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Endo/Repro > Thyroid Physiology > Flashcards

Thyroid Physiology Flashcards

1
Q

Hypothalamic Pituitary Thyroid Axis

A

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

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2
Q

Thyrotropin releasing hormone

A

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
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3
Q

Thyroid Stimulating Hormone

A

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

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4
Q

7 Steps of Thyroid Hormone Synthesis

A
  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
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5
Q

Comparison of T3 and T4

A

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

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6
Q

Thyroid Hormone Carrier Proteins

A
  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
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7
Q

Carrier proteins and thyroid hormones

A

99% of T4 and T3 bound

  • serum proteins increase during pregnancy, estrogen/androgen treatment
  • serum proteins decrease during hyperthyroidism, malnutrition, and nephritic syndrome
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8
Q

Intracellular Metabolism

A

Deiodinase I and II activate T4 to T3

Deiodinase I and III deactivate T4 to rT3

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9
Q

Deiodinase I

A

highly prevalent in kidney/liver

  • converts T4 -> T3, or T4 -> rT3
  • drugable target
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10
Q

Deiodinase II

A

present in brain, pituitary, muscle

- converts T4 -> T3

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11
Q

Deiodinase III

A

present in brain, skin, placenta

- deactivates T4 -> rT3

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12
Q

TSH stimulation of thyroid

A
  • secretion of mature thyroid hormones
  • production of new thyroid hormone batch
    • thyroid peroxidase, thyroglobulin transcription, Na/I transport activity
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13
Q

Thyroid Hormone Actions

A
  • 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
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14
Q

Hypothyroid in Infants

A

Congenital or maternal causes

  • profound mental retardation
  • short stature
  • delay motor development
  • coarse hair
  • protuberant abdomen
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15
Q

Maternal Etiology of Hypothyroidism

A

lack of iodine in diet –> RARE

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

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16
Q

Cretinism

A

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
17
Q

Physiological Effects of Low Thyroid Hormone in Adults

A
  • Lethargy
  • somnolence
  • slowed intellectual and speech
  • stiffness and muscle aches
  • cold intolerance
  • delayed deep tendon reflex
  • anovulation/amenorrhea
18
Q

Physiological Effects of Excess Thyroid Hormone in Adults

A
  • 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
19
Q

Thyrotoxicosis

A

ANY cause of excessive thyroid hormone [ ]

  • specturm –> thyroid storm is WORSE
  • treat immediately with beta-blocker, thioamides, corticosteroids (cover functional hypoadrenalism)
20
Q

Etiology of Hypothyroidism

A

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

21
Q

Etiology of Hyperthyroidism

A

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

22
Q

Goiter

A

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)

23
Q

Diagnostic Tests

A
  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)
24
Q

Hypothyroidism replacement

A
  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
25
Q

Thioamides

A

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
26
Q

Radioactive Iodine

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

Endo/Repro (34 decks)

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