Symptoms You Should Never Ignore - Pain, Shortness of Breath
What Is Hyperparathyroidism?
Hyperparathyroidism happens when the parathyroid glands make too much parathyroid hormone. This can affect your calcium levels and cause other health problems.
You may have hyperparathyroidism if your parathyroid glands make too much parathyroid hormone (PTH).
The parathyroid glands are four pea-sized endocrine glands in your neck, near or attached to the back of your thyroid. Endocrine glands secrete hormones necessary for the functioning of your body.
Despite having similar names and being adjacent in your neck, the parathyroid glands and the thyroid are different organs. PTH helps regulate the levels of calcium, vitamin D, and phosphorus in your bones and blood.
Some people with this condition do not experience any symptoms and may not need treatment. Others have mild or severe symptoms that may require surgery.
Keep reading to learn the causes, types, and treatment of hyperparathyroidism.
In hyperparathyroidism, one or more of your parathyroid glands becomes overactive and makes excess PTH. This could be due to a tumor, gland enlargement, or other structural problems of the parathyroid glands.
When your calcium levels are too low, your parathyroid glands respond by increasing the production of PTH.
This causes your kidneys and intestines to absorb a larger amount of calcium. It also removes more calcium from your bones. PTH production returns to typical levels when your calcium level goes up again.
Sometimes, another condition may cause you to develop hyperparathyroidism.
There are three types of hyperparathyroidism: primary, secondary, and tertiary.
Primary hyperparathyroidism
This type occurs when you have at least one overactive parathyroid gland.
Causes of parathyroid problems can include:
An increased risk of developing primary hyperparathyroidism also occurs in people who:
Secondary hyperparathyroidism
This type occurs when you have an underlying condition that causes your calcium levels to be abnormally low. Most cases of secondary hyperparathyroidism are due to vitamin D deficiency and chronic kidney failure that results in low active vitamin D and calcium levels.
Tertiary hyperparathyroidism
This type occurs after longstanding secondary hyperparathyroidism. The parathyroid glands keep making too much PTH after your calcium levels return to typical levels. This type usually occurs in people with kidney problems.
Symptoms can vary from mild to severe, depending on your type of hyperparathyroidism.
Primary hyperparathyroidism
Some people with primary hyperparathyroidism don't have any symptoms. If you do have symptoms, they can range from mild to severe. Milder symptoms may include:
More severe symptoms can include:
Secondary hyperparathyroidism
With this type, you may have skeletal abnormalities that may include:
Other symptoms can depend on the underlying cause of your hyperthyroidism, such as chronic kidney failure or severe vitamin D deficiency.
A healthcare professional might suspect you have hyperparathyroidism if routine blood tests show high calcium levels in your blood. To confirm this diagnosis, they will likely need to perform other tests.
Blood tests
Additional blood tests can help your primary care provider make an accurate diagnosis. A doctor may check your blood for high PTH levels, alkaline phosphatase levels, and low phosphorus levels.
Urine tests
A urine test can help a doctor determine how severe your condition is and whether kidney problems may be the cause. A doctor can check your urine to see how much calcium it contains.
Kidney tests
A technician might take an ultrasound of your abdomen to check for kidney abnormalities.
The treatment for hyperparathyroidism may vary depending on the cause and severity of your symptoms.
Primary hyperparathyroidism
You might not need treatment if your kidneys are working fine, if your calcium levels are only slightly high, if your bone density is within typical levels. In this case, a doctor may use yearly blood tests to monitor your kidney health and calcium levels. You may need a test every one or two years to measure your bone density.
If you are older than 50, you may not need surgery.
A doctor may recommend drinking plenty of water to reduce your risk of kidney stones. Regular exercise can help strengthen your bones.
If treatment is necessary, a doctor may recommend:
Surgery
Surgical procedures involve removing enlarged parathyroid glands or tumors on the glands. Complications are rare and include damaged vocal cord nerves and long-term, low calcium levels.
