Primary hyperparathyroidism

Introduction to primary hyperparathyroidism Hyperparathyroidism (hyperparathyroidism) is referred to as hyperparathyroidism. There are four parathyroid glands, which are closely attached to the inner side of the left and right sides of the thyroid. The gland is oval and flat, 5 to 6 mm long, 3 to 4 mm wide, about 2 mm thick, and 30 to 45 mg in weight; yellowish brown and soft. The parathyroid glands secrete parathyroid hormone, whose physiological function is to regulate the metabolism of calcium in the body and maintain the balance of calcium and phosphorus in the body. Primary hyperparathyroidism is caused by a single parathyroid adenoma (90%), less due to multiple adenomas or hyperplasia of the parathyroid glands, rarely due to adenocarcinoma. basic knowledge The proportion of illness: 0.001% Susceptible people: no special people Mode of infection: non-infectious Complications: urinary tract infection, coma, hypercalcemia

The cause of primary hyperparathyroidism

Causes

Primary hyperparathyroidism is caused by excessive secretion of parathyroid hormone caused by parathyroid adenoma, hypertrophic hypertrophy or adenocarcinoma, and its etiology is unknown. The pathological changes are as follows:

(a) parathyroid gland

There are three types of lesions.

Parathyroid adenoma

About 80% or more. Small adenomas are buried in normal glands, and the larger ones can be several centimeters in diameter. Adenomas have intact envelopes, often with cystic changes, hemorrhage, necrosis or calcification. Most of the tumor tissue belongs to the main cell, and it can also be composed of transparent cells. No residual fat cells can be found in the adenoma. 90% of lesions involve a gland, and multiple adenomas are rare. Adenomas can also occur in the ectopic parathyroid glands of the chest mediastinum, the thyroid gland, or the esophagus.

Hyperparathyroid hypertrophy

In recent years, it has been found that the number of cases caused by the proliferation of primary cells has increased (about 15%). When hypertrophic hypertrophy, the four glands are often involved, the shape is irregular, there is no capsule, and there are no cysts, hemorrhage and necrosis in the gland. The cell tissue is mainly composed of large water-like transparent cells with fat cells. Due to the tissue compression around the proliferative area, the formation of a pseudo-envelope is easily mistaken for adenoma.

Parathyroid carcinoma

The capsule, blood vessels and surrounding tissues have tumor cell infiltration, nuclear packing, and transfer.

(two) bones

The main lesions are osteoclasts or osteoblasts, bone resorption, varying degrees of bone decalcification, and connective tissue hyperplasia constitutes fibrous osteitis. In severe cases, it causes multiple cystic lesions and "brown tumors", which are prone to pathological fractures and deformities. Calcification is rare in neonatal tissues. Skeletal lesions based on bone resorption are systemic. The distribution of bone diseases is more obvious in the phalanx, skull, mandible, spine and pelvis. In addition, changes such as bone hardening may occur.

(III) Ectopic deposition of calcium salts

The kidney is an important organ for excreting calcium salts, such as urine concentration and acidity during excretion, and multiple urinary stones often occur. Calcium salt deposition can occur in the renal tubules or interstitial tissues. In addition, calcium salt deposition can occur in the lung, pleura, gastrointestinal mucosa, skin, and myocardium.

Pathogenesis

Due to excessive secretion of parathyroid hormone, calcium mobilizes from bone to blood circulation, causing hypercalcemia, while renal tubular reabsorption of inorganic phosphorus decreases, urinary phosphorus excretion increases, and blood phosphorus decreases. Due to the autonomy of the tumor and the high blood calcium, the parathyroid gland cannot be inhibited, so the blood calcium continues to increase. If the renal function is intact, the urinary calcium excretion will increase and the blood calcium will decrease slightly, but the continuous increase of parathyroid hormone , causing extensive bone resorption and decalcification, bone matrix decomposition, mucin, hydroxyproline and other metabolites increased from urinary excretion, formation of urinary stones or renal calciumosis (nephrocalcinosis), secondary infection and other factors Kidney function often suffers serious damage. In the later stage of renal insufficiency, phosphate can not be fully discharged, blood phosphorus concentration will rise, but blood calcium can be reduced, and stimulate the increase of thyroid secretion (secondary hyperfunction of tissues outside the tumor). Although the disease is mainly mobilized by osteoclasts, the osteoblast activity also has a compensatory increase, so serum alkaline phosphatase is increased every time.

Primary hyperparathyroidism prevention

The following conditions in PHPT are critical signs, should promptly correct high blood calcium, strive for early surgery, 1 long-term hypercalcemia lesions, such as kidney stones, kidney failure, fibrous cystic osteitis, hunchback, height shortening, false Sexual clubbing (indicating that there is severe osteitis at the end of the phalanx); severe myopathy, metastatic calcification (including lung, kidney, blood vessels, calcification of the joints and zonal keratopathy, "red eyes" caused by deposition of calcium phosphate in the conjunctiva" ), anemia (due to excessive PTH can induce bone marrow fibrosis and decreased hematopoietic function). 2 There are signs of severe hypercalcemia, such as blood calcium >3.5mmol / L (14mg / dl), as well as neuropsychiatric symptoms.

