Thyroid Hormone Physiology and Pharmacology - Trachte

Question 1

What are the components of the Thyroid Hormone Axis?

Answer 1

1. Hypothalamus (TRH: thyrotropin releasing hormone)
2. Anterior Pituitary (TSH: thyroid stimulating hormone)
3. Thyroid gland
4. T3/T4 hormone (T3: triiodothyronine/T4: thyroxine)

Question 2

What are the main negative regulators of Thyroid hormones?

Answer 2

Block portal system => stop release of TSH

T3/T4 => negative feed back to stop release of TSH and TRH

Question 3

What are some of the other negative regulators of Thyroid hormones?

Answer 3

Somatostatin, dopamine, and high glucocorticoids (adrenal cortex) all DECREASE TSH release

Question 4

What is the function of TRH?

Answer 4

Tetrapeptide that stimulates release of TSH from thyrotrophs of the anterior pituitary

Question 5

Why is Thyroid Hormone Axis important?

Answer 5

Has an important role in the regulation of energy homeostasis, feeding behavior, thermogenesis, and autonomic regulation.

TRH controls energy homeostasis mainly through stimulation of TSH and ultimately regulation of circulating thyroid hormone levels.

Question 6

How does TRH stimulate the target cell?

Answer 6

Couples to PLC => phospholipase C-IP3
Cascade results in Ca++ release and rapid intracellular responses including release of secretory vesicles containing TSH.

Question 7

TSH is similar to what other gonatotropin hormones?

Answer 7

LH= luteinizing hormone  
hCG= human chorionic gonadotropin
FSH = follicle stimulating hormone

Question 8

How does TSH stimulate the receptor signal transduction?

Answer 8

Receptors reside on plasmamembrane of thyroid follicular cells.

G(s)-coupled receptor => increase cAMP

TSH:TSH receptor binding stimulates many aspects of thyroid hormone synthesis and release.

Question 9

What are the 7 steps of Thyroid Hormone synthesis?

Answer 9

1. Iodide Uptake (via Na+ coupled symporter)
2. Iodide Oxidation to Iodine (organification)
3. Iodination of tyrosine-thryoglobulin
4. Conjugation of MIT/DIT thyroglobulin
5. Endocytosis of T3/T4-thyroglobulin
6. Proteolysis to mature hormone
7. Secretion of T3/T4 via exocytosis (?)

Question 10

How do T3 and T4 compare?

Answer 10

T3 is more active than T4.

T4 is converted to T3 intracellularly.

T3 has a shorter circulating t1/2 T3~ 1 d; T4~ 6d

Both T3 and T4 bind thyroid hormone receptors but it is thought most T4 is converted into T3.

Question 11

What are the transporters for thyroid hormone?

Answer 11

Thyroxine binding globulin (= TBG =thyroid binding globulin)
- binds 75% of T4 and 75% of T3

Transthyretin

Albumin

Question 12

What three things does TSH stimulate the synthesis of in order to produce thyroid hormones?

Answer 12

Thyroid peroxidase synthesis

Thyroglobulin transcription

Na+/I- transport activity (increases I- availability to the follicular cell)

Question 13

What are the main functions of thyroid hormone?

Answer 13

Promotes oxygen consumption, heat production and free radical formation

Regulation of BMR

Increased heat production

Increased glucose utilization, uptake and synthesis

Permissive sympathetic effects, ↑ heart rate, ↑ contractility (increases beta receptors)

Question 14

Why do many states mandate newborn testing of thyroid function?

Answer 14

brain doesn’t develop/grow properly if low thyroid function

Question 15

What happens if there is a congenital lack of thyroid hormone in infants?

Answer 15

(Cretinism) or maternal hypothyroidism:

• profound mental retardation
• short stature
• delay in motor development
• coarse hair
• protuberant abdomens

Question 16

What are the physiologic effects of low thyroid hormone in adults?

Answer 16

Lethargy

Somnolence

Slowed intellectual functions including speech

Stiffness and aching muscle

*Cold intolerance

Delayed deep tendon reflex relaxation

Anovulation and amenorrhea common, menorrhagia less common

Question 17

What are the physiologic effects of excess thyroid hormone in adults?

Answer 17

Increases heart rate (via funny Na+ channels)

Increase sensitivity to catecholamines via increase of number of beta adrenergic receptors in heart, skeletal muscle, adipose tissue and lymphocytes.

Amplifies catecholamine post-receptor action.

Increased O2 demand leads to increased production of erythropoietin and increases erythropoiesis.

Promotes GI motility resulting in increased defecation.

Promotes bone turnover with net bone loss and hypercalciuria.

Promotes increased protein turnover and net loss of skeletal muscle with myopathy (weakness, fatigue)

Increases hepatic gluconeogenesis and glycogenolysis and intestinal glucose absorption, therefore can worsen control of glucose levels with diabetes patients.

Increase in LDL receptor # and thereby accelerates LDL clearance.

