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Week 7: Hypothyroidism Flashcards

1
Q

Describe thyroid histological features

A
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2
Q

Identify features of thyroid histology

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3
Q

Identify features of thyroid histology

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4
Q

Where does thyroid hormone synthesis occur?

A
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5
Q

Describe the synthesis of thyroid hormones

A

TSH from pituitary to TSH receptor and protein synthesis (thyroglobulin) Thyroglobuilin to the colloid and T3 and T4 are added and T3 and T4 are cleaved off and released to the body

Iodide is brought in via Na+-Iodide symporter

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6
Q

What happens to T3 and T4 in the target cell?

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7
Q

Describe Thyroid hormone metabolism

A
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8
Q

Describe the T4 metabolism to T3

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9
Q

Describe the Wolff-Chaikoff effect

A

excess iodine causes shut down of thyroid hormone production but after awhile can escape this effect and production will resume

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10
Q

TSH structure

A
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11
Q

Describe thyroid hormone structures

A
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12
Q

Production rate of T4

A

80-100 mcg/day

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13
Q

Where is T4 produced

A

Thyroid

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14
Q

T4 storage

A

extrathyroidal pool of about 800-1000 mcg

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15
Q

T4 rate of degradation

A

10% per day

80% is deiodinated

  • 40% converted to T3
  • 40% converted to reverse T3 (rT3)
  • 20% is conjugated with glucuronide and sulfate, deaminated and decarboxylated form tetraiodothryoacetic acid (tetrac), or cleaved between the two rings
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16
Q

Pathways of thyroid hormone metabolism

A
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17
Q

T3 production rate

A

30-40 mcg/day

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18
Q

T3 storage

A

extrathyroidal T3 pool of about 50 mcg which is intracellular

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19
Q

Where is T3 produced?

A

only about 20% is produced in the thyroid

80% is produced extrathyroidal deiodination of T4 by 5’-deiodinase

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20
Q

T3 rate of degradation

A

mostly by deiodination about 75% per day

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21
Q

How are thyroid hormones stored

A

essentially circulating in the blood bound to protein

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22
Q

What are plasma thyroid hormones bound to?

4 listed

A
  • Thyroxine-binding globulin (TBG)
  • Transthyretin
  • Albumin
  • Lipoproteins
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23
Q

What is TBG?

