Lecture 16: Thyroid Disorders Part 1

Question 1

What is the cell that makes thyroid hormone? Where does it get stored?

Answer 1

Follicular cells make thyroid hormone.

Colloid is where thyroid hormone is stored.

Question 2

What does high T3 and T4 inhibit?

Answer 2

Both TRH and TSH.

Question 3

What is thyroglobulin? (Tg)

Answer 3

Large glycoprotein synthesized by follicular cells of the thyroid; released into the colloid.

Question 4

What mineral is required for normal thyroid function? What enzyme processes it?

Answer 4

Iodine is required.

Thyroid peroxidase (TPO) processes it.

30x more iodine in your thyroid than serum.

Question 5

Where is iodine deficiency most common in and what conditions is it associated with?

Answer 5

Common in developing countries.
Goiters, hypothyroidism, mental retardation.

Russia has iodine deficiency

Question 6

Clinical

Kearra, a 13-year-old female, has an intrinsic genetic deficiency that stops her from producing thyroglobulin. What would we expect to happen…
○ To her T3 and T4 levels?
○ To her TSH and TRH levels?

Answer 6

T3/T4 = Low
TSH/TRH = High

Question 7

Clinical

Pari, a 31-year-old female from India, has suffered from lifelong iodine deficiency. What would we expect to happen…
○ To her T3 and T4 levels?
○ To her TSH and TRH levels?

Answer 7

T3/T4 = Low
TSH/TRH = High

Question 8

Clinical

Michael, a 64-year-old male, just had a total thyroidectomy for thyroid cancer. What would we expect to happen to his thyroglobulin level?

Answer 8

Low

Question 9

What is a Tg molecule?

Answer 9

Precursor to multiple T3/T4

Question 10

What is the most common thyroid hormone?

Answer 10

T4

Question 11

What happens to T3 and T4 in the plasma?

Answer 11

Binds to plasma protein.
T4 is 99.8% bound.
T3 is 70-99% bound.

Question 12

Which thyroid hormone is released to tissues daily? Why?

Answer 12

T3 is released daily because it has a lower binding affinity.
T4 is only released every 6 days.

Question 13

What happens to T4 once it is absorbed by tissues?

Answer 13

It is converted to T3 by deiodinases

Question 14

What proteins bind T3 and T4?

Answer 14

• Thyroxine-binding globulin (TBG) 80% of T3/T4.
• Transthyretin (TTR)
• Albumin

Question 15

What is rT3? Why is it alarming if we have a lot?

Answer 15

rT3 is metabolically INactive.

It is elevated in states of trauma, shock, burn patients, etc…

Question 16

Clinical

What would happen to the absorption of oral thyroid hormone
replacement therapy if a pt took this medication with a meal?

Answer 16

Less absorption than normal

Question 17

Clinical

What would happen if someone was deficient in TBG, but otherwise metabolically normal…
○ To their total T3 and T4 levels?
○ To their free (unbound) T3 and T4 levels?
○ To their TSH and TRH levels?

Answer 17

• Total T3/T4 = decreased.
• Free T3/T4 = same.
• TSH/TRH = no change.

Question 18

Clinical

Estrogen increases the levels of TBG. If someone had high estrogen levels (e.g. pregnancy, contraception), what would happen…
○ To their total T3 and T4 levels?
○ To their free (unbound) T3 and T4 levels?
○ To their TSH and TRH levels?

Answer 18

• Total T3/T4 = increased
• Free T3/T4 = same
• TSH/TRH = same

Question 19

Clinical

Jamal is a healthy, euthyroid 22-year-old male who presents for a routine physical. As part of his physical, he has thyroid function studies drawn. Should we expect to see higher levels of serum T3 or serum T4 on labs?

Answer 19

Serum T4 would be higher.

Question 20

Clinical

What would an elevated level of reverse T3 (rT3) suggest?

Answer 20

Increased stress on the body.

