In late 2012, the American Academy of Clinical Endocrinologists (AACE) and the American Thyroid Association (ATA) jointly issued guidelines for the clinical management of hypothyroidism (hypothyroidism) in adults. The guidelines are based on evidence-based medicine and combine the knowledge and experience of clinical endocrinologists to give 52 representative recommendations for the clinical management of patients with ambulatory hypothyroidism and to explain the rationale for the recommendations. The guideline points out that hypothyroidism is caused by a variety of etiologies and has different clinical presentations. The development of an appropriate treatment plan depends on the correct diagnosis and the available medical conditions. Serum thyroid stimulating hormone (TSH) is the best indicator for screening patients with primary thyroid dysfunction in the outpatient setting. The standard treatment for hypothyroidism is levothyroxine sodium (LT4) replacement. Subclinical hypothyroidism with serum TSH <10mU/L should be treated with an individualized treatment plan chosen on a patient-by-patient basis. The following are some personal interpretations of the guidelines regarding the diagnosis and screening of hypothyroidism in adults. Hypothyroidism is not necessarily elevated TSH, and elevated TSH is not necessarily hypothyroidism A 49-year-old female patient with diabetes mellitus for 3 years was admitted to the hospital with poor glycemic control and blurred vision for 1 month. Amenorrhea for 4 years. No history of thyroid disease or family history. Physical examination: height 1.60m, weight 70kg, pulse 64 beats min, thyroid gland not palpable. TSH 4.65mU/L (normal range 0.35~4.94mU/L), FT4 6.43pmol/L (normal range 9.01~19.05pmol/L), free triiodothyronine (FT3) 2.79pmol/L (normal range 2.63~5.70pmol/L), anti-thyroid peroxidase antibody (TPOAb). The thyroid gland ultrasound showed normal volume with homogeneous echogenicity and no nodules were seen. In such a patient with a significantly lower FT4 but no elevated TSH, do we diagnose hypothyroidism or simple hypo-T4emia? If it is hypothyroidism, do we diagnose primary hypothyroidism or secondary hypothyroidism? T4 is completely synthesized and secreted by the thyroid gland, while only 10%-20% of T3 comes from the thyroid gland and 80%-90% is converted from T4 to T3 by peripheral tissues through the action of type II deiodinase. When hypothyroidism occurs, T4 decreases first, while T3 remains normal due to elevated TSH and enhanced type II deiodinase activity in peripheral tissues. When hypothyroidism further worsens, T3 decreases. Therefore, the guidelines recommend that serum TT3 or FT3 should not be used in the diagnosis of hypothyroidism. In view of the fact that the above patient lived for a long time in an area with moderate iodine, according to this, we considered the patient to be hypothyroid rather than simply hypotensive T4emia. Reduced serum FT4 is diagnostic of hypothyroidism, with elevated TSH in primary hypothyroidism and normal or reduced TSH in central hypothyroidism. We usually say that TSH is a sensitive indicator to determine thyroid function, whether it is contrary to T4 which is an indicator to diagnose hypothyroidism. There are various forms of classification of hypothyroidism. It can be classified according to the site of the lesion, the cause, the degree of the lesion, etc. Depending on the degree of hypothyroidism, we classify hypothyroidism into clinical hypothyroidism and subclinical hypothyroidism. Clinical hypothyroidism is characterized by an increase in serum TSH and a decrease in FT4. Subclinical hypothyroidism is characterized by elevated serum TSH but normal FT4. This definition applies only in cases where thyroid function remains stable for several weeks, the hypothalamic-pituitary-thyroid axis response is normal, and there is no new or progressive exacerbation of the disease. Based on the diagnostic basis of clinical hypothyroidism and subclinical hypothyroidism, we can clarify that their lesions originate in the thyroid gland and that both share the abnormal serological marker TSH elevation. In mild hypothyroidism, serum TSH is already elevated when T4 is normal, because TSH secretion is very sensitive to small changes in serum FT4, when serum T4 decreases 2-fold, serum TSH is already 100-fold elevated; TSH changes precede T4 and T3 by several months or years. Therefore, precisely, TSH is a sensitive indicator of primary thyroid function. Although primary hypothyroidism