Given the biochemical similarities between TSHomas and resistance to thyroid hormone, a number of additional investigations are required (). Peripheral markers of thyroid hormone action, such as sex hormone-binding globulin and angiotensin-converting enzyme levels, are often elevated in TSHomas but are normal in patients with resistance to thyroid hormone. These levels were normal in our patient. Other tests include measurement of the α-subunit and α-subunit: TSH molar ratio. TSH, follicle-stimulating hormone and leutinizing hormone share a common α-subunit, whereas a distinct β-subunit confers biological specificity. Because α-subunit is cosecreted with TSH from the pituitary gland, elevated levels are suggestive of a TSHoma. However, because α-subunit secretion increases along with leutinizing hormone and follicle-stimulating hormone after menopause, the α-subunit: TSH molar ratio is considered to be a more specific indicator. The thyrotropin-releasing hormone stimulation test is also useful in differentiating between TSHomas and resistance to thyroid hormone. Patients with the latter condition will have a normal or a hypothyroid response, (> 2-fold TSH elevation after administration of thyrotropin-releasing hormone), whereas patients with TSHomas generally have a less than 2-fold elevation of TSH after administration of thyrotropin-releasing hormone, which suggests autonomy of the thyrotropes. In contrast, patients with primary hyperthyroidism (e.g., Graves' disease) have a flat response to thyrotropin-releasing hormone testing. In a series of 25 patients with TSHomas, it was found that an elevated baseline TSH, flat or decreased response to thyrotropin-releasing hormone and elevated α-subunit or α-subunit: TSH ratio had the highest sensitivity and specificity for diagnosis of TSHomas. A mutation in the thyroid hormone receptor β gene will provide a definitive diagnosis of resistance to thyroid hormone, but in about 10% of cases there are no mutations. Documentation of elevated thyroid hormone levels in asymptomatic family members is also suggestive of resistance to thyroid hormone. The presence of a pituitary adenoma on an MRI scan and somatostatin receptors on the pituitary on a radiolabelled octreotide scan are also compatible with the diagnosis of a TSHoma. However, because as many as 15% of normal people may harbour a small, nonfunctioning pituitary adenoma, patients with resistance to thyroid hormone may have abnormal imaging findings incidentally.