MLS115 Thyroid Gland CLINICAL CHEM 2

WILLIAM CHRISTOPHER SALAZAR, RMT | MARCH 19, 2021 LE 02 TRANS 06

OUTLINE  It has the major fraction of organic iodine in the circulation

I. Thyroid Gland  A prohormone for T3 production
II. Thyroid Hormones VI. Thyroid Function Test  All circulating T4 originates in the thyroid gland – it is secreted
A. Binding Proteins A. RAIU 100% in the thyroid gland
B. Responsible for B. Thyroglobulin assay  The amount of serum T4 is a good indicator of the thyroid
Autoimmune disorders C. Reversed T3 (rT3) secretory rate
III. Clinical Disorders D. Free Thyroxine Index (FTI  Elevated thyroxine causes inhibition of TSH secretion and vice versa
IV. Hyperthyroidism or T7)  Reference value
V. Hypothyroidism E. Total T3 (TTT3), Free  5.5-12.5 ug/dL or 71-161 nmol/L (adult)
A. Primary T3(FT3), and Free  11.8-22.6 ug/dL or 152-292 nmol/L (neonate)
B. Secondary T4(FT4) T3 Uptake
C. Tertiary F. FNA A. BINDING PROTEINS
D. Congenital Thyroid Hormones Binding Proteins
LEGEND 1. Thyroxine-Binding Globulin (TBG)
Remember Lecturer Book Previous Presentation  It transports majority of T3 (affinity for T3 is lower than T4)
Trans  It transports 70-75% of Total T4

2. Thyroxine-Binding Prealbumin (transthyretin)

I. THYROID GLAND  It transports 15-20% of Total T4
 T3 has no affinity for prealbumin
 also known as the butterfly shaped gland
 consists of two lobes (one on either side of the trachea) located in the lower 3. Thyroxine-Binding Prealbumin (transthyretin)
part of the neck just below the voice box  Transports T3 and 10% of T4
 The lobes are connected by a narrow band called the isthmus they are the service of hormones
 By 11 weeks of gestation, the gland begins to produce measurable
amount of hormone B. RESPONSIBLE FOR AUTOIMMUNE DISORDERS
 Follicle is the fundamental structural unit of the thyroid gland Thyroid Hormones Responsible for Autoimmune Disorders
2 Types of Cells: conditions wherein our own body attacking specific cells or tissues
1. Follicular cells 1. Thyroperoxidase (TPO)
 Secretory and produce thyroxine – T4 and triiodothyronine -  Involved in the tissue destructive process (hashimoto’s disease)
T3 2. Thyroglobulin (Tg)
(enzymes of thyroid)  Thyroid cancer
 Each follicle is in the shape of a sphere that surrounds a viscous 3. TSH receptor (TR)
substance called colloid. The major component of colloid is the  Involved in Grave’s Disease
Thyroglobulin, which is rich in tyrosine
2. Parafollicular Cells or C-cells III. CLINICAL DISORDERS
 Situated in clusters along the interfollicular surface or spaces  Screening of thyroid disorders is recommended when a person
 They produce the polypeptide calcitonin, for calcium regulation reaches 35 years old and every year thereafter
ito ay ‘pag walang signs and symptoms that is pertaining to thyroid
II. THYROID HORMONES disorders. Maganda lang mascreen if okay or healthy pa yung
iyong thyroids.
 There is more T4 than T3 in serum, but T3 is more potent and
significant physiologically IV. HYPERTHYROIDISM
 About 80% of circulating T3 is formed following monodeiodination of  Refers to an excess of circulating thyroid hormones
T4 in peripheral tissues  Signs and symptoms
 Thyroid hormones are almost completely protein bound  Tachycardia, tremors, weight loss, heat intolerance, emotional
kumbaga naka-attached to protein molecules lability and menstrual cycle changes
 T4 = 99.97% bound = only 0.03% FREE  Primary hyperthyroidism
 T3 = 99.70% bound = only 0.30% FREE  Elevated T3 and T4, decreased TSH
 Secondary hyperthyroidism
Triiodothyronine (T3)/ 3,5,3’ triiodothyronine  Increased FT4 and TSH (due to primary lesion in the pituitary
 It has the most active thyroid hormonal activity gland)
 Almost 75-80% is produced from the tissue deiodination of T4
conversion of T4 to T3 takes place in many tissues, particularly in Hyperthyroidism - Thyrotoxicosis
the liver and the kidneys  Applied to a group of syndromes caused by high levels of Free
 The principal application of this hormone is in diagnosing T3 Thyroid hormones in the circulation
thyrotoxicosis  T3 thyrotoxicosis or plummer’s disease: FT3 is increased but FT4
 A better indicator of recovery from hyperthyroidism as well as the is normal with low TSH
recognition of recurrence of recurrence of hyperthyroidism – it is  T4 thyrotoxicosis: T3 is normal of low but T4 is increased with low
helpful in confirming the diagnosis of hyperthyroidism, especially in TSH
patients with no or minimally elevated T4
 An increase in the plasma level of T3 is the first abnormality seen in
cases of hyperthyroidism
 Reference values:
 60-160 ug/dl or 0.9-2.46 nmol/L (adult)
 105-245 ug/dl or 1.8-3.8 nmol/L (children 1-14 years old)

