Merck Manual

Please confirm that you are a health care professional

honeypot link



James L. Lewis III

, MD, Brookwood Baptist Health and Saint Vincent’s Ascension Health, Birmingham

Reviewed/Revised Jan 2023

Hyperparathyroidism occurs when one or more of the parathyroid glands become overactive, causing elevated serum levels of parathyroid hormone and leading to hypercalcemia. Patients may be asymptomatic or have symptoms of varying severity, including chronic fatigue, body aches, difficulty sleeping, bone pain, memory loss, poor concentration, depression, and headaches. Diagnosis is with serum levels of calcium and parathyroid hormone. Surgery is done to remove the overactive gland(s).

Etiology of Hyperparathyroidism

Pathophysiology of Hyperparathyroidism

Parathyroid hormone (PTH) increases serum calcium by

  • Enhancing distal tubular calcium reabsorption

  • Rapidly mobilizing calcium and phosphate from bone (bone resorption)

  • Increasing intestinal absorption of calcium by stimulating conversion of vitamin D to its most active form, calcitriol

Hyperparathyroidism is characterized as

  • Primary: Excessive secretion of PTH due to a disorder of the parathyroid glands

  • Secondary: Hypocalcemia due to non-parathyroid disorders leads to chronic PTH hypersecretion

  • Tertiary: Autonomous secretion of PTH unrelated to serum calcium concentration in patients with long-standing secondary hyperparathyroidism

Primary hyperparathyroidism

Primary hyperparathyroidism is a generalized disorder resulting from excessive secretion of parathyroid hormone by one or more parathyroid glands. It probably is the most common cause of hypercalcemia Hypercalcemia Hypercalcemia is a total serum calcium concentration > 10.4 mg/dL (> 2.60 mmol/L) or ionized serum calcium > 5.2 mg/dL (> 1.30 mmol/L). Principal causes include hyperparathyroidism... read more , particularly among patients who are not hospitalized. Incidence increases with age and is higher in postmenopausal women. It also occurs in high frequency ≥ 3 decades after neck irradiation.

Histologic examination of parathyroid tissue removed from patients thought to have primary hyperparathyroidism preoperatively shows a parathyroid adenoma in about 85% of patients, hyperplasia of ≥ 2 glands in about 15% of cases and parathyroid cancer Parathyroid cancer Most parathyroid tumors are benign. Parathyroid tumors secrete parathyroid hormone (PTH). Elevated parathyroid hormone levels ( hyperparathyroidism) causes hypercalcemia. Parathyroid adenomas... read more in < 1%.

Secondary hyperparathyroidism

Other less common causes of secondary hyperparathyroidism include

Once the hyperparathyroidism is established, hypercalcemia or normocalcemia may occur. The sensitivity of the parathyroid glands to calcium may be diminished because of pronounced glandular hyperplasia and elevation of the calcium set point (ie, the amount of calcium necessary to reduce secretion of PTH).

Tertiary hyperparathyroidism

Tertiary hyperparathyroidism results when PTH secretion becomes autonomous of serum calcium concentration. Tertiary hyperparathyroidism generally occurs in patients with long-standing secondary hyperparathyroidism, as in patients with end-stage renal disease Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more Chronic Kidney Disease of several years’ duration.

Symptoms and Signs of Hyperparathyroidism

Hyperparathyroidism is often asymptomatic. In asymptomatic patients, the disorder is typically identified by an incidental elevated calcium level.

Symptoms, when they occur, are due to hypercalcemia Hypercalcemia Hypercalcemia is a total serum calcium concentration > 10.4 mg/dL (> 2.60 mmol/L) or ionized serum calcium > 5.2 mg/dL (> 1.30 mmol/L). Principal causes include hyperparathyroidism... read more and include chronic fatigue, constipation, anorexia, nausea and vomiting, poor concentration, confusion, and depression.


