Thyroid Hormone: Pathophysiology and Disease

Overview

Thyroid Metabolism and Function

Hormone Synthesis

1. Dietary iodine is reduced to iodide in the GI tract
2. Circulating iodide is actively taken up and concentrated in the thyroid gland
3. Iodide is bound to tyrosine residues to form iodotyrosines
4. After organification, monoiodotyrosine or diiodotyrosine is coupled enzymatically by thyroid peroxidase to form T3 or T4
5. Hormones attach to thyroglobulin protein and are stored as colloid in the gland
6. Release occurs via proteolysis from thyroglobulin, diffusing into the circulation

Regulation (HPT Axis)

• Hypothalamus produces thyrotropin-releasing hormone (TRH)
• TRH stimulates the anterior pituitary to produce TSH (thyrotropin)
• TSH maintains iodide uptake and the proteolytic release of thyroid hormone
• Excess iodide inhibits synthesis and secretion (Wolff-Chaikoff effect)
• Circulating thyroid hormone feeds back negatively to inhibit TRH and TSH

T4 and T3 Kinetics

Protein Binding

• Majority bound to thyroxine-binding globulin (TBG); smaller fraction to albumin and transthyretin
• Less than 0.1% is free, unbound hormone - this is the biologically active fraction
• Changes in binding protein concentrations profoundly affect total T3/T4 serum levels

Peripheral Metabolism

• T4 is metabolized by monodeiodination to either:
  • T3 (biologically active)
  • Reverse T3 (rT3) (biologically inactive)

Cardiovascular Effects (Key for Anesthesia)

• Thyroid hormone affects tissue responses to sympathetic stimuli
• Increases intrinsic contractile state of cardiac muscle
• Increases β-adrenergic receptor number
• Decreases cardiac α-adrenergic receptors
• Drugs affecting thyroid function: amiodarone, dopamine

Tests of Thyroid Function

Thyroid-Stimulating Hormone (TSH)

• Best first-line test - immunochemiluminometric assays are sensitive and specific
• Normal: 0.4 to 4.5 μIU/mL
• TSH >20 μIU/mL: primary hypothyroidism
• Depressed TSH: signals hyperthyroidism
• Subclinical hypothyroidism: elevated TSH with normal T4
• Low TSH in a clinically hypothyroid patient: pituitary or hypothalamic disease
• Goal of replacement therapy: normalize TSH
• TSH can be suppressed by: starvation, fever, stress, corticosteroids, dopamine, and severe illness

Serum Thyroxine (T4)

• T4 concentration is influenced by thyroid hormone protein-binding capacity
• Increase or decrease in TBG levels alters total T4 but not free T4
• A free T4 assay is preferred in patients with abnormal binding proteins (e.g., pregnancy, liver disease)

Serum Triiodothyronine (T3)

• Useful in diagnosing T3 thyrotoxicosis (elevated T3, normal T4)
• Low T3 can occur in: starvation, systemic illness, or with drugs (propylthiouracil, propranolol, glucocorticoids) that inhibit T4-to-T3 conversion

Tests for Assessing Thyroid Hormone Binding

• Free hormone levels can be estimated by multiplying total hormone level by the thyroid hormone binding ratio
• Calculated from the T3-resin uptake test

Hyperthyroidism

Causes (Table 47-2)

Clinical Features

• Weight loss, heat intolerance, tachycardia, tremor, anxiety
• Atrial fibrillation (most common arrhythmia), heart failure
• Exophthalmos (Graves disease)
• High cardiac output state

Treatment of Hyperthyroidism

• Inhibit iodide organification and thyroid peroxidase
• Propylthiouracil (PTU) also inhibits peripheral T4 → T3 conversion
• Take 6-8 weeks to achieve euthyroid state (existing hormone stores must be depleted)
• Toxic reactions: skin rash, nausea, fever, agranulocytosis, hepatitis, arthralgias

• Inhibits iodide organification and thyroid hormone release
• Reduces size and vascularity of hyperplastic gland
• Useful for emergency thyroid surgery preparation
• Antithyroid drugs must be started first before iodide (prevents paradoxical worsening of thyrotoxicosis)

