Thyroid Flashcards
What stimulates and inhibits TSH?
- Stimulated by TRH
- Inhibited by somatostatin and dopamine
What is the active thyroid hormone?
T3 is active thyroid hormone
(3-5x more potent than T4)
What is secreted at a higher rate? T3 or T4?
T4 is secreted at higher rate (x20) than T3
How is the majority of T3 made?
T3 is made primarily from peripheral conversion of T4 in the liver and kidney
Where is the thyroid hormone receptor?
Nucleus
What are the two key thyroid hormone receptors?
Nuclear steroid receptor; two types: alpha (chromosome 17), beta (chromosome 3)
Describe the implications of an inactivating mutation of the thyroid hormone receptor?
Inactivating mutation causes thyroid resistance syndrome
What is Hashimoto’s thyroiditis?
Most common cause of hypothyroidism in iodine-sufficient areas of the world is chronic autoimmune thyroiditis, which is caused by cell- and antibody-mediated destruction of thyroid tissue
What are the laboratory findings of primary hypothyroidism?
high TSH, low free T4
What are the main causes of primary hypothyroidism?
- Hashimoto’s thyroiditis
- Iatrogenic disease (thyroidectomy, radiation, etc)
Describe thyroid physiology in the setting of anorexia
- Similar to sick euthyroid state
- TSH normal or slightly low
- Low T3, high reverse T3
- Normal or low T4, but normal free T4
Describe Subacute (viral/deQuervain) thyroiditis:
- Subacute thyroiditis (subacute granulomatous thyroiditis) is characterized by neck pain or discomfort, a tender diffuse goiter, and a predictable course of thyroid function evolution
- Hyperthyroidism followed by euthyroidism, hypothyroidism, and ultimately restoration of normal thyroid function
- Low iodine uptake; high T3, low TSH
Describe secondary hypothyroidism
- TSH deficiency
- Hypopituitarism (tumor, Sheehan, trauma)
- TSH-R mutation
Describe tertiary hypothyroidism
- TRH deficiency
- Damage to hypothalamus or portal blood flow
- TRH-R mutation
Describe Graves Disease
- Autoimmune disease consisting of hyperthyroidism, goiter, eye disease (orbitopathy), dermopathy (pretibial or localized myxedema)
- Hyperthyroidism is the most common feature, affecting nearly all patients, and is caused by thyroid-stimulating hormone (TSH, thyrotropin)-receptor antibodies (TRAb) that activate the receptor, thereby stimulating thyroid hormone synthesis and secretion as well as thyroid growth (causing a diffuse goiter)
- High iodine uptake; high T3, low TSH
How do you work up a thyroid nodule?
- Serum TSH (higher TSH, higher risk of malignancy)
- Thyroid ultrasound
- FNA (if TSH is high and nodules meets sonographic criteria for sampling)
What is thyroid storm?
Rare, life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis
Describe the treatment for thyroid storm?
- Beta blocker to control the symptoms and signs induced by increased adrenergic tone
- A thionamide to block new hormone synthesis
- An iodine solution to block the release of thyroid hormone
- An iodinated radiocontrast agent (if available) to inhibit the peripheral conversion of T4 to T3
- Glucocorticoids to reduce T4-to-T3 conversion, promote vasomotor stability, possibly reduce the autoimmune process in Graves’ disease, and possibly treat an associated relative adrenal insufficiency
What happens to TSH in pregnancy?
TSH – decreases in first trimester (secondary to HCG), then normalizes
What happens to total T4 in pregnancy?
Total T4 – increases; increased overall requirement (increased metabolic rate and some transfer to fetus)
What happens to free T4 in pregnancy?
Free T4 – decreases; due to increased TBG
What happens to TBG in pregnancy?
TBG – increase; secondary to increased estrogen levels
When does fetal synthesis begin?
8-10 weeks
When is fetal thyroid development is complete?
12- 14 weeks
Does TSH cross the placenta?
No
What thyroid hormones can cross the placenta?
