Thyroid Function

Prepared by:

John Gabriel B. Abcede, RN, RMT, MLS(ASCPi)CM

Assistant Professor III

Calayan Educational Foundation Incorporated
 Thyroid Gland
• Gland responsible for the
production of 2 hormones
involved in body
metabolism, neurologic
development, and calcium
homeostasis.

Anatomy
• Positioned in the lower
anterior neck and shaped
like a butterfly.
• Made up of 2 lobes, which
is bridged by a structure
called isthmus.
 Thyroid Gland
Development
• By 11 weeks of gestation, the
thyroid gland begins to produce
measurable amount of thyroid
hormones, which is critical to
neurologic development of the
fetus.

• Iodine is an essential component

of the thyroid hormone
▫ Recommended minimum daily
intake = 150 ug/day
▫ @ <50 ug/day, thyroid is unable
to manufacture hormone

• Lack of iodine results to severe

mental retardation and
cretinism.
 Thyroid Gland
Histology & Hormone Production
• Thyroid cells are organized into follicles.

• Follicular cells manufacture thyroglobulin, which is rich in the amino acid

tyrosine.

• Some of the tyrosyl residues can be iodinated, producing the building

blocks of the thyroid hormones.
 Thyroid Hormone Synthesis
• Inside the thyroid cell,
iodide diffuse across the cell
to the apical side which
touches the colloid.

• Thyroid peroxidase (TPO)

present in the membrane
oxidize and bound tyrosyl
residues on thyroglobulin,
resulting to the production
of monoiodothyronine
(MIT) and diiodothyronine
(DIT).
 Thyroid Hormone Synthesis
• TPO aids in the coupling of
the residues to form
triiodothyronine (T3) and
thyroxine (T4).

• Thyroid hormones are

stored in the core of the
thyroid follicle.
 Thyroid Hormone Metabolism
• 80% of T4 is metabolized
into T3 or reverse T3 (rT3) by
iodothyronine-5’-
deiodinase.

• T3 is 8-10x more
metabolically active than T4
and is considered as the
active form of the
hormone.
▫ T4 –prehormone
▫ Thyroglobulin–prohormone
▫ rT3 -metabolically inactive
 Thyroid Binding Proteins
• When released, only 0.04% of T4 and 0.4% of T3 are bound
by proteins.

3 major binding proteins

• Thyroxine-Binding Globulin (TBG)
• Thyroxine-Binding Prealbumin
• Albumin

• Measurement of the free hormone level may be necessary

for some individuals to eliminate confusion caused by
abnormal protein levels.
 Thyroid Hormone Regulation
• Levels of thyroid hormones
are regulated by the
hypothalamic – pituitary –
thyroid axis.
▫ Hypothalamic hormone –
TRH
▫ Pituitary hormone – TSH
▫ Thyroid Hormone – T3 & T4

• This feedback loop requires

a normally functioning
hypothalamus, pituitary and
thyroid plus the absence of
interfering agents.
 Thyroid Hormone Action
• FT3 & FT4 travel across the cell membrane.

• T4 is deionidated into T3.

• T3 combines with its nuclear receptor which leads to the

production of mRNA.

• Proteins coded for by the mRNA influence metabolism and

development.
▫ Tissue growth
▫ Brain maturation
▫ ↑ heat produc on
▫ ↑ oxygen consump on
▫ ↑ B-adrenergic receptors
 Tests for Thyroid Evaluation
Thyrotropin (TSH)
• Most useful test in assessing thyroid function because of its
ability to detect subclinical hypothyroidism &
hyperthyroidism.

• Large reciprocal change in TSH levels are seen for small

changes in free T4 levels.

• Can be used to differentiate between primary and

secondary thyroid disease.
 Tests for Thyroid Evaluation
Specimen Considerations
• Serum or plasma (EDTA or heparin) may be used.
▫ 2-8°C = 5 days
▫ Frozen = 1 month

• Circadian rhythm:
▫ Peak: 0200 & 0400
▫ Nadir: 1700 & 1800
▫ Lost in critical illness and after surgery

Methods
• Immunoassay
• EIA, IRMA, chemiluminescent
• Possible cross-reactivity with LH, FSH, & HCG
 Tests for Thyroid Evaluation
Thyroxine (T4)
• Principal hormone secreted by the thyroid gland.
• >99.9% protein bound, alterations in thyroid-hormone
binding proteins unrelated to thyroid disease can cause
total hormone levels to be abnormal.