Hypercalcemia frequently causes hypercalciuria with resultant nephrolithiasis Urinary Calculi Urinary calculi are solid particles in the urinary system. They may cause pain, nausea, vomiting, hematuria, and, possibly, chills and fever due to secondary infection. Diagnosis is based on... read more , and patients with hypercalcemia can present with pain due to passage of a kidney stone. Chronic hypercalcemia may also cause proximal weakness and muscle atrophy.

Excess parathyroid hormone stimulates osteoclastic activity, which over time can cause osteitis fibrosa cystica. In osteitis fibrosa cystica, increased osteoclastic activity causes rarefaction of bone with fibrous degeneration and cyst and fibrous nodule formation.

Diagnosis of Hyperparathyroidism

  • Serum calcium, phosphate, and PTH measurement

The diagnosis of primary hyperparathyroidism should be made based on blood and urine tests and clinical findings.

A diagnosis of hyperparathyroidism is usually first suspected when elevated serum calcium is found on routine blood tests. If calcium remains high on repeat testing, intact PTH should be checked and interpreted with the calcium level. Patients with primary hyperparathyroidism have a high PTH concentration in the absence of hypocalcemia. A minority of patients have a high-normal PTH concentration, which should be interpreted as inappropriate when the calcium concentration is elevated (and suppression of PTH would normally be expected— 1 Diagnosis reference Hyperparathyroidism occurs when one or more of the parathyroid glands become overactive, causing elevated serum levels of parathyroid hormone and leading to hypercalcemia. Patients may be asymptomatic... read more ).

In hyperparathyroidism, the serum calcium is rarely > 12 mg/dL (> 3 mmol/L), but the ionized serum calcium is almost always elevated.

Low serum phosphate concentration suggests hyperparathyroidism, especially when coupled with elevated renal excretion of phosphate. When hyperparathyroidism results in increased bone turnover, serum alkaline phosphatase is frequently increased.

Urinary calcium excretion is usually normal or high in hyperparathyroidism. Low urinary calcium suggests another diagnosis such as familial hypocalciuric hypercalcemia Familial hypocalciuric hypercalcemia Hypercalcemia is a total serum calcium concentration > 10.4 mg/dL (> 2.60 mmol/L) or ionized serum calcium > 5.2 mg/dL (> 1.30 mmol/L). Principal causes include hyperparathyroidism... read more . Chronic kidney disease suggests the presence of secondary hyperparathyroidism, but primary hyperparathyroidism can also be present. In patients with chronic kidney disease, high serum calcium and normal serum phosphate suggest primary hyperparathyroidism, whereas elevated phosphate suggests secondary hyperparathyroidism.

Imaging studies of the parathyroid(s) may be done preoperatively to localize an abnormal gland; it is not done to establish the diagnosis or determine whether surgery is needed. However, parathyroidectomy done by experienced surgeons has a high cure rate, and this has not been improved with use of preoperative imaging.

Many imaging techniques have been used effectively, including the following:

  • High-resolution CT with or without CT-guided biopsy and PTH immunoassay from thyroid venous drainage

  • Contrast-enhanced four-dimensional (4D) CT

  • MRI

  • High-resolution ultrasonography

  • Digital subtraction angiography

  • Thallium-201–technetium-99 scanning

Technetium-99 sestamibi, a radionuclide agent for parathyroid imaging, is more sensitive and specific than older agents and may be useful for identifying solitary adenomas.

For residual or recurrent hyperparathyroidism after initial parathyroid surgery, imaging is necessary and may reveal abnormally functioning parathyroid glands in unusual locations throughout the neck and mediastinum. Technetium-99 sestamibi is probably the most sensitive imaging test for these glands. Use of several imaging studies (MRI, CT, or high-resolution ultrasonography in addition to technetium-99 sestamibi) before repeat parathyroidectomy is sometimes necessary.

