Understanding Tertiary Hyperparathyroidism
Introduction
Tertiary hyperparathyroidism is a condition marked by the parathyroid glands’ overactivity, which often arises as a complication of longstanding secondary hyperparathyroidism, particularly in patients with chronic kidney disease. With a history that dates back to the early 20th century, tertiary hyperparathyroidism was initially discovered in dialysis patients, spotlighting an essential facet of chronic disease management. This article serves to clarify the nature of tertiary hyperparathyroidism, detailing risk factors, symptoms, diagnostic tests, medications, treatment procedures, and practical steps that patients can adopt at home to alleviate symptoms.
Description of Tertiary Hyperparathyroidism
Tertiary hyperparathyroidism is a complex disease that arises when the parathyroid glands – four small glands in your neck that control calcium levels in your body – produce too much parathyroid hormone (PTH). This excessive PTH release disrupts the delicate balance of calcium and phosphorus in the body, leading to a variety of health problems.
This condition represents the end stage of a progression that typically begins with primary hyperparathyroidism, where one or more of the glands become overactive. If left untreated, or in the case of certain underlying diseases such as kidney failure, this can progress to secondary hyperparathyroidism, wherein the body’s struggle to maintain calcium levels triggers all four glands to overproduce PTH. Tertiary hyperparathyroidism ensues when these glands start functioning autonomously, continuing to produce PTH even when the body has sufficient calcium.
As for the prevalence, exact figures are hard to pin down due to its association with chronic conditions like kidney disease. However, in the United States, it’s estimated that up to 10% of dialysis patients may develop tertiary hyperparathyroidism.
Risk Factors for Developing Tertiary Hyperparathyroidism
Lifestyle Risk Factors
Although tertiary hyperparathyroidism is primarily linked to pre-existing medical conditions, certain lifestyle factors can exacerbate its risk. Insufficient dietary calcium intake, vitamin D deficiency due to lack of sunlight exposure, excessive consumption of phosphorus-rich foods such as processed foods and soda, and obesity can all contribute to an increased risk of developing this disease.
Medical Risk Factors
The most significant medical risk factor for tertiary hyperparathyroidism is a history of long-term kidney disease or failure. Patients with chronic kidney disease often develop secondary hyperparathyroidism as their kidneys struggle to maintain calcium and phosphorus balance. Over time, this can progress to tertiary hyperparathyroidism. Furthermore, conditions that cause malabsorption, such as celiac disease or surgical removal of part of the intestine, can also increase the risk as they interfere with the body’s ability to absorb calcium.
Genetic and Age-Related Risk Factors
While not as common, certain genetic disorders, such as Multiple Endocrine Neoplasia type 1 (MEN1) and familial isolated hyperparathyroidism, can increase the risk of tertiary hyperparathyroidism. Additionally, age can play a role as the incidence of tertiary hyperparathyroidism appears to be higher in older patients, particularly those over 50 years of age. This may be due to age-related decline in kidney function and the cumulative impact of dietary and lifestyle habits over time.
Clinical Manifestations
Primary Hyperparathyroidism
Primary Hyperparathyroidism (PHPT) is a clinical manifestation that occurs in about 5% of patients with Tertiary Hyperparathyroidism. In PHPT, one or more of the parathyroid glands become overactive, causing a rise in parathyroid hormone (PTH) levels. This increase in PTH leads to higher calcium levels in the blood, causing a variety of symptoms such as kidney stones, bone pain, fatigue, depression, and cognitive difficulties. It is more common at the initial stages of the disease progression.
Secondary Hyperparathyroidism
Secondary Hyperparathyroidism occurs in nearly all patients with Tertiary Hyperparathyroidism. It develops as a compensatory response to chronic low calcium levels, often due to long-standing kidney disease. The body signals the parathyroid glands to produce more PTH to raise blood calcium levels, leading to enlargement of these glands. The resultant symptoms can include bone and joint pain, weakness, and cognitive changes.
Familial Hypocalciuric Hypercalcemia
About 2% of patients with Tertiary Hyperparathyroidism may show Familial Hypocalciuric Hypercalcemia. This is a genetic disorder that causes increased levels of calcium in the blood but decreased calcium in the urine. It often results in mild hypercalcemia that may go unnoticed due to the lack of severe symptoms.
Multiple Endocrine Neoplasia type 1
Multiple Endocrine Neoplasia type 1 (MEN1) is a rare inherited disorder, affecting less than 1% of Tertiary Hyperparathyroidism patients. MEN1 patients are at risk of developing tumors in their endocrine glands, which may lead to overproduction of PTH. The resultant high calcium levels may lead to kidney stones, bone loss, abdominal pain, and depression.
