The thyroid (L7) Flashcards
Blood supply to the thyroid
Superior from external carotid
Inferior from thyrocervical trunk
Venous drainage of thyroid
Superior, middle, and inferior thyroid veins that all drain into the internal jugular
Innervation of the thyroid
Middle and inferior cervical ganglia of sympathetic nervous system
Follicle of the thyroid
Epithelial cells surrounding a lumen filled with colloid
Major compound of the lumen
Thyroglobulin (TG)
Parafollicular cells (“C” cells)
Produce calcitonin and other proteins maintaining the follicle
Other cell types in the thyroid
Epithelial cells, fibroblasts, lymphocytes, adipocytes
What is the shape of follicular cells when activated by TSH?
Cuboidal
Microvilli
Extend into the colloid to facilitate transport of TG
Where are the parafollicular cells located?
In the basement membrane; no direct contact with the lumen
Two precursors necessary for thyroid hormone synthesis
Thyroglobulin and iodide
Daily dietary intake of iodine that results in thyroid deficiency
Wolf-Chaikoff effect
Intrathyroidal response that assures constancy of iodide storage in the face of changes in dietary iodide intake - increases in iodide intake decreases gland transport and hormone synthesis
How is the Wolf-Chaikoff effect used clinically?
High doses of iodine are used to shut down hormone synthesis in hyperthyroid patients
HPT axis
Hypothalamus: PVN releases TRH
TSH from anterior pituitary
T3/T4 feeds back on hypothalamus and pituitary
Intracellular “thyroid sensor”
Level of T3 in the anterior pituitary
Inhibition of thyroid stimulating hormone
Tonic inhibition by dopamine, somatostatin
T3 formation from T4
Peripherally deiodinated in thyrotropes and brain by type II deiodinase
How many steps in thyroid hormone synthesis are there?
7
NIS cotransporter
Takes up sodium and iodine on the basolateral surface of the follicle cell, “trapping” iodine inside
Thyroid peroxidase
Turns iodide to iodine
Movement of TG during T3/T4 synthesis
Transported from the follicle out the apical surface into the lumen
What is the fate of the iodine transported into the cell?
It leaves the apical membrane and is attached to the tyrosyl residues on TG
Once the tyrosyl residues are iodinated, what happens?
They are conjugated with T4 and T3
Once the TG is conjugated, what occurs?
The compound is transported back into the follicular cell and packaged into an endosome
Once inside the cell, what happens to the T3/T4 conjugated TG?
Proteolysis - TG, MIT, DIT, T3, and T4 released from vesicle
Final step in T3/T4 synthesis
Transport of T3 and T4 across basolateral membrane and release into blood
Thyroxine’s half-life
Long - ~7 days
Circulation in blood - thyroxine
Tightly bound to transport proteins; binds receptors with low affinity
Triiodothyronine - receptor activity
Binds with high affinity, low capacity
rT3
Reverse T3: biologically inactive
Carbimazole
Inhibits thryoid peroxidase; used as treatment for hyperthyroidism
T3 hormone structure
Formed by the combination of one MIT and one DIT residue
How is rT3 distinguished from T3?
Two iodinated residues on the outer ring instead of the inner ring, only one on the inner ring
T4 hormone structure
Formed by the coupling of two DIT residues
Radioactive iodine uptake scan
Used to test the function of the thyroid gland; use pertechnetate
Hot nodule
Area of increased iodine uptake and thyroid hormone synthesis; usually benign
Cold nodule
Area of dysfunctional/inactive iodine uptake and decreased thyroid hormone synthesis; can be benign or malignant
Normal uptake of radioactive iodine
25% after 24 hours
Parameters for hyper/hypothyroidism based on radioactive iodine uptake
> 60%: hyperthyroid
Organification defect
Iodine cannot be added to tyrosyl residues; tested with perchlorate (NIS inhibitor)
Type 1 deiodinase
Outer and inner ring deiodinase found in the liver, kidney, thyroid, and skeletal muscle
Type 2 deiodinase
Outer ring deiodinase found in brain, pituitary, placenta, and cardiac muscle
(THYROID SENSOR IN PITUITARY)
Type 3 deiodinase
Inner ring deiodinase found in brain, placenta, and skin
What is the difference between inner and outer ring deiodination?
Inner ring: deactivates (rT3 formation)
Outer ring: activates (T3 formation)
Which is in higher storage, T3 or T4?
T4; long half life
How much of T4 is switched over to T3?
80% peripherally; T4 has low affinity
How much of thyroid hormone is bound peripherally?
More than 99%
Breakdown of proteins binding thyroid hormone
TBG: 70%
Transthyretin: 10%
Albumin: 15-25%
Which form, T3 or T4, binds more tightly to carrier proteins?
T4; half life of 7 days vs T3’s half life of 1 day
How long is TBG?
394 AA glycoprotein
What factors affect concentration of TBG?
Hepatitis, estrogen: increase
Nephrotic syndrome, steroids: decrease
Changes in TBG and effects on T3/T4
Bioavailable T3 usually doesn’t change, but total levels of T3 and T4 do
To what family of receptors does the thyroid hormone receptor belong?
Nuclear receptor hormones; same as steroids
With what does the THR heterodimerize?
Retinoic acid receptor (RXR)
What type of cell expresses THR?
Almost every type
Physiologic effects of thyroid hormone
T3 increases mitochondrial activity and generates futile cycles, increasing oxygen consumption and heat production
Neurologic effects of thyroid hormone
Necessary for proper neural development
- Induces neural cell migration/differentiation
- Myelination
- Synaptic transmission
Cretinism
Iodine deficiency during development, causing short stature, mental retardation, and delayed motor development
Physiologic effects on the heart
Increased cardiac output by increase in resting heart rate and stroke volume
Consequence on the heart of hyperthyroidism
Possible development of arrhythmias
Etiology of goiter production
Thyroid cancer (3:1 women:men)
Hyperthyroidism; Graves’ disease
Hypothyroidism; Hashimoto’s
Etiology of Graves’ disease
Autoimmune disorder that causes stimulation of TSH receptors by long-acting thyroid stimulator (LATS)
Symptoms of Graves’ disease
Diffuse bilateral goiters Irritability Nervousness Hyperactivity Muscle wasting Weight loss Heat intolerance Tachycardia Ophthalmopathy
Histology of Graves’ thyroid
Scant colloid, tall columnar follicular cells, infiltration of lymphocytes
Etiology of Hashimoto’s thyroiditis
Autoimmune disorder; antibodies against TPO and TG. Causes destruction of thyroid tissue
Symptoms of Hashimoto’s
Lethargy Fatigue Weight gain Decreased appetite Hair loss Brittle nails Cold intolerance
What is thyroid storm?
An emergency life-threatening situation in which hyperthyroidism is coupled with severe, acute illness
Symptoms of thyroid storm
Tachycardia High fever Altered mental status Severe nausea, vomiting, diarrhea Severe circulatory collapse --> death
Treatment for thyroid storm
Carbimazole
Propylthiouracil (PTU) - acute treatment
Beta blockers to restore normal heart function