Thyroid stimulating hormone (TSH) is secreted by pituitary thyrotropic hormone cells and is mainly responsible for regulating thyroid cell proliferation, thyroid blood supply, and thyroid hormone synthesis and secretion, playing the most important regulatory role in maintaining normal thyroid function. TSH synthesis and secretion are also regulated by positive feedback from thyrotropin-releasing hormone (TRH) secreted by the hypothalamus and negative feedback from thyroid hormone secreted by the thyroid gland. When thyroid gland itself causes abnormal thyroid hormone synthesis and secretion, it can affect pituitary TSH secretion and serum TSH levels. Likewise, hypothalamic disorders that affect TRH secretion can also affect pituitary TSH secretion and serum TSH levels. Of course, diseases of the pituitary gland itself can directly affect the synthesis and release of TSH. Thus, multiple factors can affect serum TSH concentrations. Understanding the factors affecting serum TSH is of crucial clinical importance for the diagnosis and differential diagnosis of TSH-associated diseases, especially thyroid and related diseases.
In order to facilitate the diagnosis and differential diagnosis of TSH-related thyroid diseases, TSH-related thyroid diseases are classified into several categories according to serum TSH.
I. Thyroid disorders with elevated TSH
The normal range of serum TSH is 0.4-4.0 mU/L. There are some differences in the normal range of serum TSH between different testing methods, different reagents and different laboratories. Serum TSH is elevated when it is higher than the upper limit of the normal range. There are various thyroid disorders that cause elevated TSH.
1. Primary hypothyroidism
is the most common cause of elevated TSH. Abnormal thyroid development, inflammatory thyroid and destructive (injurious) thyroid disorders can lead to inadequate synthesis and secretion of thyroid hormones, resulting in primary hypothyroidism and elevated serum TSH. Regardless of the degree of primary hypothyroidism, the first manifestation is an increase in serum TSH. There is also a positive relationship between the magnitude of TSH elevation and the degree of primary hypothyroidism, i.e., higher serum TSH indicates lower thyroid function. In subclinical primary hypothyroidism, only serum TSH is elevated and serum free thyroxine (FT4) is in the normal range. In clinical hypothyroidism, in addition to elevated serum TSH, serum FT4 may be below normal.
2. Subacute and injured, destructive thyroiditis repair period
Subacute thyroiditis or subacute lymphocytic thyroiditis, injurious or destructive thyroiditis, enters the repair phase of the thyroid follicular epithelium after the inflammatory or injurious and destructive phase. At this time, the thyroxine stored in the follicular lumen of the thyroid gland has been released, while the function of thyroid follicular epithelial cells to synthesize and secrete thyroxine has not been restored. When serum TSH concentration is measured at this stage, there will be an increase in serum TSH with or without a decrease in serum thyroxine.
3. Recovery from normal thyroid function sickness syndrome
Low T3 or low T4 syndrome occurs when the body is in a systemic or severe disease. Once in the recovery phase of the disease, serum TSH will transition from the normal range to the elevated phase. As the disease fully recovers, serum TSH gradually falls back and returns to normal.
4. TSH antibodies
When TSH antibodies are present in the serum, inappropriate elevation of TSH may occur. In this case, there is a mismatch between the degree of elevation of serum TSH and FT4. Clinically, when TSH autoantibodies are present in the blood, often anti-T4 and/or anti-T3 antibodies are also present in the serum.
5. TSH-secreting tumors
When pituitary TSH cells become neoplastic, they secrete TSH autonomously, resulting in elevated serum TSH. In conjunction with elevated TSH, serum FT4 and FT3 are elevated, and clinical manifestations of thyrotoxicosis are seen to varying degrees.
6. Thyroid hormone resistance syndrome
Mutations in the thyroid hormone receptor gene of germ cells lead to reduced sensitivity of thyroid hormone receptors of body cells to thyroid hormone, especially reduced responsiveness of pituitary TSH cells to thyroid hormone, and thyroid hormone resistance syndrome, which manifests as elevated serum FT4 and FT3 and elevated serum TSH.
