Parathyroid tumors include adenomas, hyperplasia, and carcinomas. Adenomas and carcinomas are primary causes of primary hyperparathyroidism (PHPT), with adenomas being the most common, accounting for 80–85% of cases. Most adenomas are solitary, though some cases may involve multiple adenomas. Carcinomas are rare, comprising less than 6% of cases. Parathyroid hyperplasia accounts for approximately 10% of cases and often involves all parathyroid glands. It is usually secondary to renal insufficiency or long-term hemodialysis and is associated with secondary hyperparathyroidism (SHPT). Parathyroid tumors are surgically curable diseases.
Clinical Manifestations
In the early stages, there are typically no clinical symptoms. In later stages, excessive secretion of parathyroid hormone (PTH) by the adenoma, along with incomplete hormonal regulation, leads to hyperparathyroidism. Clinical manifestations can involve multiple systems and organs and present in a dispersed manner, which prevents initial diagnosis from being made by endocrinology or head-and-neck specialists. This often results in misdiagnosis or delayed diagnosis. Elevated PTH levels contribute to hypercalcemia and associated clinical damage through the following mechanisms:
- Stimulating osteoclast activity, which promotes bone demineralization.
- Enhancing renal tubular calcium reabsorption via cyclic AMP (cAMP).
- Increasing the activity of hydroxylase in proximal tubular cells, which converts low-activity 25-hydroxyvitamin D3 into the highly active 1,25-dihydroxyvitamin D3. This leads to increased gastrointestinal calcium absorption.
Severe bone demineralization eventually progresses to bone pain, fibrous osteodystrophy, and even fractures. Prolonged hypercalcemia increases calcium filtration by the glomeruli, potentially causing medullary sponge kidney, nephrolithiasis, and other complications. Anorexia and nausea are secondary to gastrointestinal damage caused by hypercalcemia. Fatigue, weakness, and lethargy are also commonly observed.
Clinically, parathyroid tumors can manifest as either asymptomatic or symptomatic forms. In Western countries, most cases are asymptomatic or have only nonspecific symptoms, such as osteoporosis, and are often diagnosed through screening due to elevated serum calcium levels. In contrast, symptomatic cases are more common in China, which differs from the epidemiology in Western countries. The reasons for this difference remain unclear.
Parathyroid tumor-induced hyperparathyroidism can be categorized into three clinical types based on symptoms:
Type I (Bone Disease Dominant)
This is the most common type and is primarily characterized by bone disorders. The average serum calcium level is 3.3 mmol/L, the average tumor weight is 5.9 g, and the average symptom duration is 3.6 years. Patients may experience bone pain and have a predisposition to fractures. Subperiosteal bone resorption is a characteristic feature, most commonly observed on the radial side of the middle finger or the outer third of the clavicle.
Type II (Kidney Stone Dominant)
This type is primarily characterized by nephrolithiasis. The average serum calcium level is 2.88 mmol/L, the average tumor weight is 1.05 g, and the average symptom duration is 6.8 years. Among patients with urinary tract stones, approximately 3% are found to have parathyroid adenomas. Prolonged hypercalcemia can lead to nitrogen retention without noticeable symptoms.
Type III (Mixed)
This type exhibits features of both Type I and Type II, with manifestations of skeletal abnormalities and urinary tract stones. Additional symptoms may include peptic ulcers, abdominal pain, neuropsychiatric symptoms, weakness, and joint pain.
Diagnosis
The diagnosis can be established based on clinical presentations of skeletal disorders and recurrent urinary tract stones, combined with hematological and imaging studies. Diagnostic differentiation is facilitated by recognizing clinical features of renal dysfunction and a history of long-term hemodialysis.
Qualitative Tests
Serum Calcium Measurement
This is the primary indicator for detecting hyperparathyroidism. Normal serum calcium levels may vary slightly between laboratories but generally fall within the range of 2.1–2.5 mmol/L.
