Thyroid: Hypothyroidism Flashcards
What is the most common cause of hypothyroidism worldwide?
Iodine deficiency
What is the most common cause of hypothyroidism in areas of iodine sufficiency?
Autoimmune disease (Hashimoto’s thyroiditis) and iatrogenic causes (treatment of hyperthyroidism)
What is the most common cause of neonatal hypothyroidism?
Thyroid gland dysgenesis (80-85%)
What are the genetic causes of congenital hypothyroidism?
PROP-1 - Combined pituitary hormone deficiencies with preservation of adrenocorticotropic hormone
PIT-1 - Combined deficiencies of growth hormone, prolactin, thyroid stimulating hormone
TSH beta - TSH deficiency
TTF-1 - Variable thyroid hypoplasia
TTF-2 Thyroid agenesis
PAX-8, NKX2-1, NKX2-5 - Thyroid dysgenesis
TSH-receptor, G S alpha (Albright hereditary osteodystrophy) - Resistance to TSH
Na+/I- symporter - Inability to transport iodide
DUOX2, DUOXA2 - Organification defect
Thyroid peroxidase - Defective organification of iodide
Thyroglobulin - Defective synthesis of thyroid hormone
Pendrin - Pendred syndrome: sensorineural deafness and partial organification defect in thyroid
Dehalogenase 1 - Loss of iodide reutilization
What is Pendred syndrome?
It is an autosomal recessive condition caused by a defect in pendrin, that is characterized by sensorineural deafness and partial organification defect in thyroid
Initial dose of treatment in congenital hypothyroidism
10-15 mcg/kg per day (dose is adjusted by close monitoring of TSH levels)
What are the different classifications of autoimmune hypothyroidism?
Hashimoto’s or goitrous thyroiditis
Atrophic thyroiditis - minimal residual thyroid tissue which is usually the end stage of Hashimoto’s thyroiditis
Subclinical hypothyroidism - phase of compensation when normal thyroid hormone levels are maintained by a rise in TSH; may have minor symptoms
Clinical or Overt hypothyroidism - unbound T4 levels fall and TSH levels rise further; more readily apparent symptoms; usually TSH >10 mIU/L
Prevalance of autoimmune hypothyroidism: Sex, Race, Age
Sex: Women
Race: Japanese
Age: 60 years
What are the best documented genetic risk factors for autoimmune hypothyroidism?
HLA-DR polymorphisms (especially HLA-DR3, DR4, DR5 in Caucasians)
How does the following affect the risk of autoimmune hypothyroidism?
High iodine intake
Low selenium intake
Decreased exposure to microorganisms in childhood
Smoking cessation
Alcohol intake
High iodine intake - increased risk
Low selenium intake - Increased risk
Decreased exposure to microorganisms in childhood - Increased risk
Smoking cessation - Increased risk
Alcohol intake - Decreased risk
Thyroid cell destruction is primarily mediated by __________
CD8+ cytotoxic T cells
Microscopic findings in Hashimoto’s thyroiditis
Marked lymphocytic infiltration of the thyroid with germinal center formation, atrophy of the thyroid follicles accompanied by oxyphil metaplasia, absence of colloid, and mild to moderate fibrosis
TRUE OR FALSE: Transplacental passage of Tg or TPO antibodies has no effect on the fetal thyroid.
TRUE
Myxedema is caused by increased dermal ________
Increased dermal glycosaminoglycan content that traps water –> skin thickening without pitting
Effect of hypothyroidism on prolactin
Prolactin levels are often modestly increased –> alterations in libido, fertility, galactorrhea
How do you define Hashimoto’s encephalopathy?
It is a steroid-responsive syndrome associated with TPO antibodies, myoclonus, and slow-wave activity on EEG.
Effect of hypothyroidism on pituitary gland
Pituitary gland may be enlarged due to thyrotroph hyperplasia
Most frequent symptoms of hypothyroidism
Tiredness and weakness
Most frequent signs of hypothyroidism
Dry coarse skin; cool peripheral extremities
In autoimmune hypothyroidism, __% of circulating unbound T3 levels are normal.
25% (therefore T3 measurements are not indicated)
TRUE OR FALSE: A normal TSH level excludes both primary and secondary hypothyroidism.
FALSE. A normal TSH level excludes primary, but not secondary, hypothyroidism.
If TSH is elevated - measure FT4
If TSH is normal - check if pituitary disease is suspected
Better measure of thyroid function in the months following radioiodine treatment - FT4 or TSH?
FT4
Target T4 levels in secondary hypothyroidism - high normal or low normal?
T4 levels at the upper half of reference interval (TSH levels cannot be used to monitor therapy)
Drugs that can cause hypothyroidism
Amiodarone
Lithium
Daily replacement dose of levothyroxine
1.6 mcg/kg BW
Goal TSH in the treatment of clinical hypothyroidism
Normal TSH, ideally in the lower half of the reference range
When to recheck TSH after instituting treatment for hypothyroidism
2 months after instituting treatment or after any subsequent change in levothyroxine dosage
How many months before patients experience full relief from symptoms?
3-6 months after normal TSH levels are restored
Levothyroxine dosage is adjusted by which increments
12.5 to 25 mcg increments
What to do if patient misses a dose of T4?
a. Take missed dose before the next day
b. Take two doses of skipped tablets at once
c. Just take the dose for the next day
Because T4 has a long half-life (7 days), patients who miss a dose can be advised to take 2 doses of the skipped tablets at once.
Drugs that can affect levothyroxine absorption
Oral estrogen containing medications or SERM
Bile acid sequestrants, ferrous sulfate, calcium supplements, sevelamer, sucralfate, proton pump inhibitors, lovastatin, aluminum hydroxide, rifampicin, amiodarone, carbamazepine, phenytoin, tyrosine kinase inhibitors
When to treat subclinical hypothyroidism?
- If a woman wishes to conceive or is pregnant
- When TSH levels >10 mIU/L
- If TSH levels <10:
a. Suggestive symptoms of hypothyroidism
b. Positive TPO antibodies
c. Any evidence of heart disease
(Must confirm that any elevation of TSH is sustained over a 3-month period before treatment is given)
Levothyroxine dose in subclinical hypothyroidism
25-50 mcg/d (with the goal of normalizing TSH)
Prior to conception, levothyroxine therapy should be targeted to maintain a serum TSH in the normal range but
<2.5 mIU/L
In pregnancy, levothyroxine dose may need to be increased by up to __%.
45%
Elderly patients may require __% less thyroxine than younger patients.
20%
TRUE: Hypothyroid patients must achieve euthyroidism before undergoing emergency surgery.
FALSE. Emergency surgery is generally safe in patients with untreated hypothyroidism, although routine surgery in a hypothyroid patient should be deferred until euthyroidism is achieved.
What is the major pathogenesis in myxedema coma?
Hypoventilation which leads to hypoxia and hypercapnia (usually precipitated by factors that impair respiration)
TRUE OR FALSE: T3 is routinely given in combination with T4 in treating hypothyroidism.
FALSE
TRUE OR FALSE: T3 may be added to T4 in treating myxedema coma.
TRUE, because T4 to T3 conversion is impaired in myxedema coma.
In myxedema coma, external warming is indicated only if the temperature is ___.
<30 degrees Celsius (as it can result in cardiovascular collapse)
TRUE OR FALSE: Parenteral hydrocortisone should be administered in myxedema coma, because there is impaired adrenal reserve in profound hypothyroidism.
TRUE
