CE/CME

Primary Hyperparathyroidism: A Case-based Review

Clinician Reviews. 2017 May;27(5):34-44

References

1. Turner J. Hypercalcaemia and primary hyperparathyroidism. Medicine. 2009;37(9):461-464.
2. Crowley R, Gittoes N. How to approach hypercalcaemia. Clin Med. 2013;13(3):287-290.
3. Kapustin JF, Schofield DL. Hyperparathyroidism: an incidental finding. Nurse Pract. 2012;37(11):9-14.
4. Cordellat IM. Hyperparathyroidism: primary or secondary disease? Rheumatol Clin. 2012;8(5):287-291.
5. MacKenzie-Feder J, Sirrs S, Anderson D, Sharif J, Khan A. Primary hyperparathyroidism: an overview. Int J Endocrinol. 2011;2011:251410.
6. Brashers VL, Jones RE, Huether SE. Alterations of hormonal regulation. In: McCance KL, Huether SE, eds. Pathophysiology: The Biologic Basis for Disease in Adults and Children. 7th ed. St. Louis, MO: Mosby; 2015:731-733.
7. Osborne JL, Klocko DJ. Woman, 66, with persistent abdominal and back pain. Clinician Reviews. 2014;24(11):34-37, 40.
8. Michels TC, Kelly KM. Parathyroid disorders. Am Fam Physician. 2013;88(4):249-257.
9. Rolighed L, Rejnmark L, Christiansen P. Bone involvement in primary hyperparathyroidism and changes after parathyroidectomy. US Endocrinol. 2013;9(2):181-184.
10. Karahan Ö, Okus A, Sevinç B, et al. Minimally invasive parathyroidectomy under local anesthesia. J Postgrad Med. 2013;59(1):21-24.
11. Fuleihan GE, Silverberg SJ. Primary hyperparathyroidism: diagnosis, differential diagnosis, and evaluation. Up-to-Date. www.uptodate.com/contents/primary-hyperparathyroidism-diagnosis-differential-diagnosis-and-evaluation. Accessed April 20, 2017.
12. Panchani R, Varma T, Goyal A, et al. A challenging case of an ectopic parathyroid adenoma. Indian J Endocrinol Metab. 2012;16:S408-S410.
13. Otasowie J, Hambleton BA. Aggression and homicidal thoughts in a patient with primary hyperparathyroidism: a case report. Br J Medical Pract. 2013;6(4):a630.
14. Bilezikian JP. Primary hyperparathyroidism: new insights, concepts and guidelines. Presented at: American Association of Clinical Endocrinologists 24th Annual Scientific and Clinical Congress; May 13-17, 2015; Nashville, TN. am2015.aace.com/presentations/Friday/F31/PrimaryHyperparathyroidismNew InsightsConceptsandGuidelines.pdf. Accessed April 20, 2017.
15. Crowther-Radulewicz CL, McCance KL. Alterations of musculoskeletal function. In: McCance KL, Huether SE, eds. Pathophysiology: The Biologic Basis for Disease in Adults and Children. 7th ed. St. Louis, MO: Mosby; 2015:1551-1555.
16. Amaral LM, Queiroz DC, Marques TF, et al. Clinical study: normocalcemic versus hypercalcemic primary hyperparathyroidism: more stone than bone? J Osteoporos. 2012;2012:128352.
17. Linda DD, Ng B, Rebello R, et al. The utility of multidetector computed tomography for detection of parathyroid disease in the setting of primary hyperparathyroidism. Can Assoc Radiol J. 2012;63(2):100-108.
18. Bann DV, Zacharia T, Goldenberg D, Goyal, N. Parathyroid localization using 4-D-computed tomography. Ear Nose Throat J. 2015;94(4-5):E55-E57.
19. 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;99(10):3561-3569.
20. Jeremiah MP, Unwin BK, Greenawald MH, Casiano VE. Diagnosis and management of osteoporosis. Am Fam Physician. 2015;92(4):261-268.
21. Wood K, Dhital S, Chen H, Sippel RS. What is the utility of distal forearm DXA in primary hyperparathyroidism? Oncologist. 2012;17(3):322-325.
22. Jayasena CN, Modi M, Palazzo F, et al. Associations of serum 25-hydroxyvitamin D with circulating PTH, phosphate and calcium in patients with primary hyperparathyroidism. Clin Endocrinol (Oxf). 2013;78(6):838-843.
23. Grey A. Nonsurgical management of mild primary hyperparathyroidism—a reasonable option. Clin Endocrinol. 2012;77(5):639-644.
24. Saponaro F, Faggiano A, Grimaldi F, et al. Cinacalcet in the management of primary hyperparathyroidism: post marketing experience of an Italian multicenter group. Clin Endocrinol (Oxf). 2013;79(1):20-26.
25. Rothe HM, Liangos O, Biggar P, et al. Cinacalcet treatment of primary hyperparathyroidism. Int J Endocrinol. 2011;2011:415719.
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Additional studies used during the management of the patient with PHPT are BMD testing and renal imaging. Secondary causes of bone loss are responsible for up to 30% of osteoporosis cases in postmenopausal women; one of these causes is PHPT.²⁰ Elevated PTH causes increased bone turnover and results in decreased bone mass with subsequent increased fracture risk.⁹ Bone density should be measured by dual-energy x-ray absorptiometry (DEXA), and the skeletal survey should include the distal one-third of the radius, hip, and lumbar spine. The distal radius is rich in cortical bone and BMD is often lowest at this site in patients with PHPT, making it the most sensitive DEXA marker for early detection of bone loss.^19,21 The hip contains an equal mix of cortical and trabecular bone and is the second most sensitive site for detecting bone loss in PHPT. The spine contains a high proportion of trabecular bone and is the least sensitive site.^19,21 Renal imaging studies, including x-ray, ultrasound, and, less frequently, CT of the abdomen and pelvis, are used to assess for nephrolithiasis and nephrocalcinosis.¹⁹

