week 9- thyroid and hepatis Flashcards
• What is rT3 (reverse T3)?
o Usu ↑ in hypothyroidism
o help dx “sick thyroid” pts (who are euthyroid) from true hypothyroid cases
o in a body under stress (illness, fasting, high cortisol) T4 is deiodinized to rT3 instead of T3
o (“step down”, instead of “step up”)= (-) charge in diff spot
o Metabolic enzyme function ↓ → Stresses inhibit 5’-deiodinase → ↓ T4 to T3, ↑ rT3
o Sxs of Wilson’s (temp) syndrome: hypothyroid, ↑rT3, corrected by giving T3 (Not accepted by mainstream)
• What is significance of BBT?
o reflects metabolic rate controlled by thyroid hormones
o N = 97.6-98.2 F
o Menstruating females take BBT on d2-4 of menses
o ↓ quite common, may = hypothyroidism
o ↑ BBT less common, may = hyperthyroidism
o Look for other sxs thyroid dz
• What are thyroid antibodies? Risk factors?
o =auto-Abs
o Stimulating: a-Thyroid receptor =Thyroid stimulating Igs (TSI)
o Blocking: a-thyroperoxidase (a-TPO); Thyroglobulin (a-TGLB)
• What is Graves dz?
o MC cause hyperthyroid (80-85%)
o dt stimulation of TSHRs by TSI, over stimulate thyroid activity
o Abs arise 2nd to defect in T-suppressor cells → clone of T-helper to interact with thyroid Ags → stimulate B cells to make TSI
o a-TPO and a-TGLB often seen
• what are ssx of graves?
o → sympatho-adrenergic activity and metabolism o ↓ TSH, ↑ T3/T4 o Exophthalmos o Warm pulsating goiter o Tachycardia o Fine tremor (hand) o Pretibial myxedema
• how is Graves diagnosed?
o ↑T3, T4; ↓TSH
o gland non-palpable or smooth symmetric goiter
• Describe fetal thyroid development, and how it’s affected by Graves?
o fetus dependent on mom’s T4 until 10-12 wks
o 20 wks, responsive to its own TSH, low thyroid function
o IgG Abs in Graves cross placenta → fetal hyperthyroid after 20 wks gestation
o Antithyroid drugs (methimazole, propylthiouracil) also cross placenta → tx both maternal and fetal hyperthyroid
• What is RAIU (radioactive iodine uptake)?
o Scintillation counter measures radioactivity 6 & 24 hrs after I(123) given
o Uptake varies greatly by iodine status: Indigenous diet (normal uptake 10% vs 90%); Amiodarone, Contrast study, Topical betadine
• What causes abnormal RAIU results?
o Sx ↑: Graves, Toxic goiter
o Sx ↓: Thyroiditis (Subacute, Active Hashimoto’s), Hormone ingestion (Thyrotoxicosis factitia, Hamburger Thyrotoxicosis); Excess I- intake in Graves’ (Jod-Basedow effect); Ectopic thyroid carcinoma (Struma ovarii)
• What is hashimoto’s thyroiditis?
o MC cause acquired primary hypo o mb caused by any environmental trigger o F>M, 8:1; Onset usu 30-50 o FHx common o Early stages may present as hyper o Early labs may show normal T4 and TSH, ↑ a-TPO, and less commonly a-Tg
• How is hashimoto’s diagnosed?
o RAIU mb ↑ or ↓
o Later: hypo, ↓T4, T3RU, ↑TSH, ↓ RAIU dt gland destruction
o Ab titers much higher in thyroiditis than Grave’s
o Gland mb TTP dt inflammation
• What is Euthyroid sick syndrome?
o T4/T3 ↓ in acute & chronic illness (any severe), fasting, starvation, sepsis, surgery, MI, BM transplant
o Abn tests w acute or chronic non-thyroidal systemic illness
o Secondary to:
o ↓ peripheral conversion T4 T3
o ↓ clearance rT3
o ↓ binding T3/T4 to TBG
• What are common causes of ESS w fidnings?
o NTI (MC): ↓T3; N TSH, T4; mb dt ↓ T3 →4
o 20% ICU pts: ↓T3/T4; N TSH; mb dt ↓ TBG, albumin
o severe illness: ↓TSH, T3/T4; HTH and Pit involved
o cirrhosis, hepatitis, acute psych: ↑ T4; TSH & T3 N or ↑
• what are screening recommendations for thyroid dz in adults?
o USPSTF: say insufficient evidence for or against routine screening
o AAFP: high-risk populations: F w FHx thyroid dz, F >35, prego, abd PE, DM, AI Hx
o ATA: start at a 35 (+ q5 yrs)
• What are some good and not-so-good indications to screen for hypothyroid?
o High suspicion: goiter, delayed reflexes
o Intermediate: Fatigue, wt gain/difficulty losing wt, Cold intolerance, Dry, rough, pale skin, Constipation, FHx, Hoarseness
o Low, non-specific sxs: Coarse, dry hair, Hair loss, Muscle cramps/aches, Depression, Irritability, Memory loss, Abn menstrual cycles, ↓ libido
• What are some good and not-so-good indications to screen for hyperthyroid?
