What Next for this Patient: Thirteen-Year-Old Boy With Breast Development and Galactorrhea
PATIENT PROFILE: It is 9:00 on Sunday morning when the first patient of the day registers during your weekend extended office hours. The triage nurse informs you that the patient is a 13-year-old boy with “chest pain.” You enter the examination room expecting to see a patient in distress. Instead, you are greeted by an alert, very nervous-appearing young man and his father. “There’s something very wrong with my son,” Kevin’s father whispers. “I’m worried he may have cancer! Show the doctor your chest.” Kevin turns 3 shades of red and pulls up his shirt, revealing bilateral breast tissue development. The father explains that Kevin has been intermittently complaining about soreness in his chest for a few weeks. He had not paid much attention until Kevin hesitated to take off his shirt before going swimming yesterday. When Kevin finally did so, it became clear that he was hiding the fact that his breast tissue had been growing. The father immediately assumed that this was pathologic and promptly sought medical attention. About 1 year ago, Kevin had received a diagnosis of bipolar disorder. His symptoms have been well controlled with olanzapine since then, and he has tolerated the medication well, except for some modest weight gain (he is slightly overweight). He takes no other medications. After Kevin’s father steps out of the room, Kevin admits that he has been really scared about the breast development. (He has repeatedly tried to “press down” the breast tissue in the hope of preventing further growth.) He swears he hasn’t tried any illegal drugs because he doesn’t want to jeopardize his perfect grade point average. Examination of the HEENT, heart, lungs, and abdomen yields normal results. Genital examination reveals Tanner stage 3 pubic hair and testicular development. There is bilateral breast tissue enlargement (3 cm) around the areola. The breasts are rubbery, but movable, and are mildly tender to palpation. There is no evidence of redness or pus. When the areola is palpated, a small drop of whitish fluid is expressed. On seeing this, Kevin bemoans, “Holy %*$@—I really am growing girl breasts now!” WHAT WOULD YOU DO NOW? A. Refer the patient to a breast surgeon for tissue reduction counseling. B. Reassure the patient that this is gynecomastia, a normal feature seen in adolescent males that should resolve within the next couple of years. C. Determine the prolactin level D. Refer the patient for genetic counseling and testing. E. Order an immediate CT or MRI scan of the head to rule out a prolactinoma, and request breast ultrasonography to rule out a neoplastic process. GYNECOMASTIA IN ADOLESCENT MALES More than 60% of male adolescents will experience gynecomastia—a physiologic increase in stromal and glandular breast tissue (Figure). The majority of these teenagers notice the breast development during early to mid puberty (Tanner stage 2 to 3). Why does gynecomastia affect some boys? The answer involves the pubertal boy’s relative production and concentration of testosterone and estrogen. The adult male normally produces both hormones, but at a concentration of 300:1. However, in the early stages of puberty, there is a short-lived physiologic reversal of this testosterone-to-estrogen ratio. Male breast tissue responds to this imbalance by enlarging (similar to the effect seen in the female breast). As puberty progresses, this hormonal imbalance eventually reverses: testosterone becomes the dominant hormone, and its presence causes male breast tissue to atrophy. This process can take from weeks to 3 years. Most boys require little more than reassurance that they are not growing breasts, turning into a girl, or dying of breast cancer. There are, of course, cases in which the gynecomastia is pathologic. In Kevin’s case, the presence of galactorrhea suggests that this may be more than a simple developmental process. Therefore, reassurance (choice B) alone is not appropriate in this scenario. The normal results of the genital and testicular examination suggest that a genetic syndrome is not the most likely diagnosis. Thus, a genetics referral (choice D) is probably not indicated at this point. Breast reduction surgery is occasionally recommended in older adolescents who have significant gynecomastia (more than 5 cm of breast tissue). However, the primary goal here is to determine why Kevin is experiencing the gynecomastia with galactorrhea (choice A is therefore incorrect). Because galactorrhea often occurs secondary to an increased concentration of prolactin, you decide to determine the blood prolactinlevel. Choice C is therefore correct. If the prolactin level is significantly elevated, a head CT or MRI scan may be indicated to rule out a pituitary tumor. I would not invest the time and money in such a workup, however, until preliminary laboratory test results are available. In addition, the