Acquired disorders that damage gonadotrophs
- Sellar mass or cyst—pituitary adenoma, craniopharyngioma, Rathke cleft cyst, meningioma
- Infiltrative lesion—lymphocytic hypophysitis, Langerhans cell histiocytosis, hemochromatosis, sarcoidosis, infection
- Metastatic lesion
- Trauma (head injury)
- Radiation exposure
- Stalk severance
- Pituitary apoplexy.
See Table 1 for a summary of the causes of male hypogonadism.
WHEN IS MRI INDICATED IN EVALUATING SECONDARY HYPOGONADISM?
The yield of pituitary-hypothalamic imaging in older men with secondary hypogonadism is fairly low in the absence of other pituitary hormone abnormalities and deficiencies. There are limited data regarding appropriate criteria for performing hypothalamic-pituitary imaging studies. However, a patient who has multiple anterior pituitary abnormalities on laboratory evaluation should undergo dedicated hypothalamic-pituitary magnetic resonance imaging (MRI).
The Endocrine Society Clinical Practice Guidelines11 recommend that MRI be performed to exclude a pituitary or hypothalamic tumor or infiltrative disease if the patient has severe secondary hypogonadism (serum testosterone < 150 ng/dL), panhypopituitarism, persistent hyperprolactinemia, or symptoms or signs of tumor mass effect such as headache, visual impairment, or a visual field defect.
WHO SHOULD UNDERGO ASSESSMENT OF TESTOSTERONE STATUS?
Screening for androgen deficiency in the asymptomatic general population is not recommended.11 The nonspecific nature of many of the signs and symptoms of androgen deficiency makes it difficult to give concrete recommendations as to who should have testosterone levels measured. Clinicians should consider testing if there is evidence of certain clinical disorders that are associated with low testosterone levels (see earlier discussion on the specific causes of primary and secondary hypogonadism).
When a male patient complains of erectile dysfunction, the investigation should include an assessment of serum testosterone. However, if a man who has a constellation of nonspecific symptoms asks for his testosterone level to be assessed (which is common, given the aggressive marketing of testosterone replacement by the pharmaceutical industry), we would recommend a basic evaluation that includes a comprehensive metabolic panel, complete blood count, and TSH level. Further testing should be determined by the history and physical examination. If no obvious explanation has been found for the patient’s symptoms at that point, assessment of serum testosterone may be warranted. More often than not the patient’s weight and limited physical activity are the driving forces behind the nonspecific symptoms, and counseling a patient on a life-style change can provide much benefit if the patient follows through with the physician’s recommendations.
Men whom we believe should not undergo assessment for testosterone deficiency are those who are acutely ill and hospitalized and those who are severely obese and are complaining of fatigue. Testosterone levels should be assessed only after the acute illness has resolved and, in a severely obese patient with fatigue, only after a thorough evaluation for sleep apnea has been undertaken.
TREAT THE UNDERLYING CAUSE, IF ONE CAN BE FOUND
If the evaluation of low testosterone leads to the diagnosis of a clear underlying condition that is amenable to treatment, such as prolactin elevation or sleep apnea, then treatment should be directed at the underlying cause, with subsequent monitoring of the patient’s symptoms and response in serum testosterone levels. In general, the use of dopamine agonist therapy in the management of hyperprolactinemia and, in cases of panhypopituitarism, of replacement therapy with levothyroxine (Synthroid), hydrocortisone, and possibly growth hormone and desmopressin (DDAVP), fall best under the purview of an endocrinologist. A caveat: serum TSH cannot be used to monitor levothyroxine replacement therapy in cases of secondary hypothyroidism. The clinical picture and serum free T4 and free T3 levels are used instead.
In the absence of a correctable (or immediately correctable) cause, testosterone supplementation can be initiated on an individualized basis in select patients who have clinical signs and symptoms of androgen deficiency if the benefits of treatment appear to outweigh the potential risks, and only after a thorough discussion with the patient.11 The Endocrine Society recommends against offering testosterone therapy to all older men with low testosterone.11
In men presenting with low serum testosterone, semen analysis is not routine. It is usually reserved for patients presenting with the primary complaint of infertility.
If an endocrine disorder such as prolactin elevation or hypothyroidism is the suspected cause of infertility, the patient should be referred to an endocrinologist for further evaluation and management. Treatment of male infertility should be directed at the underlying cause, but often requires exogenous human chorionic gonadotropin, FSH, GnRH (via a pulsatile pump), and possibly sperm harvesting from the testis with subsequent in vitro fertilization with intracytoplasmic sperm injection. It is critical that the partner be included in the evaluation of infertility.
These patients should be referred to a urologic or fertility center specializing in the diagnosis and treatment of infertility. For further information regarding male infertility, patients can be directed to www.fertilitylifelines.com.
The patient’s low serum testosterone was confirmed on subsequent measurements at 8 am, with levels of 128 and 182 ng/dL (reference range 249–836). Other laboratory values:
- LH 1.4 mIU/mL (reference range 1.2–8.6)
- FSH 2.7 mIU/mL (1.3–9.9 mIU/mL)
(Both of these values are inappropriately normal in the setting of the low testosterone.)
- TSH 248 μIU/mL (0.4–5.5)
- Prolactin 24.6 ng/mL (1.6–18.8).
The patient was started on levothyroxine replacement therapy and after 3 months was noted to be euthyroid (TSH 1.8 μIU/mL) and to have a normal serum prolactin level. Testosterone levels (8 am) at this time were 350 ng/dL and 420 ng/dL.
Therefore, the cause of this patient’s hypogonadism was severe hypothyroidism and associated mild hyperprolactinemia. This case shows that a thorough evaluation is warranted before initiating testosterone therapy.