People's Daily health client reporter Qiu Yue
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Professor Xie Zhongjian, chief physician of the Department of Metabolic Endocrinology of the Second Xiangya Hospital of Central South University, said that according to estimates, the current patients with parathyroid reduction in the mainland are about 400,000. 78% of patients suffer from injuries or removal of the parathyroid glands during prenatural surgery, and a small proportion are due to genetic or autoimmune diseases.
◆ In addition to the blood calcium index that is difficult to stabilize, patients with parathyroid reduction also face frequent fluctuations in magnesium, phosphorus, potassium and other indicators in the blood. Often, patients with severe low calcium suddenly cause mouth crookedness, eye obliqueness, and atrial fibrillation, and are rescued by 120; some have epileptic seizures due to long-term inability to supplement calcium; and some have calcififications of the basal ganglia of the brain due to perennial phosphorus.
◆ For hypothyroid patients, they need to eat Yomethyl to supplement thyroid hormones, but the drug is almost not too affecting their lives for a day or two, and for patients with hypoparathyroidism, a meal of calcium tablets without eating will cause serious problems such as hand and foot twitches, heart twitches, and epilepsy.
"I had thyroid cancer for 35 years, and in 2010 I had all my parathyroid glands removed during total thyroid resection and lymphatic dissection, and I developed hypoparathyroidism for 12 years. I felt that parathyroidism was causing me even more pain in my life than thyroid cancer. On March 31, Begonia (pseudonym) told a Health Times reporter.
Parathyroidism, that is, hypoparathyroidism, is a rare endocrine disease, patients will be due to parathyroid hormone (PTH) secretion is too little and /or insufficient effect leading to systemic calcium and phosphorus metabolism disorders, causing hypocalcemia-based short-term symptoms and long-term complications, such as kidney stones, nephrocalcinosis, renal insufficiency, intracranial calcification, cataracts, etc. There are currently no targeted and effective therapeutic agents.
Begonia uses words to record the story of his symbiosis with disease. The picture is from @Tianya wind blowing begonias.
Every day is like being on the brink of life and death
The day after the total thyroid resection, Begonia learned that not only the thyroid gland but also four parathyroid glands were removed. From that day on, she needed a lifelong calcium supplement.
"In order to supplement calcium after the operation, I infused fluids continuously for more than 200 days, and I could not break it for a day, and later the blood vessels of my hands and feet were all punctured by needles, and there were large areas of bruises on the backs of my hands and feet." Begonia said.
After that, Begonia had to switch to oral calcium tablets, but after multiple iodine 131 treatments, the gastrointestinal function was seriously impaired, resulting in the amount of 8 calcitriol and 8 calcium tablets a day still unable to maintain her blood calcium at normal levels, and low blood calcium frequent attacks.
"During the period of low blood calcium, I often had numbness in my limbs, had a severe ant feeling, and when I was severe, I couldn't even walk on my feet, and I went to the emergency room several times overnight. In addition, due to the lack of regulation of parathyroid hormone, blood calcium fluctuates greatly, and it has also been emergency rescue due to hypercalcemia crisis. It felt like I was on the brink of life and death at any moment, and it was very painful. Begonia describes life now.
In addition to the difficult to stabilize blood calcium indicators, patients with parathyroidism also face frequent fluctuations in magnesium, phosphorus, potassium, carbon dioxide and other indicators in the blood. Begonia told the Health Times reporter, "In our group of patients, there are often patients who suddenly have severe low calcium caused by crooked mouth, oblique eyes, and atrial fibrillation, and are rescued by 120; some have frequent seizures due to long-term calcium supplementation; some have calcificing of the basal ganglia of the brain due to perennial phosphorus; more commonly, patients who have been ill for a long time suffer from kidney stones, cataracts and organ calcifications." ”
Professor Xie Zhongjian, chief physician of the Department of Metabolic Endocrinology of the Second Xiangya Hospital of Central South University and director of the Institute of Metabolic Endocrinology of Central South University, introduced that there is currently no large-scale epidemiological data on parathyroid reduction in the mainland. According to data from a population study in the United States, the prevalence of hypothyroidism in the United States is about 37/100,000, and another study shows that the prevalence of hypothyroidism in Japan is about 26/100,000, according to this data, the current patients with parathyroidism in China are about 400,000 people. Among the patients currently known in China, 78% of patients with injuries or removal of parathyroid glands during prenatural surgery account for 78%, and a small proportion are caused by genetic or autoimmune diseases.
"In recent years, with the increase in the incidence of thyroid cancer, patients with parathyroidism have also shown an increasing trend, and the acute clinical manifestations of parathyroidism include convulsions, laryngospasm, stridor, convulsions or epileptic seizures, etc. In the long run, patients will also have anxiety, depression, cataracts, hypersuria calcium, kidney stones, calcification of the central nervous system and so on." Professor Xie Zhongjian said.
