Thyroid Hormones and Thyroid Disorders (PART 1)

Thyroid gland

Its composed of millions of clusters of follicles?

Thyroid hormones

Each follicle of the Thyroid gland secretes what hormones?

• T4 (tetraiodothyronine)

• T3 (triiodothyronine)

Two types of thyroid hormones secreted by the follicles of thyroid gland?

Parafollicular (C)

Another follicle of the thyroid gland that secretes calcitonin?

Thyroxine

Another name for “tetraiodothyronine”

Tetraiodothyronine

Most abundant thyroid hormone

Triiodothyronine

Most potent thyroid hormone?

• Thyroid hormones are responsible for the metabolic rate and body temperature

• The hypothalamus is stimulated either by a negative feedback loop(excess thyroid hormones) or insufficient thyroid hormones in the blood

• The anterior pituitary is stimulated by the thyrotropin releasing hormone (TRH) released by the hypothalamus

• The thyroid gland is stimulated by the thyroid stimulating hormone(TSH) released by the anterior pituitary

• Excess thyroid hormones in the blood will cause a negative feedback loop that inhibits the hypothalamus and the anterior pituitary gland to release hormones

Explain the physiology of releasing thyroid hormones

• Thyroid hormones are responsible for two functions, what are they?

• What stimulates the hypothalamus?

• What stimulates the anterior pituitary gland?

• What stimulates the thyroid gland to release thyroid hormones?

• Excess thyroid hormones in the blood will cause what feedback?

Thyrotropin

Thyroid stimulating hormone is synonymous to?

What is the process of synthesizing your thyroid hormones

• Conversion

• Organification

• Coupling

Thyroid peroxidase can catalyze 3 reactions in synthesizing your Thyroid hormones, Enumerate the 3 reactions:

Peripheral conversion

the process of converting your t4 to t3 in the blood?

Deiododinase

Enzyme that catalyzes your peripheral conversion?

Lysosomal proteases

What enzyme is responsible for cleaving the hormones attached to the thyroglobulin?

Na Iodide symporter

What transporter do iodide go through to enter from the blood stream to the follicular cell?

Differentiate wolff-chaikoff effect and Jod-basedow phenomenon

• increase = heat generation

• increase = adult height

• increase = CNS maturation

• decreased = mental retardation

• increase = upregulation

  • b1 = +chrono, dromo, ino

  • b2 = Bronchodilation, tremors, hypokalemia, hyperglycemia

Increase or decrease: Effects of thyroid hormones in terms of:

• Basal metabolic rate

• Bone growth

• Brain: Cognitive development

• Case: Congenital hypothyroidism; thyroid hormones

• B-receptor activity

Act for iodization nationwide law

ASIN law stands for?

• Iodine deficiency

• Autoimmune: Hashimoto’s disease

• Congenital hypothyroidism

• Iatrogenic

Hypothyroidism causes:

Antibodies target and destroy your thyroid peroxidase enzyme leading to decrease levels of thyroid hormones

Pathophysiology of Hashimoto’s disease?

Newborn screening

Prevention for congenital hypothyroidism?

• Primary - impaired thyroid gland

• Secondary - Impaired anterior pituitary

• Tertiary - Impaired hypothalamus

Hypothyroidism problems: differentiate the following

• Primary hypothyroidism

• Secondary hypothyroidism

• Tertiary hypothyroidism

• Radioactive iodine

• Thyroidectomy

Examples that causes iatrogenic hypothyroidism.

• Nutritional

• Autoimmune

Hypothyroidism can be caused by two primary factors:

Cretinism

Vertically challenged child is classified as what disease in the context of hypothyroidism

• Cold intolerance

• Weight gain

• Slowing of movements

• Short stature

• Bradycardia

• myxedema(non-pitting edema)

Signs and symptoms of hypothyroidism

• Levothyroxine (t4)

• Liothyronine (t3)

Management for hypothyroidism: enumerate the drugs

Liothyronine

Drug of choice for myxedema edema (severe case of hypothyroidism)

Levothyroxine

Preferred drug of choice for hypothyroidism due to its long DOA

1.6

Levothyroxine is administered ___mcg/kg/day

50mcg/day

Levothyroxine is administered in what dose for the ELDERLY?

25 mcg/day

Levothyroxine is administered in what dose for patients with Heart disease

• Synthroid

• Euthyrox

Levothyroxine is marketed in what brand names?

Cardiotoxicity

What to watch out for in using drugs for managing hypothyroidism

Liothyronine because its more active and more cardiotoxic

Which is more cardiotoxic between levothyroxine and liothyronine?

t4 and t3: 4:1

Liotrix is a combination of what, and what are its ratio?

• excess thyroid hormones causes by thyroid gland impairment

• decrease TSH

What is the pathophysiology of Hyperthyroidism?

• Thyrotoxicosis is excess thyroid hormones from any source

• Hyperthyroidism is excess thyroid hormones from thyroid gland

Differentiate thyrotoxicosis and hyperthyroidism.

• Autoimmune: Grave’s disease

• Thyroid adenoma (toxic adenoma)

• Toxic multinodular goiter

• Drug induced hyperthyroidism

Hyperthyroidism causes:

The apparent thyroid stimulating immunoglobulin binds at the TSH receptor of thyroid gland causing the release of thyroid hormones

What is the pathophysiology of Grave’s disease?

