What is Secondary Hyperparathyroidism?
The parathyroid hormone is released by special glands in our body called the parathyroid glands. This hormone is involved in maintaining the balance of calcium in our bodies and bone health. The main factors that trigger the release of this hormone are low blood calcium levels and high blood phosphate levels. On the other hand, the activity of this hormone can be suppressed by a certain form of vitamin D, known as 1,25 (OH)(2) vitamin D(3).
There’s a condition called secondary hyperparathyroidism (SHPT), where the parathyroid glands become overactive due to persistent low calcium, high phosphate, or low active vitamin D levels in the blood. As a result, these glands produce and release an excessive amount of the parathyroid hormone. This then results in an increase in the level of calcium in the blood, drawn from the bones, intestines, and kidneys.
If secondary hyperparathyroidism continues for a long time, it can lead to problems with bone strength and formation, as well as abnormal mineral deposits in organs and blood vessels. This can contribute to heart disease and can increase the risk of death due to heart problems.
Despite advancements in medicines and drugs, in some severe cases of secondary hyperparathyroidism, surgery might be necessary. Kidney transplantation is another potential treatment, but quite often, the overactivity of the parathyroid glands may continue even after the operation.
What Causes Secondary Hyperparathyroidism?
Secondary hyperparathyroidism often goes hand in hand with a lack of vitamin D and chronic kidney disease. Basically, if your kidneys are not working properly, they can’t convert vitamin D into a useable form known as 1,25-cholecalciferol.
This kidney problem leads to poor absorption of calcium in the gut, causing low calcium levels in your blood and high levels of phosphate because the kidneys can’t get rid of phosphate as they should. The body responds to this by producing more parathyroid hormone, and if this process goes on for too long, the glands producing this hormone can become overgrown.
Secondary hyperparathyroidism can also happen in cases where there is vitamin D-deficient rickets, a condition that causes soft, weak bones in children, malabsorption, a condition where your intestines can’t properly absorb nutrients from food, and pseudohypoparathyroidism, a rare disorder that closely resembles another condition called hypoparathyroidism, but with a different underlying cause.
Risk Factors and Frequency for Secondary Hyperparathyroidism
Secondary hyperparathyroidism is mainly caused by a lack of vitamin D and chronic kidney disease. Vitamin D deficiency is common, affecting half of the world’s population. On the other hand, chronic kidney disease affects about 15% of people living in the United States. People with chronic kidney disease tend to have increased PTH (Parathyroid hormone) levels, which is a distinctive symptom of secondary hyperparathyroidism. There is also a strong link between the severity of the kidney disease and the likelihood of developing secondary hyperparathyroidism, with the risk being higher in people with advanced kidney disease.
- Secondary hyperparathyroidism is mostly caused by vitamin D deficiency and chronic kidney disease.
- About 50% of people worldwide have insufficient levels of vitamin D.
- In the U.S., chronic kidney disease affects around 15% of the population.
- Increased PTH levels, a key sign of secondary hyperparathyroidism, are commonly seen in people with chronic kidney disease.
- There is a strong association between the stage of chronic kidney disease and the likelihood of developing secondary hyperparathyroidism, with a higher risk observed in advanced stages.
Signs and Symptoms of Secondary Hyperparathyroidism
Secondary hyperparathyroidism, or SHPT, is a condition that disrupts the balance of calcium and phosphorus in the body, leading to various symptoms and complications. This disorder tends to affect the bones and soft tissues first, and in some cases, even the skin.
In SHPT, the process in which your body breaks down and rebuilds bones is affected, leading to skeletal deformities. These deformities can result in misshaped bones, bone pain, and even fractures in severe cases. Some people may experience deformities in the chest, spine, pelvis, hips, and legs due to abnormal bone healing. In children, these bone deformities can lead to a condition called rickets.
