OVERVIEW

What is tertiary hyperparathyroidism?

Tertiary hyperparathyroidism (THPT) develops when secondary hyperparathyroidism (SHPT) fails to respond to effective treatment or control and progresses further.

Due to persistent and intense stimulation of the parathyroid glands, the already hyperplastic parathyroid tissue further proliferates or forms adenomas, leading to uncontrolled, autonomous overproduction of parathyroid hormone. This results in persistent hyperparathyroidism, hypercalcemia, and hypophosphatemia, which defines tertiary hyperparathyroidism.

Parathyroidectomy is an effective treatment for tertiary hyperparathyroidism.

Is tertiary hyperparathyroidism common?

Tertiary hyperparathyroidism (THPT) primarily occurs in some patients with end-stage renal disease (ESRD), which refers to the final stage of chronic kidney disease, similar to the concept of uremia, requiring treatments such as dialysis or kidney transplantation.

THPT is a relatively rare condition that arises when secondary hyperparathyroidism is not effectively treated or controlled and progresses further.

SYMPTOMS

What are the common symptoms and manifestations of tertiary hyperparathyroidism?

• Manifestations of the primary disease: Symptoms of chronic conditions that lead to this disorder, such as chronic renal insufficiency, X-linked hypophosphatemic rickets, long-term phosphate treatment for osteomalacia, intestinal malabsorption, vitamin D deficiency, and hydroxylation disorders (click related diseases for further details).
• Manifestations similar to primary hyperparathyroidism (click the disease for further details): Such as fractures, arthropathy, nephrocalcinosis, mental status changes, muscle weakness, peptic ulcers, pancreatitis, etc.

50%-80% of patients experience symptoms, but some may only show hypercalcemia in blood tests without obvious symptoms.

What other diseases can tertiary hyperparathyroidism cause?

Common complications of tertiary hyperparathyroidism include:

• Graft dysfunction: After kidney transplantation, prolonged hypercalcemia and increased urinary calcium and phosphate excretion due to restored renal function may lead to interstitial calcification, kidney stones, and an increased risk of graft failure.
• Bone metabolism disorders: Mainly characterized by a significantly increased risk of fractures.
• Vascular calcification: Persistent hyperparathyroidism and hypercalcemia can exacerbate vascular calcification, particularly coronary artery calcification, potentially increasing cardiovascular mortality.

CAUSES

What causes tertiary hyperparathyroidism?

Tertiary hyperparathyroidism develops when secondary hyperparathyroidism fails to be effectively treated or controlled, leading to further progression.

Conditions such as hypocalcemia, hyperphosphatemia, vitamin D deficiency, and elevated fibroblast growth factor 23 (FGF23) stimulate parathyroid cells, causing hyperplasia and excessive secretion of parathyroid hormone (PTH), resulting in secondary hyperparathyroidism. This primarily occurs in chronic kidney disease, X-linked hypophosphatemic rickets, osteomalacia with long-term phosphate therapy, malabsorption syndromes, and vitamin D deficiency or hydroxylation disorders.

Due to persistent and intense stimulation, the already hyperplastic parathyroid tissue further proliferates or forms adenomas. At this stage, regardless of blood calcium levels, the hyperplastic or adenomatous parathyroid glands autonomously overproduce PTH, exhibiting features similar to primary hyperparathyroidism, such as persistently high PTH, hypercalcemia, and hypophosphatemia. This condition is termed tertiary hyperparathyroidism.

Who is at risk for tertiary hyperparathyroidism?

Tertiary hyperparathyroidism mainly occurs in patients with chronic kidney disease, X-linked hypophosphatemic rickets, osteomalacia receiving long-term phosphate therapy, malabsorption syndromes, or vitamin D deficiency/hydroxylation disorders.

Is tertiary hyperparathyroidism contagious?

No, it is not contagious.

Is tertiary hyperparathyroidism hereditary?

Tertiary hyperparathyroidism itself is not hereditary, but some underlying chronic conditions (e.g., X-linked hypophosphatemic rickets) may be inherited.

DIAGNOSIS

How is tertiary hyperparathyroidism diagnosed?

When diagnosing tertiary hyperparathyroidism, doctors primarily consider the following:

• A history of long-term chronic illness;
• Prior long-term renal failure, severe vitamin D deficiency, hypophosphatemia, or prolonged phosphate therapy;
• Symptoms such as fractures, arthropathy, renal calcification, mental status changes, muscle weakness, gastrointestinal ulcers, or pancreatitis;
• Blood tests showing elevated calcium, decreased phosphorus, increased parathyroid hormone (PTH), and elevated urinary cyclic adenosine monophosphate (cAMP);
• Imaging studies (ultrasound, CT, MRI, or parathyroid scintigraphy) revealing hyperplastic or enlarged parathyroid glands.

These five criteria are generally sufficient to confirm a diagnosis of tertiary hyperparathyroidism.

What tests are needed to diagnose tertiary hyperparathyroidism?

Typically, blood, urine, and imaging tests are required.

