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    Home > Active Ingredient News > Endocrine System > Don't panic when you encounter "refractory hyperthyroidism", practical experience in diagnosis and treatment will help you quickly advance!

    Don't panic when you encounter "refractory hyperthyroidism", practical experience in diagnosis and treatment will help you quickly advance!

    • Last Update: 2021-06-18
    • Source: Internet
    • Author: User
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    This article is published by Yimaitong authorized by the author, please do not reprint without permission
    .

     Introduction: Refractory hyperthyroidism accounts for as much as 50% to 60% of patients with hyperthyroidism, which brings great troubles to patients' work, study, marriage, love, and childbirth
    .

    So, how to treat refractory hyperthyroidism is not difficult? Let's look at a case first
    .

    The case patient, female, 23 years old, went to see a doctor because she had suffered from hyperthyroidism for 6 years and was now flustered for more than a month
    .

    When the patient was 15 years old, he was weight-loss due to palpitation.
    After checking T3 and T4, he was diagnosed with hyperthyroidism (Graves disease).
    He took 15 mg/day of methimazole.
    After 2 years, his symptoms improved significantly.
    Methimazole was changed to 2.
    5 mg/day.
    Stop the drug for 1 year
    .

    T3 and T4 were rechecked from time to time, and there was no obvious abnormality
    .

    At the age of 18, the patient was nervous about taking the college entrance examination, and suffered from palpitation and increased stool frequency.
    Repeated examinations of T3 and T4 indicated recurrence of hyperthyroidism.
    He continued oral methimazole treatment in the local endocrinology department.
    Symptoms were controlled after a few months and methimazole a year later.
    The imidazole was changed to 2.
    5 mg/day, and T3 and T4 were normal after repeated examinations
    .

    In the past month or so, the patient was under high pressure due to application for civil service examinations, and he experienced palpitation, palpitations, and increased stool frequency (2~3 times a day).
    Then he checked the thyroid B-ultrasound: second-degree thyroid enlargement, two lobes enlarged, and left lobe thickness 22mm , The thickness of the right lobe is 24mm, the thickness of the isthmus is 4mm, the capsule is smooth, and the inside is medium-high echo, uneven, and no abnormal echo clusters are seen
    .

    Thyroid work: TSH 0.
    01 mIU/L, FT311.
    94 pmol/L, FT4 25.
    31 pmol/L, liver and kidney functions are normal
    .

    Consider the recurrence of hyperthyroidism, give methimazole 15 mg/day orally, and maintain between 7.
    5 mg-10 mg after the symptoms are relieved, and recheck the thyroid function to be normal: TSH 2.
    95 mIU/L, FT3 4.
    36 pmol/L, FT4 5.
    22 pmol/L
    .

    During the period, there was a history of leukopenia, and after taking leukocyte-boosting medicine, it basically returned to normal
    .

    This patient has a 6-year medical history, during which the hyperthyroidism was cured and relapsed twice, which is a typical refractory hyperthyroidism, or recurrent hyperthyroidism
    .

    Studies have shown that the prevalence of refractory hyperthyroidism in China is 50% to 60% of patients with hyperthyroidism, and in some areas it accounts for 70% or more, which has brought great troubles to patients' work, study, marriage, love, and childbirth
    .

    So how to treat refractory hyperthyroidism is not difficult? The author makes a summary with reference to readers
    .

    Definition of refractory hyperthyroidism.
    Clinically, the stubborn and refractory hyperthyroidism that has been treated with regular drugs for more than 2 years, reached the standard of cure, and reappeared after stopping the drug, and persistent and refractory hyperthyroidism is called "refractory hyperthyroidism" or "hyperthyroidism recurrence"
    .

    Causes of refractory hyperthyroidism 1.
    Disease-related factors ➤The more obvious the thyroid enlargement, especially in patients with third-degree enlargement, the symptoms of hyperthyroidism are more difficult to control, and it is easy to relapse after stopping the drug; ➤If the TRAb continues to rise, it is easy to relapse; ➤18 For children and adolescents under the age of age who are in the growth and development stage, the symptoms of hyperthyroidism are more difficult to control and the recurrence rate is high; men are more likely to relapse than women; those with a family history are more difficult to control and relapse easily
    .

     2.
    Life>
    .

     3.
    Factors related to treatment ➤ Irregular use of antithyroid drugs (ATD): Insufficient use of drugs in the initial treatment period, improper drug reduction in the dose reduction period, too short medication time in the maintenance period or too small doses, which may lead to recurrence of hyperthyroidism ➤Improper choice of treatment method: different causes of disease, treatment methods are also different
    .

    Inappropriate method selection, the curative effect is naturally poor
    .

