Disclosures Management of Hyperparathyroidism Pacific Rim - - PowerPoint PPT Presentation

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Disclosures Management of Hyperparathyroidism Pacific Rim - - PowerPoint PPT Presentation

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Disclosures Management of Hyperparathyroidism Pacific Rim Otolaryngology Head and Neck Update February 18, 2020 No financial disclosures Eric D Wirtz, MD Workup Bilezikian, John P ., et al. Guidelines for the Management of

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Management of Hyperparathyroidism

Pacific Rim Otolaryngology Head and Neck Update February 18, 2020 Eric D Wirtz, MD

Disclosures

  • No financial disclosures

Workup

Bilezikian, John P ., et al. “Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from the Fourth International Workshop.” J Clin Endocrinol Metab 2014 Oct;99(10):3561-9. . doi: 10.1210/jc.2014-1413. Epub 2014 Aug 27

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Normocalcemic Primary Hyperparathyroidism (NPHPT)

  • Elevated PTH with normal calcium without

secondary cause

  • confirm over 3-6 months
  • Total and ionized calcium
  • Replete 25(OH)D levels
  • Check renal function - PTH rises with eGFR<60 mL/

min

Ong, Gregory S Y, et al. “The importance of measuring ionized calcium in characterizing calcium status and diagnosing primary hyperparathyroidism.” J Clin Endocrinol Metab 2012 Sep;97(9):3138-45. doi: 10.1210/jc.2012-1429. Epub 2012 Jun 28

NPHPT

  • Rule out drugs as secondary cause
  • Parathyroid incidentaloma - 1/3 have NPHPT
  • NPHPT - biphasic disease?
  • 40% signs of PHPT over 3 yrs
  • 19% developed hypercalcemia
  • May have decreased bone marrow density

Lowe, H., et al. “Normocalcemic Primary Hyperparathyroidism: Further Characterization of a New Clinical Phenotype.” J Clin Endocrinol Metab 2007 Aug;92(8):3001-5. Epub 2007 May 29

What we DO know about Vitamin D

  • As vitamin D levels decrease PTH levels increase
  • Sensitivity and specificity for PHPT is improved in

Vitamin D replete individuals

  • Low 25(OH)D levels associated with larger

adenoma size

Eastell, Richard, et al. “Diagnosis of Asymptomatic Primary Hyperparathyroidism: Proceedings of the Fourth International Workshop.” J Clin Endocrinol Metab 2014 Oct;99(10):3570-9. . doi: 10.1210/jc.2014-1413. Epub 2014 Aug 27

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What we DON’T know about Vitamin D

  • What is adequate repletion of 25(OH)D?
  • Vitamin D levels for patients that have created

reference levels for PTH

  • 1,25(OH)2D (active metabolite) is believed to be

physiologic regulator of PTH secretion but we know that 25(OH)D levels also affect PTH so is it 25(OH)D and not 1,25(OH)2D that influences PTH secretion

  • Why Measure and Replete

25(OH)D?

  • Low vitamin D causes increased PTH leading to increased bone

turnover

  • Replenishing Vitamin D levels pre-operatively helps prevent

postoperative hungry bone syndrome

  • May take 6-12 months for PTH to decrease after 25(OH)D

repletion

  • Low vitamin D can cause inappropriately low UCCR
  • Vitamin D repletion shown to reduce PTH but little effect on serum

calcium

  • Sestamibi scan is more likely to show adenoma if normal vitamin D

Lowe, H., et al. “Normocalcemic Primary Hyperparathyroidism: Further Characterization of a New Clinical Phenotype.” J Clin Endocrinol Metab 2007 Aug;92(8):3001-5. Epub 2007 May 29

2nd generation vs 3rd generation PTH assay

  • 2nd generation - measures intact PTH
  • 3rd generation - antibody assay for PTH
  • 3rd generation - Lower results compared to 2nd

generation

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Differentiating Familial Hypocalciuric Hypercalcemia (FHH) from Primary Hyperparathyroidism (PHPT)

  • FHH - 20% have elevated PTH levels
  • Urinary Calcium to Creatinine ratio (UCCR) - > 0.02
  • 90% likelihood is PHPT
  • Low UCCRs are observed in PHPT patients with

vitamin D deficiency, renal insufficiency, or African-American origins

Eastell, Richard, et al. “Diagnosis of Asymptomatic Primary Hyperparathyroidism: Proceedings of the Fourth International Workshop.” J Clin Endocrinol Metab 2014 Oct;99(10):3570-9. . doi: 10.1210/jc.2014-1413. Epub 2014 Aug 27

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SLIDE 5

Guideline for Surgery in Asymptomatic PHPT

Bilezikian, John P ., et al. “Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from the Fourth International Workshop.” J Clin Endocrinol Metab 2014 Oct;99(10):3561-9. . doi: 10.1210/jc.2014-1413. Epub 2014 Aug 27

“Even in the subjects who don’t meet any criteria for parathyroidectomy, surgery is always an option because it is the only definitive therapy for PHPT”

Bilezikian, John P ., et al. “Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from the Fourth International Workshop.” J Clin Endocrinol Metab 2014 Oct;99(10):3561-9. . doi: 10.1210/jc.2014-1413. Epub 2014 Aug 27

Questions still to answer

  • Vascular and cardiovascular dysfunction?
  • Neurocognitive dysfunction?

