JC38 (Medicine) - Thyrotoxicosis and Hypothyroidism Flashcards

Question

Complications of proptosis due to thyrotoxicosis

Answer 1

Opthalmoplegia/ Diplopia Corneal ulceration Chemosis Conjunctivitis Optic atrophy

Answer 2

Fine tremor\* - Due to sympathetic overactivity Sweating, warm and moist skin\* - Due to sympathetic overactivity Onycholysis - Separation of nail from bed Palmar erythema - Signs of Grave’s disease Finger clubbing Thyroid acropachy - Soft-tissue swelling of hands and finger clubbing Abnormal pulse  Sinus tachycardia (Sympathetic overactivity)  Atrial fibrillation (Shortened refractory period of atrial cells related to sympathetic drive)  Bounding pulse and wide pulse pressure (High cardiac output associated with AS murmur)

Answer 3

Arms * *- Proximal myopathy** * *- Hyperreflexia** Legs **- Proximal myopathy**: Ask patient to stand up from squatting position **- Pretibial myxedema**  Occurs in Grave’s disease and rarely Hashimoto’s thyroiditis  Localized non-pitting edema of skin  Bilateral firm, elevated dermal nodules and plaques  Can be pink, brown or skin-colored  Hyaluronic acid accumulates in dermis and subcutis

Answer 4

Peripheral cyanosis - Reduced cardiac output Palmar crease pallor Anemia due to • Anemia of chronic disease • Iron deficiency (menorrhagia) • Folate deficiency (bacterial overgrowth) Dry and cool skin Yellow discoloration  Due to hypercarotenemia  Slowing down of hepatic metabolism of carotene Abnormal pulse Carpal tunnel syndrome  Sensory loss as carpal tunnel is thickened in myxoedema

Answer 5

Arms - Proximal myopathy - “Hung-up” biceps reflex Legs - Non-pitting edema/ Myxoedema - “Hung-up” Achilles reflex  Rapid dorsiflexion followed by slow plantar flexion after the tendon is tapped

Answer 6

Newborn: Cretinism/ Short stature/ Mental retardation/ Puffy face/ Deaf mutism/ Protuberant abdomen/ Umbilical hernia Children: Retardation of growth, mental retardation

Answer 7

Advantage: * MOST sensitive indicator of thyroid function due to short t1/2 * Normal TSH excludes a primary hyperthyroidism * Does NOT exclude secondary abnormalities (hypothalamic or pituitary) Limitations: * Cannot indicate pituitary disease * High TSH can mean hypothyroidism or secondary hyperthyroidism * Low TSH can mean hyperthyroidism or secondary hypothyroidism * Low TSH in 1st trimester pregnancy, high dose corticosteroid or dopamine use

Answer 8

Hypothyroidism: only need fT4 (fT3 normal in 25% patients due to adaptive deiodinase response) Hyperthyroidism: need both fT3 and fT4 (2-5% have only fT3 elevation in T3 toxicosis) Total T4 is related to thyroxine-binding globulin with confounding factors: * High in pregnancy, oral contraceptive, hormonal therapy * Low in androgen use, hypoalbuminaemia

Answer 9

Thyroid antibodies • Thyrotropin receptor antibodies (TRA) (Anti-TSH antibodies) • Anti-thyroid peroxidase (TPO) antibodies • Anti-thyroglobulin (TG) antibodies Anti-TSH: Grave's disease Anti- TPO: Hashimoto thyroiditis Anti-TG: Multinodular goiter

Answer 10

Autoimmune disease: Lymphocytes produce autoantibodies against self-antigen TSH receptor Thyrotropin-receptor antibody (TRAb) stimulates TSH receptor on thyroid gland: Stimulate thyroid cell hyperplasia and TH release

Answer 11

1. Diffusely enlarged thyroid gland 2. High fT3 and fT4, Suppressed TSH 3. Diffuse radioactive iodine uptake in scintigraphy scan 4. Positive TSH receptor autoantibody in serum