Hyperthyroidism promotes aromatization of androgens to estrogens and increases sex hormone binding globulins which can contribute to gynecomastia in men.

Question 18

What is Thyrotoxicosis?

Answer 18

any cause of excessive thyroid hormone concentration and its effects on organ systems

Question 19

What is Thyroid Storm?

Answer 19

Thyroid storm represents the extreme manifestation of thyrotoxicosis

Question 20

What are the potential etiologies of Hypothyroidism?

Answer 20

***Primary hypothyroidism (i.e., problem lies in thyroid gland): Congenital defects, Gland destruction (surgical, radioactive, external radiation), Iodine deficiency, Autoimmune (Hashimoto thyroiditis=chronic lymphocytic thyroiditis)

*Secondary/tertiary (i.e., problem lies in pituitary gland or hypothalamus, respectively) usually associated with other pituitary deficiencies

Thyroid hormone resistance syndromes (with normal hormone production): receptor resistance

Question 21

What happens to TRH, TSH and TH levels in primary hypothyroidism?

Answer 21

TRH levels increase

TSH levels increase

TH levels decrease

Question 22

What happens to TRH, TSH and TH levels in secondary hypothyroidism (i.e. pituitary deficiencies)?

Answer 22

TRH increase

TSH and TH decrease

Question 23

What happens to TRH, TSH and TH levels in thyroid hormone resistance hypothyroidism?

Answer 23

ALL INCREASE

Increase TRH release (no inhibitory)

Increase TSH

Increase TH

Question 24

What are the potential etiologies of Hyperthyroidism?

Answer 24

Hyperthyroidism that results in toxicosis in target tissues is called thyrotoxicosis.

Graves’ disease = Production of thyroid stimulating immunoglobulins (TSI)

Question 25

What happens to TRH, TSH and TH levels in hyperthyroidism due to Graves’ disease?

Answer 25

TRH decrease
TSH decrease
TH increase

T cells become sensitive to thyroid antigen and stimulate B cells to produce antibodies that mimic TSH. Result is hyperstimulation of thyroid hormone production, consequently causing strong negative feedback.

Question 26

Why does goiter develop in the case of iodine deficiency?

Answer 26

Increase in TRH and TSH with no negative feedback stimulates thyroid gland to maximize function and enlarge

Question 27

Why does goiter develop in the case of Graves’

disease?

Answer 27

The gland grows big and maximizes function due to thyroid stimulating immunoglobulins
-direct stimulation of the thyroid gland

Question 28

TSH test. Normal range is 0.5 to 6 U/dL.
If the level is higher than this, what does that mean?
If the level is lower than this, what does that mean?

Answer 28

Higher => Hypothyroidism

Lower => Hyperthyroidism

Question 29

When do you test T3 and T4 levels?

Answer 29

If TSH test is abnormal

Question 30

What does Thyroid-stimulating immunoglobulin (TSI) test for?

Answer 30

Graves’ disease

Question 31

What is a Thyroid scan used for?

Answer 31

A thyroid scan shows how and where iodine is distributed in the thyroid. The images of nodules and other possible irregularities help the health care provider diagnose the cause of a person’s hyperthyroidism.

Question 32

What is a Radioactive iodine uptake test used to assess?

Answer 32

The radioactive iodine uptake test measures the amount of iodine the thyroid collects from the bloodstream. Low levels of iodine uptake might be a sign of hypothyroidism, whereas high levels could support Graves’ disease diagnosis.

Question 33

What are the hypothyroidism and thyroid hormone replacement preparations?

Answer 33

Levothyroxine (T4) => long half life

Liothyronine (T3) (doesn’t last as long)

Question 34

What are Thioamides (aka Thionamides) used for?

Answer 34

treatment of hyperthyroidism and to prepare for thyroid surgery by preventing Iodide organization and thyroid peroxidase reactions to iodinate Tyrosines (shrinks thyroid)

Question 35

What are the three Thioamides that we need to know?

Answer 35

1. Methimazole and Carbimazole (metabolizes to methimazole)
2. Propylthiouracil (PTU)
3. Potassium Iodide (KI)

Question 36

What are radioactive Iodines used for?

Answer 36

131-I Used for thyroid ablation (destroy gland, results in hypothyroidism)

123-I Used for thyroid imaging

Question 37

What do Methimazole and PropylThioUracyl block?

Answer 37

inhibit thyroid peroxidase - oxidation of iodide and conjugation reactions producing T3 & T4

Question 38

What are the five types of anti-thyroid drugs?

Answer 38

***Drugs that inhibit thyroid synthesis (thioamides)

Drugs that impair release and proteolysis of thyroid hormones (iodides)

Drugs that interfere with T4 to T3 conversion (iodinated contrast media 123-I)

Drugs that alleviate peripheral symptoms of thyrotoxicosis (beta blockers)

Drugs that destroy the thyroid gland (radioactive 131-I).