Moffitt AM report PEARLS 10/21: primary biliary cirrhosis!

Take-home PEARL: cholestyramine, a bile acid sequestrant used for cholestasis-associated pruritus, also affects absorption of thyroid hormone in enterohepatic circulation, so patients with hypothyroidism receiving cholestyramine should be monitored closely for s/sx of hypothyroidism!! In fact, a clinical trial showed that low doses of cholestyramine can be an adjunctive therapy in the management of hyperthyroidism from Graves (PMID 18946743)!


A bit on primary biliary cirrhosis

  • An autoimmune disease characterized by T-lymphocyte-mediated attack on small intralobular bile ducts
    • Remember the association between PBC and antimitochondrial Ab – the Ab titer does NOT correlate with disease severity or progression!
  • Association with hypothyroidism: about 20% of patients with PBC have or will develop hypothyroidism! Note that serum thyroid hormone-binding proteins are increased in PBC so total T4 levels can be normal in these patients.
  • Medical treatment: the only approved tx is ursodeoxycholic acid (which delays progression to ESLD/transplant). Interestingly, the extent of biochemical response to UDCA in the first year of tx is a good marker for long-term prognosis. Other controversial approaches include combination of UDCA with colchicine, methotrexate, and investigational approaches including molecular therapies are in phase 2 and 3 trials.
  • Liver transplant: PBC is a common indication for transplant and should be considered when serum bili >6 or in decompensated cirrhosis
  • Recurrence post-transplant? Survival rates of >90% at 1 year and 80-85% at 5 years! Recurrence rates for PBC have been reported to be up to 30% after 10 years.


Many other hodge-podge points throughout the case:

  • Ddx for pruritus without a rash (i.e. systemic causes of pruritus): cholestasis, uremia, hematologic malignancies (eg polycythemia vera), thyrotoxicosis
  • Hypercalcemia: great flow chart below. Think about PTH-dependent vs independent. For PTH-independent causes, think about vitamin D dependent vs independent. Remember though that lab testing for 1,25-OH vitamin D levels may not be sensitive!
    • Check out an old but classic Annals paper that Tyler alluded to that Harry shared at intern report last month: a serum chloride to phosphate ratio >30 suggests a parathyroid mediated process! PMID: 4405880
    • hypercalcemia
  • Elevated alk phos: ddx liver (elevated GGT), bone (nl GGT), and placental (nl GGT)!
  • Whenever you are thinking about hypothyroidism, think about concomitant adrenal insufficiency. When you are thinking about treating for myxedema coma or severe hypothyroidism, always give steroids in addition to synthroid!
  • Granulomatous hepatitis (on liver biopsy) still has a very broad ddx. Here is a nice slide I found online (credit: Dr. Marsano from University of Loisville)
    • hepatic granulomas

Bonus point on Werner syndrome (what is this?!)

  • A rare (1 in 200,000 in the US; more common in Japan 1 in 20,000 to 40,000) autosomal recessive syndrome characterized by premature aging. Interestingly, affected individuals grow normally until puberty and then have dramatic and rapid features of normal aging starting in their 20s. Major cause of death = CVD or cancer.


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