Answer 12

*Functional assessment of thyroid* Increased uptake: * Grave's disease: diffuse uptake * TSH-secreting pituitary adenoma: diffuse uptake * Toxic adenoma: focal area of uptake only * Multinodular goiter: heterogenous uptake Decreased uptake: * Thyroiditis * T4 overdose * Iatrogenic: e.g. hemithyroidectomy *Guide FNAC decision* o Hot nodules do NOT require FNAC o Cold nodules require FNAC

Answer 13

Goiter S/S hyperthyroidism Exophthalmos/ Proptosis Pretibial Myxoedema S/S of related autoimmune diseases: MG, DM

Answer 14

Thyroid storm Thyrotoxic period paralysis (HypoK) Atrial fibrillation and heart failure

Answer 15

1. Prognostic indicator of Antithyroid drug against Grave's disease: negative TRAb after Tx means better prognosis 2. Forecast neonatal Grave's disease (TRAb passes through placenta) 3. Diagnosis of Grave's disease and monitor response to antithyroid drugs

Answer 16

1. Antithyroid drugs: * Thiouracil derivatives: Methimazole, carbimazole, propylthiouracil * Lithium 2. Surgery: thyroidectomy 3. RAI therapy 4. Ancillary drugs: Sedatives, B-blocker, Iodine

Answer 17

* Indication: Thyrotoxic crisis, before surgery to prevent thyroid storm * Example: Propanolol * MoA  Block β1-adrenoreceptors in heart • Relive palpitations  Block β1-adrenoreceptors in brain • Relieve anxiety  Block β2-adrenoreceptors in skeletal muscle • Relieve tremor * S/E:  Bronchospasm  Hypoglycemia  Heart failure (↓ CO)  Coronary artery spasm

Answer 18

* Indication: rapid onset, short-term use before thyroidectomy/ thyroid storm * Contraindication: pregnancy and breast-feeding * MoA: High iodine concentration inhibits H2O2 and peroxidase \> inhibit iodination of thyroglobulin and production of T3, T4 Decrease size and vascularity of hyperplastic thyroid gland Decrease bleeding risk during surgery * S/E: Hypersensitivity (fever, rash, angioedema, conjunctivitis..etc)

Answer 19

* Indication: Children/ Pregnancy/ Mild- moderate disease * Tx course: 12 - 18 months, onset of effects takes 4 weeks * Examples: Carbimazole/ Methimazole/ Propylthiouracil (PTU) * MoA: Carbimazole/ Methimazole: Inhibit the action of peroxidase • Inhibit iodination (organification) of tyrosine residues of thyroglobulin • Inhibits coupling of iodotyrosine and production of T3 and T4 • Suppress intra-thyroidal antigen-presenting cells PTU: Inhibits peripheral conversion of T4 into T3 * S/E: Skin rash, urticaria and pruritis Agranulocytosis (first 2 months, fever, sore throat) Rare: Hepatotoxicity, Acute arthralgia, Cholestatic jaundice, ANCA vasculitis

Answer 20

Rapid absorption into thyroid in minutes All transferable into milk Metimazole/ Carbimazole more teratogenic than PTU \>\> Give PTU until second trimester then change to methimazole/ Carbimazole

Answer 21

1. Larger goiter 2. Positive family history 3. High initial T3 or T3/T4 ratio 4. Shorter course of Tx 5. Failure to normalize TSH 6. High TSH receptor antibody levels

Answer 22

Bilateral subtotal thyroidectomy Unilateral total and contralateral subtotal lobectomy Near total thyroidectomy Pre-op preparation: * Antithyroid until euthyroid * Beta-blocker for 2 weeks * Lugol's solution 2-3 days before

Answer 23

1. Young age 2. Failed medical treatment 3. Refuse/ Refractory to anti-thyroid drugs 4. Thyroid eye signs 5. Pregnancy/ breast-feeding 6. Refuse/ Refractory to RAI therapy 7. Excessively large goiter +/- compressive symptoms

