Hypothyroidism

AETIOLOGY OF HYPOTHYROIDISM

1. Iodine Deficiency

• Most common global cause
• Uncommon in Australia due to adequate dietary iodine intake

2. Autoimmune Thyroiditis

• Hashimoto thyroiditis (chronic lymphocytic thyroiditis)
  – Most common cause in Australia

3. Thyroiditis (Hypothyroid Phase)

• May be permanent or transient
• Includes:
  • Post-viral thyroiditis
  • Autoimmune thyroiditis (e.g. Hashimoto)
  • Subacute (de Quervain) thyroiditis
  • Silent thyroiditis
  • Postpartum thyroiditis
  • Early post-ablation thyroiditis

May be preceded by:

• Viral infection
• Pregnancy
• Radioiodine therapy

Suggestive signs:

• Enlarged, tender thyroid (e.g. subacute thyroiditis)

4. Drug-Induced Hypothyroidism

• Carbimazole (CBZ) / Propylthiouracil (PTU)
• Lithium
• Radioiodine therapy (RAI)
• Amiodarone

5. Infiltrative and Granulomatous Diseases

• Riedel’s thyroiditis
• Scleroderma
• Tuberculosis
• Haemochromatosis

6. Congenital / Neonatal Causes

• Thyroid agenesis or ectopia
• Inherited enzyme defects in thyroid hormone synthesis
• Transplacental TSH receptor-blocking antibodies
• Maternal medication exposure during pregnancy
• Family history of thyroid dysfunction

7. Post-ablative or Surgical

• Radioiodine ablation
• Thyroidectomy
• Neck irradiation (external beam)

Central (Secondary / Tertiary) Hypothyroidism

Definition: Inadequate biologically active TSH owing to pituitary (secondary) or hypothalamic (tertiary) disease. Prevalence ≈ 1 : 1 000 of all hypothyroidism cases.

Why adrenal cover matters– Thyrotroph failure often co-exists with ACTH deficiency. Starting thyroxine first accelerates cortisol clearance and can precipitate adrenal crisis. Always exclude or empirically cover for secondary adrenal insufficiency if cortisol is low or undefined.

Group	Examples (common first)
Pituitary tumours / mass effect	• Non-functioning pituitary macro-adenoma (most common acquired cause) • Craniopharyngioma, meningioma, metastatic cancer, Rathke cleft cyst • Rare functional tumour: TSH-oma (gives ↑ TSH + ↑ FT4, not low FT4)
Surgery / Radiotherapy / SRS	• Trans-sphenoidal surgery, external-beam or proton therapy to sellar/parasellar region
Vascular / Traumatic	• Sheehan syndrome (post-partum pituitary infarction) • Pituitary apoplexy • Traumatic brain injury, aneurysm rupture
Inflammatory / Infiltrative / Infection	• Auto-immune or checkpoint-inhibitor hypophysitis • Sarcoidosis, Langerhans-cell histiocytosis, TB, syphilis, haemochromatosis
Congenital / Genetic	• PROP1, POU1F1, IGSF1, TSH-β or TRH-R mutations • Septo-optic dysplasia, pituitary-stalk interruption syndrome
Iatrogenic / Drugs	• High-dose glucocorticoids, dopamine agonists and somatostatin analogues can suppress TSH but rarely cause permanent central hypothyroidism; checkpoint-inhibitor hypophysitis increasingly recognised.

