R in coated tube assays, are reported to reach 99% specificity and sensitivity(11.11,11.12,16). Although rarely required, serial assays are of interest in following a patient’s course during antithyroid drug therapy, and a decrease predicts probable remission(11.2).
Other Assays Rarely Used-
General availability of assays that can reliably measure suppressed TSH has made this the gold standard to which other tests must be compared, and has effectively eliminated the need for most previously used ancillary tests. There are only rare causes of confusion in the TSH assay. Severe illness, dopamine and steroids, and hypopituitarism, can cause low TSH, but suppression below 0.1 µ/ml is uncommon and below 0.05 µ/ml is exceptional, except in thyrotoxicosis. Thyrotoxicosis is associated with normal or high TSH in patients with TSH producing pituitary tumors and selective pituitary resistance to thyroid hormone. If TSH, FT4, TRAb, and other test noted above do not establish the diagnosis, it may be wise to do nothing further except to observe the course of events. In patients with significant thyroid hyperfunction, the symptoms and signs will become clearer, and the laboratory measurements will fall into line. Measurement of BMR, T3 suppression of RAIU, TRH testing, and response to KI are of historical interest.
DIFFERENTIAL DIAGNOSIS of THYROTOXICOSIS
Graves’ disease must be differentiated from other conditions causing thyrotoxicosis. (Table -4).
Thyrotoxicosis factitia-Thyrotoxicosis may be caused by taking T4 or its analogs, most commonly due to administration of excessive replacement hormone by the patient’s physician.Hormone may be taken surreptitiously by the patient for weight loss or psychologic reasons. The typical findings are a normal or small thyroid gland, an131-I uptake of zero, a low serum TG, and, of course, a striking lack of response to antithyroid drug therapy. The problem can easily be confused with “painless thyroiditis”, but in thyrotoxicosis factitia, the gland is typically small.
Toxic nodular goiter is usually distinguished by careful physical examination and a history of goiter for many years before symptoms of hyperthyroidism developed. The thyrotoxicosis comes on insidiously, and often, in the older people usually afflicted, symptoms may be mild, or suggest another problem such as heart disease. The thyroid scan may be diagnostic, showing areas of increased and decreased isotope uptake. The results of assays for antithyroid antibodies, including TSAb, are usually negative. TMNG is typically produced by activating somatic mutations in TSH-R in one or more nodules, allowing them to enlarge and become functional even in the absence of TSH stimulation. (Interestingly, cats are well known to develop hyperthyroidism, with thyroid autonomy, often due to TSH-R gene mutations as seen in humans.)
Hyperfunctioning solitary adenoma is suggested on physical examination by atrophy of the remainder of the thyroid, and is proved by a scintiscan demonstrating preferential radioisotope accumulation in the nodule. This type of adenoma must be differentiated from congenital absence of one of the lobes of the thyroid. Toxic nodules typically present in adults with gradually developing hyperthyroidism and a nodule > 3 cm in size. These nodules are usually caused by activating somatic mutations in the TSH-R, which endows them with mildly increased function, compared to normal tissue, even in the absence of TSH. These nodules are usually, but not always, monoclonal(17). In adults toxic nodules are very rarely malignant. Rarely, functioning thyroid carcinomas produce thyrotoxicosis. The diagnosis is made by the history, absence of the normal thyroid, and usually widespread functioning metastasis in lung or bones. Invasion of the gland by lymphoma has produced thyrotoxicosis .
Thyrotoxicosis associated with subacute thyroiditis is usually mild and transient, and the patient lacks the physical findings of long-standing thyrotoxicosis. If thyrotoxicosis is found in conjunction with a painful goiter and low or absent 131-I uptake, 