What is the embryological origin of the medial portion of the thyroid? Lateral?
- Foramen cecum at the base of the tongue
- This migrates caudally until it reaches the adult resting place
- Thyroglossal duct may persist in adults
- Ultimobranchial body (part of 5th branchial arch)
- Maldescent/non-descent may result in persistent thyroglossal duct
Describe the anatomy of the thyroid
- 2 lobes and an isthmus
- Lobes -> lobules -> follicles
- Normal weight: 15-25g
- Vasculature supply from inferior and superior thyroid arteries and thyroidal veins
- Follicle microscopy: epithelial cells surrounding central colloid
What substance is required for thyroid hormone synthesis?
- RDA = 150 ug/d
Why is iodine necessary for thyroid hormone synthesis?
- How does the thyroid gland get enough?
- Function: iodine catalyzes iodine organification (attachment) to tyrosine residues of thyroglobulin
- Iodide trapping: thyroid cells actively transport Iodide from plasma into cytoplasm.
- This entrapment by the Na-I symporter is rate limiting for thyroid hormone synthesis, and is regulated by the TSH
- Iodide is stored within the thyroid as thyroglobulin
What are the major synthetic steps in thyroid hormone synthesis?
What regulates these steps?
Major synthetic steps are regulated by TSH:
- Iodine transport (Na-I symporter)
- Organification (attachment) of iodine by TPO: oxidation of iodide before incorporation into tyrosyl residues.
- Coupling: Iodine coupled to Thyroglobulin: Monoiodotyrosine, Diiodotyrosine, Tri (T3), Tetra (T4) etc.
What does the 4 refer to in T4?
Number of attached iodines
What organ/gland makes TSH?
What are the active forms of thyroid hormone?
T3 and T4
What stimulates TSH release?
TRH release by the hypothalamus
- Hypothalamus (TRH) ->
- Anterior pituitary (TSH) ->
- Thyroid (T3, T4) ->
Describe negative feedback of the thyroid hormone circuit?
T3 and T4 feed back to pituitary and hypothalamus to shut down TSH and TRH, respectively
Where is the problem in primary disorders? Secondary?
- Primary- level of thyroid
- Secondary- level of pituitary
Thyroid function tests analyze what?
- Total T3, T4 (includes what is bound to protein)
- Free T3, T4
What is TSH?
- Produced by what gland
- Stimulated by
- Inhibited by
- Promotes what processes
- Indicator of what
- Produced by anterior pituitary gland
- Stimulated by: TRH
- Suppressed by: T4, T3
- Iodine uptake
- Growth of thyroid gland
Reliable indicator of primary hypothyroidism (elevated levels when low T3/T4)
What may cause elevated levels of TSH?
- Primary hypothyroidism
- TSH producing pituitary tumors (rare; 2ndary hypothyroidism)
- Hyperthyroidism (common)
- Hypopituitarism (2ndary)
Is the majority of circulating thyroid hormone T3 or T4? Stats?
Majority of circulating hormone = T4 (98.5%)
Total hormone load is influenced by what?
Serum binding proteins
- Albumin (15%)
- Thyroid binding globulin (70%)
- Transthyretin (10%)
Describe mechanism of Grave's disease
- Levels of T3, T4, TSH
- Thyroid gland becomes unregulated; makes a whole lot of T3/T4
- T3/T4 feed back to pituitary to depress TSH levels (undetectable in assay)
Regulation of thyroid hormones is based on what?
Free component of thyroid hormone
- FT4 helps in the assessment of the pt's true metabolic status
What causes elevations in FT4? Decreases?
- Hyperthyroid phase of thyroiditis (early on, damage -> dump hormones?)
- Hypothyroid phase of thyroiditis
- Euthyroid sick syndrome
What can cause increased TBG (thyroid binding globulin)? Decreased TBG?