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CLINICAL FEATURES

• Highly variable, depending on:
  • Severity of hypothyroidism
  • Rate of onset (gradual vs abrupt)

Typical Presentation

• Insidious onset in autoimmune thyroiditis (e.g. Hashimoto)
• Symptoms may be subtle or nonspecific for years

Spectrum of Disease

• Ranges from:
  • Subclinical hypothyroidism
  • To overt hypothyroidism
  • To myxoedema coma (rare but life-threatening)

Symptom-Function Discordance

• Many symptoms (e.g. fatigue, cold intolerance, weight gain) are non-specific
• Hypothyroidism should be confirmed biochemically before initiating therapy
• Thyroxine supplementation is not recommended in euthyroid individuals with non-specific symptoms

Appearance

Symptom	Mechanism
Puffy, pale facies	Myxoedema (mucopolysaccharide accumulation in dermis → water retention) and vasoconstriction (↓ cutaneous perfusion)
Dry, brittle hair / Sparse eyebrows	↓ Thyroid hormone → ↓ hair follicle turnover & atrophy of pilosebaceous units
Dry, cool skin	↓ Eccrine gland activity and ↓ cutaneous blood flow
Thickened, brittle nails	Slowed nail matrix turnover and reduced perfusion
Myxoedema	non-pitting oedema (e.g. face, hands, lower limbs) Decreased Thyroid Hormone → Fibroblast Activation In hypothyroidism, low levels of T3 and T4 stimulate fibroblasts, especially in the dermis and subcutaneous tissue. These fibroblasts overproduce hydrophilic glycosaminoglycans (GAGs)—mainly hyaluronic acid and chondroitin sulfate. GAG Accumulation → Osmotic Fluid Retention GAGs are highly hydrophilic and bind water in the interstitial space. This leads to non-pitting oedema, unlike typical oedema where water shifts with pressure. Reduced Lymphatic Drainage Hypothyroidism also impairs lymphatic clearance, further contributing to fluid accumulation. Face: puffiness, particularly around eyes Hands and feet: thickened, coarse skin Larynx: deep, hoarse voice Tongue: macroglossia Lower limbs: bilateral non-pitting oedema (often mistaken for cardiac failure) Myxoedema Coma: – A rare, life-threatening complication of severe, untreated hypothyroidism – Features: hypothermia, hypotension, bradycardia, hypoventilation, altered mental status – Pathophysiology involves extreme fluid retention, metabolic slowing, and CNS depression.

Energy and Metabolism

Symptom	Mechanism
Cold intolerance	↓ Basal metabolic rate and impaired thermogenesis (↓ uncoupling protein activity in mitochondria)
Weight gain	Fluid retention (myxoedema) + ↓ lipolysis + ↓ metabolic rate
Fatigue	↓ Cellular ATP production, ↓ oxygen delivery, ↑ sleep disturbance

Nervous System

Symptom	Mechanism
Headache	Possibly from fluid retention (↑ intracranial pressure), sleep apnoea, or hypometabolism
Paraesthesias / Carpal tunnel syndrome	Glycosaminoglycan deposition → nerve compression (median nerve in carpal tunnel)
Cerebellar ataxia	Rare; proposed due to demyelination, fluid shifts, or autoimmune cerebellar involvement
Delayed deep tendon reflexes	↓ Sodium-potassium ATPase activity → impaired muscle contraction-relaxation cycle (notably the relaxation phase)

Cognition / Psychiatry

Symptom	Mechanism
Reduced attention / Memory loss	↓ Cerebral metabolism and neurotransmitter imbalance (↓ serotonin, norepinephrine)
Depression	Central hypothyroidism → ↓ serotonin & dopamine activity in CNS; common in autoimmune thyroiditis (esp. Hashimoto’s)

Cardiovascular

Symptom	Mechanism
Bradycardia	↓ Beta-adrenergic receptor expression and ↓ intrinsic pacemaker activity
Diastolic hypertension	↑ Systemic vascular resistance (SVR) due to ↓ vasodilation and ↑ arterial stiffness
Pericardial effusion	↑ Capillary permeability + ↓ lymphatic drainage (from myxoedema)
Decreased exercise tolerance	Combination of bradycardia, low cardiac output, and skeletal muscle dysfunction

Musculoskeletal

Symptom	Mechanism
Myalgias	Impaired glycogenolysis → muscle energy deficit; also ↑ muscle enzyme levels (e.g. CK)
Arthralgias	Synovial thickening and fluid retention; sometimes coexists with autoimmune arthritis (e.g. RA)

