Most of the T4 in your body is bound to protein. A small portion of T4 is not and this is called free T4. Free T4 is the form that is readily available for your body to use. Sometimes a free T4 level is also checked along with the T4 test. The TSH test measures the level of thyroid-stimulating hormone in your blood. The TSH has a normal test range between 0.
Understanding Thyroid Function Tests and Normal Ranges
If you show signs of hypothyroidism and have a TSH reading above 2. Symptoms include weight gain, fatigue , depression, and brittle hair and fingernails. Your doctor will likely want to perform thyroid function tests at least every other year going forward. Your doctor may also decide to begin treating you with medications, such as levothyroxine, to ease your symptoms. Both the T4 and TSH tests are routinely performed on newborn babies to identify a low-functioning thyroid gland.
If left untreated, this condition, called congenital hypothyroidism, can lead to developmental disabilities. The T3 test checks for levels of the hormone triiodothyronine. This is an autoimmune disorder associated with hyperthyroidism. A T3 resin uptake, also known as a T3RU, is a blood test that measures the binding capacity of a hormone called thyroxin-binding globulin TBG. If your T3 level is elevated, your TBG binding capacity should be low.
Euthyroid sick syndrome
Abnormally low levels of TBG often indicate a problem with the kidneys or with the body not getting enough protein. Abnormally high levels of TBG suggest high levels of estrogen in the body. High estrogen levels may be caused by pregnancy, eating estrogen-rich foods , obesity , or hormone replacement therapy. If your blood work suggests that your thyroid gland is overactive or underactive, your doctor may order a thyroid uptake test or an ultrasound test.
These tests will check for structural problems with the thyroid gland, thyroid gland activity, and any tumors that may be causing problems. Based on these findings, your doctor may want to sample tissue from the thyroid to check for cancer.
If the scan is normal, your doctor will likely prescribe medication to regulate your thyroid activity. This occurs mainly in the liver and in certain tissues where T3 acts, such as in the brain. The amount of T4 produced by the thyroid gland is controlled by another hormone, which is made in the pituitary gland located at the base of the brain, called thyroid stimulating hormone abbreviated TSH.
The amount of TSH that the pituitary sends into the blood stream depends on the amount of T4 that the pituitary sees. If the pituitary sees very little T4, then it produces more TSH to tell the thyroid gland to produce more T4. In fact, the thyroid and pituitary act in many ways like a heater and a thermostat. When the heater is off and it becomes cold, the thermostat reads the temperature and turns on the heater.
When the heat rises to an appropriate level, the thermostat senses this and turns off the heater.
paaratike.tk Thus, the thyroid and the pituitary, like a heater and thermostat, turn on and off. This is illustrated in the figure below:. T4 and T3 circulate almost entirely bound to specific transport proteins, and there are some situations which these proteins could change their level in the blood, producing also changes in the T4 and T3 levels it happens frequently during pregnancy, women who take control birth pills, etc.
Another measurement done to assess the thyroid status of patients is the Free T4 measurement. The Free T4 avoids any change the proteins could have, giving us a more accurate value for the T4 level see below. Tests to evaluate thyroid function include the following:.
A high TSH level indicates that the thyroid gland is failing because of a problem that is directly affecting the thyroid primary hypothyroidism. Such expressions of patient preference for a given therapeutic regimen clearly are highly subjective. Responses might be influenced by the method of patient recruitment; notably, patients were enrolled in the majority of these studies irrespective of their satisfaction with their prior L-T 4 monotherapy, whereas patients were invited to participate in other trials.
Symptomatic patients might be more motivated to change their traditional treatment, representing a selected group of subjects that could demonstrate a significant placebo effect on a new drug regimen. The Hawthorne effect cannot be excluded in some studies, with patients describing feeling better simply because they are participating in a trial.
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Untreated subclinical and overtly hypothyroid patients have an increased risk of atherosclerosis, coronary heart disease, and heart failure 49 — Ideally, optimal replacement therapy in hypothyroid patients should improve their prognosis and reduce their cardiovascular risk. However, some cardiovascular risk factors [such as lipid parameters, endothelial function, body mass index BMI , and diastolic hypertension] may not be completely normalized after replacement therapy 29 , 52 — This was observed in a population-based cohort study on primary hypothyroid patients who remained at an increased risk of morbidity associated with circulatory diseases and ischemic heart disease despite treatment with L-T 4 On the other hand, some patients with primary hypothyroidism may improve their lipid profile and body weight if the T 4 dosage is titrated until serum TSH is in the lower part of the reference range 52 , 54 , Combination treatment with T 3 and T 4 could theoretically reduce cardiovascular risk in patients with underlying cardiovascular risk factors.