Medications
If you are unable to have surgery, a doctor may recommend certain medications. Calcimimetics act like calcium in the blood and cause your glands to make less PTH. Bisphophonates keep your bones from losing calcium and can help reduce your risk of osteoporosis.
Secondary hyperparathyroidism
Treatment involves bringing your PTH to typical levels by treating the underlying cause.
Methods of treatment can include:
Hyperparathyroidism can occur with other conditions that may include:
If you have osteoporosis, you may experience additional symptoms. Primary hyperparathyroidism leads to osteoporosis because high levels of PTH cause the release of calcium from the bones, thereby weakening them. Symptoms may include:
A doctor can check for signs of osteoporosis with bone X-rays or by performing a bone mineral density test. This test measures calcium and bone mineral levels using X-ray devices.
Surgery treats most cases of primary hyperparathyroidism. Doctors also treat some cases of tertiary hyperparathyroidism with surgery.
If you and a doctor opted to monitor your condition rather than perform surgery, taking prescribed medications, drinking enough water, and engaging in regular exercise may help reduce or prevent symptoms.
Hyperparathyroidism occurs when at least one overactive parathyroid gland makes too much PTH. This may affect the amount of calcium in your blood and cause symptoms ranging from mild to severe.
Doctors typically recommend surgery to remove the affected parathyroid gland or glands. In some cases, especially if they don't have symptoms, they may opt to monitor your condition.
Hyperparathyroidism And Back Pain: What Is The Link?
Hyperparathyroidism can cause unusually high calcium levels in the blood. This can lead to back pain when there is damage to the kidneys or bones. It can also cause muscle pain.
Most people with hyperparathyroidism do not develop symptoms. However, when the condition is severe enough to cause symptoms, these often include musculoskeletal pain, which may affect the lower back.
Hyperparathyroidism can cause back pain in various ways. Some people develop kidney stones, which can cause intense back pain. Hyperparathyroidism can also weaken the bones, causing a loss of bone mineral density. This may cause bone pain and an increased risk of fractures.
Research also suggests that hyperparathyroidism contributes to inflammation throughout the body, potentially causing muscle pain.
Read on to learn more about the link between hyperparathyroidism and back pain.
In people with hyperparathyroidism, the parathyroid glands release an excessive amount of parathyroid hormone into the bloodstream. This causes blood calcium levels to rise.
Parathyroid hormones are responsible for tightly controlling the amount of calcium in the blood. This nutrient is important for healthy bone development, and the body uses it for various functions.
Too much calcium in the body, known as hypercalcemia, can negatively affect the bones and kidneys. Muscle pain — including in the back — is a common symptom of hyperparathyroidism.
Primary hyperparathyroidism means that another medical condition is not the reason for the symptoms. In many people, a benign tumor called an adenoma causes the condition.
Hypercalcemia is when there is too much calcium in the blood. It is also the main cause of hyperparathyroidism symptoms.
High levels of parathyroid hormone promote the release of calcium from bones into the blood, leading to excess calcium in the blood and causing the bones to become weaker. Excess calcium may lead to a kidney condition called nephrolithiasis, in which calcium stones are present in the organ.
Damage to the bones may cause bone pain in the back or hips. Nephrolithiasis can cause pain in the lower back and lower abdomen. Over time, bone damage can cause weaker bones that may break, leading to fracture-related back pain.
People with hyperparathyroidism may experience back pain due to the following reasons:
There are also many other possible causes of back pain.
In the early stages of hyperparathyroidism, a person may not have any symptoms. Instead, a doctor may diagnose the condition during routine blood tests, when calcium levels are unusually high.
Some symptoms of primary hyperparathyroidism include:
A doctor may perform various exams to determine whether hyperparathyroidism is causing back pain. These may include:
Diagnosing hyperparathyroidism
If a doctor suspects that hyperparathyroidism is causing back pain, they will perform blood and urine tests.
Blood tests showing high calcium levels may require further evaluation. A doctor may recommend additional testing for elevated levels of parathyroid hormone.