Second, thyroid disease with reduced TSH
Serum TSH is reduced when it is below the lower limit of the normal reference range. There are likewise various causes of reduced TSH.
1. Primary hyperthyroidism
Primary hyperthyroidism is the most common cause of decreased serum TSH. These include various causes of primary hyperthyroidism, such as Graves’ disease, toxic nodular goiter, and toxic thyroid adenoma. In addition to the presence of serum TSH below the lower limit of the normal range, there is also an elevation of FT3 and FT4 in these diseases.
2. The injury phase of various thyroiditis
In all kinds of thyroiditis, including subacute thyroiditis, subacute lymphocytic thyroiditis, postpartum thyroiditis and drug-related thyroiditis, when in the stage of thyroid inflammation or thyroid destruction or injury, the thyroid follicular epithelial cell structure is destroyed, resulting in increased release of thyroid hormone stored in the thyroid follicular lumen into the blood, causing transient thyrotoxicosis and a decrease in serum TSH, along with Serum thyroid hormones are elevated to varying degrees. At this time, thyroid uptake of 131I is suppressed.
3. Thyroid cancer
In a few thyroid cancers, especially follicular carcinoma, the tumor cells can secrete thyroid hormone at the same time. This causes a decrease in serum TSH and an increase in serum thyroxine.
4. Various pituitary diseases
Various pituitary disorders affecting TSH cell function, including various pituitary adenomas, pituitary inflammatory diseases, pituitary hemorrhagic diseases, or injurious diseases, when affecting the synthesis and secretion of TSH by TSH cells, may result in a decrease in TSH accompanied by a decrease in T4. That is, central, also known as secondary hypothyroidism, occurs.
5. TSH gene mutation
Mutations in the TSHB gene result in abnormal TSH and central hypothyroidism. Serum TSH is reduced. FT4 and FT3 are reduced.
6. human chorionic gonadotropin (HCG)
Associated thyrotoxicosis various physiological or pathological causes of increased HCG in the body, such as multiple pregnancy, choriocarcinoma, and chylothorax, present with increased HCG, which leads to an increase in serum thyroid hormone levels due to the TSH-like effect of HCG, along with a decrease in TSH.
7. Other disease states or medications
Causes of lower TSH Some diseases and medications can also cause TSH to fall below the lower limit of the normal range. One of the most common causes is an increase in cortisol. This can be caused either by the use of exogenous glucocorticoids or by an increase in endogenous cortisol, such as that caused by Cushing’s syndrome.
Thyroid disorders with normal TSH
A normal range of TSH can also be seen in a variety of thyroid disorders.
1. Thyroid cancer
In thyroid follicular cell-derived tumors, especially papillary thyroid cancer, thyroid function is mostly normal and serum TSH is normal. In medullary thyroid carcinoma, thyroid function is also normal and serum TSH is normal.
2. Chronic lymphocytic thyroiditis
In chronic lymphocytic thyroiditis, when thyroid function is not affected, thyroid function tests are in the normal range and serum TSH is also normal.
3. Thyroid nodules or nodular goiter
In the case of thyroid nodules or nodular goiter, thyroid function is also mostly normal and serum TSH is also in the normal range.
4. Normal thyroid function morbidity syndrome
When the body is in the critical stage of a systemic or serious disease, thyroid function may be affected at the same time and low T3 or even low T4 syndrome may occur.
In conclusion, serum TSH is one of the most sensitive indicators of the functional status of the thyroid gland, especially in the evaluation of primary hyperthyroidism and primary hypothyroidism. Problems in any of the hypothalamic, pituitary, and thyroid axes can show up in TSH. Also, non-thyroidal diseases, especially systemic and systemic diseases, can lead to changes in thyroid function and changes in serum TSH. Similarly, the presence of thyroid disease can also result in no changes in thyroid function and no changes in serum TSH. Therefore, there is a need to understand and understand the factors that influence changes in serum TSH in order to better diagnose and identify TSH-related disorders, especially thyroid and its related disorders.