3. Robbins: Thyroid Flashcards
Describe the morphology of the thyroid
What is the mechanism of T3/T4 release from the thyroid?
Where is thyroglobulin made and stored?
Colloid
What is thyroglobulin converted into?
T4 (thyroxine) and lesser amounts, into T3 (triidothyronine).
Which thyroid hormones binds to [thyroid hormone nuclear receptors] in target cells with greater affinity and have greater activity?
T3
Actions of thyroid hormone
- Increase in the basal metabolic rate (MAIN)
- Carb/lipid catabolism
- Protein synthesis
_________ = chemicals that inhibit the function of the thyroid gland
Goitrogens: [↓ T3/T4 —> ↑ TSH —> enlargement of the thyroid].
What is the MOA of the antithyroid agent, propylthiouracil?
Decreases TH production
- Inhibits the oxidation of iodide by TPO => thus, blocks production of TH
- Inhibits the peripheral conversion/deiodination of T4 => T3
What occurs when large doses of iodide are given?
- Acts as a goitrogen: Blocks release of thyroid hormones by inhibiting the proteolysis of thyroglobulin.
- Thyroid hormone is made and incorperated into colloid, but not released into blood.
Hyperthyroidism is also called _______.
Thyrotoxicosis
Hyperthyroidism/Thyrotoxicosis
- What is it?
- Types and MCC
- Hypermetabolic state d/t increase levels of free T3/4
- Primary hyperparathyroidism (MC) and secondary hyperparathyroidism.
Types of Primary Hyperparathyroidism
Which is the MC?
- Diffuse hyperplasia (Graves disease) of thyroid => MC
- Hyperfunctioning mulinodular goiter
- Hyperfunctioning thyroid adenoma
Types of Secondary Hyperparathyroidism
- Pituitary thyrotroph adenoma
How does the clinical presentation of hyperthyroidism vary?
Symptoms exist on a continuum
- 1. Apathetic hyperthyroidism
- 2. Regular hyperthyroidism
- 3. Thyroid storm
Symptoms of Regular Hyperthyroidism
-
Hypermetabolic state due to too much T3/T4 and overactive sympathetic NS
- Increase in BMR => perspiration, flushing and heat intolerance
- Cardiac manifestations: tachycardia, palpitatio, sinus tachycardia (NL rhythm, but increase rate: a-fib)
- Exophthalmos
- Overative sympathetic NS: nervousness, excited, restless, insomnia, emotionally unstable
Thyroid Storm
What is it?
Symptoms
If left untreated what is a common cause of death?
Thyroid storm = abrupt onset of SEVERE hyperthyroidism that occurs MC in patients with Graves disease and most likely due to acute elevation of catecholamines
- Febrile
- Cardiac manifestation: tachycardia and CHF
- GI symptoms: diarrhea and jaundic
- Death: due to cardiac arrhythmia
Who is more likely to get thyroid storm?
- Ppl with Graves disease who are/have
- Pregnancy/postpartum
- Hemithyroidectomy
- Take amiodarone
Apathetic hyperthyroidism
What is it?
- Thyrotoxicosis that occurs in older adults who have co-morbidities that mask symptoms. Present with
- Unexplained WL
- Worsening CV disease
T3/T4 & TSH levels
Primary and secondary hyperthyroidism
- Primary: ↑ T3/T4 and ↓ TSH levels
- Secondary: ↑ T3/T4 and ↑ TSH levels
TRH stimulation test
- NL rise in TSH =______
excludes secondary hyperthyroidism
Once a diagnosis of thyrotoxicosis is made, how can we determine etiology?
- Measure radioative iodine uptake by thyroid gland
- ↑ uptake by whole gland = Graves
- ↑ uptake by 1 nodule = Toxic adenoma
- ↓ uptake = thyroiditis
Treatment of Hyperthyroidism
- Treat manifestations with B-blocksrs or NSAIDS
-
Treat underlying disease with:
- High doses of iodide (Wolf-Chaikoff effect)
- Thionamide
- Radiodine ablation
- Surgery
MC etiology of Hyperthyroidism
Graves disease
What is Graves Disease?
AI disorder caused by (+) of thyroid epithelial cells by TSI (thyroid stimulating immunoglobulins) autoAb to the TSH-receptor that mimic TSHs action.
Graves Disease
- Triad of symptoms
- Hyperthyroidism with gland enlargment
- Infiltrative ophthalmopathy –> exophthalmos
- Pretibial myxedema/dermopathy = scaly/indurated skin on shins
Graves Disease
- MC in:
- Most common antibody subtype
- HLA subtypes associated with Graves disease:
- Lab findings
- W 20-40 YO
- Thyroid stimulating immunoglobulin (TSI)
- HLA-DR3 and B8
- ↑ free T3/4; ↓ TSH; ↑ uptake of radioactive iodine (bc thyroid follicles are STILL being stimulated by TSI)
The exopthalmos associated with Graves Disease is caused by what underlying process?
- CD4-helper T cells infiltration of retroorbital space and release TSI =>
- TSI Ab bind to TSH-receptor on fibroblasts => proliferate
- EOM begin to swell due to edema + inflammation
- Accumulation of EC matrix components (GAG and chondroitin sulfate)
- ↑ number and expansion of adipocytes
- Eyeball pushes forward.
The exopthalmos associated w/ Graves disease appears to stem from activation of which cells in the orbit and via which receptor?
Orbital preadipocyte fibroblasts, which have TSH receptors
Gross morphology of Graves Disease
- Soft, symmetrical enlargement of thyroid due to diffuse hypertrophy and hyperplasia of follicular epithelial cells
Histology of the thyroid in untreated Graves Disease
- Follicular epithelial cells are taller and more crowded –> formation of small papillae WITHOUT fibrovascular cores that project into the lumen and encroach on the colloid
- Colloid has scalloped margins with resorption droplets (colloid in endocytotic vesicles made by pseudopodial extensions of cytoplasm at the lumen)
- Lymphiod infiltrates + germinal centers
How do the papillae seen in graves disease differ histologically from those of papillary carcinoma?
Lack fibrovascular cores
Hypothyroidism
- MC in whom?
- Due to?
- Increases with age; W
- Primary hypothyroidism *** vs. Secondary hypothyroidism
Primary hypothyroidism can be _______, _______, _____
Congenital vs Autoimmune vs Iatrogenic
Congenital hypothyroidism is most often due to _________
Endemic iodine deficiency in the diet during pregnancy.
Inborn errors of thyroid metabolism causing congenital hypothyroidism is known as what?
Dyshormonogenetic goiter: where one of multiple steps leading to thyroid hormone synthesis is defective:
- Iodide transport into thyrocyte
- Organification of iodine (binding of iodine to tyrosine resides of the storage protein, thyroglobulin)
- Iodotyrosine coupling to form active T3/4