There is no solution to the dilemma of treatment
"At present, the treatment of parathyroidism in the world is mainly to maintain the blood calcium level of patients by combining active vitamin D with calcium supplementation, but this treatment scheme is only a symptomatic treatment, hormone replacement therapy is the best choice for endocrine gland dysfunction, but the world has not yet developed the ideal hormone replacement drug." Professor Xie Zhongjian said.
There is no drug for the cause, the patient can only be temporarily relieved of symptoms, Begonia has witnessed a number of patients because of the inability to control blood calcium through drugs and sudden epilepsy or heart convulsions, and finally pulled away by ambulance rescue.
"Even if our blood calcium index is up to standard through calcium supplementation, it may not be able to make the body really feel comfortable, and it may not be guaranteed that we can cope with unexpected situations in life, such as mood swings, temperature changes or physiological periods, which may cause sudden hypocalcemia." Begonia said.
According to Begonia' recollection, one summer, due to the hot weather and the lack of ventilation in the environment at that time, she sweated a lot. Although she had just taken her medicine for less than half an hour, she still had convulsions. She immediately realized that there was a problem with blood calcium, and quickly replenished the dosage of the dose 2 times in a row, and the symptoms of convulsions gradually eased after an hour.
"Since the body has no ability to self-regulate blood calcium, encountering some special circumstances can lead to sudden hypocalcemia. We can't predict these environments, we can only guard against them at any time. I now have 3 days of medication when I go out to deal with unexpected situations. Begonia said.
Begonia uses words to record the story of his symbiosis with disease. The picture is from @Tianya wind blowing begonias.
According to Professor Xie Zhongjian, the human body has a sophisticated regulation system for blood calcium, once the human body perceives that the blood calcium concentration has decreased, the parathyroid glands will accelerate the synthesis and secretion of parathyroid hormone, while acting on the bones, kidneys and intestines, these organs will organically divide labor and cooperation, such as bones to increase bone absorption and release calcium, kidney synthesis of active vitamin D and promote the absorption of calcium by the intestine, thereby forming a perfect blood calcium regulation mechanism. The treatment regimen of active vitamin D combined with calcium can only act on the intestine, and the half-life is short, and the efficacy maintenance time is also very short, and the effect naturally cannot be compared with the regulatory function of parathyroid hormone.
"At present, there are four major treatment dilemmas in the treatment of parathyroidism." Professor Xie Zhongjian pointed out that first, the patient's blood calcium level is difficult to stabilize, in patients treated with active vitamin D combined with calcium, only about half of the blood calcium of such patients can be stabilized in the normal range; second, the level of blood calcium and urinary calcium in patients is difficult to take into account, often blood calcium standards, urinary calcium exceeds the standard, resulting in a great increase in the risk of kidney complications; third, the patient's ectopic calcification is difficult to improve, especially the calcification of the central nervous system will bring great risk to the patient's life Fourth, even if all indicators are controlled within the normal range, patients still often have anxiety, depression and other conditions, which seriously affects the quality of life.
A number of hormone replacement drugs have been approved abroad, but the effect is not ideal
"For patients with hypothyroidism, they need to eat Eucale to supplement thyroid hormones, but cutting off the drug for a day or two will hardly affect their lives, while for patients with hypothyroidism, a meal of calcium tablets without eating will cause serious problems such as hand and foot convulsions, heart twitches, epilepsy and so on." Begonia said.
The research and development of parathyroid hormone has actually been carried out for many years, at present, there are also some parathyroid hormone drugs used to treat osteoporosis in foreign countries that have been approved for the treatment of parathyroidism, such as recombinant human parathyroid hormone (1 to 34) and new recombinant parathyroid hormone (1 to 84), but these drugs have not been widely used.
In 2015, the US FDA approved the new recombinant parathyroid hormone (1 to 84) for the treatment of refractory hypothyroidism. The PHASE III clinical trial of the drug - REPLACE study showed that 50 to 100 μg / day, 1 time / day subcutaneous injection of new recombinant parathyroid hormone (1 to 84) can effectively reduce the need for calcium and vitamin D in adult patients with hypothyroidism, 43% of patients can stop vitamin D, and calcium requirements are also reduced to less than 500 mg per day.
"Because these two drugs have not been able to solve the bottleneck problem of half-life, far from achieving the purpose of maintaining the balance of calcium and phosphorus metabolism in the human body, most patients using this drug still need to continue to take calcium and active vitamin D, which increases the patient's medication burden, and the new recombinant parathyroid hormone (1 to 84) has poor improvement in urinary calcium, and due to the potential risk of long-term use caused by osteosarcoma, domestic and foreign guidelines only recommend it for supplementary treatment when conventional treatment is difficult to control." Professor Xie Zhongjian said.
