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Flashcards in Thyroid Deck (111)
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1
Q

What are the three hormones secreted by the thyroid gland?

A

Triiodothyronine (T3),t1/2 1-2 dys (9%)
Thyroxine (T4), t1/2 6-7 dys (90%)
Calcitonin

2
Q

Which is more potent T3 or T4?

A

T3 is 4x more potent than T4

3
Q

Where is the majority of T3 produced?

A

Majority of T3 produced from peripheral conversion of T4 to T3

4
Q

What medications inhibit the peripheral conversion of T4 to T3?

A

Inhibited by beta-blockers, corticosteroids, amiodarone

5
Q

What is the biosynthesis of thyroid hormones?

A

Hypothalamus produces thyrotropin-releasing hormone (TRH)
Stimulates pituitary gland to synthesize and release thyroid stimulating hormone (TSH)
Circulating TSH stimulates thyroid gland
Concentrate iodine
Synthesize thyroid hormone
release thyroid hormone
Peroxidase enzymes catalyze iodination of tyrosine on thyroglobulin forming MIT and DIT
Coupling of 1 DIT and 1 MIT or 2 DIT, to form T3 and T4

6
Q

What do cardiac glycosides do to iodine concentration?

A

Cardiac Glycosides-by inhibiting potassium accumulation can block iodide uptake

7
Q

What do bromine, fluorine, and lithium do to iodine concentration?

A

Bromine, Fluorine, Lithium- block transport of iodide into thyroid

8
Q

What is the ratio release of T3:T4?

A

Release ratio (T4:T3) = 4:1 (releasing more T4 than T3

9
Q

Is T3 or T4 absorbed at a higher rate and which is more active?

A

T3 absorbed at higher rate, more active

10
Q

How is T3 transported into the plasma?

A

Thyroid Binding Globulin (TBG)
Albumin
Thyroid Binding PreAlbumin (TBPA)

11
Q

What percentage of thyroid hormone is protein bound?

A

99%

12
Q

What is the only portion of hormone that is available to elicit biological effect and regulate TSH?

A

Free hormone

13
Q

What are the effects of thyroid hormone?

A
  • Determination of basal metabolic rate
  • Influence of growth through stimulation of growth hormone synthesis and action
  • Body temp
  • Fetal development
  • Cardiac rate and contractility
  • Peripheral vasodilatation
  • Red cell mass and circulatory volume
  • Respiratory drive
  • Peripheral nerves (reflexes)
  • Hepatic metabolic enzymes
  • Bone turnover
  • Skin and soft tissue effects
14
Q

What is a clinical and biochemical syndrome resulting from decreased thyroid hormone?

A

Hypothyroidism

15
Q

What is a clinical and biochemical syndrome resulting from increased thyroid hormone?

A

Hyperthyroidism

16
Q

What labs should be assessed for thyroid dysfunction?

A

Total T4- free and bound
Free T4 (FT4)- more reliable than total T4 and T3 levels
Sensitive TSH- evaluates the negative feedback system

17
Q

What is TSH increased in?

A

Increased in primary hypothyroidism (something is wrong with the thyroid its not releasing enough thyroid hormone and its feedback to the pituitary saying to release TSH)

18
Q

What is sensitive TSH decreased in?

A

Decreased in primary hyperthyroidism (thyroid is producing thyroid hormone and sending feedback to pituitary saying not to release TSH)

19
Q

What are the thyroid function test results with hyperthyroid?

A

Total T4- Elevated
Free T4- Elevated
Total T3- Elevated
TSH- LOW

20
Q

What are the thyroid function test results with hypothyroid?

A

Total T4- low
Free T4- low
Total T3- low
TSH- ELEVATED

21
Q

What are the increased thyroid binding globulin thyroid function test results?

A

Total T4- Elevated
Free T4- Normal
Total T3- Elevated
TSH- Normal

22
Q

What is a serum TSH concentration above statistically defined upper limit of reference range?

