Thyroid disease workup

International Ala-Too University

Medical faculty
Department of Therapeutic Disciplines and Family Medicine
Lecturer: Damirbek Abibillaev
Anatomical & physiological basics
• The thyroid gland, located in the anterior neck just below the cricoid
cartilage, consists of 2 lobes connected by an isthmus.
• Follicular cells in the gland produce the 2 main thyroid hormones:
• Tetraiodothyronine (thyroxine, T4)
• Triiodothyronine (T3)
• These hormones act on cells in virtually every body tissue by combining
with nuclear receptors and altering expression of a wide range of gene
products.
• Thyroid hormone is required for normal brain and somatic tissue
development in the fetus and neonate, and, in people of all ages,
regulates protein, carbohydrate, and fat metabolism.
Anatomical & physiological basics
• T3 is the most active form in binding to the nuclear receptor; T4 has
only minimal hormonal activity. However, T4 is much longer lasting
and can be converted to T3 (in most tissues) and thus serves as a
reservoir or prohormone for T3. A 3rd form of thyroid hormone,
reverse T3 (rT3), has no metabolic activity; levels of rT3 increase in
certain diseases.
• Additionally, parafollicular cells (C cells) secrete the
hormone calcitonin, which is released in response to hypercalcemia
and lowers serum calcium levels
Anatomical & physiological basics
• Synthesis of thyroid hormones requires iodine.
• Iodine, ingested in food and water as iodide, is actively concentrated
by the thyroid and converted to organic iodine (organification) within
follicular cells by thyroid peroxidase.
• The follicular cells surround a space (follicle) filled with colloid, which
consists of thyroglobulin, a glycoprotein containing tyrosine within its
matrix.
• Tyrosine in contact with the membrane of the follicular cells is
iodinated at 1 (monoiodotyrosine) or 2 (diiodotyrosine) sites and then
coupled to produce the 2 forms of thyroid hormone.
Anatomical & physiological basics
• T3 and T4 remain incorporated in thyroglobulin within the follicle
until the follicular cells take up thyroglobulin as colloid droplets. Once
inside the thyroid follicular cells, T3 and T4 are cleaved from
thyroglobulin.
• Free T3 and T4 are then released into the bloodstream, where they
are bound to serum proteins for transport. The primary transport
protein is thyroxine-binding globulin (TBG), which has high affinity
but low capacity for T3 and T4. TBG normally carries about 75% of
bound thyroid hormones.
Anatomical & physiological basics
• About 0.3% of total serum T3 and 0.03% of total serum T4 are free and in
equilibrium with bound hormones. Only free T3 and free T4 are available
to act on the peripheral tissues.
• All reactions necessary for the formation and release of T3 and T4 are
controlled by thyroid-stimulating hormone (TSH), which is secreted by
pituitary thyrotropic cells.
• TSH secretion is controlled by a negative feedback mechanism in the
pituitary.
• TSH secretion is also influenced by thyrotropin-releasing hormone (TRH),
which is synthesized in the hypothalamus.
• Most circulating T3 is produced outside the thyroid by monodeiodination
of T4. Only one fifth of circulating T3 is secreted directly by the thyroid.
Laboratory testing – TSH measurement
• TSH measurement is the best means of determining thyroid dysfunction.
• Normal results essentially rule out hyperthyroidism or hypothyroidism,
except in patients with central hypothyroidism due to disease in the
hypothalamus or pituitary gland or in rare patients with pituitary resistance
to thyroid hormone.
• Serum TSH can be falsely low in very sick people, especially in patients
receiving glucocorticoids or dopamine (Euthyroid Sick Syndrome) .
• Changes in the serum TSH level in the presence of normal serum T4, free
T4, serum T3, and free T3 levels define the syndromes of subclinical
hyperthyroidism (low serum TSH) and subclinical hypothyroidism (elevated
serum TSH).
Laboratory testing – T4 measurement
• Total serum T4 is a measure of bound and free hormone.
• Changes in levels of thyroid hormone–binding serum proteins produce
corresponding changes in total T4, even though levels of physiologically active
free T4 are unchanged.
• Thus, a patient may be physiologically normal but have an abnormal total serum
T4 level.
• Free T4 in the serum can be measured directly, avoiding the pitfalls of
interpreting total T4 levels.
• Free T4 index is a calculated value that corrects total T4 for the effects of varying
amounts of thyroid hormone–binding serum proteins and thus gives an estimate
of free T4 when total T4 is measured.
• The thyroid hormone–binding ratio or T4 resin uptake is used to estimate protein
binding.
Laboratory testing – T3 measurement
• Total serum T3 and free T3 can also be measured.
