In the case of pituitary adenomas that do not produce significant amounts of intact tropic hormones, diagnostic differentiation between sellar- and tumors of nonpituitary origin (eg, meningiomas or craniopharyngiomas) can be difficult. In addition, if such nonsecreting adenomas are very small, then they can be difficult to distinguish from physiological pituitary enlargements.
In a proportion of these cases, free alpha-subunit may be elevated, aiding in diagnosis. Overall, 5% to 30% of pituitary adenomas produce measurable elevation in serum free alpha-subunit concentrations. There is also evidence that an exuberant free alpha-subunit response to thyrotropin-releasing hormone (TRH) administration may occur in some pituitary adenoma patients that do not have elevated baseline free alpha-subunit levels. A more than 2-fold increase in free alpha-subunit serum concentrations at 30 to 60 minutes following intravenous administration of 500 mcg of TRH is generally considered abnormal, but some investigators consider any increase of serum free alpha-subunit that exceeds the reference range as abnormal. TRH testing is not performed in the laboratory, but in specialized clinical testing units under the supervision of a physician.
In pituitary tumors patients with pre-treatment elevations of serum free alpha-subunit, successful treatment is associated with a reduction of serum free alpha-subunit levels. Failure to lower levels into the normal reference range may indicate incomplete cure, and secondary rises in serum free alpha-subunit levels can indicate tumor recurrence.
Small thyrotropin (TSH)-secreting pituitary tumors are difficult to distinguish from thyroid hormone resistance. Both types of patients may appear clinically euthyroid or mildly hyperthyroid and may have mild-to-modest elevations in peripheral thyroid hormone levels along with inappropriately (for the thyroid hormone level) detectable TSH, or mildly-to-modestly elevated TSH. Elevated serum free alpha-subunit levels in such patients suggest a TSH secreting tumor, but mutation screening of the thyroid hormone receptor gene may be necessary for a definitive diagnosis.
Constitutional delay of puberty (CDP), is a benign, often familial condition, in which puberty onset is significantly delayed, but eventually occurs and then proceeds normally. By contrast, hypogonadotrophic hypogonadism (HH) represents a disease state characterized by lack of gonadotropin production. Its causes are varied, ranging from idiopathic over specific genetic abnormalities to hypothalamic and pituitary inflammatory or neoplastic disorders. In children, it results in complete failure to enter puberty without medical intervention. CDP and HH can be extremely difficult to distinguish from each other. Intravenous administration of 100 mcg gonadotropin releasing hormone (GnRH) results in much more substantial rise in free alpha-subunit levels in CDP patients, compared with HH patients. A >6-fold rise at 30 or 60 minutes post-injection is seen in >75% of CDP patients, while a less than 2-fold rise appears diagnostic of HH. Increments between 2-fold and 6-fold are non diagnostic.
GnRH testing is not performed in the laboratory, but in specialized clinical testing units under the supervision of a physician.