A

Sub-clinical hypothyroidism

23
Q

What are the CV effects of sub-clinical hypothyroidism?

A

Increased risk of coronary heart disease

24
Q

What are the fertility and pregnancy effects of sub-clinical hypothyroidism?

A

Placental abruption risk 3x higher
Preterm delivery risk 2x higher
Women with thyroid autoantibodies have increased risk for abortion

25
Q

What are the signs and sx of HYPOthyroidism?

A
Tiredness
Lethargy, Muscle pains
Weight gain
Intolerance to cold
Dry skin, Coarse skin
Bradycardia
Mental impairment
Dry thinning hair
26
Q

What are the effects of hypothyroidism on the cardiovascular system?

A
Systolic Dysfunction 
Reduced stress tolerance during exercise
Cardiac autonomic dysfunction
Reduced oxygen uptake during exercise
Diastolic hypertension
Increased arterial stiffness
Pro-atherosclerotic profile
Increased total cholesterol
Increased LDL
Insulin resistance
Pro-coagulative pattern 
Decreased fibrinolytic capacity
Decreased activity
Von Willebrand factor
Factor VIII
27
Q

What are the effects of hypothroidism on digitalis (digoxin)?

A

Decreased volume of distribution (push them into digoxin toxicity)

28
Q

What are the effects of hypothyroidism on insulin?

A

Impaired degradation

29
Q

What are the effects of hypothyroidism on warfarin?

A

Delayed catabolism of clotting factors

30
Q

What are the causes of primary hypothyroidism?

A

Hashimotos Disease
Iatrogenic hypothryoidism
Iodine deficiency

31
Q

What are the causes of secondary hypothyroidism?

A
Pituitary disease (Most common reason)
Hypothalamic disease
32
Q

What are the increased risk factors for hypothyroidism?

A

Postpartum women
Family history of autoimmune thyroid disorders
Patients with previous head and neck of thyroid irradiation or surgery
Other autoimmune endocrine (DM type 1, adrenal insufficiency)
Non endocrine conditions (celiac disease, vitiligo, MS, pernicious anemia, Down’s syndrome)

33
Q

What are the signs and sx of hypothyroidism in the elderly?

A
Hypothyroidism often with few specific signs or symptoms, often subtle
Hoarseness
Deafness
Confusion
Dementia
Ataxia
Depression
Dry skin
Hair loss
34
Q

What is an autoimmune disease resulting in fibrosis of the thyroid gland, antibodies to TSH receptor?

A

Hashimotos thyroiditis

35
Q

What is the most common cause of hypothyroidism?

A

Hashimotos Thyroiditis

36
Q

How does hashimotos thyroiditis work?

A

Selective destruction of thyroid gland ↓ thyroid hormone and ↑ TSH levels

37
Q

What does congenital (infantile) hypothyroidism result in?

A

Dwarfism and mental retardation (cretinism)

38
Q

What is myxedema?

A

Patients appear to have edema beneath the skin (Thickening of facial features, puffy & pallid skin, somnolence, slow mentation, muscle weakness, hypothermia, hoarseness, dryness/loss of hair) (End stage hypothyroidism)
Due to removal or loss of functioning thyroid gland

39
Q

What is the most severe form of hypothyroidism that sometimes causes a coma?

A

Myxedema

40
Q

What are the clinical features of myxedema?

A

Hypothermia
Advanced hypothyroid symptoms
Altered sensorium (from delirium to coma)

41
Q

What are the drug treatments for HYPOthyroidism?

A
Thryoid USP Armour
Thyroglobulin Proloid
Levothyroxine, synthroid, levothroid, levoxyl, unithroid
Liothyronine, thyro-tabs, cytomel
Liotrix
42
Q

What is the content of Levothyroxine, synthroid, levothroid, levoxyl, unithroid?

A

Synthetic T4

43
Q

What is the content of Liothyronine, thyro-tabs, cytomel?