A

Thyroxine-binding globulin

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24
Q

Liver failure effects on TBG

A

Increased TBG due to hyper estrogenic state that occurs in cirrhosis

Elevated estrogen leads to increased TBG production in the liver

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25
TBG levels
TBG increase in pregnancy or OCP use (estrogen TBG), cirrhosis due to hyperestrogenic state, also OCP
26
T4 binding globulins
27
T3 binding globulins
TTR = Transthyretin
28
Regulation of thyroid function
29
TSH secretion properties
75 -150 mU/day (15-30 mcg/day) TSH secretion is pulsatile TSH concentrations are 50 - 100% higher in the late evening than during the day
30
Cellular effects of thyroid hormone
* T4 is converted to T3 (which is the active thyroid hormone) * DNA synthesis of various proteins * bone growth * CNS maturation * Increased O2 consumption (increase Na+K+ATPase and metabolic enzymes) * Increase β1 activity in the heart increasing heart rate and contractility * increase glycogenolysis * increase in CO2 and ventilation * Increase renal function * Decreased muscle mass * Decreased adipose from freeing up substrate
31
What is hypothyroidism
deficiency of thyroid hormone
32
What is primary hypothyroidism?
An issue within the thyroid | (High TSH levels)
33
What is secondary hypothyroidism?
(Low TSH) Issue with the pituitary
34
What is tertiary hypothyroidism?
(Low TRH, low TSH) hypothalamic disease
35
Thyroid hormone resistance
Rare
36
Primary hypothyroidism prevalence
95% of all hypothyroidism
37
Prevalence of hypothyroidism
* 2% of adult women * 0.2% of adult men
38
Clinical features of hypothyroidism
Constitutional symptoms * Cold intolerance * Fatigue * lethargy * weakness * hoarseness Integument * Thickened/yellowed, dry, non-pitting edema ("Myxedema") of hands/feet/periorbital region * dry, cool skin * Alopecia * Hair- brittle and dry * brittle nails Cardiovascular * reduced contractility * reduced rate * reduced cardiac output * pericardial/pleural effusions * increased peripheral vascular resistance * CHF-rare Gastrointestinal * decreased appetite * constipation * weight gain (5-10% increase) Gynecologic * menorrhagia * menstrual irregularities Musculoskeletal * Myalgias * arthralgias * hypothyroid myopathy * proximal muscle weakness * CK elevation Hematologic * anemia * normocytic, normochromic anemia Neurologic * delayed relaxation phase of DTRs * difficulty concentrating * poor memory * somnolence * depression * headache * paresthesias
39
Constitutional symptoms of hypothyroidism
* Cold intolerance * Fatigue * lethargy * weakness * hoarseness
40
Integument symptoms of hypothyroidism
* Thickened/yellowed, dry, non-pitting edema ("Myxedema") of hands/feet/periorbital region * dry, cool skin * Alopecia * Hair- brittle and dry * brittle nails
41
Cardiovascular symptoms of hypothyroidism
* reduced contractility * reduced rate * reduced cardiac output * pericardial/pleural effusions * increased peripheral vascular resistance * CHF-rare
42
What is this depicting?
Severe hypothyroidism periorbital edema
43
What is this depicting?
* Severe hypothyroidism * periorbital swelling * loss of the outer third of eyebrows
44
45
Gastrointestinal symptoms of hypothyroidism
* decreased appetite * constipation * weight gain (5-10% increase)
46
Gynecologic symptoms of hypothyroidism
* menorrhagia * menstrual irregularities
47
Musculoskeletal symptoms of hypothyroidism
* Myalgias * arthralgias * hypothyroid myopathy * proximal muscle weakness * CK elevation
48
Hematologic symptoms of hypothyroidism
* anemia * normocytic, normochromic anemia
49
Neurologic symptoms of hypothyroidism
* delayed relaxation phase of DTRs * difficulty concentrating * poor memory * somnolence * depression * headache * paresthesias
50
Hypothyroid myopathy
* proximal muscle weakness * CK elevation
51
Type of anemia seen with hypothyroidism
normocytic normochromic anemia
52
Causes of primary hypothyroidism
Iodine deficiency (undeveloped world from iodine salt in developed) Iatrogenic * surgery * radioablation * external radiation therapy Autoimmune thyroid destruction Drugs interfering with hormone synthesis (lithium (bipolar), amiodarone, interferon alpha, tyrosine kinase inhibitors) Infiltrative diseases Congenital thyroid agenesis or defects in hormone synthesis
53
Drugs that can interfere with thyroid hormone synthesis 4 listed
* Lithium (bipolar) * amiodarone * interferon-alpha * tyrosine kinase inhibitors
54
Infiltrative disease that can cause primary hypothyroidism 7 listed
* fibrous thyroiditis (Riedel's thyroiditis) * Hemochromatosis * Sarcoidosis * amyloidosis * scleroderma * leukemia * cystinosis
55
What is the most common type of thyroid disease in developed regions?
Autoimmune (Hashimoto's) Thyroiditis
56
Autoimmune (Hashimoto's) Thyroiditis epidemiology
* most common type of thyroid disease in iodine-sufficient regions * mainly in females * aged 30-50 * also common in children * Can be associated with polyglandular autoimmune disease (celiac, pernicious anemia, adrenal insufficiency)
57
Hashimoto's Thyroiditis can be associated with? 5 listed
* Can be associated with polyglandular autoimmune disease (celiac, pernicious anemia, adrenal insufficiency) * Turner Syndrome * Down syndrome * HLA-DR5 * Increased risk of non-Hodgkin Lymphoma (typically of B-cell origin)