TREATMENT/MANAGEMENT

Conservative medical management

PHPT is a complex disease process, and careful evaluation is required when determining whether medical versus surgical management is appropriate. Clinical presentation ranges from no symptoms to multisystem disease. Conservative medical management, which includes regular monitoring, is an acceptable strategy in an asymptomatic patient with a low fracture risk and no nephrolithiasis.¹ Conservative care includes maintaining normal dietary calcium intake and adequate hydration, regular exercise, vitamin D supplementation, annual laboratory studies, BMD testing, and the avoidance of thiazide diuretics and lithium.¹ Guidelines, from the Fourth International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism, for monitoring asymptomatic PHPT patients recommend

Annual measurement of serum calcium
BMD measurement by DEXA every 1 to 2 years
Annual assessment of eGFR and serum creatinine
Renal imaging or a 24-h urine stone profile if nephrolithiasis is suspected.¹⁹

Long-term medical management of PHPT is difficult because no agents are available to suppress hypercalcemia or completely block PTH release.¹²

Maintaining serum 25(OH)D at a level > 20 ng/mL significantly reduces PTH secretion, in comparison to levels < 20 ng/mL, and does not aggravate hypercalcemia.²² The Endocrine Society recommends a minimum serum 25(OH)D level of 20 ng/mL and notes that targeting a higher threshold value of 30 ng/mL is reasonable.¹⁹ The daily requirement for vitamin D3, 800 IU to 1,000 IU, is a good starting point for supplementation.⁴ Measurement of 1,25(OH)₂D levels lacks value and is not recommended for patients with PHPT. Calcium intake should follow established guidelines and is not limited in PHPT.¹⁹

Surgical management

Surgical management is indicated for symptomatic patients.²³ Indications include nephrolithiasis, nephrocalcinosis, osteitis fibrosa cystica, or osteoporosis. Surgery is considered appropriate for individuals who do not meet these criteria if there are no medical contraindications.¹⁴ The Fourth International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism revised the indications for surgery in 2014 to include asymptomatic patients, since surgery is the only definitive treatment for PHPT. Current guidelines for when to recommend surgery in the asymptomatic patient with PHPT are listed in Table 4.¹⁹

Preoperative localization and referral to an experienced surgeon is of utmost importance for a good outcome. An expert surgeon will usually perform a minimally invasive parathyroidectomy (MIP) and obtain intraoperative PTH levels; in some cases, a full neck exploration is necessary. PTH has a half-life of less than five minutes and is an accurate tool for determining whether the culprit gland has been successfully removed.⁵

Modern imaging studies, less invasive surgical techniques, and intraoperative measurements of PTH have decreased the need to conduct full neck exploration. MIP offers a smaller incision, less tissue dissection, and lower morbidity, and can be offered without the risks associated with general anesthesia.¹⁰ The goal of surgery is to restore normocalcemia and, in turn, prevent bone mineral loss and systemic effects of hypercalcemia over the long term.¹⁰ Surgical management for an ectopic parathyroid adenoma is controversial because these are often found in the mediastinum, requiring invasive surgery.¹²

Primary Hyperparathyroidism: A Case-based Review

References

TREATMENT/MANAGEMENT

Conservative medical management

Surgical management

Pages

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