o High: goiter, thyroid bruit, lid lag, proptosis
o Med: Fatigue, Wt loss despite ↑appetite, Heat intolerance/sweating, Fine tremor, FHx, ↑BMs, ↑HR/palpitations, Staring gaze
o Low: Nervousness, Insomnia, Breathlessness, Light or absent menstrual periods, Wt loss, Muscle weakness, Warm moist skin, Hair loss
• What is recommended prenatal thyroid screening?
o Universal screening before preg not recommended
o Prenatal serum TSH testing is recommended if high risk or known thyroid dysfunction
o Non-Consensus on TSH screening for all prego vs high-risk at time of first visit or by 9th wk
• What is neonatal thyroid screening for congenital hypothyroid?
o All infants screened at 2-4 d
o congenital hypo usu unaffected at birth, dt placental transfer of T4; but must get tx by 2-3wks
o otherwise → mental retardation
o if mom is hypo, significant impairment of neurointellectual development despite early tx
o 3 screening strategies: (1) primary TSH, backup T4 in infants w ↑ TSH, (2) primary T4, backup TSH w ↓T4, (3) both T4 and TSH (IDEAL)
- Total T4: ↑
- T3RU: ↑
- FTI: ↑
- TSH: ↓
- FT4: ↑
- Total T3: ↑
o Primary hyper
- Total T4: ↓
- T3RU: ↓
- FTI: ↓
- TSH: ↑
- FT4: ↓
- Total T3: ↓/N
o Primary hypo
- Total T4: ↑
- T3RU: ↓
- FTI: N
- TSH: N
- FT4: N
- Total T3: N
pregnancy
• What is viral hepatitis?
o 5 viruses, A-E
o affinity for hepatocyte, induce liver injury, usu immune-mediated mechanism
o Diff physical,chemical composition, mechanisms to replicate within infected cells
• Hx of viral hepatitis?
o Contagious jaundice, 8th century, Pope Zacharias ordered isolation of affected
o Virchow, 1865, epidemic jaundice dt mucous plug in the papilla of Vater
o early 20th century linking vaccination, blood drawing, blood transfusion and parenteral tx of syphilitic pts w contaminated needles, development of “serum hepatitis”
o WW II, >200,000 cases of jaundice in american, >5 million cases in germans
o MacCallum 1940’s, suggested both enteric (“infectious hepatitis”, “hepatitis A”) and parenteral/sexual (“serum hepatitis”, “hepatitis B”) transmission could occur
o mid-20th century, “A & B” had diff clinical courses, suggesting different etiologies
• What was the Willowbrook state school’s role in elucidating hepatitis viruses?
o 1950s and 60s: 1000s of intellectually disabled children, mostly w trisomy 21 →jaundice freq, ↑ LFTs; Newly admitted children exposed to infectious material, w parental consent → criticism
o found diff filterable infx agents caused 2 clinical patterns of hepatitis
o One inoculum of serum (MS1, initials of infected child) → illness, short inc, like epidemic hepatitis (A)
o Another, MS2 (same child who later developed the 2nd form of jaundice) →illness, longer inc, like B
o Boggs used MS1 in Marmoset monkeys (1967), Humans incarcerated at Joliet State Penitentiary (US Army 1970)
• How was hepatitis B discovered?
o 1963, Dr. Baruch Blumberg (nobel prize 1976), identified a protein (“Australia Ag” reacted to Abs from pts w hemophilia and leukemia
o Assoc w infx hepatitis 1966
o virus specifically seen by electron microscopy in 1970
• how was hepatitis A discovered?
o 1973, NIH, in fecal samples from ppl inoculated w MS1 serum from Willowbrook
o Electron microscopy: 27 nm spherical viral particles, aggregates after incubation of fecal samples w convalescent serum
o successfully adapted to grow in culture by end of 1970’s
• how was hepatitis D discovered?
o 1977, Rizetto in Turin, identitied new Ag in both liver and serum in carriers of HBsAg
o HDV= defective virus, genome is negative circular ssRNA, encodes single nucleocapsid protein (delta Ag)
o To replicate, Requires envelope of HBV w HBsAg
• How was hepatitis C discovered?
o End of 1970’s, found most cases of post-transfusion hepatitis were not dt A, B, D (20% dt cardiac surgery w blood transfusion)
o known as non-A, non-B hepatitis (NANBH)
o identified by Houghton, 1989, Chiron Corporation
o Retrospective testing showed 90% of non-A, non-B hepatitis was HVC
• What is hepatitis E?
o epidemic waterborne, similar to A
o first recognized in India in 1980
o Causative agent identified in Uzbekistan in 1983
o Genome cloned in 1990 and fully sequenced shortly after
• What are “infectious” and “serum” viral hepatitis? NANB?
o Infectious: became known as HAV
o Serum: B, D
o NANB: E (enterically transmitted), C (parenterally transmitted), F, G?
• What are sources of virus for the 5 hep viruses? Route of transmission?
o A, E: feces
o B, C, D: blood/blood-derived body fluids
o A, E: fecal, oral
o B, C, D: percutaneous, permucosal
• Which of the 5 hep viruses can be chronic infx? How are they prevented?
o Chronic: B, C, D
o A, B: pre/post-exposure immunization
o C: blood donor-screening; risk behavior modification
o D: pre/post-exposure immunization; risk behavior modification
o E: ensure safe drinking water
