Galactorrhea in an Adolescent Girl

Patricia Ryan-Krause, MS, MSN, RN, CPNP

Disclosures

J Pediatr Health Care. 2009;23(1):54-58. 

In This Article

Case Study Answers

Some of the more common differential diagnoses of galactorrhea include pregnancy or a terminated pregnancy; central nervous system (CNS) disorder such as pseudotumor cerebri, tumors, or neurocutaneous disorders; certain medications such as oral contraceptives, opiates, tetrahydrocannabinol, atypical antipsychotics, or amphetamines, among numerous others; nipple stimulation; and chest wall irritation from infectious or mechanical causes (Greydanus, Matytsina, & Gains, 2006). Some common differentials of primary amenorrhea include pregnancy, constitutional delay, genetic disorders, CNS tumors, and chronic illnesses such as Crohn's disease, sickle cell anemia, and cystic fibrosis (Bielak & Harris, 2008).

The initial diagnostic evaluation of DK in the office included a pregnancy test that was negative and a urinalysis that was unremarkable. At a community laboratory a complete blood cell count was obtained, as well as levels of thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, estradiol, and prolactin. All of these values were within normal range except that DK's prolactin level was markedly elevated at 276.9 ng/mL (normal values for a Tanner IV-V female: 3.2-20.0 ng/mL). This finding of hyperprolactinemia, in conjunction with DK's history of headaches and absence of menarche, suggested a pituitary prolactinoma, a type of adenoma or benign growth. In consultation with a pediatric endocrinologist, additional blood work was ordered, including a complete metabolic panel, AM cortisol level, and growth hormone levels. These values were obtained to evaluate general health status as well as to assess adrenal, pituitary, and gonadal function to determine possible effects of the likely adenoma on these other endocrine functions. This additional blood work also explored the possibility of other types of hormone-secreting tumors. Results indicated that DK's growth hormone production was slightly suppressed, but the extraordinarily high levels of prolactin continued to point to prolactinoma as the diagnosis.

Blood work was not sufficient to make a definitive diagnosis of prolactinoma, so a head magnetic resonance image (MRI) was obtained. A neurosurgeon reviewed the MRI and noted a 16 x 11 x 12 mm partially necrotic mass rising from the sella turcica and slightly compressing the optic chiasm. The diagnosis of pituitary macroadenoma was established without a pathologic analysis. Because of the compression on the optic chiasm, DK was referred to a neuro-ophthalmologist for further evaluation. His findings revealed very slight visual field defects in the right nasal area as well as mild atrophy of the right optic disc.

Although rare in children, a prolactinoma is the most common type of pituitary adenoma (Colao et al., 1998). It is characterized by secretion of varying levels of prolactin by the anterior pituitary gland (Casanueva et al., 2006, Pena and Rosenfeld, 2001, Singh and Aggarwal, 2005). These tumors are uncommon, although the exact incidence is unclear because of variation in reporting and lack of consensus about the age range which is considered pediatric (Webb & Prayson, 2008). Most data suggest that the overall in incidence is 1% to 10% of all childhood brain tumors (Webb & Prayson). Prolactinomas are designated as microadenomas if they are less than 10 mm in diameter and macroadenomas if they are greater than 10 mm (Cannavo et al., 2003). By this definition, DK had a macroadenoma. There is a higher incidence of all prolactinomas among females but a higher incidence of macroadenomas in males (Singh & Aggarwal).

The etiology of prolactinomas is not entirely clear, but research suggests that they may occur as a result of a genome change that causes mutated pituitary stem cells. Environmental factors may then permit the growth of these mutated cells. There is a familial tendency to prolactinomas, which supports a genetic component in the etiology (Casanueva et al., 2006). The tumors generally are benign, but they may have significant impact on the quality of life of children because of the possibility of frequent, severe headaches and the potential effects on growth and development, especially puberty and menarche (Singh and Aggarwal, 2005, Webb and Prayson, 2008). As noted with DK, children may present with delayed puberty, delayed menarche, headaches or visual disturbances.

The management of DK's prolactinoma required specialized care from a variety of providers including an endocrinologist, neuro-ophthalmologist, neurosurgeon, and cardiologist. It was an excellent opportunity for the NP to work collaboratively with these specialists, coordinate multiple appointments and referrals (including insurance authorization), provide support to the family, help answer the family's many questions, and obtain clearance from the endocrinologist and neurosurgeon for unrestricted activities and sports. Because this disorder is not encountered frequently, it was a tremendous learning experience for the NP.

A variety of management options exist for a prolactinoma. Treatment often depends on the size of the lesion and the type of symptoms (e.g., increased intracranial pressure or damage to structures like the optic disc) it may be causing (Singh & Aggarwal, 2005). The mainstays of management are medical, surgical, and/or radiation (Casanueva et al., 2006).