Specimen Considerations
• Serum or plasma (EDTA or heparin) may be used.
▫ 2-8°C = 7 days
▫ Frozen = 1 month
▫ Grossly hemolyzed samples may cause dilutional effect
• For newborn screening, whole blood may be collected by
heel puncture 48-72 hours after birth.
• T4 autoantibodies interfere with some immunoassays.
 Tests for Thyroid Evaluation
Methods
• Immunoassay (competitive)
▫ RIA, EIA, FIA, CLIA
▫ Dissociation from proteins are done by adding barbital,
salicylate, ANS, thimerosal & phenytoin

• Chromatography
▫ Electron capture gas chromatography
▫ HPLC
▫ ID/MS-MS (reference method)
 Tests for Thyroid Evaluation
Triidothyronine (T3)
• Principal active thyroid hormone.

• Most of this are produced from deiodination of T4 in the

tissues (liver), but some are secreted directly by the thyroid
gland.

• Levels usually reflect its progenitor.

• Clinical conditions are known that affect peripheral

conversion of T3 → T4 result in clinical hypothyroid state in
the presence of normal or elevated T4.

• Compared to T4, it is less tightly bound to serum proteins.

 Tests for Thyroid Evaluation
Specimen Considerations
• Serum (preferred), plasma (EDTA or heparin)
▫ Serum specimens must be tested within 24 hours
▫ 2-8°C = >24 hours
▫ Frozen = 30 days
• Avoid repeated freeze-thawing.
• Turbid samples may require centrifugation before testing.

Methods
• Radioimmunoassay
• Enzyme Immunoassay
• FIA
• CLIA
 Tests for Thyroid Evaluation
Methods for Free Hormone Analysis
• Free hormones (FT3 and FT4) reflect the actual physiologic
levels of thyroid hormones.

• Usually involve separation of free and bound fractions

(dialysis, ultracentrifugation) and the measurement of free
concentration (immunoassay, mass spectrometry).
 Tests for Thyroid Evaluation
Thyroxine-Binding Globulin (TBG)
• TBG concentration is the primary regulator of total and free T3 &
T4 concentrations.

• Estrogen-induced TBG excess and congenital TBG deficiency are

the most significant TBG abnormalities that affect the
interpretation of thyroid function test results.

Specimen Considerations
• Serum (preferred), plasma (EDTA or heparin)
▫ Store at 2-8°C if not tested within 24 hours
▫ Frozen = 1 month

Measurement
• Immunoassay (RIA)
▫ Interference from human antimouse (HAMA) antibodies &
rheumatoid factor.
 Tests for Thyroid Evaluation
Reverse Triiodothyronine (rT3)
• Produced by monodeiodination of T4 and is biologically inert.

• Increased in euthyroid sick syndrome.

▫ A state of adaptation or dysregulation of the thyrotropic feedback
control wherein levels of T3 & T4 are abnormal, but the thyroid
gland does not appear to be dysfunctional.
▫ Seen in starvation, critical illness, or in patients in ICU.

• Decreased in renal failure

• Specimen considerations: same as in T3

• Measurement: immunoassay (RIA)

▫ Limited diagnostic value.
 Other Tools for Thyroid Evaluation
Nuclear Medicine Evaluation

Radioactive iodine uptake (RAIU)

• Assesses metabolic activity of thyroid

• Evaluates & treats thyroid cancer

• Given orally, a % of dose is taken up by thyroid gland.

• High uptake suggests metabolic activity.

• Low uptake suggests metabolic inactivity.