Serum Phosphorus Measurement
Serum phosphorus levels have less diagnostic value compared to serum calcium. Normal serum phosphorus levels typically range between 0.65–0.97 mmol/L.
Parathyroid Hormone (PTH) Measurement
This test provides the most reliable direct evidence of hyperparathyroidism. In patients with parathyroid tumors, PTH levels are often several times higher than normal, rather than showing just a slight increase.
Urinary cAMP Measurement
In primary hyperparathyroidism, urinary excretion of cAMP is significantly elevated. This reflects parathyroid activity and aids in the diagnosis of hyperparathyroidism.
Renal Function Tests
Secondary hyperparathyroidism often presents with renal failure and elevated serum creatinine levels.
Localization Examinations
Ultrasound Examination
Normal parathyroid glands appear round or oval, with a diameter of 2–4 mm, and show low internal echogenicity. The gland is situated anteriorly to the thyroid and laterally adjacent to the common carotid artery and internal jugular vein. Adenomas typically present as solitary nodules, appearing as oval, elliptical, or elongated hypoechoic masses with well-defined borders. A thin capsule reflection may be visible, and the internal echogenicity is usually homogeneous, with an echo intensity significantly lower than that of thyroid tissue. When the tumor undergoes cystic degeneration or necrosis, the internal echogenicity may become inhomogeneous. Parathyroid hyperplasia manifests as enlargement of multiple parathyroid glands. Parathyroid carcinomas may exhibit calcifications or incomplete capsules.
CT Examination
On plain CT scans, adenomas exhibit lower density than normal thyroid tissue and are characterized by homogeneous density, resembling major neck blood vessels. Cystic degeneration or necrosis within the tumor may result in hypodense areas, sometimes presenting as cystic structures. Enhanced scans show significant contrast enhancement. Parathyroid hyperplasia is generally difficult to visualize on CT; in cases of marked hyperplasia, distinguishing it from adenomas can be challenging, although all four glands are often affected. Parathyroid carcinoma appears lobulated, with inhomogeneous density and incomplete capsules.
MRI Examination
MRI effectively detects abnormal signals from parathyroid lesions. Adenomas and hyperplasia typically show slightly increased signals on T1- and T2-weighted images with homogeneous enhancement. Parathyroid carcinoma generally manifests as an irregular lesion with inhomogeneous signals and inhomogeneous enhancement after contrast administration.
Radionuclide Scanning
Parathyroid tumors, particularly adenomas, have a high diagnostic value with radionuclide scanning due to the strong uptake of technetium-99m (99mTc) by chief cells. Parathyroid tumors appear on scans as rounded areas of radionuclide concentration with well-defined borders. Radionuclide scanning, being non-invasive and highly sensitive, demonstrates an accuracy rate exceeding 90% for tumor localization, making it a preferred routine method for parathyroid tumor assessment. However, radionuclide scanning offers limited information regarding tumor morphology, structure, and blood perfusion and lacks specific indicators to differentiate between benign and malignant tumors.
Treatment
Once a diagnosis of a parathyroid tumor is confirmed, surgical treatment is preferred, provided the patient's condition permits. Preoperative evaluation should include comprehensive data from imaging studies such as ultrasound, CT, and radionuclide scanning. During surgery, intraoperative rapid frozen section examination is routinely performed, with the surgical approach tailored to the specific characteristics of each tumor.
Postoperative Complications and Management
Patients should be carefully monitored postoperatively, with attention given to calcium and parathyroid hormone levels. Adequate calcium supplementation is required to minimize complications. Serum calcium levels may drop significantly within 24–48 hours after surgery, leading to symptoms such as numbness in the face, perioral region, or extremities. Severe cases may experience tetany. Intravenous administration of a 10% calcium gluconate solution can address hypocalcemia, with dosage adjusted to the severity of symptoms. Serum calcium levels typically normalize within 3–4 days postoperatively. A postoperative decrease in serum calcium often indicates successful surgical removal of the affected gland.