Introduction

INTRODUCTION

THESE UPDATED CLINICAL PRACTICE GUIDELINES (CPGs) (1–3) summarize the recommendations of the authors, acting as a joint American Association of Clinical Endocrinologists (AACE) and American Thyroid Association (ATA) task force for the diagnostic evaluation and treatment strategies for adults with hypothyroidism, as mandated by the Board of Directors of AACE and the ATA.

The ATA develops CPGs to provide guidance and recommendations for particular practice areas concerning thyroid disease, including thyroid cancer. The guidelines are not inclusive of all proper approaches or methods, or exclusive of others. the guidelines do not establish a standard of care, and specific outcomes are not guaranteed. Treatment decisions must be made based on the independent judgment of health care providers and each patient's individual circumstances. A guideline is not intended to take the place of physician judgment in diagnosing and treatment of particular patients (for detailed information regarding ATA guidelines, see the Supplementary Data, available online at www.liebertpub.com/thy).

The AACE Medical Guidelines for Clinical Practice are systematically developed statements to assist health care professionals in medical decision making for specific clinical conditions. Most of their content is based on literature reviews. In areas of uncertainty, professional judgment is applied (for detailed information regarding AACE guidelines, see the Supplementary Data).

These guidelines are a document that reflects the current state of the field and are intended to provide a working document for guideline updates since rapid changes in this field are expected in the future. We encourage medical professionals to use this information in conjunction with their best clinical judgment. The presented recommendations may not be appropriate in all situations. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances.

The guidelines presented here principally address the management of ambulatory patients with biochemically confirmed primary hypothyroidism whose thyroid status has been stable for at least several weeks. They do not deal with myxedema coma. The interested reader is directed to the other sources for this information (4). The organization of the guidelines is presented in Table 1.

Serum thyrotropin (TSH) is the single best screening test for primary thyroid dysfunction for the vast majority of outpatient clinical situations, but it is not sufficient for assessing hospitalized patients or when central hypothyroidism is either present or suspected. The standard treatment is replacement with L-thyroxine which must be tailored to the individual patient. The therapy and diagnosis of subclinical hypothyroidism, which often remains undetected, is discussed. L-triiodothyronine in combination with L-thyroxine for treating hypothyroidism, thyroid hormone for conditions other than hypothyroidism, and nutraceuticals are considered.