However, very few published trials of patients on combined T 3 and T 4 treatment vs. L-T 4 monotherapy have evaluated lipid profiles and cardiovascular parameters during randomized controlled trials Table 1. The available data indicate that no significant differences have been seen in total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglycerides 36 , 40 , 41 , 46 , 47 during combined treatment with T 3 and T 4.
A slight improvement in lipid profile was noted only when associated with TSH suppression during combined treatment 38 , 42 , Few studies compared the effects of combined therapy vs. L-T 4 monotherapy on cardiovascular parameters 42 , 43 , 58 , and only two of these studies performed a complete Doppler echocardiographic evaluation 43 , A definitive conclusion cannot be reached, however, because these studies did not normalize TSH and thyroid hormone levels during combined therapy, and their results were not compared with a control group of matched euthyroid subjects.
Although no significant differences in heart rate or systolic and diastolic function were observed between the two regimens of monotherapy vs. It is well known that slight variations in thyroid hormone levels during L-T 4 therapy may affect body weight, body composition, and energy expenditure Patients experiencing weight gain while hypothyroid often complain of persistence of the increase in body weight even after treatment and full normalization of serum TSH levels 29 , 52 , Thus, hypothyroid-treated patients may have a higher BMI with an increased fat mass and decreased lean body mass than control subjects 29 , 53 , Although many factors may influence BMI, small changes in TSH levels, induced by variations in L-T 4 dosage to obtain TSH suppression, may improve resting energy expenditure and fat mass in hypothyroid patients maintaining a higher body weight despite adequate substitution therapy However, increasing evidence suggests that TSH suppressive doses of L-T 4 can be associated with adverse effects on both bone metabolism and the heart 2 , 3.
As a consequence, current guidelines and recommendations suggest titration of L-T 4 dosages to TSH levels in the reference range and not lower. In two double-blind randomized studies, there was a mean body weight change with a decrease of 1. In these two studies, the stated patient preference for, and greater satisfaction with, combination therapy was linked to their significant reduction in body weight and improvement in BMI 38 , In one of these two studies 38 , a decrease in body weight, but not a decrease in serum TSH, correlated with increased satisfaction with the study medication.
For example, the fact that increases in serum SHBG are seen in hyperthyroidism led some investigators to determine whether alterations in SHBG during combination treatment vs.
L-T 4 monotherapy 36 , 38 — 41 , 43 , 46 , 47 , 58 , 59 might indicate relative thyroid hormone overdosage Table 1. Hypothyroidism in adults results in reduced bone turnover with impaired osteoclastic bone resorption and osteoblastic bone formation T 3 enhances expression and synthesis of osteocalcin and alkaline phosphatase. In the skeleton, D2 activity plays a crucial role in maintaining optimal bone mineralization Conflicting results have been reported on the potential role of TSH receptors in bone Few studies have evaluated the effects of combination therapy on markers of bone turnover 38 , 39 , 41 — 43 , 46 Table 1.
In those reports, increases in serum markers of bone turnover were observed when treatment was associated with TSH suppression during treatment 38 , 39 , Initiation of thyroid hormone replacement therapy for hypothyroidism is associated with an increased bone turnover, especially in the first years after the diagnosis and especially in the age group above 50 yr 62 , with a strong dose-response relation 63 ; the available studies did not give any data on the duration of hypothyroidism and on the length of previous treatment with T 4.
Any possible clinical improvement that might have been attributed to the combined T 3 and T 4 treatment could have been obscured in these studies by a relative undertreatment or overtreatment during L-T 4 therapy, essentially constituting states of subclinical hypo- or hyperthyroidism. However, in similar fashion to the previous reports, euthyroidism was not reached in the majority of these studies because the investigators induced overtreatment in most cases as documented by TSH suppression, high FT 3 levels, peripheral parameters of thyroid hormone action SHBG, heart rate, markers of bone metabolism in the thyrotoxic range, all associated with the appearance of hyperthyroid signs and symptoms atrial arrhythmias, weight loss, and increased bone turnover.
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The majority of studies evaluating combined T 3 and T 4 treatment used one or two daily doses of T 3. This may have induced spikes in serum T 3 after each dose with a progressive decline of T 3 levels related to its rapid turnover and short half-life with loss of any potential beneficial effects in the tissues Patients with autoimmune hypothyroidism may have a progressive thyroid failure with the potential development of mild, subclinical, or overt hypothyroidism 1 — 3.