But it’s not just the bones that are affected in SHPT. The disease can also lead to a condition called calcification, where calcium deposits form in parts of the body. This can happen in arteries, tissues around joints, skin tissues, and even the eyes, leading to symptoms like muscle weakness, red eyes, and intense itching. This intense itching is often seen in people with advanced kidney disease due to calcium and phosphorus deposits on the skin. Calcification can also occur in the heart, leading to various heart conditions and increased risk of death.
In severe cases, SHPT can lead to a condition called calciphylaxis, where the skin breaks down and forms ulcers due to blocked arteries. This condition is often linked to high levels of parathyroid hormone (PTH), calcium, and phosphorus. Complications of calciphylaxis include an increased risk of infections and sepsis, or blood poisoning, leading to a higher risk of death.
Aside from the physical symptoms, SHPT can be associated with psychological and neurological problems and malnutrition.
Testing for Secondary Hyperparathyroidism
If your doctor suspects you have secondary hyperparathyroidism (SHPT), they will routinely check certain elements in your blood samples. These elements include parathyroid hormone, calcium, phosphorus, vitamin D levels, and the functionality of the kidneys.
Because SHPT can lead to issues with bone health, it is recommended that dialysis patients regularly check their bone mineral density. This is to assess if they are at risk of fractures that can occur from diseases causing your bones to weaken.
Some specific signs hint at bone problems related to SHPT when looking at X-ray images. An increased bone density, particularly in the spine and torso (referred to as “osteosclerosis”) can be a clue. Another sign is the so-called “Rugger jersey” spine sign. However, these changes might not mean your bones are strong. On the contrary, they may actually be quite vulnerable to breakages.
Osteomalacia, which is softening of the bone due to poor mineralization, is another bone condition that can be associated with SHPT, and presents with a specific sign referred to as “looser zones” on imaging.
One severe stage of SHPT is when a “brown tumor” appears in the bone. This reflects a lot of activity where your bone is being broken down by your body’s cells (osteoclasts) and there’s an increase in connective tissue cells (fibroblasts). These changes cause a visible change that can be seen on an X-ray or similar imaging, often appearing as a clear, defined area. These brown tumors often appear in hands, feet, facial bones, and skull. It’s worth mentioning though that these tumors can sometimes be mistaken for cancerous growths in the images.
Anther form of bone condition resulting from SHPT shows up as “osteitis fibrosa cystica” on an X-ray. This can present as bone absorption underneath the outer layer of your bones (especially at the ends of your fingers, collarbones, ulna bone in your arm, and skull). You might also see thinning of the outer layer of your long bones, bone cysts, and increased density of the spongy part of the bone.
Besides changes within the bone, there could also be calcifications around your joints, in your blood vessels, and in rare cases, inside your organs. However, there’s no defined guidance on lab or imaging tests specifically for these calcifications in patients with SHPT.
Treatment Options for Secondary Hyperparathyroidism
The treatment for secondary hyperparathyroidism (SHPT), a disease that causes changes in levels of calcium, phosphorus, and vitamin D in the body, aims to maintain normal levels of these substances and manage levels of parathyroid hormone (a hormone that helps control calcium levels in the blood). However, meeting the recommended guidelines for patient care, set by organizations like the U.S. National Kidney Foundation and the Kidney Disease Improving Global Outcomes, can be challenging over time.
Medications that bind to excess phosphate in the body or mimic the function of the parathyroid hormone, alongside vitamin D supplements, are used as part of the treatment plan. Modifications may also be made in the patient’s diet, such as limiting consumption of foods high in phosphate, which include soda drinks, meat, cheese, and other dairy products.
Phosphate binders come in different versions like those that contain or do not contain calcium. Binders that contain calcium are known to increase mineral buildup in blood vessels and soft tissues and may have lower survival rates compared to calcium-free binders.
Vitamin D supplements can lower parathyroid hormone levels and provide potential health benefits to patients suffering from chronic kidney disease. However, more thorough investigations are needed to substantiate these findings from previous observational studies.