Vitamin D Toxicity
Vitamin D toxicity is a rare clinical manifestation in patients with Tertiary Hyperparathyroidism, affecting less than 1% of patients. It arises from taking high doses of vitamin D supplements, leading to excessive calcium absorption. Symptoms can include nausea, weight loss, heart rhythm problems, and kidney damage.
Sarcoidosis
Less than 1% of Tertiary Hyperparathyroidism patients might develop Sarcoidosis, a disease that leads to inflammation and granulomas in various body organs. Sarcoidosis can increase calcium levels in the blood and urine, leading to symptoms like fatigue, pain, and kidney stones.
Malignancy-related Hypercalcemia
Malignancy-related hypercalcemia occurs in about 1% of patients with Tertiary Hyperparathyroidism. It’s caused by certain types of cancer that produce a protein similar to PTH, leading to high calcium levels. This condition can cause severe symptoms such as thirst, frequent urination, nausea, and cognitive difficulties.
Thyrotoxicosis
Thyrotoxicosis, which is a condition resulting from an excess of thyroid hormone, may occur in about 1% of Tertiary Hyperparathyroidism patients. The excessive thyroid hormone can increase bone resorption, leading to high calcium levels in the blood, causing symptoms like rapid heart rate, weight loss, and tremors.
Diagnostic Evaluation
The diagnosis of Tertiary Hyperparathyroidism is made through a series of blood and imaging tests to measure levels of certain substances in the body and visualize the parathyroid glands. The evaluation aims to establish a high level of PTH alongside high calcium levels, which distinguishes tertiary from secondary hyperparathyroidism.
Serum Calcium Test
A serum calcium test measures the amount of calcium in your blood. The test is straightforward and involves drawing a blood sample from a vein in your arm. It is an important test for diagnosing Tertiary Hyperparathyroidism as the condition is associated with high calcium levels in the blood. Calcium plays a critical role in many bodily functions, including bone health, nerve transmission, and muscle contraction.
For a diagnosis of Tertiary Hyperparathyroidism, results would typically show a serum calcium level above the normal range, which is usually 8.6 to 10.2 milligrams per deciliter (mg/dL). High calcium levels, combined with elevated PTH levels, suggest the diagnosis of Tertiary Hyperparathyroidism. If the test comes back negative, it doesn’t necessarily rule out the condition, as calcium levels can fluctuate. Your healthcare provider may recommend further testing.
Serum Phosphorus Test
The serum phosphorus test, also a simple blood test, measures the level of phosphate in your blood. Phosphate, like calcium, is crucial for bone health. In Tertiary Hyperparathyroidism, your phosphate levels may be lower than normal due to the overproduction of PTH, which leads to excessive phosphate excretion through the kidneys.
Results indicating Tertiary Hyperparathyroidism would show phosphate levels below the standard range, typically 2.5 to 4.5 milligrams per deciliter (mg/dL). A low phosphate level, coupled with high calcium and PTH levels, can suggest Tertiary Hyperparathyroidism. However, if the test comes back negative (with normal phosphate levels), your healthcare provider will likely pursue other tests to confirm a diagnosis.
Serum Parathyroid Hormone (PTH) Test
The serum PTH test measures the amount of parathyroid hormone in the blood. This test, like the others, involves drawing blood from a vein in the arm. PTH plays a vital role in regulating calcium levels, and an overproduction of PTH is a hallmark of Tertiary Hyperparathyroidism.
For a diagnosis of Tertiary Hyperparathyroidism, the serum PTH test would show abnormally high levels of PTH. Along with elevated calcium levels, this can indicate Tertiary Hyperparathyroidism. If the test comes back negative, with PTH levels in the normal range, it may indicate that other factors are causing the symptoms, and further evaluation is required.
Serum Creatinine Test
The serum creatinine test measures the level of creatinine, a waste product that your kidneys filter out of your body, in your blood. This test provides information about your kidney function, which is vital because chronic kidney disease can lead to Tertiary Hyperparathyroidism.
In Tertiary Hyperparathyroidism, serum creatinine levels may be elevated, suggesting impaired kidney function. However, if creatinine levels are normal, it doesn’t exclude the diagnosis, especially in early stages of kidney disease. Further kidney function tests and imaging may be necessary.
24-hour Urine Calcium Excretion
This test measures the amount of calcium excreted in the urine over 24 hours. It’s done by collecting all urine produced over a 24-hour period for laboratory analysis. In Tertiary Hyperparathyroidism, urine calcium levels are typically high due to the excessive PTH leading to increased bone resorption and calcium release.