• Attenuate excessive sympathetic manifestations
• Used in all hyperthyroid patients unless contraindicated
• Propranolol impairs peripheral T4 → T3 conversion over 1-2 weeks
• Propranolol (titrated) + potassium iodide (2-5 drops q8h) = standard preoperative regimen
• Preoperative preparation: 7 to 14 days
• Target heart rate: <90 bpm for emergency surgery
• β-Blockers do NOT prevent thyroid storm

• Reduce thyroid hormone secretion
• Reduce peripheral T4 → T3 conversion
• Used in severe thyrotoxicosis management

• Effective for thyrotoxicosis in non-pregnant patients
• Contraindicated in pregnancy (crosses placenta, can destroy fetal thyroid)
• Side effect: hypothyroidism in 10-60% in first year, +2%/year thereafter

Anesthetic Considerations - Hyperthyroidism

• Continue all antithyroid medications through the morning of surgery
• Goal: avoid tachycardia, hypertension, hyperthermia
• Heart failure from atrial fibrillation may improve with rate control, but LV dysfunction from hyperthyroidism may not respond to β-blockers alone
• Major risk: Thyroid storm

Thyroid Storm

Management (Table 47-3)

Hypothyroidism

Pathophysiology

Clinical Features

Diagnosis

• Elevated TSH (primary hypothyroidism)
• Low free T4
• Normal TSH with low T4 = secondary (pituitary/hypothalamic) disease

Treatment

• Levothyroxine (T4) oral replacement; goal is normalization of TSH
• Severely hypothyroid patients: start low, titrate slowly (risk of precipitating angina or arrhythmia in older patients)
• IV T4 or T3 used in myxedema coma

Anesthetic Considerations - Hypothyroidism

• Asymptomatic/mild hypothyroidism: does not significantly increase anesthetic risk; not a contraindication to surgery
• Moderate-to-severe hypothyroidism: should be corrected before elective surgery to prevent multisystem complications
• Risks: hypothermia, hypoglycemia, hypoventilation, hyponatremia, heart failure, heightened anesthetic sensitivity
• Addisonian crisis risk: coexisting adrenal insufficiency possible (Schmidt syndrome in autoimmune thyroiditis)

Myxedema Coma

• Severe hypothyroidism with altered consciousness, hypothermia, and hemodynamic compromise
• Management: IV thyroid hormone, glucocorticoids (before thyroid hormone to prevent adrenal crisis), supportive care

Thyroid Function in Critical Illness (Euthyroid Sick Syndrome)

• Critical illness alters thyroid hormone metabolism without true thyroid disease
• Low T3 levels (decreased T4 → T3 conversion), with rT3 elevated
• T4 and TSH may also be low in prolonged illness
• Low T3 correlates with severity of illness and mortality
• Drugs (e.g., dopamine) can depress thyroid function via central mechanisms
• Treatment with thyroid hormone in sick euthyroid patients is generally not recommended (no proven benefit)

Anesthesia for Thyroid Surgery

• Large thyroid mass can distort the upper airway - anticipate difficult intubation
• Obtain preoperative chest X-ray for tracheal deviation/narrowing
• CT scan of upper airway/trachea for better detail of airway compromise
• Inspiratory stridor or wheezing (especially supine) indicates airway compromise
• Awake fiberoptic intubation may be necessary
• Postoperative risks: hematoma (airway emergency), recurrent laryngeal nerve injury (hoarseness/stridor), hypoparathyroidism (hypocalcemia)

Key Points Summary (from Stoelting's)

1. The major risk in the poorly controlled thyrotoxic patient is thyroid storm - treat aggressively with β-blockers, iodide, and antithyroid drugs
2. Asymptomatic/mild hypothyroidism does not significantly increase anesthetic risk and is not a contraindication to surgery
3. Moderate-to-severe hypothyroidism should be corrected before surgery to prevent multisystem complications
4. Antithyroid medications should be continued through the morning of surgery
5. Preoperative β-blockade targets HR <90 bpm before emergency surgery in hyperthyroid patients
6. Radioactive iodine is contraindicated in pregnancy
7. Euthyroid sick syndrome in critical illness: low T3, elevated rT3 - thyroid hormone replacement generally not beneficial