Thyroid physiology and testing

Question 1

Know the hypothalamic-pituitary-thyroid feedback axis

Answer 1

TRH - TSH - TH (T3 and T4). T3 is bioactive and the one for feedback. T4 is converted to T3 by deiodinases in hypo and pituitary, and in liver, brown fat and kidney.

Question 2

Know the anatomy of the thyroid and clinical relevance of anatomical features of the thyroid

Answer 2

Thyroid is on your trachea. Parathyroids are on the back. Usually autotransplantation when removing thyroid. Also watch for the Recurrent laryngeal nerve (behind thyroid)

Question 3

What is the best test to measure thyroid function?

Answer 3

TSH measure is the BEST single screen (normal 0.2 - 4.0 mU/L). Reflects T3 levels. Easy diagnosis of hyper or hypo thyroid.

Question 4

Understand TPO and TSH receptor antibodies

Answer 4

TPO implies autoimmune disease (destructive). Doesn’t distinguish b/w graves or hasimoto’s. TSH-R Ab are TSH agonists in Graves only. Can also cross placenta (IgG).

Question 5

When would the TSH test not be reliable?

Answer 5

Abnormal TSH: Pituitary or hypo disease, ICU, Some psych problems, Some drugs (dopamine suppress TSH), After Tx with Radioactive I. Normal TSH but hypothyroid: pituitary tumor or surgery (other hormones affected first). Still recommend testing TSH first.

Question 6

Stages of primary hypothyroidism

Answer 6

Chart. Thyroid starts to just make T3 to compensate (step 3).

Question 7

Understand subclinical hyperthyroidism and hypothyroidism

Answer 7

Earliest abnormality is increased or decreased TSH. Patient usually asymptomatic. Causes same as overt disease

Question 8

Know iodine metabolism and the regulation of thyroid hormone synthesis and thyroid hormone metabolism

Answer 8

active transport of iodide by sodium-iodide symporter (NIS) (regulated by I feedback). Iodination of tyrosines, then coupling of iodotyrosines on Tg. Storage on thyroglobulin (Tg): endocytosis of colloid and recycling of I- and amino acids by lysosomal enzymes. Secretion of T4 > T3 into blood

Question 9

Know the half life of T4 and T3. Importance?

Answer 9

T4 = 7 day. T3 = 0.75 days. Giving T4 supplement is better because it won’t spike and drop fast, more stable. Less frequent adjustment needed.

Question 10

Compare and contrast T3 ad T4

Answer 10

Both Transported by TBP and albumin in blood, so Free T3: .03% T4: ,003%

Question 11

Know the conversion of T4 to T3 by deiodinases and the physiological and clinical significance

Answer 11

Converted by deiodinases. Impaired by fasting, illness/acute trauma (acts like protection), some drugs (can use propranolol or high glucocorticoids to lower T3 in thyroid storm).

Question 12

Know the categories of actions of thyroid hormone on the body

Answer 12

T3 binds to nuclear receptors and affects transcription. Affects metabolism, growth and development, and others.

Question 13

Metabolic effects of TH

Answer 13

Increases: Catabolism and anabolism, BMR (basal metabolic rate), O2 consumption and heat, CHO absorption and utilization, protein breakdown (muscle), fat breakdown, cholesterol metabolism. Decreased serum cholesterol (LDL)

Question 14

Growth effects of TH

Answer 14

Act as “tissue growth factors”, Small amounts stimulate protein synthesis, Increase GH/IGF-1 production, Essential for CNS maturation in fetus - maternal hypothyroidism results in poor fetal CNS development and mental retardation

Question 15

Other effects of TH

Answer 15

Cardiovascular system (beta adrenergic receptors): increased HR, contractility, BP. Potentiation of SNS (beta-2 adrenergic receptors). Reproductive system: necessary for normal function and fertility

Question 16

Know the adverse effects of iodine deficiency and iodine excess on the thyroid

Answer 16

Excess can result in hypo or hyper: Wolff-Chaikoff and Jod-Basedow effects. shuts off the iodine transporter.

Question 17

Know the Wolff-Chaikoff effect

Answer 17

Excess iodine can inhibit organification (conversion into TH) of iodide and hence TH synthesis will be decreased. We exploit this effect in treating thyroid storm. A normal thyroid “escapes” from this effect in about 2 weeks. In patients prone to hypothyroidism - escape may not occur, and hypothyroidism may continue, eg autoimmune thyroid disease (Hashimoto’s)

Question 18

Know the Jod-Basedow effect

Answer 18

Iodide-induced hyperthyroidism. In normal individuals, iodide decreases TH release. In some patients, especially those with hyperthyroidism, excess iodide may be used as a substrate for TH metabolism, promoting and worsening the hyperthyroid state. In patients usually with other autoimmune thyroid disease, eg Hashimoto’s thyroiditis, an iodine load may trigger hyperthyroidism. This is less common than the Wolff-Chaikoff effect.

Question 19

Worldwide issues with iodine deficiency

Answer 19

Iodine deficiency is the most common cause of Hypothyroidism, Goitre, Mental retardation, Preventable brain damage. Decreased child survival, Mental retardation, Reproductive impairment, Hypothyroidism, Deaf mutism, Cretinism, Neurologic deficits, Goitre, Late hyperthyroidism

Question 20

Radioactive Iodine uptake test

Answer 20

I taken up by NIS. Increase with higher TH synth (graves, toxic nodules). Decreased when thyroid inflammation and leak of stored T3/T4 are causing the hyperthyroidism (autoimmune/viral)

Question 21

Other uptake tests for thyroid function

Answer 21

99m technitium - lower radiation dose, shorter T1.2 than 131-I. Doesnt’ give info about steps in I/TH metabolism. Does give size, shape, areas that are “hot or cold”, higher uptake in Graves, lower in thyroiditis. Scans show clear shape if taken up. Thyroiditis is really fuzzy/not formed.

Question 22

What is Thyroid ultrasound useful for?

Answer 22

evaluate: Palpable nodules / masses, Evaluate painful gland, Facilitate FNA biopsy of nodules, Look for parathyroid adenomas (not the best choice), Best use is assessing presence and size of nodules (accurate; thyroid scan is fuzzy and imprecise)

Question 23

What is Thyroid ultrasound NOT useful for?

Answer 23

Not helpful in evaluating hyperthyroidism per se; not helpful to evaluate causes of hypothyroidism or an abnormal TSH; not routine; not needed to evaluate diffuse goitres without palpable nodules

Question 24

Understand the purpose of each thyroid imaging technique

Answer 24

To test Thyroid FUNCTION: do thyroid scan with 99mTc or 131I. To test Thyroid SIZE/nodules: do thyroid ultrasound