However, in these patients, residual T 3 production from the thyroid gland is thought to be maintained to a variable degree due to the healthy follicular elements within the thyroid gland. This may explain why lower doses of L-T 4 are necessary to replace patients with autoimmune hypothyroidism compared with athyreotic patients 3. However, according to the experience of some expert clinicians 64 , 65 , patients with autoimmune hypothyroidism frequently remain symptomatic despite L-T 4 monotherapy.
These patients may complain of mood dysfunction and impaired quality of life because of the underlying autoimmune diathesis, which may reflect a chronic and progressive disease, or because of the potential association with other comorbidities. Neurocognitive function and psychological well-being were not completely restored in an uncontrolled study on patients with primary autoimmune hypothyroidism despite adequate long-term L-T 4 replacement therapy These results led several investigators to evaluate the effects of combination treatment with T 3 and T 4 in hypothyroid patients with autoimmune disease 37 — 39 , Although no differences were observed in cognitive function, mood, psychological symptoms, quality of life, or thyroid disease-related symptoms in the majority of these studies, it is important to note that TSH was not completely normalized in some of these trials, suggesting that biochemical euthyroidism was not achieved in two of these trials 38 , It remains unsettled whether or not combined treatment with T 3 and T 4 may be beneficial in patients with an autoimmune basis for their hypothyroidism.
However, the requisite increase in deiodinase activity needed to produce a physiological amount of circulating T 3 has not been demonstrated during replacement therapy with L-T 4 in humans. Furthermore, our understanding of possible homeostatic changes in thyroid hormone economy and deiodinase activity has been confounded by recent observations of alterations during long-term TSH-suppressive therapy in thyroidectomized patients with differentiated thyroid cancer DTC Some studies have reported that hypothyroid thyroidectomized patients on L-T 4 replacement therapy need higher serum T 4 levels to obtain similar serum TSH levels and lower serum T 3 concentrations compared with euthyroid controls 72 , Moreover, normal serum FT 3 and significantly higher serum FT 4 levels have been observed after total thyroidectomy in a prospective study in patients receiving L-T 4 treatment compared with their prethyroidectomy levels, especially in those with suppressed TSH It must be emphasized that recent studies have documented the adverse effect of high FT 4 levels in patients receiving L-T 4 therapy There is a possible link between depression and impaired thyroid function 76 , On the other hand, there are conflicting results on the relationship between the presence of positive thyroperoxidase antibodies and depression 77 — A recent population-based study found no association between antithyroid antibodies and depression or anxiety Among studies that have investigated the effects of combined T 3 and T 4 treatment in depressed hypothyroid patients 36 , 37 , only one reported a beneficial effect of this treatment in depressed patients with an improvement in mood and cognition Several meta-analyses have described beneficial therapeutic effects of T 3 in combination with tricyclic antidepressants compared with placebo in euthyroid patients with resistant depression 82 , In one recent study, the addition of T 3 has been able to enhance the antidepressant effect of sertraline in euthyroid patients without significant adverse effects Double-blind placebo-controlled studies are needed to investigate the potential beneficial effects of combined T 3 and T 4 treatment in hypothyroid patients with persistent depression despite TSH normalization during L-T 4 therapy.
Individuals with a polymorphism in D2 may have important clinical implications that could explain why normal serum levels of T 3 may not be sufficient to normalize symptoms and improve the quality of life in some hypothyroid patients receiving L-T 4 replacement therapy alone. The D2 Thr92Ala polymorphism D2-Thr92Ala has been associated with insulin resistance, obesity, and hypertension 85 , On the other hand, the Thr92Ala 12 polymorphism has also been associated with a variation in the HPT axis 22 , 23 , altered bone turnover 60 , cognition, and response to thyroid hormone replacement therapy 67 , 87 — In a study from Italy, the presence of the D2-Thr92Ala polymorphism was able to predict the need for a higher T 4 intake in consecutive cancer patients, previously treated by near total thyroidectomy and radioiodine ablation Although this observation is highly intriguing, the same polymorphism was not associated with a requirement for higher T 4 doses to normalize serum TSH levels in patients with autoimmune hypothyroidism Appelhof et al.
Although this polymorphism had no impact on circulating thyroid hormone levels, it was associated with impaired baseline psychological well-being and a worse baseline GHQ score in patients on L-T 4 Interestingly, the results of this study suggest that circulating T 3 levels may not directly reflect intracellular T 3 levels because this polymorphism had no impact on circulating thyroid hormone levels These data suggest that the evaluation of changes in persistent specific symptoms of hypothyroidism may be useful for the selection of patients that could benefit from combined T 3 and T 4 treatment.
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