Answer 24

 Hypoparathyroidism  Thyroid storm  Tracheomalacia - trachea cartilage collapse  Vocal cord paralysis: RLN or SLN damage  Wound complications: seroma, hypertrophic scar  Hemorrhage • Compression and edematous effect compresses on trachea

Answer 25

Indications: * Thyrotoxic heart disease; Refractory to antithyroid drugs; ablation of residual tumor after thyroidectomy; Relapse post-op; C/O surgery Contraindication: * Pregnancy/ breast-feeding (transplacental, fetal risks) MoA: * Taken up by Na-I symporter and incorporated into thyroglobulin * Emit B-radiation to cause necrosis of follicular cells, fibrosis and destroy colloid * Destroy intra-thyroid T-suppression cells, Inhibit release of TSH-receptor antibodies S/E: * Hypothyroidism * Risk of thyroid eye disease after Tx * Thyroid storm due to radiation thyroiditis

Answer 26

Low relapse rate Simple procedure Economical No immediate complications

Answer 27

1. TSH-receptor antibody stimulate orbital fibroblasts to differentiate into adipocytes/ adipogenesis 2. Increase TSH receptor expression on orbital fibroblast after differentiation into adipocytes 3. Orbital adipocytes hypertrophy and exerts pressure on eyeball

Answer 28

Extra-ocular muscles: edema, mononuclear cell infiltration, Mucopolysaccharide deposits, Fibrosis Retrobulbar fat: Lymphocyte infiltration, fat replaced by fibrous tissue, collagen tissue replaced by hyaluronic acid Optic nerve: atrophy, replaced by fibrous and fatty connective tissue

Answer 29

False Can be hyper-, hypo- or euthyroid 80% opthalmopathy first develop eye signs within 18 months of thyrotoxicosis

Answer 30

1. Anti-thyroid treatment to achieve euthyroid 2. Immunosuppressants against infiltrative ophthalmopathy: * Steroid - IV or oral methylprednisolone * Cyclosporin A * Plasmapharesis for autoantibody * Immunoglobulin * TNF-a inhibitor * IGF-1 receptor inhibitor 3. Orbital irradiation 4. Orbital decompression/ extra-ocular muscle operation

Answer 31

Pathophysiology: hyperthyroidism results in □ ↑Na+/K+/ATPase activity + ↑insulin release (esp after carbohydrate load) → intracellular shift of K+ □ Consequences: paralysis and hypokalemia

Answer 32

Always preceded by thyrotoxic S/S (thyrotoxic state essential for pathogenesis) Attacks of motor paralysis: proximal \> distal, LL \> UL, seldom respiratory/bulbar muscles → Signs: typically hypotonia with hypo/areflexia → Course: weekly/monthly attacks lasting mins-days Precipitants: - Events a/w ↑adrenaline release: rest after strenuous activity, stress, SABA use - Events a/w ↑insulin release: namely ↑carbohydrate load Cardiac arrhythmia due to severe hypoK

Answer 33

Mx: usually spontaneous recovery □ Cardiac monitoring □ K supplement: use IV K 10-20mmol/h over 2h to accelerate recovery → Watch out for rebound hyperkalemia (40-59%) when transcellular shift reverses → IV propranolol may be useful to reverse excessive ↑Na+/K+/ATPase activity in refractory cases □ Manage hyperthyroidism □ Other prophylactic Tx: low salt diet, moderate carbohydrate intake ± propranolol

Answer 34

Cretinism Juvenile myxedema Adult myxedema Myxedema coma

Answer 35

Autoimmune: Lymphocytic thyroiditis, Atrophic thyroiditis, Hashimoto's thyroiditis Silent thyroiditis e.g. Post-partum thyroiditis

Answer 36

RFs: older female, family history, HLA-DR3, High iodine intake, smoking Pathology: T-cell mediated autoimmune disease against thyroid tissue Anti-thyroid antibody after T-cell mediated thyroid injury: Anti-thyroglobulin, Anti-TPO Histology: profuse lymphocytic infiltration, lymphoid germinal centres and destruction of thyroid follicles ± fibrosis

