Endocrine
The treatment is settled: levothyroxine, titrated to TSH. What remains contested is the TSH target, subclinical hypothyroidism thresholds, and the T4/T3 combination question that comes up in almost every chronic hypothyroid consultation.
Scope: Primary hypothyroidism in non-pregnant adults. Includes subclinical hypothyroidism. Excludes central hypothyroidism, hypothyroidism in pregnancy, and thyroid cancer follow-up.
Where they agree
Where they diverge
Comparison
| Domain | NZ - NZF / HealthPathways | AU - RACP / Endocrine Society | International - BTA 2019 / ATA 2014 |
|---|---|---|---|
| Diagnosis | TSH is the primary test. If TSH is elevated, confirm with free T4. Positive TPO antibodies (anti-thyroid peroxidase) support autoimmune aetiology (Hashimoto's thyroiditis) but do not change management. TSH reference range varies by laboratory (typically 0.4-4.5 mIU/L). Overt hypothyroidism: elevated TSH + low free T4. Subclinical hypothyroidism: elevated TSH + normal free T4. Do not test free T4 in isolation as a screening test. | Consistent approach. RACP recommends TSH as first-line. Thyroid antibodies (TPO) add prognostic value in subclinical hypothyroidism (higher progression risk with positive antibodies) but do not alter initial management. Same TSH thresholds as NZ. | Consistent. TSH is the most sensitive indicator of thyroid status. Free T3 has no routine role in diagnosing primary hypothyroidism. BTA 2019 emphasises TSH as the gold standard; ATA 2014 similarly recommends TSH-based diagnosis. |
| Treatment - levothyroxine initiation | Eltroxin (levothyroxine sodium) is the NZ brand; NZF recommends consistency of formulation when possible. Starting dose: 50-100 mcg daily in young, healthy adults; 25-50 mcg in adults >60 or with cardiac disease; 12.5-25 mcg in severe or longstanding hypothyroidism or significant cardiac history (titrate slowly over months). Take on an empty stomach, 30-60 minutes before food, consistently. Avoid co-administration with calcium, iron, PPIs (reduce absorption). PHARMAC funds levothyroxine.Funded | Eutroxsig is the main Australian brand. Same starting doses and titration principles as NZ. Same absorption considerations. PBS-funded. | BTA 2019 / ATA 2014: 1.5-1.6 mcg/kg/day as a target dose in otherwise healthy adults. Lower in elderly. Titration principle: check TSH at 6-8 weeks, adjust by 12.5-25 mcg increments. Same absorption guidance. Consistent formulation recommended. |
| TSH target - highlight row | NZF and HealthPathways recommend titrating to keep TSH within the laboratory reference range (approximately 0.4-4.5 mIU/L). No NZ guideline specifies a tighter lower-range target. In practice, most NZ GPs aim for TSH around 1.0-2.5 mIU/L for symptomatic benefit, but this is not mandated. For elderly patients (≥70): accept TSH in the upper-normal range (2.0-4.5); do not chase a low-normal TSH in this group. | RACP / Endocrine Society of Australia broadly consistent with maintaining TSH within the reference range. Some specialist guidance suggests lower half of range for symptomatic patients. For elderly: avoid aggressive TSH lowering to prevent AF and cardiac risk. | BTA 2019: Target TSH in the lower half of the reference range (0.4-2.0 mIU/L) for most treated patients. For patients ≥65, particularly post-RAI or post-thyroidectomy: accept TSH 1.0-5.0 mIU/L. ATA 2014: keep TSH within the normal reference range; no specific target within range. |
| Subclinical hypothyroidism (TSH 4.5-10) - highlight row | Treat if: symptomatic AND TSH persistently elevated on two measurements 3 months apart AND patient under 65. In asymptomatic patients: monitor every 6-12 months (30-50% normalise spontaneously). Do not treat asymptomatic subclinical hypothyroidism in adults ≥65 - the TRUST trial showed no benefit and potential harm. TPO antibody positivity increases progression risk (~2-4%/year); may justify closer monitoring. TSH >10 mIU/L: treat regardless of symptoms or age. | Consistent with international consensus. RACP: treat TSH >10 or if symptomatic with TSH 4.5-10 in younger adults; avoid in asymptomatic elderly. Similar evidence-based caution about harm in elderly. | BTA 2019 / ATA 2014: TSH >10 = treat (Class recommendation, strong). TSH 4.5-10 = individualise; trial of treatment if symptomatic; avoid in asymptomatic elderly. The 2019 BTA guidelines provide the clearest age-stratified framework. |
