Concept and pathogenesis
Secondary hyperparathyroidism (SHPT) is a syndrome in which the parathyroid glands are stimulated to overproduce parathyroid hormone by low blood calcium or high blood phosphorus due to various causes. SHPT is mainly seen in patients with chronic renal failure (CRF) and is one of the most important complications affecting the prognosis of patients with CRF or uremia. The exact mechanism is not fully understood.
Hazards:
The abnormal elevation of parathyroid hormone in SHPT not only causes hypertransformational osteodystrophy, but also involves the cardiovascular system, central and peripheral nervous system, and other endocrine glands, increasing the morbidity and mortality of patients.
Clinical manifestations
The clinical features of SHPT are characterized by clinical symptoms of multi-organ damage.
1, progressive bone pain, height reduction, pathological fractures, skeletal deformities, muscle lesions, and periarticular calcification.
2, Progressive aggravated pruritus, skin scratching, skin thickening, and grayish skin tone may occur; skin calcification.
3.Biochemical examination: hyperparathyroidism appears in the early stage of renal failure and gradually worsens. Alkaline phosphatase (ALP) is elevated, and both are elevated at the same time to reflect the state of high bone turnover, which has greater significance for diagnosis; unlike primary hyperparathyroidism where blood calcium is elevated, SHPT blood calcium concentration is reduced or normal, and blood phosphorus concentration is elevated or normal. If persistent hypercalcemia occurs, it often indicates the formation of autocrine parathyroid hyperplastic nodules or adenomas.
4. Hematologic system: progressive worsening of renal anemia, leukopenia, platelet insufficiency, and reduced efficacy of erythropoietin therapy;
5, X-ray examination can be seen diffuse bone decalcification or pathological fracture, bone deformity, bone fiber cystic change, sclerosis and other manifestations. Such as cranial speckle decalcification, long bone sparse change, sternal deformity, compression fracture of thoracolumbar spine, etc.
6.Radionuclide tomography (ECT) shows radioactive concentration areas (ranging from 2 to 4) in the neck, ultrasound can detect hypoechoic nodules in the neck, and CT or MRI can find hypointense shadow in the neck.
7. Other extraosseous tissues such as calcification, stenosis and incomplete closure of the heart valves may be present.
The pathological features of SHPT in uremia are related to the long-term stimulation of parathyroid glands by low calcium and high phosphorus and active vitamin D deficiency, resulting in proliferation and diffuse hyperplasia of parathyroid cells. Parathyroid hyperplasia may further develop into nodular hyperplasia, when SHPT becomes resistant to medical therapy and parathyroid hormone levels are further elevated and cause spontaneous hypercalcemia with the release of large amounts of calcium and phosphorus from the skeletal pool.
Pharmacological treatment.
1.Phosphorus lowering therapy ( using phosphorus binding agents)
2. Correction of low blood calcium (calcium salts or vitamin D preparations);
3.Activated vitamin D: The application of active vitamin D includes intravenous and oral, and oral is divided into daily low-dose and high-dose intermittent therapy;
4.Calcium-sensitive receptor promoter; (Sinacace)
Interventional therapy: Ultrasound-guided parathyroid anhydrous alcohol injection.
Surgical treatment.
In 1964, Mcphaul, first reported the successful treatment of chronic renal failure secondary to hyperparathyroidism by major parathyroidectomy, and the treatment has been gradually promoted abroad with remarkable efficacy. The American Kidney Disease Foundation K/DOQI, KDIGO and the Japanese Society of Dialysis Medicine guidelines recommend parathyroidectomy (PTX) as a surgical treatment for refractory SHPT with the core aim of preventing cardiovascular complications and improving the prognosis of patients. They proposed the following indications for surgical treatment of secondary parathyroid.
1, SHPT patients with persistent iPTH greater than 800 pg/mL (normal value 16-62 pg/mL) should be operated as soon as possible to stop the malignant consequences of the rapid development of bone disease if combined with the appearance of severe clinical symptoms, such as skeletal deformities, fractures and uremic small artery disease;
2. Persistent hypercalcemia and/or hypophosphatemia that are not treated with medication;
3, previous resistance to active vitamin D medication;
4. High-frequency color ultrasound of the neck showing at least one enlarged parathyroid gland, greater than 1 cm in diameter or 0.5 cm3 in volume, with abundant blood flow;
5. Normal liver function and coagulation index.
ECT to exclude other ectopic parathyroid glands. The contraindications are:
1, cardiopulmonary function cannot tolerate general anesthesia;
2, severe anemia or severe coagulation abnormalities;
3. Ectopic parathyroid glands outside the neck as confirmed by ECT. Relative contraindications are those who have severe systemic vascular calcification formation. The procedure has been gradually carried out in China, and it has been reported in the relevant literature that it is effective in relieving the symptoms of patients with secondary hyperparathyroidism after surgery.
