Hyperparathyroidism in Emergency Medicine
- Author: Philip N Salen, MD; Chief Editor: Erik D Schraga, MD more...
Background
The parathyroid glands regulate serum calcium and phosphorus levels through the secretion of parathyroid hormone (PTH), which raises serum calcium levels while lowering the serum phosphorus concentration. The regulation of PTH secretion occurs through a negative feedback loop in which calcium-sensing receptors on the membranes of parathyroid cells trigger decreased PTH production as serum calcium concentrations rise.
Primary hyperparathyroidism, which accounts for most hyperparathyroidism cases, results from excessive release of PTH and manifests as hypercalcemia.[1] Patients with hypercalcemia who have normal renal function and no malignancy must be suspected of having primary hyperparathyroidism and must be subsequently tested for elevated PTH levels.
Hyperparathyroidism is often incidentally discovered during routine laboratory testing when hypercalcemia is noted. In 80% of patients with hyperparathyroidism, the symptoms of hypercalcemia are mild or are not notable at the time of discovery. Management of these patients is not clear-cut because routine laboratory tests have not been shown to assist in predicting development of overt manifestations of the disease. Conversely, patients with overtly symptomatic hyperparathyroidism (eg, those with urinary tract stones, bone pain, cognitive abnormalities) and those with marked hypercalcemia (calcium levels >10.2 mg/dL) should be referred for consideration for parathyroidectomy.[2]
Pathophysiology
Primary hyperparathyroidism is one of the most common causes of hypercalcemia and should be considered in any individual with an elevated calcium level.[3] Primary hyperparathyroidism is usually the result of a single benign adenoma; a minority of patients have hyperplasia in all 4 parathyroid glands. Parathyroid carcinoma accounts for an insignificant minority (< 0.5% of patients with hyperparathyroidism).
Asymptomatic primary hyperparathyroidism manifests with serum calcium concentrations only slightly elevated to within 1 mg/dL above the upper limit of the reference range. Within the setting of asymptomatic primary hyperparathyroidism, the parathyroid hormone (PTH) level is typically 1.5-2 times the upper limit of the reference range. Hypophosphatemia and hyperchloremia are typically seen only in patients who are highly symptomatic patients and have advanced hyperparathyroidism.
When hyperparathyroidism manifests with hyperplasia in all 4 glands, familial-genetic syndromes should be considered within the differential diagnosis. Syndromes to be considered include type I and type II multiple endocrine neoplasia (MEN) or, less commonly, familial hypocalciuric hypercalcemia and hyperparathyroidism–jaw tumor syndrome. Also, a syndrome of familial isolated hyperparathyroidism has been observed. Radiation therapy to the head and neck predisposes patients to parathyroid tumors.
Secondary hyperparathyroidism occurs when the parathyroid glands become hyperplastic after long-term hyperstimulation and release of PTH. In secondary hyperparathyroidism, elevated PTH levels do not result in hypercalcemia. This has been classically attributed to an underlying state of hypocalcemia in those with chronic renal failure (CRF). However, hypocalcemia is not necessary for the development of secondary hyperparathyroidism in this setting. Eventually, nearly all patients on maintenance dialysis will develop secondary hyperparathyroidism.[4] Calcium balance is an issue of concern due to findings of accelerated vascular calcification in patients on dialysis.
Additional risk factors for the development of secondary hyperparathyroidism include phosphorus retention, intrinsic parathyroid gland abnormalities, diminished serum calcitriol levels, and resistance to PTH by skeletal tissue. Rickets and malabsorption syndromes are rarer causes.
With long-term hyperstimulation, the glands function autonomously and produce high levels of PTH even after correction of chronic hypocalcemia. Tertiary hyperparathyroidism refers to hypercalcemia caused by autonomous parathyroid function after long-term hyperstimulation.
Epidemiology
Frequency
United States
Primary hyperparathyroidism is a common endocrine disease that affects nearly 1 in 500 women and 1 in 2000 men per year, most often in the fifth, sixth, and seventh decades of life.[5]
Mortality/Morbidity
Most patients, who are predominantly elderly, present with mild elevations of serum calcium and are not overtly symptomatic. Usually, the rate of progression of hyperparathyroidism is slow, and monitoring these patients and medically managing the disease is usually safe.
All patients with symptomatic biochemically confirmed primary hyperparathyroidism should be referred for surgical treatment. In symptomatic patients, there is evidence that has demonstrated that after parathyroidectomy, cognitive function improves, bone density improves, fracture rate declines, and the incidence of ureteral colic declines. Furthermore, cardiovascular disease and premature death also appear to decrease after surgery in symptomatic patients.[6] Complication rates and symptom relief are similar in younger and older patients who undergo surgery.[3]
Of note, many "supposedly asymptomatic" patients do not realize that their hyperparathyroid symptoms may be a manifestation of their disease until after these symptoms diminish or wondrously disappear after parathyroidectomy.[7]
Sex
Most individuals with hyperparathyroidism are older women.[3]
Age
Although hyperparathyroidism can arise at any age, its occurrence rises markedly after age 40 years. Hyperparathyroidism is rare in children.