Gastrointestinal

Symptom	Mechanism
Anorexia	Slowed gastric emptying, reduced taste/smell, low metabolic demand
Constipation	↓ Gut motility due to autonomic dysfunction and ↓ smooth muscle activity

Reproductive System

Symptom	Mechanism
Menstrual irregularities / Menorrhagia	Altered GnRH pulsatility → anovulation; ↑ TRH also stimulates prolactin → inhibits ovulation
Infertility	Anovulatory cycles, luteal phase defects, ↑ prolactin; thyroid hormones essential for normal reproductive axis function

Clinical History and exam

Domain	Essential Questions / Details
Presenting symptoms	• Hypothyroid – fatigue, weight ↑, cold intolerance, constipation, menorrhagia, dry skin, hair loss, depression, bradycardia symptoms • Hyperthyroid – weight ↓, heat intolerance, palpitations, tremor, diarrhoea, anxiety/insomnia, oligomenorrhoea, muscle weakness • Compressive – dysphagia, dyspnoea, orthopnoea, stridor, “tight collar,” neck discomfort • Voice change – hoarseness (possible RLN involvement / malignancy)
Timeline & triggers	Onset, speed of growth, episodic vs persistent, recent illness, pregnancy/post-partum, iodinated contrast, Amiodarone/Lithium
Associated autoimmune disease	T1DM, coeliac, vitiligo, pernicious anaemia, Addison disease, alopecia areata
Drug & toxin exposure	Amiodarone, Lithium, immune-checkpoint inhibitors, anti-thyroid drugs, iodine supplements/kelp, prior neck irradiation
Obstetric / gynaecologic	Pre-existing thyroid disease, infertility, miscarriage, postpartum thyroiditis; current pregnancy (ask gestation)
Past thyroid interventions	Surgery, radio-iodine, external beam radiotherapy, previous TFT pattern
Family history	Autoimmune thyroid disease, goitre, medullary / papillary carcinoma, MEN-2, familial non-medullary thyroid cancer
Social & diet	Region of iodine deficiency/excess, diet (seaweed), smoking (increases Graves’ orbitopathy risk)
Red-flag “B” symptoms	Rapid growth, night sweats, unexplained weight loss, pain, haemoptysis

Targeted Thyroid Examination

Step	Findings & Their Significance
General survey	Body habitus, agitation vs lethargy, myxoedematous facies, hyperactivity, cachexia
Vitals	Pulse rate/rhythm (AF, tachy, brady), BP (wide pulse pressure vs diastolic HTN), temp (sub-febrile in thyrotoxicosis)
Hands	Fine postural tremor (hyper), warm moist palms vs cool dry skin (hypo), onycholysis, palmar erythema; delayed ankle jerk relaxation (hypo)
Face / Eyes	Lid lag, stare, exophthalmos, chemosis (Graves); periorbital puffiness, loss of outer ⅓ eyebrows (hypo)
Neck inspection	Scars, visible goitre nodularity, retrosternal fullness, venous distension on arm-raising (Pemberton sign)
Palpation of thyroid	Size, symmetry, consistency (smooth, rubbery, firm, hard), tenderness (sub-acute thyroiditis), nodules, thrill/bruit (toxic goitre)
Dynamic tests	• Swallow: gland & nodules rise • Tongue-protrusion: thyroglossal cyst rises • Pemberton: facial congestion/stridor suggests retrosternal extension
Lymph nodes	Central & lateral cervical chains (malignancy metastasis, Hashimoto nodes)
Voice / RLN	Ask patient to speak / say “eee” – hoarse, breathy voice ⇒ recurrent laryngeal nerve palsy
Cardiovascular	AF, tachyarrhythmia, flow murmur (↑ CO), S3 (thyrotoxic cardiomyopathy); bradycardia, pericardial effusion signs (hypo)
Respiratory	Stridor, tracheal deviation, obstructive symptoms with large goitre
Neuromuscular	Proximal myopathy, hyper-reflexia vs slowed relaxing phase of reflexes, carpal tunnel signs
Skin & extremities	Pretibial myxoedema, vitiligo, hyperhidrosis, dry coarse skin, brittle nails

