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Endo Repro 1 > Thyroid Gland Physio > Flashcards

Thyroid Gland Physio Flashcards

1
Q

What is the functional unit of the thyroid gland?

A

the thyroid follicle

surrounded by a single layer of epithelial cels, the follicle itself is filled with colloid

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2
Q

What do C cells secrete?

A

calcitonin

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3
Q

What is colloid composed of?

A

newly synthesized thyroid hormones attached to thyroglobulin

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4
Q

What does iodine + tyrosine make?

A

monoiodotyrosine (MIT) or diiodotyrosine (DIT)

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5
Q

What do 2 DIT’s make?

A

3,5,3’5’-tetraiodothyronine (thyroxine, or T4)

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6
Q

What does MIT + DIT make?

A

3,5,3’-triiodothyronine (T3)

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7
Q

What is the major secretory product of the thyroid gland?

A

T4

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8
Q

What occurs in the peripheral conversion of T4 to T3

A

10% undergo outer ring deiodination (activation) via deiodinase type 1 and 2

1% undergo inner ring deiodination (inactivation) via deiodinase type 3

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9
Q

What are the clinical states associated with reduction in the conversion of T4 to T3?

A

fasting, medical/surgical stress, catabolic diseases

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10
Q

What does a deficiency of deiodinase mimic?

A

dietary deficiency of iodide

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11
Q

What is favored when the availability of iodide is restricted?

A

formation of T3

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12
Q

What do perchlorate and thiocynate inhibit?

A

Na/I transporter on basolateral membrane

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13
Q

What does propylthiouracil (PTU) inhibit?

A

peroxidase (TPO)

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14
Q

What do high levels of iodide inhibit?

A

organification and synthesis of thyroid hormones (Wolff-Chaikoff effect)

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15
Q

How is iodine stored in colloid follicles?

A

as iodinated tyrosines of thyroglobulin

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16
Q

What is the iodide trap/leak?

A

exchange of iodidne from ECF into thyroid gland and vice versa
twice as much iodide is trapped in the thyroid gland as what leaks back into ECF

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17
Q

Will a hyperactive tyroid gland take up more or less radio-labeled iodine?

A

more

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18
Q

What are the main binding proteins o thyroid hormones?

A

thyroxine-binding globulin (TBG) synthesized in liver, has higher affinity for T4 than T3
transthyretin (TTR)
albumin

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19
Q

What are the percentages of bound versus free circulating thyroid hormones?

A

99% bound to plasma proteins

1% free

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20
Q

What are the half lives of T4 and T3?

A

T4: 6 days
T3: 1 days

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21
Q

How can circulating levels of TBG be assessed with a T3 resin uptake test?

A

This test is a way to measure how much TBG is circulating in the blood

  • TBG not saturated under normal conditions, T4 binds first (higher affinity)
  • add exogenous T3 to fill up other binding sites, will have leftover unbound T3
  • add resin (anti-T3 Ab) to bind free T3

exogenous T3 added - T3 on resin = T3 bound to TBG, giving estimate of how much TBG is in circulation

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22
Q

What levels of T4/T3 are expected in hyperthyroidism?

A
  • MORE T4 bound to TBG -> fewer binding sites for exogenous T3
  • MORE free exogenous T3 -> more T3 resin uptake
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23
Q

What levels of T4/T3 are expected in hypothyroidism?

A
  • LESS T4 bound to TBG -> more binding sites for exogenous T3
  • LESS free exogenous T3 -> less T3 resin uptake
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24
Q

What levels of T4/T3 are expected with high TBG?

A
  • MORE binding sites for T4 and exogenous T3
  • increased T4 synthesis
  • decreased T3 resin uptake
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25
Q

What levels of T4/T3 are expected with low TBG?

A
  • LESS binding sites for T4 and exogenous T3
  • decreased T4 synthesis
  • increased T3 resin uptake
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26
Q

What levels of T4/T3 are expected during pregnancy?

A
  • MORE TBG = less free T4/T3 (more bound)
  • increased T4/T3 synthesis, but levels still within normal limits
    NOTE: similar to high TBG, person is said to be clinically euthyroid in pregnancy
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27
Q

What levels of T4/T3 are expected during hepatic failure?

A
  • decreased TBG production = fewer binding sites for exogenous T3
  • LESS TBG = more free T4/T3 -> negative feedback inhibits T4/T3 synthesis
28
Q

What is the role of TSH?