A

Synthetic T3

44
Q

Which two hypothyroidism managements are rarely used today due to allergic reactions?

A

Thyroid USP; (Thyrar, Thyroid Strong, S-P-T)

Thyroglobulin (Tg; Proloid)

45
Q

Levothyroxine (Synthroid, Levothroid, Levoxyl, Unithroid)- MOA

A

Isomer of T4 (L-thyroxine) is converted to T3

46
Q

What is the DOC for hypothyroidism?

A

Levothyroxine (Synthroid, Levothroid, Levoxyl, Unithroid)

Due to being chemically stable, inexpensive, free antigenicity, uniform potency

47
Q

Should Levothyroxine (Synthroid, Levothroid, Levoxyl, Unithroid) be taken with food or on an empty stomach?

A

TAKE ON AN EMPTY STOMACH

48
Q

What is different about the script for levothyroxine?

A

MUST check the DO NOT substitute line

49
Q

Levothyroxine- ADRs

A
Arrhythmias
Tachycardia
Anginal pain
Cramps
HA
Restlessness
Sweating
Weight loss
Osteoporosis
50
Q

Levothyroxine- contraindications

A

Thyrotoxicosis

51
Q

Levothyroxine- Monitoring

A

Every 6-8 weeks until TSH normalized, then every 6-12 months
If doses changed, recheck TSH in 2-3 months
Clinical evaluation of symptoms indicative of treatment response

52
Q

Levothyroxine- drug interactions

A

Altered absorption -Cholestyramine, Ferrous sulfate, Sucralfate, Aluminum hydroxide

Increased metabolism- Rifampin, Phenytoin, Carbamazepine

Oral (if pt is on these drugs then levo is no longer DOC) Contraceptives/Estrogens
Increase thyroid binding globulin, resulting in lower free thyroid hormone
Lithium
Inhibits synthesis and release of thyroid hormone
Amiodarone
Blocks conversion to T4 to T3
Warfarin
Increases metabolism of clotting factors

53
Q

Liothyronine Sodium (Cytomel, Triostat)- Indications

A

Initial therapy of myxedema (skin disorder) and myxedema coma
Short-term suppression of TSH in patients undergoing surgery for thyroid cancer.
Patients w/5’-deiodinase deficiency who cannot convert T4 to T3.

54
Q

Is Liothyronine used for maintenance?

A

Liothyronine generally not used for maintenance replacement therapy because of its short half-life and duration of action.

55
Q

Liotrix (Euthroid, Thyrolar)- indications

A

Used for thyroid hormone replacement
The idea is that the combo mimics the normal ratio secreted by the thyroid gland but is not any more effective than levothyroxine.

56
Q

How do you treat myxedema coma?

A

IV bolus levothyroxine 300-500mcg
Maintenance 75-100 mcg IV until able to switch to PO
IV hydrocortisone 100mg q 8h until coexisting adrenal suppression is ruled out
Supportive therapy- ventillation, euglycemia, blood pressure, body temp maintained

57
Q

How do you treat with congenital hypothyroidism?

A

Initial therapy within 45 days of birth at 10-15mcg/kg/d, associated with improved IQ’s in treated infants
Dose progressively decreased to typical adult dose beginning 11-20 years
AGGRESSIVE THERAPY IMPORTANT FOR NORMAL DEVELOPMENT

58
Q

What is hypothyroidism in pregnancy associated with?

A

Associated with increased risk of still-births
IQ of children born to women with untreated hypothyroid have lower IQ
Thyroid necessary for fetal growth; provided by mom during first 12 weeks of gestation
Congenital deficiency associated with decreased physical/ mental activity, CV, GI, neuromuscular function

59
Q

Where does the fetus get thyroid hormone?

A

hormone comes form mom during first 12 wks of pregnancy and not until after 12 wks so they produce their own.

60
Q

What is the treatment for hypothyroidism in pregnant patients?