    Individual patients are not sensitive to ATD.
    If ATD is used for treatment, hyperthyroidism is difficult to control; ➤Worries about drug side effects: Many patients are worried about the side effects of drugs and inappropriately reduce or stop drugs and shorten the course of treatment, which leads to prolonged treatment of hyperthyroidism or recurrence after healing
    .

     Treatment of refractory hyperthyroidism The treatment of refractory hyperthyroidism mainly includes anti-ATD, iodine 131 therapy (also known as isotope therapy) and thyroidectomy.
    ATD is the most commonly used in China, but isotope therapy is commonly used in the United States; thyroidectomy is rarely used.
    For ordinary patients, it is not recommended to be the first choice, but for patients with severe goiter, large thyroid nodules (suspected of thyroid cancer), and patients who cannot receive the first two treatments, it is recommended
    .

     1.
    ATD is suitable for patients with high possibility of symptom relief (especially female patients with mild goiter and TRAb negative or low titer) and diseases that increase the risk of surgery, short life expectancy, or moderate to severe activities Patients with Graves' ophthalmopathy
    .

    ATD treatment is divided into three stages: control period (initial treatment period), dose reduction period and maintenance period
    .

    The most common cause of acupuncture-refractory hyperthyroidism is the problem of irregular use of ATD.
    The following treatment is recommended: ➤Control phase: Give a sufficient dose and give methimazole (MMI) 20-30 mg/day according to the patient’s condition.
    Or propylthiouracil (PTU) 100~150 mg/time, 3 times/day, usually onset after 1 to 2 weeks, after 4 to 8 weeks, the symptoms of hyperthyroidism can be relieved, FT3 and FT4 return to normal, and then enter the reduction Dosage phase; ➤Dose reduction phase: Generally, reduce once every 2 to 3 weeks, and reduce MMI 5-10 mg (or PTU 50-100 mg) each time.
    After 2 to 3 months, when the patient’s condition is well controlled, daily MMI When the dosage is 2.
    5-10 mg or the PTU dosage is 25-100 mg, it can be transferred to the maintenance phase; ➤Maintenance phase: at least 1.
    5 to 2 years or even longer.
    According to reports, long-term continuous MMI treatment is ≥5 years Graves disease has the highest remission rate of hyperthyroidism
    .

    Therefore, for hyperthyroidism caused by Graves disease, long-term MMI treatment has become an option for clinical management and better control of hyperthyroidism after ATD discontinuation, and low-dose long-term maintenance therapy is safe, and the occurrence of major adverse events is very rare
    .

    Note: At any stage of medication, especially when the patient suffers from infection or mental stimulation, the dosage of the medication should be increased, and the dosage should be gradually reduced as above after the condition is stable
    .

    ➤Drug discontinuation stage: For Graves disease hyperthyroidism, discontinuation requires not only a sufficient course of treatment, but also clinical manifestations of no hyperthyroidism.
    The thyroid gland is significantly reduced, and the TRAb in the two reexaminations is negative
    .

    It is currently believed that as long as the TRAb is positive, the course of treatment must be extended to continue the drug treatment, and then the drug should be discontinued according to the condition after becoming negative
    .

    ➤Relapse treatment: Refractory hyperthyroidism is characterized by easy relapse after stopping the drug.
    If you continue to receive ATD treatment, it is generally required to increase the dose during the maintenance treatment phase, such as the maintenance dose of methimazole 10 ~ 15 mg/day, and propylthiouracil maintenance The dose is 100 ~ 200 mg/day, and the course of treatment should be extended appropriately.
    During the treatment, you should still pay attention to regular monitoring of TRAb.
    If the antibody titer does not decrease, do not stop the drug in a hurry.
    After continuing the treatment, review the TRAb to turn negative, and then gradually reduce the dose according to the patient’s condition Discontinue the drug
    .

    2.
    Iodine 131 treatment Iodine 131 treatment is currently the safest treatment for hyperthyroidism, and it is also a powerful weapon for the treatment of refractory hyperthyroidism.
    Its one-time cure rate is about 85%, and the total cure rate is more than 95%.
    It is suitable for newly diagnosed hyperthyroidism, Patients with hyperthyroidism who have recurred after surgical treatment of hyperthyroidism or have not cured for a long time with drug treatment
    .

    This method has a high cure rate, a low recurrence rate (1% to 2%), and is safe and simple
    .

    Although 10% to 30% of patients will have hypothyroidism after treatment, it is easy to diagnose and simple to treat.
    Therefore, the proportion of treated patients has been on the rise in the past 20 years
    .

