01-16 Hypothyroidism Flashcards
What are the three types of hypothyroidism?
- primary - most common
—thyroid is site of dz process - secondary - uncommon
—hypothal and/or pituitary are lesion locus(i) - thyroid hormone resistance - rare
—usually receptor mutation (including thyrotrophs in pituitary)
Distinguish between the 3 types of hypothyroidism based on:
—Goiter
—TSH level
—T4 level
1°: yes goiter; ↑ TSH; ↓ T4
2°: no goiter; ↓ TSH; ↓ T4
R: yes goiter; ↑ TSH; ↑ T4
—TSH high in R b/c pituitary also resistant
—cardiac thyroid R is diff, so R pts present w/ hypo sx BUT also tachycardia
One might expect that the TSH would be low in patients with 2° hypothyroidism. A recent study, however, showed that the mean TSH in such cases was 2.4μ/L (normal 0.28-4.2). How might this be explained?
They make some TSH, but a fair fraction of it REGISTERS on bioassay but is NOT bioactive b/c they have pituitary cancer.
—Due to the factor that it is not post-translationally modified properly.
—Peptide heterodimers are fine, but it is not fully glycosylated.
What are the glycoprotein hormones?
—basic structure
pituitary members: FSH, LH, TSH placental member: CG (fxn ~= LH) STRUCTURE —heterodimers of α & β peptide chains —subunits glycosylated which is req'd for fxn —all α-chains are the same
Most common causes of hypothyroidism
—basic demographics
1. Primary hypothyroidism is common worldwide —Endemic goiter (iodine deficiency) ——> 200,000,000 cases ——mountainous, non-coastal areas ——public health issue —Hashimoto's most common in W countries ——3.5 cases/1,000 women/year ——0.6 cases/1,000 men/year ——high incidence in elderly thyroid preparations among the most common prescriptions
- 2° disease much less common
Epidemiology of neonatal hypothyroidism
1:4000 worldwide
Québec Score for Neonatal Hypothyroidism
BIG POINTS: typical facies (3pts), dry skin (1.5pts), open posterior fontanel (1.5pts)
Others (all 1 pt): feeding problems, constip, inactivity, hypotonia, umbilical hernia, large tongue, mottled skin
Dx if score is > 8.6
Thyroid hormone acts at the level of gene transcription: What classes of genes are the targets?
Developmental: (only fxn in cold blooded animals) i. CNS (severe effects!) ii. Long bone growth Metabolism: i. Mitochondrial # & fxn ii. Metabolic clearance of endogenous and exogenous molecules —LDL: ↓ LDLR in hypothy; looks like FH —CPK: ↑ CPK in hypo b/c ↓ clear. —cortisol —hyaluronic acid: ↓ clear. w/ hypo: eyes & carpal —digoxin: ↓ clear. w/ hypo —anesthetics Expression of ß-adrenergic receptors i. Skeletal and cardiac striated muscle
Why does galactorrhea sometimes occur in 1° hypothyroidism?
↑ TRH can stimulate lactotrophs
P.E. findings for hypo ranked by incidence
**Slowed reflexes (80%) dry, coarse skin (80) fatigue/lethargy (80) puffy face/hands (75) cold intol (75) hoarseness (puffy vocal) (60) wt gain (5-10lbs) (60) tingling fingers (carpal) (55) heavy menses (20) bradycardia (15)
Myxedema:
—cause
—locations
—seen in moderate to severe hypothyroidism
—Reduced clearance of ground substance
—periorbital; carpal tunnel; vocal; tongue; generalized puffiness
—Non-pitting edema due to hygroscopic nature of hyaluronic acid
DDx for 1° Hypothyroidism
iodine deficiency —most common worldwide Hashimoto's —most common in W —Abs against thyroglob or TPO —assoc'd w/ polyglandular failure (vitiligo) congenital hypothyroidism —various mutations: agenesis, iodine handling, TSH receptor Subacute thyroiditis —viral, qqf pain, usu. temporary Ablation Drugs —lithium, amiodarone, PTU, methimazole
DDx for 2° Hypothyroidism
#1) Hypothalamic disease —tumors (craniopharyngioma) —infiltrative diseases —trauma, surgery, radiation #2) Pituitary disease —tumors —surgery, radiation —hemorrhage (Sheehan
Resistance to thyroid hormone
—incidence
—phenotype
—cause
—rare
—variable phenotype (cretin –> clinically normal with small goiter)
—-depends on the nature of the mutation
— -point mutation (missense, nonsense, premature stop codon)
— -deletion
—usually due to mutations in ß-1 subtype of nuclear T3 receptor
—dominant negative mutation affects function of wild type receptor
[IMAGE]
A patient was started on thyroxine therapy for primary hypothyroidism 7 days ago. He calls your office and suggests that his TSH be checked now to determine whether The prescribed dose is adequate. Is this a good idea? Why?
No, b/c the half life is 7 days, so he’s nowhere near steady state yet.
dosing thyroxine in pregnancy
need to ↑ dose b/c placenta degrades T4
—NOT due to ↑ in [TBG]
tx of hypothyroidism w/ coexistant hypoadrenalism (e.g. due to polyglandular failure syndrome, panhypoptuitarism)
may precipitate adrenal crisis from > turnover of cortisol, so replete cortisol first!
A patient has an ↑ TSH but nl T4
—What would you call this?
—Would you treat them?
subclinical hypothyroidism
—yes, treat them
tx in myxedema coma
profound hypothyroidism, coma, hypothermia
medical emergency, high dose T4 replacement; consider T3
How might initiation of thyroid hormone replacement therapy in a hypothyroid patient aggravate underlying myocardial ischemia?
Effects of thyroid hormone on the heart:
1. > heart rate
2. < peripheral resistance and BP
3. > myocardial efficiency
—Angina or MI may be precip in vulnerable pts.
—Gradual replacement, after correction of coronary artery stenoses if possible.
—Occasionally, full replacement may not be possible.
