I. Overview
Hypothyroidism (hypothyroidism) is a systemic hypometabolic syndrome caused by decreased synthesis and secretion of thyroid hormones or insufficient tissue utilization. The prevalence of clinical hypothyroidism is about 1%, more common in women than in men, and the prevalence increases with age.
Classification
1. Classification according to the site of lesion occurrence.
(1) Primary hypothyroidism (primary hypothyroidism): hypothyroidism caused by the lesion of the thyroid gland itself, which accounts for more than 95% of all hypothyroidism. The three main causes of primary hypothyroidism are autoimmunity, thyroid surgery and treatment of hyperthyroidism (hyperthyroidism), which account for more than 90% of cases.
(2) Central hypothyroidism (central hypothyroidsm) or secondary hypothyroidism (secondary hypothyroidism): hypothyroidism caused by hypothalamic and pituitary lesions that reduce the production and secretion of thyrotropin-releasing hormone (TRH) or thyrotropin (TSH), among which hypothyroidism caused by hypothalamic lesions that lead to TRH deficiency is called triphasic hypothyroidism. Hypothyroidism caused by hypothalamic lesions is called tertiary hypothyroidism. External pituitary irradiation, pituitary macroadenoma, craniopharyngioma, and postpartum hemorrhage are the more common causes of hypothyroidism.
(3) Resistance to thyroid hormones: Hypothyroidism caused by impairment of the biological effect of thyroid hormones in peripheral tissues.
2. Classification according to the cause of the lesion:
For example, drug-related hypothyroidism; post-surgical or post-treatment hypothyroidism; idiopathic hypothyroidism; post-surgical hypothyroidism of pituitary or hypothalamic tumors, etc.
3. Classification according to the degree of hypothyroidism:
Clinical hypothyroidism (overt hypothyroidism) and subclinical hypothyroidism (subclinical hypothyroidsm).
Diagnosis
1. Medical history
A detailed medical history is helpful for the diagnosis of this disease. For example, thyroid surgery, 131I treatment for hyperthyroidism, history of Graves’ disease, Hashimoto’s thyroiditis and family history, etc.
2. Clinical manifestations
The onset of the disease is insidious, the course of the disease is long, and many patients lack specific symptoms and signs. The symptoms are mainly based on reduced metabolic rate and decreased sympathetic excitability, and early patients with mild disease can have no specific symptoms. Typical patients suffer from cold, weakness, swelling of the hands and feet, drowsiness, memory loss, low sweating, joint pain, weight gain, constipation, menstrual disorders or excessive menstruation in women, and infertility.
3.Physical examination
Typical patients may have sluggish expression, unresponsiveness, hoarseness, hearing impairment, pale face, facial and/or eye edema, thick lips and large tongue, often with teeth marks, dry, rough, flaky skin, low skin temperature, edema, ginger skin on the palms of hands and feet, sparse and dry hair, prolonged heel reflex, and slow pulse rate. In a few cases, pre-cavernous mucinous edema is present. The disease may involve the heart with pericardial effusion and heart failure. In severe cases, mucus edema coma can occur.
4.Laboratory diagnosis
Serum TSH and total T4 (TT4) and free (FT4) are the first-line indicators for the diagnosis of hypothyroidism. In primary hypothyroidism, serum TSH is increased and TT4 and FT4 are decreased. the level of increased TSH and decreased TT4 and FT4 correlates with the degree of the disease. Serum total T3 (TT3) and free T3 (FT3) are normal in the early stage and decreased in the late stage. Because T3 is mainly derived from the conversion of T4 in peripheral tissues, it is not used as a necessary indicator for the diagnosis of primary hypothyroidism. In subclinical hypothyroidism, only TSH is elevated, and TT4 and FT4 are normal.
Thyroid peroxidase antibody (TpoAb) and thyroglobulin antibody (TgAb) are important indicators for determining the cause of primary hypothyroidism and for diagnosing autoimmune thyroiditis (including Hashimoto’s thyroiditis and atrophic thyroiditis). The significance of TPOAb is generally considered to be more certain. Japanese scholars have confirmed that lymphocyte infiltration is present in the thyroid gland of TPOAb-positive patients by fine needle aspiration cytology of the thyroid gland. If a positive TPOAb is accompanied by an increase in serum TSH level, it means that thyroid cells have been damaged. After a 5-year follow-up of individuals with positive thyroid antibodies and normal thyroid function, our scholars found that the incidence of clinical hypothyroidism and subclinical hypothyroidism increased significantly in those with TPOAb >50IU/ml and TgAb >40IU/ml at the time of the initial visit.
