Approach

Although classical overt primary hypothyroidism presents with a constellation of physical symptoms and signs confirmed by an elevated thyroid-stimulating hormone (TSH), many patients have no symptoms or vague symptoms that are not specific to hypothyroidism.[1]​​[50]

Clinical evaluation

Symptoms of hypothyroidism include lethargy, fatigue, depression, change in voice, cold intolerance, menstrual irregularity, constipation, and weight gain.​[1][2]​​[51]​​ Physical signs may include slow speech and movement; coarse, dry skin; eyelid oedema; bradycardia; hypertension; and delayed tendon reflexes.[1]​​[52][53][54]​​​​ Goitre is more common in areas of iodine deficiency, and may also be present in autoimmune (Hashimoto) thyroiditis.[12][17][25]​​​

Diagnostic testing

TSH is the most sensitive and specific for diagnosing primary hypothyroidism. It should be ordered in the initial work-up if there is a clinical suspicion of hypothyroidism.[1]​ Normal TSH range is 0.4 to 4.0 mIU/L (there may be some variation in laboratory norms). TSH levels are elevated in primary hypothyroidism, although in sub-clinical disease levels may only be mildly elevated. Thyroid function test results can be affected by acute illness, and so should be avoided during an acute illness (unless the acute illness is suspected to be due to thyroid dysfunction).[55]

Free thyroxine (T4) should then be obtained to quantify the degree of hypothyroidism or if suspicion of disorders other than primary hypothyroidism.[1]​ Normal free T4 range is 9.00 to 23.12 picomol/L (0.8 to 1.8 nanograms/dL). In cases where the TSH is only mildly elevated, the patient is not symptomatic and the serum free T4 is normal, the diagnosis is sub-clinical hypothyroidism.[3]

Auto-antibody testing is not necessary for diagnosis, but helps distinguish autoimmune primary hypothyroidism.[1]​ It is recommended that pregnant women with TSH concentrations >2.5 mIU/L should be evaluated for antithyroid peroxidase antibody status.[56]

It is prudent to obtain TSH, full blood count, and fasting blood glucose in patients who present with non-specific fatigue and weight gain. One study found patients with hypothyroidism had a higher risk of anaemia compared with euthyroid participants, and suggested that a reduced thyroid function at baseline increased the risk of developing anaemia during study follow-up; however, the underlying mechanisms of this link is unclear.[57]

Total cholesterol and low density lipoprotein, concentrations may be elevated in hypothyroidism.[2]​​

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