A 24-hour urine calcium excretion test revealing high levels of calcium can indicate Tertiary Hyperparathyroidism. However, normal levels do not rule out the condition, and further tests may be needed, especially if symptoms persist.
Bone Density Scan (DXA)
A Bone Density scan, or DXA scan, is an imaging test that uses X-rays to measure the amount of minerals, mainly calcium, in your bones. This test is important for Tertiary Hyperparathyroidism because the condition can lead to a loss of bone density due to high levels of PTH.
A DXA scan showing reduced bone density can support a diagnosis of Tertiary Hyperparathyroidism. However, normal bone density does not exclude the condition, especially in the early stages. Your healthcare provider may recommend additional tests based on your symptoms and medical history.
Sestamibi Parathyroid Scan
A Sestamibi parathyroid scan is a specialized imaging test designed to visualize the parathyroid glands. It involves injecting a small amount of a radioactive substance called Sestamibi into the body, which is absorbed by the parathyroid glands. The scan can identify overactive or enlarged glands, a key sign of Tertiary Hyperparathyroidism.
Results indicating Tertiary Hyperparathyroidism would show increased uptake or ‘hot spots’ at the site of the parathyroid glands. This suggests overactivity and possible enlargement of the glands. If the scan does not show abnormal uptake, it doesn’t necessarily exclude the diagnosis. Additional diagnostic tests or a different imaging modality may be required, especially if symptoms persist.
Ultrasound of the Neck
An ultrasound of the neck is a non-invasive imaging test that uses sound waves to create images of structures in the neck, including the parathyroid glands. While this test may not definitively diagnose Tertiary Hyperparathyroidism, it can provide valuable information about the size and location of the parathyroid glands and any potential abnormalities.
A neck ultrasound showing enlarged parathyroid glands can suggest Tertiary Hyperparathyroidism. However, normal ultrasound findings do not necessarily exclude the condition. Depending on the situation, your healthcare provider may order additional tests or a different type of imaging test.
4D-CT scan of the Parathyroids
A 4D-CT scan of the parathyroids is a sophisticated imaging test that provides detailed images of the parathyroid glands. The ‘4D’ refers to 3D images taken over time (the fourth dimension). This test is particularly useful in cases where other imaging tests haven’t provided clear results.
A 4D-CT scan showing enlarged or overactive parathyroid glands would support a diagnosis of Tertiary Hyperparathyroidism. If the scan is negative, further investigations may be necessary, particularly if symptoms continue or other test results suggest Tertiary Hyperparathyroidism.
What if all Tests are Negative but Symptoms Persist?
If all tests are negative but symptoms persist, it’s essential to discuss this with your healthcare provider. Tertiary Hyperparathyroidism is a complex condition, and its diagnosis can sometimes be challenging. Your provider may recommend repeating some tests or conducting additional ones. Furthermore, they might consider other potential causes for your symptoms. Patient experience is crucial in such scenarios; therefore, your input about how you’re feeling is invaluable. Remember, healthcare is a partnership, and your contribution is essential for achieving the best outcomes.
Health Conditions with Similar Symptoms to Tertiary Hyperparathyroidism
Primary Hyperparathyroidism
Primary hyperparathyroidism is a disorder in which one or more of the parathyroid glands produce excessive parathyroid hormone, leading to high levels of calcium in the blood. It’s often caused by a benign tumor or enlargement of these glands.
It shares symptoms such as bone pain, fatigue, and frequent urination with tertiary hyperparathyroidism. However, a distinguishing factor is that primary hyperparathyroidism typically occurs without prior kidney disease or vitamin D deficiency. Specific tests, like a serum calcium and parathyroid hormone test, can help differentiate these two conditions. Higher-than-normal levels of both calcium and PTH usually indicate primary hyperparathyroidism.
Secondary Hyperparathyroidism
Secondary hyperparathyroidism is a condition where the parathyroid glands produce excessive amounts of hormone due to low levels of calcium in the blood, often due to vitamin D deficiency or chronic kidney disease.
This condition shares many symptoms with tertiary hyperparathyroidism, including bone deformities and fractures, depression, and muscle weakness. However, secondary hyperparathyroidism often arises from long-term kidney disease, while tertiary hyperparathyroidism typically occurs after long-standing secondary hyperparathyroidism. Tests like serum PTH and calcium, as well as a kidney function test, can help distinguish between these conditions. In secondary hyperparathyroidism, PTH levels will be high, but calcium levels will be low or normal.
