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][26]

Clinical evaluation

Symptoms of hypothyroidism include lethargy, fatigue, depression, change in voice, cold intolerance, menstrual irregularity, constipation, and weight gain.[1] Physical signs include slow speech and movement; coarse, dry skin; eyelid oedema; bradycardia; hypertension; and delayed tendon reflexes.[1][27][28]​ Goitre is generally uncommon. It is more common in areas of iodine deficiency.[1][9] Goitre may also be present in autoimmune (Hashimoto) thyroiditis.[15]​​

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.

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.[2]

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 thyroid peroxidase antibody (TPOAb) status.[29]

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 the study follow-up; however, the underlying mechanisms of this link is unclear.[30]

Total cholesterol and low density lipoprotein, concentrations may be elevated in hypothyroidism.[1]

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