Diagnosis reference

  • 1. Bilezikian JP, Khan AA, Silverberg SJ, et al: Evaluation and management of primary hyperparathyroidism: Summary statement and guidelines from the Fifth International Workshop. J Bone Miner Res Aug. 19, 2022. doi: 10.1002/jbmr.4677

Treatment of Hyperparathyroidism

  • Sometimes medical management of hypercalcemia

  • Often surgical parathyroidectomy

Treatment for hyperparathyroidism depends on severity.

Medical management

Conservative management with methods to ensure that serum calcium concentrations remain low may be used for patients with who are either asymptomatic primary hyperparathyroidism with no indications for surgery. It may also be used for patients at high risk for surgery due to unrelated medical problems, but this is usually limited to patients with a shorter life expectancy because maintaining low serum calcium levels long-term may result in bone disease.

Patients should do the following:

  • Remain active (ie, avoid immobilization that could exacerbate hypercalcemia)

  • Follow a low-calcium diet

  • Drink plenty of fluids to minimize the chance of nephrolithiasis

  • Avoid drugs that can raise serum calcium (eg, thiazide diuretics)

Serum calcium and renal function are monitored every 6 months. Bone density is monitored every 12 months. However, recurrent hypercalcemia, subclinical bone disease, and hypertension are concerns. Patients with hypercalcemia alone can be managed with cinacalcet. Osteoporosis is treated with bisphosphonates.


In patients with symptomatic or progressive hyperparathyroidism, surgery is indicated. The indications for surgery in patients with asymptomatic, primary hyperparathyroidism are controversial. Surgical parathyroidectomy increases bone density and may have modest effects on symptoms that impact quality of life, but most patients do not have progressive deterioration in biochemical abnormalities or bone density. Many experts recommend surgery in the following circumstances (1 Treatment reference Hyperparathyroidism occurs when one or more of the parathyroid glands become overactive, causing elevated serum levels of parathyroid hormone and leading to hypercalcemia. Patients may be asymptomatic... read more ):

  • Serum calcium 1 mg/dL (0.25 mmol/L) greater than the upper limits of normal

  • Hypercalciuria (> 250 mg/day [> 6.25 mmol/day] in women or > 300 mg/day [>7.5 mmol/day] in men) or the presence of nephrolithiasis

  • Creatinine clearance < 60 mL/minute (< 1 mL/second)

  • Vertebral bone fracture or bone density at the hip, lumbar spine, or radius that is 2.5 standard deviations below controls (T score = −2.5)

  • Age < 50 years

  • The possibility of poor adherence with follow-up

Surgery consists of removal of adenomatous gland(s). Parathyroid hormone concentration can be measured before and after removal of the presumed abnormal gland using rapid assays. A fall of ≥ 50% 10 minutes after removal of the adenoma indicates successful treatment. In patients with disease of > 1 gland, several glands are removed, and often a small portion of a normal-appearing parathyroid gland is reimplanted in a more accessible location in the body such as the belly of the sternocleidomastoid muscle or subcutaneously in the forearm to prevent hypoparathyroidism. Rarely, this residual gland is the source of recurrent secondary hyperparathyroidism, which can be managed with additional surgical removal.

Parathyroid tissue is also occasionally preserved using cryopreservation to allow for later autologous transplantation in case persistent hypoparathyroidism develops.

Serum calcium must be monitored several times a day in the immediate postoperative period. When surgery is done for mild hyperparathyroidism, the serum calcium concentration drops to just below normal within 24 to 48 hours. In patients with more severe or prolonged hyperparathyroidism, particularly secondary hyperparathyroidism with severe osteitis fibrosa cystica, prolonged, symptomatic hypocalcemia may occur postoperatively.

When symptomatic hypocalcemia is expected, loading with 10 to 20 g elemental calcium in the days before surgery may prevent a precipitous postoperative decline in calcium. Even with preoperative calcium administration, large doses of calcium and vitamin D may be required in the postoperative period while bone calcium is repleted.

