Primary Hyperparathyroidism

What is Primary Hyperparathyroidism?

Primary hyperparathyroidism is a somewhat common health problem related to your body’s hormone regulation. It’s caused by an overproduction of parathyroid hormone (PTH) and too much calcium in the bloodstream. This condition can lead to kidney-related and bone-related complications. In most recent cases, patients have been found with mildly high levels of calcium in their blood.

In the past, hyperparathyroidism was often referred to as a disease of “stones, bones, groans, and moans.” This term was coined by Fuller Albright, which paints a picture of the symptoms – kidney stones, bone pain, abdominal discomfort, and changes in mental health. In the early stages, however, there might not be any symptoms. It’s also worth noting that conditions such as depression, anxiety, fatigue, cognitive dysfunctions like memory loss, and other psychological symptoms might occur in about 23% of patients severely inflicted with this condition.

Historically, hyperparathyroidism was diagnosed when patients suffered recurring kidney stones or bone diseases. It was also possible to see the effects of hyperparathyroidism on X-rays, where it could cause peculiar changes in your bones. However, now bone density scans can detect changes well before they show up on X-rays.

The condition itself is caused by the overproduction of PTH by one or more of the four small glands located towards the back of your thyroid gland. It’s important to note that these parathyroid glands are very small, about 6mm by 4mm, and weigh only between 20 to 40mg. Surgery is generally considered the most effective treatment but, under certain circumstances, observation or medication can also be appropriate.

It’s important to understand that the release of parathyroid hormone is controlled by a complex interaction among calcium levels in your blood, phosphorus, vitamin D, activated vitamin D, and a hormone called fibroblast growth factor-23 (FGF23). Mainly, calcium levels in your blood regulate the release of parathyroid hormone. A form of Vitamin D called Calcitriol also plays a part in reducing PTH release. Therefore, a basic understanding of how our body maintains calcium levels and the progression of primary hyperparathyroidism is essential for diagnosing and managing this disorder.

What Causes Primary Hyperparathyroidism?

Parathyroid glands are made up of two types of cells: Chief cells and Oxyphil cells. The chief cells produce a hormone known as PTH. Oxyphil cells are larger, but we don’t know exactly what they do yet-maybe they help chief cells with their task or do something else.

The secretion of PTH is connected to the level of ionized calcium in your body. If the calcium level goes up, the production of PTH goes down. The reverse is also true, if the calcium level goes down the production of PTH rises. PTH helps keep a balance in the body by managing the absorption of calcium and phosphate into your bones and also controlling the amount of calcium and phosphate your kidneys remove.

Now, you can have a situation in which your parathyroid glands produce too much PTH, and this is known as hyperparathyroidism. It’s actually one of the more common hormonal disorders, with diabetes and thyroid disorders being more prevalent. The main cause of hyperparathyroidism is usually a non-cancerous growth in one or all of the parathyroid glands.

There can also be cases where hyperparathyroidism is caused by a parathyroid cancer, but this is pretty rare. These cancers can be quite severe and often pose more of a threat due to the excessive amount of calcium in the blood than due to the cancer itself.

An entirely different condition named parathyromatosis can mimic parathyroid carcinoma. In this case, small nests of active parathyroid tissue are left over or get spread after surgery on the parathyroid gland leading to persisting hyperparathyroidism. This condition is rare and therapy is often a challenging task.

Sometimes, people can have high levels of PTH even though they have normal levels of calcium. This is called normocalcemic primary hyperparathyroidism. In many cases, this doesn’t need any treatment other than a periodic checkup.

On a different note, hyperparathyroidism can also be due to certain medications, for example, lithium. As with normocalcemic primary hyperparathyroidism, many who have this condition don’t show symptoms, and hence, don’t realize they have the condition.

Cancer, unfortunately, can cause a similar condition to hyperparathyroidism. The kinds of cancer most often associated with this condition are lung cancer and kidney cancer. They produce a protein that works the same way as PTH, leading to similar symptoms.

Lastly, there are genetic conditions that can cause hyperparathyroidism. They include multiple endocrine neoplasias, tumor-jaw syndrome, familial hypocalciuric hypercalcemia, and severe neonatal hyperparathyroidism. These conditions can often be identified by either certain early symptoms or a family history of specific diseases.

