Hypothyroidism

Hypothyroidism is a clinical syndrome resulting from a deficiency of thyroid hormones, with widespread organ-specific effects. In infants and children: slowing of growth and development with serious permanent consequences. In adults, clinical manifestations are due to thyroxine deficiency (T4) and insufficient cellular effects of T3: (1) slowing of cellular metabolism (2) development of interstitial edema due to delayed metabolism of glycosaminoglycans.

Pathophysiology

T4 is peripherally converted to the active form, T3. Majority of T3 comes from deiodination in the liver and is done on an as-needed basis - therefore the levels are difficult to interpret as a diagnostic test.

Classification and Etiology of Hypothyroidism

1. Transient
   1. Silent thyroiditis, including postpartum
   2. Subacute thyroiditis
   3. Withdrawal of supraphysiologic thyroxine treatment
2. Primary (thyroid gland)
   1. Chronic autoimmune thyroiditis (Hashimoto's): most common cause in the developed world
      1. Associated with TPO Ab, other autoimmune diseases (DM2, SLE, RA). More common in women, and younger people tend to have a goiter
   2. Thyroidectomy
   3. Neck radiation
   4. Radioiodine treatment
   5. Excessive iodine intake (Wolff-Chiakoff effect)
      1. amiodarone
      2. iodine contrast media
   6. Antithyroid drugs
   7. Lithium salts
   8. Environmental iodine deficiency
   9. Infiltrative diseases
   10. Congenital hypothyroidism
3. Secondary (hypopituitarism)
   1. Parasellar mass
   2. Inflammatory of infiltrative disease
   3. Vascular, traumatic, iatrogenic
   4. Sheehan syndrome
4. Tertiary (too little TRH release)

Clinical Features and Natural History of Disease

Outside of the scope of these notes.

Diagnosis of Hypothyroidism

Treatment

Long-Term Hormonal Replacement

• Levothyroxine (L-T4) monotherapy
  • Frequency: OD, qam or qhs, long half life so only take once a day. Just be consistent and pragmatic.
  • Absorption issues common with
    • Iron
    • Soy products (be careful in children on soy milk)
  • Dosage: ~1.6 mcg/kg/d (lean body mass) in adults, with less in elderly. For most adults this is 100 to 150 mcg/d. Since this is lean body mass, for obese patients consider using 1.4 mcg/kg/d
  • Titrate to TSH in the reference range (2-3 mIU/L),
    • In young healthy adults, start with a full replacement dose and target a low-normal TSH.
    • In older people (65+) titrate up slowly. Start with 25-50 mcg and move up by increments of 12.5-25 mcg. Target is high normal range.
    • Titrate via measuring TSH 4-8 weeks after start and after new therapies
    • Sensitive to generic/branding/formulation. May need to recheck TSH if preparation changes. Especially important with thyroid cancer that needs narrow ranges.
• Iodine products should not be used in regions with adequate iodine intake except in pregnant women
• Start cortisol first with coexisting adrenal insufficiency
  • This is because the half-life of the serum cortisol normalizes, and this can trigger an acute adrenal crisis with underlying adrenal insufficiency
• Monitoring of treatment via serum TSH should be done at ~6 weeks since last adjustment. If secondary or tertiary, use the FT4. Symptom resolution will lag behind T4 normalization by 2-3 months.
• Increasing the dose may be necessary with:
  • Oral LT4 malabsorption
  • Drugs that cause malabsorption --> space out by a few hours
  • Starting estrogen products (increases the TBG)