Primary hyperparathyroidism is an abbreviated form of hyperparathyroidism, which is a series of disorders of bone calcium metabolism caused by excessive secretion of PTH, increased renal reabsorption of calcium, increased urinary excretion of phosphorus, increased synthesis of p1,25(OH)2D, and increased bone resorption. According to the family history, the combination of other endocrine tumors and the type of endocrine tumors, hyperparathyroidism can be divided into sporadic hyperparathyroidism and hereditary hyperparathyroidism, including multiple endocrine adenoma type I (MEN1), multiple endocrine adenoma type IIA (MEN2A), and isolated familial hyperparathyroidism.
Clinical manifestations
(A) Manifestations of hypercalcemia: Symptoms due to increased blood calcium often affect multiple systems.
1. Psychoneurological manifestations: often dizziness p insomnia p weakness p apathy p depression, irritability, hypersensitivity, paranoia, memory loss, unresponsiveness, or severe headache, and occasionally mental excitement-oriented manifestations such as hallucinations and paranoia. Metabolic coma can occur when blood calcium is greater than 3.75mmol/L. Some patients can first appear delirium p followed by coma, which can even lead to sudden death.
2, gastrointestinal manifestations: when the serum calcium is greater than 3mmol/L, due to decreased smooth muscle tone of the digestive tract, gastrointestinal peristalsis is weakened resulting in loss of appetite p nausea p vomiting p constipation p abdominal distension p abdominal pain, etc. These symptoms may be partly due to hypercalcemia stimulation of gastric mucosa G cells to increase gastrin secretion resulting in peptic ulcers or complications of acute pancreatitis.
3, cardiovascular manifestations: hypercalcemia often has bradycardia, may also occur tachycardia and preterm contraction, typical ECG changes are Q-T interval shortening; may also have hypotension.
4, motor system performance: may have easy fatigue, limb muscle weakness, generalized pain p joint pain and muscle pain, mainly). For proximal muscle weakness, muscle weakness is often accompanied by myalgia, aggravated by exercise, and difficult to recover after rest, severe cases have muscle atrophy or even general failure, tendon reflexes are mostly normal. Electromyography shows decreased motor unit time frame, decreased amplitude, and increased polyphasic potentials, while motor nerve conduction velocity and terminal sensory potentials are mostly normal. These manifestations may be related to extensive soft tissue calcification.
5. Urological manifestations: hypercalcemia can inhibit the effect of ADH on distal tubular water reabsorption, therefore, in severe hypercalcemia, polyuria can occur, especially nocturia and polyuria, and even uremia; in addition, because PTH inhibits the renal tubular reabsorption of phosphorus, urinary phosphorus excretion increases, and patients are prone to kidney stones or renal calcification, urinary system infection and renal insufficiency.
(B) Skeletal lesions: The main manifestation is widespread bone and joint pain, mostly starting from the lower extremities and lumbar region, gradually developing to the whole body, and in severe cases, activity is limited, turning over is difficult, bedridden, and pathological fractures and bone deformities, such as thoracic collapse, hunchback and short stature, are likely to occur. However, in the past 50 years, the incidence of primary hyperparathyroidism has gradually decreased, and the degree of lesions has also tended to become less severe.
(C) Hyperparathyroidism nephropathy: Long-term hypercalcemia can affect the concentration function of renal tubules, increase urinary calcium and urinary phosphorus excretion, appear polydipsia and polyhydramnios, and secondly, cause.
1. multiple kidney or ureteral stones.
2, renal calcification.
3, renal hypofunction.
(iv) Other lesions.
1, soft tissue calcification: ectopic calcification of tendons, cartilage, etc., leading to non-specific joint pain.
2, skin calcium salt deposition: can cause itching of the skin.
3, hypertension: the incidence can be up to 50%, which may be related to hyperalgesia, but curing hyperparathyroidism cannot completely relieve hypertension.
4, anemia: severe patients can develop anemia, which is caused by fibrosis of bone marrow tissue.
5, cholelithiasis: hypercalcemia can cause limestone bile in the gallbladder and common bile duct, causing obstructive jaundice.
