Thyroid Flashcards
What 2 categories of hormone are synthesized from Tyrosine?
- Catecholamines
- Thyroid hormones
Describe the functional unit of the thyroid gland.
- A follicle is the functional unit
- picture each follicle as a balloon
- the balloon is made of follicular cells, the air inside is Colloid, outside the balloon are BVs
What is the active thyroid hormone?
T3 (triiodothyronine)
What is the most prevalent form of thyroid hormone in the serum?
T4 (thyroxine; converted to T3 in tissues)
Describe the combinations of DIT and MIT.
DIT+DIT= T4
MIT+DIT=T3
Describe how Iodide gets into follicular cells.
- Na+/I- symporter (NIS) brings I- in
- NIS is secondary transport, uses Na+ gradient from Na/K ATPase
How does Iodide get thru the apical membrane of follicular cells?
-Pendrin
Where is Thyroperoxidase (TPO) located?
-on the colloid-apical membrane of the follicular cells
What are the 3 functions of TPO?
- Oxidize Iodide (I-) to Iodine (I0)
- Organification of Iodine (add I to tyr residue on Tg)
- Conjugates/couples DIT+MIT, or DIT+DIT
Describe the synthesis and exocytosis of Thyroglobulin.
- synthesized on the rER
- glycosylation: improves water solubility
- immediately exocytosed to colloid space
- very few tyr residues are available for Iodination
What class of drug is a competitive inhibitor for TPO?
Thiocarbamides
Describe the process of thyroid hormone SECRETION (after TPO conjugated MIT, DIT)
- the Iodinated Thyroglobulin is sitting in the colloid
- TSH stimulates Endocytosis of Thyroglobulin
- proteases chop Thyroglobulin up
- MIT and DIT are recycled
- Exocytosis of T3 and T4 into blood
Describe the TSH-R and its signal transduction.
G protein coupled receptor
G(as): (works with cAMP+pkA)
If lab results reveal increased MIT:DIT and T3:T4 ratios, what will you suspect?
-some type of Iodine deficiency
What the hell is the Wolff-Chaikoff effect?
-in situation of hyperthyroidism = temporary inhibition of TPO (can lead to hypothyroidism)
What step of thyroid hormone synthesis will be inhibited by the administration of Iodide?
-Uptake of Iodide from the blood by the follicular cell (slows action of Na/I symporter)
What step of thyroid hormone synthesis will be inhibited by the administration of Methimazole?
-all 3 steps done by TPO
What step of thyroid hormone synthesis will be inhibited by the administration of Propylthiouracil (PTU)?
- all 3 steps done by TPO
- PLUS peripheral conversion of T4 to T3 (via 5’-deiodinase)
What step of thyroid hormone synthesis will be inhibited by the administration of Dexamethasone?
-peripheral conversion of T4 to T3
What amino acid is integral for organification of Iodine?
-Tyrosine
Describe the relationship of thyroid function and Iodide uptake.
-higher activity of gland = higher uptake of tagged I (diagnostic test)
What is the difference between T3 and reverse T3?
- T3: distal ring has one Iodine
- reverse T3: distal ring has 2 Iodines
How do peripheral tissues regulate their metabolism?
-by fooling with the proportion of T4 converted into T3 (active) vs. that converted into reverse T3 (inactive)
All Steroid hormones except what are carried around by proteins in the blood?
DHEA (its sulfated)
A cell’s T3/T4 Receptor is found _________.
in the nucleus!
All tissues in the body can regulate their metabolic activity by thyroid hormones EXCEPT:
- brain
- gonads
Describe the relationship of thyroid hormones and neural tissue.
- thyroid hormone ESSENTIAL for neural development
- however, mature neural tissue does not need/use thyroid hormones
What specific neural defects occur in the perinatal period if the mother/infant has hypothyroidism?
-abnormal synapses
-decreased dendritic branching and myelination
= CRETINISM
Describe thyroid hormone’s effects on cardiac tissue.
- increases # of beta receptors
- permissive effect on catecholamines
What is the connection between Primary Hypothyroidism and hyperprolactinemia?
- Hashimoto’s: lo T4, thus hi TSH and TRH
- recall: TRH also stimulates PRL!
- therefore, Hashimoto’s can present additionally with Prolactinoma signs (dry men, wet women)
Describe how a thyroglossal duct cyst forms.
- thryoid gland starts as pouch from proximal esophagus (@base of tongue)
- it moves inferiorly as fetus grows
- thyroglossal duct is the ‘trail’, may persist as cyst or pyramidal extra lobe
How can a thyroglossal duct cyst be diagnosed?