Pearls & Pitfalls

  • Serum calcium must be monitored several times a day in the immediate postoperative period following parathyroidectomy

In patients with severe hypercalcemia with primary hyperparathyroidism who are unable to undergo parathyroidectomy, medical treatment is indicated. Cinacalcet, a calcimimetic agent that increases the sensitivity of the calcium-sensing receptor to extracellular calcium, may lower parathyroid hormone and calcium levels.

Hyperparathyroidism in renal failure

Although primary hyperparathyroidism can occur, hyperparathyroidism in patients with renal failure is usually secondary. Secondary hyperparathyroidism in patients with renal failure can result in a number of symptoms, including

  • Osteitis fibrosa cystica with arthritis, bone pain, and pathologic fractures

  • Spontaneous tendon rupture

  • Proximal muscle weakness

  • Extraskeletal calcifications, including soft tissue and vascular calcification

  • Pruritis

Secondary hyperparathyroidism can develop in patients with moderate chronic kidney disease (estimated glomerular filtration rate < 60 mL/minute), but it is usually more advanced in patients who require long-term dialysis. The interplay between phosphate retention, hypocalcemia, decreased active vitamin D concentration, and increased fibroblast growth factor-23 stimulates parathyroid secretion in patients with renal failure.

Hyperphosphatemia Hyperphosphatemia Hyperphosphatemia is a serum phosphate concentration > 4.5 mg/dL (> 1.46 mmol/L). Causes include chronic kidney disease, hypoparathyroidism, and metabolic or respiratory acidosis. Clinical... read more should be prevented or treated if present. Treatment combines dietary phosphate restriction and phosphate-binding agents, such as calcium carbonate, calcium acetate, lanthanum, or sevelamer. Despite the use of phosphate binders, dietary restriction of phosphate is also needed. Aluminum-containing compounds have been used to limit phosphate concentration in the past, but they should be avoided, especially in patients receiving long-term dialysis, to prevent aluminum accumulation in bone resulting in severe osteomalacia.

Vitamin D administration is potentially hazardous in patients with chronic kidney disease because it can increase phosphate as well as calcium concentrations and lead to accelerated vascular calcification; vitamin D administration requires frequent monitoring of calcium and phosphate levels. Treatment is generally limited to patients with renal failure patients and secondary hyperparathyroidism. Although oral calcitriol is often given along with oral calcium to suppress secondary hyperparathyroidism, the results are variable in patients with end-stage renal disease. The parenteral form of calcitriol, or vitamin D analogs such as paricalcitol, may better prevent secondary hyperparathyroidism in such patients, because the higher attained serum concentration of 1,25(OH)2D directly suppresses PTH release.

The oral calcimimetic, cinacalcet, modulates the set point of the calcium-sensing receptor on parathyroid cells and decreases PTH concentration in dialysis patients without increasing serum calcium. Symptomatic hypocalcemia can develop with cinacalcet. It should not be started in patients with hypocalcemia at baseline, and calcium should be monitored frequently when titrating cinacalcet dose. Adherence can be limited by gastrointestinal intolerance.

Another calcimimetic, etelcalcetide, is a parenteral alternative.

Simple osteomalacia may respond to calcitriol 0.25 to 0.5 mcg orally once a day. In patients with osteomalacia caused by having taken large amounts of aluminum-containing phosphate binders, removal of aluminum with deferoxamine is necessary before calcitriol administration can reduce bone lesions.

Treatment of severe hyperparathyroidism

Progressive, severe elevation of parathyroid hormone level that cannot be lowered by medical means without causing significant hyperphosphatemia or hypercalcemia requires surgery to prevent or reverse symptoms. A subtotal parathyroidectomy is done with reimplantation of a portion of the most normal appearing gland in the belly of the sternocleidomastoid muscle or subcutaneously in the forearm.