Question 21

Clinical

Would we expect to see symptoms of hyperthyroidism (overactive thyroid), hypothyroidism (underactive thyroid), or euthyroidism (normally functioning thyroid) in a patient with elevated rT3?

Answer 21

Underactive thyroid symptoms.
Hypothyroidism because rT3 is metabolically inactive.

Question 22

What is the general effect of thyroid hormones on tissues?

Answer 22

Increased functional activity.

Question 23

Which thyroid hormone binds with greater affinity to cell receptors?

Answer 23

T3 has 10-15x more affinity.

Question 24

What complex is formed by T3 binding to receptors?

Answer 24

Thyroid receptor-Retinoid x receptors (TR-RXR complex)

Question 25

What does the TR-RXR complex do?

Answer 25

Altering gene expression, usually causing a target gene to be expressed.

Question 26

What are the growth effects of thyroid hormone?

Answer 26

* Promotes growth of skeletal tissue and skeletal maturation. * Promotes growth/maturation of brain in fetal phase, first few years of life. | Fetal thyroid levels are checked on birth.

Question 27

What are the effects of thyroid hormone on carbohydrate metabolism?

Answer 27

Promotes all aspects: * Glucose absorption/uptake * Gluconeogenesis * Glycolysis * Insulin secretion

Question 28

What are the effects of thyroid hormone on fat metabolism?

Answer 28

Promotes all aspects: * Increased FFA and decreased body fat * Decreased concentrations of cholesterol, phospholipids, and TGs. * Reduce fatty deposits in liver.

Question 29

What are the effects of thyroid hormone on BMR?

Answer 29

* Increased thyroid hormone = 60-100% increase in BMR. * Decreased thyroid hormone = 50% reduction in BMR.

Question 30

# Clinical Iris is a 6-year-old female with congenital hypothyroidism (underactive thyroid) that has not been treated well up to this point. What effect would we expect to see on her stature (height), and why?

Answer 30

Short due to decreased bone growth.

Question 31

# Clinical What body habitus would you expect a patient with chronic, untreated hyperthyroidism to have, and why?

Answer 31

Very skinny, thin body habitus due to increased BMR.

Question 32

# Clinical Diego is a 44-year-old male who suffers from obesity, hyperlipidemia, and fatty liver disease. He has been told he has a thyroid abnormality on his labs. Would you expect him to be hyper-, hypo-, or euthyroid?

Answer 32

Hypothyroidism

Question 33

What are the effects of thyroid hormone on the heart?

Answer 33

* Minor increase will increase heart strength. * Major increases will weaken heart due to protein catabolism.

Question 34

What are the effects of excess or reduced thyroid hormone on muscles?

Answer 34

* Excess = muscle weakness due to protein catabolism. * Reduced = sluggish, slow post-contraction relaxation.

Question 35

What are the effects of thyroid hormone on the endocrine system?

Answer 35

Increased secretion of most hormones.

Question 36

# Clinical Latisha is an obese 32-year-old female with heavy menses and a history of thyroid disease. Assuming her thyroid is causing her irregular menses, what thyroid disorder is she more likely to have (overactive or underactive)?

Answer 36

Underactive thyroid. (Hypothyroidism)

Question 37

# Clinical Robert is an 87-year-old male with hypothyroidism and dementia. He presents with acute onset of increased anxiety, agitation and insomnia. His daughter says “I think he has not been taking his thyroid medication the way he is supposed to.” Is he more likely to have taken extra doses of his thyroid hormone therapy, or have missed doses?

Answer 37

Extra doses, since he has signs of increased agitation and insomnia

Question 38

What tests make up a typical thyroid panel?

Answer 38

* TSH * T3 * T4 * Free T4/FT4

Question 39

What can interfere with TSH tests? What should we do?

Answer 39

Check thyroid levels at the same time because TSH is highest at 10pm and lowest at 10am.

Question 40

What two interpretations can we infer from a high TSH?

Answer 40

* Low T3/T4 (usual) * Overfunctioning pituitary gland

Question 41

What interpretations can we infer from a low TSH?