TABLE 1. ORGANIZATION OF CLINICAL PRACTICE GUIDELINES FOR HYPOTHYROIDISM IN ADULTS

    Page
  Introduction 1201
  Methods 1201
  Objectives 1204
  Guidelines for CPGs 1204
  Levels of scientific substantiation and recommendation grades (transparency) 1204
  Summary of recommendation grades 1205
  Topics Relating to Hypothyroidism 1205
  Epidemiology 1205
  Primary and secondary etiologies of hypothyroidism 1206
  Disorders associated with hypothyroidism 1207
  Signs and symptoms of hypothyroidism 1207
  Measurement of T4 and T3 1207
  Pitfalls encountered when interpreting serum TSH levels 1208
  Other diagnostic tests for hypothyroidism 1209
  Screening and aggressive case finding for hypothyroidism 1209
  When to treat hypothyroidism 1210
  L-thyroxine treatment of hypothyroidism 1210
  Therapeutic endpoints in the treatment of hypothyroidism 1213
  When to consult an endocrinologist 1214
  Concurrent conditions of special significance in hypothyroid patients 1214
    Hypothyroidism during pregnancy 1214
    Diabetes mellitus 1215
    Infertility 1215
    Obesity 1215
    Patients with normal thyroid tests 1215
    Depression 1215
    Nonthyroidal illness 1215
  Dietary supplements and nutraceuticals in the treatment of hypothyroidism 1216
  Overlap of symptoms in euthyroid and hypothyroid patients 1216
  Excess iodine intake and hypothyroidism 1216
  Desiccated thyroid 1216
  3,5,3′-Triiodothyroacetic acid 1217
  Thyroid-enhancing preparations 1217
  Thyromimetic preparations 1217
  Selenium 1217
  Questions and Guideline Recommendations 1217
Q1 When should anti-thyroid antibodies be measured? 1217
R1   TPOAb measurements and subclinical hypothyroidism 1217
R2   TPOAb measurements and nodular thyroid disease 1217
R3   TPOAb measurements and recurrent miscarriage 1217
R4   TSHRAb measurements in women with Graves' disease who have had thyroidectomy or RAI treatment before pregnancy 1217
Q2 What is the role of clinical scoring systems in the diagnosis of patients with hypothyroidism? 1218
R5   Do not use clinical scoring systems to diagnose hypothyroidism 1218
Q3 What is the role of diagnostic tests apart from serum thyroid hormone levels and TSH in the evaluation of patients with hypothyroidism? 1218
R6   Do not use indirect tests to diagnose hypothyroidism 1218
Q4 What are the preferred thyroid hormone measurements in addition to TSH in the assessment of patients with hypothyroidism? 1218
R7   When to use free T4 vs. total T4 1218
R8   Using free T4 to monitor L-thyroxine treatment 1218
R9   Estimating serum free T4 in pregnancy 1218
R10   Prohibition against using T3 to diagnose hypothyroidism 1218
R11   Measuring TSH in hospitalized patients 1218
R12   Serum T4 vs. TSH for management of central hypothyroidism 1218
Q5 When should TSH levels be measured in patients being treated for hypothyroidism? 1218
R13   When to measure TSH in patients taking L-thyroxine for hypothyroidism 1218
Q6 What should be considered the upper limit of the normal range of TSH values? 1218
R14.1   Reference ranges for TSH, age, and lab variability 1218
R14.2   Reference ranges for TSH in pregnant women 1218
Q7 Which patients with TSH levels above a given laboratory's reference range should be considered for treatment with L-thyroxine? 1219
R15   Treating patients with TSH above 10 mIU/L 1219
R16   Treating if TSH is elevated but below 10 mIU/L 1219
Q8 In patients with hypothyroidism being treated with L-thyroxine what should the target TSH ranges be? 1219
R17   Target TSH when treating hypothyroidism 1219
Q9 In patients with hypothyroidism being treated with L-thyroxine who are pregnant, what should the target TSH ranges be? 1219
R18   Target TSH when treating hypothyroid pregnant women 1219
Q10 Which patients with normal serum TSH levels should be considered for treatment with L-thyroxine? 1219
R19.1   L-thyroxine treatment in pregnant women with "normal" TSH 1219
R19.2   L-thyroxine treatment in women of child-bearing age or pregnant with "normal" TSH and have positive TPOAb or history of miscarriage or hypothyroidism 1219
R19.3   L-thyroxine treatment in pregnant women or those planning pregnancy with TPOAb and serum TSH is >2.5 mIU/L 1219
R19.4   Monitoring of pregnant women with TPOAb or a "normal" TSH but >2.5 mIU/L who are not taking L-thyroxine 1219
Q11 Who, among patients who are pregnant, or planning pregnancy, or with other characteristics, should be screened for hypothyroidism? 1220
R20.1.1   Universal screening of women planning pregnancy included assisted reproduction 1220
R20.1.2   Aggressive case finding for hypothyroidism for women planning pregnancy 1220
R20.2   Age and screening for hypothyroidism 1220
R21   Aggressive case finding for hypothyroidism—whom to target 1220
Q12 How should patients with hypothyroidism be treated and monitored? 1220
R22.1   Form of thyroid hormone for treatment of hypothyroidism 1220
R22.2   L-thyroxine and L-triiodothyronine combinations to treat hypothyroidism 1220
R22.3   Prohibition against using L-thyroxine and L-triiodothyronine combinations to treat pregnant women or those planning pregnancy 1220
R22.4   Prohibition against using desiccated thyroid hormone to treat hypothyroidism 1220
R22.5   Prohibition against using TRIAC (tiratricol) to treat hypothyroidism 1220
R22.6   Resuming L-thyroxine treatment for hypothyroidism in patients without cardiac events 1220
R22.7.1   L-thyroxine treatment for overt hypothyroidism in young healthy adults 1220
R22.7.2   L-thyroxine treatment for overt hypothyroidism in patients older than 50 to 60 years 1220
R22.8   L-thyroxine treatment for subclinical hypothyroidism compared to overt hypothyroidism 1220
R22.9   Order of L-thyroxine treatment and glucocorticoids in patients with adrenal insufficiency and hypothyroidism 1221
R23   L-thyroxine treatment for hypothyroidism—time to take, method of taking, and storage 1221
R24   Free T4 as the target measurement when treating central hypothyroidism 1221
R25.1   Testing and treating women with hypothyroidism as soon as they become pregnant 1221
R25.2   Goal TSH in pregnant women with hypothyroidism 1221
R25.3   Monitoring pregnant women with hypothyroidism 1221
R26   Monitoring hypothyroid patients who start drugs affecting T4 bioavailability or metabolism 1221
R27   Prohibition against targeting specific TSH values in hypothyroid patients who are not pregnant 1221
Q13 When should endocrinologists be involved in the care of patients with hypothyroidism? 1221
R28   Type of hypothyroid patient who should be seen in consultation with an endocrinologist 1221
Q14 Which patients should not be treated with thyroid hormone? 1221
R29   Need for biochemical confirmation of the diagnosis before chronic treatment of hypothyroidism 1221
R30   Prohibition against using thyroid hormone to treat obesity 1221
R31   Thyroid hormone treatment and depression 1222
Q15 What is the role of iodine supplementation, dietary supplements, and nutraceuticals in the treatment of hypothyroidism? 1222
R32.1   Prohibition against using iodine supplementation to treat hypothyroidism in iodine-sufficient areas 1222
R32.2   Inappropriate method for iodine supplementation in pregnant women 1222
R33   Prohibition against using selenium as treatment or preventive measure for hypothyroidism 1222
R34   Recommendation regarding dietary supplements, nutraceuticals, and products marked as "thyroid support" for hypothyroidism 1222
  Areas for Future Research 1222
  Cardiac benefit from treating subclinical hypothyroidism 1222
  Cognitive benefit from treating subclinical hypothyroidism 1223
  L-thyroxine/L-triiodothyronine combination therapy 1223
  L-triiodothyronine monotherapy 1223
  Thyroid hormone analogues 1223
  Screening for hypothyroidism in pregnancy 1223
  Agents and conditions having an impact on L-thyroxine therapy and interpretation of thyroid tests 1223
  Author Disclosure Statement 1224
  Acknowledgments 1224
  References including authors' evidence level (EL) rankings 1224
  Supplementary Data Online at www.liebertpub.com/thy
   1. Supplementary information regarding ATA and AACE guidelines  
   2. Complete list of guideline recommendations  

     Note: When referring to therapy and therapeutic preparations in the recommendations and elsewhere, L-thyroxine and L-triiodothyronine are generally used instead of their respective hormonal equivalents, T4 and T3.

     AACE, American Association of Clinical Endocrinologists; ATA, American Thyroid Association; CPG, Clinical Practice Guideline; RAI, radioactive iodine; T3, triiodothyronine; T4, thyroxine; TPOAb, anti–thyroid peroxidase antibodies; TRIAC, 3,5,3′-triiodothyroacetic acid; TSH, thyrotropin; TSHRAb, TSH receptor antibodies.