Red-Flag Examination Findings (Urgent Review / Referral)

Finding	Possible Cause
Rapidly enlarging painful neck mass	Thyroid lymphoma, sub-acute thyroiditis, anaplastic Ca
Hard fixed nodule, cervical nodes, hoarseness	Thyroid carcinoma with invasion/RLN palsy
Goitre + facial plethora/stridor on arm raising (Pemberton +)	Retrosternal goitre causing SVC / tracheal compression
Thyrotoxic crisis signs (fever, delirium, tachy-arrhythmia)	Thyroid storm – medical emergency

Investigations:

• TSH (Thyroid-Stimulating Hormone)
  • Produced by Anterior pituitary, Stimulates the thyroid gland to produce T4 and T3.
• T4 (Thyroxine)
  • Produced by: Thyroid gland
  • Main circulating thyroid hormone (90%)
    • T4 better reflects thyroid gland output.
    • as T3 has a shorter half-life (~1 day) compared to T4 (~7 days)
    • and T3 is more susceptible to acute illness, stress, drugs, and diurnal variation.
  • Weakly active; acts as a prohormone.
  • Converted peripherally into:
    • T3 (active)
    • Reverse T3 (inactive)
  • Types:
    • Total T4: Includes both bound and free forms.
    • Free T4 (FT4): Unbound, biologically active form.
      • Preferred test in clinical practice.→ used in both hypo- and hyperthyroidism.
• T3 (Triiodothyronine)
  • More potent than T4 (3–4×)
  • Shorter half-life
  • Derived mainly from peripheral conversion of T4.
  • Responsible for most physiological effects of thyroid hormone.
  • Types:
    • Total T3: Bound + free.
    • Free T3 (FT3): Unbound, active form.
    • Useful in T3 toxicosis and hyperthyroidism.

1 Initial screening

Test	Why / when	Interpretation trigger
TSH (single best screen)	Order if – symptoms – risk factors (e.g. T1DM, autoimmune disease, lithium/amiodarone use, pregnancy/planning), or – incidental biochemical clues (↑ lipids, anaemia, hyponatraemia).	If TSH above lab reference range proceed to step 2.

2 Confirmatory thyroid-function tests

Scenario (first result)	Follow-up test(s)	When to repeat	Likely diagnosis
↑ TSH ≥ 10 mIU/L or marked symptoms	• Add FT4 now → ↑ TSH / ↓ FT4 • Repeat TSH ± FT4	≥ 6 weeks (steady-state)	Overt primary hypothyroidism (thyroid failure) Start or titrate levothyroxine (check anti-TPO)
↑ TSH 4 – 10 mIU/L with normal FT4	• Repeat TSH ± FT4 • Add anti-TPO Ab	8 – 12 weeks (2–3 mths) – if ↑ TSH + normal FT4 persists its →→	Sub-clinical primary hypothyroidism Treat if TSH ≥ 10 mIU/L, symptoms, pregnancy, or +anti-TPO
Normal / low TSH + low ↓ FT4	Morning cortisol ± short Synacthen (treat adrenal insufficiency first). Full pituitary panel: prolactin, LH/FSH, testosterone/estradiol, IGF-1. MRI pituitary with contrast (look for macro-adenoma, hypophysitis, apoplexy).	As guided by endocrinology	Central (secondary) hypothyroidism or non-thyroidal illness Assess pituitary–adrenal axis; correct cortisol first
↑ TSH + ↑ FT4	Exclude – TSH-secreting adenoma – thyroid-hormone resistance – assay interference Check compliance (large “catch-up” thyroxine doses)		Needs endocrine referral ± pituitary imaging

Note: TSH half-life ≈ 7 days; re-testing before four weeks can give misleading results.