- midline anterior neck mass
- moves with swallowing
Increased levels of thyroid hormone will increase synthesis of __________, which directly increases BMI in nearly every tissue.
Na/K ATPase
Hashimoto’s thyroiditis is associated with HLA ______ and may increase risk of what type of cancer?
- HLA-DR5
- hi risk for Non-Hodgkin’s lymophoma (in the thyroid)
Name 4 causes of hypothyroidism.
- Iodine deficiency
- Hashimoto’s
- drugs (ex Li)
- surgical removal or radioablation
Since Hashimoto’s is an autoimmune condition, what cell type will infiltrate the thyroid?
Lymphocytes (may see Germinal Centers)
Lack of maternal Iodine will cause a baby to present how?
-pot bellied, mentally retarted, short, protruding umbilicus, puffy face, protruding fat tongue
aka cretinism
Pt presents with hypothyroidism following a VIRAL infection, and has a VERY TENDER THYROID. What’s the name and inflammatory pattern seen.
- Subacute (de Quervain’s) Thyroiditis
- granulomatous inflammation
Patient comes in with hypothyroidism, and a ROCK HARD THYROID. It is found that the surrounding areas, as well as the thyroid itself, are fibrotic. What 2 disorders do we need to differentiate here?
- Riedel’s thyroiditis (YOUNG females often)
- Anaplastic Carcinoma (only OLD patients)
TSI antibody is found in what disease, and what is its function?
- Grave’s dz (primary hyperthyroidism)
- IgG that resembles TSH, stimulates R on thyroid gland
What two characteristic external symptoms will be found in Grave’s disease?
- Proptosis/exophthalmos
- Pretibial myxedema (doughy)
Describe the development of Exophthalmos in a Grave’s disease patient.
- fibroblasts behind eye have TSH-R
- TSI Ab will stimulate+cause release of glycosaminoglycans/mucopolysaccharides (push eye fwd)
- hi symp stimulation from hi thyroxine=stimulation of levator palpebra superioris
What is the number one risk in Grave’s disease and the treatment for it?
- thyroid storm (death by arrhythmia)
- Tx: B blocker+PTU+steroids
What are some key findings on histo and blood tests in Grave’s disease?
-scalloping of follicles (colloid pulls away from epith)
- hi blood glucose
- hypocholesterolemia
- hi radioactive Iodine uptake (due to hi activity)
To sample cells from the thyroid, what technique is always used?
-Fine needle aspirate (bloody organ!)
Name the 4 types of Carcinoma in the thyroid gland.
Papillary carcinoma
Follicular carcinoma
Medullary carcinoma
Anaplastic carcinoma
What type of carcinoma will you find nuclei with clearnings in the center?
-Papillary carcinoma (clearings=ground glass=Orphan Annie nuclei)
The 2 follicular cancers of the thyroid have a fibrous capsule. How do you differentiate between them?
- follicular CARCINOMA: cells have spread beyond capsule (malig)
- follicular ADENOMA: cells within capsule (benign)
Medullary carcinomas of the thyroid produce hi levels of ________ from _______ cells.
- Calcitonin
- Parafollicular/C cells
Which carcinoma often presents with sheets of cells within Amyloid stroma?
Medullary carcinoma (the calcitonin can deposit as Amyloid)
Medullary carcinoma has a high association with what 2 conditions?
- MEN 2A
- MEN 2B
Follicular carcinoma likes to metastasize where?
-to the BLOOD (weird for a carcinoma)
What is the difference between MEN 2A and 2B?
2A: aka Sipple dz (Parathyroid involved)
2B: Oral ganglioneuromatosis involved (marfan habitus)
What are the similarities btw MEN 2A and 2B?
- both involve Medullary Thyroid CA
- both involve Pheochromocytomas
- both associated with ret gene
- both have AD inheritance
Which thyroid carcinoma has a high association with childhood radiation, as well as Psammoma bodies?
-Papillary carcinoma
Carcinomas typically like to spread to the lymph nodes. Name the 4 exceptions that like to go to the blood.
- Renal cell carcinoma (renal v)
- Hepatocellular carcinoma (portal v)
- Follicular carcinoma of the thyroid
- Choreocarcinoma
A patient has hyperthyroidism and has a cystic mass of the ovary. What is the dx?
Struma ovarii (germ cell teratoma of the ovary that is mostly thyroid tissue)