Secondary hyperparathyroidism happens when another condition leads the levels of parathyroid hormone to increase. This causes the parathyroid glands to work harder, elevating blood calcium levels. Chronic kidney disease is the most common cause.
A doctor may screen for signs of secondary hyperparathyroidism, potentially by testing kidney function.
There are various treatment options for back pain, including medication and nonsurgical and surgical interventions. Doctors will be able to advise on the best option for people with hyperparathyroidism who are experiencing back pain.
If further examination of the back pain reveals that hyperparathyroidism has progressed, doctors may recommend surgery. Typically, the following signs may show that the disease is advanced:
Surgery to remove the parathyroid glands is the only way to cure hyperparathyroidism.
In some cases, a doctor may recommend a type of surgery called bilateral neck exploration. During this procedure, a surgeon assesses which glands are overactive and then removes only those glands.
In people with no symptoms, it may be possible to avoid surgery. Alternative options include:
People with this condition should also avoid becoming dehydrated, as this may cause calcium levels to increase in the body.
People should consider contacting a doctor if their back pain does not improve after a few weeks or if they experience any of the following:
Hyperparathyroidism does not always cause symptoms, especially in mild cases. However, by the time symptoms appear, there may be damage to the bones and kidneys, and a person may have significant pain.
Treating hyperparathyroidism can prevent it from getting worse and help minimize symptoms, such as back pain. A person with elevated blood calcium levels should discuss the treatment and management options with a doctor.
In some cases, it may be possible to avoid surgery, but a person must monitor their condition and tell a healthcare professional if the symptoms get worse.
Secondary Hyperparathyroidism
Secondary hyperparathyroidism is a complex endocrine condition characterized by excess circulating parathyroid hormone (PTH) resulting from an underlying condition, most commonly chronic kidney disease (CKD) or vitamin D deficiency.1 Uncontrolled secondary hyperparathyroidism can lead to serious health consequences, including cardiovascular disease (CVD) and renal osteodystrophy.
First-line secondary hyperparathyroidism treatments include phosphate binders, vitamin D receptor activators, and calcimimetics.1 Surgical management can be considered for patients with secondary hyperparathyroidism that is refractory to other treatments.2 This article summarizes the etiology, risk factors, diagnostic workup, and management of patients with secondary hyperparathyroidism.
Types of HyperparathyroidismParathyroid hormone helps regulate calcium metabolism. Primarily acting on the kidneys and bones, PTH increases serum calcium and phosphorus by stimulating osteoclasts, causing bone resorption and decreased renal elimination.3
Through action on the kidneys, PTH also increases the production of 1,25 dihydroxyvitamin D, which increases calcium absorption.3 Calcium has a negative feedback effect on PTH release; increased serum calcium suppresses PTH release.3
Primary vs Secondary or Tertiary HyperparathyroidismExcess production of PTH results in hyperparathyroidism. The 3 types of hyperparathyroidism are as follows4:
Secondary hyperparathyroidism is most often due to CKD. According to the 2017 Kidney Disease Improving Global Outcomes (KDIGO) guideline on the treatment of CKD-mineral and bone disorder (CKD-MBD), patients with stage 3a to 5 CKD should be monitored for secondary hyperparathyroidism.1
Causes of Secondary Hyperparathyroidism: Etiology, Risk FactorsConditions that cause hypocalcemia can lead to secondary hyperparathyroidism. The most common causes of hypocalcemia are CKD and vitamin D deficiency.5
Risk factors that increase a person's risk of developing CKD include the following6,7:
Risk factors for vitamin D deficiency include the following8:
Risk factors for secondary hyperparathyroidism in patients with CKD include the following1,9,10:
Chronic kidney disease and vitamin D deficiency, 2 of the most common causes of secondary hyperparathyroidism, are common in the United States (US).5 According to the Centers for Disease Control and Prevention, an estimated 35.5 million US adults (more than 1 in 7) have CKD.11 Up to 50% of patients have persistent secondary hyperparathyroidism after undergoing kidney transplantation.12 According to National Health and Nutrition Examination Survey data from 2001 to 2018, the prevalence of severe (serum 25-hydroxyvitamin D levels of <25 nmol/L) and moderate (25-50 nmol/L) vitamin D deficiency was 2.6% and 22%, respectively.13
Complications of Secondary HyperparathyroidismThe morbidities associated with secondary hyperparathyroidism are primarily related to renal osteodystrophy and CVD in patients with CKD.5
