TSH-Secreting Adenomas

From Lewis S Blevins Jr., MD  –  TSH-secreting (thyrotroph) adenomas are rare and account for less than 1% of all pituitary adenomas. They usually lead to excess production of thyroid hormone (hyperthyroidism), but can also be associated with long-standing primary hypothyroidism. TSH-secreting adenomas can co-secrete other hormones including growth hormone, prolactinoma, and gonadotropins. Most tumors are macroadenomas but microadenomas are increasingly recognized because of the recognition of the pattern of laboratory tests suggestive of TSH hypersecretion.

Symptoms and Signs
Common symptoms and signs are the same as those seen in hyperthyroidism of various causes and include anxiousness, tremulousness, restlessness, insomnia, weight loss, sweating, heat intolerance, and palpitations. Tumor mass effects, such as visual field disturbances and headaches, are common as most patients have large tumors. A goiter is usually present. Some patients have widening of the palpebral fissures and a stare. Unilateral proptosis has been reported as a consequence of invasion of tumor into the orbital cavity. Weight loss is not uncommon.

Radiographic Features
Most tumors are macroadenomas. They tend to invade local structures including the cavernous sinus. Many extending to the suprasellar cistern and compresses the visual pathways. Microadenomas are less common.

Laboratory Features
Serum free T4 and T3 levels are elevated in most patients. Serum TSH levels are either elevated or inappropriately normal. TSH levels may be “normal” yet associated with hyperthyroidism because the mass of TSH secreted per time, such as in a 24-hour day, is elevated. Studies have showed that the biological activity of TSH in these patients is greater in some patients than the biologic activity of normal TSH. The serum alpha subunit is usually elevated. The molar ratio of TSH to alpha subunit is abnormal. T3 administration does not usually suppress TSH secretion by these tumors. Before the development of TSH assays, and the recognition that inappropriately normal TSH levels can be due to TSH producing pituitary adenomas, a number of these patients were thought to have Graves’ disease or other forms of hyperthyroidism. Their thyroid glands were surgically removed or ablated with radioiodine therapy leading to aggressive pituitary tumor growth presumably because the pituitary tumor was no longer partially restrained by hyperthyroidism.

Differential Diagnosis
Central or pituitary resistance to thyroid hormone is a genetic disorder due to a mutation in the T3 receptor in cells of the pituitary and perhaps the hypothalamus. Affect the patient’s are hyperthyroid with inappropriately normal or elevated TSH levels in the setting of elevations of free T4 and T3. The principal difference between this disorder and TSH secreting adenoma as is that a pituitary tumor is not present in patients who have central resistance to thyroid hormone.
Long-standing primary hypothyroidism may be associated with TSH cell hyperplasia of the pituitary gland that can lead to enlargement, nodular transformation, and perhaps autonomous TSH secretion. In these patients, however, they’re usually hypothyroid. Therapeutic T4 and T3 dosages given in attempt to normalize the TSH result in hyperthyroidism and yet the TSH remains elevated.

Transsphenoidal surgery is the primary treatment for thyrotroph adenomas. Successful resection depends on the scale and expertise of the operating neurosurgeon, the size of the tumor, and the growth pattern of the lesion with particular reference to whether the invasive component of the tumor can be completely resected. This patient to have residual disease will likely require radiation therapy to prevent tumor growth. Therapy with somatostatin analogs can normalize T4 and T3 levels and 95% of patient’s uncontrolled TSH levels in more than two thirds of patients. Some patients enjoy regression of the tumor size. Antithyroid drugs, such as propylthiouracil or methimazole, are useful to control hyperthyroidism in some patients. Beta blockers can also be used to alleviate symptomatic hyperthyroidism while awaiting beneficial effects of other treatments.

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