Lucan · Conditions

Hypothyroidism

Australian guidance: eTG Endocrinology — Hypothyroidism + RACGP

1. Definition and epidemiology

Hypothyroidism is a clinical state of inadequate thyroid hormone production causing reduced metabolic activity across all organ systems. It affects approximately 4 to 5% of the Australian population, with overt hypothyroidism (raised TSH plus low free T4) present in around 1 to 2% and subclinical hypothyroidism (raised TSH with normal free T4) accounting for the remainder. Prevalence is substantially higher in women and increases with age, with women over 60 years carrying the greatest burden of disease.

2. Pathophysiology

The thyroid gland normally secretes thyroxine (T4) and tri-iodothyronine (T3) under hypothalamic-pituitary control via the thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH) axis (Robbins Ch 24). Hashimoto thyroiditis, the dominant aetiology in Australia and New Zealand, is an organ-specific autoimmune condition in which CD4-positive T-helper cells mount a response against thyroid peroxidase (TPO), thyroglobulin, and the TSH receptor, driving lymphocytic infiltration, follicular destruction, and progressive fibrous replacement of the gland. The resulting fall in circulating T4 removes negative feedback on the pituitary, leading to rising TSH as compensatory stimulation. Once follicular reserve is sufficiently depleted, T4 falls below the reference range and overt hypothyroidism is established. Additional aetiologies include radioiodine ablation and thyroidectomy for hyperthyroidism or malignancy, external beam radiation to the neck, iodine deficiency (uncommon in Australia but relevant in pregnancy), and drug-induced thyroid suppression (amiodarone, lithium, interferon). In the subclinical state, residual follicular mass maintains T4 within range despite elevated TSH, representing early compensated gland failure.

3. Clinical presentation and diagnostic criteria

Hypothyroidism produces a constellation of features reflecting slowed metabolism and catecholamine hyposensitivity. Classical symptoms include fatigue, cold intolerance, weight gain, constipation, bradycardia, dry skin, hair thinning or loss, periorbital oedema, and cognitive slowing colloquially described as "brain fog." Deeper deficiency produces myxoedema characterised by non-pitting oedema of the face and extremities, husky voice, carpal tunnel syndrome, delayed relaxation of deep tendon reflexes (hung reflex), and in severe cases myxoedema coma. Menorrhagia and subfertility are common in premenopausal women. Dyslipidaemia (raised LDL cholesterol, hypertriglyceridaemia) and hyponatraemia may be the presenting biochemical finding. Neonatal or early childhood hypothyroidism (cretinism) results in irreversible intellectual disability if untreated.

Diagnostic criteria per eTG and RACGP: - Overt hypothyroidism: TSH above the laboratory reference range AND free T4 (FT4) below the reference range, OR TSH above 10 mIU/L regardless of FT4 level. - Subclinical hypothyroidism: TSH above the reference range with FT4 within the normal range.

4. Investigations and AU-specific cutoffs

The investigation sequence is as follows:

1. Serum TSH: the single best first-line test; a normal TSH reliably excludes primary hypothyroidism. AU laboratory reference ranges typically use 0.4 to 4.0 mIU/L for non-pregnant adults.
2. Free T4: reflex-ordered when TSH is elevated to distinguish overt from subclinical disease. A TSH above 10 mIU/L is treated as overt regardless of the FT4 result.
3. Anti-TPO antibodies: confirm autoimmune aetiology (Hashimoto thyroiditis) and assist risk stratification; anti-TPO positivity in subclinical hypothyroidism predicts progression to overt disease at roughly 5% per year.
4. Thyroid ultrasound: not required for diagnosis but indicated when a goitre or nodule is palpated to assess structural pathology.
5. Fasting lipid profile: raised LDL and triglycerides are common and typically reverse with adequate replacement.
6. Full blood count: macrocytic anaemia may co-exist due to associated pernicious anaemia or folate deficiency.
7. Sodium: hyponatraemia from inappropriate ADH secretion occurs in severe hypothyroidism.

In pregnancy, trimester-specific reference ranges for TSH must be applied; local laboratory ranges are preferred. Where unavailable, RANZCOG recommends using an upper limit of 4 mIU/L throughout pregnancy as a practical threshold. First-trimester TSH is physiologically suppressed by beta-hCG cross-reactivity at the TSH receptor, so the non-pregnant upper limit should not be applied in early gestation.