Answer 41

* High T3/T4 * Underfunctioning pituitary * Underfunctioning hypothalamus

Question 42

What drug can affect TSH, T3/T4?

Answer 42

Lithium can cause simultaneous increased TSH with decreased T3/T4.

Question 43

When do we use Free T4? When can we not?

Answer 43

We can use it to reduce confounding factors if serum protein levels are off. Neonates have high levels of FT4 so we prefer total T4 for neonates.

Question 44

What two interpretations can we infer from an elevated T3/T4 or elevated FT3/FT4?

Answer 44

* Excess amounts of thyroid hormone. * Increased serum proteins, such as TBG.

Question 45

What two interpretations can we infer from low levels of T3/T4 or FT3/FT4?

Answer 45

* Insufficient amounts of thyroid hormone * Protein-depleted state

Question 46

What usually causes just low T3/FT3?

Answer 46

Decreased conversion of T4 to T3, aka liver disease or severe illness.

Question 47

What usually causes low T4/FT4 only?

Answer 47

T3-only medications such as cytomel.

Question 48

Where is TBG released from?

Answer 48

Liver

Question 49

When do we order a TBG level?

Answer 49

Determining if a patient is hypo/hyperthyroid or if they just have abnormal levels of bound/unbound T3/T4.

Question 50

What 2 interpretations can we infer from high TBG?

Answer 50

* Elevated estrogen * Infectious hepatitis

Question 51

What 4 interpretations can we infer from low TBG?

Answer 51

* Hypoproteinemia * Ovarian failure * Elevated testosterone levels * Major Stress

Question 52

When is a TRH stimulation test used?

Answer 52

* Differentiate etiology of hypothyroidism * Evaluate degree of pituitary suppression in hyperthyroidism pts.

Question 53

What can interfere with a TRH stimulation test?

Answer 53

* Exaggerated in women/pregnancy * Diminished in the elderly and those with MDD.

Question 54

What is a normal TRH stimulation test?

Answer 54

2x increase in baseline TSH within 30 minutes.

Question 55

If we have no increase in TSH in a TRH stimulation test, what kind of hypothyroidism is it?

Answer 55

Secondary hypothyroidism

Question 56

If we have a delayed increase in baseline TSH after a TRH stimulation test, what kind of hypothyroidism is it?

Answer 56

Tertiary hypothyroidism

Question 57

If we have a blunted TSH response due to maximal pituitary suppression by T3/T4 in a TRH stimulation test, what does that suggest?

Answer 57

Hyperthyroidism

Question 58

What is the most common demographic for hypothyroidism?

Answer 58

Female pts > 60

Question 59

What can occur to a fetus due to maternal hypothyroidism?

Answer 59

Decreased IQ, since thyroid hormone is needed for brain development in a fetus.

Question 60

What are the 3 types of hypothyroidism?

Answer 60

* Primary: failure of thyroid to release T3/T4 * Secondary: failure of pituitary to release TSH * Tertiary: failure of hypothalamus to release TRH

Question 61

What is the MC etiology of hypothyroidism worldwide? Developed countries?

Answer 61

Worldwide: Iodine deficiency Developed: Hashimoto's thyroiditis

Question 62

What two medications can induce hypothyroidism?

Answer 62

* Amiodarone * Lithium

Question 63

What kind of symptoms does hypothyroidism typically present?

Answer 63

* Fatigue, general weakness, weight gain * Dry skin, hair loss * Dysphagia, constipation, poor appetite * Cognitive impairment, paresthesias * Depression * Hoarseness * Arthralgias, myalgias * Dyspnea * Lower libido, ED, irregular menses

Question 64

What kind of signs does hypothyroidism typically present?

Answer 64

* Weight gain * Dry skin, spare/coarse hair, thin/brittle nails * Bradycardia, edema * Delayed DTR relaxation, carpal tunnel syndrome * Thinning of the outer eyebrows * Serous effusions * Cold extremities

Question 65

What labs should we order for an initial workup of hypothyroidism?