- High estrogen states (pregnancy, OCP, HRT)
- Liver disease (early)
- Androgens or anabolic steroids
- Liver disease (late)
Describe T3 resin uptake
- Evaluation of what?
- High/low uptake indicates what
- Used to evaluate binding proteins
- Patient’s serum + tracer amount of 125I-T3
- During incubation the binding proteins in the patient’s serum and the resin compete for the tracer until equilibrium is established
- Resin separated and counted for radioactivity
- High uptake = low binding protein levels
- Low uptake = increased binding protein levels
What Abs directed against the thyroid may result in auto-immune thyroid diseases?
- Anti-microsomal Ab
- Anti-thyroglobulin Ab
- Anti-TPO (thyroid peroxidase) Ab
What do Abs to the thyrotropin receptor cause?
- Some stimulate thyroid gland function (thyroid stimulating immunoglobulins, TSI)
- Others inhibit TSH binding (thyroid binding inhibitory Ig, TBII)
What are possible results of anti-thyroid antibodies?
Depends on the type of Ab, possible:
What is Hashimoto's disease (what Abs present)?
- Anti-thyroglobulin Ab
- Anti-thyroid peroxidase Ab
What is Graves' disease (what Abs present)?
- TSI (thyroid stimulating immunoglobulins)
What are thyroglobulin (Tg) levels in disease?
- Increased in ALL thyroid disease
- Useful for thyroid cancer surveillance post surgery and radioiodine ablation
- NOT useful for initial thyroid cancer diagnosis
What is TRH - Produced by what organ/gland
- Release profile/timing
- Downregulated by what
- Stimulates what
- Produce by hypothalamus
- Release is pulsatile, circadian
- Travels through portal venous system to adenohypophysis (anterior pituitary)
- Stimulates TSH formation
- Downregulated by T3, T4
What are diagnostic tests for thyroid function?
- Thyroid uptake scan (RAIU)
- Ultrasound of the thyroid
- Fine needle aspiration
Describe RAIU and SCAN
- Uptake varies by what
- Scintillation counter measures radioactivity after I123 administration.
- This is used to assess the functional status of thyroid tissue.
- Hyperfunctioning thyroid tissue shows up as a “hot” scan indicating hyperthyroidism
- Non-functioning thyroid tissues appears as a “cold” defect (suspicious of malignancy).
Uptake varies greatly by iodine status:
- Amiodarone, Radio-contrast use
In what hyperthyroid symptoms do you have high RAIU?
- Graves' disease
- Toxic MN goiter
- Toxic nodule
In what hyperthyroid symptoms do you have low RAIU?
- Active Hashimoto's
- Hormone ingestion
- Thyrotoxicosis facititia
- Hamburger thyrotoxicosis
What is seen here?
RAIUS Left to right:
- Toxic MNG
- "Warm" nodule
- Hot nodule
- Cold (photopenic nodule)
What is seen here?
RAIUS Left to right:
- Diffuse toxic goiter
What is normal 4 hr RAIU?
Describe the 24 hr results of RAIU and thyroid condition
> 25%: Hyperthyroid
20-25%: Equivocal (check TSH)
5-9% Equivocal (check TSH)
< 5%: Thyroiditis
What may cause variations in RAIU?
Dependent on dietary iodine intake!!
What are contradindications for RIAUS (radioactive iodine)?
- Pregnancy (test B-hCG)
- No ATD (anti-thyroid drugs) for 7d
- No LT4 for 4d
- No recent use of iodine or radiocontrast (do NOT want to do contrast CT)
When would you want a thyroid ultrasound?
- Evaluate thyroid nodularity: single vs. multinodule goiter
- Assess size and location of nodules
- Assess solid vs. cystic nodules
- Monitor progress of thyroid nodule
- To guide needle biopsy of nodules
- To monitor local recurrence of thyroid cancer
What are indications for fine needle aspiration?
- Evaluation of thyroid nodule/mass for malignancy
- Damage to the neurovascular bundle