Why do we have a thyroid gland? (2)
- Secretes thyroid hormone.
2. Secretes calcitonin.
Areas/organs with lots of receptors for thyroid hormones
Lungs, Heart, Pituitary, Skeletal muscle, Liver, Intestine
General physiologic effects of thyroid hormone
Increase use of energy, increase catabolism of muscles and fat, increased development of bone tissue, chronotropic and inotropic effects in heart
General effects of calcitonin
Regulates circulating calcium levels by decreasing osteoclast (breakdown) activity in bone tissue. “Preserves” the bone, and therefore decreases free calcium in the blood.
Cells that secrete thyroid hormone and calcitonin.
Follicle and parafollicular cells, respectively.
Location of synthesis of thyroid hormones.
Colloid material surrounded by follicular cells separated by parafollicular cells.
Main thyroid hormones and levels of activity.
Tetraiodothyronine (T4) is most secreted from thyroid, with iodine subs at foiur places.
Triiodothyronine (T3) is main active hormonal form, and has three substitutions.
Main organs that use iodine.
Thyroid (incorporate into hormones).
Kidney (excrete).
Synthesis of T3 and T4
- Active transport of I- across basement membrane of follicular cell through NIS.
- Pendrin transporter pulls I- through apical membrane into colloid.
3a. I- converted to I+ through H2O2 and thyroidal peroxidase
3b. I+ (or other) attached to tyrosine residues on Thyroglobulin (Tg) complex to make DIT and MIT.
3c. DIT and MIT combine in various ways to get T3, T4, and alanine. - Tg complex is endocytosed into follicular cell and broken up.
5a. MIT and DIT recycled through Pendrin transporters.
5b. T4 converted to T3 through 5’ deiodinase. - T4 and T3 diffuse out of basement membrane of follicular cell.
State of T3 and T4 in blood.
Mostly bound to proteins, 95% of these to TBG (thyroxin binding globulin). Makes very stable, with long half life. The pituitary responds and regulates FREE hormones, so if there is a lot of free hormone, the pituitary will slow secretion of hormones from thyroid. However, because the hormones are free in blood, they’ll break down faster.
How is T4 converted to T3?
Three deiodinases, all if which need SELENIUM:
D1 - most important (liver, kidney, thyroid)
D2 - Target organs have own deiodinase ability (Brain, pituitary, BAT, heart, skeletal muscle)
D3 - The mighty ducks. Makes reverse T3, which is inactive, but sometimes necessary (placenta, skin, brain)
What is needed to convert between T4 and T3?
Deiodinase (1, 2, 3) and SELENIUM
What is the effect of starvation on levels of T4, T3, and RT3? Why?
T4 will decrease just a bit. Usually it will want to convert mostly to T3, but T3 induces metabolic, calorie-burning activity. So, in starvation mode, RT3 will be made instead, in order to conserve energy.
Regulation of thyroid
Classic feedback loop. The products of thyroid (free T3 and T4) downregulate secretion of Thyrotropin releasing hormone (TRH) at hypothalamus. Reduction of TRH means reduced TSH (thyroid stimulation hormone) from pituitary to thyroid, which means less T3 and T4 made. Use TSH plus the T3 and T4 levels to determine hyper or hypo thyroidism.
Where do T3 and T4 act?
In the nucleus, as elements of gene promotion. Attracted to specific response elements, which then kick off the co-repressers in favor of T3/4 and a coactivator, and then expression happens.
What type of genes do T3 and T4 upregulate?
Genes that cause you to spend energy! Alpha myosin heavy chain (muscle cell proteins of contraction) Sarcoplasmic reticulum Ca++ ATPase beta adrenergic receptors G proteins (need ATP!) Sodium potassium ATPase Potassium channels
Types of hypothyroidism and causes.
- Primary - something wrong with the organ (thyroid). Disease, lack, Hashimoto’s autoimmune destruction.
- Secondary - something wrong with TSH release, either due to problem in pituitary, or even farther upstream in the hypothalamus.
- Iodine deficiency.
What is myxedema?
Adult hypothyroidism, but is also the term used for the skin condition due to adult hypothyroidism. Dry, waxy swelling of skin and abnormal mucin deposits, especially in face.
How to tell what type of hypothyroidism a patient’s got?
- If primary (something wrong with thyroid), then patient will NOT respond to a dose of TSH (which would normally induce thyroid activity), but will only respond to injections of T4 or T3 (usually T4, lasts longer)
- If dose with TRH and level of TSH in blood stream rises, then we know that the problem is in the hypothalamus.
- Treat with iodine and improve - nutritional deficiency.
What happens to the thyroid when iodine levels get low?
The thyroid can’t make enough T3 and T4, so the hypothalamus “reads” a lower level of T3 and T4 in blood, and upregulates pituitary which upregulates thyroid, which switches into overdrive and works harder. Causes hypertrophy and a goiter!
Causes of Hyperthyroidism.
- Grave’s disease - antibodies to TSH receptor make it constitutively turned “on,” so looks a lot like a regular goiter.
- Solitary toxic adenoma - one part of thyroid is just doing its own thing, regardless of input from brain, and is making too much hormone
- Hashimoto thyroiditis - early stage when inflammation is causing excess production, which ultimately breaks the organ and moves the patient into the classic phase of the disease, in which patient exhibits hypothyroidism
- TSH-secreting pituitary tumor
- Mutations on TSH receptors to turn on all the time.
- OTHER!
Thyrotoxicosis
Above and beyond hyperthyroidism, which is caused by excessive thyroid function. This is just TOO MUCH HORMONE.
Symptoms of Hyperthyroidism
THE TWITCHES! Nervousness Weight loss Hyperphagia - hungry all the time! Heat intolerance (already overheated inside) Warm, soft skin High BMR - Cry me a river, Kate Moss.
Symptoms adult hypothyroidism.
Low BMR Coarse, sparse hair Dry, yellowish skin Poor cold tolerance (because already running low) Slow mentation Poor memory
