The diagnosis of hypothyroidism and of its cause requires the evaluation of several clinical, laboratory, and instrumental parameters to manage the patient properly (Table 1).

Table1. Differential diagnosis of hypothyroidism

Hormonal evaluation

A small decrease in thyroid secretion may produce only minor changes in serum concentrations of thyroid hormones that remain within the normal range. The most sensitive index of a reduction in serum thyroid hormone concentration is serum TSH because of a decrease in feedback inhibition of pituitary TSH secretion. Thus, elevated serum TSH is the earliest laboratory abnormality in patients with primary hypothyroidism.

The combination of normal thyroid hormones and elevated TSH has been long defined as subclinical hypothyroidism. However, this term may be misleading because it suggests the absence of symptoms and signs of hypothyroidism, whereas they may be present if thy roid hormone deficiency does actually exist. Indeed, an isolated increase in serum TSH may arise as a consequence of mild thyroid failure due to a recognized pathogenic event in an otherwise normal thyroid gland (most commonly autoimmune thyroiditis), and in this case grading of hypothyroidism based on biochemical criteria should be preferred. Differently, a slight TSH elevation may depend on inherited defects that produce a minor impairment of TSH action on thyroid cells, leading to isolated hyperthyrotropinaemia and an apparent euthyroid state. A mild increase in serum TSH can also be observed in obese subjects, which is secondary to the obesity state and is reversible after weight loss. Distinction among these conditions is important to decide on the opportunity of starting the replacement therapy.

With the progression of thyroid dysfunction, serum levels of T4 fall below the normal limit while serum T3 may still be normal. This is because high TSH levels induce preferential secretion of T3 by residual thyroid tissue.

The lack of TSH response to reduced thyroid hormone levels com plicates the diagnosis of central hypothyroidism, and the finding of low serum T4 is a prerequisite for the diagnosis of this condition. Usually in central hypothyroidism, basal serum TSH concentrations are inappropriately low with respect to reduced serum thyroid hormones. Yet, in some instances serum TSH may be slightly elevated due to secretion of immunoreactive but biologically inactive TSH.

Assays for measurement of total thyroid hormones in serum are gradually being replaced by methods that determine the free (un bound) fraction of T4 and T3. Although measurement of free T4 and free T3 concentrations is more cumbersome as compared to that for total T4 and T3, free T4 and free T3 determinations are preferred because free thyroid hormones are those capable of entering the cell and therefore represent the biologically active hormone. Indeed, the concentrations of total thyroid hormones may be elevated or reduced in spite of normal free fractions, due to changes in the concentrations of serum transport protein. Current free thyroid hormone immunoassays are valuable in most clinical instances but more accurate methodologies may be required in selected cases.

The initial assessment of thyroid function may be accomplished by testing of TSH first, followed by reflex testing for free T4 if TSH is outside the reference range. The implementation of appropriate TSH reference ranges is essential to achieve optimal effects on case detection. However, it must be emphasized that TSH alone is not reliable for the detection of central hypothyroidism and may be misleading in other clinical settings, including treated hyperthyroidism and hypothyroidism before stabilization of the hormonal equilibrium, combined therapy with T4 and T3, and non- thyroidal illness.

Measurement of the serum TSH response to thyrotropin- re leasing hormone (TRH) (200– 500 μg intravenously) may be useful in selected patients with a borderline to low value of T4 and borderline to high or borderline to low values of basal TSH, to identify subclinical primary or central hypothyroidism, respectively. An exaggerated response will be observed in primary hypothyroidism whereas in central hypothyroidism the serum response of TSH may be reduced or abnormally prolonged. The TRH test may be useful also to measure the increase in serum T3 levels following the rise in serum TSH. In people with normal thyroid function, serum T3 increases 30– 100% above the baseline value 120– 180 min after the injection of 200 μg TRH. In central hypothyroidism, the T3 response may be impaired or absent in spite of a normal peak of TSH, indicating secretion of biologically inactive TSH. Evaluation of the nocturnal surge of TSH in samples taken every 30 min from 11.00 p.m. to 2.00 a.m. may be useful to confirm the diagnosis of central hypothyroidism. At variance with people with normal thy roid function, the TSH surge is blunted or absent in central hypo thyroid patients.

A transient phase of central hypothyroidism may occur in patients with non- thyroidal illness, particularly hospitalized patients with medical or psychiatric illnesses. In these cases, repeated hormonal measurements are useful since values usually become normal as patients recover from that illness.

