Thyroid Hormones and Anti-Thyroid Drugs

Follicle cells produce ____?

C-cells produce ______?

Thyroid hormones (T4/T3)

Calcitonin

What is the only active form of thyroid hormone?

Triiodothyronine (T3)

What is the precursor to thyroid hormone?

Tyrosine

What form of thyroid hormone can be converted to the active form?

T4

What mechanism allows iodine to get into the follicular cell?

Na/K-ATPase coupled w/ Na-I symporter

What is going to bring I- into the colloid cell?

Pendrin (I- channel)

Explain how thyroid hormone is made in the colloid?

Iodine is coupled w/ thyroglobulin by thyroid peroxidase and resulting thyroglobulin w/ iodine will be proteolized to liberate T3/T4

T3 will act like a ___ hormone meaning?

Steroid hormone meaning it goes into the nucleus binding to TRE and produces a gene change to make proteins

What are the two inactive forms of Thyroid hormone?

T4 -> rT3

T3- T2

What is the neuroendocrine function of thyroid hormone?

Increasing sensitivity to SNS

Increased stimulation to all other endocrine organs

What is the effect of T3 on cardiac system?

Increase CO, (HR contractility and BP)

How does T3 affect respiratory and metabolic systems?

Increase O2 consumption

Increase erythropoiesis to increase O2 delivery and normal sensitivity to O2 and CO2 centers

TRH is secreted by?

TSH is secreted by?

Thyrotropin releasing hormone - hypothalamus

Thyroid stimulating hormone - anterior lobe of the pituitary

If we are hypothyroid we will see ____ T4 and _____ TSH.

If we are hyperthyroid we will see ___ T4 and _____ TSH.

Decreased, Increased.

Increased, Decreased.

What are some signs of hypothyroidism?

Bilat alopecia

Rear leg weakness, lethargy

Mild agression

How does TSH work?

Increases lysosome export of T3 and T4

Increases production of thyroglobulin by stimulating thyroid peroxidase, Na/I symporter and increasing transcription factors for thyroglobulin proteins

What is the poster child for hypothyroidism?

Dobermans

What is primary hypothyroidism?

An autoimmun dz due to lymphocytic thyroiditis attacking the colloid cells

What is congenital hypothyroidism?

Recessive mutations in thyroid peroxidase so that animals cannot connect iodine to thryroglobin, will see lots of developmental abnormalities (common in terriers)

Hypothyroidism can ve secondary to ___ or ___?

Dz or nutritional status

What is the most common cause of drug induced hypothyroidism?

What are other more rare causes?

Trimethoprim/sulfonamides (antibiotics) primary cause

Glucocorticoids

Phenobarbital

What are indications of levothyroxine?

primary and secondary hypothyroidism in dogs, cats, horses birds and reptiles (Basically just t4)

What are the Pharmacokinetics of Levothyroxine?

PO - reduced bioabalibility w/ food

Can give as liquid but 2x more bioavalibiltiy so monitor dose

In vasculature high protein binding

Hepatic metabolism (All of the metabolic pathways)

8-11hr 1/2 life (dog - cat)

____ % of T4 is free and ___% of T3 will be free?

0.1%

1.0%

What are AE of Levothyroxine?

Iatrogenic hyperthyroidism or thyroxotoxicosis

(monitor T4 and will be more common w/ synthetic T3 prep)

What are CI of levothyroxine?

Thyrotoxicosis

Acute myocardial infractions (heart attack)

Untreated adrenal insufficiency (drug will Increases SNS symptoms and can't respond to stress)

What are some symptoms of hyperthyroidism?

Polyphagia,

wt loss w/ atrophy

Poor coat

Hyper activity

PU/PD

Devil blue eyes

(Poss enlarged thyroid lobes)

What is the most common endocrine disorder in cats?

Hyperthyroidism

What can cause hyperthyroidism?

Adenocarcinomas

altered TSH sensitivity

High levels of dietary iodine/ soy

What is a common overlapping pathology we might see w/ hyperthryoridism? Why do we not see this until we've tx hyperthyroidism?

CKD. Wont see till tx b/c hyperthyroidism will increase CO and perfusion to the kidneys increasing GFR so it will mask the decreased kidney function

What are the pharmacodynamics of methimazole?

Inhibition of thyropiroxidase resulting in the inhibition of I coupling preventing the formation of thyroglobulin

What are the Pharmacokinetics of Methimazole?

PO or transdermal (better availability po but tastes bitter)

Concentrates in thyroid colloid

Liver metabolism

2-10hr 1/2 life

What are AE of Methimazole?

Unmasking CKD,

Antinuclear antibodies (myasthenia like syndrome/ lupus)

GI symptoms

Thrombocytopenia and leucopenia (increase bleeding and infection risk)

Hepatopathy

Self induced excoriation

All AE of Methimazole can be reversed if? How long does this take?

D/C the drug

Can take several weeks to resolve- can require new cell synthesis?

How long will it take to see affects w/ methimazole?

3-4 W/ b/c it takes time to accumulate in colloid - no direct effect on circulating T3/T4

When might we start to see AE of Methimazole?

Weeks to months -

Self excoriation - 6w

Lupus 3m

Myesthinea - 6m

What is I131?

A radioactive iodine molecule used to tx hyperthyroidism

What are the pharmacodynamics of I131?

Concentrates in thyroid colloid and will produce low energy beta particles and destroys cells in colloid.

I131 will not destroy what cell?

C-cells- will maintain Ca2+ homeostatsis

What should we consider when recommending I131?

Irreversible- should assess CKD first w/ methimazole

-Expensive tx animal will need to be kept in hospital to reduce risk of radioactivity to clients

What is the drug of chose for thyrotoxicosis? Why?

Propranolol

- Decreases HR via B1

- inactivates T4 by blocking type 1 and 2 Monodeioninases that convert it to T3

What are signs of thyrotoxicosis?

Tachycardia/ arrhythmia

Hypertension

Tachypnea (In L CHF)

Hypokalemia

Venous thromboembolism

Seizures

Sudden death