 years, and those treated for more than 5 years. The prolactinoma recurrence rate within 12 months of treatment withdrawal did not significantly differ between the groups. Moreover, microadenomas and macroadenomas showed a similar recurrence risk, although patients with pituitary deficits at diagnosis had a higher rate of recurrence. [14]  Most endocrinologists would recommend a drug holiday at 2 years of therapy to determine whether, after 3 months of observation, drug treatment needs to be continued. Patients requiring drug treatment at three years would obviously include a significant number of those who failed the drug holiday at 2 years. One would, therefore, not expect any difference in the recurrence rate at 3 years or after, as borne out in this study.

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Patient Education

The symptoms of prolactinoma should be explained to the patient, and patients should be advised to report any new or worsening symptom.

Female patients of reproductive age 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 eMedicineHealth's Women's Health Center and Pregnancy Center. Also, see eMedicineHealth's patient education articles AmenorrheaBirth Control Overview, and Birth Control Methods.

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