| disease | Parathyroid Osteodystrophy |
Parathyroid osteodystrophy refers to skeletal changes that occur under conditions of hyperparathyroidism. It was only about 50 years ago that hyperparathyroidism was recognized as a disease, initially thought to be very rare and difficult to diagnose. Later, it became clear that this condition is not uncommon, with diverse clinical manifestations affecting multiple systems of the body.
bubble_chart Clinical Manifestations
Hyperparathyroidism is more common in middle-aged women, accounting for 70%. Its clinical manifestations mainly include the following aspects:
(1) Skeletal changes: Cystic fibrous osteitis causes widespread bone pain throughout the body, most commonly in the lower limbs, often misdiagnosed as wind-dampness pain, lumbar muscle strain, or fibrositis. Cysts in the mandible can alter facial appearance, leading patients to seek dental care first. Occasionally, fibrous osteitis occurs at the ends of long bones, resulting in pathological fractures before the disease is diagnosed. Only one-fourth of hyperparathyroidism cases involve skeletal changes.
Radiographic findings show generalized multiple bone loss, presenting as cystic or osteoporotic patterns. The most diagnostically valuable early radiographic sign is subperiosteal bone erosion at the tips of the distal phalanges, which is more reliable than erosion of the lamina dura. Common sites of bone erosion include the outer third of the clavicle, the distal femur, the medial aspect of the femoral neck, and the medial aspect of the proximal tibia.
A few cases present as solitary cystic lesions, often seen in the femoral neck or knee, making diagnosis difficult.
(2) Urinary tract stones: This is a major manifestation of hyperparathyroidism, accounting for half of cases, with kidney stones being more common and renal calcification less frequent. A minority of cases exhibit both fibrous osteitis and renal calcification, often accompanied by elevated blood urea nitrogen. In cases with kidney stones alone, unless bilateral, blood urea nitrogen levels do not rise. However, renal calcification invariably leads to urea nitrogen retention, even in cases where fibrous osteitis is present without radiographic signs of calcification. Urea nitrogen retention is more likely in patients with fibrous osteitis than in those with kidney stones, suggesting that most kidney stone cases are primary hyperparathyroidism, while some fibrous osteitis cases are secondary hyperparathyroidism.(3) Hypercalcemia: Symptoms include generalized weakness, fatigue, anorexia, nausea, vomiting, constipation, thirst, nocturia, poor concentration, and drowsiness, which are often overlooked.
(4) Gastrointestinal manifestations: More common in primary and tertiary hyperparathyroidism, with upper abdominal pain and indigestion as the main symptoms. The primary cause of upper abdominal pain is concurrent peptic ulcer.
(5) Other aspects: Some patients may present with psychiatric symptoms and seek mental health care. There are also reports of hyperparathyroidism during lactation, leading to hypocalcemic convulsions in infants. A few cases exhibit scleral calcification. Parathyroid tumors are typically small and soft, making them difficult to palpate during neck examination.
bubble_chart Auxiliary Examination
(1) Hypercalcemia Normal blood calcium levels range from 9.0 to 10.3 mg/dl, and levels exceeding 10 mg/dl should raise suspicion of abnormality. More than 40% of serum calcium is bound to proteins, forming protein-bound calcium. The concentration of plasma proteins is related to plasma specific gravity. Since increases or decreases in plasma protein levels can cause the total serum calcium to rise or fall by approximately 0.25 mg/dl, the total serum calcium must be corrected using the normal serum specific gravity value of 1.027. In cases of hypoproteinemia, uncorrected blood calcium levels may appear normal, but after correction, the total blood calcium increases, and it is found that the dissociated calcium ions are elevated.
(3) Radioimmunoassay of Parathyroid Hormone Hypercalcemia is a necessary condition for diagnosing hyperparathyroidism. However, in a small number of cases, blood calcium levels are not elevated, or the hyperparathyroidism is intermittent, with calcium fluctuations of less than 1 mg%. Diagnosing such cases is very challenging. Currently, radioimmunoassay of parathyroid hormone can be performed.