Risk Factors and Frequency for Primary Hyperparathyroidism

Primary hyperparathyroidism is the main cause of the high calcium levels in the blood that are often diagnosed in women after menopause. Women are three to four times more likely to develop this compared to men, especially during the ages of 50 and 60. Various factors can increase the risk of developing this condition, including certain genetic mutations, low calcium diet, obesity, extended use of specific medications like furosemide, previous neck radiation therapy, lithium therapy, high blood pressure, and lack of physical activity. Previously, thiazides were considered a risk factor, but recent studies have shown that they reveal existing parathyroid issues rather than causing them. If a person’s calcium blood levels remain high even after stopping thiazide therapy, it may suggest hyperparathyroidism.

The main reason for diagnosing primary hyperparathyroidism is due to widespread laboratory testing, which usually uncovers high calcium levels in the blood, even in symptomless patients. Before 1970, this condition was usually diagnosed due to specific symptoms like kidney stones or bone pain. Nowadays, most cases are diagnosed when blood tests ordered for other reasons reveal high calcium levels. In parts of the world where vitamin D deficiency is common and routine blood tests are infrequent, the disease is usually diagnosed due to symptoms like skeletal abnormalities and kidney stones.

• The incidence rate of hyperparathyroidism in the United States is estimated to be 233 per 100,000 women and 85 per 100,000 men per year.
• In North America, it’s more frequent among Black people than White people, with Asians and Hispanics having a lower incidence.
• Parathyroid cancer is very rare, representing less than 0.5% of all primary hyperparathyroidism cases. Usually, it is associated with higher calcium and PTH levels in the blood compared to benign primary hyperparathyroidism.
• There’s a connection between hyperparathyroidism and a genetic disorder known as hyperparathyroidism-jaw tumor syndrome, where up to 15% will develop parathyroid cancer. Other conditions associated with this syndrome include Wilms tumors, hamartomas, and polycystic kidney disease.

Signs and Symptoms of Primary Hyperparathyroidism

Primary hyperparathyroidism is a condition where the parathyroid glands, which control calcium use in the body, produce too much of the hormone that regulates calcium. In the past, this condition was often diagnosed due to patients experiencing kidney stones, bone pain, fractures, muscle weakness, or bone deformities. Nowadays, however, many people who have primary hyperparathyroidism show no symptoms and are only diagnosed when high calcium levels are found during routine blood tests.

Doctors will ask patients if they have a history of kidney stones, bone pain, muscle weakness, depression, or use of certain medications or supplements. Even though many patients are asymptomatic, up to 55% might have undiagnosed kidney stones or bone calcification, and up to 75% of those with symptoms may present with kidney pain or stones. Therefore, calcium levels in the blood should be measured in all patients with kidney stones. When calcium levels exceed 12 mg/dL, patients are more likely to notice symptoms such as:

• Loss of appetite
• Changes in mental state
• Constipation
• Dehydration
• Increased urination
• Increased thirst

About 40% of patients with primary hyperparathyroidism will also have high calcium levels in their urine. Patients who have both primary hyperparathyroidism and kidney stones remain at risk for future stones for up to 10 to 15 years after successful parathyroid surgery. It is recommended that patients with kidney stones undergo 24-hour urine testing even after successful surgery to minimize other chemical risk factors.

Physical examinations of patients with primary hyperparathyroidism are usually normal, however, it can help rule out other causes of high calcium levels. For example, parathyroid tumors are rarely palpable, but a large, firm mass in the neck of a patient with high calcium levels should raise suspicion of parathyroid cancer. Other potential symptoms and problems related to high calcium levels and hyperparathyroidism include:

• Abdominal pain
• Body aches
• Bone pain
• Heart rhythm problems
• Depression, memory loss, or forgetfulness
• Difficulty sleeping
• Constant Fatigue
• Fractures
• Frequent illnesses without apparent cause
• Headaches
• High blood pressure
• Joint pain
• Loss of appetite
• Muscle weakness
• Osteoporosis and increased risk of fractures
• Increased urination
• Difficulty concentrating

In rare cases, acute primary hyperparathyroidism or “parathyroid crisis” may occur. This is a potentially life-threatening condition characterized by sudden, extremely high calcium levels, often associated with parathyroid cancers. Calcium levels higher than 15 mg/dL can lead to coma and death and should be treated as a medical emergency. Treatments include intravenous fluids, medications, dialysis, and emergency surgery. In addition, patients may experience long-term bone complications due to high parathyroid hormone levels. This condition, known as osteitis fibrosa cystica, is rare but causes bone pain, swelling, decreased mineral density, and fractures. Treatment involves addressing the underlying parathyroid condition, often through surgery.