5.Other tests
Mild to moderate anemia, total serum cholesterol and cardiac enzyme profile may be elevated. In some cases, elevated serum prolactin and enlarged butterfly saddle need to be differentiated from pituitary prolactinoma.
IV. Treatment
Treatment goal: clinical signs and symptoms of hypothyroidism disappear, and TSH, TT4, FT4 values are maintained in the normal range. Levothyroxine (L-T4) is the main replacement drug for this disease. Lifetime replacement is usually required; spontaneous remission of hypothyroidism due to Hashimoto’s thyroiditis has also been reported. In recent years, some scholars have suggested that the upper limit of serum TsH should be controlled at =300ug/L) can lead to a significant increase in the prevalence and incidence of autoimmune thyroiditis and subclinical hypothyroidism, and promote the development of hypothyroidism in people with positive thyroid autoantibodies; iodine supplementation in iodine-deficient areas to iodine excess can promote the development of subclinical hypothyroidism to clinical hypothyroidism. Therefore, maintaining iodine intake in the safe range of 100-199ug/L urinary iodine is the basic measure to prevent and treat hypothyroidism. It is especially important for susceptible people with genetic background, positive thyroid autoantibodies and subclinical hypothyroidism.
V. Subclinical hypothyroidism
The literature reports that the prevalence of subclinical hypothyroidism in the general population ranges from 4% to 10% in various countries. In the United States, the prevalence is 4.0%~8.5%, and in China, it is 0.91%~6.05%. The prevalence increases with age and is more common in women. The prevalence can reach about 20% in women over 60 years of age. The disease generally does not have specific clinical symptoms and signs.
Because the disease relies on laboratory diagnosis, it is important to exclude other causes of elevated serum TsH.
1, TSH measurement interference: the presence of anti-TSH autoantibodies in the subject can cause a false increase in serum TSH measurement;
2, recovery period of low T3 syndrome: serum TSH can be increased to 5-20mIU/L; the mechanism may be an adjustment of the body to stress;
3, 20% of patients with central hypothyroidism show mild TSH increase (5-10mIU/L);
4. Renal insufficiency: 10.5% of patients with end-stage renal disease have increased TSH, which may be related to slowed TSH clearance, excessive iodine intake, and loss of thyroid hormones bound to eggs;
5. Glucocorticoid deficiency can lead to mild TSH elevation;
6. Physiological adaptation: exposure to cold for 9 months increases serum TSH by 30% to 50%.
The main hazards of this disease are.
1, abnormal lipid metabolism and its resulting atherosclerosis:Some scholars believe that subclinical hypothyroidism is a risk factor for the occurrence of ischemic heart disease, which can cause disorders of lipid metabolism and abnormal heart function. The Rotterdam study concluded that subclinical hypothyroidism is an independent risk factor for ischemic heart disease, along with hypertension, hyperlipidemia, and hyperglycemia; a meta-analysis of 13 papers related to interventional treatment of subclinical hypothyroidism found that:L-T4 replacement therapy reduced serum total cholesterol and LDL cholesterol levels by 0.21 mmol/L ( 8 mg/dl) and 0.26 mmol/L ( 8 mg/dl), respectively, in patients with subclinical hypothyroidism. dl) and 0.26mmol/L (10mg/dl)] and increased HDL cholesterol by 0.26mmol/L (10mg/dl). Therefore, it is a concern to cut from the perspective of subclinical hypothyroidism to prevent and treat ischemic heart disease.
2. Development of clinical hypothyroidism: The British Whickham prospective study confirmed that the annual incidence of development of clinical hypothyroidism in simple autoantibody positive thyroid gland, simple subclinical hypothyroidism and autoantibody positive thyroid gland combined with subclinical hypothyroidism were 2%. Logstic regression analysis showed that TSH>6mIU/L (OR=3.4), positive thyroid autoantibodies (OR=5.3), and positive thyroid autoantibodies (OR=5.3) at the time of initial visit. Primary iodine deficiency supplementation to iodine overload (OR=8.0) were the influencing factors that thyroid function was not easily restored to normal in patients with subclinical hypothyroidism.