A
  • to regulate the growth of the thyroid gland (trophic effect)
  • to regulate the secretion of thyroid hormones
29
Q

What is TSH regulated by?

A
  • thyrotropin-releasing hormone (TRH)
  • free T3

NOTE: TSH secretion occurs at a steady rate (unlike GH)

30
Q

What are the two actions of TSH on the thyroid gland?

A
  1. increase the synthesis and secretion of thyroid hormones

2. trophic effect on thyroid gland

31
Q

What is the secondary messenger for TSH?

A

cAMP

32
Q

What are the stimulatory factors affecting thyroid hormone secretion?

A

TSH, thyroid-stimulating immunoglobulins, increased TBG levels (pregnancy)

33
Q

What are the inhibitory factors affecting thyroid hormone secretion?

A

iodide deficiency, deiodinase deficiency, excessive iodide intake (Wolff-Chaikoff effect), perchlorate/thiocynate, PTU, decreased TBG (liver disease)

34
Q

What new proteins are synthesized under the direction of thyroid hormones?

A

Na/K-ATPase, transport proteins, B-adrenergic receptors, lysosomal enzymes, proteolytic proteins, structural proteins,

in cardiac muscle: myosin, Ca-ATPase, B-adrenergic receptors

35
Q

What effects do thyroid hormones have on BMR?

A

increase BMR via up-regulation of: Na/K-ATPase, oxygen consumption, heat production

NOTE: the increase in BMR produced by a single dose of thyroxine (T4) occurs after several hours, but is long-lasting (more than 6 hrs)

hyperthyroidism -> high BMR
hypothyroidism -> low BMR

36
Q

What effects do thyroid hormones have on metabolism?

A

increase: glucose absorption, glycogenolysis, gluconeogenesis, lypolysis, protein synthesis & degradation (net catabolic)

37
Q

What effects do thyroid hormones have on cardiovascular function?

A

increase: cardiac output, up-regulation of B-adrenergic receptors (heart becomes more sensitive to SNS stimulation)

NOTE: both direct and indirect effects lead to an increase in blood volume (via RAAS) -> increase in cardiac chronotropy and ionotropy

38
Q

What effects do thyroid hormones have on growth?

A

increase: growth formation and bone maturation

39
Q

What effects do thyroid hormones have on lipid metabolism?

A
  • stimulate fat metabolism (increase concentration of FA in plasma)
  • enhance oxidation of FA
  • plasma concentration of cholesterol & triglycerides inversely correlated with thyroid hormones (increase in blood cholesterol concentration in hypothyroidism)
  • required for conversion of carotene -> vitamin A (hypothyroid patients can suffer from blindness and yellowing of the skin)
40
Q

What effects do thyroid hormones have on carbohydrate metabolism?

A
  • increased gluconeogenesis and glycogenolysis to generate free glucose
  • enhancement of insulin-dependent entry of glucose into cells
41
Q

What are the direct effects of thyroid hormones on the heart?

A
  • increase cardiac muscle Na/K-ATPase
  • increase ventricular contractility/finction
  • decrease peripheral vascular resistance
42
Q

What are the indirect effects of thyroid hormones on the heart?

A
  • increase in heat production and CO2 in tissues
  • decrease peripheral resistance
  • decrease diastolic blood pressure
  • reflex: increase adrenergic stimulation
43
Q

What are the effects of excess thyroid hormones on metabolism?

A

heat intolerance, weight loss, increase in BMR

44
Q

What are the effects of thyroid deficiency on metabolism?

A

cold intolerance, weight gain, decrease in BMR

45
Q

What are the effects of excess thyroid hormone on bones?

A

osteoporosis

46
Q

What are the effects of thyroid deficiency on bones?

A

stunted growth

47
Q

What are the effects of excess thyroid hormone on the CNS?

A

agitation, anxiety, difficulty concentrating, hyperreflexia

48
Q

What are the effects of thyroid deficiency on the CNS?

A

cretinism (congenital), in adults: listlessness, slowed movement, somnolence, impaired memory, decreased mental capacity

49
Q

What are the effects of excess thyroid hormone on skin?

A

sweating

50
Q

What are the effects of thyroid deficiency on skin?

A

dryness, myxedema

51
Q

What are the effects of excess thyroid hormone on the CV system?

A

tachycardia, Afib, palpitations, high output heart failure

52
Q

What are the effects of thyroid deficiency on the CV system?