Other In Vitro Tests

Antithyroglobulin and antithyroperoxidase antibodies are sensitive markers of thyroid autoimmunity. Thus, if present, they may contribute to the diagnosis of autoimmune thyroiditis, often pre ceding the appearance of thyroid dysfunction, represent a prognostic index for the development of postpartum thyroiditis, and help to predict the outcome of iodine- or drug- induced hypothyroidism. Antithyroperoxidase antibodies and, less frequently, antithyroglobulin antibodies are observed in most patients with chronic autoimmune thyroiditis but hypothyroid patients with serum negative Hashimoto’s disease have also been reported, who display a milder clinical picture compared with classic Hashimoto’s thyroiditis. Screening for antithyroperoxidase and antithyroglobulin anti bodies in patients with non- thyroidal autoimmune diseases may be helpful for early recognition of concurrent autoimmune thyroid dis eases, in the context of polyglandular autoimmune syndromes.

TSH- receptor antibodies can either have stimulating activity (thyroid- stimulating antibody), as in Graves’ disease, or block the receptor (TSH- receptor blocking antibody) preventing TSH stimulation of the follicular cell. TSH- receptor blocking antibodies are highly specific for autoimmune thyroiditis. They are found in up to 30% of patients with chronic autoimmune thyroiditis and can produce or add to the development of hypothyroidism by blocking the thyroid response to TSH. Hypothyroidism produced by TSH- receptor blocking antibodies can spontaneously remit following disappearance of antibody from serum. Assays for TSH- receptor antibodies measure the ability of a patient’s IgG to inhibit the binding of 125I- TSH to its receptor in thyroid membrane preparations. Radioreceptor assays are now easy to perform, inexpensive, and provide reliable results but do not distinguish thyroid- stimulating antibodies from TSH- receptor blocking antibodies. For this purpose, methods that assess the capacity of IgG to stimulate or to prevent TSH- induced cAMP production in thyroid preparations are necessary.

Endogenous antibodies against thyroid hormones may develop in patients with autoimmune thyroiditis. These antibodies usually have no clinical relevance, but may interfere on assays for serum total and free T4 and T3, producing artefactual results depending on the technique used to measure the hormones. The presence of T4 or T3 antibodies should always be suspected in autoimmune patients with unexpected results of thyroid hormone assays. These antibodies can be detected easily by immunoprecipitation of radiolabelled T4 or T3 with the patient’s serum.

Thyroglobulin is present at low concentrations in serum of people with normal thyroid function, and is elevated in all states associated with enlargement, hyperfunction, or injury of the thyroid gland. Measurement of serum thyroglobulin has no meaning for the diagnosis or the management of hypothyroidism, but may be useful to estimate the amount of residual thyroid tissue after surgery or other thyroid destructive events. Furthermore, detectable serum thyroglobulin in congenital hypothyroidism excludes thyroid agenesis. Increased levels of serum thyroglobulin in iodine deficiency have also been observed. Antithyroglobulin antibodies in serum interfere with measurement of thyroglobulin and therefore this test should not be performed in such patients.

Measurement of urinary iodide provides information about the daily iodide intake in epidemiological studies. The demonstration of elevated concentrations of urinary iodide in a hypothyroid patient may be useful if exposure to excessive iodide is suspected.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم بين الحرمين ينفّذ أعمال غسل الساحة الوسطية والطرق المؤدية إليها

جمعية العميد تصدر كتابًا علميًّا عن الكليَّات القرآنيَّة

لإحياء التراث الإسلامي.. قسم شؤون المعارف يقيم دوراتٍ وندواتٍ تخصصية في تحقيق المخطوطات

قسم الحزام الأخضر يباشر زراعة نحو 2000 شتلة في واحاته

المزيد

الآخبار الصحية

ما هي أفضل العصائر لصحة القلب وتقوية المناعة والنوم العميق؟

الأطعمة الغنية بالبروتينات النباتية تقلل خطر الأمراض المزمنة

وجع الأوتار قد يخفي خطرا صحيا مرتبطا بالقلب

أزمة "السفينة الموبوءة"..الأرجنتين تحقق في مصدر تفشي "هانتا"

المزيد

الآخبار التكنلوجية

باحثون يحددون تأثير القهوة على الميكروبيوم والمزاج

روسيا.. ابتكار تقنية لمعالجة سبائك التيتانيوم لحماية الطائرات والسيارات

بكين وواشنطن تدرسان إطلاق محادثات رسمية حول الذكاء الاصطناعي

لأول مرة في الولايات المتحدة.. تشغيل مفاعل مصغر نووي يغذي الذكاء الاصطناعي بالطاقة

المزيد

مواضيع ذات صلة

Tests for Activity of Antimicrobial Combinations

Bactericidal Tests

Commercial Susceptibility Testing Systems

Conventional Testing Methods: Agar Dilution

Conventional Testing Methods: Broth Dilution

Laboratory Diagnosis of Autoimmune Hemolytic Anemia

Blood Coagulation Tests

Western Blot Immunoassays

Indirect Fluorescent Antibody Tests and Other Immunomicroscopic Methods

Enzyme-Linked Immunosorbent Assays

Laboratory Diagnosis of Thyrotoxicosis

Laboratory Findings of Beta-Thalassemia Syndromes