Familial Hypocalciuric Hypercalcemia
Familial hypocalciuric hypercalcemia (FHH) is a genetic disorder affecting the body’s ability to regulate calcium. People with FHH have high levels of calcium in their blood but low levels in their urine.
FHH shares symptoms with tertiary hyperparathyroidism, including excessive thirst and urination. However, FHH is generally a benign condition and doesn’t typically cause kidney stones or bone disease, unlike tertiary hyperparathyroidism. A 24-hour urine calcium test can help distinguish between these conditions. In FHH, despite high blood calcium levels, urine calcium levels are characteristically low.
Multiple Endocrine Neoplasia Type 1
Multiple endocrine neoplasia type 1 (MEN1) is a rare genetic disorder that primarily affects the parathyroid, pituitary, and pancreatic glands, leading to overactivity and tumors in these glands.
Like tertiary hyperparathyroidism, MEN1 can cause kidney stones, bone disease, and stomach ulcers. However, MEN1 also causes symptoms not typically seen in tertiary hyperparathyroidism, like pituitary and pancreatic tumors. Genetic testing can confirm a diagnosis of MEN1, and blood tests can identify hormone levels not usually associated with tertiary hyperparathyroidism.
Vitamin D Toxicity
Vitamin D toxicity, or hypervitaminosis D, occurs when there are excessive levels of vitamin D in the body, often due to over-supplementation. It can lead to hypercalcemia, causing symptoms similar to tertiary hyperparathyroidism.
Common symptoms of both conditions include nausea, excessive thirst, and kidney problems. However, a history of excessive vitamin D intake and blood tests showing extremely high vitamin D levels can differentiate vitamin D toxicity from tertiary hyperparathyroidism.
Sarcoidosis
Sarcoidosis is an inflammatory disease that can affect multiple organs but most commonly affects the lungs and lymph glands. In some cases, it can lead to hypercalcemia, causing symptoms similar to tertiary hyperparathyroidism.
Shared symptoms include fatigue, kidney stones, and bone pain. However, sarcoidosis can also cause lung problems, skin rashes, and eye inflammation, which are not typical in tertiary hyperparathyroidism. Tests showing elevated levels of serum angiotensin-converting enzyme (ACE) and abnormal chest X-rays can help differentiate sarcoidosis from tertiary hyperparathyroidism.
Malignancy-Related Hypercalcemia
Malignancy-related hypercalcemia is a condition where there are high calcium levels in the blood due to cancer. It’s most commonly associated with breast cancer, lung cancer, and multiple myeloma.
Common symptoms with tertiary hyperparathyroidism include excessive thirst, frequent urination, and kidney problems. However, a history of cancer and tests like a complete blood count, bone scans, and tumor markers can help differentiate malignancy-related hypercalcemia from tertiary hyperparathyroidism.
Thyrotoxicosis
Thyrotoxicosis is a condition characterized by an excessive amount of thyroid hormones in the body, often due to an overactive thyroid gland.
Thyrotoxicosis and tertiary hyperparathyroidism share symptoms like bone loss and irregular heart rhythms. However, thyrotoxicosis also includes symptoms like weight loss, anxiety, and tremors, which aren’t typical in tertiary hyperparathyroidism. Tests showing elevated levels of thyroid hormones and low thyroid-stimulating hormone (TSH) can differentiate thyrotoxicosis from tertiary hyperparathyroidism.
Treatment Options for Tertiary Hyperparathyroidism
Medications
Calcimimetics (e.g. Cinacalcet)
Calcimimetics, such as Cinacalcet, are medications that mimic calcium to control high parathyroid hormone levels. They are often used when parathyroidectomy isn’t an option or if waiting for surgery.
By increasing the sensitivity of the parathyroid glands to calcium, these medications reduce the amount of parathyroid hormone produced, thereby lowering calcium levels in the blood. Expected outcomes include relief from symptoms and potential prevention of further complications such as kidney stones and bone disease.
Vitamin D Analogs (e.g. Calcitriol)
Vitamin D analogs like Calcitriol are often used to treat tertiary hyperparathyroidism associated with chronic kidney disease.
These medications work by helping the body absorb more calcium from the diet, which reduces the amount of parathyroid hormone produced. Patients may expect an improvement in symptoms over weeks to months with regular use.
Phosphate Binders (e.g. Sevelamer)
Phosphate binders like Sevelamer are used to control high phosphate levels in patients with kidney disease, which can contribute to tertiary hyperparathyroidism.
These medications work by binding to dietary phosphate in the digestive tract, reducing its absorption and lowering levels in the blood. Expected outcomes include reduced parathyroid hormone levels and potential prevention of further complications.
