Hyperparathyroidism in Emergency Medicine

Updated: Oct 13, 2021
  • Author: Philip N Salen, MD; Chief Editor: Erik D Schraga, MD  more...
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Practice Essentials

Primary hyperparathyroidism is one of the most common causes of hypercalcemia and should be considered in the differential of any individual presenting with an elevated calcium level. [1]  Primary hyperparathyroidism (PHPT), hypersecretion of parathormone (parathyroid hormone: PTH) from the parathyroid glands, results in persistent hypercalcemia and usually hypercalciuria. [2]   Rarely, PHPT manifests as a component of genetically transmitted endocrine diseases, specifically multiple endocrine neoplasia syndromes. PHPT causes symptoms in multiple organ systems throughout the body via its impact on calcium homeostasis. The most recognizable symptoms are renal and skeletal complications: nephrolithiasis, nephrocalcinosis, osteitis fibrosa cystica, and osteoporosis. [2]  PHPT also manifests more subtly with nonspecific symptoms in other organ systems including: cardiovascular, gastrointestinal, rheumatic, and neuropsychiatric. Untreated PHPT can lead to irreversible changes including skeletal deformations and renal insufficiency.



The parathyroid glands regulate serum calcium and phosphorus levels by the secretion of parathyroid hormone (PTH), which elevates serum calcium levels while depressing serum phosphorus levels. 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 (PHPT), which accounts for most hyperparathyroidism cases, results from excessive release of PTH and manifests as hypercalcemia. [3] Patients with hypercalcemia who have normal renal function and no malignancy must be suspected of having primary hyperparathyroidism and must be evaluated for hyperparathyroidism.

Hyperparathyroidism is often incidentally discovered during routine laboratory testing when hypercalcemia is noted. For 80% of patients with hyperparathyroidism, the symptoms of hyperparathyroid induced hypercalcemia are mild or are not notable at the time of discovery. Management of asymptomatic PHPT patients is not clear-cut because routine laboratory tests have not been predictive of 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. [4]



PHPT is usually the result of a single benign adenoma; a minority of patients have hyperplasia of all 4 parathyroid glands. Parathyroid carcinoma manifests rarely, less than 0.5%, as a cause of hyperparathyroidism.

Asymptomatic PHPT 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 PHPT, 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.

Hypercalciuria, more than 300 mg daily of urinary calcium excretion, is observed in a significant subset of PHPT patients (30%). The most frequent complication of symptomatic PHPT is nephrolithiasis, which occurs in about 20% of patients. [5]  PHPT also can decrease glomerular filtration rates, inducing chronic kidney disease.

When hyperparathyroidism manifests with hyperplasia in all 4 glands, familial-genetic syndromes should be contemplated as causal 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. Radiation therapy to the head and neck increases the risk of development of 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. Secondary hyperparathyroidism has been attributed to a physiologic response to the hypocalcemia present in those with chronic renal failure (CRF). However, hypocalcemia is not an absolute requirement for the development of secondary hyperparathyroidism in CRF. Nearly all patients on maintenance dialysis will develop secondary hyperparathyroidism regardless of their calcium level. [6] Calcium homeostasis becomes an issue of concern because of accelerated vascular calcifications seen 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 of secondary hyperparathyroidism.

With long-term parathyroid 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.



Causes include the following:

  • A single parathyroid adenoma is the underlying pathology of PHPT in 85% of cases.

  • Diffuse hyperplasia of all parathyroid glands occurs in approximately 15% of cases. More than half of multiple parathyroid gland involvement cases are part of multiple endocrine neoplasia syndromes.

  • Parathyroid carcinoma is an uncommon cause of PHPT.

  • Secondary hyperparathyroidism is a frequent complication of chronic renal failure. [7]  Secondary hyperparathyroidism occurs when the parathyroid glands are chronically stimulated to release PTH. Hypocalcemia, hyperphosphatemia, and depressed 1.25 vitamin D (calcitriol) levels are the main triggers for the development of secondary hyperparathyroidism in chronic renal failure, malabsorption syndromes, and rickets. [8]

  • Tertiary hyperparathyroidism results when long-standing secondary hyperparathyroidism progresses to autonomous hypersecretion of PTH even after correction of chronic hypocalcemia.

  • External radiation to the head, neck, and chest regions is associated with an increased likelihood of developing parathyroid tumors. Parathyroid adenomas manifesting after radiation exposure are usually hyperfunctioning and often manifest as symptomatic PHPT. [9]  Patients with radiation-induced hyperparathyroidism are also more likely to have coexistent nodular goiter and thyroid gland carcinoma than patients with spontaneous hyperparathyroidism. [10]




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]

Sex- and age-related demographics

Most individuals with PHPT, asymptomatic and symptomatic, are postmenopausal women. [1]  The incidence of affected women reaches 21 per 1000 in women older than the age of 50. [2]  Asymptomatic PHPT is a disease that affects mainly women in their middle years. Women with PHPT outnumber men by approximately 3:1. [11]  

Although hyperparathyroidism can manifest at any age, PHPT occurrence rises markedly in persons older than 40 years. The disease manifests most commonly within the first decade after onset of menopause. 