Second, laboratory tests
(A) elevated blood calcium: normal adult serum calcium concentration value is 2.10-2.63mmol/L. Changes in serum albumin concentration can change the total serum calcium value, every increase (decrease) of 10g/L of serum albumin will increase (decrease) the total serum calcium by about 0.2mmol/L. Determination of fasting sitting or lying blood can reflect the total calcium concentration more accurately. Serum calcium above 2.65 mmol/L is considered high; if it exceeds 2.75 mmol/L, hypercalcemia can be identified.
(ii) Elevated blood iPTH.
(iii) Urinary calcium: Urinary calcium excretion indirectly reflects the levels of blood calcium, PTH and 1,25(OH)2D. The upper limit of 24-hour urinary calcium excretion is 0.1 mmol per kilogram of body weight in a normal person with a daily calcium intake of 1,000 mg; if low calcium (400 mg/day) and low sodium (100 mmol/day) diet, the upper limit of 24-hour urinary calcium is 5 mmol.
(D) Blood phosphorus and renal function measurement: normal adult fasting blood phosphorus 0.87-1.45mmol/L, >1.45mmol/L is high blood phosphorus, <0.87mmol/L is low blood phosphorus. Hypophosphatemia is generally present in patients with hyperparathyroidism, but because blood phosphorus is also influenced by other factors such as diet and renal function, its diagnostic value for hypercalcemia is much less than that of blood calcium itself.
(E) Bone conversion biochemical measurements: Patients with primary hyperparathyroidism have accelerated bone resorption and bone formation, and are in a high conversion state. Therefore, serum (plasma) TRAP, urinary HOP, urinary (blood) NTX, ICTP, crosslap, urinary NTX, and iPTH and symptoms of hyperparathyroidism are reflected as indicators of bone resorption; blood OC, ALP (B-ALP), and PICP are reflected as indicators of bone formation. PICP were all elevated to varying degrees. However, in patients with malignancy-associated hypercalcemia, because of the unique characteristics of their bone tissue, i.e., bone resorption is decoupled from bone formation, and the increase in bone resorption is not accompanied by an increase in bone formation, the bone resorption index is high and the bone formation index is low in such patients, and this feature is helpful to differentiate them from patients with high PTH-secreting hypercalcemia.
III. Imaging examinations
(i) X-ray examination.
The degree of hyperparathyroidism in patients is positively correlated with the degree of osteoporosis. Different degrees of osteoporosis are shown on X-ray plain films as: subperiosteal bone resorption p reduction of bone trabeculae p thinning of bone cortex, and in severe cases, bone cyst formation p pathological fracture or skeletal deformity.
(B) CT of the neck and mediastinum: CT examination of the parathyroid glands is mostly used for localization and characterization on the basis of a clear diagnosis of hyperparathyroidism, and conventional CT is of little significance for localization of the parathyroid glands. Therefore, for parathyroid adenomas and hyperplasia, thin-layer and enhanced CT scans are mostly used to facilitate the display of small lesions.
(iii) Magnetic resonance imaging (MRI): conventional MRI examination usually cannot show normal parathyroid glands.
(iv) Neck ultrasonography: High-resolution real-time ultrasonography is also difficult to show normal parathyroid glands. However, due to the noninvasive nature of ultrasound, short operation time and repeatability, together with the clinical application of high-frequency high-resolution real-time ultrasound electronic scanner and Doppler color flow display (CDFI), it is still important for the characterization and localization of parathyroid gland lesions.
In addition, ultrasound-guided fine-needle biopsy is useful for the histological diagnosis of parathyroid gland diseases; ultrasound-guided percutaneous puncture injection of alcohol sclerotherapy for parathyroid adenomas has also achieved satisfactory efficacy and is expected to replace some of the surgical treatments.
(E) Radioisotope examination: parathyroid imaging is useful for preoperative localization of parathyroid adenoma and postoperative follow-up observation, and can show lesions with a diameter of 25px or more. Especially for those with a history of neck surgery, parathyroid imaging is not affected by neck scarring and fibrosis, and is helpful for preoperative determination of the location and number of parathyroid adenomas.
(vi) Bone mineral density measurement: bone loss in patients with primary hyperparathyroidism is dominated by cortical bone Kosowicz et al. concluded that the amount of bone mineral in cortical bone is less than 20% of that in reticular bone, which is a unique manifestation of hyperparathyroidism osteoporosis and can be used to differentiate osteoporosis in this disease from osteoporosis due to other causes.