Renal OsteodystrophyRenal osteodystrophy is a group of bone disorders that can lead to an increased risk of fractures. It is caused by the dysregulation of minerals such as calcium and phosphorus in CKD. Examples of renal osteodystrophy including the following14:
Calcium and phosphate dysregulation in secondary hyperparathyroidism can accelerate vascular calcification, increasing the risk of cardiovascular events and death. Vascular calcification in skin and soft tissue, especially when severe (such as in calciphylaxis) can also lead to vascular compromise of the tissue and the formation of skin ulcers.15
Diagnosis of Secondary HyperparathyroidismBecause there is no currently accepted optimal value for PTH in patients with CKD stage 3a to 5, when evaluating a patient with suspected secondary hyperparathyroidism, clinicians should consider the upper limit of normal based on the assay used and patterns of progressively rising PTH or PTH levels consistently above normal.1
In secondary hyperparathyroidism, increased PTH is typically associated with hypocalcemia and hyperphosphatemia, though calcium levels may be normal in some patients.15 In the initial stages of secondary hyperparathyroidism, as PTH levels start to increase, phosphorus and calcium levels remain within normal limits.16
Bone-related signs and symptoms of secondary hyperparathyroidism include the following4,17:
Other common signs and symptoms of secondary hyperparathyroidism include the following4,18:
According to the KDIGO guideline, since the optimal PTH level for patients with CKD is unknown, monitoring of serum PTH, calcium, and phosphate, and alkaline phosphatase activity should begin in CKD stage 3a. The recommended screening frequencies for adults with secondary hyperparathyroidism is summarized in Table 1.1,19
Table 1. Secondary Hyperparathyroidism Recommended Screening Frequencies in Adultsa CKD Stage Serum PTH Monitoring Frequency Serum Calcium and Phosphate Monitoring Frequency Alkaline Phosphatase Activity Stage 3a Baseline Baseline Baseline Stages 3a and 3b Frequency determined by baseline level and disease progression Every 6 to 12 months Every 12 months(more frequently if PTH is elevated) Stage 4 Every 6 to 12 months Every 3 to 6 months Stage 5 Every 3 to 6 months Every 1 to 3 monthsCKD = chronic kidney disease; PTH = parathyroid hormone.
aThe frequency of monitoring may be increased for patients with CKD-MBD undergoing treatment or in patients with identified biochemical abnormalities.
From Kidney Disease: Improving Global Outcomes guideline1 and Lucca LJ et al.19
The diagnostic workup for secondary hyperparathyroidism includes the following laboratory tests1,18:
The differential diagnosis for secondary hyperparathyroidism should include primary hyperparathyroidism and tertiary hyperparathyroidism. Tertiary hyperparathyroidism can occur as a result of longstanding and severe secondary hyperparathyroidism.5,20
Secondary Hyperparathyroidism TreatmentThe goal of treatment for secondary hyperparathyroidism is to normalize serum calcium, phosphate, and PTH levels.21 Because no optimal serum PTH level has been established, in general, a patient's target PTH should be below the upper limit of normal PTH for the assay used. The target PTH level in patients with CKD stage 5 can be maintained at a level 2 to 9 times the upper limit of normal of the assay.1
Although currently available therapies can effectively decrease calcium and phosphorus levels, clinical trials in patients with CKD-MBD have failed to show improvement in cardiovascular outcomes.22
Dietary ManagementAccording to the KDIGO guideline, limiting dietary phosphorus intake is recommended for patients with CKD stages 3, 4, and 5 with clinically significant hyperphosphatemia.1 The dietary restriction of phosphorus is one of the first steps in managing secondary hyperparathyroidism.21
Although a low-phosphorus diet may be helpful in patients with CKD, secondary hyperparathyroidism, and hyperphosphatemia, such a diet can be difficult for patients to follow because of the high prevalence of phosphorus in the Western diet. Phosphorus is commonly found in protein-rich foods and as additives to processed foods.23 Strict phosphorus restrictions can also limit access to other nutrients.24,25 To help ensure adequate nutritional intake, patients should avoid foods that have a high phosphate-to-protein ratio, such as processed foods and fast foods, and instead consume foods that have a high biological value, such as eggs and meats.1,26
PharmacotherapyThe goals of pharmacotherapy for secondary hyperparathyroidism are to decrease serum phosphate and calcium levels and control PTH and vitamin D levels.5 This may be achieved through the use of phosphate binders, vitamin D, and vitamin D analogs.5
When dietary modifications alone are not sufficient to control phosphate levels or when patients are unable to adhere to a low-phosphorus diet, phosphate binders may be necessary to manage phosphate burden and help ensure adequate protein intake.25 Phosphate binders should be used in combination with a low-phosphorus diet.
