Physiology

The thyroid gland is responsible for regulating the overall metabolic tone of an individuals body. This is accomplished through the release of two hormones, T3 and T4. T4 is converted to T3 in target tissues, and the two hormones are responsible for regulating growth and development, BMR, thermoregulation, catecholamine sensitivity, and protein synthesis rate. Thyroid peroxidase is used to place I^- ions onto tyrosine residues of the protein thyroglobulin in the thyroid follicle. These tyrosine are then linked to form T3 and T4 trapped in thyroglobulin. Upon stimulation of the thyroid from TSH (released in response to TRH), the follicular cells uptake iodinated thyroglobulin and cleave off T3 and T4, releasing it to the blood stream to be transported by thyroxine-binding globulin and transthyretin, along with a small portion transported by albumin. Approximately 0.04% of T4 in plasma is free, as the proteins have a high binding affinity, and the reservoir of T3 and T4 in the body lasts approximately 2-3 months.

Labs

	Purpose	Low	High	Units
TSH	Pituitary function	0.5	4.5	mIU/L
FT4	Thyroid hormone output	0.7	1.9	ng/dL

• ATgA
  • Anti-thyroglublin Igs
  • (+) in autoimmune thyroid disease
• TPO-Ab
  • Anti-thyroperoxidase Igs
  • More sensitive than ATgA
• TRAb
  • Thyroid receptor stimulating Ig
  • Diagnostic of Grave’s Disease

Hyperthyroidism

Causes

• Excessive iodine supplementation
  • Amiodarone
    • 12mg Iodine / 400mg
  • Interferon
  • Li
  • Iodinated compounds
• Grave’s Disease
• Thyroid producing adenoma
• Subacute thyroiditis
  • Damaged follicles release hormone

SSx

• Hyperthermia
• Weight loss
• Increased HR
• Exophthalmos
• Warm, sweaty skin
• Increased appetite
• Hyperglycemia
• Decreased lipids

Treatment

• Thioamides
  • 20-30mg PTU ≈ 1mg methimazole
  • Methimazole
    • Initial Dose
      • Mild: 10-20mg QD
      • Moderate: 30-40mg QD
      • Severe: 60mg QD
    • Maintenance: 5-15mg QD NTE 60mg QD
    • No renal adjustment
    • Safe in 2nd and 3rd trimester and during lactation
  • Propylthiouracil (PTU)
    • Initial: 50-150mg TID
    • Maintenance: 100-200mg QD NTE 1200mg QD
    • Renal adjustment
    • Safe in 1st trimester only
    • Not for use when breastfeeding
    • Black box warning for hepatic failure
    • Inhibits conversion of T4 to T3, making it preferable for thyroid storm
  • SEs
    • N / V
    • Maculopapular rash
      • Give diphenhydramine
    • Wheals, hives, SOB
      • 50% cross reactivity
      • Treat w/ RAI or surgery, no more thioamides
    • Agranulocytosis
    • Hepatitis
      • LFTs at baseline and PRN
• Radioactive Iodine
  • Absolute CI in pregnancy, lactation, and planning pregnancy w/i 4-6mo
  • Avoid physical contact > 5d after dose
• Surgical thyroidectomy
• Adjunctive β-Blockers
  • HR < 90
  • Short term only
  • Propranolol 10-40mg Q6H PRN
    • Partially blocks T4 into T3
  • Metoprolol 25-50mg QID
  • Atenolol 25-100mg QD or BID
  • Can consider Non-DHP CCBs as well
  • Avoid ISA β-blockers

Monitoring

• TSH at baseline, q4-8wks until stable / first 3-4mo, then q3-4mo
• TSH q4-6wks after thioamide D/C for 1st 3-4mo, then yearly

Hypothyroidism

Causes

• Amiodarone
• Li
• Interferons
• Bexarotene
• Hashimoto’s Thyroiditis (autoimmune condition killing thyroid)
• Radiation exposure
• Iodine Deficiency
• Congenital conditions
• Pituitary damage

SSx

• Pale, cool skin
• Bradycardia
• Lethargy
• Decreased appetite
• Wt gain
• Hypoglycemia
• Increased lipids

Treatment

• Thyroid hormone replacement
• Levothyroxine (T4, Tirosint, Synthroid, Levoxyl, Unithroid)
  • First line
  • Take on empty stomach 60min before meal or 3hr after
  • See dosing table below
• Liothyronine (T3, Cytomel, Triostat)
  • Rapid absorption can cause cardiac toxicities
  • More expensive
  • BID-QID dosing
• Liotrix (T4 and T3, Thyrolar)
  • 4:1 T4:T3
  • Expensive
  • Fluctuating and often elevated T3
• Desiccated Thyroid (Armour Thyroid, Nature Thyroid, NP Thyroid)
  • Can cause allergy
  • No reason to use

Pt Characteristics	Dosing	Comment
Healthy Adult	1.6 mcg/kg QD (IBW in obese) Average dose ≈ 100mcg QD Increase 12.5-25mcg q6-8wks PRN	TSH after reaching steady state (≈ 1wk)
> 65yo	< 1.6 mcg/kg QD Start 25-50 mcg QD Increase 12.5-25 mcg q6-8wks PRN as tolerated	Decreased clearance
CVD (CAD, Angina, etc)	12.5-25 mcg QD Increase 12.5-25 mcg q4-6wks PRN as tolerated	Can precipitate an MI, severe angina, or other CV event
Hyperthyroidism > 1yr	25mcg QD Titrate by 25 mcg q4-6wks	Sensitive to CV effects Steady state may be delayed due to decreased clearance
Pregnancy	May need to increase dose by 45% Adjust by 25 mcg every trimester and check TSH Resume pre-pregnancy dose immediately after delivery and check TSH in 6-8wks	Maintain FSH and FT4 in ULN to prevent fetal hypothyroidism

Monitoring

• TSH and FT4 q6-8wks after any dose change or until stablized, then q3-6mo x1yr, then yearly
• SSx should resolve in 2-3wks (Max 4-6wks)
  • Anemia, hair, and skin changes may take 6mo