    Iodine 131 is the first choice for the treatment of hyperthyroidism in North American countries such as the United States and Canada, but it is contraindicated for pregnant women, breastfeeding women, and infants
    .

    3.
    Surgical treatment Generally, subtotal thyroidectomy is adopted, which has the advantages of definite curative effect, short treatment period and high cure rate (up to 90%)
    .

    Because of its invasiveness, it may cause damage to the recurrent laryngeal nerve and hypoparathyroidism.
    If the thyroid tissue is insufficiently removed, the patient will have recurrence of postoperative hyperthyroidism, so it is generally not the first choice
    .

    It is suitable for those who are eager to control hyperthyroidism in a short period of time (4-6 months), those who are preparing for pregnancy, giant goiter hyperthyroidism, hyperthyroidism combined with thyroid tumors, especially suspected or diagnosed as malignant, hyperthyroidism requiring surgery in the second trimester, suffering from In patients with severely active Graves ophthalmopathy, ATD treatment with serious adverse reactions (such as liver damage of more than 2.
    5 times the transaminase after taking the drug, leukopenia), and a long course of disease, no obvious improvement, and patients who are unwilling to receive isotope therapy how to prevent refractory The occurrence of hyperthyroidism 1.
    Adjust your life>
    .

     2.
    Grasp the indications and choose the appropriate treatment method.
    ATD treatment is suitable for patients with mild hyperthyroidism, pregnant or breastfeeding hyperthyroidism and those who do not agree to surgery or iodine 131 treatment; surgery is the first choice for autonomous high-functioning thyroid adenomas; ADT is not sensitive or Those with contraindications choose surgical treatment or iodine 131 treatment
    .

     3.
    Correctly dispose of the side effects of antithyroid drugs.
    The adverse effects of ATD are an important factor in clinically refractory hyperthyroidism.
    Many patients are worried about the side effects of drugs and inappropriately reduce or stop the drugs and shorten the course of treatment.
    Relapse
    .

    In order to effectively prevent the side effects of antithyroid drugs, clinical attention should be paid to the following points: ➤ Reasonable choice of drugs: From the perspective of safety, except for patients with hyperthyroidism and hyperthyroidism in early pregnancy, choose as far as possible with relatively small side effects and relatively safe Higher methimazole
    .

     ➤Check blood routine and liver function closely: Before and during medication, blood routine and liver function should be closely monitored.
    By comparing the test indicators before and after medication, it helps to identify whether the abnormality of the test result is caused by the drug or hyperthyroidism.
    Caused by itself
    .

    Since most of the side effects of ATD occur in the first 2 to 3 months of medication, the frequency of testing should be strengthened, especially in the first half month of medication, it is best to have blood routine and liver function tests twice a week.
    In order to find the problem in time
    .

     ➤Properly handle drug side effects as appropriate: Mild adverse reactions include: slight reduction in white blood cells or mild liver function abnormalities, rash, itching, gastrointestinal discomfort, etc.
    , which are mostly transient, and can be used to increase white blood cells, protect liver, anti-allergic, etc.
    Symptomatic treatment, if necessary, glucocorticoids can be added or antithyroid drugs can be replaced, generally do not need to stop the drug
    .

    Serious adverse reactions include agranulocytosis, acute liver necrosis, exfoliative dermatitis, anti-neutrophil plasma antibody (ANCA) positive small vasculitis, etc.
    Such patients must stop anti-thyroid drugs immediately and take active rescue measures
    .

    When the condition is stable, switch to radioactive iodine 131 or surgery
    .

     Conclusion In short, as long as refractory hyperthyroidism can actively deal with the causes of recurrence, standardize the use of antithyroid drugs, choose the correct treatment method, and effectively prevent the side effects of antithyroid drugs, it is not difficult to cure refractory hyperthyroidism clinically
    .

    Reference materials: [1] Ouyang Canhui, Zhang Chi.
    Research progress on factors affecting the recurrence of hyperthyroidism[J].
    Shandong Medicine,2020,60(05):91-94.
    [2]Guidelines for primary diagnosis and treatment of hyperthyroidism (Practice Edition·2019) [J].
    Chinese Journal of General Practitioners, 2019(12): 1129-1130-1131-1132-1133-1134-1135.
    [3] Zhang Junxia, ​​Xiang Guangda.
    Clinical treatment of refractory hyperthyroidism Strategy[J].
    Journal of Clinical Internal Medicine,2019,36(08):508-510.
    [4]Jia Xiaomeng,Hu Xiaodong,Lu Zhaohui.
    Clinical diagnosis and treatment of refractory hyperthyroidism[J].
    Chinese Journal of Practical Internal Medicine,2019, 39(04):316-320.

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