Phosphate binders work by forming an insoluble phosphate complex in the gut that prevents phosphate absorption into the bloodstream.26 Phosphate binders used to treat hyperphosphatemia include the following26:
Patient adherence to phosphate binders can be challenging due to high pill burden and adverse effects, including the following26,27:
The usual starting doses for phosphate binders and special considerations for patients with secondary hyperparathyroidism are summarized in Table 2.1,25,26,28-31
Table 2. Phosphate Binders in Adults: Starting Doses and Special Considerations Drug Usual Starting Dose Special Considerations Aluminum hydroxide 600 mg to 1200 mg orally 3 times a day with a meal Use should be limited to short periods of time and avoided in patients with CKD stage 5 due to the risk of aluminum toxicity Calcium carbonate 500 mg to 600 mg orally 3 times a day with a meal Inexpensive but requires large doses to be effective; it may increase risk of vascular calcification Lanthanum carbonate(chewable tablet) 500 mg to 1500 mg orally, in divided doses with a meal Indicated for patients with end-stage renal diseaseMore expensive option but has a lower pill burdenTissue accumulation can occur with unknown long-term effects Lanthanum carbonate(oral powder) 750 to 1500 mg orally (sprinkled over food), in divided doses Sevelamer carbonate(tablet) 800 mg to 1600 mg orally 3 times a day with a meal Only indicated for patients with CKD on dialysisRequires consideration of the patient's previous exposure to phosphate bindersDifferent formulations can be switched on a gram-for-gram basis Sevelamer carbonate (powder) 0.8 g to 1.6 g orally 3 times a day with a meal Sevelamer hydrochloride (tablet) 800 mg to 1600 mg orally 3 times a day Sucroferric oxyhydroxide 500 mg orally 3 times a day with a meal Only indicated for patients with CKD on dialysisIron-based phosphate binderCKD = chronic kidney disease.
From Kidney Disease: Improving Global Outcomes guideline,1 Barreto et al,25 Chan et al,26 Iwamuro et al,28 Kharsa et al,29 Drugs.Com,30 and Coyne et al.31
Vitamin D Supplements and AnalogsBecause vitamin D deficiency is one of the most common causes of secondary hyperparathyroidism, vitamin D supplements are recommended to correct vitamin D deficiency or insufficiency, and vitamin D analogs are recommended to treat secondary hyperparathyroidism in patients with CKD.1
Per the KDIGO guideline, serum 25(OH)D monitoring is recommended for patients with CKD stages 3 to 5. Treatment strategies for vitamin D deficiency or insufficiency are in line with recommendations for the general population.1
Treatment for vitamin D deficiency includes supplementation with nutritional vitamin D such as ergocalciferol (a synthetic form of vitamin D2) or cholecalciferol (a synthetic form of vitamin D3). Ergocalciferol and cholecalciferol are inactive forms of vitamin D that are converted to their active forms by the liver and kidney.32
Vitamin D analogs are recommended for the treatment of secondary hyperparathyroidism in patients with CKD.4 Vitamin D analogs provide a form of vitamin D that does not require activation by the liver or kidney. Vitamin D analogs treat secondary hyperparathyroidism by improving calcium absorption and suppressing PTH secretion.