Allerheiligen DA, Schoeber J, Houston RE, et al. Hyperparathyroidism. Am Fam Physician. Apr 15 1998;57(8):1795-802, 1807-8. [Medline].
Jacobs DS, Kasten BL, DeMott WR, Wolfson WL. Laboratory Test Handbook. Williams & Wilkins;1990:284-7.
Boonen S, Vanderschueren D, Pelemans W, Bouillon R. Primary hyperthyroidism: diagnosis and management in the older individual. Eur J Endocrinol. Sept 2004;151(3):297-304. [Medline].
Brommage D, Gallgano C. The role of cinacalcet in treating secondary hyperparathyroidism. Nephrol Nurs J. Mar-Apr 2005;32(2):229-31. [Medline].
Ruda JM, Hollenbeak CS, Stack BC. A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995 to 2003. Otolaryngology- Head and Neck Surgery. March 2005;132:359-372.
Udelsman R, Pasieka JL, Sturgeon C, Young JE, Clark OH. Surgery for asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. J Clin Endocrinol Metab. Feb 2009;94(2):366-72. [Medline].
Perrier ND. Asymptomatic hyperparathyroidism: a medical misnomer?. Surgery. Feb 2005;137(2):127-31. [Medline].
Sorensen HA. Surgery for primary hyperparathyroidism. BMJ. Oct 12 2002;325(7368):785-6. [Medline].
Udelsman R, Pasieka JL, Sturgeon C, Young JE, Clark OH. Surgery for asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. J Clin Endocrinol Metab. Feb 2009;94(2):366-72. [Medline].
Khan A, Grey A, Shoback D. Medical management of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. J Clin Endocrinol Metab. Feb 2009;94(2):373-81. [Medline].
Beard CM, Heath H 3rd, O'Fallon WM, et al. Therapeutic radiation and hyperparathyroidism. A case-control study in Rochester, Minn. Arch Intern Med. Aug 1989;149(8):1887-90. [Medline].
Tezelman S, Rodriguez JM, Shen W, et al. Primary hyperparathyroidism in patients who have received radiation therapy and in patients who have not received radiation therapy. J Am Coll Surg. Jan 1995;180(1):81-7. [Medline].
National Institutes of Health. Consensus conference. Diagnosis and management of asymptomatic primary hyperparathyroidism. Conn Med. Jun 1991;55(6):349-54. [Medline].
Carter AB, Howanitz PJ. Intraoperative testing for parathyroid hormone: a comprehensive review of the use of the assay and the relevant literature. Arch Pathol Lab Med. Nov 2003;127(11):1424-42. [Medline].
Boggs JE, Irvin GL 3rd, Carneiro DM, Molinari AS. The evolution of parathyroidectomy failures. Surgery. Dec 1999;126(6):998-1002; discussion 1002-3. [Medline].
Guarda LA. Rapid intraoperative parathyroid hormone testing with surgical pathology correlations: the "chemical frozen section". Am J Clin Pathol. Nov 2004;122(5):704-12. [Medline].
Irvin GL, Carneiro DM. Management changes in primary hyperparathyroidism. JAMA. Aug 23-30 2000;284(8):934-6. [Medline].
Alexander HR Jr, Chen CC, Shawker T, et al. Role of preoperative localization and intraoperative localization maneuvers including intraoperative PTH assay determination for patients with persistent or recurrent hyperparathyroidism. J Bone Miner Res. Nov 2002;17 Suppl 2:N133-40. [Medline].
LeGrand SB, Leskuski D, Zama I. Narrative review: furosemide for hypercalcemia: an unproven yet common practice. Ann Intern Med. Aug 19 2008;149(4):259-63. [Medline].
VanderWalde LH, Liu IL, O'Connell TX, Haigh PI. The effect of parathyroidectomy on bone fracture risk in patients with primary hyperparathyroidism. Arch Surg. Sep 2006;141(9):885-9; discussion 889-91. [Medline].
Coker LH, Rorie K, Cantley L, et al. Primary hyperparathyroidism, cognition, and health-related quality of life. Ann Surg. Nov 2005;242(5):642-50. [Medline]. [Full Text].
al Zahrani A, Levine MA. Primary hyperparathyroidism. Lancet. Apr 26 1997;349(9060):1233-8. [Medline].
Bilezikian JP. Management of acute hypercalcemia. N Engl J Med. Apr 30 1992;326(18):1196-203. [Medline].
Bilezikian JP, Silverberg SJ. Clinical practice. Asymptomatic primary hyperparathyroidism. N Engl J Med. Apr 22 2004;350(17):1746-51. [Medline].
Potts JT. Diseases of the parathyroid gland and other hyper- and hypocalcemic disorders. In: Harrison's Principles of Internal Medicine. 14th ed. 1998:2227-32.
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