The diagnostic criteria for hyperparathyroidism are: ①hypercalcemia, ②hypophosphatemia, and ③subperiosteal bone resorption at the tips of the distal phalanges. However, it still needs to be differentiated from many diseases, including multiple myeloma, osteoporosis, Paget's disease of bone, and even metastatic tumors. Needle biopsy is not helpful in diagnosing hyperparathyroidism; it can only exclude some diseases, and sometimes the biopsy may even cause confusion. Because giant cells can be found in the biopsy material, it is sometimes misdiagnosed as multiple giant cell tumors of bone, or even diagnosed as malignant giant cell tumors of bone due to the continuous appearance of lesions.
Locating and characterizing lesions in the parathyroid glands is even more challenging. Diagnosis can be made using selenium isotope scanning, selective stirred pulse angiography, and examination via the inferior thyroid vein catheter to measure the content of parathyroid hormone in the inferior thyroid vein.
bubble_chart Treatment Measures
Once the diagnosis is confirmed, surgery is the only effective treatment. Without treatment, bone lesions will progress to pathological fractures; if only kidney stones are removed, the stones will continue to form, and progressive renal impairment will occur. For hyperparathyroidism with bone lesions, the decision for surgery is not difficult. Contraindications for surgery include: ① cases in very poor general condition, ② grade III chronic renal impairment, even if not yet in the terminal stage, surgery is still not advisable.
The principle of surgery is to resolve the issue in one operation, and exploration of the mediastinum may be performed if necessary. A second surgery is highly challenging and should be avoided whenever possible. A single adenoma can be very small, barely larger than a normal parathyroid gland; adenomas may also be found in two parathyroid glands, while hyperplasia can involve all parathyroid glands. Therefore, the surgeon must be familiar with the anatomy of the parathyroid glands and their variations. Normally, individuals have four parathyroid glands, but some may have 2 to 6. The upper pair of parathyroid glands is mostly located at the posterior one-third of the thyroid, while the lower pair is mostly located behind the root of the nose of the thyroid. In a small number of cases, the parathyroid glands are located within the thyroid, with the majority situated within the thyroid capsule, and only a very few embedded within the thyroid tissue itself.
Patients with bone lesions usually have larger adenomas, while those with kidney stones have smaller ones. Higher blood calcium levels are typically associated with larger adenomas.
During surgery, locating the adenoma is generally not difficult. A brownish-yellow tumor can be seen when dissecting the thyroid, and it should be confirmed by frozen section after removal. Only confirmation as an adenoma can rule out parathyroid hyperplasia. If no obvious adenoma is found and it is uncertain whether parathyroid hyperplasia is present, a frozen section of the parathyroid should be performed. If the result shows normal parathyroid tissue, hyperplasia can be ruled out, suggesting the possibility of a very small, hard-to-detect adenoma or an ectopic parathyroid gland. If necessary, the upper posterior mediastinum may be explored. For cases where the parathyroid is located within the thyroid tissue, a thyroid lobectomy may be performed.
For parathyroid hyperplasia, three parathyroid glands should be removed, and the fourth should undergo subtotal resection, leaving about 50–150 mg of tissue, though it is difficult to determine the exact amount left during the procedure.
Parathyroid carcinoma should be excised along with the surrounding fatty tissue, and usually, adjacent thyroid tissue should also be removed.
Within 24 hours after removing the tumor or hyperplastic parathyroid glands, blood calcium levels drop to normal or even below normal. Because the repair of bone lesions post-surgery requires calcium, low blood calcium levels may persist for a considerable time, especially in patients with poor renal function. Therefore, patients with low blood calcium should be supplemented with vitamin D postoperatively. Severe hypocalcemia may lead to convulsions and finger numbness, which can be alleviated with calcium supplementation. In severe cases, intravenous calcium gluconate can quickly control convulsions.
After surgery, bone changes improve rapidly, with pain, muscle weakness, and systemic symptoms disappearing entirely within weeks or months. The improvement of bone demineralization takes longer, generally around 2 years or even more. Deformities will remain permanent. During the convalescence stage, calcium and vitamin D should be supplemented, and activity should still be restricted, as pathological fractures may still occur during this stage. Any orthopedic procedures should only be performed after the disease is under control.
