Week 7: Hypothyroidism Flashcards
Describe thyroid histological features
Identify features of thyroid histology
Identify features of thyroid histology
Where does thyroid hormone synthesis occur?
Describe the synthesis of thyroid hormones
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
What happens to T3 and T4 in the target cell?
Describe Thyroid hormone metabolism
Describe the T4 metabolism to T3
Describe the Wolff-Chaikoff effect
excess iodine causes shut down of thyroid hormone production but after awhile can escape this effect and production will resume
TSH structure
Describe thyroid hormone structures
Production rate of T4
80-100 mcg/day
Where is T4 produced
Thyroid
T4 storage
extrathyroidal pool of about 800-1000 mcg
T4 rate of degradation
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
Pathways of thyroid hormone metabolism
T3 production rate
30-40 mcg/day
T3 storage
extrathyroidal T3 pool of about 50 mcg which is intracellular
Where is T3 produced?
only about 20% is produced in the thyroid
80% is produced extrathyroidal deiodination of T4 by 5’-deiodinase
T3 rate of degradation
mostly by deiodination about 75% per day
How are thyroid hormones stored
essentially circulating in the blood bound to protein
What are plasma thyroid hormones bound to?
4 listed
- Thyroxine-binding globulin (TBG)
- Transthyretin
- Albumin
- Lipoproteins
What is TBG?
Thyroxine-binding globulin
Liver failure effects on TBG
Increased TBG due to hyper estrogenic state that occurs in cirrhosis
Elevated estrogen leads to increased TBG production in the liver
TBG levels
TBG increase in pregnancy or OCP use (estrogen TBG), cirrhosis due to hyperestrogenic state, also OCP
T4 binding globulins
T3 binding globulins
TTR = Transthyretin
Regulation of thyroid function
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
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
What is hypothyroidism
deficiency of thyroid hormone
What is primary hypothyroidism?
An issue within the thyroid
(High TSH levels)
What is secondary hypothyroidism?
(Low TSH)
Issue with the pituitary
What is tertiary hypothyroidism?
(Low TRH, low TSH)
hypothalamic disease
Thyroid hormone resistance
Rare
Primary hypothyroidism prevalence
95% of all hypothyroidism
Prevalence of hypothyroidism
- 2% of adult women
- 0.2% of adult men
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
Constitutional symptoms of hypothyroidism
- Cold intolerance
- Fatigue
- lethargy
- weakness
- hoarseness
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
Cardiovascular symptoms of hypothyroidism
- reduced contractility
- reduced rate
- reduced cardiac output
- pericardial/pleural effusions
- increased peripheral vascular resistance
- CHF-rare
What is this depicting?
Severe hypothyroidism
periorbital edema
What is this depicting?
- Severe hypothyroidism
- periorbital swelling
- loss of the outer third of eyebrows
Gastrointestinal symptoms of hypothyroidism
- decreased appetite
- constipation
- weight gain (5-10% increase)
Gynecologic symptoms of hypothyroidism
- menorrhagia
- menstrual irregularities
Musculoskeletal symptoms of hypothyroidism
- Myalgias
- arthralgias
- hypothyroid myopathy
- proximal muscle weakness
- CK elevation
Hematologic symptoms of hypothyroidism
- anemia
- normocytic, normochromic anemia
Neurologic symptoms of hypothyroidism
- delayed relaxation phase of DTRs
- difficulty concentrating
- poor memory
- somnolence
- depression
- headache
- paresthesias
Hypothyroid myopathy
- proximal muscle weakness
- CK elevation
Type of anemia seen with hypothyroidism
normocytic normochromic anemia
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
Drugs that can interfere with thyroid hormone synthesis
4 listed
- Lithium (bipolar)
- amiodarone
- interferon-alpha
- tyrosine kinase inhibitors
Infiltrative disease that can cause primary hypothyroidism
7 listed
- fibrous thyroiditis (Riedel’s thyroiditis)
- Hemochromatosis
- Sarcoidosis
- amyloidosis
- scleroderma
- leukemia
- cystinosis
What is the most common type of thyroid disease in developed regions?
Autoimmune (Hashimoto’s) Thyroiditis
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)
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)
Serological tests for Hashimoto’s Thyroiditis
Autoantibodies
- Thyroglobulin
- Thyroid peroxidase
- Thyroid Na/I transporter (not measurable)
Histological features of Hashimoto’s Thyroiditis
Histology of Hashimoto’s Thyroiditis
germinal centers forming
lymphocytic infiltrate Hurthle cells or oncocytic cells are hallmark of Hashimoto’s Thyroiditis
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
What is postpartum thyroiditis?
- Destructive thyroiditis induced by an autoimmune mechanism within one year of parturition
- Can also occur after spontaneous or induced abortion
*
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
How long does postpartum thyroiditis last?
postpartum hypothyroidism lasts several weeks up to 6 months
Postpartum thyroiditis clinical presentation
- Mildly enlarged, diffuse, nontender thyroid gland
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
Treatment of Postpartum thyroiditis
Treat with T4 if symptomatic but is transient so just wait
What is Riedel Thyroiditis?
Thyroid replaced by fibrous tissue with inflammatory infiltrate
fibrosis may extend to local structures (eg trachea, esophagus), mimicking anaplastic carcinoma
Riedel Thyroiditis clinical presentation
fixed, hard (rock-like) painless goiter
1/3 of patients become hypothyroidic
Riedel Thyroiditis histological features
Riedel Thyroiditis associations
Considered a manifestation of IgG4-related systemic disease (eg, autoimmune pancreatitis, retroperitoneal fibrosis, noninfectious aortitis)
What is congenital hypothyroidism
1:2000 to 1:4000 newborns
One of the most common preventable causes of intellectual disability
Congenital hypothyroidism cause
85% are sporadic
15% hereditary (autosomal recessive)
Congenital Central hypothyroidism
defects in the production of TSH due to either hypothalamic or pituitary dysfunction
1:16,404 newborns
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
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
What is cretinism?
untreated maternal hypothyroidism due to severe iodine deficiency
Types of cretinism
- Myxedematous cretinism
- Neurologic cretinism
Myxedematous cretinism
intellectual disability
short stature
hypothyroidism
iodine deficiency
thyroid injury predominantly late in pregnancy and continuing after birth
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
Thyroid hormone and development
Thyroid hormone is essential for normal maturation of the central nervous system
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)
Causes of secondary hypothyroidism
Causes of tertiary hypothyroidism
How to Diagnose hypothyroidism and type
Lab findings in subclinical hypothyroidism
Lab findings in overt hypothyroidism
Lab findings in primary hypothyroidism
Lab findings in secondary hypothyroidism
Treatment for hypothyroidism
What is Myxedema coma?
Signs and symptoms of Myxedema coma
Evaluation of myxedema coma
History and physical exam
Check TSH, Free T4, cortisol
Treatment of myxedema coma
Nontthyroidal illness AKA
Euthyroidal sick Syndrome
What is Euthyroidal sick syndrome
Euthyroid sick syndrome problem with low T3
T4 levels in nonthyroidal illness
Recommended labs for hypothyroidism
Treatment in critically ill patients
