THYROID FUNCTION, LEVELS AND

DISORDERS

HazelPaterson
MLS203Clinical Chemistry
MLS year 2 SemB
LEARNING OBJECTIVES
 Name the hormones produced by the thyroid
 State which processes that the thyroid hormone is involved in
 Describe the thyroid anatomy and its development
 Describe, in detail, thyroid hormone synthesis
 Explain the organization of the thyroid gland
 Describe the control of thyroid function
 Describe the tests of thyroid evaluation and note what values

will be elevated in specific disorders

 Describe autoimmune disorders affecting the thyroid
 Describe hypothyroidism, give an example of this and explain

it diagnosis and treatment

 Describe thyrotoxicosis, give an example of this and explain it

diagnosis and treatment

INTRODUCTION
 The Thyroid is responsible for two hormones:
 Thyroid hormone

 Calcitonin

 Calcitonin is secreted by the parafollicular cells and is

involved in calcium homeostasis
 Thyroid hormone is critical to the regulating of
bodymetabolism
 neurologic development

 numerous other body functions

THYROID ANATOMY
AND DEVELOPMENT
 The thyroid is
positioned in the lower
anterior neck
 It is made up of two

lobes.
 These rest on each side

of the trachea with a

band of thyroid tissue,
called the isthmus running
anterior to
trachea and bridging
the lobes
 posterior of the thyroid

gland are the

parathyroid glands
THYROID DEVELOPMENT
 thyroid hormone is vital for neurological
development
 Iodine is component of thyroid hormone. In certain
parts of Malawi, iodine deficiency exists and neither the
mother nor the foetus can produce thyroid hormone and
they both develop hypothyroidism.
 Infant can develop mental and cretinism.
 congenital hypothyroidism can occur when mum has
normal thyroid function as foetus is protected by
maternal thyroid hormone crossing the placenta.
 After or at birth the baby will need attention and

Initiation of adequate doses of thyroid hormones or the

neurological impairment to the child will be significant.
THYROID HORMONE SYNTHESIS
 Thyroid hormone is made primarily from the trace
element iodine.
 Iodine is found in the following foods:
 Iodine enriched bread and vitamins
 Dairy products
 Seafood
 Iodised salt

 The recommended daily intake of iodine is 150ug,

 in westernised countries many people will exceed this,
 if iodine is <50ug daily, the thyroid cannot manufacture
adequate amounts of thyroid hormone hypothyroidism occurs.
HISTOLOGY OF THE THYROID GLAND
ORGANISATIONOF THE THYROID
GLAND

 Thyroid cells are organised into follicles, follicles

are spheres of thyroid cells surrounding a core of a
viscous substance termed colloid. Themajor
component of the colloid is thyroglobulin, a
Glycoprotein manufactured exclusively by thyroid
follicular cells. Thyroglobulin is rich in the amino
acid tyrosine. Some of the tyrosine residues can be
iodinated producing the building blocks of thyroid
hormone.
ORGANISATIONOF THE THYROID
GLAND
 iodine is actively transported into the thyroid cell by the
Na+/I- symporter, located on the basementmembrane.
 Inside the thyroid cell, iodine diffuses across the cell to

the apical side of the follicle, which abuts the core of

colloid.
 Here, catalysed by the membrane bound enzyme called

thyroid peroxidise (TPO), concentrated iodide is

oxidised and bound with tyrosyl residues on
thyroglobulin. This results in the production of
monoiodothyronine (MIT) and diiodothyronine.
 This same enzyme also aids in the coupling of two

tyrosol residues to form triiodothyronine (t3) (oneMIT

residue and one DIT residue) or thyroxin (two DIT
residues)
ORGANISATION OF THE THYROID
GLAND
 These are the two active forms of thyroid hormone.
 This thyroglobulinmatrix, with branches now

holding the t3 and t4 is stored in the core of the

thyroid follicle.
 Thyroid stimulating hormone (TSH) signals for the

follicular cell to ingest a microscopic droplet of

colloid by endocytosis.
 Inside the follicular cell these droplets are ingested

by intracellular liposome’s into t4 and t3 and other

products. T4 and t3 are then secreted by the thyroid
gland in to the circulation
 Activating of thyroid hormone is dependent on the
location and the number of thyroid atoms.
 Outer ring deiodination with T4 of (5’deiodination)
leads to production of 3,5,3,’-Triiodothyronine (T3).
 T3 is 3-8 times more active than t4 and often
considered to be the more active form of thyroid
hormone.
IODOTHYRONINE 5’DEIODINASE
 There are three forms of iodothyronine
5’deiodinase, themost abundant form is found
mainly in the liver and kidney and is responsible for
the largest contribution to the circulating t3 pool.
 Certain drugs (e.g.. glucocorticoids) can slow the

activity of this deiodinase and are used in the

treatment of severe hyperparathyroidism.
 Activity of the deiodination enzymes gives another

level of control on thyroid hormone activity beyond

hypothalamic pituitary control through
thyrotropin-releasing hormone (TRH) and (TSH).
CONTROLOF THYROID FUNCTION
 TRH is synthesized and stored in the hypothalamus.
 It stimulates cells in the anterior pituitary gland to

manufacture and release thyrotropin (TSH)