A

Treatment: levothyroxine
20% requires dose increase during pregnancy/ decrease after (if they have hypothyroidism before pregnancy)
Typically require 36 mcg/day increase in dosage
Mostly important during the first 12 wks of pregancy

61
Q

What does hyperthyroidism result from?

A

Overproduction of endogenous hormone
Exposure to excess endogenous hormone
Elevated free and total T3, T4 or both serum

62
Q

What is the TSH level with hyperthyroidism?

A
Low serum concentrations TSH
Suppressed TSH
Peaks among 20-39 yo
Declines among 40-79 yo
Increases among 80+
Female>men
Subclinical
TSH 13.2 mcg/dL
63
Q

What are the signs and sx of HYPERthyroidism?

A
Nervousness
Anxiety
Palpitations
Increased basal metabolic rate (BMR)
Weight loss
Increased appetite
Increased body temp (heat intolerance)
Sweating
Fine Tremor
Tachycardia
Classical ophthalmic signs
64
Q

What is the most common cause of hyperthyroidism?

A

Graves Disease

65
Q

What is an autoimmune syndrome that includes hyperthyroidism, diffuse thyroid enlargement, myxedema and thyroid acropachy?

A

Graves disease

66
Q

What is happening with graves disease?

A

Antibodies against thyroid cell
IgG type antibodies against the TSH receptors that bind to and activate the receptor.
Genetic predisposition
8x more likely in women than men

67
Q

What is the TSH level with Graves disease?

A

TSH undetectable from negative feedback from elevated thyroid hormone (thryoid levels get so high that the TSH levels drop to nearly undetectable)

68
Q

What is hyperthyroidism in pregnancy almost always caused by?

A

Graves Disease
Inappropriate production of human chorionic gonadotropin (hCG) can cause subclinical or overt hyperthyroidism
Gestational trophoblastic disease

69
Q

In untreated women with hyperthyroidism caused by graves disease what are the complications that are more common?

A
Spontaneous abortion
Premature delivery
Low birth weight
Eclampsia
Pregnancy itself can improve Graves with decreased doses of drug or even discontinuation of treatment by 3rd trimester
70
Q

What is the treatment of choice for graves disease and pregnancy?

A

PTU is drug of choice at lowest effective dose

Methimazole has some data suggesting possible teratogenicity
RAI contraindicated in pregnancy
Surgery not recommended

71
Q

What should patient treated for hyperthyroidism during pregnancy be reevaluated for?

A

Pts treated for hyperthyroidism during pregnancy need to be reevaluated postpartum- disease can worsen

72
Q

What is a life threatening medical emergency characterized by sever thyrotoxicosis, high fever (often >103F), tachycardia, tachypnea, dehyration, delirium-coma, N/V, and diarrhea associated with hyperthyroidism?

A

Thyroid storm

73
Q

What are the precipitating factors for thyroid storm?

A

Infection, trauma, surgery radioactive iodine treatment, withdrawl from antithyroid drugs

74
Q

What is the tx for thyroid storm?

A

Aggressive treatment lowers mortality to 20%
Suppression of thyroid hormone formation and secretion
Anti-adrenergic therapy
Administration corticosteroids
Treatment of complications

75
Q

What are the thioamides for tx of hyperthyroidism?

A

Propylthiouracil (PTU) (DOC in pregnancy)

Methimazole (Tapazole)

76
Q

Propylthiouracil (PTU), Methimazole (Tapazole) (thioamides)- MOA

A

Thioamide

MOA: Block thyroid hormone Synthesis

77
Q

Propylthiouracil (PTU), Methimazole (Tapazole) (thioamides)- indications

A

Management of hyperthyroidism
Thyrotoxic crisis- to get patient undercontrol before you undergo surgery or radiation
In the preparation of patients for surgical subtotal thyroidectomy

78
Q

Does MMI or PTU have less side effects?

A

MMI

79
Q

Which is more potent MMI or PTU?