3 Auto-antibodies

Test	Indication	How to use the result
Anti-TPO Ab	• Persistent sub-clinical pattern • Pregnancy/planning pregnancy • Strong clinical suspicion with equivocal TFTs	Positivity confirms autoimmune thyroiditis (≈ 95 % Hashimoto).
Anti-TG Ab	Limited to differentiated thyroid-cancer follow-up.	Not useful in routine hypothyroid work-up.

4 When (and when not) to image

Imaging	Indication	Guideline stance
Thyroid ultrasound	Palpable goitre asymmetric enlargement discrete nodule cervical lymphadenopathy.	Routine hypothyroidism alone is not an indication
Radionuclide scan	Functional assessment of a nodule or toxic picture – never for uncomplicated primary hypothyroidism.
MRI pituitary	Central pattern (normal/low TSH + low FT4) or other hypopituitarism features.

5 Baseline / adjunct tests

Purpose	Tests
Exclude mimics & screen comorbidity	FBC (macrocytosis in B12 deficiency) lipids fasting glucose/HbA1c CMP (hyponatraemia) CK (myopathy) coeliac serology
Pregnancy	Use trimester-specific TSH cut-offs; do not delay treatment if TSH > 4 mIU/L.

6 When to treat or refer

Situation	Action
TSH ≥ 10 mIU/L (any FT4)	Start levothyroxine unless frail/elderly – consider 12.5–25 µg start.
TSH 4–10 mIU/L plus symptoms, positive TPO, pregnancy/planning, goitre, or progressive rise	Consider treatment; otherwise monitor 6–12 monthly.
Central, uncertain cause, or atypical biochemical patterns	Endocrinology referral.

Quick Pocket Rule

1. TSH first → if raised, add FT4.
2. Repeat in ≥ 6 weeks to prove persistence (8–12 w if mild).
3. Add anti-TPO once sub-clinical confirmed.
4. Image only if you can feel it or suspect central disease.

MANAGEMENT

1. Initial steps

Biochemical pattern (confirm on repeat ≥ 6 weeks)	Start levothyroxine?	Nuances & Australian guideline details
↑ TSH + ↓ FT4  (overt primary hypothyroidism)	Yes – in virtually every adult (dose-adjust for frail/elderly, CHD).	RACGP & Therapeutic Guidelines recommend prompt replacement once the diagnosis is biochemically confirmed. www1.racgp.org.au
TSH > 10 mIU/L + normal FT4  (sub-clinical)	Yes – treatment is advised even if asymptomatic.	Meta-analyses show higher risk of heart failure events and progression; benefit of therapy outweighs risk. www1.racgp.org.au
TSH 4 – 10 mIU/L + normal FT4  (sub-clinical)	Usually watchful waiting, but consider a trial if any of the following are present: • Typical hypothyroid symptoms • Pregnancy, planning pregnancy or infertility work-up • Goitre or nodules • Progressive TSH rise on serial tests • Cardiovascular disease or dyslipidaemia • Persistently positive anti-TPO plus TSH drifting upward (eg > 8 mIU/L).	Anti-TPO positivity alone is not an automatic green light; it flags higher progression risk. RACGP “First-Do-No-Harm” advises repeat TFTs at 3 mths, then 6 mths, then yearly, and start therapy if TSH continues to rise or symptoms emerge. racgp.org.au airgp.co.uk
Normal / low TSH + ↓ FT4  (central pattern)	Do not start thyroxine yet. 1️⃣ Check morning cortisol; give hydrocortisone if adrenal insufficiency suspected. 2️⃣ Request full pituitary panel + contrast MRI. 3️⃣ Refer to endocrinology for coordinated hormone replacement.	Starting thyroxine first can precipitate an adrenal crisis in ACTH-deficient patients. airgp.co.uk
↑ TSH + ↑ FT4	Unusual: exclude lab interference, TSH-secreting adenoma, thyroid-hormone resistance, or erratic “catch-up” dosing. Endocrine referral ± pituitary MRI.	airgp.co.uk

