Secondary Hyperparathyroidism

Secondary hyperparathyroidism is a condition where the parathyroid glands produce too much parathyroid hormone in response to an underlying health problem, most commonly chronic kidney disease or vitamin D deficiency.

Table of contents

• What is Secondary Hyperparathyroidism?
• Associated Anatomy
• Causes and How It Develops
• Who Is Affected
• Symptoms
• Diagnosis
• Treatment Options
• What Happens If Left Untreated

What is Secondary Hyperparathyroidism?

Secondary hyperparathyroidism is a condition in which a disease outside of the parathyroid glands causes all of the parathyroid glands to become enlarged and overactive.^[1] The most common causes of this condition are kidney failure and vitamin D deficiency.^[2]

This condition is different from primary hyperparathyroidism. In primary hyperparathyroidism, one or more parathyroid glands develop a growth or become enlarged on their own, causing them to make too much parathyroid hormone (PTH)—a substance that controls calcium levels in the blood.^[3] In secondary hyperparathyroidism, the parathyroid glands respond to an underlying health problem by producing more hormone to try to fix it.^[4]

The parathyroid glands normally help maintain the right amount of calcium in the blood and in tissues that depend on calcium to work correctly. This balance is especially important for nerves, muscles, and bones.^[3]

Associated Anatomy

• Parathyroid glands
• Kidneys
• Bones
• Intestines

You have four parathyroid glands, each about the size of a pea or a grain of rice. They are located in the neck behind the thyroid gland, at the tops and bottoms of each lobe of the thyroid.^[3] These glands secrete PTH, which sends signals to your bones to release calcium, to your kidneys to hold onto calcium and remove phosphate, and indirectly to your intestines to absorb calcium.^[6]

Causes and How It Develops

Secondary hyperparathyroidism is commonly associated with vitamin D deficiency and chronic kidney disease.^[4] When kidneys fail, they can no longer convert vitamin D into the active form that the body needs. At the same time, failing kidneys cannot remove enough phosphate from the body.^[5]

Hypocalcemia—a condition where calcium levels in the blood are too low—is the most important trigger for increased PTH secretion in secondary hyperparathyroidism.^[4] When the kidney cannot make enough vitamin D or remove phosphorus from the body, calcium levels drop. These low calcium levels stimulate the parathyroid glands to make more PTH.^[5]

Over time, this constant stimulation causes the parathyroid glands to grow and become overactive, and patients can develop secondary hyperparathyroidism. The increased PTH causes calcium to be released from bones, which can make them weak and brittle.^[4] Prolonged secondary hyperparathyroidism is often associated with disturbances in bone health, as well as calcium deposits in blood vessels and organs, which can lead to serious heart and blood vessel problems.^[4]

Secondary hyperparathyroidism also occurs in vitamin D-deficient rickets, malabsorption (when the intestines cannot properly absorb nutrients from food), and after some surgeries involving the intestines.^[4] A few other causes can stem from inadequate dietary intake of calcium or conditions that prevent the body from absorbing fats properly.^[7]

Who Is Affected

The most common causes of secondary hyperparathyroidism are vitamin D deficiency and chronic kidney disease.^[4] About 50% of the world population is affected by vitamin D insufficiency.^[4] Chronic kidney disease affects about 15% of the population in the United States.^[4]

In chronic kidney disease, there is a strong connection between the severity of kidney disease and the likelihood of having increased PTH levels. The more advanced the kidney disease, the more common secondary hyperparathyroidism becomes.^[4]

Symptoms

Many people with secondary hyperparathyroidism do not have obvious symptoms and may be diagnosed during routine blood tests.^[6] When symptoms do occur, they can include bone and joint pain, which are common, as well as limb deformities in severe cases.^[7]

Other symptoms may include:^[6]

• Muscle weakness
• Tiredness or fatigue
• Depression
• Trouble concentrating
• Loss of appetite
• Nausea and vomiting
• Confusion or forgetfulness

Patients with kidney failure and secondary hyperparathyroidism can often have PTH levels in the hundreds and even thousands.^[5] Occasionally, patients will develop a serious condition called calciphylaxis, where calcium deposits form in the skin and muscles, causing painful skin lesions that over time can cause tissue death and ulcers.^[5]

Diagnosis

Secondary hyperparathyroidism is often discovered when a blood test done for another reason shows abnormal calcium levels.^[3] The diagnosis is made by measuring PTH levels along with calcium, phosphate, and vitamin D levels in the blood.^[4]

In secondary hyperparathyroidism, PTH levels are elevated due to decreased levels of calcium or active vitamin D. It is usually seen in cases of chronic kidney disease or defective calcium receptors on the surface of parathyroid glands.^[7]

After diagnosis, healthcare professionals may recommend additional tests to check bone health and kidney function. These may include a bone density test to check if bones are weak or brittle, urine tests to see how well the kidneys are working, and imaging tests.^[10]

Treatment Options

The best treatment for secondary hyperparathyroidism is typically aimed at fixing the cause of the parathyroid problem.^[5] For patients with secondary hyperparathyroidism from vitamin D deficiency, the best treatment is raising vitamin D levels to the normal range.^[5]

For patients with secondary hyperparathyroidism from kidney failure, treatment consists of several approaches:^[7]

• Dietary restriction of phosphorus
• Phosphate binders (medicines that bind extra phosphate so it cannot be absorbed)
• Supplements containing active forms of vitamin D, such as calcitriol
• Calcimimetics—drugs that “trick” parathyroid cells into making less PTH

Calcimimetics can lower PTH levels by about 50% on average. The main side effects include nausea and vomiting.^[5] For patients with kidney failure, the only complete treatment is a kidney transplant. Most people with secondary hyperparathyroidism will improve after kidney transplantation, but many will continue to have some degree of residual hyperparathyroidism after the transplant.^[7]

Unfortunately, medical therapy does not work in up to 25% of patients, and surgery is sometimes necessary.^[5] Surgery is only done for patients in whom optimal medical therapy is not working.^[5] The main reasons for an operation include worsening bone density, severe uncontrollable itching, calciphylaxis, PTH levels that are consistently higher than 800, and inability to control calcium and phosphorus levels in the blood by dialysis.^[5]

The main types of surgery include removing most of the parathyroid tissue or removing all four parathyroid glands and placing a piece of parathyroid tissue in the forearm. However, since none of these operations fix the underlying cause of the secondary hyperparathyroidism, patients are at high risk for the disease to come back.^[5]

What Happens If Left Untreated

If left untreated, secondary hyperparathyroidism will progress to tertiary hyperparathyroidism, where correction of the underlying cause will no longer stop excess PTH secretion. This means the parathyroid gland enlargement becomes permanent.^[7] In contrast with secondary hyperparathyroidism, tertiary hyperparathyroidism is associated with high calcium levels rather than low calcium levels.^[7]

Long-lasting secondary hyperparathyroidism that doesn’t respond to treatment can cause the parathyroid glands to become permanently enlarged and continuously produce PTH.^[6] This condition has a high impact on illness and death rates in dialysis patients, mainly because of bone problems and calcium deposits in blood vessels and the heart.^[4]