 TSH circulates to the thyroid gland stimulates increased

productionand release of thyroid hormone

 If the hypothalamus and pituitary sense that there is an

inadequate amount of thyroid hormone in circulation,

TRH and TSH secretion increases.
 If thyroid hormones levels are too high, TRH and TSH

releasewill be inhibited
 Questions????
ACTION OF THE THYROID HORMONES
 Once released from the thyroid gland, thyroid hormone
circulates in the bloodstream where free T4 and T3 are
available to travel across the cell membrane.
 In the cytoplasm t4 is deiodinated to T3, the active form
of the throid hormone.
 The t3 then combines with the thyroid hormone
responsive genes leading to production of messenger
RNA that in turn leads to the production of proteins that
influence metabolism and development
ACTION OF THE THYROID HORMONES
 Effects of the thyroid hormone include tissue
growth, brain maturation, increased heat
production and increased oxygen consumption and
increased number of B-adrenergic receptors.
 Clinically in patients with thyrotoxicosis (excessive

thyroid hormone) these patients will have

symptoms of increasedmetablosimsuch as
tachycardia, and tremor, individuals with
hypothyroidismwill have symptoms of lowered
metabolismsuch as edema and constipation.
CARRIERS FOR CIRCULATING THYROIDHORMONES

 More than 99% of circulating T4 and T3 is bound to

plasma carrier proteins
 Thyroxine-binding globulin (TBG), binds about 75%
 Transthyretin (TTR), also called thyroxinebinding
prealbumin (TBPA), binds about 10%-15%
 Albumin binds about 7%

 Only ~0.02%of the total T4 in blood is unbound or free.

 Only ~0.4%of total T3 in blood is free
THYROIDHORMONES STIMULATE METABOLIC
ACTIVITIES IN MOST TISSUES
 Thyroid hormones (specifically T3) regulate rate of
overall body metabolism
 T3 increases basal metabolic rate
 Calorigenic effects
 T3 increases oxygen consumption by most peripheral tissues
 Increases body heat production
METABOLIC EFFECTS OF T3
Carbohydratemetabolism :
 Increases absorption of glucose from GIT

 Enhances the glucose uptake by cells

 Increases glycogenolysis

 Accelerate gluconeogenesis
LIPID METABOLISM
 Stimulates lipolysis and release of free fatty acids and
glycerol
 Induces expression of lipogenic enzymes

 Decreases cholesterol in plasma by Stimulates

metabolismof cholesterol to bile acids
 Facilitates rapid removal of LDL from plasma
Proteinmetabolism
 Increases the synthesis of protein in the cells
EFFECTSOF THYROIDHORMONESON THE
CARDIOVASCULAR SYSTEM
 Increase heart rate
 Increase force of cardiac contractions

 Increase stroke volume

 Increase Cardiac output

EFFECTS OF THE THYROID HORMONES IN
GROWTH AND
TISSUE DEVELOPMENT

• Increase growth and maturation of bone

• Increase tooth development and eruption
• Increase growth andmaturation of epidermis,hair follicles
and nails
• Increase rate and force of skeletal muscle contraction
• Inhibits synthesis and increases degradation of
mucopolysaccharides in subcutaneous tissue
EFFECTSOF THE THYROIDHORMONESON
THENERVOUS SYSTEM

• normal CNS neuronal development

• Enhanceswakefulness and alertness
• Enhancesmemory and learning capacity
• Required for normal emotional tone
• Increase speed and amplitude of peripheral nerve reflexes
TESTS OF THYROID EVALUATION – BLOOD
TESTS
 capable of diagnosing primary hypothyroidism
with elevated levels of TSH.
 Modern tests 3rd generation TSH

chemiluminometric assays have detection limits of

0.01mU/L and can more accurately distinguish
between euthyroidismand hyperthyroidism.
 2nd and 3rd generation TSH assays routinely used to

monitor and adjust the thyroid hormone

replacement therapy and hypothyroidism
 The sensitivity of 3rd generation TSHassays had led

to the ability to detect what it termed subclinical .

