Is it appropriate to initiate testosterone (hypogonadism treatment) in a patient with undiagnosed testicular masses, primary hypogonadism, and low testosterone levels, despite negative positron emission tomography (PET) imaging and testicular tumor markers, with a leading differential diagnosis of lymphoma and recent findings of cirrhosis and prominent upper abdominal lymph nodes on PET computed tomography (CT) scan?

From the Guidelines

It is not advisable to initiate testosterone therapy in a patient with undiagnosed testicular masses, primary hypogonadism, and low testosterone levels, despite negative positron emission tomography (PET) imaging and testicular tumor markers. The patient's condition requires a thorough urologic workup to rule out malignancy, particularly given the leading differential diagnosis of lymphoma and recent findings of cirrhosis and prominent upper abdominal lymph nodes on PET computed tomography (CT) scan 1.

Key Considerations

• The presence of undiagnosed testicular masses necessitates a cautious approach, as initiating testosterone replacement therapy could potentially stimulate growth of an undiagnosed malignancy or mask symptoms that might aid in diagnosis 1.
• The patient's low testosterone levels, while indicative of primary hypogonadism, should not be addressed with hormone replacement therapy until the etiology of the testicular masses is established and malignancy has been definitively ruled out 1.
• The noted cirrhosis and abdominal lymphadenopathy require further evaluation, as these findings could be related to the testicular abnormalities or represent separate pathologies that might influence treatment decisions 1.

Diagnostic Approach

• A solid mass in the testis identified by physical exam or imaging should be managed as a malignant neoplasm until proven otherwise, according to the American Urological Association guideline 1.
• Scrotal ultrasound (US) with Doppler should be obtained in patients with a unilateral or bilateral scrotal mass suspicious for neoplasm, as recommended by the guideline 1.
• Patients with normal serum tumor markers (STM) and indeterminate findings on physical exam or testicular US for testicular neoplasm should undergo repeat imaging in 6-8 weeks, as suggested by the guideline 1.

Treatment Implications

• Exogenous testosterone therapy can inhibit intratesticular testosterone production and suppress spermatogenesis, thus impairing fertility, as noted in the AUA/ASRM guideline 1.
• Human chorionic gonadotropin (hCG) is the usual first-line drug for the treatment of idiopathic hypogonadotropic hypogonadism (IHH) for restoration of testosterone production and spermatogenesis, according to the guideline 1.
• Clinicians should not prescribe exogenous testosterone therapy in males pursuing or planning to pursue family building in the near future, as it can result in inhibition of gonadotropin secretion and decreased spermatogenesis 1.

From the FDA Drug Label

Testosterone cypionate injection is indicated for replacement therapy in the male in conditions associated with symptoms of deficiency or absence of endogenous testosterone. Primary hypogonadism (congenital or acquired)-testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome; or orchidectomy. Hypogonadotropic hypogonadism (congenital or acquired)-idiopathic gonadotropin or LHRH deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation.

The patient has primary hypogonadism and low testosterone levels, which are indications for testosterone replacement therapy. However, the presence of und diagnosed testicular masses and a leading differential diagnosis of lymphoma raises concerns.

• The FDA label does not provide guidance on initiating testosterone therapy in patients with undiagnosed testicular masses or suspected lymphoma.
• The label also does not address the patient's recent findings of cirrhosis and prominent upper abdominal lymph nodes on PET CT scan. Given the uncertainty and potential risks, it is not appropriate to initiate testosterone therapy without further evaluation and diagnosis of the testicular masses and lymphoma. 2

From the Research

Testosterone Therapy in Men with Undiagnosed Testicular Masses

• The decision to initiate testosterone therapy in a patient with undiagnosed testicular masses, primary hypogonadism, and low testosterone levels should be made with caution, considering the potential risks and benefits 3, 4, 5.
• According to the Endocrine Society clinical practice guideline, testosterone therapy is recommended for men with symptomatic androgen deficiency to induce and maintain secondary sex characteristics and to improve their sexual function, sense of well-being, muscle mass and strength, and bone mineral density 5.
• However, the guideline also recommends against starting testosterone therapy in patients with certain conditions, such as breast or prostate cancer, a palpable prostate nodule or induration, or prostate-specific antigen greater than 4 ng/ml 5.
• In this case, the patient has a leading differential diagnosis of lymphoma and recent findings of cirrhosis and prominent upper abdominal lymph nodes on PET CT scan, which may increase the risk of adverse outcomes with testosterone therapy 6, 7.
• The benefits of testosterone therapy in men with age-related hypogonadism are uncertain, and there are important risks, including a potential risk of major adverse cardiac events and increases in blood pressure that can increase the risk of myocardial infarction and stroke 7.

Considerations for Testosterone Therapy

• Before initiating testosterone therapy, it is essential to confirm the diagnosis of hypogonadism and rule out other potential causes of low testosterone levels, such as testicular masses or other underlying medical conditions 3, 4.
• The patient's symptoms and medical history should be carefully evaluated, and the potential benefits and risks of testosterone therapy should be discussed with the patient 5, 6.
• Regular monitoring of the patient's response to therapy and potential adverse events is crucial to ensure safe and effective treatment 5, 6.