Primary and Secondary Hyperparathyroidism

The parathyroid gland is a set of four or more pea-sized organs in the neck. Its main job is to make parathyroid hormone (PTH), which controls calcium levels in your bloodstream.

When the parathyroid gland is overactive (hyperparathyroidism), excess PTH is produced, leading to a rise in blood calcium levels. If blood calcium levels get too high (hypercalcemia), symptoms and complications like bone loss and kidney problems can develop.

This article reviews the types, causes, diagnosis, and treatment of hyperparathyroidism. It also discusses the role of calcium and vitamin D in disease development and management.

Types of Hyperparathyroidism and What Causes It

The two main types of hyperparathyroidism are:

• Primary hyperparathyroidism
• Secondary hyperparathyroidism

Primary

Primary hyperparathyroidism is a parathyroid gland disease that results in excess PTH production.

The excess PTH pulls calcium into the bloodstream from the bones. The PTH also signals the gut to absorb more calcium and the kidneys to hold on to calcium and not lose it through urine. All of these PTH-driven actions result in elevated blood calcium levels.

Three causes of primary hyperparathyroidism are:

• Adenoma is a benign (noncancerous) growth of cells within the parathyroid gland. This is the most common cause, occurring in around 80% of cases.
• Hyperplasia is the enlargement of all four parathyroid glands, accounting for 15% to 20% of cases.
• Cancer is an abnormal (cancerous) growth of cells within the parathyroid gland. Parathyroid cancer is very rare, occurring in less than 1% of cases.

(Note that when research or health authorities are cited, the terms for sex or gender from the source are used.)

Secondary

Secondary hyperparathyroidism is not a disease of the parathyroid gland. Instead, it's a normal and appropriate reaction of the parathyroid gland to another health problem going on in the body that is causing low blood calcium levels.

The low blood calcium levels are most commonly due to vitamin D deficiency or chronic kidney disease.

Vitamin D Deficiency

Vitamin D is created by your body when your skin is exposed to the sun. Vitamin D can also be obtained through supplements or foods like salmon, tuna, egg yolk, and vitamin D-fortified orange juice.

Since vitamin D plays a role in ensuring sufficient calcium absorption in the gut, a deficiency can lead to low calcium levels.

Vitamin D deficiency has many potential causes, including:

• Low sun exposure
• Poor intake of vitamin D-containing foods
• Digestive conditions associated with inadequate vitamin D gut absorption, like celiac disease or Crohn's disease
• Diseases that impact the metabolism of vitamin D into its active form (e.g., chronic liver disease)

Chronic Kidney Disease

Chronic kidney disease leads to an abnormality in kidney vitamin D activation. As a result of insufficient vitamin D levels in the body, low calcium levels develop. The low calcium levels trigger the parathyroid gland to release parathyroid hormone in an attempt to raise calcium levels.

Hyperparathyroidism Symptoms

Symptoms of hyperparathyroidism depend on the type.

Primary

Most people with primary hyperparathyroidism have no or minimal symptoms.

If symptoms are present, they are due to high blood calcium levels and include:

• Bone and joint pain
• Unusual tiredness
• Mild depression
• Constipation
• Excess thirst and frequent urination

Long-term manifestations of primary hyperparathyroidism include:

• Kidney stones, which may lead to blood in the urine (hematuria) and severe, sudden flank pain (renal colic)
  
• Osteoporosis (bone thinning), which increases the risk of fractures (bone breaks)
• High blood pressure and other heart/blood vessel complications (e.g., stroke or heart failure)

Secondary

The symptoms of secondary hyperparathyroidism are related to the underlying condition.

For example, a person with secondary hyperparathyroidism from vitamin D deficiency may have muscle aches or mild weakness. If the vitamin D deficiency is severe, symptoms of rickets or osteomalacia can develop, such as:

• Rickets (bone softening in childhood): Symptoms include swollen wrists and ankles, delayed tooth development, bone pain, bowed leg deformity, and poor growth.
• Osteomalacia (bone softening in adulthood): Symptoms include fatigue, bone pain, muscle pain and weakness, and a waddling gait.

Vitamin D deficiency also increases a person's risk for osteoporosis and fractures.

Secondary hyperparathyroidism from chronic kidney disease is also linked to osteoporosis and bone fractures. In addition, it can raise the risk of death from heart disease and anemia, although more research is needed to understand these connections.

Very rarely, secondary hyperparathyroidism from chronic kidney disease can lead to calciphylaxis, a condition associated with skin necrosis (tissue death) and severe open wounds that are difficult to heal.

Diagnosis: How Do You Know You Have Hyperparathyroidism?

The diagnosis of hyperparathyroidism is based on results from a blood calcium test and blood parathyroid hormone test.