Tetraiodothyronine (T4)/ 3,5,3’,5’ tetraiodothyronine

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 The principal secretory product

TRANS #6 Balilo, Candia, Roales, Villa EDITORS

2.06 Thyroid Gland LE 02 TRANS 06
 T3 and T4 are decreased while TSH is increased
 It is also caused by destruction or ablation of the thyroid gland
 Other causes: surgical removal of the gland, use of radioactive iodine
for hyperthyroidism treatment, radiation exposure; drugs such as
lithium
Hypothyroidism – Primary Hypothyroidism
 Primarily due to deficiency of elemental Iodine

Hyperthyroidism – Grave’s disease

 Diffuse toxic goiter
 Most common cause of thyrotoxicosis
 An autoimmune disease in which antibodies are produced that active
the TSH receptor
stimulates the TSH to produce
 It occurs 6x more commonly in women than in men
 Features: exophthalmos (bulging eyes) and pritibial myxedema
 Diagnostic test: TSH receptor antibody test

Hyperthyroidism – Riedel’s thyroiditis

 The thyroid turns into a woody or stony-hard mass

Hyperthyroidism – Subclinical hyperthyroidism

 Shows no clinical symptoms but TSH level is low, and TF3 and FT4
are normal

Hyperthyroidism – Subacute granulomatous

 Subacute nonsuppurative thyroiditis, De Quevain’ thyroiditis
(painful thyroiditis)
 It is associated with neck pain, low-grade fever and swings in
thyroid function test
sa thyroid function test malaking pinagbabago sa test result
 The thyroidal peroxidase (TPO) antibodies are absent; ESR and
thyroglobulin levels are elevated

V. HYPOTHYROIDISM

 It develops whenever insufficient amounts of thyroid hormone are

available to tissues.
 It is treated with thyroid hormone replacement therapy
(levothyroxine)
 Signs and symptoms: bradycardia, weight gain, coarsened
skin, cold intolerance and mental dullness

A. PRIMARY HYPOTHYROIDISM

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Primary Hypothyroidism – Hashimoto’s disease
 Chronic autoimmune thyroiditis
 It is the most common cause of primary hypothyroidism
 It is characterized by a thyroid replaced by a nest of lymphoid
tissue – sensitized T lymphocytes/autoantibodies bind to cell
membrane causing cell lysis and inflammatory reaction
 It is associated with enlargement of the thyroid gland (goiter)
 Lab result: high TSH and positive TPO antibody

Primary Hypothyroidism – Hashimoto’s disease

Primary Hypothyroidism – Myxedema

 It describes the peculiar nonpitting swelling of the skin
 The skin becomes infiltrated by mucopolysaccharides
 Clinical features: “puffy” face, weight gain, slow speech,
eyebrows thinned, dry and yellow skin, and anemia
 Myxedema coma is the severe form of primary hypothyroidism

B. SECONDARY HYPOTHYROIDISM
Hypothyroidism - Secondary Hypothyroidism
 Due to pituitary destruction or pituitary adenoma
 Lab result: T3 and T4 levels are low, TSH is also decreased

C. TERTIARY HYPOTHYROIDISM
Hypothyroidism - Tertiary Hypothyroidism
 Due to hypothalamic disease
 Lab results: T3 and T4 levels are low, TSH is also decreased

D. CONGENITAL HYPOTHYROIDISM
Hypothyroidism - Congenital Hypothyroidism
 Also known as cretinism
 It is a defect in the development or function of the gland
defective from birth
 Symptoms: physical and mental development of the child are
retarded
 Screening test: T4 (decreased)
 Confirmatory test: TSH (increased)
 Interpretation
 TSH value <10 mIU/L – no further test
 TSH value 10 – 20 mIU/L – repeat test in 2-6 weeks
 TSH value >20 mIU/L – for endocrinologic evaluation to
diagnose hypothyroidism