Primary hyperparathyroidism complications Complications, urinary tract infection, coma, hypercalcemia

Due to the destruction of renal tubular structure, the disease is complicated by repeated urinary tract infections, which eventually leads to the reduction of renal units, the formation of irreversible renal failure, and the concurrent parathyroid crisis. It is also called acute parathyroid gland. Hyperfunction, manifested as symptoms, coma, vomiting, polyuria, loss of water and other hypercalcemia syndrome, blood calcium more than 4.0mmol / L, necessary emergency measures, a small number of patients may have psychiatric symptoms such as hallucinations, paranoid , multiple endocrine neoplasia type I (gastrin, pituitary tumor, with parathyroid adenoma sometimes associated with gastrointestinal carcinoma, called Wermer syndrome) or type II (Sipple syndrome: pheochromocytoma, thyroid Medullary carcinoma with hyperparathyroidism).

Symptoms of primary hyperparathyroidism Common symptoms Loss of appetite, nausea, constipation, parathyroid function, hyperactivity, polyuria, skin itching, lethargy, weight loss, osteoporosis

The disease is more common in people aged 20 to 50, and more women than men. The onset is slow, and there are those who have discovered kidney stones repeatedly. There are bone pain as the main manifestation. Those with neurological symptoms are high in blood calcium, and those who have multiple endocrine neoplasia are also found. There are always asymptomatic people. The clinical manifestations can be summarized into the following four groups:

(1) Hypercalcemia and hypophosphatemia

For early symptoms, it is often overlooked.

1. Digestive system: There may be symptoms such as weak stomach, constipation, bloating, nausea, vomiting and the like. Some patients with duodenal ulcer disease may be related to the secretion of gastrin from the gastric mucosa by hypercalcemia. If accompanied by islet gastrinoma, such as Zollinger Ellison syndrome, peptic ulcer is difficult to treat, some patients may be associated with multiple pancreatitis, the cause is unknown, may be due to calcium deposition in the pancreas The pancreatic duct is blocked.

2. Muscle: The muscles of the limbs are slack, the tension is reduced, and the patient is prone to fatigue and weakness. Bradycardia, sometimes arrhythmia, ECG shows a shortened QT interval.

3. Urinary system: Because of the high calcium level, there is a lot of calcium excreted from the urine. Patients often complain of polyuria, thirst, and polydipsia. The incidence of urinary stones is also high, generally between 60% and 90%. Clinically, There are renal colic, hematuria or secondary urinary tract infection, which can cause renal damage and may even lead to renal failure after repeated episodes. The characteristics of urinary stones caused by this disease are multiple, recurrent, bilateral, and stones often have increasing and increasing activity, together with renal parenchymal calcium deposition, which has diagnostic significance for this disease. Renal tubular calcium deposition and calcium deposition can cause renal failure. In general urinary stones, about 2% to 5% are caused by this disease.

In addition to the above-mentioned syndromes, ectopic calcification of the renal parenchyma, cornea, cartilage or pleura may occur.

(two) skeletal symptoms

There is bone pain at the beginning, which can be located on the back, spine, hip, chest ribs or limbs, accompanied by tenderness. Lower limbs can not support weight, walking difficulties, often misdiagnosed as arthritis or muscle lesions; skeletal deformities gradually appear after a long time (some patients still have bone sacs such as local bulge). Shortened in length, can have pathological fractures, and even bedridden.

(3) Other syndromes

A small number of patients may have psychiatric symptoms such as hallucinations, paranoia, multiple endocrine neoplasia type I (gastrinoma, pituitary tumor, with parathyroid adenoma sometimes associated with gastrointestinal carcinoma, called Wermer syndrome) or type II (Sipple syndrome: pheochromocytoma, medullary thyroid carcinoma with hyperparathyroidism).

Examination of primary hyperparathyroidism

X-ray inspection:

The main changes seen on the X-ray were: 1 subperiosteal cortical absorption and decalcification. 2 cyst-like changes are less common. 3 fractures and/or deformities. Decalcification, fractures, and deformities of systemic bones such as the pelvis, skull, spine, or long bones are common in this disease, but are absorbed by the subperiosteal cortex of the phalanx, decalcified by the skull, and absorbed by the alveolar bone. And bone cysts form a good lesion of the disease (positive rate of 80%), which is helpful for diagnosis. A small number of patients may still have osteosclerosis and ectopic calcification. This morphological change of bone may be related to the effect of parathyroid hormone on osteoclasts and osteoblasts, calcitonin compensation and pathological glandular presentation. Intermittent activities related. Multiple recurrent urinary stones and renal calciumosis can be seen in the X-ray, which is valuable for diagnosis.