• Screen for precipitating or associated factors:
  • iodine excess/deficiency, amiodarone, lithium, thyroiditis, pituitary disease, adrenal insufficiency (rule out Addison’s before LT4 to avoid adrenal crisis).
• Baseline tests:
  • fT4, TSH, anti-TPO (guides prognosis), ± ECG if older/ischaemic heart disease.

2. Levothyroxine (LT4) initiation

Population	Starting dose	Notes
Healthy adults	50–100 µg once daily (≈1.6 µg/kg/day full replacement)	Round to nearest tablet take fasting with water 30–60 min before breakfast (or ≥3 h after last meal at bedtime).
≥65 y or IHD	25–50 µg daily (12.5 µg if very frail/active angina)	Slow titration prevents ischaemia.
Pregnancy (known hypothyroidism)	Immediately ↑ total weekly dose by ~30 % (e.g. +2 extra tablets/week) on positive pregnancy test	Target trimester TSH below: 1st 0.1–2.5 mIU/L. 2nd 0.2–3.0 mIU/L. 3rd 0.3–3.0 mIU/L.
Poor compliance (specialist)	Supervised weekly total dose may be considered	Endocrinologist supervision only

Tablet storage:

• Oroxine® and Eutroxsig® need refrigeration, Store 2 – 8 °C, Once a blister strip is removed from the fridge it may be kept below 25 °C for ≤ 14 days, then discard the remainder..
• Eltroxin®, Levoxine®, APO-Levothyroxine® are true room-temperature products (≤ 25 °C, dry, out of sunlight).

3. Monitoring & titration

1. Re-check TSH ± fT4 at 4–6 weeks after any dose change.
   • Adjust by 12.5–25 µg/day aiming for TSH within reference range (lower half if persistent symptoms). racgp.org.au racgp.org.au
2. Steady-state interval: ≥6–8 weeks before further adjustment (LT4 t½ ≈ 7 days).
3. Maintenance review: once stable, TSH every 6–12 months or sooner if: weight change, new drugs affecting LT4, pregnancy plans, gastrointestinal disease. insightplus.mja.com.au

Target ranges

• Non-pregnant: 0.4–4.0 mIU/L (aim 0.5–2.5 if symptomatic).
• Pregnancy: trimester-specific (see above); refer if TSH > 4 mIU/L or difficult control. seslhd.health.nsw.gov.au

4. Drug & food interactions

• Empty-stomach dosing is recommended because food, beverages, and common supplements substantially reduce and unpredictably vary levothyroxine absorption, leading to volatile TSH control and potential under- or over-treatment.

• A large RCT showed equivalent TSH control when LT4 was taken at least 3 h after the last meal at night.
• This works because the stomach is again empty.

↓ Absorption (separate ≥4 h)	↑ Clearance / dose-requirement
Calcium carbonate ferrous sulfate multivitamins phosphate binders bile-acid sequestrants PPI coffee/espresso	OCP/estrogen carbamazepine phenytoin rifampicin sertraline tyrosine-kinase inhibitors

5. Special groups & situations

• Malabsorption: coeliac, IBD, short-bowel, lactose intolerance, H. pylori gastritis – may need high doses or liquid formulation. insightplus.mja.com.au
• Sub-clinical hypothyroidism (non-pregnant):
  • Treat if TSH > 10 mIU/L.
  • Consider 25–50 µg trial if TSH 5–10 mIU/L and symptoms, +TPO, or goitre; otherwise monitor 6–12 mo. www1.racgp.org.auracgp.org.au
• Iodine supplementation: all pregnant & breastfeeding women 150 µg/day unless contraindicated. racgp.org.au

6. Referral triggers (Endocrinology)

• Age ≤ 18 y, pregnancy, cardiac or pituitary disease
• Structural thyroid disease (goitre, nodule)
• Persistent symptoms or abnormal TSH despite adequate dosing
• Combined endocrine disease, difficulty achieving pregnancy targets. racgp.org.au

7. Patient counselling points

• Take LT4 on an empty stomach, same time daily; avoid food/coffee for ≥30 min.
• Keep tablets in original blister, < 25 °C, dry place.
• Alert GP if weight change, new meds, or planning pregnancy.