| T4/T3 combination therapy - highlight row | Liothyronine (T3) is funded under PHARMAC Special Authority - requires endocrinologist initiation for patients with persistent symptoms on adequate levothyroxine therapy after exclusion of other causes. NOT for routine use. A small number of patients do appear to have genuine benefit from combination therapy; if referred to endocrinology, T3 access through SA is possible. Do not initiate T3 from primary care without endocrine input.SA - specialist only | T3 available but TGA-restricted; not routinely recommended. Similar to NZ - endocrinologist-initiated in selected patients only. | BTA 2019: Combination T4/T3 therapy should NOT be used routinely. A trial may be considered in patients with persistent symptoms despite adequate T4 titration, after excluding depression, anaemia, B12 deficiency, coeliac disease, and adrenal insufficiency. If trialled: use sustained-release T3 if available; titrate carefully; reassess after 3 months; if no benefit, discontinue. ATA 2014: similar cautious stance - some patients may be genetic poor converters of T4 to T3 (DIO2 polymorphism). Evidence base is limited; individualised decision with specialist support. |
| Monitoring frequency | Recheck TSH 6-8 weeks after each dose change. Once stable on a consistent dose, annual TSH monitoring is appropriate for most patients. More frequent monitoring may be needed in acute illness, pregnancy planning, or if symptoms change. Absorption issues (PPI use, coeliac disease) may require more frequent review. | Same as NZ. RACP: 6-8 weeks after dose changes; then annual review once stable. No difference from NZ guidance. | BTA 2019 / ATA 2014: Check TSH at 6-8 weeks after each dose adjustment and 6-12 months after initial therapy started. Once stable, annual TSH is standard. More frequent monitoring for symptoms, life changes, or co-medication changes. |
| Special situations: pregnancy and other states | Pregnancy: refer to obstetric medicine or endocrinology; TSH targets are tighter in each trimester (first trimester TSH <2.5 mIU/L); levothyroxine dose typically increases 25-30% in first trimester. Amiodarone-induced hypothyroidism: treat with levothyroxine; continue amiodarone if cardiologically necessary. Post-thyroidectomy: endocrine or surgical follow-up; doses often higher. Adrenal insufficiency: always exclude before treating hypothyroidism in central hypothyroidism - replacing T4 without cortisol can precipitate an adrenal crisis. | Consistent with NZ on pregnancy and amiodarone management. Similar referral pathways for specialist situations. | BTA 2019 / ATA 2014: Consistent approach to pregnancy (tighter TSH targets, dose increase expected). Amiodarone-induced: treat with levothyroxine. Post-thyroidectomy: specialist follow-up. Adrenal assessment critical in central hypothyroidism. |
NZ clinical context
Practical NZ prescribing, the T4/T3 question, and what to do with the symptomatic patient on optimal T4
The most common clinical problem is the patient with TSH in the normal range who still feels unwell. This is genuinely difficult. Before attributing symptoms to thyroid disease, exclude: depression, anaemia, iron deficiency (even without anaemia), B12 deficiency, coeliac disease, sleep disorder, and perimenopause. Do not escalate levothyroxine dose to achieve a low-normal TSH in a patient who is euthyroid - this risks atrial fibrillation and bone loss.
Levothyroxine is poorly absorbed when taken with food, coffee, calcium supplements, iron, cholestyramine, or PPIs. A patient on long-term PPI who has rising TSH often simply needs a timing change (take T4 on an empty stomach, 1 hour before morning coffee). Document timing advice at every review. The dose may not need to increase; the absorption may just need optimising.
If symptoms persist after TSH is optimised and other causes excluded, the question of T3 supplementation arises. The evidence is inconsistent: some high-quality RCTs show no benefit; some show improvement in quality of life in a subgroup. Genetic testing for DIO2 polymorphisms (which affect T4-T3 conversion) is not routinely available in NZ. If T3 is being considered: refer to endocrinology. Liothyronine under Special Authority is accessible through this route. Do not initiate T3 from primary care.
Use the lowest effective dose in patients ≥70. Iatrogenic subclinical thyrotoxicosis (suppressed TSH) in elderly patients increases atrial fibrillation risk by approximately 3-fold and increases osteoporotic fracture risk. Check TSH at least annually and reduce dose if TSH is persistently suppressed. A TSH of 2.0-4.5 mIU/L in an octogenarian is appropriate and may cause less harm than aggressive normalisation.
Generic levothyroxine from the same manufacturer is equivalent to branded Eltroxin, but brand switching should be avoided without rechecking TSH. If a patient's TSH becomes unstable and you suspect a formulation change, check whether the pharmacy has switched manufacturer. If yes, retest TSH 6-8 weeks after stabilisation on the new brand.
Bottom line for NZ practice
What this means in the consulting room
Sources