 Lowfree T4 Normal freeT4 High free T4

Low Secondary Subclinical hyperparathyroidi

TSH hypothyroidism hyperthyroidism sm
Severenonthyroid
al
illness
Normal Secondary Normal Artifact
TSH hypothyroidism Pituitaryhyperthyr
Severenonthyriod oidism
al Laboratorydraww
illness ithin 6
hoursof
thyroxinedose
High Primary Subclinical Test artefact
Pituitaryhyperthyroidism
TSH hypothyroidism hypothyroidism Thyroid hormone system
SERUM T3 AND T4
 usuallymeasured by radioimmunoassay (RIA),
chemiluminometric assay or similar immunometric
technique.
 Because more than 99.9% of thyroid hormone is

protein bound, alteration in thyroid hormone

binding proteins, unrelated to thyroid disease,
frequently lead to total t4 and t3 levels outside of
the normal range.
 Therefore assays have been developed to measure

free t4 and t3, the biologically active forms of

thyroid hormone, and free t4
 kits have replaced total t4 determination
THYROGLOBULIN
 Thyroglobulin is synthesized and stored exclusively in the
thyroid
 This prohormone in the circulation is proof of the presence of

thyroid tissue so thyroglobulin and ideal marker for thyroid

cancer patients
 patients with well differentiated thyroid cancer who have been

treated with surgery or radioactive iodine ablation should

have undetectable thyroglobulin levels
 This is measured by ELISA or RIA
 the accuracy of the test is dependent on the specificity of the

antibody used and the absence of antithyroglobulin antibodies

 even with modern methods, antithyroglobulin autoantibodies

interfere with measurements and lead to unreliable

thyroglobulin results.
 For this reason it is really important that in conjunction with

the thyroglobulin test that the thyroglobulin autoantibodies

are also looked for
PREVALENCE OF THYROID AUTOANTIBODIES

Antibody General Graves Autoimmune

population disease hypothyroidism

Antithyroglobulin 3 12-30 35-60

Thyroid 10-15 45-80 80-99

peroxidise

Anti- TSH 1-2 70-100 6-60

receptor
THYROID AUTOIMMUNITY
OTHER TOOLS FOR THYROID EVALUATION
 Nuclearmedicine
 Ultrasound

 Fine needle aspiration

DISORDERS OF THE THYROID -
HYPOTHYROIDISM
 Defined as low free t4 level with a normal or high
TSH
 This is one of themost common disorders of the

thyroid gland affecting 5-15% of women over 65

 Symptoms depend on the degree of the condition

and the rapidity of its onset

HYPOTHYROIDISM
HYPOTHYROIDISM
 Becuase of the diffuse
distribution of thyroid
hormone receptors and the
many metabolic effects of
the thyroid hormone,
hypothyroidism can lead to
many other abnormalities
 Hypothyroidism can be

divided into 1y, 2y or 3y

disease, dependent on the
location of the effect, the
most common cause is
chronic lymphocytic
thyroiditis which is an
autoimmune disease
targeting the thyroid gland,
often showing and enlarged
gland or goitre.
OTHER CAUSES OF HYPOTHYROIDISM
 Iodine deficiency
 Thyroid surgery

 Radioactive treatment

Condition comments

Chronic lymphocytic thyroiditis TPOAb or TgAb positive in 80-99%of

1y (Hashimoto's thyroiditis) cases
Treatment for toxic goiter- subtotal History and physical exam(neck scar)
thyroidectomy or radioactive iodine are key to diagnosis
Excessive iodine intake History and urinary iodine
Sub acute thyroiditis measurement useful
Usually transient

Hypopituatarism Caused by adenoma, radiation therapy

2y or destruction of the pituitary

Hypothalamic dysfunction rare

3y
TREATMENT OF HYPOTHYROIDISM
 Thyroid hormone replacement therapy (t4)
THYROTOXICOSIS
 Thyrotoxicosis is a constellation of findings that
result when peripheral tissues are presented with
and respond to an excess of thyroid hormone
 Can be caused by
 Excessive thyroid hormone ingestion
 Leaking thyroid follicles
 Excessive thyroid hormone production
THYROTOXICOSIS
GRAVES DISEASE
 Most common cause of thyrotoxicosis
 It is an autoimmune disease in which antibodies are
produced that activate the TSH receptor
 Common signs include goitre and opthalmopathy
 Women are 5 x more likely to get the disease
 Familial link 15%
 Lab findings will usually document a high free T4 and or
t3 level with an undetectable TSH
 Thyroid stimulating immunoglobulins (TSIs) and TSH
receptor antibodies are usually positive in this condition
 RAIU will be elevated
TREATMENT
 Radioactive iodine or surgery
 Beta blockers may be used initially to reduce the
adrenergic excess
TOXIC ADENOMA AND MULTINODULAR GOITRE

 Relatively common causes of hyperthyroidism

 Caused by autonomously functioning thyroid tissue
 Neither TSH or TSHreceptor – stimulating immunoglobulin is
required
 In some, receptor mutations have been identified and these
have the same effect as chronic stimulation of the
TSHreceptors on thyroid hormone production
 Clinically these will present as hyperthyroidismand palpable
thyroid nodules
 When the area is scanned these appear “hot” i.e. they avidly
uptake radioactive iodine, in relation to the suppressed TSH
TREATMENT
 Surgery
 Radioactive iodine- tends to only destroy the
hypersecreting areas of the thyroid gland leaving the
normal (suppressed) areas undamaged
 Medication propylthiouracil (PTU) and methimazole
(MMI)
 These medications will block the thyroid hormone
production but will not lead to remission
SOURCES
 http://fitsweb.uchc.edu/student/selectives/Luzietti
/Thyroid_hormones.htm