bilateral nature of this patient’s gynecomastia suggests that this is not a neoplastic process; therefore, breast ultrasonography (choice E) is not indicated—at least not at this point in the workup. Further examination reveals sharp retinal fundi bilaterally without evidence of papilledema. The lateral visual fields are also intact. Also, results of the neurologic examination are completely normal. In addition, the patient denies headaches, morning nausea and vomiting, and any visual changes. These findings suggest that symptoms are probably not the result of a prolactinoma. Several hours after the visit with Kevin, the laboratory calls to report that his prolactin level is 52 ng/mL (normal, 3 to 19 ng/mL). WHEN IS GYNECOMASTIA ABNORMAL? The typical adolescent male with gynecomastia has breasts less than 4 cm in diameter (under the areola). The breast masses appear rubbery and nonfixed and are often bilateral and tender to palpation. If there is no history that suggests drug use, adverse effects of a medication, or liver or thyroid disease, then physiologic gynecomastia is the likely diagnosis. Reassurance is the only treatment necessary. Be aware that obese teenage boys may have fatty breast tissue development (also known as “pseudogynecomastia”) that is unrelated to the effects of testosterone and estrogen. This tissue may be permanent, even after weight loss. These boys may ultimately be candidates for breast reduction surgery. Consider the possibility of a pathologic process when breast development exceeds 4 to 5 cm or is rapidly progressive, or when the breast tissue is hard and fixed or associated with any other physical findings. Remember that new-onset physiologic gynecomastia generally does not form in an adolescent who has reached Tanner stage 5 of pubertal development. Therefore, a genital examination is a mandatory part of determining whether the breast development is within normal limits. A differential diagnosis for gynecomastia is presented in the Table. If you suspect a pathologic cause of gynecomastia, then the diagnostic workup should reflect your suspicions. For example, if you are concerned about a testicular abnormality (such as a mass), consider testicular ultrasonography and measurement of estradiol, human chorionic gonadotropin, serum testosterone, and luteinizing hormone levels: these may point to a Leydig or Sertoli cell tumor. Alternatively, the patient who lacks secondary sex characteristics (eg, pubic hair) or who has other feminizing features (or features of hypogonadism) may have undiagnosed Klinefelter syndrome (or a variant thereof). A genetic karyotype (in addition to the testosterone, estradiol, and luteinizing hormone levels) may help secure the diagnosis. BACK TO THE CASE . . . As noted, the presence of galactorrhea suggests that Kevin may have something more than simple physiologic gynecomastia. The elevated prolactin level is worrisome and suggests the possibility of a pituitary tumor. As you get ready to call Kevin’s family to arrange an MRI scan, you think to yourself, “What about Kevin’s medication?” A quick Medline search reveals that olanzapine is a “next-generation antipsychotic” commonly used as a mood stabilizer to treat bipolar symptoms. Like many drugs that antagonize dopamine receptors, olanzapine can potentially elevate blood prolactin levels and subsequently produce gynecomastia with galactorrhea. It is quite possible that the psychotropic medication caused the gynecomastia and galactorrhea. Consultation with a child/adolescent psychiatrist is in order. In this setting, discontinuation of the offending psychotropic medication generally leads to a dramatic decrease in prolactin levels within 4 weeks. The gynecomastia and galactorrhea also resolve—or at least improve— concurrently. Neuroimaging can usually be delayed during this period. If symptoms improve (and prolactin levels decline), imaging is not necessary. When the dosage cannot be decreased or changed because the patient truly needs the medication, close monitoring of prolactin levels is mandatory. The addition of a dopamine agonist (such as bromocriptine) may be necessary to treat the hyperprolactinemia. This can be done in consultation with a pediatric endocrinologist. This case underscores the need to be vigilant for diagnostic “zebras.” Fortunately, most cases of male adolescent gynecomastia are short-lived and spontaneously resolve with little more intervention than reassurance. When physiologic gynecomastia becomes excessive or causes significant psychological distress, there are some limited treatment options. The efficacy and safety of drugs such as testosterone, tamoxifen, and danazol have been evaluated, although only a few studies have involved adolescents. Moreover, none of these drugs have been approved for use in gynecomastia. Ultimately, surgical excision may be necessary in disfiguring cases. REFERENCE: 1. Braunstein GD. Gynecomastia. N Engl J Med. 1993;328:490-495.