Thyroid and HPT Axis Flashcards
What is the blood supply of the thyroid?
Superior and Inferior Thyroid Arteries
What is the cell type found in inactive follicles?
Squamous Epithelium
What is the cell type found in active follicles?
Cuboidal Epithelium
What is the follicle?
Epithelial cells surrounding lumen - lumen filled with colloid
What is the function of the C cells (parafollicular cells)?
Produce calcitonin and maintain the follicle
What are the 2 precursors of thyroid hormone?
Thyroglobulin (TG) and Iodide
What is the Wolf-Chaikoff effect?
Increases in iodide intake decrease gland transport and hormone synthesis and vice- versa.
Allows for constant iodine storage even with dietary changes.
How is the Wolf-Chaikoff effect used clinically?
Very high iodide doses are used to rapidly shut down thyroid hormone production in hyperthyroid patients
What are the different thyroid hormones?
T3
T4
rT3
What is T4?
Thyroxine.
Tightly bound to transport proteins in blood Binds to receptor with low affinity
What is T3?
Triiodothyronine.
Primary active form
Binds with high affinity, low capacity to receptor
What is rT3?
Reverse Triiodothyronine.
Inactive
What are the components of the HPT axis?
Hypothalamus - PVN
Pituitary - Thyrotropes
Thyroid
How is the HPT axis regulated?
Negative feedback by T4/T3 in hypothalamus.
Negative feedback in pituitary by intracellular T3
What does the polarization of the thyroid follicle refer to?
Different functions of the apical and basolateral membranes
What is the function of the apical follicle?
Apical surface is exposed to the lumen (colloid) and thyroid hormone synthesis occurs here with the iodination of TG
What is the function of the basolateral follicle?
Basolateral surface is exposed to the blood and is responsible for the uptake of iodine and the release of thyroid hormone
What occurs with iodide trapping?
TSH stimulates iodide (I-) trapping by increasing the activity of the NIS (sodium iodide symporter) co- transporter in the basal membrane of the follicular epithelial cell.
What happens after iodide transported into the follicle?
I- transported to follicular lumen and oxidized by thyroid peroxidase (TPO) to form iodine (I).
What is iodination?
Tyrosyl residues on TG will have iodine added to them
What is the conjugation of iodinated tyrosines?
Conjugation of iodinated tyrosines to form T4 and T3-linked thyroglobulin (TG)
What is the function of the drug carbimazole?
Inhibits thyroid peroxidase.
Iodide will not be oxidized into iodine.
What happens of following conjugation of iodinated tyrosine?
- Conjugated thyroglobulin with T4/T3 enters follicular epithelial cell.
- Packaged in endosomes
- TG, MIT, DIT, T4, T3 released from vesicle
- T4/T3 secreted into circulation
What is the function of the radioactive iodide uptake scan?
Measures iodide uptake and used to determine function of thyroid gland.
Normal is 25% in 24 hours
> 60% = hyperthyroid
What is the function of Type I thyroid hormone conversion?
Outer and inner ring deiodinase
Liver, kidney, thyroid, skeletal muscle
Primary source of T3 in circulation
What is the function of Type II thyroid hormone conversion?
Outer ring deiodinase
Brain, pituitary, placenta, cardiac muscle
What is the function of Type III thyroid hormone conversion?
Inner ring deiodinase
Brain, placenta, skin
What are the transport proteins for thyroid hormone?
Thyroxine-binding globulin
Transthyretin
Albumin
What thyroid hormone is the most tightly bound in circulation?
T4
What is the thyroid hormone receptor?
Nuclear receptor family
- same as steroid hormones
- forms heterodimers with
- retinoic acid receptor (RXR)
What is the receptor affinity of thyroid hormone receptor for T3 and T4?
High affinity, low capacity for T3
Low affinity for T4 – very little biological activity at physiological concentrations
What are the functions of thyroid hormone?
Increases BMR (Stimulates hepatic gluconeogenesis/proteolysis/lipolysis)
Promotes CNS maturation
Increases beta-adrenergic receptors
Increases thermogenesis
What is the cause of cretinism?
T3 is crucial for normal brain development
Cretinism is caused by iodine deficiency during development
What are the effects of cretinism?
Short stature/impaired bone formation Mental retardation
Delayed motor development
What is the effect of thyroid hormone on the heart?
T3 increases cardiac output
Why are goiters formed in hyper and hypothyroidism?
Hyper - thyroid overstimulation
Hypo - no negative feedback on thyroid which will increase TSH levels and form goiter
What is the cause of Graves Disease?
Autoimmune – antibodies stimulate TSH receptor (Long Acting-Thyroid Stimulator – LATS) which lead to increased T3/T4
What are some symptoms of Graves Disease?
Diffuse symmetrical goiters with hyperthyroid
symptoms: tachycardia, opthalmopathy, irritability, hyperactivity, heat intolerance, weight loss, nervousness, muscle wasting
What is the cause of Hashimoto’s Disease?
Autoimmune destruction of thyroid follicles that will destroy TPO and TG which causes hypothyroidism
What are some symptoms of Hashimoto’s Disease?
Diffuse goiter with hypothyroid symptoms: lethargy, fatigue, hair loss, cold intolerance, brittle nails decreased appetite, weight gain
What is the cause of thyroid storm?
Hyperthyroid disorder coupled with severe acute illness
What are the symptoms of thyroid storm?
High fever Tachycardia Altered mental status Severe nausea, vomiting, diarrhea Severe circulatory collapse ----- resulting in death
What is the function of thyroid peroxidase (TPO)?
Converts iodide into iodine
