5: Diagnosis and Management of Hyperthyroidism and Hypothyroidism Duncan J Topliss and Creswell J Eastman
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EndocrinologyMJA Practice Essentials MJEndocrinologyA Practice Essentials 5: Diagnosis and management of hyperthyroidism and hypothyroidism Duncan J Topliss and Creswell J Eastman Despite the development of highly sensitive laboratory tests, clinical assessment and judgement remain paramount THYROID DYSFUNCTION is common. In the United States, hypothyroidism is present in 4.6% of the population (clini- ABSTRACT The Medical Journal of Australia ISSN: 0025-729X 16 cal, 0.3%; and subclinical, 4.3%) and hyperthyroidism in ■ The most common cause of hyperthyroidism in 1.3%February (clinical, 2004 0.5%; 180 4and 186-193 subclinical, 0.7%).1 A long-term ©The Medical Journal of Australia 2003 www.mja.com.au Australia is Graves disease, caused by a defect in studyMJA in Practicethe United Essentials Kingdom –Endocrinology found the incidence of immunoregulation in genetically predisposed individuals, hyperthyroidism was 0.8 per 1000 women annually, and leading to production of thyroid-stimulating antibodies. hypothyroidism was 3.5 per 1000 women annually.2 ■ Each of the three modalities of therapy for Graves disease — thionamide drugs, subtotal or total thyroidectomy, and Diagnosis of thyroid dysfunction radioactive iodine ablation — can render the patient euthyroid, but all have potential adverse effects and Thyroid function testing: Measurement of serum thyroid may not eliminate recurrences. stimulating hormone (TSH), using second- or third-genera- tion assays, is a sensitive index of primary thyroid disease.3 ■ Hypothyroidism occurs in about 5% of the adult population; most present with “subclinical” Assay of free thyroxine (T4) and triiodothyronine (T3) reliably eliminates the difficulties in interpretation of total hypothyroidism (mild thyroid failure), characterised by thyroid hormone levels caused by the common variations in raised levels of serum thyroid stimulating hormone (TSH) serum thyroid hormone-binding protein, best exemplified but normal free thyroxine (T4). by the oestrogen-induced rise in thyronine-binding globulin ■ The most common cause of hypothyroidism in Australia which increases total thyroid hormone levels. However, free is autoimmune chronic lymphocytic thyroiditis, hormone assays are still subject to in-vitro and in-vivo characterised by raised circulating levels of thyroid artefacts in severe non-thyroidal illness, severe disturbances peroxidase antibody. of binding proteins, and heparin therapy.4 Thus, if clinical assessment is not concordant with thyroid function results, ■ Symptoms and signs of hypothyroidism are often mild or additional tests and specialist opinion may be necessary. subtle and, when there is clinical suspicion, thyroid Interpretation of thyroid function results is summarised in function tests are needed; if serum TSH level is raised, Box 1. free T4 and thyroid peroxidase antibody should be Antibody testing: The most common cause of thyroid measured. dysfunction in Australia is autoimmunity. The most sensi- ■ Replacement therapy with thyroxine is the cornerstone tive in-vitro index for this is measurement of thyroid peroxi- of therapy (1.6µg/kg lean body weight daily, taken on an dase antibody level,1 but this can occasionally give false empty stomach); combination therapy with thyroxine and negative results (eg, in juvenile autoimmune thyroiditis). In liothyronine (T3) is promoted, but there is little evidence primary hypothyroidism, a raised level of thyroid peroxidase of its clinical benefit. antibody is evidence for autoimmune chronic lymphocytic thyroiditis. MJA 2004; 180: 186–193 In hyperthyroidism, the role of routine antibody testing is less clear. Diagnosis of Graves disease is usually possible clinically, and measurement of thyroid peroxidase antibody or TSH-receptor antibody may not contribute to diagnosis Series Editors: Donald J Chisholm and Jeffrey D Zajac or management. However, measurement of TSH-receptor antibody has a role when the cause of hyperthyroidism is Department of Endocrinology and Diabetes, Alfred Hospital, obscure, in assessing the risk of neonatal hyperthyroidism in Melbourne, VIC. pregnant women with a history of Graves disease, and in Duncan J Topliss, MD, FRACP, FACE, Director, and Associate Professor, assessing the risk of relapse after a course of antithyroid Department of Medicine, Monash University, Melbourne, VIC. drugs in Graves disease. Institute of Clinical Pathology and Medical Research, Westmead Hospital, Sydney, NSW. Radionuclide scanning: Radionuclide thyroid scanning is Creswell J Eastman, AM, MD, FRACP, FRCPA, Director, and Clinical not routinely necessary for diagnosing Graves disease or Professor, Department of Medicine, University of Sydney, Sydney, NSW. toxic multinodular goitre, but is useful when the cause of Reprints: Associate Professor Duncan Topliss, Department of hyperthyroidism is not apparent (eg, when no goitre is Endocrinology and Diabetes, Alfred Hospital, Melbourne, VIC 3004. palpable, when neck pain or tenderness suggests subacute duncan. [email protected] thyroiditis, or when a solitary “hot” nodule is suspected). 