Answer 37

Clinical presentation: □ Goitre: usually small or moderately sized, diffuse, painless → Characteristically firm, rubbery → Atrophic variant: predominantly TSHr-blocking Ab → no goiter □ Hypothyroidism (25%) Natural Hx: gradual loss in thyroid function over years

Answer 38

Ix: □ TFT: may have ↑TSH + ↓fT4 □ Thyroid Ab: anti-TPO Ab (90-100%), anti-Tg Ab (80-90%), anti-TSHr (10-20%) Mx: T4 replacement: treats hypothyroidism + shrinks goiter

Answer 39

□ Subacute granulomatous (de Quervain’s, giant cell) thyroiditis □ Subacute lymphocytic thyroiditis □ Postpartum thyroiditis □ Palpation thyroiditis

Answer 40

S/S: ## Footnote □ Pain at thyroid, exacerbate by swallowing or neck movement, only in Quervain's, not others □ Goitre: palpable ± tenderness □ Fluctuating thyroid status > transient hypothyroidism or thyrotoxicosis without hyperthryroidism □ Systemic symptoms: fever, ↑WBC, ↑ESR Clinical course: □ Thyrotoxic phase (4-6w) → Due to damage to follicles release of stored T4 until depletion → ↓iodine uptake (↓TSH, follicular damage) □ Hypothyroid phase (4-6mo) due to damage to follicular cells → ↓synthesis of thyroid hormones □ Resolution Mx: self-limiting → do NOT give antithyroid medications □ No Mx: spontaneous resolution! □ *NSAIDs/corticosteroids* for severe cases → manage systemic upset + pain □ *Temporary β-blocker* for hyperthyroid phase (usually mild) → for symptomatic control only □ *Temporary T4 replacement* for hypothyroid phase if pronounced or symptomatic

Answer 41

``` □ Causes: during ↑requirement (eg. pregnancy, pubertal) or from food (goitrogen, iodine excess/deficiency) ```

Answer 42

Pathology: recurrent episodes of hyperplasia and involution (due to unknown stimulus) → hyperplastic nodules growing at varying rates → some may secrete thyroid hormone autonomously (toxic MNG, Plummer disease) TFT findings: → 25% with complete suppression of TSH → T4/3 can be within reference range (subclinical thyrotoxicosis) or elevated (toxic MNG) S/S: classically AF + multinodular goitre in elderly → Large goiter ± compressive S/S or retrosternal extension → Haemorrhage into nodule/cyst → sudden painful swelling → Thyrotoxic symptoms/complications, eg. AF

Answer 43

Mx: → No treatment + annual TFT to screen for toxic MNG in small, non-toxic MNG - Consider T4 suppression therapy in selected patients → aim low-normal TSH → Early definitive treatment for large or toxic MNG (as relapse is invariable after cessation of ATD)49 - Total thyroidectomy for large goitres with compression or cosmetic concerns - RAI for small toxic goitres

Answer 44

Neonatal cord blood TSH screening: fT4 \<12pmol/L, TSH \>7mlU/L Causes: 1. Athyroesis 2. Dyshormonogenesis 3. Ectopic thyroid gland 4. Hypothalamic - Pituitary hypothyroidism 5. Maternal factors: Anti-thyroid drugs, Iodine deficiency, TSH-autoantibodies, Premature birth 6. Associated conditions: Down's syndrome, Trisomy 18…etc

Answer 45

1. Hypothyroidism - lead to hyperlipidaemia due to decrease lipolysis, increase risk of Coronary atherosclerosis 2. Must treat coronary atherosclerosis prior to T4 supplementation: Initiation of thyroxine raises CO and worsens IHD 3. Give 4-6 weeks to equilibrate thyroxine

Answer 46

 General features • Severe hypothyroidism with hypothermia, respiratory failure with hypoxia and coma, convulsions, confusion  General management • Treatment of precipitating causes • Maintenance of body temperature • Correction of hypoglycemia with D10 • Correction of fluid and electrolytes with NS ± vasopressors  Medical treatment • Liothyronine (T3) • Levothyroxine (T4)