Answer 65

* Serum TSH/FT4 * CMP * CBC

Question 66

What labs screen for hashimoto's thyroiditis?

Answer 66

Anti-thyroid peroxidase antibody (anti-TPO) Anti-thyroglobulin antibody (anti-Tg)

Question 67

What would prompt us to order a thyroid US?

Answer 67

Presence of thyromegaly or thyroid nodule on PE.

Question 68

What kind of patients may have limited thyroid US results?

Answer 68

Obesity

Question 69

What might an enlarged thymus suggest?

Answer 69

Autoimmune thyroiditis

Question 70

What might an enlarged pituitary suggest?

Answer 70

Hyperplasia of TSH-secreting cells

Question 71

What pulmonary condition are people with hypothryoidism at higher risk for?

Answer 71

Bacterial pneumonia risk

Question 72

What is the life-threatening crisis of hypothyroidism?

Answer 72

Myxedema Crisis

Question 73

What is the classic patient that has a myxedema crisis?

Answer 73

Elderly women who have a stroke or stop taking their thyroid medications.

Question 74

What is the typical presentation for a myxedema crisis?

Answer 74

* Hypothermia * Hypotension * Hypoventilation * Hyponatremia * Hypoglycemia * Cognitive impairment

Question 75

What is the treatment for a myxedema crisis?

Answer 75

IV levothyroxine therapy If in myxedema coma, add IV T3 also. Supportive: * Warming blankets * Intubation * Tx underlying cause

Question 76

What is subclinical hypothyroidism? MC demographic?

Answer 76

* Normal serum FT4 with elevated TSH. * MC in seniors.

Question 77

How does subclinical hypothyroidism present?

Answer 77

Asymptomatic or mild.

Question 78

How is subclinical hypothyroidism treated?

Answer 78

Observation if no s/s. Trial of LT4 if symptomatic. Usually resolves spontaneously.

Question 79

What is the first-line therapy for hypothyroidism?

Answer 79

Levothyroxine (synthetic T4)

Question 80

What are the second-line options for hypothyroidism?

Answer 80

* Combined T3/T4: Armour thyroid * Synthetic T3: Liothyronine

Question 81

What should you evaluate for prior to starting levothyroxine?

Answer 81

* Adrenal insufficiency * Angina

Question 82

What are the dosing considerations for levothyroxine?

Answer 82

* Take on empty stomach with water at regular time. * ~4 weeks peak response * Different preps = different bioavailability

Question 83

What is the main goal of hypothyroidism therapy?

Answer 83

Normalizing TSH levels

Question 84

What is the BBW of all thyroid medications?

Answer 84

Do not use as treatment for obesity.

Question 85

# Clincal A patient has an increased TSH level. What, if any, adjustment should be made to her thyroid hormone replacement medication?

Answer 85

Increased her thyroid hormone dose, which will lower her TSH.

Question 86

# Clinical A patient has a normal TSH level. What, if any, adjustment should be made to her thyroid hormone replacement medication?

Answer 86

Keep thyroid hormone medication dosage the same.

Question 87

# Clinical A patient has an decreased TSH level. What, if any, adjustment should be made to her thyroid hormone replacement medication?

Answer 87

Decrease her thyroid hormone dosage, which will increase her TSH.

Question 88

History of what conditions may require slightly higher TSH?

Answer 88

History of CAD or AFIB.

Question 89

What are we worried about in very low levels of serum TSH?

Answer 89

* Risk of Afib * Osteoporosis

Question 90

What is levothyroxine indicated for?

Answer 90

* Hypothyroidism * TSH suppression (Cancer/goiter)

Question 91

What kind of patients need slightly less levothyroxine?

Answer 91

Elderly or CAD.

Question 92

What are the SE of levothyroxine?

Answer 92

Hyperthyroidism effects.

Question 93

What are the CIs of levothyroxine?

Answer 93

* Allergy * Acute MI * Thyrotoxicosis * Uncorrected adrenal insufficiency

Question 94

What is in armour thyroid?

Answer 94

Ground-up animal thyroid