TRH, T4, and T3
Describe normal fetal thyroid physiology
- Fetus dependent on maternal thyroid hormone in first 20 weeks of pregnancy
- Fetal TSH plateaus at 28 weeks
- Increases production of T4 is compensated by peripheral conversion to RT3 (to conserve caloric expenditure)
What is a risk associated of PTU?
Agranulocytosis, check CBC
What is a risk associated with methimazole?
Aplasia cutis (congenital absence of skin)
What is the preferred treatment of hyperthyroidism during pregnancy?
PTU
Describe hyperthyroidism during pregnancy. What is the most common cause?
- Graves’ disease is the most cause of thyrotoxicosis in pregnancy
- Clinical triad: Goiter, thyroid ab, TSH-R Ab
- TSH-R antibodies can cross placenta
- PTU is preferred treatment
How does PTU affect the fetus?
Moderate doses suppress fetal T4 and increase TSH (h/e clinically euthyroid when born)
Excessive doses (OR if positive transplacental passage of TSH-like ab) - Neonatal goiter
Describe treatment issues of treating hypothyroidism in pregnant women
- Will likely need increase in thyroid treatment in hypothyroid women who become pregnant
- Don’t check sooner than 8 weeks
- Increased intravascular volume (dilutes thyroid)
- Placental transport to fetus
- Increase in TBG (Estrogen induces increases in TBG)
Describe recommendations for post postpartum management of hypothyroidism
- Post-partum, return to pre-pregnancy dosing
- Follow closely for 6 months with TSH levels due to high incidence of postpartum thyroiditis
How you titrate hypothyroid medications in pregnancy
Recommendations are to increase by 30%, then check monthly and adjust treatment based on TSH values (using pregnancy specific reference ranges)
When does thyroidal hyperactivity disappear in neonatal physiology?
After 3-4 weeks
Describe normal neonatal physiology of TSH
TSH: peaks 30 min, fall to baseline by 48-72h (response to TRH surge due to rapid neonatal cooling)
Describe normal neonatal physiology of free/total T4
Free/Total T4: Peak by 24-48h
Describe normal neonatal physiology of T3
T3: Peak by 24h
Describe normal neonatal physiology of RT3
RT3: High pregnancy levels continue for 3-5d, fall to normal by 2 weeks
What are causes of goiter in the neonate?
- Inborn errors of thyroid hormone production
- Maternal thyroid antibodies
- Blocking antibodies cause fetal hypoT and rare goiter
- Stimulating TSHR antibodies are classic to cause goiter + hyperthyroidism
- Maternal antithyroid drugs (PTU) or iodine rich drugs like amiodarone
- Activating TSH-R mutation (autosomal dominant)
- McCune Albright Syndrome
Describe fetal/neonatal physiology when mother is take PTU or iodine rich drugs like amiodarone.
Fetus: Increased TSH, reduced T4
Newborn: Labs normalize by DOL4-5 -> euthyroid
How common is postpartum thyroiditis?
Common (5-10%) auto-immune phenomenon after delivery
What are risk factors for postpartum thyroiditis?
- Personal or family history of autoimmune disease
- Previous PP episode
- Insulin-requiring DM (25% develop)
- Presence of thyroid Abs, also associated with postpartum depression
What are the rates of transient thyrotoxicosis followed by hypothyroidism for both transient hyper and hypothyroidism?
33% transient hyperthyroidism alone
44% transient hypothyroidism alone
What antibodies are associated with postpartum thyroiditis?
thyroid microsomal antibodies (like Hashimoto’s)
What proportion of patients with postpartum thyroiditis require long-term treatment?
10%; recurrence in subsequent pregnancy is high
Management options if TSH levels prior to pregnancy are 2.5-4 mIU?
- monitoring levels and treating when TSH >4 mIU/L
- treating with levothyroxine to maintain TSH <2.5 mIU/L
When to treat TSH…
If anti-TPO Abs present?
in first trimester?
when the TSH is >2.5 mIU/L
What level of TSH is associated w/ miscarriage?
> 4
