hypothyroidism

clinical identity

Pathological slowing of metabolic processes due to thyroid hormone deficiency. The exam focuses on who to screen (Canada vs USA), when to treat subclinical disease, assay interference, and the obstetrical algorithms.

clinical features

history

• General: Fatigue, cold intolerance, weight gain (despite reduced appetite), lethargy.
• Neuro/Psych: Poor concentration, memory impairment, depression, delayed relaxation of reflexes (especially ankle jerk), carpal tunnel syndrome.
• CV: Bradycardia, dyspnoea on exertion, mild hypertension.
• GI: Constipation.
• Derm/Hair: Dry, coarse skin; brittle nails; hair loss (including lateral eyebrows).
• Reproductive: Menorrhagia, infertility, reduced libido.

examination

• General: Puffy face (periorbital oedema), hoarse voice, pallor.
• Neck: Goitre (diffuse or nodular).
• Skin: Dry, rough, cool skin. Non-pitting oedema (myxoedema).
• Neuro: Slowed movements, ataxia (rare), delayed relaxation of deep tendon reflexes.

screening & diagnosis

canadian screening guidelines (CTFPHC 2019)

• Asymptomatic Adults: Recommends AGAINST routine screening (TSH measurement) in primary care.
• Indication to test: “Case finding” only—must have symptoms, goitre, or high-risk factors (strong family history, autoimmune disease, past head/neck radiation, drugs like Amiodarone/Lithium)

diagnosis

• Overt Hypothyroidism: $\uparrow$ TSH + $\downarrow$ fT4.
• Subclinical Hypothyroidism (SCH): $\uparrow$ TSH + Normal fT4.

assay interference (discordant labs)

Suspect when clinical picture does not match labs (e.g., TSH > 50 but patient asymptomatic, or TSH $\uparrow$ with normal/high fT4).

• Heterophile Antibodies (HAMA): Human Anti-Mouse Antibodies interfere with the assay sandwich.
  • Risk Factor: Exposure to lab/farm animals or veterinary work.
• Rheumatoid Factor: Can cross-link assay antibodies (reported, though anecdotally less common).
• Macro-TSH: TSH complexed with IgG/IgA (biologically inactive, but measured by assay).
• Workup:
  • 1st Step: Serial Dilution (loss of linearity suggests interference).
  • Other steps: PEG precipitation (for Macro-TSH), use of heterophile blocking tubes.

subclinical hypothyroidism (SCH): Who needs Levothyroxine?

treatment indications (non-pregnant)

1. TSH > 10 mIU/L: Treat everyone (risk of progression to overt disease/CV risk).
2. TSH < 10 mIU/L: Generally monitor, but consider trial of Rx if:
   • Significant symptoms (fatigue, constipation, cold intolerance).
   • Goitre.
   • Anti-TPO Antibody Positive (predicts higher rate of progression).
   • Pregnancy/planning pregnancy (see below).

evidence: treating the elderly

TRUST Trial (Stott et al. NEJM 2017): In adults >65 years with SCH (TSH 4.6–19.9), treatment with levothyroxine provided NO benefit in symptoms or cognitive function. Supports more conservative approach to mild SCH in the elderly; “normal” TSH shifts higher with age.

management: general principles

• Standard of Care: Levothyroxine (T4) Monotherapy.
  • Dosing: Full replacement = 1.6 µg/kg/day.
  • Titration: Check TSH every 4–6 weeks until stable. Goal TSH 0.5–4.0 mIU/L.
• Elderly/Cardiac Disease: “Start low, go slow.”
  • Start 12.5–50 µg/day to avoid precipitating angina/AFib.
• Administration: Empty stomach, water only, 60 mins before food. Separate from Calcium/Iron/PPIs by 4 hours.

alternative therapies (ATA 2014)

• Liothyronine (T3) / Combination Therapy:
  • Recommendation: AGAINST routine use. No consistent evidence of benefit over T4 monotherapy.
  • Risks: T3 peaks may cause palpitations/skeletal/cardiac toxicity.
• Desiccated Thyroid (Animal Extract):
  • Recommendation: AGAINST. Non-physiologic T4:T3 ratio (4:1 vs human 14:1) $\to$ risk of iatrogenic thyrotoxicosis.

management: pregnancy

Based on ATA 2017 Guidelines. Fetal neurodevelopment relies on maternal T4 (especially T1).

1. pre-existing hypothyroidism

• The “2-Pill Rule”: Increase Levothyroxine dose by 20–30% (2 extra pills/week) immediately upon positive pregnancy test.
• Goal: Maintain TSH < 2.5 mIU/L (or within trimester-specific range).
• Post-partum: Return to pre-pregnancy dose immediately after delivery.

2. subclinical hypothyroidism diagnosed in pregnancy

Treatment decision depends on TSH level and Antibody status (Anti-TPO).

TSH Level	Anti-TPO Negative (-)	Anti-TPO Positive (+)
< 2.5 mIU/L	No Treatment	No Treatment
2.5 – 4.0 mIU/L	No Treatment	Consider Treatment (ATA: weak rec)
4.0 – 10.0 mIU/L	Consider Treatment	RECOMMEND Treatment
> 10.0 mIU/L	Treat	Treat

iodine supplements

While iodine is crucial in pregnancy, women on Levothyroxine do NOT need iodine supplementation (the pill provides the substrate).

myxoedema coma

Life-threatening decompensated hypothyroidism. Mortality 20–50%.

• Triggers: Sepsis, cold exposure, drugs (sedatives), MI, medication non-adherence.
• Clinical: Altered LOC (coma), Hypothermia (<35.5°C), Hypotension, Bradycardia, Hypoventilation, Hyponatremia.

management protocol

Diagnosis is clinical. Do NOT wait for labs to treat.

1. Corticosteroids (FIRST LINE):
   • Hydrocortisone 100 mg IV q8h.
   • Reason: Must cover for co-existing Adrenal Insufficiency (Schmidt’s syndrome) or pituitary failure before giving thyroid hormone (which accelerates cortisol metabolism $\to$ adrenal crisis).
2. Thyroid Hormone Replacement:
   • Levothyroxine (T4): IV Loading dose 200–400 µg $\times$ 1.
     • Note: IV dose is ~75% of PO dose. Use lower end (200 µg) if cardiac history/elderly.
     • Follow with 1.6 µg/kg/day daily (IV then PO).
   • Liothyronine (T3): IV Loading dose 5–20 µg $\times$ 1.
     • Reason: Peripheral conversion of T4$o$T3 is impaired in sick states. T3 crosses blood-brain barrier faster.
     • Follow with 2.5–10 µg q8h.
     • Caution: Avoid/reduce T3 if history of arrhythmia or ischemia.
3. Supportive:
   • Passive Warming: Blankets. Avoid active external warming (vasodilation $\to$ shock).
   • Fluids/Pressors: Often fluid refractory; may need alpha-agonists.
   • Ventilation: Mechanical support often required.