Amiodarone

Example drug that causes drug induced hyperthyroidism

• AIT1: Patients with history of thyroid problems: caused by the excess iodine content from iodine

• AIT2: Patients without history of thyroid problem: caused by the destruction of thyroid cells causing a leak of thyroid hormones

Differentiate AIT1 and AIT2

Thionamides

First line management for AIT1

Glucocorticoids

First line management for AIT2

• Heat intolerance

• Weight loss

• B-receptor upregulation

• Triad of Grave’s disease

• Agitation

Signs and symptoms of hyperthyroidism

• Hyperthyroidism

• Opthalmopathy

• Dermopathy

Triad of Grave’s disease

• Tachycardia

• Palpitation

• Tremors

Hyperthyroidism in terms of B-receptor activity: symptoms

Exopthalmos

bulging of one or both eyes is termed as what?

Pretibial myxedema

Dermopathy in hyperthyroidism is manifested in what disease?

• Anti-thyroid

• Beta blockers

• Corticosteroid

• Surgery

Hyperthyroidism can be managed by 4 factors:

• Thionamides

• Inorganic anions

• Iodide

• Radiocontrast dye

• Radioactive iodine (RAI)

Examples of Anti-thyroids

• Propylthiouracil

• Methimazole (Thiamazole)

Thionamides consist of two drugs:

Carbimazole

It is the prodrug of methimazole?

Inhibits thyroid peroxidase

Mechanism of action of Thionamides:

Propylthiouracil

• A thionamide

• Fast onset, short duration of action

• Used for thyroid storm

• good for pregnant women (1st trimester)

Propylthiouracil

Which thionamide inhibits the conversion of t4 to t3?

Hepatitis

What to watch out for PTU?

Hepatitis

PTU contains blackbox warning due to what toxicity?

Methimazole

• A thionamide

• Long onset, long duration of action

• Teratogenic

• More potent

Aplasia cutis

Methimazole is teratogenic therefore we need to watch out for?

Cholestatic jaundice

What to watch out for in taking methimazole?

Hypothyroidism

What to watch out for in taking thionamides?

Methimazole

Between the thionamides, which is more potent?

Pruritis rash

Most common adverse effect in taking methimazole?

Agranulocytosis (BEN)

Most serious adverse effect in taking methimazole?

after 1 hour of administration

When do PTU peak?

inversely proportional

Relationship between granulocytes and agranulocytes

Inhibits iodide transport via Na I symporter

MOA of inorganic anions

• perchlorate

• Pertechnetate

• Thiocyanate

Enumerate the Inorganic anions

• ClO4-

• TcO4-

• SCN-

Chemical formula of:

• Perchlorate

• Pertechtenate

• Thiocyanate

Potassium perchlorate

Drug of choice in inorganic anion in treating amiodarone-induced hyperthyroidism

Aplastic anemia

What to watch out for in taking inorganic anions

RBC, WBC, PLT

Aplastic anemia is categorized as decreased in what?

Inorganic anions

Anti thyroids that are obsolete

Wolff chaikoff effect

MOA of iodides

Iodides

Anti thyroid agents used for short term only <7 days

• Potassium iodine oral solution (SSKI)

• Lugol’s solution

Examples of Iodides

• Thyroid storm

• Preoperative tx for thyroidectomy

Iodides are used for the treatment of":

Iodides

Excess of this initially makes the thyroid less active, hense reducing its size and blood supply. what anti thyroid agent class is this?

Iodides

These anti thyroid agents are contraindicated to patients that are:

• Pregnant

• undergoing RAI

• Conjuntivitis

• Rhinitis

• Acne-like rash

• sialadenitis

• metallic-taste

What to watch out for in taking iodides

Anaphylactoid reaction

Iodides can rarely lead to what reaction?

• Inhibits the peripheral conversion of t4 to t3

MOA of Radiocontrast dye

• Ipodate

• Iopanoic acid

Enumerate the Radiocontrast dye

Destruction of thyroid gland through B-particle emission

MOA of Radioactive Iodine (RAI)

Iodine 131

The only isotope for the treatment of thyrotoxicosis in RAI

• pregnant

• lactating mothers

• children

RAIs are contraindicated to patietns that are:

• Leukemia

• Hypothyroidism

What to watch out for in taking RAIs

Hypothyroidism

Which is more preferred: hypo or hyper thyroidism

• Blocks B receptors = downregulation

MOA of beta blockers in hyperthyroidism

CLAP beta blockers (they have intrinsic sympathomimetic activity)

• Carteolol, celiprolol

• labetolol

• acebutolol

• pindolol

• penbutolol

What beta blockers do we avoid in treating hyperthyroidism

• Propanolol

• atenolol

• metoprolol

Which beta blockers are recommended for hyperthyroidism

inhibits the peripheral conversion of t4 to t3

Additional MOA of propanolol

• tremors

• palpitations

• hypokalemia

activation of beta 2 receptors causes these effects:

• Propylthiouracil

• Radiocontrast dye

• Propanolol

• Corticosteroids

Drug agents that can inhibit peripheral conversion of t4 to t3

Inhibits the peripheral conversion of t4 to t3

MOA of corticosteroid

• Dexamethasone

• Hydrocortisone

Example drugs under corticosteroids used for hyperthyroidism

• Propylthiouracil

• Iodides

• Corticosteroids

Drug agents that are used in the management of thyroid storm

hypothyroidism

What to watch out for in thyroidectomy