Gynecomastia: What Primary Care Clinicians Need to Know

This transcript has been edited for clarity.In this podcast, we're going to talk about gynecomastia and how we diagnose and manage it in primary care. Let's start with a patient whom hopefully we might all identify in our own clinical practice. David is a 54-year-old cyclist who's getting a hard time from his cycle buddies because, over the past few months, he's developed some bilateral breast enlargement, more so on the left. There's some mild associated tenderness. There's no nipple discharge. There's no history of any skin changes around the nipples or around the chest area. Past medical history includes hypertension. Systemic inquiry reveals no weight change and no change in sexual function. Libido and erectile function are normal. David has no headache or visual disturbance. Importantly, there are no testicular lumps. His current medications are losartan (50 mg), indapamide (2.5 mg), amlodipine (10 mg), spironolactone (25 mg), and atorvastatin (20 mg) for the primary prevention of cardiovascular disease. David does not report any anabolic or street drug use.There's no family history of note, and David’s current alcohol intake is around 28 units weekly. Examination revealed a BMI of 31 and a waist-to-height ratio of 0.58, so he's in that category of increased cardiometabolic risk. In terms of his chest examination, there was bilateral breast enlargement evident — again, more so on the left, with glandular tissue palpable. There was no local lymphadenopathy in the head, neck, or axilla, and there were no peripheral stigmata of chronic liver disease. Testicular examination was reassuring. What are your thoughts? Is this pseudogynecomastia caused by excess adipose tissue? Or is the gynecomastia perhaps physiologic in origin due to falling testosterone levels? Or does David have an underlying endocrine etiology, perhaps hyperthyroidism or hypogonadotropic hypogonadism? Or is this iatrogenic, caused by his drugs (specifically, spironolactone)? Or are you worried about something a wee bit more sinister, like breast cancer? Or do you think something else is going on? Gynecomastia is the commonest male breast complaint we'll see in primary care, and, reassuringly, the majority of cases are benign. However, it can signify nefarious underlying pathology, including breast cancer, testicular tumors, liver cirrhosis, and certain endocrine disorders.What is gynecomastia? Gynecomastia is enlargement of male glandular tissue, whereas pseudogynecomastia is caused by excess adipose tissue and does not need further assessment. Physiologic gynecomastia is common in newborns, adolescents, and in men over the age of 50 years as testosterone levels fall.Any male aged 50 years or older with unilateral gynecomastia, with or without nipple discharge and with or without any skin changes, should be referred urgently to a rapid-access breast clinic to exclude underlying malignancy. Additionally, the presence of a bloody nipple discharge or unilateral ulceration of the nipple would also warrant an urgent referral to a breast clinic. Endocrine causes of gynecomastia include hyperthyroidism, primary hypogonadism secondary to certain genetic conditions (such as Klinefelter or Kallmann syndrome), hypogonadotropic hypogonadism, and hyperprolactinemia. Urologic causes of gynecomastia include testicular tumors, viral orchitis, and testicular infiltration in hemochromatosis, as well as chronic kidney disease. Finally, chronic liver disease, cirrhosis, and malabsorptive disorders can also cause gynecomastia. However, one of the commonest culprits in primary care are drugs. There are many, many drugs that are associated with gynecomastia, including prescribed medications, street drugs, and anabolic steroids. Common iatrogenic culprits include finasteride, calcium channel blockers, spironolactone (of course, David's on that), ACE inhibitors, metronidazole, olanzapine, risperidone, fluoxetine and other antipsychotics and mental health drugs, gabapentin and pregabalin, venlafaxine, quetiapine, opioids, digoxin, amiodarone, sildenafil, many chemotherapy drugs, methotrexate, estrogen, steroids, androgens, proton pump inhibitors, and H2 histamine blockers such as cimetidine and ranitidine. So, you can see a wide range of drugs that can be associated with gynecomastia. How do we assess and manage David in primary care? Well, from the history, we want to elicit duration and rapidity of onset of his gynecomastia. If his gynecomastia is of relatively short duration and was quite rapid in onset, of course, that is a red flag, and we should be more concerned about underlying malignancy.Is there any associated sexual dysfunction, loss of libido, erectile dysfunction that might suggest an endocrine hypogonadotropic underlying cause? Is there any systemic upset, fever, or weight loss? And importantly, as we've discussed, are there any skin changes or nipple changes? Additionally, what is his alcohol consumption? Again assess his risk for liver disease and possible cirrhosis. A medication review, as we've already discussed, is a key part of assessing someone with gynecomastia. What are his prescribed medications? Is there any history of illicit drug use, street drugs, and specifically anabolic steroids? And what about examination? Well, on examination, we are looking for breast enlargement — glandular tissue. Is there any glandular tissue evident? We're looking for stigmata of chronic liver disease. We're looking for any signs of hyperthyroidism. We're looking for evidence of any local lymphadenopathy, which again may raise suspicion of an underlying malignancy, and we should always do a testicular examination as well, to exclude any testicular growths.In terms of investigations, we should of course be guided by that person sitting in front of us, David. Investigations to consider include an early-morning testosterone, and we might also consider luteinizing hormone, follicle-stimulating hormone, sex hormone-binding globulin, free androgen index, estradiol, and prolactin levels. We might also want to check kidney function, thyroid function, liver function, and calculate a Fibrosis-4. And to exclude any testicular growths, you might want to consider checking an alpha-fetoprotein or a beta-human chorionic gonadotropin. When do we need to refer people with gynecomastia to secondary care? Once again, most individuals with gynecomastia do not warrant further investigation or treatment. We should be guided by our assessment in primary care and consider referral to our endocrinology colleagues, our urology colleagues, or a breast clinic, depending on our findings.Remember, those with physiologic or pseudogynecomastia can be reassured, and we can simply treat any underlying causes, such as switching medications that might be culprits. Remember, we should refer directly to a rapid-access breast clinic if there is any clinical suspicion of breast malignancy, if there's any persistent painful gynecomastia over 6 months with normal blood tests, and if there's a unilateral lump with no obvious underlying cause, no physiologic cause, no drug-induced cause, no family history of note, or any underlying genetic predisposition, such as Klinefelter syndrome.Going back to David, what do we think is going on? In David's case, it probably is iatrogenic secondary to that spironolactone I started him on for his resistant hypertension. I might consider switching him from spironolactone to eplerenone or perhaps an alternative full-fledged antihypertensive, bisoprolol, doxazosin, or amiloride.I would also discuss weight management sensitively, which may be contributing to some pseudogynecomastia as well. And, of course, if we can help David facilitate some weight loss, that will reduce his overall lifetime cardiometabolic risk. For someone like David, we should be aiming for a waist-to-height ratio of less than 0.52.