Hypothyroidism - Subclinical Hypothyroidism

 Lab result: T3 and T4 are normal but TSH is slightly increased

VI. THYROID FUNCTION TEST

TRH Stimulation Test (Thyrotropin Releasing Hormone)
 It measures the relationship between the TRH and TSH
secretions
 It is used to differentiate euthyroid and hyperthyroid patients
 It may also be helpful in the detection of thyroid hormone
resistance syndromes
 It is used to confirm borderline cases and euthyroid Grave’s
disease

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 Dose needed: 500 ug TRH by IV Reference value: 38 – 44 ng/dL
 Increased: primary hypothyroidism
 Decreased: hyperthyroidism D. Free Thyroxine Index (FTI or T7)
 It indirectly assesses the level of Free T4 in the blood
TSH Test  It is based on equilibrium relationship of bound T4 or FT4
 The most important thyroid function test  It is important in correcting euthyroid individuals
 The best method for detecting clinically significant thyroid  It is elevated in hyperthyroidism and decreased in
disfunction hypothyroidism
 It is the most clinically sensitive assay for the detection of  Reference value: 5.4 – 9.7
𝑇𝑇4 𝑥 𝑇3𝑈(%)
primary thyroid disorders  𝐹𝑇𝐼 = 𝑜𝑟 𝑇𝑇4 𝑥 𝑇𝐻𝐵𝑅
100
 It helps in the early detection of hypothyroidism
 It is used to differentiate primary hypothyroidism from E. Total T3(TTT3), Free T3(FT3), and Free T4(FT4)
secondary hypothyroidism  FT4 test is used to differentiate drug induced TSH elevation and
 It is used to monitor and adjust thyroid hormone replacement hypothyroidism
therapy  The value of TT3 or FT3 is in confirming hyperthyroidism
 the sensitivity of the third generation TSH assay has led to the ability
 Direct/reference method: Equilibrium dialysis (FT4)
to detect what is termed as subclinical disease- or a mild degree of
thyroid dysfunction (due to large reciprocal change in TSH levels
F. T3 Uptake
seen for even small changes in FT4)
 Reference value: 0.5 – 5 uU/mL  It measures the number of available binding sites of the thyroxine
 Increased TSH binding proteins, most notably TBG; a test for TBG
TBG – Thyroid Binding Globulin
 Primary hypothyroidism
 Increased: hyperthyroidism, euthyroid patients, chronic liver
 Hashimoto’s thyroiditis
disease
 Thyrotoxicosis due to pituitary tumor
 Decreased: hypothyroidism, oral contraceptives, pregnancy, acute
 TSH antibodies
hepatitis
 Thyroid hormone resistance  Reference value: 25-35%
 Decrease TSH
 Primary hyperthyroidism G. Fine Needle Aspirate (FNA)
 Secondary and Tertiary hypothyroidism  The most accurate tool in the evaluation of thyroid nodules
 Treated Grave’s Disease
 Euthyroid sick disease
 Over replacement of thyroid hormone in hypothyroidism END OF TRANSCRIPTION

A. Radioactive Iodine Uptake (RAIU)

‘Every morning you have two choices: continue to sleep with
 Used to measure the ability of the thyroid gland to trap iodine
your dreams or wake up and chase them.’
 It is helpful in establishing the cause of hyperthyroidism
 Radioactive iodine is ingested by mouth and measured after 4-6 hours
and 24 hours

B. Thyroglobulin (Tg) assay

 Normally used as a postoperative marker of thyroid cancer

 It is used in monitoring the course of metastatic or recurrence of
thyroid cancer (a well differentiated tumor typically displays a 10- fold
increase in Tg in response to a high TSH)
 When measuring Tg as a tumor marker for thyroid cancer, always
check simultaneous sample for thyroglobulin antibodies
 Differentiates subacute thyroiditis (increased Tg) from
 thyrotoxicosis factitia (decreased Tg)
 Increased: untreated and metastatic differentiated thyroid
cancer, nodular goiter and hyperthyroidism
 Decreased: infants with goitorous hypothyroidism and
thyrotoxicosis factitial (decreased Tg)
 Reference value:
 3-42 ng/ml or ug/ml (adult)
 38-48 ng/ml or ug/ml (infant)
 Methods for testing: double-antibody RIA, ELISA, IRMA,
Immunochemiluminescent assay (ICMA)
 Differentiates subacute thyroiditis (increased Tg) from
thyrotoxicosis factitia (decreased Tg)

C. Reverse T3 (rT3)

 Rt3 is formed by removal of one iodine from the inner ring of T4

 It is an end product of T4 metabolism; the 3rd major circulating
thyroid hormone
 It identifies patients with euthyroid sick syndrome (elevated rT3)
 It is used to assess the borderline or conflicting laboratory results


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