From the Guidelines
For a male with gynecomastia and mildly elevated alpha-fetoprotein (AFP) of 9.6 ng/mL with otherwise normal hormonal workup, I recommend prompt testicular ultrasound and abdominal imaging to evaluate for testicular or liver pathology. The elevated AFP, even if mild, raises concern for a testicular germ cell tumor or hepatocellular disease that could be causing the gynecomastia, as suggested by the guidelines from the National Comprehensive Cancer Network 1. According to the American Society of Clinical Oncology, benign liver disease, constitutively elevated AFP, tumor lysis, hepatocellular carcinoma, and other cancers can cause false-positive test results for serum tumor markers, including AFP 1. Schedule a urological consultation for further evaluation and possible testicular examination. Consider repeating the AFP measurement in 2-4 weeks to track any changes, as recommended by the American Society of Clinical Oncology 1. If testicular imaging is negative, proceed with abdominal CT or MRI to evaluate the liver. A comprehensive medication review is essential as certain medications like spironolactone, finasteride, and some antipsychotics can cause gynecomastia. If all imaging and repeat AFP testing are normal, consider a liver function panel to rule out hepatic causes of elevated AFP. The connection between elevated AFP and gynecomastia lies in potential testicular tumors that may produce estrogens or liver dysfunction affecting hormone metabolism, as suggested by the guidelines from the National Comprehensive Cancer Network 1. Even with normal estradiol levels, local tissue estrogen effects or receptor sensitivity could be contributing factors. It is also important to note that the majority of male breast problems are benign with gynecomastia as the most common etiology, and men with breast symptoms and their referring providers are typically concerned about whether or not it is due to breast cancer, as stated in the American College of Radiology guidelines 1. However, in this case, the mildly elevated AFP warrants further investigation to rule out any potential underlying conditions that may be causing the gynecomastia.
From the Research
Evaluation of Male Gynecomastia
The patient presents with gynecomastia and a mildly elevated alpha-fetoprotein (AFP) tumor marker of 9.6, with normal beta-hCG, luteinizing hormone, FSH, estradiol, prolactin, and thyroid panel.
- The initial step in the evaluation of gynecomastia is to rule out underlying pathological conditions, reversible causes, and to discriminate it from other breast lumps, particularly breast cancer 2.
- A thorough medical history and physical examination of the breast and genitalia, including testicular ultrasound, are essential components of the evaluation 2.
- Laboratory investigations, such as testosterone, estradiol, sex hormone-binding globulin, luteinizing hormone, follicular stimulating hormone, thyroid stimulating hormone, prolactin, human chorionic gonadotropin, and alpha-fetal protein, may be included in the evaluation 2.
- The mildly elevated AFP level in this patient may be associated with focal nodular hyperplasia (FNH), as reported in a case study where a patient with gynecomastia was found to have FNH with expression of AFP in FNH cells 3.
- Testicular tumors can also present with gynecomastia, and the possibility of a testicular tumor must be considered in any male presenting with gynecomastia 4.
- The patient's normal hormone levels and mildly elevated AFP level suggest that further evaluation, including imaging studies and possibly a biopsy, may be necessary to determine the underlying cause of the gynecomastia 2, 3, 4.
- Men with gynecomastia may be at increased risk for certain malignancies, including testicular cancer and squamous cell carcinoma of the skin 5.
Further Evaluation and Management
- Breast imaging, such as ultrasound or mammography, may be used to further evaluate the patient's gynecomastia, especially if the clinical examination is equivocal 2.
- If the clinical picture is suspicious for a malignant lesion, core needle biopsy should be performed 2.
- The patient's mildly elevated AFP level and normal hormone levels suggest that a thorough evaluation, including imaging studies and possibly a biopsy, is necessary to determine the underlying cause of the gynecomastia 2, 3, 4.
- Treatment of the underlying cause of the gynecomastia, if identified, is essential, and watchful waiting may be recommended after treatment of underlying pathology or discontinuation of substances associated with gynecomastia 2.