REVIEW ARTICLE Update on the Management of Hyperthyroidism and Hypothyroidism Kenneth A. Woeber, MD, FRCPE linical aspects, laboratory investigation, and treatment of hyperthyroidism and hy- pothyroidism are reviewed in light of recent information. Special circumstances, such as hyperthyroidism during pregnancy, Graves ophthalmopathy, iodine-induced hy- perthyroidism, and subclinical hypothyroidism, are also considered. C Arch Intern Med. 2000;160:1067-1071 Hyperthyroidism and hypothyroidism are than 70 years, however, the classic clini- common disorders, especially in women. cal manifestations may be lacking and goi- In the 20-year follow-up of the original ter may be absent.3 Instead, anorexia with Whickham survey, which involved sev- wasting, atrial fibrillation, or congestive eral thousand randomly selected adults 18 heart failure may be the predominant years or older at enrollment, 0.8 per 1000 manifestations. Furthermore, the cause of surviving women per year developed hy- hyperthyroidism will differ between young perthyroidism and 3.5 per 1000 per year and elderly patients. In young patients developed spontaneous hypothyroid- Graves disease is almost always the cause, ism.1 In 1995, the American Thyroid As- whereas in elderly patients toxic nodular sociation published guidelines for the man- goiter is also a common cause. agement of these disorders.2 In this article, I provide an update of their management Laboratory Investigation in light of more recent information. Measurement of serum thyrotropin, HYPERTHYROIDISM using at least a second-generation assay (detection limit, approximately 0.05 Although the terms hyperthyroidism and thy- mIU/L), is the most sensitive test for rotoxicosis are frequently used interchange- screening for hyperthyroidism, a normal ably, in the strictest sense hyperthyroidism result virtually excluding hyperthyroid- refers to hyperfunction of the thyroid gland, ism, except in the rare instance where it whereas thyrotoxicosis refers to any state is due to thyrotropin hypersecretion. An characterized by thyroid hormone excess, undetectable value is the hallmark of including ingestion of excess thyroid hor- hyperthyroidism, but a low or sometimes mone and thyroiditis. This article, there- an undetectable value using a second- fore, will be principally concerned with the generation assay may occur in some management of hyperthyroidism caused by healthy elderly patients, in patients with Graves disease or associated with toxic nonthyroid illness, or in patients taking a nodular goiter. glucocorticoid or dopamine hydrochlo- ride. In these circumstances, a third- Clinical Considerations generation assay (detection limit, approximately 0.005 mIU/L) will afford A diagnosis of hyperthyroidism is sug- the necessary distinction, because in gested by the presence of a constellation hyperthyroidism serum thyrotropin is of symptoms and signs. In patients older still undetectable, whereas in the other conditions thyrotropin is almost always From the Department of Medicine, University of California, San Francisco, detectable, albeit low.4 Confirmation is Mount Zion Medical Center. sought in measurement of serum free ARCH INTERN MED/ VOL 160, APR 24, 2000 WWW.ARCHINTERNMED.COM 1067 ©2000 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 thyroxine (FT4). Occasionally, as a single daily dose, improving disorder has the potential to enter measurement of serum free triiodo- compliance.5 Moreover, in doses up a spontaneous remission. It is gen- thyronine (FT3) will be necessary to 30 mg/d, methimazole may carry erally considered the treatment of in a patient with clinical manifesta- a lower risk of agranulocytosis. choice for young patients with a tions of hyperthyroidism and an Treatment is usually initiated small goiter or patients with active undetectable serum thyrotropin with 30 mg of methimazole daily or ophthalmopathy (vide infra). Anti- and normal serum FT4 levels, 100 mg of propylthiouracil 3 times thyroid drugs are not indicated as defining the entity of triiodothyro- daily. The patient should be alerted long-term therapy in toxic nodular nine toxicosis. to the major, albeit rare (,1%), ad- goiter, since hyperthyroidism does In a patient with overt oph- verse effects of these drugs, includ- not remit. The likelihood of a long- thalmopathy, no additional testing ing agranulocytosis, liver disease, term remission is positively influ- is required, because the patient cer- and a lupuslike syndrome that tend enced by the duration of antithy- tainly has Graves disease. However, to occur within the first several roid drug therapy, and a duration of in a woman of child-bearing age, it months of therapy. Baseline labora- 1 to 2 years is recommended, with is essential to