A

MMI generally has fewer side effects
MMI 10x more potent than PTU
Requires lower dosages

80
Q

Propylthiouracil (PTU), Methimazole (Tapazole) (thioamides)- ADRS

A

If given in excessive amounts over a long period, thioamides may cause hypothyroidism and enlargement of the thyroid gland.
Most serious ADRs—these usually occur in ~ 0.5% of pts w/in first 3 months of therapy
Arganulocytosis-must obtain baseline white blood cell count (stop if develop fever or sore throat)
Hepatotoxicity-baseline white blood cell count (stop if pt. develops fever or sore throat)
Vasculitis-drug induced lupus or anti-neutrophil

Most frequent ADRs
Rash
Arthralgia
Myalgia
Cholestatic jaundice
Lymphadenopathy
Drug fever
Psychosis
Alopecia
81
Q

Iodines and Iodine-Containing Agents (Potassium Iodine (KI)(Thyro-block,Lugol’s)- MOA

A

Iodine causes inhibition of thyroid hormone secretion

82
Q

Iodines and Iodine-Containing Agents (Potassium Iodine (KI)(Thyro-block,Lugol’s)-indications

A

Indications- trying to get the thyroid gland down in size before surgery
Preoperatively for thyroidectomy (7-14 days)
Used after RAI (3-7 days), to allow RAI to concentrate in thyroid

83
Q

Iodines and Iodine-Containing Agents (Potassium Iodine (KI)(Thyro-block,Lugol’s)-contraindications

A

Should not be given to breastfeeding women, can cause a goiter in infants.

84
Q

When should iodine and iodide not be given?

A

Iodine and iodide are given 10-14 days prior to partial thyroidectomy w/PTU or methimazole. They should not be given long-term because they loose their effectiveness.

85
Q

Iodines and Iodine-Containing Agents (Potassium Iodine (KI)(Thyro-block,Lugol’s)- ADRS

A
Hypersensitivity rxn
HA
Lacrimation
Conjunctivitis
Laryngitis
Thyrotoxicosis in patients w/nontoxic goiter
Drug fever
Acneform rash
Metallic taste in mouth
86
Q

What is the DOC for hyperthyroidism?

A

Radioiodine

87
Q

Radioiodine- Indications

A

Agent of choice for Graves, toxic autonomous nodules, toxic multinodulor goiters

88
Q

Radioiodine MOA

A

Goal is to destroy overactive thyroid cells:

89
Q

Radioiodine- major disadvantage

A

Hypothyroidism in most patients
Can not be used in pregnancy
Hypothyroid often occurs months-years after RAI
Women more likely to become hypothyroid
African Americans are most likely to be resistant to RAI (require multiple doses)

90
Q

Lithium Carbonate- MOA

A

Lithium inhibits thyroidal incorporation of I- into thyroid gland
Inhibits the secretion of thyroid hormones from follicular cells

91
Q

Lithium carbonate- Indications

A

Offers no advantage over thioamide but maybe used for temporary control of thyrotoxicosis in patients allergic to thioamides and iodine.

92
Q

Beta-Adrenergic Antagonists

A

Used to ameliorate thyrotoxic symptoms: palpitations, anxiety, tremor, heat intolerance
Symptoms of thyrotoxicosis mimic symptoms associated with sympathetic stimulation, thyroid hormone ↑ β1 receptors in the heart by 50-100%
Adjunct therapy- no effect on peripheral thyrotoxicosis and therapeutic effect

93
Q

What are the corticosteroids?

A

Dexamethasone
Prednisone
Methylprednisolone
Hydrocortisone

94
Q

Corticosteroids (Dexamethasone, Prednisone, Methylprednisolone, hydrocortisone)- Effects and indications

A

Effects:
Decreases thyroid action
Decreases immune response in Grave’s disease
USEFUL IN THYROIDITIS AND THYROID STORM

95
Q

What are the indications for a thyroidectomy?

A

Large glands
Severe ophthalmopathy
Lack of remission on treatment

96
Q

On who should thyroidectomy not be done one?

