176. Thyroid Physiology

Question 1

What is the function of thyroid hormone?

Describe the HPT Axis

How does TSH activate Thyroid Cells? What does it do specifically?

Answer 1

Fx: essential for growth/development of CNS, regulates myocardial contraction/relaxation, affects GI motility, modulates EE, modulates lipid metabolism

HPT: Hypothalamus blocked by T3 (-fb), secretes SS (-), DA (-), TRH (+)
Pituitary blocked by T3 (-fb), SS (-), DA (-), stim by TRH, secretes TSH (+)
Thyroid stim by TSH (+), secretes T4 (80%), T3 (20%, fb) to peripheral cells

TSH binds to GPCR on thyroid cell = thyroid differentiation/growth, hormone synthesis, peroxide generation, iodination

Question 2

What are the steps of thyroid hormone synthesis?

How are thyroid hormones transported?

How do thyroid hormones (T4 and T3) act on peripheral cells?

Answer 2

Na/I symporter takes up I- from blood; PDS protein transporter moves I- across apical side to colloid lumen

1. Organification: TPO enzyme converts I-, thyroglobulin, peroxide to MIT (1I) or DIT (2I)
2. Coupling: TPO enzyme converts multiple MITs and DITs to T3 and T4

Serum: 0.03% T4 and 0.3% T3 circulate freely
Most protein bound to TBG (highest affinity), albumin (binds more T3/T4 due to higher conc in blood), transthyretin (binds better than albumin but less in blood)

T4: prohormone converted to T3 (active form) in target tissues - express DIO1 and DIO2 to convert T4 to T3; DIO3 converts T4 to rT3 (inactive form)

Action: T3 acts on nuclear receptor to stim or inhibit gene expression
No T3 bound - corepressor binds - gene silencing, histone deacetylation
T3 bound = corepressor dissociates, coactivator binds = transcriptional activation, histone acetylation

Thyroid Hormone Receptor A and B: DNA binding domain and ligand binding domain

Question 3

Biochemical Function Tests

• what levels can you measure in blood?
• what antibodies are useful for what diseases?
• tumor markers?

Answer 3

TSH, Total T4, Total T3, Free T3, Free T4
Antibodies: TSH Receptor (Graves’), Thyroperoxidase (Hashimoto’s), Thyroglobulin (measure when checking thyroglobulin)

Thyroglobulin: tumor marker for papillary/follicular thyroid cancer
Calcitonin: tumor marker for MTC

Question 4

What labs have inverse logarithmic relationship?

What are these labs values in central/subclinical/true hypothyroidism, and subclinical/hyperthyroidism?

Answer 4

TSH + fT4 (small change in fT4 = big change in TSH = strong negative feedback)
Central Hypothyroid: low fT4, normal TSH (problem with hypothalamus-pit axis)
Subclinical Hypothyroid: normal fT4, high TSH
Hypothyroidism: low fT4, HIGH TSH
Subclinical Hyperthyroid: normal fT4, low TSH
Hyperthyroid: LOW TSH, high T3/T4

Question 5

How are thyroglobulin (TG) levels used?

Why are TG antibodies measured?

Answer 5

TG: used in thyroid cancer surveillance (TG = tumor marker), detectable TG in pt with resected thyroid = residual/recurrent thyroid/thyroid cancer tissue
increase in TG may only be detectable in high TSH (need withdrawal from thyroid hormone for accurate results)

TG antibodies: 10% normal people have antibodies against TG, 20% thyroid cancer pts have antibodies against TG
Can make TG look falsely LOW
indicates residual/recurrent thyroid cancer tissue (lose antibodies = good sign cancer is gone)

Question 6

Thyroid Ultrasound

• use in thyroid disease
• signs of malignancy in US (3)
• why US is performed
• signs of thyroid cyst, solid nodule, complex nodule

Answer 6

Modality of choice for evaluation of thyroid structure!
Gives no functional info :(, used to dx structural alterations
Malignancy signs: hypoechoic signal, irregular borders, microcalcifications
Performed to determine if fine needle biopsy indicated

Cyst: echo-free center (black), smooth back wall, acoustic enhancement (deeper than cyst)

Solid Nodule: many echo reflections, back wall indistinct, no acoustic enhancement

Complex Nodule: cyst and solid features combined

Question 7

Isotope and PET Scans

• use in thyroid disease
• difference between 123I and 131I
• signs of Graves’ Disease, Toxic Adenoma, Cold Nodule

Answer 7

Provides fx info and assess extent of disease, malignancy, or mets
Limited structural info :(
Uptake of tracer (%initial dose) quantified to estimate metabolic fx

123-I: used for thyroid and whole body scan (only emits gamma radiation)
131-I: emits gamma radiation AND beta particles (DAMAGES tissue), destroys thyroid cells where 131-I accumulates, used as tx for thyroid cancer and hyperthyroid disease (Graves’ Disease)

Graves’ Disease: high + diffuse uptake in both lobes (symmetrical over-uptake)
Toxic Adenoma: increased focal uptake and suppressed uptake diffusely elsewhere
Cold Nodule: focal area of decreased uptake = area of underproduced hormone = CONCERNING FOR MALIGNANCY

Question 8

Thyroid CT + MRI
- use in thyroid disease

Pemberton Sign - what is it? what does it assess?

Answer 8

CT/MRI: no fx info, limited role in structure evaluation
assess for retrosternal extension, tracheal compression (good for assessing nearby tissue), good for tumor staging

Pemberton sign: raise both arms over head for 60s
If positive = exacerbates tracheal/vasculature compression = less venous return (vein bulging), new SoB (signs of GOITER)

Question 9

What is goiter? What is most common cause of it?

Answer 9

Goiter = enlarged thyroid

Iodine deficiency disorder = most common cause of thyroid disorders worldwide

• 20 million people have intellectual disability because of IDD
• MOST preventable cause of cognitive impairment
• insufficient regions: Russia, N EU, SE asia, Mid East, parts of Africa
• excess regions: Nepal, Columbia, parts of Africa