A

bradycardia, decreased contractility, decreased cardiac output, heart failure

53
Q

What are the effects of excess thyroid hormone on the intestines?

A

diarrhea

54
Q

What are the effects of thyroid deficiency on the intestines?

A

constipation

55
Q

What are some symptoms of hyperthyroidism?

A

increased BMR, weight loss, negative nitrogen balance, increased heat production, sweating, increased cardiac output, dyspnea, tremor/muscle weakness, exopthalmos (eye bulging), goiter

56
Q

What are some causes of hyperthyroidism?

A

Graves disease, thyroid neoplasm, excess TSH secretion, exogenous T4/T3

NOTE: TSH levels will be decreased if there is feedback inhibition of T3 on anterior lobe
TSH levels will be increased if defect itself is in anterior pituitary

Tx: TPU, thyroidectomy, iodide 131 (destroys thyroid), B-adrenergic antagonists

57
Q

What are some symptoms of hypothyroidism?

A

decreased BMR, weight gain, positive nitrogen balance, decreased heat production, cold sensitivity, decreased cardiac output, hypoventilation, lethargy/mental slowness, drooping eyelids, growth retardation, mental retardation, goiter

58
Q

What are some causes of hypothyroidism?

A

thyroiditis (Hashimoto’s), surgery for hyperthyroidism, iodide deficiency, cretinism, decreased TRH or TSH

NOTE: TSH levels will be increased by negative feedback if primary defect is in thyroid gland
TSH levels will be decreased if defect is in hypothalamus or anterior pituitary

Tx: thyroid hormone replacement therapy. Lower doses T4 required in older patients, because metabolism of T4 decreases and plasma half-life increases with age
**NOTE: in women beyond menopause, overprescribing T4 can contribute to development of osteoporosis!!!

59
Q

What is primary hyperthyroidism?

A

Graves disease (most common cause of thyrotoxicosis)

NOTE: Thyroid-stimulating immunoglobulins can stimulate TSH receptors without TSH hormone
-> causes TSH levels to be lower than normal because high circulating levels of thyroid hormone inhibits TSH secretion via negative feedback

60
Q

What is secondary hyperthyroidism?

A

TSH-secreting pituitary

61
Q

What are major clinical signs of Graves disease, and how is it diagnosed?

A

Sx: exopthalmos and periorbital edema

Dx: elevated serum free and total T4 or T3, plus clinical signs of goiter and opthalmophaty
- presence of circulating thyroid-stimulating immunoglobulins (TSI) also helps distinguish Graves disease from adenoma of pituitary thyrotrophs

62
Q

What are the causes of primary hypothyroidism?

A

agenesis, gland destruction (Hashimoto’s thyroiditis), inhibition of thyroid hormone synthesis and release (iodine deficiency, inherited enzyme defects, drugs interfering with homeostasis), hypothalamic disease, pituitary disease, resistance to thyroid hormones

63
Q

What is Hashimoto’s thyroiditis?

A

thyroid hormone synthesis is impaired by thyroglobulin or TPO antibodies, leading to DECREASE in T4/T3 secretion
**TSH levels are high!
has a trophic effect (goiter)

64
Q

What are the causes and symptoms of cretinism?

A

iodide deficiency, maternal intake of anti-thyroid meds, impaired development of thyroid gland, inherent deficit in the synthesis of thyroid hormones

Sx: feeding problems, respiratory difficulty, protruding tongue, curse facial features, growth retardation, mental retardation, jaundice, dry skin, hypotonia

65
Q

What does hypothyroidism due to iodine deficiency cause?

A

leads to transient decrease in the synthesis of thyroid hormones
TSh levels are elevated
goiter: if gland maintains normal levels of thyroid hormones, patient is euthyroid and asymptomatic
if gland cannot maintain normal levels of thyroid hormones, patient exhibits hypothyroid

66
Q

What can cause a goiter?

A

multiple imbalances and disease within HPT axis

  • HYPERthyroidism: Graves disease, TSH-producing tumor (secondary hyperthyroidism)
  • primary HYPOthyroidism: lack of adequate iodine in the diet, sporadic hypothyroidism, chronic thyroiditis (Hashimoto’s, autoimmune deficiency)
67
Q

What is the TSH test used to diagnose?

A

BOTH hyper and hypothyroidism

  • TSH levels will be low in hyperthyroid diseases, T4/T3 will be high
  • TSH levels will be high in hypothyroid diseases, T4/T3 will be low

Endo Repro 1 (6 decks)

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