The prognosis is excellent for patients after successful parathyroidectomy.

Asymptomatic patients who do not have indications for surgery have an excellent prognosis. Significant bone loss and other symptoms may be absent for years in subsequent follow-up visits.

The skeletal status of individuals with primary hyperparathyroidism plays an important role in management decisions. Surgical intervention is often recommended for patients with primary hyperparathyroidism and low bone mineral density, based on data from observational studies that demonstrate increases in bone mineral density after surgical treatment. [12]

The prognosis of secondary hyperparathyroidism is related to the underlying advanced chronic renal failure and resultant chronic hypocalcemia.


Most patients, who are predominantly middle aged or elderly, present with mild elevations of serum calcium and are not overtly symptomatic. Usually, the rate of progression of PHPT is slow, and monitoring these patients and medically managing the disease is usually safe.

All patients with biochemically confirmed, symptomatic PHPT should be referred for surgical parathyroidectomy. In symptomatic patients, there is evidence 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 parathyroidectomy in symptomatic patients. [13]  Complication rates and symptom relief are similar in younger and older patients who undergo surgery. [1]

Of note, many "supposedly asymptomatic" patients do not realize that their hyperparathyroid symptoms are a manifestation of their PHPT until after these symptoms diminish or disappear following parathyroidectomy. [14]


When the diagnosis of hyperparathyroidism is delayed, patients are more likely to present with complications or sequelae of their disease. Recurrent nephrolithiasis with consequent ureteral colic results from hyperparathyroidism induced hypercalciuria. Hyperparathyroid induced osteoporosis increases the risk of fractures compared to the general population. [2]  Brown tumor, a musculoskeletal complication of hyperparathyroidism, is a focal bone lesion caused by increased osteoclastic activity and fibroblast proliferation encountered in primary and, more rarely, in secondary hyperparathyroidism. [7]  Rheumatologic diseases such as gout and pseudogout have been associated with hyperparathyroidism induced alterations in calcium homeostasis. [15] The risk of pancreatitis is approximately 10 times higher in PHPT patients than in the general population. [2] Another gastrointestinal manifestation of PHPT is its association with chronic autoimmune atrophic gastritis. PHPT is associated with a higher incidence of arterial hypertension and an increased risk of overall cardiovascular mortality. [2]

Maternal hyperparathyroidism can lead to profound hypocalcemia and tetany, coma, and death in newborns in a syndrome known as neonatal severe hyperparathyroidism.

Nocturia and polyuria may result from the effects of elevated calcium levels on the renal tubule. Approximately 20% of patients with hyperparathyroidism have nephrolithiasis.

CNS disturbances, coma, and death may result from markedly elevated serum calcium levels when left untreated.

Skeletal sequelae, osteoporosis or pathologic fractures, may occur.

Cardiovascular complications, such as heart failure, valvular or vascular calcifications, may occur.

Surgical complications

Surgical complications include the following:

  • Hypoparathyroidism

  • Recurrent laryngeal nerve damage

  • Hemorrhage

  • Infection

  • Unsuccessful surgery

    • Persistent or recurrent disease occurs in a low percentage of individuals who undergo surgery for primary hyperparathyroidism. [16]

    • Persistent primary hyperparathyroidism is defined as the presence of elevated serum calcium levels and PTH levels documented within 6 months of the initial operation. The most common cause of persistent primary hyperparathyroidism is the presence of a missed parathyroid adenoma, which is usually in an ectopic location in this setting. Less commonly, persistent disease may be secondary to inadequate resection of unappreciated multigland disease. [16]


Patient Education

Educate patients about prescribed medications. Educate patients regarding the importance of periodic laboratory and radiologic testing.

Information for patients

Hyperparathyroidism is a disease of the 4 parathyroid glands that are next to the thyroid gland in the neck. The parathyroid glands release a hormone called parathormone (parathyroid hormone) that is important for maintaining the normal calcium levels in the body. Primary hyperparathyroidism, the most common kind of hyperparathyroidism, occurs when too much parathormone is released from one or more of the parathyroid glands and is most commonly caused when one of the four parathyroid glands grows abnormally large. Secondary hyperparathyroidism occurs when the parathyroid glands respond to a stimulus within the body to release too much parathormone. Hyperparathyroidism causes high levels of calcium in the blood. The most common symptoms of hyperparathyroid induced hypercalcemia are kidney stones, which can cause flank pain, and weak bones, which can break more easily. Other symptoms of hyperparathyroidism are feeling weak, tired, and depressed.

Hyperparathyroidism is diagnosed by checking the blood for high levels of calcium and parathormone.

Many patients with primary hyperparathyroidism have mild forms of the disease, do not have symptoms, and do not need treatment. Some patients with symptoms of weak bones or kidney stones need to have their parathyroid glands surgically removed.