AACE guidelines for indications for referral to a specialist in cases of hypothyroidism:

• Patients aged 18 years or less
• Patients unresponsive to therapy
• Pregnant patients
• Cardiac patients
• Presence of goitre, nodule, or other structural changes in the thyroid gland
• Presence of other endocrine disease

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Pregnant Patients

🔹 Iodine Supplementation

• All pregnant women should take iodine 150 micrograms/day, unless contraindicated.

🔹 TSH Changes in Pregnancy

• bHCG has thyrotropic effects, lowering TSH reference ranges in pregnancy:
  • 1st trimester: TSH 0.1–2.5 mIU/L
  • 2nd trimester: TSH 0.2–3.0 mIU/L
  • 3rd trimester: TSH 0.3–3.0 mIU/L

Refer to endocrinology if TSH is outside trimester-specific reference ranges.

Overt Hypothyroidism in Pregnancy

• Prevalence: ~0.3–0.5%
• Diagnostic criteria:
  • TSH >2.5 mIU/L with low free T4, or
  • TSH >10 mIU/L, regardless of T4 level
• Risks:
  • Miscarriage, preeclampsia, preterm delivery
  • Impaired fetal neurocognitive development
• Management:
  • Start levothyroxine
  • Aim: TSH within trimester-specific reference range
  • Monitor TSH every 4 weeks

Subclinical Hypothyroidism (SCH) in Pregnancy

• Prevalence: 2–2.5%
• Diagnostic criteria:
  • TSH 2.5–10 mIU/L with normal free T4
• Risks:
  • Associated with obstetric complications (less clear for neurocognitive risk)
• Management:
  • Either:
    • Start levothyroxine to normalise TSH, or
    • Monitor TSH 4-weekly
  • Check TPO antibodies while awaiting specialist input

Known Hypothyroidism Prior to Pregnancy

• Increase levothyroxine dose as soon as pregnancy is confirmed:
  • Typical: increase by 2 extra tablets per week or by 25–30%
• Aim: TSH <2.5 mIU/L
• Monitor TFTs every 4 weeks

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Subclinical Hypothyroidism in Non-Pregnant Women

🔹 Definition

• Persistently elevated TSH with normal T4
• Affects:
  • 4–8% of general population
  • 15–18% of women >60 years

🔹 Progression Risk

• Annual risk of progression to overt hypothyroidism: 4–18%
• Higher risk if:
  • TPO antibodies positive (2× risk)
  • Goitre present
  • Higher baseline TSH
  • History of:
    • Radioiodine ablation
    • Neck irradiation
    • Chronic lithium use

🔹 Potential Harms of Untreated SCH

• Progression to overt hypothyroidism
• Cardiovascular disease, dyslipidaemia
• Neuropsychiatric effects

🔹 Treatment Recommendations (per AFP)

TSH Range	Additional Findings	Suggested Management
>10 mIU/L	–	Start levothyroxine
5–10 mIU/L	Symptomatic	Consider 3–6 month trial of thyroxine
5–10 mIU/L	Anti-TPO+ or goitre present	Thyroxine therapy is a reasonable option

• Initial dose: 25–50 µg/day
• Target TSH: 1.0–3.0 mIU/L
• Monitoring:
  • Repeat TSH at 6–8 weeks post-initiation or dose change
  • Annual monitoring once stable