3. Subclinical hypothyroidism during pregnancy affects the neurointelligence of offspring.
In 2004, the American Thyroid Association (ATA), the American Academy of Clinical Endocrinologists (AACE) and the American Endocrine Society (TES) held a special meeting and reached the following consensus: the disease is classified into two conditions, the first is TSH>10mIU/L, and L-T4 replacement therapy is advocated; the goals and methods of treatment are the same as The goals and methods of treatment are consistent with clinical hypothyroidism, and serum TsH concentrations should be monitored regularly in replacement therapy, because L-T4 excess can lead to atrial fibrillation and osteoporosis. The second is that TSH is between 4.0 and 10 mIU/L, and L-T4 therapy is not advocated, with regular monitoring of TSH changes. In patients with TSH 4~10mIU/L with positive TPOAb, the change of TSH should be closely observed, because these patients are prone to develop clinical hypothyroidism. Current opinions on screening for subclinical hypothyroidism are also inconsistent. Some scholars suggest screening for this disease in high-risk groups, i.e. people over 60 years of age, those with a history of thyroid surgery or 131I treatment, those with a past history of thyroid disease, and those with a personal and family history of autoimmune disease.
VI. Pregnancy and hypothyroidism
Patients with clinical hypothyroidism have reduced fertility. Maternal hypothyroidism during pregnancy is associated with gestational hypertension, placental abruption, spontaneous abortion, fetal distress, preterm delivery, and the occurrence of low birth weight infants. In a 40-year retrospective study, the incidence of gestational hypertension was 3.8% in normal controls and 11.6% in clinically hypothyroid groups; spontaneous abortion was 3.3% and 8.0%; preterm birth was 3.4% and 9.3%; perinatal fetal death was 0.9% and 8.1%; and low birth weight was 6.8% and 22%, respectively. There is no sufficient clinical information on the pregnancy complications of subclinical hypothyroidism.
In recent years, the impact of maternal subclinical hypothyroidism in early pregnancy on the first stage of fetal brain development has received much attention. Until fetal thyroid function is fully established (i.e., before 20 weeks of gestation), maternal thyroid hormones are the primary source of fetal brain development, and maternal thyroid hormone deficiency can lead to impaired mental development in the offspring. Initial fetal brain development is directly dependent on T4 levels in the maternal circulation, but not on T3 levels. Haddow et al. first found that the offspring of mothers with hypothyroidism at 17 weeks of gestation, who were not given L-T4 treatment group, had 7 points lower intelligence quotient (IQ) at age 7-9 years compared to the offspring of normal control mothers; while the offspring of the group given L-T4 treatment group had no difference in IQ from the offspring of normal control group.
The reference ranges for TsH and thyroid hormones during pregnancy are different from those of the general population due to a number of factors. There are no pregnancy-specific TSH reference ranges. It is generally believed that the reference range of TsH in early pregnancy should be 30%~50% lower than that of the non-pregnant population. Currently, some international scholars have proposed 2.5mIU/L as the upper limit of the normal range of TSH in early pregnancy, and exceeding this upper limit can be diagnosed as hypothyroidism in pregnancy. Due to the large fluctuation of FT4 during pregnancy, it is internationally recommended to apply TT4 to assess the thyroid function of pregnant women. TT4 concentration increases during pregnancy and is approximately 1.5 times the normal value in non-pregnancy. If TSH is normal during pregnancy (0.3-2.5mIU/L) and only TT4 is below 100nmol/L ( 7.8ug/dl), hypothyroidism can be diagnosed.
Treatment.
If hypothyroidism has been diagnosed before pregnancy, the L-T4 dose should be adjusted to bring the serum TSH to within the normal range before considering pregnancy. During pregnancy, the L-T4 replacement dose is usually increased by 30% to 50% compared to the non-pregnant state. If you have no previous history of hypothyroidism and are diagnosed with hypothyroidism during pregnancy, L-T4 therapy should be administered immediately with the aim of bringing serum TsH to a specific normal range in pregnancy as soon as possible. Some foreign scholars suggest that this range should be 0.3-2.5 mIU/L. The earlier the standard is reached, the better (preferably within 8 weeks of gestation). After achieving the TSH standard, TSH, FT4 and TT4 should be monitored every 6-8 weeks. prospective intervention studies in pregnant women with subclinical hypothyroidism, hypotensive T4emia and TPOAb-positive women are being conducted in several countries and there is no consensus on treatment.