 Other Tools for Thyroid Evaluation
• Because TSH stimulates iodine
uptake, TSH levels must be taken
into account
▫ ↑ uptake, undetectable TSH =
autonomous production (Grave’s
Disease)
▫ ↓ uptake, undetectable TSH =
thyroid hormone ingestion, high
iodine intake, thyroid hormone
leakage

• Evaluation of thyroid nodules

▫ ↑ uptake = hot nodules = unlikely
to be thyroid cancer
▫ ↓ uptake = cold nodules =
cancerous.
Other Tools for Thyroid Evaluation (cont’d)
• Thyroid Ultrasound
▫ Has become more significant in past
several years
▫ Capable of detecting thyroid nodules
of exceptionally small size (<1 cm)

• Fine-Needle Aspiration
▫ Often the first step & most accurate
tool in evaluation of nodules
▫ Routine use allows prompt
identification & treatment of
malignancies & avoids unnecessary
surgery in benign cases.
▫ Small-gauge needle is inserted into
nodule & cells are aspirated.
 Disorders of the Thyroid
Hypothyroidism
• Low free T4 level with a normal or
high TSH

• One of most common disorders of

thyroid gland, occurring in 5–15%
of women >65 years old

• Can lead to hyponatremia, anemia,

hyperlipidemia

• Can be divided into primary,

secondary, or tertiary disease
 Disorders of the Thyroid

• Most common cause in developed

countries is chronic lymphocytic
thyroiditis.

• Individuals should be tested

beginning at age 35 & every 5
years thereafter; more frequently
if risk factors are present.

• Treated with thyroid hormone

replacement therapy
 Disorders of the Thyroid
Thyrotoxicosis
• A constellation of findings that result
when peripheral tissues are
presented with, & respond to, an
excess of thyroid hormone

• Possible causes
▫ Excessive thyroid hormone
ingestion
▫ Leakage of stored thyroid
hormone from thyroid follicles
▫ Excessive thyroid gland production
of thyroid hormone
(hyperthyroidism)

• Symptoms: anxiety, emotional

lability, weakness, tremor,
palpitations, heat intolerance,
perspiration, weight loss
 Disorders of the Thyroid
Graves’ Disease
• Most common cause of
thyrotoxicosis

• An autoimmune disease in which

antibodies are produced that
activate TSH receptor

• Features: thyrotoxicosis, goiter,

ophthalmopathy, & dermopathy

• Strong familial disposition: 15% of

patients have close relative with this
condition.

• Women are 5 times more likely than

men to develop it.

• Lab testing shows high free T4 and/or

T3 level with undetectable TSH.
 Disorders of the Thyroid
• Symptoms of ophthalmopathy:
orbital soft tissue swelling, injection
of conjunctivae, proptosis, double
vision, & corneal disease

• Treatments
▫ Medication: beta-blockers,
propylthiouracil, methimazole
▫ Radioactive iodine: destruction
of thyroid tissue to make patient
hypothyroid; lifelong treatment
with thyroid replacement therapy
is usually required
▫ Surgery: preferred in cases of
thyroid cancer or to avoid eye
problems associated with
radioactive iodine treatment
 Disorders of the Thyroid
Toxic Adenoma and
Multinodular Goiter
• Caused by autonomously functioning
thyroid tissue

• Neither TSH nor TSH receptor-

stimulating immunoglobulin is
required to stimulate thyroid
hormone production.

• Associated with receptor mutations

in some toxic nodules

• Occur in patients with

hyperthyroidism & palpable nodules

• Treatment: surgery, radioactive

iodine, or medication
 Disorders of the Thyroid
Amiodarone-Induced Thyroid Disease
• Amiodarone is a drug used to treat cardiac arrhythmias

• Fat-soluble with a long half-life (50 days)

• 37% of molecular weight is iodine.

• Effects
▫ Inhibits thyroid hormone production (Wolff-Chaikoff effect)
▫ Blocks T4 to T3 conversion

• Leads to hypothyroidism in 8–20% of patients &

hyperthyroidism in 3%
 Disorders of the Thyroid
Subacute Thyroiditis

• Characterized by transient changes in thyroid hormone levels

• Associated with inflammation of thyroid gland, leakage of stored thyroid

hormone, repair of gland

• Three classifications
▫ Postpartum: occurs in 3–16% of women in postpartum
▫ Painless: similar to postpartum type, except with no associated
pregnancy
▫ Painful: characterized by neck pain, low-grade fever, myalgia, tender
diffuse goiter, swings in thyroid function test
 Nonthyroidal Illness
• Abnormalities in thyroid function tests of hospitalized patients
(especially critically ill patients)

• Characterized by low total T4, free T4, & TSH

• Less T4 is converted to active T3, leading to decreased levels of

T3 and higher levels of reverse T3.

• Central hypothyroidism & thyroid hormone-binding changes

are associated with severe illness.

• Changes may be appropriate adaptations to illness.