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
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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.