Bilezikian, John P ., et al. “Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from the Fourth International Workshop.” J Clin Endocrinol Metab 2014 Oct;99(10):3561-9. . doi: 10.1210/jc.2014-1413. Epub 2014 Aug 27

Intra-operative PTH

  • Miami criterion with addition of “into normal level”
  • drop of PTH by 50% and into the normal levels
  • Increases specificity from 66.7% to 88.9%
  • Helps prevent leaving multi-glandular disease
  • LSU study - sestamibi fails to identify 73% of

patients with multi-glandular disease.

Gill, Matthew T, et al. “Intraoperative parathyroid hormone assay: a necessary tool for multiglandular disease.” Otolaryngol Head Neck Surg. 2011 May;144(5):691-7. doi: 10.1177/0194599811398597.

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Radiologic Evaluation

  • Ultrasound - 72% sensitivity and 58% specificity
  • Technetium-99m scintigraphy (MIBI) - 83%

sensitivity and 47% specificity

  • Ultrasound and MIBI used in combination

increases sensitivity of localization to 90%

  • SPECT/CT - up to 93% sensitivity

Payne, Sakeena J., et al. “Radiographic evaluation of non-localizing parathyroid adenomas.” Am J Otolaryngol. 2015 Mar-Apr;36(2):217-22. doi: 10.1016/j.amjoto.2014.10.036. Epub 2014 Nov 6. Levy, Joshua M., et al. “Can ultrasound be used as the primary screening modality for the localization of parathyroid disease prior to surgery for primary hyperparathyroidism? A review of 440 cases.” ORL J Otorhinolaryngol Relat Spec. 2011;73(2):116-20. doi: 10.1159/000323912. Epub 2011 Mar 10. Johnson, Nathan A, Carty, Sally E, Tublin, Mitchell E. “Parathyroid Imaging.” Radiol Clin North Am. 2011 May;49(3):489-509, vi. doi: 10.1016/ j.rcl.2011.02.009.

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Non-localizing study

  • repeat sestimibi at high-volume institution
  • small study 13 patients presented with non-

localizing sestamibi - these were repeated at high-volume institution and all were localizing on repeat study - also found to have higher percentage of correct quadrant localization compared to only correct side

Singer Michael C, et al. “Improved localization of sestamibi imaging at high-volume centers.” Laryngoscope. 2013 Jan;123(1):298-301. doi: 10.1002/lary.23675. Epub 2012 Sep 24.

Non-localizing Study

  • 4D-CT
  • In non-localizing U/S and SPECT-CT
  • 84% sensitivity and 81% specificity to localization

to correct side

  • 76.5% sensitivity and 91.5% specificity to

localization to correct quadrant

  • Statistically significant lower radiation than SPECT-

CT - 13.8 vs 18.4 mSv

Hinson Andrew M, et al. “Preoperative 4D CT Localization of Nonlocalizing Parathyroid Adenomas by Ultrasound and SPECT-CT.” Otolaryngol Head Neck Surg. 2015 Nov;153(5):775-8. doi: 10.1177/0194599815599372. Epub 2015 Aug 6.

Natural History of PHPT

  • Stability of disease in asymptomatic patients?
  • 15 yrs of prospective follow-up
  • 1/3 of subjects demonstrate more overt

features of disease

Rubin, MIshaela R, et al. “The Natural History of Primary Hyperparathyroidism with or without Parathyroid Surgery after 15 Years.” J Clin Endocrinol Metab 2008 Sep;93(9):3462-70. . doi: 10.1210/jc.2007-1215. Epub 2008 Jun 10

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SLIDE 8

How often to screen when no surgery

Bilezikian, John P ., et al. “Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from the Fourth International Workshop.” J Clin Endocrinol Metab 2014 Oct;99(10):3561-9. . doi: 10.1210/jc.2014-1413. Epub 2014 Aug 27

When Surgery is Not Warranted

Bilezikian, John P ., et al. “Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from the Fourth International Workshop.” J Clin Endocrinol Metab 2014 Oct;99(10):3561-9. . doi: 10.1210/jc.2014-1413. Epub 2014 Aug 27

Medical Management

  • Calcium intake
  • calcium supplements associated with significant

decrease in PTH levels and an increase in femoral neck BMD

  • calcium should not be limited in pts with PHPT
  • Vitamin D repletion

Jorde, Rolf, et al. “The effects of calcium supplementation to patients with primary hyperparathyroidism and a low calcium intake.” Eur J Nutr 2002 Dec;41(6):258-63

Medical Management

  • Estrogen
  • Therapy in post-menopausal women with PHPT may

reduce bone resorption - analyze risk/benefit ratio

  • Bisphosphonate
  • PHPT - Improved BMD at lumbar spine and hip
  • Bone turnover markers decrease
  • Stable serum calcium

Marconi, Claudio, et al. “Medical management of primary hyperparathyroidism: proceedings of the Fourth International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism.”J Clin Endocrinol Metab. 2014 Oct;99(10):3607-18. doi: 10.1210/jc.2014-1417. Epub 2014 Aug 27.

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SLIDE 9

Medical Management

  • Cinacalcet - effective at lowering and often

normalizing serum calcium and increasing serum phosphate

  • often see significant reduction in urinary calcium

excretion

  • does not affect BMD

Marconi, Claudio, et al. “Medical management of primary hyperparathyroidism: proceedings of the Fourth International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism.”J Clin Endocrinol Metab. 2014 Oct;99(10):3607-18. doi: 10.1210/jc.2014-1417. Epub 2014 Aug 27.