Hypothyroidism is a clinical condition characterized by inadequate production of thyroid hormones by the thyroid gland, resulting in a generalized reduction in metabolic activity. The most common causes include chronic autoimmune thyroiditis (Hashimoto thyroiditis), thyroid surgery, and radioactive iodine therapy. Less common causes include central hypothyroidism due to pituitary or hypothalamic disease, iodine deficiency, certain medications, and congenital disorders. If left untreated, hypothyroidism may lead to dyslipidaemia, cardiovascular disease, infertility, neurocognitive impairment, and, in severe cases, myxoedema coma. Early diagnosis and appropriate levothyroxine replacement therapy restore normal thyroid function and prevent long-term complications.

Risk Factors

• Female sex

• Increasing age

• Family history of thyroid disease

• Chronic autoimmune thyroiditis

• Previous thyroid surgery

• Previous radioactive iodine therapy

• Pregnancy and postpartum period

• Type 1 diabetes mellitus and other autoimmune diseases

• Down syndrome or Turner syndrome

• Neck irradiation

• Medications (e.g., lithium, amiodarone, interferon)

• Iodine deficiency or excess

Clinical Presentation

Symptoms depend on the degree and duration of thyroid hormone deficiency and usually develop gradually.

Common symptoms include:

• Fatigue

• Depression

• Memory loss

• Dry, rough skin

• Hair loss

• Constipation

• Hoarse voice

• Increased cholesterol levels

• Cold intolerance

• Weight gain

• Bradycardia

• Menstrual irregularities

• Infertility

• Puffy face

• Slow reflex relaxation

Severe untreated hypothyroidism may present as myxoedema coma, characterized by hypothermia, hypotension, hypoventilation, altered consciousness, and multiple organ dysfunction.

Diagnostic Criteria

Hypothyroidism is diagnosed by thyroid function testing.

Primary hypothyroidism

• Elevated TSH with low free T4 (FT4)

Subclinical hypothyroidism

• Elevated TSH with normal FT4

Central hypothyroidism

• Low or inappropriately normal TSH with low FT4

Clinical features supporting the diagnosis include:

• Fatigue

• Depression

• Memory impairment

• Dry, rough skin

• Hair loss

• Constipation

• Hoarse voice

• Hypercholesterolaemia

Investigations

Initial investigations include:

• Serum thyroid stimulating hormone (TSH)

• Free thyroxine (FT4)

Additional investigations when indicated:

• Thyroid peroxidase antibodies (TPO-Ab)

• Lipid profile

• Complete blood count

• Thyroid ultrasound (if goitre or autoimmune thyroiditis is suspected)

Management

Indications for Treatment

Levothyroxine therapy is recommended for:

• Persistent TSH >10 mU/L because of the increased risk of progression to overt hypothyroidism, congestive heart failure, cardiovascular disease, and mortality.

Consider treatment in patients with persistent TSH 4.5–10 mU/L, particularly when TSH is persistently >7 mU/L, if any of the following are present:

• Age younger than 65 years with increased cardiovascular risk

• Previous cardiovascular disease

• Hypertension

• Documented diastolic dysfunction

• Dyslipidaemia

• Diabetes mellitus

• Smoking

• Goitre

• Positive thyroid peroxidase antibodies

• Ultrasound evidence of autoimmune thyroiditis

• Pregnancy

• Infaired fertility

A therapeutic trial of levothyroxine may also be considered in symptomatic middle-aged patients. If symptoms improve significantly, treatment may be continued.

Treatment should also be considered in patients with persistent mildly elevated TSH (4.5–10 mU/L) together with positive thyroid antibodies and thyroid ultrasound findings consistent with autoimmune thyroiditis.

Pharmacological Management

Clinical (Overt) Hypothyroidism

Levothyroxine: 1.6–1.8 micrograms/kg/day based on ideal body weight.

Subclinical Hypothyroidism

Levothyroxine: 1.1–1.2 micrograms/kg/day.

Administration

• Take levothyroxine after at least 2 hours of fasting and 30 minutes before food intake.

• Alternatively, take at bedtime at least 3 hours after the evening meal.

• Young healthy adults with overt hypothyroidism may begin with full replacement doses.

• Routine combination therapy with levothyroxine and triiodothyronine (T3) is not recommended.

• Routine use of thyroid extracts, T3 monotherapy, compounded thyroid hormones, iodine-containing preparations, dietary supplements, and over-the-counter thyroid products is not recommended.

• Reassess and adjust the dose following major body weight changes, ageing, or pregnancy.

Monitoring

• Measure TSH 6–8 weeks after any levothyroxine dose adjustment.

• Once euthyroidism is achieved, monitor TSH annually throughout life.

• Target TSH: 0.2–4.0 mU/L.

• FT4 measurement may be useful during the early stages of treatment.

• In patients with central hypothyroidism, treatment should be guided by serum FT4, aiming for levels slightly above the mid-normal reference range.

• Allow 8–12 weeks for TSH equilibration after any dose adjustment before making further changes.

Management During Pregnancy

When elevated TSH is confirmed, measure FT4 to classify hypothyroidism:

• TSH 2.5–10.0 mU/L with normal FT4: Subclinical hypothyroidism

• TSH 2.5–10.0 mU/L with low FT4: Overt hypothyroidism

• TSH ≥10.0 mU/L: Overt hypothyroidism regardless of FT4 level

Women planning pregnancy should achieve euthyroidism before conception because maternal hypothyroidism is associated with impaired fetal neural development. Levothyroxine requirements commonly increase during pregnancy, and the dose may need to be doubled. Following delivery, the dose should usually be reduced to the pre-pregnancy requirement with subsequent thyroid function reassessment.

Prognosis

The prognosis of hypothyroidism is excellent when diagnosed early and treated appropriately with lifelong levothyroxine replacement. Most patients achieve complete resolution of symptoms and normal thyroid function with adequate therapy and regular monitoring. Untreated or inadequately treated hypothyroidism may lead to dyslipidaemia, cardiovascular disease, infertility, pregnancy complications, cognitive impairment, and, in severe cases, myxoedema coma, which carries a high mortality rate. Regular follow-up and appropriate dose adjustment during ageing, pregnancy, and major weight changes are essential for maintaining long-term euthyroidism.