Three surgical approaches are commonly used: subtotal parathyroidectomy, total parathyroidectomy + autotransplantation, and total parathyroidectomy. Total parathyroidectomy + autologous transplantation is the most common of the three. Subtotal parathyroidectomy is rarely used due to its high recurrence rate. There is a controversy among domestic scholars as to whether transplantation should be performed after total parathyroidectomy or not. There is a risk of akinetic bone disease due to parathyroid gland deficiency and the risk of bone injury not healing easily after total parathyroidectomy, and the recurrence of transplantation is also a problem that requires multiple operations. For this reason, some scholars have proposed a modified surgical approach, near-total parathyroidectomy, in which a very small portion of the four parathyroid glands explored, combined with pathological findings, is preserved in situ as a relatively normal gland. The comparative surgical results and recurrence rates of this approach are being further explored.
Preoperative examination: routine preoperative general examination: routine blood count, liver and kidney function, coagulation function, electrolytes, pretransfusion examination, electrocardiogram, chest X-ray, cardiac ultrasound, etc. to assess the patient’s tolerance for surgery. Other targeted special examinations: parathyroid and thyroid high frequency color Doppler ultrasound, ECT scan i.e. 99mTc-MIBI duplex scan; intact parathyroid hormone (iPTH).
Preoperative preparation: stop anticoagulants one week before surgery, take oral osteopontin 0.25ug twice a day, calcium carbonate 1.5~2g three times a day; perform heparin-free hemodialysis one day before surgery; exercise cardiopulmonary function.
Postoperative management: Routinely monitor vital signs after surgery, prepare tracheotomy kits at the patient’s bedside, and regularly observe incisional drainage and any respiratory difficulties. Pay special attention to the presence of convulsions and other symptoms of low calcium, and test serum calcium, phosphorus and alkaline phosphatase levels on the next day after surgery, and then recheck them once a day, and change to weekly tests after one week. Calcium supplementation principle: keep total serum calcium above 1.8 mmol/Ll, routine postoperative intravenous infusion of calcium gluconate or fasting oral calcium carbonate to reach elemental calcium 1~2g/d, oral bone triol 0.5μg/d; if serum calcium is lower than 1.8 mmol/L or convulsions occur, immediately give 1g of calcium gluconate intravenous push (each g of calcium gluconate contains 90mg of elemental calcium), and 1g of Calcium gluconate/h was maintained by micro-intravenous pump, while the oral calcitriol dose was increased to a maximum amount of 4 μg/d. Later, the intravenous calcium supplementation was gradually reduced and maintained by oral calcium supplementation + calcitriol; if the serum calcium was greater than 2.8 mmol/L, the amount of calcium preparation and calcitriol was reduced by half or discontinued. Half or full dose of heparin hemodialysis was performed after 1 to 2 days postoperatively depending on the wound condition.
Surgical complications: Hypocalcemia is the most common postoperative complication, which is considered to be caused by a rapid decline in parathyroid hormone and increased bone mineralization leading to bone starvation syndrome and delayed graft function. The blood calcium level needs to be closely tested, and calcium and vitamin D supplementation should be taken at the right time and in the right amount. other complications include laryngeal return nerve injury, wound infection, hematoma, wound dehiscence, hypotension, arrhythmia, and recurrence, which occur at a low rate.
Surgical results: According to the relevant data, after parathyroidectomy for patients with refractory secondary hyperparathyroidism, almost all patients with postoperative bone pain and skin pruritus were significantly relieved on the same day or the next day after surgery; most patients with other symptoms including muscle weakness, restless legs, insomnia, and dryness improved rapidly in the recent postoperative period; patients with regressed human syndrome stopped height shortening; some patients were unable to walk before surgery, and those requiring wheelchairs could walk on their own. Some patients who could not walk before surgery could walk independently on their own if they needed a wheelchair; the use of EPO was reduced and the effect after use was significantly improved compared with that before surgery; most of the detected parathyroid hormone levels could be reduced to normal levels, calcium and phosphorus indexes could be kept within the normal range, and the nutritional status was significantly relieved; some male patients’ sexual function could also be improved after surgery.
As mentioned above, secondary hyperparathyroidism is one of the most common complications of chronic renal failure, causing serious harm to several systems (especially the bone and joint system and the cardiovascular system) and seriously affecting the quality of life and survival of patients. It is worthwhile to promote this treatment so that more patients with uremic secondary hyperparathyroidism can benefit from it.