58
Serological tests for Hashimoto's Thyroiditis
Autoantibodies * Thyroglobulin * Thyroid peroxidase * Thyroid Na/I transporter (not measurable)
59
Histological features of Hashimoto's Thyroiditis
60
Histology of Hashimoto's Thyroiditis
germinal centers forming lymphocytic infiltrate Hurthle cells or oncocytic cells are hallmark of Hashimoto's Thyroiditis
61
Hashimoto's Thyroiditis Clinical presentation
Hashitoxicosis * hyperthyroid early in course due to release of T4/T3 from ruptured thyroid follicles * then become hypothyroidic Chronic inflammation over years leads to hypothyroidism May present with moderately nontender thyroid Later thyroid becomes atrophic and fibrotic
62
What is postpartum thyroiditis?
* Destructive thyroiditis induced by an autoimmune mechanism within one year of parturition * Can also occur after spontaneous or induced abortion *
63
How is postpartum thyroiditis different from other types
* hyperthyroid phase from thyroid follicle destruction with low TSH * may have brief euthyroid phase (normal level) * becomes hypothyroidic * High TSH and high 24-hour RAI uptake (which is a test for hyperthyroidism) * 20-30% have hyper followed by transient hypothyroidism * 40-50% have only transient hypothyroidism * hypothyroidism lasts several weeks r up to 6 months * 20-40% have only the hyperthyroidism
64
How long does postpartum thyroiditis last?
postpartum hypothyroidism lasts several weeks up to 6 months
65
Postpartum thyroiditis clinical presentation
* Mildly enlarged, diffuse, nontender thyroid gland
66
Postpartum thyroiditis associations
* Consider in women * Type 1 DM * Hx of postpartum thyroiditis after a previous pregnancy * Hx of high serum antithyroid peroxidase antibody concentrations prior to pregnancy * Clinical manifestations of postpartum thyroiditis * Postpartum depression
67
Treatment of Postpartum thyroiditis
Treat with T4 if symptomatic but is transient so just wait
68
What is Riedel Thyroiditis?
Thyroid replaced by fibrous tissue with inflammatory infiltrate fibrosis may extend to local structures (eg trachea, esophagus), mimicking anaplastic carcinoma
69
Riedel Thyroiditis clinical presentation
fixed, hard (rock-like) painless goiter 1/3 of patients become hypothyroidic
70
Riedel Thyroiditis histological features
71
Riedel Thyroiditis associations
Considered a manifestation of IgG4-related systemic disease (eg, autoimmune pancreatitis, retroperitoneal fibrosis, noninfectious aortitis)
72
What is congenital hypothyroidism
1:2000 to 1:4000 newborns One of the most common preventable causes of intellectual disability
73
Congenital hypothyroidism cause
85% are sporadic 15% hereditary (autosomal recessive)
74
Congenital Central hypothyroidism
defects in the production of TSH due to either hypothalamic or pituitary dysfunction 1:16,404 newborns
75
Congenital hypothyroidism clinical manifestations during pregnancy and at birth
More than 95% of infants with congenital hypothyroidism have few if any clinical manifestations of hypothyroidism at birth Some maternal T4 crosses the placenta so pregnant women with hypothyroidism are mainly treated with T4
76
Congenital hypothyroidism clinical manifestations of infants who did not undergo screening
6 Ps * Pot-bellied * Pale * Puffy-faced child * protruding umbilicus * protuberant tongue * poor brain development lethargy hoarse cry feeding problems (needing to be awakened to nurse) Constipation Macroglossia umbilical hernia large fotnanels hypotpponia dry skin hypothermia prolonged jaundice
77
What is cretinism?
untreated maternal hypothyroidism due to severe iodine deficiency
78
Types of cretinism
* Myxedematous cretinism * Neurologic cretinism
79
Myxedematous cretinism
intellectual disability short stature hypothyroidism iodine deficiency thyroid injury predominantly late in pregnancy and continuing after birth
80
Neurologic cretinism
Intellectual disability deaf mutism gait disturbances spasticity But not hypothyroidism Hypothyroidism in the mother during early pregnancy but a euthyroid state postnatally due to adequate iodine intake in the newborn
81
Thyroid hormone and development
Thyroid hormone is essential for normal maturation of the central nervous system
82
What is consumptive hypothyroidism
* very rare form of hypothyroidism * excessive degradation of thyroid hormone due to ectopic production of the type 3 deiodinase * Metabolized T4 to reverse T3 and T3 to T2 * Vascular and fibrotic tumors and in patients with gastrointestianl stromal tumors (GISTs)
83
Causes of secondary hypothyroidism
84
Causes of tertiary hypothyroidism
85
How to Diagnose hypothyroidism and type
86
Lab findings in subclinical hypothyroidism
87
Lab findings in overt hypothyroidism
88
Lab findings in primary hypothyroidism
89
Lab findings in secondary hypothyroidism
90
Treatment for hypothyroidism
91
What is Myxedema coma?
92
Signs and symptoms of Myxedema coma
93
Evaluation of myxedema coma
History and physical exam Check TSH, Free T4, cortisol
94
Treatment of myxedema coma
95
Nontthyroidal illness AKA
Euthyroidal sick Syndrome
96
What is Euthyroidal sick syndrome
97
Euthyroid sick syndrome problem with low T3
98
T4 levels in nonthyroidal illness
99
Recommended labs for hypothyroidism
100
Treatment in critically ill patients

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