Hyperthyroidism

Question 1

Etiologies of hyperthyroidism

Answer 1

• Graves disease
• Toxic multinodular goiter (GOF mutations in TSH receptor-> autonomous T4/T3 producing cells)
• Iodine-induced thyrotoxicosis: jod-basedow (iodine supplementation in iodine deficient goiters leads to hyperthyroidism b/c there’s increased machinery and now fuel to make the hormones)
• Autonomous hyper functioning nodule
• Subacute thyroiditis
• Post-partum thyroiditis
• Factitious thyrotoxicosis
• TSH-mediated thyrotoxicosis

Question 2

Physiologic response to hyperthyroidism

Answer 2

• There is increased heat production secondary to increased activity in Na/K ATPase, Ca ATPase, FA turnover, and beta adrenergic activity
• Exaggerated response to b adrenergic due to increased number and sensitivity of beta-adrenergic receptors, despite normal circulating catecholamine levels
• There is tachycardia and increased CO (B1), coupled w/ vasodilation (B2)
• There is increased blood volume to compensate for global vasodilation

Question 3

Signs and Sx of hyperthyroidism

Answer 3

• Nervousness, anxiety, heat intolerance, palpitations, SOB, weight loss, trouble sleeping and concentrating, frequent bowel movements
• Tremors, muscle atrophy/weakness, tachycardia, sweating, restlessness, rapid speech

Question 4

Grave’s disease 1

Answer 4

• Autoimmune hyperthyroidism, most common form
• Due to genetic predisposition (HLA-DR3 and HLA-B8) plus an inciting event (viral, bacterial, environmental)
• This leads to damage of the thyroid, causing an inflammation (IFNg->Th2) reaction to occur
• The B cells produce Abs to various epitopes from the thyroid, including TPO and TSH receptor

Question 5

Grave’s disease 2

Answer 5

• Anti-TPO Ab doesn’t participate in pathogenesis (used as a marker for immune dysfxn), but TSH receptor Ab is an agonist for the TSH receptor
• This Ab is TSI (thyroid stimulating immunoglobulin), and leads to growth and excess secretion of thyroid hormone (preferential T3 secretion) from the gland
• Leads to a diffusely enlarged gland: a globally smooth goiter
• If there is a carotid bruit its pathognomonic for graves disease

Question 6

Infiltrative ophthalmopathy of grave’s

Answer 6

• Usually parallels the thyrotoxicosis, but has its own progression
• Abs are made against EOMs and orbital adipocytes produce cytokines (IL1, TNF, IFNg) causing a local immune response
• This leads to proliferation of adipocytes and fibroblasts, causing enlargement of orbital contents which impairs venous outflow
• May see proptosis, periorbital edema, hyperemia/congestion of vessels, conjunctivitis/chemosis
• Pts have decreased range of movement of EOMS: they can’t look up + out b/c of the tension that puts on the medial and inf rectus muscles
• Can Rx eye Sx w/ lubrication, GCCs, surgical decompression

Question 7

Dermopathy (pretibial myxedema) of graves

Answer 7

• Mucopolysaccharide infiltrate of the skin over the tibia
• Due to a localized immune reaction leading to IgG stimulation of fibroblasts
• No effective Rx

Question 8

Lab values in graves disease

Answer 8

• Markedly elevated T3/T4 levels (T3/T4 ratio > 20:1, extremely high compared to normal ratio of 1:20)
• Very low TSH levels (<.01)
• Positive anti-TPO
• RAIU (radioactive iodine uptake) is increased diffusely

Question 9

General Rx for hyperthyroidism

Answer 9

• Block the beta-adrenergic excess: BBs
• Block the excess in thyroid hormone synthesis: thioamides
• Destroy thyroid gland by surgical excision or RAI

Question 10

Thioamides

Answer 10

• PTU or tapazole: both inhibit all steps of thyroid hormone synthesis catalyzed by TPO
• PTU also inhibits conversion of T4->T3 in peripheral tissues (1 5’D)
• 18mo Rx w/ gradual response due to large stores of T4/T3 that must be depleted
• Side effects: skin rash, cholestatic hepatitis, agranulocytosis is rare but life threatening
• If pt gets sore throat or fever tell them to stop taking the meds and go to ER
• Both are contradicted in pregnancy
• Remember after Rxing someone with these drugs to bring down T4/T3 levels, the TSH level will lag behind normalization of T3/T4 levels 4-8 wks before coming down to a normal range

Question 11

BBs

Answer 11

• Propanolol is preferred since it blocks both B1 and B2

- Prevents many of the Sx involved w/ hyperthyroidism

Question 12

Iodine Rx and RAI

Answer 12

• High levels of normal iodine can be used to suppress TSH/TSI interaction to inhibit release of T4/T3
• Response is rapid, generally used for a few days in conjunction w/ thioamides before surgery or in acute situation
• Cannot be used long term when pt is pregnant
• I131 Rx: destroys thyroid gland using beta emissions, used very frequently on pts w/ graves disease, multi nodular toxic goiter, toxic adenomas
• Makes the pt hypothyroid by 10 yrs in those w/ graves disease (other diseases may remain euthyroid)
• Surgery can be done in graves, but is preferred in those w/ adenomas and toxic multi nodular goiters (TMNG)
• Indications for surgery: very large goiter or resistant to RAIU, desires early pregnancy, pregnancy w/ allergy to ATD

Question 13

Subacute thyroiditis 1

Answer 13

• Caused by inflammation of the thyroid 2-3 wks post viral syndrome (URI)
• Thyroid is diffusely enlarged and very tender to palpation (pain my be referred to ears)
• Systemic signs of viral illness: fever, increased ESR, myalgia, sore throat
• Elevation of T3 and T4 (T3:T4 < 18:1), RAIU >1% (not overactive in any areas)
• Tg in serum is markedly elevated (due to dumping of thyroid hormones/Tg)

Question 14

Subacute thyroiditis 2

Answer 14

• Temporal pattern: hyperthyroid phase (w/ low TSH) for 4 wks, then hypothyroid phase (high TSH and variable RAIU) for 8 wks, then recovery phase after 12 wks (euthyroid)
• Rx: symptomatic using GCCs, propanolol
• Thioamides are contraindicated as thyrotoxicosis is secondary to dumping of thyroid hormone (not making more)

Question 15

Post-partum thyroiditis

Answer 15

• Painless thyroiditis w/ unknown cause
• Usually present 8 weeks after birth when immune system reactivates
• Thyroid is diffusely but minimally enlarged, firm and non-tender
• Low RAIU w/ same clinical course of subacute thyroiditis
• T3:T4 <18:1, but there is + anti-TPO Ab
• Give BB for Sx relief
• Eventually all women will become hypothyroid (may recur esp during future pregnancies)