Endocrinology - Lecture 2 Flashcards
Where is the thyroid gland located?
Inferior to the larynx
T/F - The thyroid gland has more vascular flow per gram of tissue than the kidney.
True - it has an important endocrine function so it needs to be highly vascularized
Where does the thyroid develop?
At the base of the tongue and it moves downward during development
What does the internal structure of the thyroid gland consist of?
A series of hollow follicles formed by spheres of epithelial cells and filled with colloid
What is colloid?
A gel filling the follicle
What does the apical surface of follicle (epithelial) face?
Colloid
What does the basal surface of the follicle (epithelial) cells face?
Blood supply
What is the function of follicle cells?
They dump all of the ingredients needed to make thyroid hormone into the follicle, and thyroid hormone is made extracellularly in the colloid
Why is thyroid hormone made in the colloid?
Thyroid hormone is lipid soluble, so it can be stored in the gel of the colloid
How is Thyroid hormone synthesized?
1) Iodide is transported from the blood across the basal side of the follicle cells via a Na/I transporter
2) Iodide diffuses down its concentration gradient across the apical membrane into the colloid of the follicle
3) The follicle cells also synthesize a large-tyrosine-rich protein called thyroglobulin (TG), and the enzyme thyroid peroxidase - and both go into the colloid
4) 3 or 4 Iodides are oxidized by thyroid peroxidase and linked to TG
Describe the Na/I transporter
A co-transporter from the blood into follicle cells
Na naturally moves down the concentration gradient and I goes along for the ride
This is the rate limiting step for TH synthesis because I is rare in the body
How does the I conc. gradient maintain balance?
As soon as I reaches the colloid, it gets integrated
What’s the difference between T3 and T4?
T3 is a tri-iodothyronine made from a DIT and an MIT
T4 is a tetra-iodothyronine made from two DITs
What stimulates the release of thyroid hormone?
TSH being released from the anterior ptuitary in response to TRH from the hypothalamus
What are the steps of secretion of thyroid hormone?
1) In response to TSH, droplets of colloid containing TG+T3/4 are pinocytosed into the follicle cell
2) The droplet fuses with lysozyme with enzymes that cleave off the TG
3) T3 and T4 are released in the cytoplasm by lysosomal hydrolysis
4) T3 and T4 diffuse into the capillaries, and the amino acids from the degraded TG are recycled into new TG
Which thyroid hormone is secreted from the thyroid more?
T4 makes up 90% of the TH secreted
But T3 is more biologically active (binds to receptors with greater affinity)
What happens to most of the T4? Why?
80% of the T4 that gets secreted is converted to T3 in the liver and kidney
The extra I is sent back to the thyroid to be recycled
This maximizes the concentration gradient for free I in circulation
What effect does TH have on the endocrine system?
It has a negative feedback by acting on the anterior pituitary and limits the secretion of TSH and TRH receptors
What other effect does TSH have on follicle cells?
It stimulates follicle cell metabolism and replicaiton
Where are TH receptors found?
Nuclei in almost all cells in the body
What are the 4 isoforms of TH receptors?
a1, a2, B1, B2
Different tissues may express different receptors
What happens when TH binds to a receptor?
It dimerizes with another TH receptor and forms a DNA binding protein that regulates gene transcription
What does TH regulate?
Many of the proteins that are responsible for effects on cellular metabolism
What do unbound TH receptor dimers do?
They can also bind to DNA and typically inhibit transcription
(aka, if there is no TH, transcription is inhibited)
What ways can TH increase metabolism?
Increase Na/K ATPase activity
Increase the synthesis of respiratory enzymes
Increase substrate availability
Increase cellular heat produciton
Effect mitochondria growth and replication
What effect does TH have on the sympathetic nervous system?
It upregulates B-adrenergic receptors that are critical for responses to the symp-ns
AKA it increases sensitivities to catecholamines
What effect does TH have on growth?
Helps synthesize growth hormone (GH)
It also reacts with GH in periphery to have bone growth
How does TH effect the central nervous system?
It helps in development and function (especially the myelination of axons)
It also helps in attention and reflexes (maintaining myelination)
What is the main cause of hypothyroidism?
Typically a defect to the thyroid itself, or an iodine deficiency
Without iodine, there is insufficient prduction of TH, and there lacks a negative feedback, which increases TRH and TSH, which leads to the growth of a goiter
What are some of the minor causes of hypothyroidism?
Autoimmune throiditis - lacks synthesis of TH
Damage or destruction - surgical, radiation, etc
Dysfunction associated with another illness
What are the causes of secondary defects associated with hypothyroidism?
Deficits in TRH or TSH synthesis, release, or receptor deficits
Chronic symptoms of hypothyroidism
Abnormal circulating concentrations of TH and TSH
Goiter (primary defect only)
Cretinism and mental retardation if condition is during development
Symptoms of mild hypothyroidism
Sensitivity to cold
Slight weight gain
Symptoms of moderate hypothyroidsm
Fatigue Reduced bloodflow Changes in skin tone Sluggish gastrointestinal activity Discoloration of skin
Symptoms of severe hypothyroidism
Myxedema
Severe bloating
What primary defects cause hyperthyroidism?
Thyroid tumors that produce TH without regulation
Inflammation of the gland that leads to production of excess TH
How can Grave’s disease cause hyperthyroidism?
Antibodies are produced against TSH, and antibodies are able to activate the TSH receptor, so there is no negative feedback against the synthesis of TH
Thyrotoxicosis factitia
Hyperthyroidism that results from consuming excess thyroid hormone either from medication or inappropriately processed meat
Symptoms of hyperthyroidims
Abnormal circulating concentrations of TH (high) and TSH (low) Goiter Heat intolerance Weight loss Increased appetite Sweating CT behind eye swells
Treatment for hyperthyroidism
Surgical removal of gland
Destruction of gland using radiactive I
Antithyroid drugs
B-blocks
What are some dental issues that can arise due to Hypothyroidism
Delayed dental eruption leading to malocclusion
Anterior open bite
What are some dental issues that can arise due to Hyperthyroidism?
Increased susceptibility to caries
Increased susceptibility to periodontal disease
Accelerated dental eruption
Maxillary and mandibular osteoperosis