• Blood tests: Include renal function, calcium, phosphorus, and PTH levels, showing impaired kidney function, hypercalcemia, hypophosphatemia, and elevated PTH.
• Urine tests: Mainly measure urinary cAMP, which is elevated.
• Imaging: Ultrasound, CT, MRI, or parathyroid scintigraphy can detect hyperplastic or enlarged parathyroid glands.

What precautions should be taken during parathyroid scintigraphy for diagnosing tertiary hyperparathyroidism?

Parathyroid scintigraphy is particularly helpful for diagnosing tertiary hyperparathyroidism, especially in patients with prior thyroid/parathyroid surgery or ectopic parathyroid glands.

Since calcium channel blockers may reduce the sensitivity of the scan, they should be discontinued before the test. Common calcium channel blockers include antihypertensive drugs like nifedipine, amlodipine, and felodipine.

Which diseases are easily confused with tertiary hyperparathyroidism? How to differentiate them?

Tertiary hyperparathyroidism and primary hyperparathyroidism both present with hypercalcemia and elevated PTH, making differentiation challenging.

The key distinction lies in medical history: tertiary hyperparathyroidism typically follows chronic renal failure or kidney transplantation, whereas primary hyperparathyroidism is not associated with long-term chronic kidney disease.

TREATMENT

Which department should I visit for tertiary hyperparathyroidism?

Endocrinology, Thyroid Surgery, Thyroid and Breast Surgery, General Surgery.

Can tertiary hyperparathyroidism heal on its own?

Tertiary hyperparathyroidism cannot heal on its own and requires timely treatment.

How is tertiary hyperparathyroidism treated?

The primary treatment for tertiary hyperparathyroidism is surgical removal of the parathyroid glands. The main surgical methods include total parathyroidectomy without autotransplantation, total parathyroidectomy with autotransplantation, and subtotal parathyroidectomy. Currently, total parathyroidectomy without autotransplantation is not recommended, as this method may lead to long-term hypoparathyroidism, severe hypocalcemia, and prolonged calcium replacement therapy.

For patients with contraindications to surgery, or those within one year after kidney transplantation with declining serum parathyroid hormone levels but experiencing hypercalcemia, cinacalcet may be an effective alternative under close monitoring to prevent risks such as loss of transplant kidney function due to hypercalcemia.

Does tertiary hyperparathyroidism require hospitalization?

Hospitalization is necessary for tertiary hyperparathyroidism when the condition is unstable or when surgical treatment is required.

What are the common side effects of medications for treating tertiary hyperparathyroidism?

When using cinacalcet, adverse reactions mainly include gastrointestinal effects (such as nausea, vomiting, and diarrhea), hypocalcemia (which may cause muscle spasms), and prolonged QT interval on electrocardiograms (posing a risk of arrhythmia).

It is recommended to start with a low dose of cinacalcet (25 mg/day) for safety, taking it after meals or with gastric mucosal protective drugs.

If a few patients cannot tolerate the side effects, the medication should be discontinued.

What are the common risks of surgical treatment for tertiary hyperparathyroidism?

The most common complication after parathyroidectomy is hypocalcemia. Other relatively common complications include hyperkalemia, surgical incision bleeding (since the surgery is performed in the neck, significant bleeding may compress the trachea, leading to respiratory distress and, in severe cases, life-threatening conditions), infection, and recurrent laryngeal nerve injury (manifesting as hoarseness).

DIET & LIFESTYLE

What should patients with tertiary hyperparathyroidism pay attention to in their diet?

• Patients who do not undergo surgery should avoid a high-calcium diet.
• Before surgery, a low-calcium diet may stimulate parathyroid hormone secretion, so moderate calcium intake is recommended. After surgery, hypocalcemia may occur, and a high-calcium diet should be adopted.
• Consume fiber-rich foods to maintain regular bowel movements.

Foods high in calcium include: milk and dairy products, soy milk, tofu, orange juice, and dark green leafy vegetables.

What should patients with tertiary hyperparathyroidism pay attention to in daily life?

• Limit physical activity appropriately, avoid heavy lifting, and ensure the bed is not too soft to prevent pathological fractures. When going out, be accompanied to prevent falls.
• Patients with existing fractures should rest in bed, elevate the affected limb, monitor blood circulation at the fracture site, turn over frequently to prevent pressure sores, and pat the back gently to prevent lung infections—while avoiding excessive movement to prevent new fractures.

PREVENTION

How to prevent tertiary hyperparathyroidism?

Tertiary hyperparathyroidism develops when the underlying causes of secondary hyperparathyroidism are not effectively addressed. Therefore, the key to preventing tertiary hyperparathyroidism is actively treating the primary conditions that lead to secondary hyperparathyroidism.

Additionally, for most patients with kidney failure, the parathyroid glands may already exhibit excessive hyperplasia or adenomas. If a kidney transplant is planned, it is advisable to undergo parathyroid surgery before the transplant to prevent refractory tertiary hyperparathyroidism and avoid potential dysfunction of the transplanted kidney.