Xie Zhongjian told the Health Times reporter that the treatment needs of patients with endocrine diseases are very simple, that is, what hormones are needed to supplement what hormones, but recombinant human parathyroid hormone (1 to 34) and the new recombinant parathyroid hormone (1 to 84) are drugs mainly used for the treatment of osteoporosis, and the mechanism of action of parathyroidism is not the same. Drugs treating hypothyroidism requires their blood levels to be consistently stabilized within the normal physiological range, but none of the currently approved drugs can do so.
"I heard that there are now long-acting parathyroid hormone drugs in clinical trials, and we are very much looking forward to the progress of science and technology that can bring dawn to our lives and allow us to truly get rid of the pain of disease and live a more quality of life." Begonia said.
Resources:
Mannstadt M, Clarke BL, Vokes T, et al. Efficacy and safety ofrecombinant human parathyroid hormone (1-84) inhypoparathyroidism (REPLACE): a double-blind, placebocontrolled, randomised, phase 3 study. Lancet DiabetesEndocrinol, 2013, 1(4): 275-283。
Latest progress: The parathyroid-acting therapeutic drug has entered Phase III clinical trials in China
TransCon PTH is a long-acting parathyroid hormone treatment for adult patients with hypoparathyroidism. The drug was developed by Danish biopharmaceutical company Ascendis Pharma, and Shanghai Weisheng Pharmaceutical, China, was responsible for the development and promotion of the treatment regimen in Greater China, and is currently undergoing Phase III clinical trials in China.
Lu Anbang, CEO and director of Weisheng Pharmaceutical, told reporters that although TransCon PTH has not yet been approved for listing at home and abroad, the results from foreign Phase III clinical data are very good. Positive data were obtained in phase III clinical trials abroad in March: the primary composite endpoint and all key secondary endpoints in the TransCon PTH group showed statistically significant improvements compared with the control group, with 78.7% of treated patients reaching the primary endpoint compared with 4.8% of patients in the control group.
Lu noted that the drug normalizes blood and urine calcium levels, serum phosphate levels, bone transitions, or addresses short-term symptoms and long-term complications in patients with hypoparathyroidism. TransCon PTH has also been granted orphan drug status by the U.S. Food and Drug Administration (FDA).
Based on the good data of foreign clinical trials, the phase III clinical trial of the drug in mainland China was approved in May 2021, and the first patient was successfully enrolled in the same year. Lu Anbang told reporters that the current recruitment of phase III clinical trials in China is still in progress. It is planned to be launched in 7 hospitals to recruit 500 volunteers. "If the domestic phase III clinical success, perhaps in the future, patients with parathyroid hypothyroidism can return to life like ordinary people by injecting a dose of hormone every day." Luanbang said. (Qiu Yue)
Related Reading:
Parathyroid tumor that was almost let go
I had a parathyroid tumor removal operation at Tampa General Hospital in Florida on December 12, 2013, with a size of 1.6 cm × 0.7 cm. Insomnia, hyperactivity, weakness... This tumor tormented me for 6 years, and even "evaded" the diagnosis of some doctors at one point.
In 2007, I began to have symptoms such as insomnia, hyperactivity, and poor sleep. The neurologist advised me to increase my exercises. However, if I don't exercise, I will lose my strength. Lying down at 10:30 p.m., waking up from a deep sleep at 12:00 p.m., sometimes halfway through the 500-meter road, I suddenly don't have the strength to walk the next half.
Parathyroid hormone was also done, and the results showed that the values were within the normal range. Seeing an endocrinologist, I checked the full set of parathyroid glands, and the results showed that blood calcium was lower than the normal high limit, blood VD was lower than the normal low limit, parathyroid hormone was normal, 24-hour urine calcium was close to the normal high limit, and isotope scans did not see any tumors and nodules. The diagnosis is not parathyroid gland disease, and the treatment is VD supplementation and calcium supplementation. However, after treatment, the blood pressure was higher, the heart rate disorder became more and more serious, the hip bone hurt so much that I couldn't sleep well, and I couldn't walk.
Finally, I thought of looking up online. The diagnostic criteria for parathyroid disease made me wonder: "Calcium in the blood was once above the normal limit" alone is enough to diagnose parathyroid disease. Immediately, I chose to have surgery.
More advanced isotopic scans clearly showed the tumor on the left side of my parathyroid gland! Eventually, the symptoms will eventually resolve.
According to Health Times, June 6, 2014, Issue 1126, 20th Edition, Chen Keqingwen, Maryland, USA