Thyroid Flashcards by Nicholas Leung

Pituitary gland

Synthesize and release thyroid stimulating hormone to stimulate thyroid

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Hypothalamus

Releases thyrotropin releasing hormone to stimulate the pituitary gland

TRH suppressed by dopamine, corticosteroids, somatostatin

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Thyroid stimulating hormone

Causes iodine uptake for synthesis
T3/T4 release into circulation

Stimulates synthesis of iodine transporter, thyroid peroxidase, thyroglobulin

Low T4, high TSH

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Iodine metabolism

Oxidize iodide by thyroid peroxidase
Able to iodinate tyrosines

Ether linkage between iodotyrosine to form T3/T4

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Goiter

Can present in both iodine deficiency and iodine excess

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Most abundantly produced

Thyroxine

2 Tyrosine + 4 iodines

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Most active metabolite

Greater affinity to thyroid receptor

Triiodothyronine

Not a good indicator of hypothyroidism

Synthesized in peripheral tissues

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Deiodinase Activity

Type 1: plasma membrane of liver kidney thyroid, T3 enter bloodstream

Type 2: ER of pituitary, brain cells
T3 greedy and intercellular

Type 3: inactivator, T4-RT3, T3-T2

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Thyroid hormone actions

Necessary for normal growth and metabolic stability in bone & CNS

Heart beta sensitivity and inotrope

Lipolysis of adipocytes

CHO absorption, O2 consumption

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Grave’s disease

TSH receptor stimulating antibodies (TSI Ab) Grave receptor Ab

Can lead to TNT to fetus

CD8+ cells mediate toxicity

Increases with increased iodine

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Hashimoto’s disease

Hypothyroid

Anti thyroid peroxidase antibody
Antibody against Na-I symporter

Can’t produce thyroid hormone
Lymphocyte infiltration and WBC damage thyroid cells

Prevalent in Japanese

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Primary hypothyroidism

Iodine deficiency

Autoimmune:Hashimoto’s

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Secondary hypothyroidism

Hypopituitarism

TSH deficient or inactive

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Hypothyroid signs

Dry skin (diminished sweating)

Edema (puffy face, hands, feet)
Weight gain
Myxedema

Pale, Yellow tinge
Sexual dysfunction
Cardio dysfunction, diastolic HTN
Dry brittle hair

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Thyrotoxicosis signs

Weight loss (increased metabolism)
Increased appetite

Tremor
Tachycardia, high cardiac output

Warm moist skin
Dermopathy

Decreased male sexual function

Bone resorption and osteoporosis

Enlarged, firm thyroid with bruit

Lid retraction, stare

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Solitary toxic nodule

Mild hyperthyroid
Palpable nodule
Hot on scan

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HCG & TSH induced thyrotoxicosis

hCG binds to TSH receptor

TSH secreting pituitary tumor

Diffuse (simple goiter)

Iodine deficiency
Compensatory hypertrophy

Goitrogens: Brussels sprouts, cabbage
PTU, MMI, lithium

Thyroid nodules

90% benign
Increase with age

Hashimoto’s is benign

Malignant: papillary carcinoma

Thyroid secretes

Calcitonin

Thyroglobulin

Provides tyrosine for T4 synthesis

Hashimoto’s and Grave’s have antibodies against thyroglobulin

Pendrin

Defect results in iodination malfunction
Goiter, hypothyroidism

Exchange iodine to the colloid

To be utilized with tyrosine on thyroglobulin

Target tissue uptake

MCT8 in liver, kidney, thyroid, brain for T3 uptake (X chromosome gene) defect in men

OATP for T4 uptake in tissues

Thyroid hormone metabolism

Conjugation by

Glucuronidation

Sulfation

Hyperthyroidism treatment

1) thioamides inhibit thyroid peroxidase and deiodinase T4 conversion to T3 Methimazole - preferred less AE Propylthiouracil 2) cholecystographic inhibit D1, D2 Iospanoic acid amiodarone - block T3 binding to THR Iodine, radioioidine Propranolol for beta symptoms

Iodine MOA

Large amounts of iodine - auto regulation - inhibit TH formation Wolff chaikoff Small iodine - fail autoregulation - increase thyroid hormone formation Jod-basedow

Hypothyroidism treatment

Give T4 in general, body has choice to utilize it Give T3 if you know specific T3 defect in OATP uptake

Thyroid TSH T4 screening

For women > 50 years old

TSH range

0.5-4.7 mIU/L

T4 levels

Free T4 0.8-2.7ng/dL

Drugs that increase T4

Amphetamines Propranolol Nadolol

Drugs that decrease T4

Glucocorticoids Lithium Phenobarbital Phenytoin

If hypothyroid

Need to lower dose of digoxin, insulin Avoid opioids and respiratory depression

Levothyroxine counseling

AE: CHF, angina, MI, osteoporosis Take on empty stomach Separate from dairy Mg

Myxedema

Longstanding hypothyroidism Stupor, coma Hypothermia 74F Decrease Na, glucose Give IV levothyroxine bolus 500mcg, followed by 50-100 mcg Hydrocortisone IV Vasopressors, fluids, warm blanket Can give liotrix T4-T3 combo

Hyperthyroidism treatment

Surgery (give thionamide, potassium iodide, propranolol before) Give propranolol also 7 days post-op Radioactive iodine Antithyroid drugs: 4-8 weeks, taper monthly based on T4

Propylthiouracil

Initial: 300mg divided TID PO Maintenance: 100mg divided TID PO AE: hepatotoxicity Inhibits D1

Methimazole

15 mild - 60 severe mg/ divided TID Maintenance: 10mg AE: myopathy

Hyperthyroidism relapse

Give radioactive iodine Concentrated in thyroid Disrupt T4 synthesis ~ Wolff chaikoff Propranolol for adrenergic symptoms Can give potassium iodide as adjunct

Thyroid storm

Fever, Tachycardia Dyspbea, Dehydration, Coma Maybe due to infection, T4 OD Treat precipitating cause Give PTU 1000mg/day divided Potassium iodide TID 1 hour after PTU Esmolol IV Propranolol PO APAP fever, cool blanket, fluids

Euthyroid sick syndrome

Normal T4 Low T3 Low TSH Impaired T4-T3 conversion Treat underlying condition not thyroidism

T3 levels

Total: 100-200 ng/dL