• Because T3 is tightly bound to TBG (although 10 times less so than
T4), total serum T3 levels are influenced by alterations in serum TBG
level and by drugs that affect binding to TBG.
• Free T3 levels in the serum are measured by the same direct and
indirect methods (free T3 index) described for T4 and are used mainly
for evaluating thyrotoxicosis.
Laboratory testing - TBG
• TBG is increased in pregnancy, by estrogen therapy or estrogen-
progestin oral contraceptive use, and in the acute infectious
hepatitis.
• TBG may also be increased by an X-linked mutation in the gene
encoding TBG.
• It is most commonly decreased by illnesses that reduce hepatic
protein synthesis, use of anabolic steroids, the nephrotic syndrome,
and excessive corticosteroid use.
• Large doses of certain drugs, such as phenytoin and aspirin and their
derivatives, displace T4 from its binding sites on TBG, which
spuriously lowers total serum T4 levels.
Laboratory testing - autoantibodies
• Autoantibodies to thyroid peroxidase are present in almost all
patients with Hashimoto thyroiditis and in most patients with Graves
disease.
• These autoantibodies are markers of autoimmune disease but
probably do not cause disease.
• However, an autoantibody directed against the thyroid-stimulating
hormone receptor on the thyroid follicular cell is responsible for the
hyperthyroidism in Graves disease.
• Antibodies against T4 and T3 may be found in patients with
autoimmune thyroid disease and may affect T4 and T3 measurements
but are rarely clinically significant.
Laboratory testing - Thyroglobulin
• The thyroid is the only source of thyroglobulin, which is readily detectable
in the serum of healthy people and is usually elevated in patients with
nontoxic or toxic goiter.
• The principal use of serum thyroglobulin measurement is in evaluating
patients after near-total or total thyroidectomy (with or without iodine-
131 ablation) for differentiated thyroid cancer.
• Normal or elevated serum thyroglobulin values indicate the presence of
residual normal or cancerous thyroid tissue in patients receiving TSH-
suppressive doses of levothyroxine or after withdrawal of levothyroxine.
• However, thyroglobulin antibodies interfere with thyroglobulin
measurement.
Screening for thyroid dysfunction
• Screening for thyroid disease is recommended for all
newborns to detect congenital hypothyroidism, which
may impair normal development if untreated.
• For patients, including pregnant women with risk factors,
the serum TSH should be measured and is the best test to
screen for both hyper- and hypothyroidism.
• Because of the increased prevalence of subclinical
hypothyroidism in older adults, some authorities
recommend screening on an annual basis for those > age
70, although it is uncertain whether treating older
persons detected with subclinical hypothyroidism has any
benefit.
Radioactive iodine uptake
• Radioactive iodine uptake can be measured.
• A trace amount of radioiodine is given orally or intravenously; a scanner
then detects the amount of radioiodine taken up by the thyroid.
• The preferred radioiodine isotope is iodine-123, which exposes the patient
to minimal radiation (much less than iodine-131).
• Thyroid iodine-123 uptake varies widely with iodine ingestion and is low in
patients exposed to excess iodine.
• The test is valuable in the differential diagnosis of hyperthyroidism (high
uptake in Graves disease, low uptake in thyroiditis).
• It may also help in the calculation of the dose of iodine-131 needed for
treatment of hyperthyroidism.
Radioactive imaging
• Imaging using a scintillation camera can be done after radioisotope
administration (radioiodine or technetium 99m pertechnetate) to
produce a graphic representation of isotope uptake.
• Focal areas of increased (hot) or decreased (cold) uptake help
distinguish areas of possible cancer (thyroid cancers exist in < 1% of
hot nodules compared with 10 to 20% of cold nodules).
Results of thyroid function tests in
hyper/hypothyroidism

Physiologic 24-hour
State Serum TSH Serum Free T4 Serum T3 Radioiodine
Uptake

Hyperthyroidsm

Untreated Low High High High

T3 toxicosis Low Normal High Normal or high

Hypothyroidism

Primary,
High Low Low or normal Low or normal
untreated

Secondary to
Low or normal Low Low or normal Low or normal
pituitary disease
Results of thyroid function tests in various clinical
conditions
Physiologic 24-hour
State Serum TSH Serum Free T4 Serum T3 Radioiodine
Uptake

Euthyroidism

Patient
Normal Normal Normal Low
taking iodine

High in patient
Patient taking Normal in patient
taking T3, normal
exogenous Normal taking T4, low in Low
in patient taking
thyroid hormone patient taking T3
T4

Patient
Normal Normal High Normal
taking estrogen

Euthyroid sick Normal, low, or

Normal or low Low Normal
syndrome high