Thyroid Physiology

Question 1

Hypothalamic Pituitary Thyroid Axis

Answer 1

Thyrotropin releasing hormone (TRH) released by hypothalamus –> Thyroid stimulating hormone (TSH) released by anterior pituitary –> Stimulate thyroid to release T3 and T4

Negative Regulators -> somatostatin, dopamine, high glucocorticoids all decrease TSH release

Question 2

Thyrotropin releasing hormone

Answer 2

translated as preprohormone -> mature is tripeptide

• stimulates release of TSH from thyrotrophs in anterior pituitary
• regulates energy homeostasis, feeding, thermogenesis, autonomic regulation
• bind to TRH receptors in anterior pituitary -> promote release of TSH

Question 3

Thyroid Stimulating Hormone

Answer 3

alpha and beta chains –> beta is specific to TSH and confers hormonal specificity
- receptor is GPCR -> stimulates many aspects of thyroid hormone synthesis and release

Question 4

7 Steps of Thyroid Hormone Synthesis

Answer 4

1. Dietary Iodine is required, active transport of I into thyroid follicular cell
2. Oxidation of I to I2 = organification
3. Iodination of tyrosines make MIT, DIT
4. Conjugation of MIT and DIT to T3, T4 (thyroid peroxidase dependent)
5. Endocytosis of conjugates
6. Proteolysis of conjugates into mature T3 and T4
7. Movement of T3 and T4 out of cell

Question 5

Comparison of T3 and T4

Answer 5

T3 is more active, shorter circulating half-life
T4 us converted to T3 intracellularly
- they both bind thyroid hormone receptors

Question 6

Thyroid Hormone Carrier Proteins

Answer 6

1. Thyroxine binding globulin (TBG) -> binds 75% of T4 and T3, 1 binding site for 1 thyroid hormone
2. Transthyretin -> binds 20% of T4, 5% of T3, 2 binding sites for hormones
3. Albumin -> binds 5% of T4 and 20% of T3, several binding sites

Question 7

Carrier proteins and thyroid hormones

Answer 7

99% of T4 and T3 bound

• serum proteins increase during pregnancy, estrogen/androgen treatment
• serum proteins decrease during hyperthyroidism, malnutrition, and nephritic syndrome

Question 8

Intracellular Metabolism

Answer 8

Deiodinase I and II activate T4 to T3

Deiodinase I and III deactivate T4 to rT3

Question 9

Deiodinase I

Answer 9

highly prevalent in kidney/liver

• converts T4 -> T3, or T4 -> rT3
• drugable target

Question 10

Deiodinase II

Answer 10

present in brain, pituitary, muscle

- converts T4 -> T3

Question 11

Deiodinase III

Answer 11

present in brain, skin, placenta

- deactivates T4 -> rT3

Question 12

TSH stimulation of thyroid

Answer 12

• secretion of mature thyroid hormones
• production of new thyroid hormone batch
  
  • thyroid peroxidase, thyroglobulin transcription, Na/I transport activity

Question 13

Thyroid Hormone Actions

Answer 13

• normal growth, development, and metabolism
• promotes oxygen consumption, heat productions, free radical formation
• regulates BMR, increase glucose utilization, permissive to sympathetic effects (increase HR and contractility)
• if replacement therapy started a few days after birth in deficiency patient, growth is normal

Question 14

Hypothyroid in Infants

Answer 14

Congenital or maternal causes

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

Question 15

Maternal Etiology of Hypothyroidism

Answer 15

lack of iodine in diet –> RARE

- Hasimoto’s thyroiditis -> blocking anti-TSH receptor antibodies

Question 16

Cretinism

Answer 16

hypothyroidism in infants

• respiratory difficulty, cyanosis, jaundice, poor feeding, harsh cry, umbilical hernia
• proximal tibial and distal femur epiphysis have certain lengths –> if shorter it suggests hypothyroidism

Question 17

Physiological Effects of Low Thyroid Hormone in Adults

Answer 17

• Lethargy
• somnolence
• slowed intellectual and speech
• stiffness and muscle aches
• cold intolerance
• delayed deep tendon reflex
• anovulation/amenorrhea

Question 18

Physiological Effects of Excess Thyroid Hormone in Adults

Answer 18

• increased HR and contractility (increased sensitivity to catecholamines) –> increased O2 demand –> increased EPO
• promotes GI motility and hyperdefecation
• promotes bone turnover -> net loss and hypercalcuria
• promotes protein turnover -> muscle loss and myopathy
• increase muscle contraction and relaxation
• increased gluconeogenesis and glycogenolysis -> diabetes
• increase LDL receptor #
• early bone closure -> precocious puberty
• impairs GnRH -> infertility

Question 19

Thyrotoxicosis

Answer 19

ANY cause of excessive thyroid hormone [ ]

• specturm –> thyroid storm is WORSE
• treat immediately with beta-blocker, thioamides, corticosteroids (cover functional hypoadrenalism)

Question 20

Etiology of Hypothyroidism

Answer 20

Primary
- congenital, gland destruction, iodine deficiency, autoimmune (Hashimoto)
Secondary
- associated with other pituitary deficiencies

Question 21

Etiology of Hyperthyroidism

Answer 21

Graves’ disease -> production of thyroid stimulating immunoglobulins (TSI)
- T cells become sensitive to thyroid antigen –> B-cells produce antibodies that mimic TSH –> hyperstimulation of thyroid hormone production

Question 22

Goiter

Answer 22

enlarged thyroid gland
Hypothyroidism –> thyroid is stimulated to grow and produce by can’t so there is no negative feedback and the thyroid enlarges
Hyperthyroidism -> Graves’ (TSI is unregulated and causes thyroid hypertrophy)

Question 23

Diagnostic Tests

Answer 23

1. TSH test -> most accurate measure of thyroid activity
2. T3 and T4 -> levels of free T3 and T4 in blood
3. TSI test -> measures TSI levels –> Graves’ disease
4. Radioactive iodine uptake -> measures amount of iodine thyroid collects from bloodstream
5. Thyroid Scan -> how and where iodine is distributed in thyroid (nodules/irregularities)

Question 24

Hypothyroidism replacement

Answer 24

1. Levothyroxine (T4) –> narrow therapeutic index, AlOH, Fe, Ca decrease absorption
2. Liothyronine (T3) -> shorter onset and half-life, greater potency because of T3 action
   S.E. = hyperthyroidism

Question 25

Thioamides

Answer 25

treat hyperthyroidism (Graves') and prepare for thyroid surgery 1. Methimazole & Carbimazole - inhibit thyroid peroxidase 2. Prophylthiouracil (PTU) - inhibis thyroid peroxidase and deiodinase I 3. Potassium Iodide (KI) -> block radiation uptake

Question 26

Radioactive Iodine

Answer 26

1. 131-I --> thyroid ablation 2. 123-I --> thyroid imaging S.E. = allergic rxns, sore teeth and gums, excess salivation