Testing for Primary Hyperparathyroidism

If you have high calcium levels in your blood, your doctor may suspect you have a condition called hyperparathyroidism. When looking for this, they’ll send you for lab tests. Usually, high calcium and low phosphate levels together suggest hyperparathyroidism. But to confirm it, you need a test that shows high calcium levels and signs of too much parathyroid hormone (PTH).

Sometimes, your body might have just enough PTH. But if it’s not lowering the amount of calcium in your blood, it’s still a sign of hyperparathyroidism. As you age, your PTH levels naturally increase. And if there’s not enough vitamin D in your body, your “normal” PTH levels will be higher than usual.

Some substances can affect hormones levels in your blood during tests. For example, biotin, also known as vitamin B-7, can mess with the accuracy of your PTH test. So if you’re taking biotin, you’ll need to stop and retest your PTH levels. Also, if you’re taking certain medications like lithium and thiazide, you might need to stop them for some months and retest your calcium and PTH levels. If PTH levels stay high, this points towards hyperparathyroidism.

Your doctor might order more tests to differentiate between primary hyperparathyroidism and familial hypocalciuric hypercalcemia, a genetically inherited condition. These tests measure the amount of calcium and creatinine (a waste product) in your urine over a 24-hour period. Family history and a review of your previous medical records can also be crucial, as most people with hyperparathyroidism have had high calcium levels for many years before they get a definitive diagnosis.

Imaging tests can help your doctor locate overactive parathyroid glands before surgery. These tests include neck ultrasound and special nuclear medicine scans. But sometimes, they can give false results or may not be useful if you have disease in multiple glands. Also, these imaging tests are most effective when performed by experienced technicians.

In some cases where the results of ultrasound and nuclear medicine scans are not clear, you may need a more detailed scan, like a 4-dimensional CT scan. This method gives a more detailed picture of your parathyroid glands and helps the surgical team with planning. There are newer imaging techniques being developed too that show promise in finding overactive parathyroid glands.

Your doctor might also order imaging tests for your bones. Why? Because hyperparathyroidism can significantly affect your bones. DEXA scans and similar techniques help assess the quantity and quality of your bone. Newer imaging technologies reveal that too much PTH can have more significant effects on your bones than previously thought. These tests help detect tiny bone changes and prevent fractures, which can occur even when the bone density appears normal.

Treatment Options for Primary Hyperparathyroidism

In 2022, a group of medical experts developed updated guidelines for handling a condition known as primary hyperparathyroidism. This condition is typically treated with surgery, but for some patients, especially elderly individuals with mild symptoms and no major complications, simply monitoring the condition may be more appropriate. Some patients may also be treated with medications. The decision whether to recommend surgery depends on factors such as age, severity of the disease and potential complications, as well as other health conditions the patient may have and the risk associated with surgery and anesthetics.

Patients who are not eligible for surgery may benefit from medical management of primary hyperparathyroidism. They should not avoid calcium as this could stimulate more production of PTH (parathyroid hormone). In cases of bone disease, calcium is often supplemented. Research has shown that chronic deficiency of vitamin D is a risk factor for hyperparathyroidism, so medical experts recommend supplements to ensure that patients with the condition maintain vitamin D levels above 30 ng/mL.

Monitoring is essential for patients receiving treatment for hyperparathyroidism. This could involve having yearly tests to measure levels of calcium and vitamin D, as well as kidney function. It may also include repeat tests for calcium excretion, abdominal imaging for calcifications, and x-rays of the spine if needed. Dexa scans, which measure bone density, are recommended either yearly or every other year.

Medications for primary hyperparathyroidism aim to treat low bone density or high calcium levels. Some drugs can reduce calcium but generally don’t increase bone density, whilst others improve bone density but aren’t very effective at reducing calcium. If both conditions need to be treated, a combination of therapies is usually recommended. These may include:

– Drugs like bisphosphonates and denosumab that can increase bone density
– Medications such as cinacalcet that activate the calcium-sensing receptor and can lower levels of PTH and calcium
– Estrogen therapy for postmenopausal women with primary hyperparathyroidism
– Oral phosphates that can reduce calcium levels.