A

Should not be done on patients with low RAI uptake

97
Q

What should be given up until the thryoidectomy?

A
Propylthiouracil (PTU) or methimazole (MMI) until pt is euthyroid (6-8 weeks) followed by iodide 500 mg/day x 10-14 days
Beta blocker (propranolol/ nadolol) pre- and post-surgery to maintain HR <90 bpm
98
Q

What are the complications of thyroidectomy?

A
Complications depend on how much of the thyroid is removed. 
Hyperthyroidism
Hypothyroidism
Hypoparathyroidism
Vocal cord abnormalities
99
Q

What are the drug interactions that need to be considered when adding a thyroid agent or an antithyroid agent?

A

WARFARIN
LITHIUM
Diabetes medication requirements may change
Potassium iodide used as expectorants
CARDIAC GLYCOSIDES SUCH AS DIGOXIN MAY REQUIRE DOSE ADJUSTMENTS
AMIODARONE
CNS depressants

100
Q

What drugs can cause decreased TSH?

A
Dopamine
Levodopa
Bromocriptine
Octreotide
Amphetamin
Glucocorticoids (dexamethasone, hydrocortisone)
101
Q

What drugs can cause increased TSH?

A

Metoclopramide
Amiodarone
Iodinated contrast media

102
Q

What drugs can cause increased free T4?

A
IV fureosemide
IV heparin
Amiodarone
Iodinated contrast media
NSAIDS
Salicylates
Salsalate
Diclofinac
Naproxen
103
Q

What drugs can cause decreased free T4?

A

Phenytoin

Carbamazepine

104
Q

Where does most T3 result from?

A

Peripheral conversion of T4

105
Q

What drugs inhibit the conversion of T4 to T3?

A

Beta blockers and corticosteroids interfere minimally (Propranolol, atenolol, metoprolol)
Corticosteroids reduce T3 (useful in thyroid storm or severe hyperthyroidism)
Amiodarone and iodinated contrast media can inhibit conversion in the peripheral and pituitary gland

106
Q

What can cause drug induced thyroid disease?

A
Iodides 
Iodine induced hyperthryoidism
Iodine induced hypothyroidism
Lithium
Interferon alpha (IFNalpha)
107
Q

What iodides cause thyroid disease?

A
In multiple prescription products
Amiodarone
Radiocontrast dye
Povidone iodine- soaps used prior to surgery
Iodinated glycerol
In non-prescription products
Cough and cold
Kelp
Herbals
Dietary supplements/ weight loss products
108
Q

When does iodine induced hyperthryoidism (Jod-Basedow diease) develop and how is it treated?

A

Develops within 3-8 weeks after exposure in up to 5% pts

Treatment with thioamides and beta blockers

109
Q

What is the treatment of iodine induced thyroid disease?

A

Up to 10% of amiodarone treated patients will develop

Treat with levothyroxine replacement

110
Q

What is the treatment of lithium induced thyroid disease?

A

Up to 50% of pts can develop hypothyroidism
Important to monitor TSH first
Goiter may develop in pts without developing hypothyroidism
More likely in patients on lithium treatment for >2 years
More likely in patients with pre-existing autoantibodies
Treatment with levothyroxine can reverse hypothyroidism
Can spontaneously resolve without treatment
Stopping lithium does not always resolve symptoms or goiter
May require surgical intervention

111
Q

What thyroid disease results from interferon alpha?

A

used For hepatitis C treatment or chemotherapy
Not likely with interferon beta
Prevalence 2.5% to 20% induced thyroid disease
Can occur within 6-8 weeks of starting therapy or occur 6-23 months after start
Hypothyroidism most likely, hyperthyroid may occur
Typically dysfunction is transient and does not necessitate treatment in all cases
Can “unmask” pre-existing thyroid disorder
Hypothyroidism resolves spontaneously within 2-3 months after stopping therapy in most patients- may take longer