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primary hyperparathyroidism

Also see hyperparathyroidism. Autonomous overproduction of parathyroid hormone with no evidence of secondary parathyroid stimulation. Etiology: - parathyroid adenoma ~85% - parathyroid hyperplasia ~15% - parathyroid carcinoma ~1% - 95% sporadic - associated with MEN1 & MEN2/2A - neonatal severe primary hyperparathyroidism (rare) Epidemiology: - most common cause of hypercalcemia in outpatients [10] - higher incidence in women, age 50+ years Pathology: - patients with normal serum PTH (intact) more likely to have multiple adenomas [12] Clinical manifestations: - often asymptomatic - bone disease - osteoporosis - deformities, fractures - osteitis fibrosa cystica - von Recklinghausen's bone disease - thin cortex, marrow fibrosis, hemorrhage, cysts esp jaw - renal disease - calcium stones - hypertension - nephrocalcinosis - urinary frequency - gastrointestinal - nausea - peptic ulcer (associated with high serum gastrin) - constipation - gallstones - pancreatitis - ileus - CNS disturbance - CNS depression - lethargy - seizures - other - weakness - fatigue - calcification of aortic valve & mitral valve, stomach, lungs, myocardium, blood vessels Laboratory: - see hyperparathyroidism - serum calcium (high) - mean serum calcium prior to parathyroidectomy 10.9 mg/dL - serum ionized Ca+2 is not necessary if the serum albumin is normal [15[ - a normocalcemic variant is described [7] - other than serum calcium, other laboratory values similar [7] - serum phosphate low [10] - serum PTH high or inappropriately normal (upper 1/2 of reference interval) [10] - 6% of patients have preoperative serum PTH (intact) <= 50 pg/mL (mean 40 pg/ml)* [12] - 94% of patients have preoperative serum PTH (intact) > 60 pg/mL (mean 107 pg/ml)* [12] - normal serum PTH (intact) is < 60 pg/mL - basic metabolic panel for eGFR - 24 hour urine calcium - high in 30% of primary hyperparathyroidism - low in hypocalciuric hypercalcemia, vitamin D toxicity, thiazide use [10] - calcium/creatinine in 24 hour urine* - 25-OH vitamin D in serum* [10] (50% with vitamin D deficiency) * rule out familial hypocalciuric hypercalcemia before diagnosing primary hyperparathyroidism * rule out vitamin D deficiency (all patients) Radiology: - see hyperparathyroidism Complications: - fractures, including hip fractures - vertebral fractures less common with normocalcemic variant [7] Differential diagnosis: - familial hypocalciuric hypercalcemia (FHH) - FHH with calcium/creatinine in 24 hour urine of < 0.01 - secondary hyperparathyroidism - normal serum calcium, elevated serum PTH - celiac disease - autoimmune disease: diabetes type 1, autoimmune thyroiditis (hypothyroidism) - malabsorption: vitamin D deficiency, iron deficiency Management: - serum calcium, skeletal complications & renal function determine choice between medical & surgical management [10] - parathyroidectomy generally treatment of choice [4] - parathyroidectomy is associated with a lower risk of any fracture & hip fracture than non-operative management among older adults [8] - does not lower 8-year risk of symptomatic nephrolithiasis [11] - no important outcome differences noted between parathyroidectomy & observation [9] - does not prevent progression of chronic renal failure in adults > 60 years [13] - bisphosphonates increase bone mineral density, but increase risk of any fracture, including hip fracture relative to observation (RR=1.5) [4] - thiazides may reduce hypercalciuria & lower risk for calcium kidney stones [5] - check serum calcium periodically - cautious treatment of vitamin D deficiency (see hyperparathyroidism) - also see hyperparathyroidism