The American College of Clinical Endocrinologists advocates routine screening for TsH in pregnant women for the timely detection and treatment of clinical hypothyroidism and subclinical hypothyroidism. The prevalence of subclinical hypothyroidism in women of childbearing age is about 5%. Some authors advocate pre-pregnancy screening for those at high risk of developing hypothyroidism. High-risk groups for hypothyroidism include those with a personal and family history of thyroid disease; those with a history of goiter and thyroid surgery and 131I treatment; and those with a personal and family history of autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes mellitus. It is important to enhance education for women of childbearing age who already have hypothyroidism, so that they can understand the adverse effects of hypothyroidism on pregnancy and fetal brain development.
VII. Mucinous edema coma
Mucinous edema coma is a rare and life-threatening serious illness, mostly seen in elderly patients, usually triggered by concurrent diseases. Clinical manifestations include drowsiness, mental abnormalities, xerosis or even coma, pale skin, hypothermia, bradycardia, respiratory failure and heart failure. The prognosis of the disease is poor, with a 20% mortality rate.
Treatment.
1, remove or treat the causative factors: infection causative factors accounted for 35%.
2, supplementation of thyroid hormone:L-T4 300-400 ug immediately intravenously, followed by L-T4 50-100ug/d, intravenously until the patient can take it orally and then switch to tablets. If L-T4 injection is not available, L-T4 tablets can be ground up and administered nasally by gastric tube. If symptoms do not improve, switch to T3 (liothyronine) intravenously at 10 ug every 4 hours or 25 ug every 8 hours. The conversion of T4 to T3 is severely inhibited in mucinous edema coma, the oral preparation is poorly absorbed in the intestine, and too rapid and rapid supplementation of thyroid hormone can induce and aggravate heart failure.
3.Insulation: Avoid using electric blankets, as they can lead to vasodilation and insufficient blood volume.
4.Supplementation of glucocorticoids:Intravenous hydrocortisone 200~400mg/d.
5.Symptomatic treatment: with respiratory failure, hypotension and anemia take appropriate rescue treatment measures.
6.Other supportive therapy.
VIII. Central hypothyroidism
This disease is a decrease in thyroid hormone synthesis due to insufficient synthesis and secretion of TSH in the pituitary gland or TRH in the hypothalamus. In typical cases, serum TsH and thyroid hormones are shown to be reduced in TsH and TT4; however, basal serum TSH concentrations can be normal or mildly elevated (l0 mlU/L) in about 20% of patients.
The prevalence of this disease is 0.005 %. The highest prevalence is in children and adults aged 30 to 60 years. In children, the cause is craniopharyngioma, and in adults, the cause is macroadenoma of the pituitary gland, surgery and radiation therapy to the pituitary gland, head injury, Sheehan syndrome, and lymphocytic pituitaryitis. When treated with dopamine, TSH and T4 production can be reduced by 60% and 56% due to dopamine suppression of pituitary TSH production; in patients on long-term L-T4 replacement therapy, pituitary TSH suppression can persist for up to 6 weeks after withdrawal of L-T4. The disease often has gonadal and adrenal involvement, and attention should be paid to asking about related symptoms, such as postpartum absence of breast and amenorrhea in women, hypogonadism in men, lighter skin pigmentation, and loss of axillary and pubic hair. Both gonadal and adrenal cortical functions should be examined.
Differentiation of central hypothyroidism from primary hypothyroidism: The former is reduced and the latter is increased by basal TSH. When central hypothyroidism (mainly hypothalamic hypothyroidism) presents with normal or mildly elevated TSH, a TRH stimulation test is required to differentiate it. In typical hypothalamic hypothyroidism, the TSH secretion curve after TRH stimulation shows a delayed appearance of peak (60-90 min after injection) and a continuous hypersecretion state until l20 min; in pituitary hypothyroidism, the TSH response after TRH stimulation is sluggish and shows a low flat curve (less than 2-fold increase or increase).