5. Management

Management is guided by eTG Endocrinology and RACGP guidance and stratified by disease severity.

Overt hypothyroidism requires treatment with levothyroxine (LT4) in all patients regardless of symptom burden, because of the cardiovascular, neurological, and metabolic consequences of untreated disease. The starting dose in otherwise healthy adults is 1.6 micrograms per kilogram per day orally, taken 30 to 60 minutes before food or other medications to maximise absorption. Elderly patients and those with ischaemic heart disease should begin at 25 micrograms per day with incremental increases every 4 to 6 weeks to avoid precipitating angina or arrhythmia. The treatment target is a TSH within the lower half of the reference range (approximately 0.5 to 2.5 mIU/L) for most adults; TSH is rechecked 6 to 8 weeks after any dose adjustment.

Subclinical hypothyroidism management is individualised. Treatment is generally recommended when TSH exceeds 10 mIU/L, when symptoms are present and attributable to thyroid dysfunction, or in women who are pregnant or planning pregnancy. For TSH values between 4 and 10 mIU/L in an asymptomatic patient, observation with annual TSH monitoring is acceptable. Anti-TPO positivity strengthens the case for treatment given the higher risk of progression.

In pregnancy, overt hypothyroidism must be treated promptly. Women on pre-existing levothyroxine commonly require a 30 to 50% dose increase from early in the first trimester, achievable by taking two additional doses per week. TSH should be monitored at least once per trimester, with the treatment goal being TSH in the lower half of the trimester-specific reference range. RANZCOG does not recommend treating subclinical hypothyroidism in pregnancy, as high-quality RCT evidence involving over 100,000 women has not demonstrated maternal or neonatal benefit from thyroxine treatment in this setting.

6. Pharmacology and AU PBS notes

Levothyroxine sodium (LT4) is the sole first-line agent and the PBS-listed standard of care for hypothyroidism in Australia.

AU brand names include: Eutroxsig (Aspen Pharmacare), Oroxine (Sigma). Both are available in 50 microgram and 100 microgram scored tablets. Dose titration uses combinations of these strengths (e.g. 75 mcg = one 50 mcg plus half of a 100 mcg tablet).

PBS listing: levothyroxine is listed on the Pharmaceutical Benefits Scheme (PBS) for hypothyroidism without streamlined authority code; it is a general benefit item available to all patients with a confirmed diagnosis. No authority is required.

Absorption notes: LT4 absorption is impaired by calcium supplements, iron tablets, cholestyramine, antacids, proton pump inhibitors, and soy-based foods. These should be separated from LT4 by at least 4 hours.

Liothyronine (LT3) is not PBS-listed in Australia and its routine use is not endorsed by current AU guidelines. Combination LT4/LT3 therapy lacks evidence of superiority over LT4 monotherapy and is not recommended as standard practice.

Iodine supplementation: NHMRC recommends 150 micrograms of iodine daily for all women who are pregnant, planning pregnancy, or breastfeeding, as the fetus and breastfed infant depend on adequate maternal iodine for thyroid hormone synthesis. This is provided in most AU pregnancy multivitamin preparations.

7. Complications and monitoring

Untreated or undertreated hypothyroidism carries significant morbidity. Cardiovascular complications include atherogenic dyslipidaemia, diastolic dysfunction, pericardial effusion, and a two-fold increase in coronary artery disease risk. Neuropsychiatric complications include cognitive impairment, depression, and peripheral neuropathy. Infertility and pregnancy loss are associated with overt hypothyroidism; adequately treated hypothyroidism in pregnancy is not associated with adverse maternal or neonatal outcomes. Myxoedema coma is a rare but life-threatening decompensation triggered by physiological stressors such as sepsis, cold exposure, or surgery, requiring intensive care, IV levothyroxine, and IV hydrocortisone (to cover concurrent adrenal insufficiency).

Monitoring schedule once on stable replacement: - TSH every 6 months for the first year after initiation, then annually once stable. - Fasting lipid profile annually until normalised on replacement. - Thyroid function every trimester in pregnancy; also check within the first trimester of each new pregnancy in known hypothyroid women. - Anti-TPO positive patients without overt disease on observation: TSH annually, with low threshold to treat if TSH trends upward or symptoms develop. - Screen for co-existing autoimmune conditions: type 1 diabetes (fasting glucose annually), coeliac disease (anti-tissue transglutaminase IgA at diagnosis), pernicious anaemia (B12 if macrocytosis present).

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.