Calcimimetics are drugs that increase the sensitivity of the calcium-sensing receptors in the parathyroid gland leading to reduced production of parathyroid hormone. These include cinacalcet and etelcalcitide, commonly used in dialysis patients. While these pharmaceuticals could suppress the parathyroid hormone, they may also cause side effects like nausea, low levels of calcium in the blood, irregular heartbeats, worsening heart failure, and convulsions.
If medical treatment for SHPT is unsuccessful or the disease proves resistant to it, surgery to remove the parathyroid gland, known as parathyroidectomy, may be considered. This might be required, for instance, if the patient’s condition involves calciphylaxis (a severe problem involving calcium forming within blood vessels), persistent itchiness, excess calcium or phosphorus in the blood, anemia resistant to erythropoietin (a hormone that stimulates the production of red blood cells), high levels of parathyroid hormone, and extra bone formation outside of the skeleton.
The size of the parathyroid gland can guide the decision for medical therapy or surgery. Glands that are larger than a certain size are usually unresponsive to medical treatment. It is estimated that about 15% of patients will need surgery within 10 years and 38% within 20 years after starting dialysis treatment.
Surgical techniques include subtotal parathyroidectomy, which leaves a small part of the gland, or total parathyroidectomy which removes the entire gland. Total parathyroidectomy sometimes includes a process called autotransplantation, where small amounts of healthy tissue are moved to a new location in the body. Although these surgical methods have similar outcomes, subtotal parathyroidectomy generally results in a shorter hospital stay and a lower chance of low calcium levels following surgery.
An unusual complication after surgery for secondary hyperparathyroidism is the “hungry bone syndrome,” which leads to a decrease in calcium levels. However, this can be prevented by administering high doses of calcium and using a special form of dialysis fluid rich in calcium after surgery.
What else can Secondary Hyperparathyroidism be?
When doctors consider a diagnosis of secondary hyperparathyroidism, they also think about two other related conditions – primary and tertiary hyperparathyroidism. Here’s what differs between them:
- In primary hyperparathyroidism, the parathyroid glands produce too much parathyroid hormone (PTH). This drives up the levels of calcium and phosphate in the body.
- In secondary hyperparathyroidism, the body has low calcium levels and high phosphate levels. This makes the parathyroid glands produce more PTH.
- As for tertiary hyperparathyroidism, the parathyroid glands produce extremely high levels of PTH. This results in both calcium and phosphorus levels being high in the body.
What to expect with Secondary Hyperparathyroidism
Secondary hyperparathyroidism can significantly affect a person’s life because of complications like disorders related to bones and minerals, heart-related complications, and calciphylaxis, a serious condition where blood clots block small blood vessels in the skin. Such complications might lead to symptoms including muscle pain, bone pain and even fractures.
Even though medical treatments aim to reach certain health goals as per kidney disease guidelines, there isn’t a lot of direct evidence suggesting that medications like vitamin D analogs or calcimimetics can improve survival rates. However, calcimimetics have been shown to enhance some outcomes. For example, they can increase the success rate of parathyroidectomy (a surgery to remove parathyroid glands), help avoid fractures and heart-related hospitalizations, and improve health-related quality of life.
Parathyroidectomy is necessary when medical treatment cannot control the disease. For patients with end-stage renal disease who are undergoing dialysis, the need for parathyroidectomy increases over time. Approximately 15% of these patients undergo the surgery in 5 to 10 years from the start of their dialysis. A study also showed that parathyroidectomy effectively relieved most of the initial symptoms within a week of the procedure. However, patients might continue to experience mild to moderate symptoms for as long as six months after surgery.
Procedures like surgery and medications such as calcimimetics can improve survival rates in early stages of chronic kidney disease when standard therapy is not effective. However, surgery has not been shown to offer any improvements in heart-related illnesses or death rates in patients with secondary hyperparathyroidism undergoing dialysis.