Specific

neonatal severe primary hyperparathyroidism

General

hyperparathyroidism

References

  1. Bilezikian JP, Khan AA, Potts JT et al Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the third international workshop. J Clin Endocrinol Metab. 2009 Feb;94(2):335-9. PMID: 19193908
  2. Marcocci C, Cetani F. Clinical practice. . N Engl J Med. 2011 Dec 22;365(25):2389-97. Review PMID: 2218798
  3. http://www.pathologyoutlines.com/parathyroid.html
  4. Yeh MW, Zhou H, Adams AL et al The Relationship of Parathyroidectomy and Bisphosphonates With Fracture Risk in Primary Hyperparathyroidism: An Observational Study. Ann Intern Med. Published online 5 April 2016 PMID: 27043778 http://annals.org/article.aspx?articleid=2511009
  5. Tsvetov G et al. Thiazide treatment in primary hyperparathyroidism - a new indication for an old medication? J Clin Endocrinol Metab 2017 Apr 1; 102:1270 PMID: 28388724 http://press.endocrine.org/doi/10.1210/jc.2016-2481
  6. Alore EA, Suliburk JW, Ramsey DJ et al Diagnosis and Management of Primary Hyperparathyroidism Across the Veterans Affairs Health Care System. JAMA Intern Med. Published online July 15, 2019. PMID: 31305864 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2737917 - Wentworth K, Shoback D. Applying the Guidelines for Primary Hyperparathyroidism. The Path Not Taken. JAMA Intern Med. Published online July 15, 2019. PMID: 31305872 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2737913
  7. Palermo A, Naciu AM, Tabacco G et al. Clinical, biochemical, and radiological profile of normocalcemic primary hyperparathyroidism. J Clin Endocrinol Metab 2020; April 9. 105:dgaa174 PMID: 32271382 https://academic.oup.com/jcem/article-abstract/105/7/dgaa174/5818374?redirectedFrom=fulltext
  8. Seib CD, Meng T, Suh I et al. Risk of fracture among older adults with primary hyperparathyroidism receiving parathyroidectomy vs nonoperative management. JAMA Intern Med 2021 Nov 29; [e-pub]. PMID: 34842909 PMCID: PMC8630642 (available on 2022-11-29) https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2786213
  9. Pretorius M et al. Mortality and morbidity in mild primary hyperparathyroidism: Results From a 10-year prospective randomized controlled trial of parathyroidectomy versus observation. Ann Intern Med 2022 Apr 19; PMID: 35436153 https://www.acpjournals.org/doi/10.7326/M21-4416 - Pretorius M et al. Effects of parathyroidectomy on quality of life: 10 years of data from a prospective randomized controlled trial on primary hyperparathyroidism (the SIPH-Study). J Bone Miner Res 2021 Jan; 36:3 PMID: 33125769 https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbmr.4199
  10. Medical Knowledge Self Assessment Program (MKSAP) 19 American College of Physicians, Philadelphia 2022 - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  11. Seib CD et al. Kidney stone events following parathyroidectomy vs nonoperative management for primary hyperparathyroidism. J Clin Endocrinol Metab 2022 Jul; 107:e2801. PMID: 35363858 PMCID: PMC9202696 (available on 2023-04-01) https://academic.oup.com/jcem/article/107/7/e2801/6562390 - Huang S-Y et al. Parathyroidectomy for nephrolithiasis in primary hyperparathyroidism: Beneficial but not a panacea. Surgery 2022 Jan; 171:29. PMID: 34364687 https://www.surgjournal.com/article/S0039-6060(21)00659-0/fulltext - Seib CD et al. Association of parathyroidectomy with 5-year clinically significant kidney stone events in patients with primary hyperparathyroidism. Endocr Pract 2021 Sep; 27:948. PMID: 34126246 https://www.endocrinepractice.org/article/S1530-891X(21)01082-X/fulltext
  12. Wang R et al. Hypercalcemia with a parathyroid hormone level of <= 50 pg/mL: Is this primary hyperparathyroidism? Surgery 2023 Jan; 173:154. PMID: 36202653 https://www.surgjournal.com/article/S0039-6060(22)00673-0/fulltext
  13. Seib CD et al. Estimated effect of parathyroidectomy on long-term kidney function in adults with primary hyperparathyroidism. Ann Intern Med 2023 Apr 11; [e-pub] PMID: 37037034 https://www.acpjournals.org/doi/10.7326/M22-2222
  14. NEJM Knowledge+ Endocrinology
  15. Insogna KL. Primary hyperparathyroidism. N Engl J Med. 2018;379:1050-1059. PMID: 30207907
  16. Bilezikian JP, Brandi ML, Eastell R 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. PMID: 25162665
  17. Zhu CY, Sturgeon C, Yeh MW. Diagnosis and Management of Primary Hyperparathyroidism. JAMA. 2020 Mar 24;323(12):1186-1187. PMID: 32031566 Review.