Postoperatively, calcium can fall precipitously in patients with severe or long standing osteitis fibrosa cystica and is managed with oral and parenteral calcium and cholecalciferol. If the reimplanted parathyroid tissue does not produce parathyroid hormone and the PTH level remains very low or undetectable, the patient will be at risk of developing osteomalacia as well as symptomatic hypocalcemia. Prolonged administration of as much as 2 mcg of calcitriol given orally once a day and ≥ 2 g of elemental calcium supplement per day is generally needed to support the calcium level. If after subtotal parathyroidectomy, patients with end-stage renal disease remain symptomatic due to hypocalcemia, adjustment can be made to the dialysate concentration of calcium.

Treatment of tertiary hyperparathyroidism

Tertiary hyperparathyroidism occurs when long-term stimulatory effects causing secondary hyperparathyroidism result in adenomatous transformation of parathyroid tissue. Patients with hypercalcemia as well as severe elevation of PTH while not taking cholecalciferol or calcium-containing phosphate binders suggests the presence of tertiary hyperparathyroidism.

Adenomatous cells do not respond to medical treatment and require surgical intervention.

Treatment reference

  • 1. Bilezikian JP, Khan AA, Silverberg SJ, et al: Evaluation and management of primary hyperparathyroidism: Summary statement and guidelines from the Fifth International Workshop. J Bone Miner Res Aug. 19, 2022. doi: 10.1002/jbmr.4677

Key Points

  • Primary hyperparathyroidism causes hypercalcemia which is often asymptomatic.

  • Diagnosis is made by finding elevated PTH levels in a patient with hypercalcemia.

  • Primary hyperparathyroidism is most often due to solitary adenomas but these can be multiple in hereditary multiple endocrine neoplasia syndromes.

  • Treatment can be conservative in asymptomatic patients but usually requires surgical parathyroidectomy in patients with symptoms, severe hypercalcemia, or severe osteoporosis.

  • Secondary hyperparathyroidism is most often due to advanced renal disease and related to decreased vitamin D and calcium levels as well as persistent hyperphosphatemia.

  • Medical treatment is with continuous reduction in phosphate intake, phosphate binders, vitamin D, and calcimimetics.

  • Surgery is reserved for patients with severe and uncontrolled hyperparathyroidism.

Drugs Mentioned In This Article

Drug Name Select Trade
Calcidol, Calciferol, D3 Vitamin, DECARA, Deltalin, Dialyvite Vitamin D, Dialyvite Vitamin D3, Drisdol, D-Vita, Enfamil D-Vi-Sol, Ergo D, Fiber with Vitamin D3 Gummies Gluten-Free, Happy Sunshine Vitamin D3, MAXIMUM D3, PureMark Naturals Vitamin D, Replesta, Replesta Children's, Super Happy SUNSHINE Vitamin D3, Thera-D 2000, Thera-D 4000, Thera-D Rapid Repletion, THERA-D SPORT, UpSpring Baby Vitamin D, UpSpring Baby Vitamin D3, YumVs, YumVs Kids ZERO, YumVs ZERO
AcidFree, Alka-Mints, Alka-Seltzer, Alka-Seltzer Heartburn Relief, Alkets , Antacid Fast Dissolve, Calcarb 600, Calci-Chew , Calci-Mix , Calcium Antacid, Cal-Gest , Caltrate, Maalox, Maalox Antacid Barrier, Maalox Quick Dissolve, Mylanta Children's, Nephro-Calci , Pepto-Bismol Children's, Rolaids Extra Strength, Titralac, Titralac Extra Strength, Tums, Tums Chewy Bites , Tums Cool Relief, Tums E-X, Tums Freshers, Tums Kids, Tums Lasting Effects, Tums Smooth Dissolve, Tums Smoothies, Tums Ultra
Calphron, Eliphos, PhosLo, Phoslyra
RenaGel, Renvela
Calcijex, Rocaltrol, Vectical
Zemplar, Zemplar Multi-Dose Vial Solution, Zemplar Solution
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
quiz link

Test your knowledge

Take a Quiz!