Prolactin secretion by the anterior pituitary is under hypothalamic inhibitory control exerted by release of dopamine. Recent data suggest that the first-line approach to adolescent patients with prolactin-secreting macroadenomas is dopamine-agonist medications because they are effective and act very rapidly (Chanson & Salenave, 2004). These medications have a high affinity for dopamine-2 receptors, so they are useful in conditions in which excess prolactin is secreted. Dostinex (cabergoline), the medication prescribed for DK, has a long half-life and is usually prescribed once or twice weekly. Adverse effects of the medication may include dizziness and nausea (http://www.fda.gov). Dopamine-agonists such as Dostinex (cabergoline) and bromocriptine significantly improve prolactin levels in 90% of patients and cause a reduction in tumor size in 60% of patients (Howell, Wasilewski, Mazewski, Hudgins, & Meacham, 2005).

Although dopamine-agonists are the usual treatment for prolactinomas, some patients experience intolerable gastrointestinal adverse effects, such as severe nausea, or other adverse effects, such as extreme lightheadedness (United States Food and Drug Administration, n.d.). In some patients these medications are ineffective in reducing the tumor mass. In these situations, surgery becomes an option (Colao et al., 1998). Surgical treatment of both microadenomas and macroadenomas is considered a very effective treatment, with a 91.3% initial remission rate for microadenomas and a 53.2% initial remission rate for macroadenomas (Kreutzer et al., 2008). Some prolactinomas, especially in men, require both surgery and follow-up radiation (De Menis et al., 2001).

Because the use of dopamine agonist medications generally has been so successful, radiation therapy has become the last treatment of choice for primary management of prolactinomas. Radiation continues to be used postoperatively for other types of adenomas, such as growth hormone-secreting adenomas (Chanson & Salenave, 2004) and in conjunction with surgery for males with prolactinomas (De Menis et al., 2001).

DK immediately started taking Dostinex, 0.25 mg twice weekly. After 4 weeks of dopamine-agonist treatment, DK's prolactin level decreased from 276 ng/mL to 3.3 ng/mL, with the only adverse effect being minor lightheadedness. Soon after she started taking Dostinex, DK was evaluated by a neurosurgeon to determine if surgery would be needed as an additional or alternative option to medication. The surgeon believed that medical management alone would be effective and surgery could be avoided because DK had no further galactorrhea, significant improvement in her headaches, and a marked decrease in her prolactin level. Despite the elimination of surgery as an option, DK's mother expressed continued stress and anxiety about her daughter's care and prognosis.

Because DK had such a dramatic response to Dostinex, her dose was reduced from 0.25 mg twice weekly to 0.25 mg weekly. The NP assisted the family in establishing a regular day and time each week to take the medication because compliance was an important component of this management. A repeat MRI 2 months after the initial diagnosis revealed a significant reduction in the tumor size from 16 x 11 mm to 11 x 5 mm. The neurosurgeon was confident that medical management was effective and the possibility of surgical intervention was eliminated for DK.

DK continued to be followed by pediatric endocrinology every 4 to 6 months. After the first four months of therapy, DK achieved menarche and has had menses every 18 to 20 days. Her menses are heavy and accompanied by dysmenorrhea but no management plan has been implemented except ibuprofen prior to onset of menses. The endocrinologist discouraged the use of oral contraceptives to improve dysmenorrhea and regulate cycles while DK was taking a dopamine-agonist medication.

After approximately 18 months of therapy, DK's prolactin levels increased to 32 ng/mL, so she resumed her previous schedule of twice-weekly medication. By this time generic cabergoline was prescribed instead of trade Dostinex. A repeat MRI showed that the tumor had decreased from an initial size of 16 x 11 x 12 mm to 8 x 4 mm. A small residual adenoma remained, but the necrotic fluid had reabsorbed.

After 2 years of treatment with cabergoline, new research raised concerns about this medication causing problems with cardiac valves (Drug Information On-Line, n.d.). The research suggested that problems might occur with higher doses of cabergoline used to treat Parkinson's disease, not the small dose that DK was taking. Nonetheless, DK was referred to a pediatric cardiologist for evaluation. Both her electrocardiogram and echocardiogram were normal. Because long-term effects were not known, the cardiologist suggested a follow-up visit to a cardiology clinic in 5 years and continued monitoring of the literature for other potential adverse effects of cabergoline.

Around the time of the cardiology visit, DK reported blurry vision in one eye and failed the vision screen at school. She returned to the neuro-ophthalmologist for re-evaluation and was found to have near normal distance vision and normal visual fields with no further atrophy of the optic disc. DK was reassured that her vision concerns were not related to the prolactinoma, and she was given a mild prescription for glasses to be used for distance work in school. DK's concerns suggested that there continued to persistent anxiety related to the tumor.

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