186 MJA Vol 180 16 February 2004 MJA Practice Essentials Endocrinology 1: Interpretation matrix for thyroid function results* High T4 Normal T4 Low T4 High TSH In vivo or in vitro artefact Mild thyroid failure (primary) Primary hypothyroidism Pituitary hyperthyroidism [TSHoma] (also termed subclinical hypothyroidism Thyroid hormone resistance and diminished thyroid reserve) Normal TSH As above Normal (in patients taking thyroxine, Pituitary or hypothalamic hypothyroidism Sampling within 6 h of thyroxine dose TSH > 3 mU/L may indicate subtle Severe non-thyroidal illness underreplacement) Low TSH Hyperthyroidism Subclinical hyperthyroidism Pituitary or hypothalamic hypothyroidism (for this diagnosis, TSH must be Subtle thyroxine overreplacement Severe non-thyroidal illness suppressed rather than just low) Thyroid autonomy (multinodular goitre or autonomous functioning thyroid nodule) Non-thyroidal illness T4 = serum free thyroxine. TSH = thyroid stimulating hormone. * The Health Insurance Commission restricts financial reimbursement to serum TSH alone, except in specified clinical circumstances, when additional measurements of free T4 and free triiodothyronine (T3) are sanctioned. We suggest that practitioners routinely request “thyroid function tests” and provide clear clinical information to enable the laboratory to perform additional tests if justified. The information should include the suspected condition (especially if hypopituitarism) and medications (eg, thyroxine, carbimazole or propylthiouracil, amiodarone or phenytoin). Hyperthyroidism Management of Graves disease The terms hyperthyroidism and thyrotoxicosis are used The three modalities of therapy for Graves disease are: interchangeably, irrespective of whether the disorder is ■ blocking synthesis of thyroid hormone with antithyroid caused by endogenous overproduction or excessive inges- drugs; tion of thyroid hormones. Causes of hyperthyroidism are ■ subtotal or “near-total” thyroidectomy; and shown in Box 2. Most common in Australia are Graves ■ destruction of the thyroid by radioactive iodine (radio- disease and toxic multinodular goitre. Management of iodine ablation). hyperthyroidism depends on the cause (particularly whether While each modality is satisfactory in rendering the 6 it is self-limiting, as in subacute thyroiditis), the size and patient euthyroid, none is ideal, as all have a risk of adverse nature of the goitre, intercurrent illnesses or medication effects and none but total thyroidectomy eliminates the risk and, especially in Graves disease, patient preference. of recurrence. Although total thyroidectomy virtually elimi- nates this risk, it is at the expense of a certain requirement for thyroid hormone replacement. Selecting treatment for Graves disease an individual depends on many factors, not least being patient choice and physician bias. In the United States, Graves disease is caused by stimulation of the thyroid by radioiodine is the preferred primary modality, but, in antibodies which bind to TSH receptors and mimic the Europe and Australia, antithyroid drug therapy is preferred effect of prolonged TSH stimulation. These TSH-receptor for patients with a first episode of Graves hyperthyroidism, antibodies result from abnormal immunoregulation permit- ahead of radioiodine and, lastly, surgery.7 ting generation and expansion of clone(s) of antibody- Antithyroid drugs: Most patients with Graves disease producing cells in genetically predisposed individuals with 5 require short-term (several months) treatment with an specific HLA-D subtypes. Spontaneous exacerbations and antithyroid drug (thionamide) before consideration of remissions of Graves disease can occur. The environmental triggers are still not well characterised, but postpartum exacerbation is common, and such a history should be 2: Causes of hyperthyroidism sought routinely when Graves disease is diagnosed. Excess iodine can precipitate active Graves disease by providing ■ Graves disease ■ hCG-mediated more substrate for hormone synthesis and possibly also by ■ Multinodular goitre (hyperemesis gravidarum, disturbing immune function. Persistence or recurrence of ■ Autonomously functioning trophoblastic disease) ■ Graves disease is more likely when there is a previous history single thyroid nodule Fetal and neonatal hyperthyroidism of recurrent disease, in the presence of a large goitre, when (adenoma) ■ Thyroiditis (subacute, (TSH-receptor-antibody- T excess