With primary hyperparathyroidism, most individuals will have a high calcium and PTH level.

With secondary hyperparathyroidism, individuals have a high PTH and a normal or low blood calcium level. Additional blood tests, such as vitamin D and creatinine levels (a measure of kidney function), are also ordered to determine the cause of secondary hyperparathyroidism.

When evaluating for hyperparathyroidism, healthcare providers usually order studies besides blood tests to check for disease complications, especially bone loss and kidney stones.

Results from these studies also help guide management, like whether parathyroid surgery is needed.

These studies include:

• A dual-energy X-ray absorptiometry (DEXA) scan of the spine, hips, and test called a 1/3 radius (1/3R), which measures cortical bone, to check for osteoporosis
• A 24-hour urinary calcium level (measures the amount of calcium in a 24-hour urine collection sample) to assess for kidney stone risk
• A computed tomography (CT) scan (a type of X-ray that creates three-dimensional body images) to check for asymptomatic kidney stones
  

Primary Hyperparathyroidism Treatment

Surgical removal of the parathyroid gland (parathyroidectomy) is the only cure for primary hyperparathyroidism. Nonsurgical therapies may be advised in certain situations.

Surgery

Parathyroidectomy for primary hyperparathyroidism has a cure rate of 95% to 98%. It's indicated in all people with symptoms of primary hyperparathyroidism.

In asymptomatic individuals, surgery is indicated if one or more of the following criteria is met:

• High blood calcium level, specifically 1.0 milligram per deciliter (mg/dL) above normal
• Kidney disease
• Low bone density or prior history of fragility fracture (bone break from minimal trauma)
• Age younger than 50 years old

Nonsurgical Treatment

Nonsurgical therapies for primary hyperparathyroidism are generally only considered in people who cannot tolerate surgery or who have a mildly high calcium level and no symptoms or evidence of complications (e.g., low bone density or the presence of kidney stones).

The main aim of nonsurgical therapies is to control blood calcium levels so they don't get too high and cause complications.

Such therapies might include:

• A medication called Sensipar (cinacalcet) to lower calcium levels
• An osteoporosis medication like Fosamax (alendronate) to increase bone density
• A vitamin D supplement to obtain a 25-hydroxy vitamin D level of more than 30 nanograms per milliliter (ng/mL).

Appropriate calcium intake/supplementation is also advised.

Nutritional guidelines from the Institute of Medicine (IOM) are generally followed for calcium. The IOM recommends:

• 800 milligrams (mg) per day of calcium for females less than 50 years and males less than 70 years
• 1,000 mg per day of calcium for females older than 50 and males older than 70

Secondary Hyperparathyroidism Treatment

The treatment of secondary hyperparathyroidism involves correcting the root cause.

For instance, people with vitamin D deficiency from poor food intake or low sun exposure may be treated with prescription vitamin D supplements.

Vitamin D deficiency from gut malabsorption requires additional therapies like eating a gluten-free diet if diagnosed with celiac disease.

Treating secondary hyperparathyroidism from chronic kidney disease is complex and requires the careful attention of a nephrologist (a doctor specializing in kidney care).

Therapies may include taking a calcimimetic (a drug that blocks PTH release) and a vitamin D analog (a manufactured active form of vitamin D).

Keep in mind that a parathyroidectomy is required to control secondary hyperparathyroidism in around 15% of people 10 years after the onset of dialysis.

Living Well With Hyperparathyroidism

The key to living well with hyperparathyroidism involves following up with your healthcare team. Whether or not you undergo surgery, close monitoring is required to ensure the right balance of calcium and PTH in your body.

For instance, if you underwent surgery for primary hyperparathyroidism, you must obtain periodic blood tests to check calcium and PTH blood levels after surgery. You will also need calcium supplements after the operation until your body adjusts.

If surgery is not performed for primary hyperparathyroidism, annual monitoring of your blood calcium levels, kidney function, and bone density is essential to ensuring no disease progression and subsequent need for surgery.

In the end, health risks will be minimized if a person's hyperparathyroidism is cured or managed well. With surgery—the only curable treatment—research has found long-term improvements in quality of life.

Summary

Hyperparathyroidism is an overactive parathyroid gland that releases excess parathyroid hormone (PTH).

Hyperparathyroidism may result from a diseased parathyroid gland (primary hyperparathyroidism) or be a normal response to compensate for low calcium blood levels (secondary hyperparathyroidism).

Primary hyperparathyroidism does not usually cause symptoms but can lead to bone loss and kidney stones if not treated. The good news is that primary hyperparathyroidism can be cured by surgically removing the parathyroid gland.

The symptoms and management of secondary hyperparathyroidism are based on the underlying cause, most commonly vitamin D deficiency or chronic kidney disease.