• Summary
• Key Points
  • Definitions
  • Clinical Presentation
  • To Screen or Not to Screen?
  • Diagnosis
  • Pharmacologic Therapy
  • When to Consider Treating Subclinical Hypothyroidism
  • Monitoring Treatment and Endpoints
  • When to Consult an Endocrinologist
  • Other Considerations
• References

SUMMARY:

Hypothyroidism is a common and easily treatable condition encountered in primary care. The most common cause of hypothyroidism worldwide is iodine deficiency, particularly in developing nations; in the US, it is chronic autoimmune (Hashimoto’s) thyroiditis. Hypothyroidism is 5 to 10 times more common in women and is often associated with other autoimmune disorders (type I diabetes, Addison’s disease, lupus). In many cases it is iatrogenic, caused by radioactive iodine therapy or surgery for hyperthyroidism or thyroid cancer, or drugs such as lithium, amiodarone, interferon alpha, or tyrosine kinase inhibitors. The American Thyroid Association (ATA), in conjunction with the American Association of Clinical Endocrinologists (AACE), offers a useful practice guideline for managing this prevalent endocrine disorder. Of note, the following summary applies to primary hypothyroidism and does not address management of central hypothyroidism or hypothyroidism in pregnancy, which are considered separate topics.

KEY POINTS:

Definitions

• Overt hypothyroidism
  • High TSH (usually above 10 mU/L)
  • Low free T4
• Subclinical hypothyroidism
  • TSH above the upper reference range (4.5 to 10 mU/L)
  • Normal free T4

Clinical Presentation 

• Dry skin
• Sensitive to cold
• Fatigue
• Muscle cramps
• Voice changes
• Constipation
• Weight gain/obesity
• Thinning hair
• Impaired Memory
• Irregular menses
• Depression
• Findings associated with severe hypothyroidism
  • Carpal tunnel syndrome | Sleep apnea | Pituitary hyperplasia (causing hyperprolactinemia and associated galactorrhea) | Hyponatremia

To Screen or Not to Screen?

Controversial—Recommendations Vary by Organization

• ATA: Screen all adults every 5 years beginning at age 35
• AACE: Screen “older” patients (age not specified)
• USPSTF does not recommend routine screening
• However, there is strong evidence to support “case finding” (screening in selected populations)
  • Autoimmune disease | Pernicious anemia | First-degree relative with autoimmune thyroid disease | History of radiation to neck or thyroid surgery | Abnormal thyroid exam | Psychiatric disorder | Taking amiodarone or lithium

• Other disorders that can be used to support hypothyroid screening include
  • Adrenal insufficiency | Alopecia | Anemia | Cardiac dysrhythmia | Changes in skin texture | Congestive heart failure | Constipation | Dementia | Diabetes mellitus, type 1 | Dysmenorrhea and other menstrual disorders | Hypercholesterolemia | Hypertension | Mixed hyperlipidemia | Malaise and fatigue | Myopathy, unspecified | Prolonged QT interval | Vitiligo | Weight gain

Diagnosis 

Check serum TSH and free T4

• Multiple clinical scoring systems exist but are not recommended for diagnosis
• Not necessary or recommended to check T3 (total or free)
• Mild TSH elevation common in older people and does not necessarily represent subclinical hypothyroidism
• Do not check TSH in hospitalized patients unless suspicion for primary thyroid process (e.g. myxedema coma)

When to measure Thyroid peroxidase antibody test (TPOAb)

• Subclinical hypothyroidism | Nodular thyroid | Recurrent miscarriage
  • Patients with subclinical hypothyroidism and TPOAb+ are almost twice as likely to progress to overt hypothyroidism (annual risk 4.3% vs 2.6%)

Pharmacologic Therapy

• Levothyroxine (Synthroid)
  • Alternative therapies
    • Combination levothyroxine/L-triiodothyronine | Desiccated thyroid hormone
  • ‘Thyroid enhancing’ dietary supplements e.g. iodine in iodine sufficient areas and nutraceuticals are NOT recommended or endorsed
• Starting dose
  • Overt hypothyroidism: 1.7 mg/kg
  • Young, healthy adults: Full replacement dose
  • Patients 50 to 60 years old
    • Without cardiovascular disease: 50 mcg
    • With cardiovascular disease: 12.5 to 25 mcg, and monitor for development of angina
  • Subclinical hypothyroidism: start with 25 to 75 mcg
• When to take levothyroxine
  • 30 to 60 minutes before breakfast or
  • Bedtime 4 hours after last meal
  • Take with water and avoid other medications that interfere with absorption (e.g. calcium carbonate, iron supplements, aluminum containing antacids)

When to Consider Treating Subclinical Hypothyroidism

• Symptoms consistent with hypothyroidism
• TPOAb+
• Cardiovascular disease/heart failure
• Improvement in atherosclerotic risk factors (lipids, endothelial function) with treatment

Monitoring Treatment and Endpoints

• Initially: Check TSH and Free T4 four to eight weeks after initiation or change in dose
• Once therapeutic dose achieved: Check TSH at 6 months and then yearly thereafter
• If patient has initiated or stopped a drug that interferes with absorption or metabolism of levothyroxine
  • Check TSH and Free T4 four to eight weeks
  • Examples: Estrogen or androgen | Carbamazepine | Phenobarbital | Phenytoin | Rifampin | Sertraline | Tyrosine kinase inhibitors
• Avoid overtreatment
  • Happens in 20% of patients treated with levothyroxine
  • Adverse consequences include cardiovascular (angina, atrial fibrillation), skeletal (osteoporosis), psychiatric
• Therapeutic endpoint: Normalization of TSH and Free T4

Normalization of a variety of clinical and metabolic endpoints including resting heart rate, serum cholesterol, anxiety level, sleep pattern, and menstrual cycle abnormalities…are further confirmatory findings that patients have been restored to a euthyroid state

• Therapeutic goal:  TSH 0.45 to 4.12

When to Consult an Endocrinologist

• Children/infants
• Difficulty achieving or maintaining euthyroid state
• Pregnancy or women planning conception
• Cardiac disease
• Structural thyroid abnormality (goiter, nodule)
• Comorbid endocrine disease
• Unusual constellation of thyroid function test results

Other Considerations

Do Not Use Thyroid Hormone to Treat

• Symptoms of hypothyroidism without biochemical confirmation (TSH/free T4)
• Obesity
• Depression

Adrenal Insufficiency

• Often associated with concurrent hypothyroidism
• Treat adrenal insufficiency with steroids first, then reassess thyroid function

Interruptions in Treatment

• If <6 weeks with no intervening cardiac event or significant weight loss, can resume full dose
• Preop setting
  • Hypothyroidism affects perioperative outcomes
  • Levothyroxine should be given preoperatively

Patients taking Biotin

• Hold the supplement for ≥2 days prior to TFT’s especially if taking more than 10 mg

Factors that Alter Thyroxine and Triiodothyronine Binding in Serum

• Increased T4-binding globulin (TBG)
  • Inherited | Pregnancy| Estrogens| Hepatitis| Porphyria| Heroin| Methadone| Mitotane| 5-FU| SERMS (e.g., tamoxifen, raloxifene)

• Decreased TBG
  • Inherited| Androgens| Anabolic steroids| Glucocorticoids| Severe Illness| Hepatic failure| Nephrosis| Nicotinic acid| L-Asparaginase

• Binding inhibitors
  • Salicylates| Furosemide| Free fatty acids| Phenytoin| Carbamazepine| NSAIDs (variable, transient)| Heparin

References:

Clinical Practice Guidelines for Hypothyroidism in Adults: Cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association

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