accounts for 99% of the causes of hypothyroidism, it is important to note that TSH is not necessarily elevated in hypothyroidism. Insufficient TSH synthesis can cause central hypothyroidism, which is characterized by reduced or normal or mildly elevated TSH serology and usually reduced FT4. Other causes of low or reduced TSH include sick syndrome (ESS) with normal thyroid function, also known as low T3 syndrome or, in severe cases, low T3-T4 syndrome; subcutaneous octreotide may suppress TSH secretion, but this does not lead to permanent central hypothyroidism. Subcutaneous octreotide may suppress TSH secretion, but this does not lead to permanent central hypothyroidism, but oral bexatotene almost always leads to permanent central hypothyroidism. Patients with anorexia nervosa may have reduced TSH and FT4, similar to patients with severe disease and central hypothyroidism due to pituitary and hypothalamic lesions. Another issue to keep in mind when diagnosing hypothyroidism is that an elevated TSH does not necessarily mean hypothyroidism; TSH can fluctuate up or down 50% of the mean value from day to day. Recent studies have shown that TSH has a 40% variability when blood samples are taken consecutively at the same time of day, with the lowest TSH values occurring in the evening and the highest during sleep. In view of this, when a single test reveals elevated serum TSH and normal FT4, the test should be repeated within 3 months to rule out experimental error and temporary elevation of TSH. Clinically, the condition in which TSH is elevated and T4 is not decreased is most commonly identified as inappropriate TSH hypersecretion. TSH hypersecretion syndrome includes both pituitary TSH tumors and thyroid hormone resistance syndrome, and both TSH hypersecretion syndrome and hypothyroidism can be characterized by elevated TSH, but the difference lies in the levels of FT4 and FT3. Elevated TSH is not a condition of hypothyroidism: it is important to note that TSH is elevated in the absence of treatment for adrenocortical insufficiency and that glucocorticoid treatment can normalize TSH. Therefore, the diagnosis of subclinical hypothyroidism should be determined after glucocorticoid application when adrenocortical hypofunction is present. other rare conditions in which elevated TSH is not hypothyroidism are seen in patients with central hypothyroidism due to secretion of biologically inactive TSH isoforms, combined with nonfunctioning pituitary tumors. mildly elevated TSH, usually not higher than 6 mU/L or 7 mU/L. heterophilic or interfering antibodies. including human anti-animal (most commonly human anti-mouse) antibodies, rheumatoid factor, and anti-TSH autoantibodies can cause pseudo-elevation of TSH. In non-thyroidal disease recovery, TSH is usually below 20 mU/L. Universal screening is not recommended, but screening for hypothyroidism only in special populations. The prerequisites for universal screening of a disease include the following: the disease is sufficiently prevalent, epidemic, and an important health problem; signs and symptoms are insidious and not easily diagnosed early; the screening process is safe and the diagnostic method is simple and accurate; interventions are effective Safe; cost-effective in terms of costs and benefits of screening and interventions; and evidence-based to support that treatment of the disease is associated with a reduction in morbidity or improvement in health status. The ATA recommends screening for hypothyroidism in adults beginning at age 35 years and every 5 years thereafter, although the above criteria are the most direct guidance for screening (Table 1). AACE recommends routine testing for TSH in the older population (specific age not defined), especially in women. The American Academy of Family Physicians recommends that routine screening should be performed in asymptomatic older adults older than 60 years of age. The American College of Physicians recommends case screening for women older than 50 years of age. In contrast, neither the Royal College of Physicians of London, nor the U.S. Preventive Services recommends screening for thyroid disease in adults. The guidelines for adults with hypothyroidism recommend consideration of screening for hypothyroidism in patients older than 60 years; active case finding (Aggressive case finding) is recommended for the general population younger than 60 years, for pregnant women, and for women planning pregnancy (including assisted reproduction), rather than universal screening.