Bisphosphonates (e.g. Alendronate)
Bisphosphonates, such as Alendronate, are medications used to slow bone loss and reduce the risk of fractures.
These drugs work by inhibiting bone breakdown, helping to balance the process of bone remodeling. Bisphosphonates are typically used in patients with tertiary hyperparathyroidism who also have osteoporosis. Patients can expect a decrease in bone pain and a reduction in the risk of fractures over time.
Calcitonin
Calcitonin is a hormone that helps regulate calcium levels in the body. In cases of hypercalcemia due to tertiary hyperparathyroidism, calcitonin can be used as a short-term treatment to quickly lower calcium levels.
It works by inhibiting bone resorption and increasing kidney excretion of calcium. While it’s not a long-term solution, it can provide rapid symptom relief in acute situations.
Procedures
Parathyroidectomy
Parathyroidectomy is a surgical procedure to remove one or more of the parathyroid glands. It’s often the definitive treatment for tertiary hyperparathyroidism.
This procedure is typically performed when medications can’t adequately control the disease or when there are complications like severe bone disease or kidney stones. Post-surgery, patients often experience normalization of calcium and PTH levels and significant symptom improvement.
Minimally Invasive Parathyroidectomy (MIP)
Minimally invasive parathyroidectomy (MIP) is a less invasive surgical option, where the surgeon removes the overactive gland through a small incision in the neck.
Used when a single gland is overactive, MIP involves less pain and a shorter recovery period compared to a conventional parathyroidectomy. Most patients experience significant symptom improvement and normalization of calcium levels following the procedure.
Radio-guided Parathyroidectomy
Radio-guided parathyroidectomy is a surgical procedure where a small, radioactive tracer is used to pinpoint the overactive gland(s).
This procedure is generally reserved for cases where previous surgery was unsuccessful or when the overactive gland is not in its usual location. Post-surgery, patients can expect normalization of calcium and PTH levels and symptom improvement.
Cryoablation
Cryoablation is a procedure where cold temperatures are used to destroy the overactive parathyroid tissue. This procedure is less invasive than surgery and may be used in patients who are not good candidates for parathyroidectomy.
It works by freezing the overactive tissue, which then gradually shrinks and disappears. Improvement in symptoms can be expected over weeks to months following the procedure.
Alcohol Ablation
Alcohol ablation involves injecting ethanol into the overactive parathyroid gland under ultrasound guidance. Like cryoablation, it’s less invasive than surgery and is often reserved for patients who cannot undergo parathyroidectomy.
This procedure works by causing the overactive tissue to shrink and scar, reducing its activity. Patients can expect symptom improvement over weeks to months post-procedure.
Improving Tertiary Hyperparathyroidism and Seeking Medical Help
In addition to medical treatments and procedures, certain lifestyle changes and home remedies can also help manage tertiary hyperparathyroidism symptoms and improve overall health. These include:
- Regular exercise: Regular physical activity can help strengthen bones and improve overall health. It’s essential to consult with a healthcare provider before starting a new exercise routine.
- Hydration: Staying well-hydrated can help prevent kidney stones, a common complication of tertiary hyperparathyroidism.
- Diet: A diet rich in calcium and vitamin D can help keep bones healthy. However, avoid excessive vitamin D supplements as they can lead to hypercalcemia.
- Reduced sodium intake: A low-sodium diet can help prevent fluid retention and high blood pressure.
- Limited alcohol intake: Excessive alcohol can interfere with calcium absorption and bone health.
- Avoiding thiazide diuretics: These medications can increase calcium levels in the blood and worsen hyperparathyroidism.
- Regular follow-ups: Regular kidney function and bone density tests can help monitor the condition and prevent complications.
Conclusion
Tertiary hyperparathyroidism is a complex condition that can significantly impact a person’s quality of life. However, with a comprehensive understanding of the condition, its causes, symptoms, and the various treatment options available, patients can actively participate in their healthcare decisions.
Early diagnosis and treatment are crucial in managing the disease and preventing complications. Regular follow-ups, adherence to medications, and adopting healthy lifestyle practices can also go a long way in living well with this condition.
At our telemedicine practice, we are committed to providing patient-centered care that is convenient and easily accessible. Our team of dedicated professionals is ready to assist with managing your condition from the comfort of your home. Don’t hesitate to reach out to us if you suspect you have symptoms of tertiary hyperparathyroidism or if you need help managing your condition.
Brief Legal Disclaimer: This article is for informational purposes only and not intended as medical advice. Always consult a healthcare professional for diagnosis and treatment. Reliance on the information provided here is at your own risk.