According to the KDIGO guideline, routine use of vitamin D analogs or calcitriol is not recommended for patients with CKD who are not on dialysis.1 Supplementation with nutritional or dietary vitamin D may be an alternative treatment to vitamin D analogs; however, no clinical trials showing efficacy with these agents currently exist.4 The usual starting doses and special considerations of vitamin D analogs for patients with secondary hyperparathyroidism and CKD are summarized in Table 3.
Table 3. Vitamin D Analogs: Usual Starting Dose and Special Considerations Drug Usual Starting Dose Special Considerations Calcitriol 0.25 mcg to 0.5 mcg orally once daily Indicated for the management of secondary hyperparathyroidism in patients with moderate to severe renal failure with or without dialysisActive form of vitamin D3 Doxercalciferol For patients not on dialysis: 1 mcg orally once dailyFor patients on dialysis: 10 mcg orally 3 times weekly at dialysis Indicated for the treatment of secondary hyperparathyroidism in CKD stages 3 and 4 Paricalcitol 1 mcg to 2 mcg orally daily or 2 mcg to 4 mcg orally 3 times a week Indicated for the treatment and prevention of secondary hyperparathyroidism in CKD stages 3 and 4CKD = chronic kidney disease.
From Miedziaszczyk et al12 and FDA-approved prescribing information.32-35
CalcimimeticsAccording to the KDIGO guideline, calcimimetics are recommended to treat secondary hyperparathyroidism in patients with CKD Stage 5.1 Calcimimetics suppress PTH secretion by increasing the sensitivity of the calcium-sensing receptor on the parathyroid gland.36 Cinacalcet and etelcalcetide are currently the only calcimimetics approved in the United States for secondary hyperparathyroidism.37
Cinacalcet is a calcimimetic indicated to treat secondary hyperparathyroidism in patients with end-stage CKD on dialysis.38 It is also indicated as a treatment for primary hyperparathyroidism and hypercalcemia in patients with parathyroid carcinoma.38
The recommended starting dose of cinacalcet for secondary hyperparathyroidism is 30 mg/d.38 The dose can be titrated as needed to achieve the target PTH level by 30 mg every 2 to 4 weeks up to 180 mg/d.38
The most common adverse effects of cinacalcet are nausea and vomiting. Other adverse effects include the following38:
Etelcalcetide is an intravenous agent approved for treating secondary hyperparathyroidism in patients with CKD on hemodialysis. The starting dose is 5 mg IV per dialysis session and may be titrated up to a maximum dose of 15 mg IV.39 Common adverse effects of etelcalcetide include decreased blood calcium. Other adverse effects include the following36:
The indications for hyperparathyroidism surgery with a parathyroidectomy are ill-defined. The following factors should be considered40,41:
Clinicians should monitor the following in patients undergoing treatment for secondary hyperparathyroidism1:
The prognosis for patients with secondary hyperparathyroidism varies based on disease severity and the presence of comorbid conditions.5 Secondary hyperparathyroidism can significantly affect a patient's quality of life and increase the risk of CVD and bone disease.5
Clinical trials showing improvement in survival with vitamin D analogs and calcimimetics are currently lacking.42 Approximately 15% of patients with secondary hyperparathyroidism on dialysis will require a parathyroidectomy after 10 years of starting dialysis and 38% after 20 years.2 In a retrospective cohort study, Li et al found patients with severe secondary hyperparathyroidism on peritoneal dialysis had a significantly higher rate of infection-related mortality compared to patients with non-severe secondary hyperparathyroidism on peritoneal dialysis.43
Secondary Hyperparathyroidism GuidelinesThe latest guidance on treating secondary hyperparathyroidism is the KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD).
References
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