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Toronto Notes 2019 Thyroid
• thionamides:propylthiouracil(PTU)ormethimazole(MMI)
■ PTU and MMI inhibit thyroid hormone synthesis by inhibiting peroxidase-catalyzed reactions,
thereby inhibiting organification of iodide, blocking the coupling of iodotyrosines
■ PTU also inhibits peripheral deiodination of T4 to T3
■ continue treatment until remission occurs (20-40% of patients achieve spontaneous remission at
6-18 mo of treatment)
■ small goitre, mild hyperthyroidism, and low TSI titres are good indicators for long-term remission
with medical therapy
■ major side effects: hepatitis, agranulocytosis, and fever/arthralgias
■ minor side effects: rash
■ MMI preferred vs. PTU due to longer duration of action (once daily dosing for most), more rapid
resolution of hyperthyroidism , and lower incidence of side effects
■ in pregnancy: use PTU during first 16 weeks of pregnancy and MMI after. MMI is contraindicated
in the first trimester due to risk of aplasia cutis; MMI is preferred in the second and third trimester
due to the potential risk of hepatotoxicity with PTU in the second and third trimesters
• symptomatictreatmentwithβ-blockers
• thyroidablationwithradioactiveI-131ifPTUorMMItrialdoesnotproducediseaseremission
■ high incidence of hypothyroidism after I-131 requiring lifelong thyroid hormone replacement ■ contraindicated in pregnancy
■ may worsen ophthalmopathy
• subtotalortotalthyroidectomy(indicatedforlargegoitres,suspiciousnoduleforCa,orifpatientis intolerant to thionamides and refusing RAI ablation)
■ risks: hypoparathyroidism and vocal cord palsy
• ophthalmopathy/orbitopathy
■ smoking cessation is important
■ prevent drying of eyes and ulceration of cornea ■ high dose prednisone in severe cases
■ orbital radiation, surgical decompression
Prognosis
• courseinvolvesremissionandexacerbationunlessglandisdestroyedbyradioactiveiodineorsurgery • lifetimefollow-upneeded
• riskofrelapseis37%,21%,and6%intreatmentwiththionamides,radioiodineablation,andsurgery,
respectively
Subacute Thyroiditis (Thyrotoxic Phase)
Definition
• acuteinflammatorydisorderofthethyroidglandcharacterizedbyaninitialthyrotoxicstate,followed by acute inflammatory disorder of the thyroid gland characterized by an initial thyrotoxic state (hyperthyroidism) followed by hypothyroidism, and then eventually euthyroidism in most cases
• twosubtypes:painful(“DeQuervain’s”)andpainless(“Silent”)
Etiology and Pathophysiology
• acuteinflammationofthethyroidglandcharacterizedbygiantcellsandlymphocytes
• disruptionofthyroidfolliclesbyinflammatoryprocessresultsinthereleaseofstoredhormonerather
than excessive production of new thyroid hormone
• presumedtobecausedbyaviralinfectionorpost-viralinflammation
• painful=viral(usuallyprecededbyURTI),DeQuervain’s(granulomatousthyroiditis)
• painless=postpartum,auto-immune,lymphocytic
■ occurs in 5-10% of postpartum mothers and is symptomatic in 1/3 of patients
Clinical Features
• painful(thyroid,ears,jaw,andocciput)orpainless
• feverandmalaisemaybepresent,especiallyinDeQuervain’s
• postpartum:thyrotoxicosis2-3mopostpartumwithasubsequenthypothyroidphaseat4-8mo
postpartum
• maybemistakenlydiagnosedaspostpartumdepression
Laboratory Investigations
• initialelevatedfreeT4,T3,lowTSH,markedlyreducedRAIU
• markedelevationofESRinpainfulsubtypeonly
• asdiseaseprogresses,valuesconsistentwithhypothyroidismmayappear
Treatment
• DeQuervain’s–highdoseNSAIDs,prednisonemayberequiredforseverepain,fever,ormalaise
• β-adrenergicblockadeisusuallyeffectiveinreversingmostofthehypermetabolicandcardiac
symptoms in both subtypes
• ifsymptomaticallyhypothyroid,maytreatshort-termwiththyroxine
Prognosis
• fullrecoveryinmostcases,butpermanenthypothyroidismin10%ofpainlessthyroiditis
• postpartum:mostresolvespontaneouslywithoutneedforsupplementation,howevermayrecurwith
Endocrinology E25
Other Medications Used in the Treatment of Graves’
Glucocorticoids have been useful in the treatment of severe Graves’ hyperthyroidism and thyroid storm, by inhibiting the conversion of peripheral T4 to T3
Lithium is also used to treat Graves’ hyperthyroidism. It acts by blocking thyroid hormone release, but its toxicity has limited its use in practice
Caution with Thionamides
These drugs are effective in controlling hyperthyroidism and induce permanent remission in 20-30% of patients with Graves’ disease. They inhibit thyroid hormone synthesis. They are most often employed to achieve a euthyroid state before definitive treatment. Adverse effects include teratogenicity, agranulocytosis, hepatotoxicity, and ANCA-positive vasculitis
subsequent pregnancies