Endocrine: Hyperthyroidism

Hyperthyroidism & Diagnosis

Presentation

Thyroid Storm (Thyrotoxic Crisis)

Sudden Release of Large Amounts of Thyroid Hormone
Development is Independent of TSH Levels
Causes:
- Cessation of Thioamide Medication
- Severe Illness
- Trauma
- Thyroid Manipulation During Surgery
Often Have Previously Undiagnosed Graves’ Disease
Aspirin Can Exacerbate (Decreases Protein Binding to Thyroid Hormone – More Free-T3/T4)
High Mortality (8-25%)
- Most Common Cause of Death: High-Output Cardiac Failure

Causes

Graves’ Disease
Toxic Nodules
- Solitary Toxic Nodule
- Toxic Multinodular Goiter (Plummer Disease)
Jod-Basedow Phenomenon – Patient with Iodine Deficiency Suddenly Given Excess Iodine
Thyroiditis or “Hashitoxicosis” – Initial Hyperthyroidism Seen Prior to Development of Hypothyroidism
- *See Endocrine: Thyroiditis & Hypothyroidism
Amiodarone-Induced Thyrotoxicosis (AIT) – Type 1
- *See Endocrine: Thyroiditis & Hypothyroidism
Excess Exogenous Hormone Administration (Iatrogenic or Factitious)

Diagnosis

Initial Test: TSH (Low) & Free T4/T3
- TSH Has the Highest Sensitivity & Specificity
Next Step: Thyroid Receptor Antibodies, US and/or Radioactive Iodine Scan
Radioactive Iodine Scan:
- High Diffuse/Symmetric Uptake: Graves’ Disease
- High Asymmetric Uptake/Multiple Hot Nodules: Toxic Multinodular Goiter
- High Uptake in Single Hot Nodule: Solitary Toxic Nodule
- Minimal/No Uptake: Thyroiditis, Iodine-Induced or Excess Exogenous Hormone Administration
Suspicious or Nonfunctioning Nodules Require FNA

Exophthalmos ¹

Thyroid Scan ²

Pathophysiology

Treatment

Immediate Control of Symptomatic Thyrotoxicosis: β-Blockers
First-Line Management: Thioamides or Radioactive Iodine (RAI)
- If Primarily Treating with Thioamides – Treat for 12-18 Months
  - If Fails: Consider RAI or Thyroidectomy
Indications for Total/Near-Total Thyroidectomy:
- Suspicious Nodule (Most Common Reason)
- Noncompliant with Medication
- Planning Pregnancy in < 6 Months
- Other Indications for Cervical Surgery (Compressive Goiter, Parathyroidectomy, etc.)
- Low RAI Uptake
- Medication or RAI Failure
- Moderate-Severe Orbitopathy

Solitary Toxic Nodule/Adenoma

Toxic Multinodular Goiter (Plummer Disease)

Diffuse Hyperplasia of Thyroid Follicular Cells Independent of TSH
- Decreased TSH Causes Atrophy in Other Areas of the Thyroid
- Variations Cause Multiple Nodules
Second Most Common Cause of Hyperthyroidism
More Common in Areas with Low Iodine Intake
Most Common in Women

Treatment

Immediate Control of Symptomatic Thyrotoxicosis: β-Blockers
First-Line Management: Surgery or Radioactive Iodine (RAI)
- Surgery is Generally Preferred Unless Contraindicated (High-Risk, Elderly or Frail)
May Consider Conservative Management Only if Asymptomatic with Subclinical Hyperthyroidism
Antithyroid Medications are Generally Not Used for Toxic Nodules Unless Pregnant to Bridge for Surgery After Delivery

Antithyroid Medications (Thioamides)

Methimazole
- Mechanism: Inhibits TPO
- Generally the First-Line Choice Due to Hepatotoxicity of PTU
- Contraindications: Pregnancy (Risk Cretinism)
  - May Be Safe in Second/Third Trimester After Organogenesis
- Side Effects: Agranulocytosis
Propylthiouracil (PTU)
- Mechanism: Inhibits TPO & Peripheral Conversion of T4 to T3
- Safe in Pregnancy Mn
- Side Effects: Hepatotoxic & Agranulocytosis
Exophthalmos is Resistant to Thioamide Treatment

β-Blockers

Radioactive Iodine (RAI)

Sodium Iodide-131 (¹³¹I)
RAI is Taken into Thyroid Hormone Causing Ionizing Destruction of Thyroid Follicular Cells
Consider Pre-Treatment with Thioamides & β-Blockers to Prevent Transient Exacerbation
- Must Stop Thioamides 2-3 Days Before Treatment & Hold 2-3 Days After to Allow RAI Uptake
Contraindications:
- Thyroid Malignancy
- Pregnancy
- Lactation
- Children < 5 Years Old
- Moderate-Severe Orbitopathy/Exophthalmos (May Worsen)
Side Effects:
- Transient Hyperthyroidism Exacerbation
- Neck Pain
- Sialoadenitis

Thyroidectomy

Procedure:
- Graves’ Disease: Total/Near-Total Thyroidectomy
- Solitary Toxic Nodule: Lobectomy
- Toxic Multinodular Goiter: Total/Near-Total Thyroidectomy
Preoperative Antithyroid Medication:
- Preoperative Euthyroid State Can Prevent Thyroid Storm
- Indications:
  - Graves’ Disease: All Patients Should be Made Euthyroid Preoperatively
  - Toxic Nodules: Only Patients at High-Risk for Complications of Persistent Hyperthyroidism (Elderly or Cardiovascular Disease)
- Approach:
  - Thioamides, β-Blocker & Potassium Iodide for 7-14 Days Preoperatively
  - Lugol’s Solution (Saturated Solution of Potassium Iodide/SSKI)
    - Wolff-Chaikoff Effect: High Dose Iodine Inhibits TSH
    - Also Decreases Intraoperative Blood Loss (Debated & Recently Questioned)
    - Generally Only Used in Graves’ Disease, Not Toxic Nodules
During Pregnancy:
- Used Only if Antithyroid Medication First Failed or Contraindicated
- Best Time: Second Trimester
  - First Trimester: Risk Fetal Development
  - Third Trimester: Risk Preterm Labor

Antithyroid Medications (Thioamides) in Pregnancy