MOFFITT ENDOCRINE REPORT PEARLS 5/17/17: Hypercalcemia of Malignancy and PTHrP!

Hey Everyone! Thanks to Vaibhav for presenting the case of an older woman with newly diagnosed bladder cancer who presented with weight loss and failure to thrive, found to have severe hypercalcemia with workup pending. We suspected she might have PTHrP-mediated hypercalcemia, a known association with urothelial carcinomas. Pearls on PTHrP below!

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Top Pearls:

  1. PTHrP is the most common cause of hypercalcemia in non-metastatic solid tumors
  2. PTHrP-related hypercalcemia is typically a finding in advanced disease with poor prognosis
  3. PTHrP acts primarily on bone and kidneys to cause hypercalcemia, not the GI tract

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For those who want more info:

Check out Myung’s pearls on hypercalcemia:

https://ucsfmed.wordpress.com/2017/02/15/hypercalcemia/

*Important general pearls on hypercalcemia of malignancy: 1) It occurs in 10-30% of patients with advanced tumors. 2) It is the most common cause of hypercalcemia in the inpatient setting. 3) Prognosis is poor (up to 50% 30-day mortality).

Now some more specific info on PTHrP!

What is PTHrP?

  • Normal gene product expressed in several tissues
  • Also called humoral hypercalcemia of malignancy (HHM)
  • The most common cause of hypercalcemia in patients with non-metastatic solid tumors
  • Most often in patients with advanced disease and poor prognosis (not usually an early finding)
  • Solid tumor associations: SCC, renal/bladder, breast, ovarian
  • Liquid tumor associations: NHL, CML (blast phase), T-cell leukemia/lymphoma

How is PTHrP related to PTH?

  • First 13 N-terminal amino acids are homologous to PTH (PTH = 84 AAs, PTHrP =139-173 AAs)
  • Binds to same PTH-1 receptor as PTH: bone resorption, renal Ca reabsorption/phos wasting
  • Structural divergence after first 13 amino acids: less likely to stimulate 1,25 vit D production, does not increase intestinal Ca absorption
  • Thus, PTHrP hyperCa is from bone/renal only, while PTH hyperCa is also from GI
  • Lab findings in PTHrP hyperCa: 1) elevated PTHrP, 2) low PTH, 3) normal/low 1,25-vit D

How is measurement of PTHrP useful (aside from diagnosis)?

  • Tumor marker: helps to assess treatment response
  • Prognostic marker: worse survival if PTHrP level > 12 pmol/L, which predicts less robust response of hyperCa to bisphosphonate therapy

HyperCa Malignancy

Evernote: https://www.evernote.com/shard/s272/sh/f935a1b0-b47f-45e7-8ef0-611a9c5c1e55/ba948d973b82ab3470b7c86533c6a7d7

 

Have a great day everyone!

SamMy

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