Disclosures Management of Hyperparathyroidism Pacific Rim - PowerPoint PPT Presentation

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 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

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 What we DO know about NPHPT Vitamin D • Rule out drugs as secondary cause • Parathyroid incidentaloma - 1/3 have NPHPT • As vitamin D levels decrease PTH levels increase • NPHPT - biphasic disease? • Sensitivity and specificity for PHPT is improved in Vitamin D replete individuals • 40% signs of PHPT over 3 yrs • Low 25(OH)D levels associated with larger • 19% developed hypercalcemia adenoma size • May have decreased bone marrow density Lowe, H., et al. “Normocalcemic Primary Hyperparathyroidism: Further Characterization of a New Clinical Phenotype.” J Clin Eastell, Richard, et al. “Diagnosis of Asymptomatic Primary Hyperparathyroidism: Proceedings of the Fourth International Workshop.” J Clin Endocrinol Metab 2007 Aug;92(8):3001-5. Epub 2007 May 29 Endocrinol Metab 2014 Oct;99(10):3570-9. . doi: 10.1210/jc.2014-1413. Epub 2014 Aug 27

What we DON’T know about Why Measure and Replete Vitamin D 25(OH)D? • Low vitamin D causes increased PTH leading to increased bone • What is adequate repletion of 25(OH)D? turnover • Vitamin D levels for patients that have created • Replenishing Vitamin D levels pre-operatively helps prevent postoperative hungry bone syndrome reference levels for PTH • May take 6-12 months for PTH to decrease after 25(OH)D • 1,25(OH) 2 D (active metabolite) is believed to be repletion physiologic regulator of PTH secretion but we know • Low vitamin D can cause inappropriately low UCCR that 25(OH)D levels also affect PTH so is it 25(OH)D and not 1,25(OH) 2 D that influences PTH secretion • 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

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

Guideline for Surgery in Asymptomatic PHPT “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 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 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 Intra-operative PTH • Miami criterion with addition of “into normal level” • drop of PTH by 50% and into the normal levels • Vascular and cardiovascular dysfunction? • Increases specificity from 66.7% to 88.9% • Neurocognitive dysfunction? • Helps prevent leaving multi-glandular disease • LSU study - sestamibi fails to identify 73% of patients with multi-glandular disease. Bilezikian, John P ., et al. “Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from the Gill, Matthew T, et al. “Intraoperative parathyroid hormone assay: a necessary tool for multiglandular disease.” Otolaryngol Head Neck Surg. Fourth International Workshop.” J Clin Endocrinol Metab 2014 Oct;99(10):3561-9. . doi: 10.1210/jc.2014-1413. Epub 2014 Aug 27 2011 May;144(5):691-7. doi: 10.1177/0194599811398597.

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.

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 Natural History of PHPT • 4D-CT • In non-localizing U/S and SPECT-CT • Stability of disease in asymptomatic patients? • 84% sensitivity and 81% specificity to localization • 15 yrs of prospective follow-up to correct side • 76.5% sensitivity and 91.5% specificity to • 1/3 of subjects demonstrate more overt localization to correct quadrant features of disease • Statistically significant lower radiation than SPECT- CT - 13.8 vs 18.4 mSv Rubin, MIshaela R, et al. “The Natural History of Primary Hyperparathyroidism with or without Parathyroid Surgery after 15 Years.” J Clin Hinson Andrew M, et al. “Preoperative 4D CT Localization of Nonlocalizing Parathyroid Adenomas by Ultrasound and SPECT-CT.” Otolaryngol Endocrinol Metab 2008 Sep;93(9):3462-70. . doi: 10.1210/jc.2007-1215. Epub 2008 Jun 10 Head Neck Surg. 2015 Nov;153(5):775-8. doi: 10.1177/0194599815599372. Epub 2015 Aug 6.

How often to screen when When Surgery is Not no surgery Warranted Bilezikian, John P ., et al. “Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from the 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 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 Medical Management • Estrogen • Calcium intake • Therapy in post-menopausal women with PHPT may reduce bone resorption - analyze risk/benefit ratio • calcium supplements associated with significant decrease in PTH levels and an increase in • Bisphosphonate femoral neck BMD • PHPT - Improved BMD at lumbar spine and hip • calcium should not be limited in pts with PHPT • Bone turnover markers decrease • Vitamin D repletion • Stable serum calcium Marconi, Claudio, et al. “Medical management of primary hyperparathyroidism: proceedings of the Fourth International Workshop on the Jorde, Rolf, et al. “The e ff ects of calcium supplementation to patients with primary hyperparathyroidism and a low calcium intake.” Eur J Nutr Management of Asymptomatic Primary Hyperparathyroidism.”J Clin Endocrinol Metab. 2014 Oct;99(10):3607-18. doi: 10.1210/jc.2014-1417. 2002 Dec;41(6):258-63 Epub 2014 Aug 27.

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.