10/7- Intro to Thyroid Disorders Flashcards
What is the embryological origin of the medial portion of the thyroid? Lateral?
Medial:
- Foramen cecum at the base of the tongue
- This migrates caudally until it reaches the adult resting place
- Thyroglossal duct may persist in adults
Lateral:
- Ultimobranchial body (part of 5th branchial arch)
- Maldescent/non-descent may result in persistent thyroglossal duct
Describe the anatomy of the thyroid
- Lobes
- Weight
- Vasculature
- Microscopy
- 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?
Iodine
- RDA = 150 ug/d
Why is iodine necessary for thyroid hormone synthesis?
- How does the thyroid gland get enough?
- Storage?
- 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?
Pituitary (anterior)
What are the active forms of thyroid hormone?
T3 and T4
What stimulates TSH release?
TRH release by the hypothalamus
Overview
- Hypothalamus (TRH) ->
- Anterior pituitary (TSH) ->
- Thyroid (T3, T4) ->
- Tissue
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?
- TSH
- 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
TSH/Thyrotropin
- Produced by anterior pituitary gland
- Stimulated by: TRH
- Suppressed by: T4, T3
Stimulates:
- Iodine uptake
- Growth of thyroid gland
Reliable indicator of primary hypothyroidism (elevated levels when low T3/T4)
What may cause elevated levels of TSH?
Depressed levels?
Elevations:
- Primary hypothyroidism
- TSH producing pituitary tumors (rare; 2ndary hypothyroidism)
Depressions:
- 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
Thyroidoxitosis
- 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?
Increased levels:
- Hyperthyroidism
- Hyperthyroid phase of thyroiditis (early on, damage -> dump hormones?)
Decreased levels:
- Hypothyroidism
- Hypothyroid phase of thyroiditis
- Euthyroid sick syndrome
What can cause increased TBG (thyroid binding globulin)? Decreased TBG?
Increased TBG:
- High estrogen states (pregnancy, OCP, HRT)
- Liver disease (early)
Decreased TBG:
- Androgens or anabolic steroids
- Liver disease (late)
Describe T3 resin uptake
- Evaluation of what?
- Process
- 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?
Varied effects
- 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:
- Hyperthyroidism
- Hypothyroidism
- Goiter
- Atrophy