Laboratory inspection:

(A blood

1. Most of the early blood calcium is increased, which is most meaningful for diagnosis. If the blood calcium exceeds 2.7mmol/L (10.8mg/dl) repeatedly, it should be regarded as a suspected case, and more than 2.8mmol/L (11.0mg/dl) is more significant. In early cases, the increase in blood calcium is mild and can be fluctuating, so it should be repeated several times. Blood calcium is often maintained at normal levels and is extremely rare in this disease. However, when renal dysfunction occurs, blood calcium is often lowered, and there is a parallel relationship between serum calcium concentration and serum parathyroid hormone concentration and parathyroid tumor weight.

2. Most of the blood phosphorus is lower than 1.0mmol/L (3.0mg/dl), but the diagnostic significance is not as high as calcium. Especially in the case of renal dysfunction in advanced cases, phosphorus excretion is difficult and blood phosphorus can be increased.

3. Determination of serum parathyroid hormone: determination of serum iPTH and blood calcium can be divided into: 1 primary hyperparathyroidism requires surgery, 2 high calcium causes further examination of the two groups. In pathologically confirmed primary hyperparathyroidism, serum iPTH and calcium were significantly higher than normal in 90% of patients. If only the increase of blood calcium and iPTH is not increased, the increase of blood calcium caused by cancer or other reasons should be considered. The blood iPTH can also be significantly increased in secondary hyperparathyroidism, but the blood calcium is mostly normal or low. The normal serum values of a group in China were 23.5±0.12 in winter and 19.2±7.7pg/ml in summer.

PTH can be measured by radioimmunoassay (RIA), which mainly measures the middle or carboxy terminus of PTH, which is an inactive fragment. Although it is well correlated with clinical practice, it can be interfered by renal insufficiency. Therefore, the current use of dual-site immunoradiometric (IRMA) method for the determination of PTH full molecule, clinically relevant, the results are not interfered with kidney disease, can be well resolved normal, parathyroidism, primary hyperparathyroidism and tumor Caused by hypercalcemia.

4. Plasma 1,25(OH)2D: Excessive PTH in this disease can excite renal 1a-hydroxylase activity and increase plasma 1,25(OH)2D content. The normal serum values of a group in China were 13.2±3.8ng/ml in winter and 18.9±6.5ng/ml in summer.

5. Serum alkaline phosphatase: in the case of pure urinary stones, early can be normal, but there are bone disease manifestations, almost all increased to varying degrees, more than 12 gold units, sometimes up to 70 gold units.

6. Serum anti-tartaric acid acidity: Tartrate resistance acid phosphatase (TRAP) increased serum TRAP concentration when bone resorption and bone turnover increased. In this disease, serum TRAP is often doubled, and if the surgical treatment is successful, it can be significantly decreased within 1 to 2 weeks after surgery, and even reaches normal. The normal value of a group of Peking Union Medical College Hospital is 7.2±1.9IU/L.

(2) Increased urinary calcium and phosphorus excretion

Mainly because of increased blood calcium after renal tubular filtration increased, urinary calcium also increased. After 3 days of low-calcium diet (less than 150mg of calcium per day), 24-hour urinary calcium excretion can still be above 200mg, while normal people are below 150mg; if under normal diet, the urinary calcium often exceeds 250mg. However, the amount of urinary calcium excretion can be affected by many factors such as vitamin D and the intensity of sunlight, as well as the presence or absence of urinary stones. Therefore, the significance of urinary calcium should be analyzed. Acid should be collected when collecting urine to prevent calcium salt precipitation from affecting the results. If there is a urinary tract infection, there are still proteinuria, pyuria, hematuria and so on. In addition, it has been found that urinary cAMP and hydroxyproline excretion increase, and the latter increases the sensitivity of bone resorption.

(C) Cortisol inhibition test

A large number of glucocorticoids have anti-vitamin D effects (inhibition of intestinal absorption of calcium, etc.), which can reduce hypercalcemia caused by sarcoidosis, vitamin D poisoning, multiple myeloma, metastatic cancer or hyperthyroidism. However, the blood calcium caused by this disease is too high. The method is oral hydrocortisone 50 mg, 3 times a day for 10 days.

Diagnosis and differentiation of primary hyperparathyroidism

diagnosis

Diagnosis can be based on medical history, clinical symptoms, and laboratory tests.

Differential diagnosis

In the differential diagnosis, it is mainly caused by hypercalcemia caused by other causes and secondary hyperparathyroidism, such as cancer with or without metastasis, often with hypercalcemia, other such as multiple myeloma, nodules Disease (sarcoidosis), milk-alkali syndrome, vitamin D, thiazide diuretic poisoning, etc. have hypercalcemia, but generally can be inhibited by cortisol, and the disease is not inhibited by hypercalcemia. Serum alkaline phosphatase increased in this disease and myeloma was normal. In addition, secondary hyperparathyroidism must be distinguished.

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