Week 3: Hyperthyroidism

Question 1

Etiologies of hyperthyroidism, based on elevated or suppressed RAIU

Answer 1

1. Elevated RAIU (radioactive iodine uptake)
   - Graves’ disease
   - toxic multinodular goiter
   - toxic adenoma
   - TSH secreting pituitary tumor
   - hydatidform mole
   - choriocarcinoma
2. Suppressed RAIU
   - exogenous T4/T3
   - subacute thyroiditis
   - postpartum thyroiditis
   - painless thyroiditis
   - exogenous iodides
   - radiation thyroiditis
   - metastatic follicular cancer
   - struma ovari

Question 2

Metabolic adaptation to hyperthyroidism

Answer 2

1. increase in O2 consumption and heat generation (increase basal metabolic rate)
   - increase in Na/K ATPase activity
   - fatty acid turnover
   - myosin and Ca ATPase activity
   - increase number and sensitivity of beta adrenergic response
2. increase heart rate and cardiac output
   - b1 and T3
3. peripheral vasodilation
   - b2 and T3

Question 3

Symptoms of hyperthyroidism

Answer 3

• nervousness and anxiety
• heat intolerance and sweating
• increase appetite and weight loss
• palpitations and SOB
• muscle weakness
• easy fatiguability
• sleep disturbance
• increase frequency of bowel movements

Question 4

Signs of hyperthyroidism

Answer 4

• restless and rapid rate of speech
• warm, moist, smooth skin
• dynamic precordium with supra ventricular arrhythmias
• muscle weakness
• fine tremors
• widened pulse pressure
• examine for eye disease (graves): bulging eyes, EOM-inferior and media rectus dysfxn, conjunctivitis, edema
• examine for pretibial myxedema

Question 5

epidemiology and Pathophysiology of grave’s disease

Answer 5

• 5:1 female to male, usually around reproductive years
• genetic predisposition ( HLA-DR3 and HLA B8), and inciting event leads to thyroid injury
• thyroid expresses class II antigens on cell surface. abnormal antigen presentation on follicular cell precipitates immune response and production of IgG. Th2 dominant response.
• TSI: thyroid stimulating immunoglobulini binds to and stimulates TSH receptor, producing glandular growth and excess secretion of T3
• -leads to hyperthyroidism, pretibial myxedema, and opthalmopathy

Question 6

Features of Grave’s Disease

Answer 6

1. Goiter, usually hyperthyroid
2. Opthalmopathy
3. Pretibial myxedema (infiltrative dermopathy)

Question 7

Pathogenesis of Graves’ opthalmopathy

Answer 7

• orbital preadipocytes mature into adipocytes that express TSH receptors
• increase in orbital fatty tissue
• activated T cells within orbit react with local TSH receptors to produce cytokines
• g-INF, TNF-b, Il-1b stimulate glycosaminoglycan deposition as well as fibroblast proliferation
• leads to proptosis, EOM enlargement and dysfunction, periorbital congestion

Question 8

Laboratory findings in Graves’ disease

Answer 8

• elevated T4 and T3 (T3: T4 is 20:1)
• suppressed TSH levels (<0.01)
• positive anti-TPO antibody.
• RAIU elevated with diffuse uptake

Question 9

Therapy of hyperthyroidism

Answer 9

1. Acute
   - block thyroid hormone synthesis with thioamide drugs (PTU and methimazole/tapazole)
   - reduce adrenergic symptoms with beta blocker: propranolol or atenolol (selective)
2. Chronic
   - long term remission with anti-thyroid drugs in up to 50% of patients
   - 131I ablation
   - surgery

Question 10

Antithyroid drugs

Answer 10

• treat 12-18months
• repeat TFTs in 6-8 weeks after start. If patient is compliment, should take no more than 4 months of therapy
  1. Methimazole (MMI)
• inhibits thyroid peroxidase
• no effect on T4 to T3
• one a day dosing
• use this first unless pregnant (PTU drug of choice in first trimester), or allergic
  2. Propylthiouracil (PTU)
• inhibits thyroid peroxidase
• inhibits T4 to T3 mediated by type 1 5’-deiodinase
• 2-3x daily

Question 11

Adverse effects with PTU and MMI

Answer 11

• skin reaction
• cholestatic hepatitis
• agranulocytosis: if fever and sore throat, do CBC
• pregnancy: both can cross placenta and can depress fetal thyroid gland, don’t use in first trimester.

Question 12

Other treatments for Graves with failure of antithyroid medications

Answer 12

1. Radioactive iodide
   - indications: unlikely to remit with thionamides, allergy to thionamides, lack of patience
   - avoid during pregnancy
2. Surgery

Question 13

Subacute thyroiditis

Answer 13

• etiology: viral, associated with HLA Bw35
• symptoms: viral symptoms, tender thyroid, thyrotoxicosis,
• low RAIU, elevated T3, T4, suppressed serum TSH
• Rx: beta blockers for symptoms. No role for anti thyroid drugs. NSAIDs, oral corticosteroids, L-T4 during hypothyroid phase

Question 14

Pattern of illness for subacute thyroiditis

Answer 14

• 0-4 weeks: hyperthyroid phase
• 4-12 weeks: hypothyroid phase: decreased T4, elevated TSH, variable RAIU
• 12+ weeks: recovery phase. Normal thyroid function

Question 15

Post partum thyroiditis

Answer 15

• 8% in US
• autoimmune pathogenesis, associated with HLA B,D
• patients with Type 1 DM, hx of autoimmune disease are at highest risk
• presents with hypothyroid, hyperthyroid, or both. May or may not have goiter
• Rx with beta blocker
• 20% will remain permanently hypothyroid with any episode