However, the preferred treatment for hyperparathyroidism is still surgery, especially for patients with symptoms such as recurrent kidney stones or overt bone disease. Following surgery, patients usually experience a significant improvement in their bone density, a reduced risk of fractures and kidney stones and their calcium and PTH levels also normalize.

Even though surgery can be an option for all patients with primary hyperparathyroidism if agreed upon by both patient and doctor and no contraindications are present, it is usually performed by experienced surgeons to ensure success. It is considered the gold standard treatment for symptomatic patients.

Pre-surgery scans are recommended especially when a minimally invasive technique is used. These scans not only help find and locate abnormal parathyroid tissue but also verify the success of surgery. Abnormal parathyroid tissues can be removed successfully using minor surgical procedures, leading to an increase in bone density that can persist for up to 15 years.

However, untreated patients with primary hyperparathyroidism face progressive loss of cortical bone. These patients are recommended surgery if they develop symptoms, complications, worsening hypercalcemia, or experience events such as low trauma fracture or significant reduction in kidney function or bone density.

Finally, some patients can experience severe and prolonged low levels of calcium, known as “Hungry Bone Syndrome,” immediately after the surgical correction of primary or secondary hyperparathyroidism. This is often accompanied by low levels of phosphate and magnesium, and a spike in alkaline phosphatase. Treatment generally includes high dose oral supplements of calcium and vitamin D. If the calcium level is very low, intravenous calcium supplementation may be necessary.

What else can Primary Hyperparathyroidism be?

When a doctor is trying to identify the cause of primary hyperthyroidism, they’ll evaluate several conditions that may cause similar symptoms. They’ll use specialized tests to rule out these potential causes:

• Secondary hyperparathyroidism
• Normocalcemic primary hyperparathyroidism
• Familial hypocalciuric hypercalcemia
• Malignancy-related hypercalcemia
• Granulomatous diseases
• Hyperthyroidism
• Lithium therapy
• Thiazide therapy
• Milk-alkali syndrome
• Vitamin A intoxication
• Vitamin D intoxication

What to expect with Primary Hyperparathyroidism

In the United States, most patients with a condition called primary hyperparathyroidism are diagnosed when a routine blood test reveals higher than normal calcium levels. This condition is considered mild and without symptoms for about 80% of patients, with their test results remaining stable over a long period. However, over time, their bone strength (bone mineral density) may decrease.

Patients with significantly high calcium levels are at greater risk for complications and need to be considered for parathyroid surgery. This surgical procedure, known as parathyroidectomy, can effectively cure the disorder. The benefits of this surgery include improved bone strength and reduced risk of kidney stones (nephrolithiasis).

Possible Complications When Diagnosed with Primary Hyperparathyroidism

Complications of primary hyperparathyroidism, a condition of excessive parathyroid hormone in the blood, can be quite varied and severe. They can lead to:

• Loss of bone mineral density
• Fractures
• Bone pain
• Hungry bone syndrome, a high rate of bone mineral turnover
• Problems with the gastrointestinal system (stomach and intestines)
• Neuropsychiatric issues, which affect a person’s emotions, and how they perceive the world
• Nephrocalcinosis, a buildup of calcium in the kidneys
• An increased chance of developing kidney stones (nephrolithiasis)

Preventing Primary Hyperparathyroidism

It’s important for patients to understand all treatment options available for hyperparathyroidism, a condition where the body makes too much parathyroid hormone, causing disruptions in calcium balance. Even if you’re at higher risk or feel unsure about surgery, it’s crucial to understand that the only definitive solution to this problem is a procedure called parathyroidectomy, i.e., surgical removal of the affected parathyroid glands.

You should also prepare for the possibility of experiencing what’s known as “hungry bone syndrome” or low calcium levels in your blood (postoperative hypocalcemia) after surgery.

When executed by a skilled surgeon who specializes in parathyroid procedures, surgery can successfully treat over 90% to 95% of patients with primary hyperparathyroidism. This means surgery could be a viable option for all patients with this condition if both the patient and doctor agree and there are no reasons to avoid it.

If you choose to manage the condition with medicine alone, the importance of routine check-ups and diagnostic tests cannot be stressed enough as these will help monitor your condition’s progress.