determine whether tory data should include a leuko- reported remission rates ranging she is pregnant, because this will cyte count and liver function tests, from 37% to 70%. Initial work had clearly influence the subsequent and monitoring of the leukocyte suggested that adding levothyrox- management (vide infra). In a count may predict agranulocytosis. ine sodium to long-term antithy- patient without ophthalmopathy, The patient should be instructed to roid drug therapy in patients with measurement of thyroid radioio- notify the physician immediately if Graves disease resulted in a greater dine (131I) uptake should be per- symptoms suggesting one of these likelihood of remission when the an- formed to establish the cause of adverse reactions appear. With- tithyroid drug was withdrawn. The thyrotoxicosis, ie, whether it is due drawal of the drug will result in reso- rationale for this approach was that to hyperthyroidism, in which case lution of the adverse reaction, but the antithyroid drugs might also ex- the uptake will be high, or to some both antithyroid drugs are contra- ert an immunosuppressive action, other condition where thyroid indicated thereafter, and the pa- and combination therapy permit- hyperfunction is lacking, such as tient will have to be treated with 131I ted the use of a higher dose of anti- thyroid hormone ingestion or thy- or surgery. With minor adverse re- thyroid drug. However, several more roiditis, in which case the uptake actions, such as pruritus, the patient recent studies6-9 have failed to con- will be low. A 131I scintiscan may be can be switched to the alternate firm these earlier findings. There are helpful in a patient with a nodular agent. no absolute predictors of outcome goiter, because it will serve to After treatment has been initi- following withdrawal of therapy, but define the functional characteristics ated, the patient should be fol- certain features, such as a small goi- of the gland. lowed up at approximately monthly ter, favor remission, whereas oth- intervals and the antithyroid drug ers, such as persistence of undetect- Treatment dose reduced to a maintenance dose able thyrotropin or high thyrotropin as a euthyroid state is approached. receptor antibody titer, favor re- Hyperthyroidism may be treated with The speed with which this is at- lapse.8 antithyroid drugs, 131I, or subtotal tained is determined by the sever- Following withdrawal of long- thyroidectomy, the type of treat- ity of disease, goiter size, and dose term therapy, the patient should ment being determined by the form of antithyroid drug. During this in- continue to be seen every 3 months of hyperthyroidism, the age of the pa- terim period, a b-adrenergic recep- for the first year, since relapse is most tient, the size of the goiter, and the tor blocking agent, such as pro- likely within this period. Thereaf- presence of coexisting conditions. pranolol hydrochloride, may be used ter, the patient should be seen an- to control the hyperadrenergic mani- nually, since relapse may occur in Antithyroid Drugs. Methimazole festations, such as tremor, anxiety, later years. Should relapse occur, the and propylthiouracil, the 2 drugs and palpitations, if these are trouble- patient should be treated with 131Ior available in the United States, are some, provided the patient does not subtotal thyroidectomy, although thioamides that are concentrated in have obstructive pulmonary dis- antithyroid drug therapy could be re- thyroid tissue and inhibit hormone ease or other contraindications to its instituted if the patient wishes to biosynthesis. In the United King- use. Measurement of serum FT4 avoid ablative therapy. dom and Europe, carbimazole is the rather than thyrotropin should be commonly used drug; it is virtually used to monitor treatment, since se- Radioiodine. 131I is the treatment of completely converted to methima- rum thyrotropin may remain unde- choice for patients with Graves hy- zole in vivo. In large doses, propyl- tectable for many months after a eu- perthyroidism who relapse after thiouracil also inhibits the periph- thyroid state is restored. Thereafter, long-term antithyroid drug therapy, eral tissue conversion of thyroxine the patient should be seen every 3 for patients with severe thyrocar- to triiodothyronine. Methimazole is months if long-term therapy is diac disease, for most patients with used in preference to propylthioura- planned. toxic multinodular or uninodular cil, because it has a longer inhibi- Long-term antithyroid drug goiter, and for patients with a ma- tory effect on glandular hormone therapy is only appropriate for jor adverse reaction to antithyroid synthesis and can therefore be taken Graves hyperthyroidism, since this drugs. 131I therapy is absolutely