THYROID GLAND

INTRODUCTION
 The thyroid gland produces thyroid hormones, which have diverse effects
throughout the human body
 The thyroid gland is a very vascular organ that is located in the neck
 It consists of two lobes, one on each side of the trachea, just below the
larynx or voice box.
 The two lobes are connected by a narrow band of tissue called the
isthmus.
 Internally, the gland consists of follicles, which produce thyroxine and
triiodothyronine hormones.
 The thyroid gland weighs 25 – 30g in adults
 INTRODUCTION
 The thyroid gland produces two principal hormones
 thyroxine (T4) (tetraiodothyronine) and
 triiodothyronine (T3)
 It also secretes calcitonin, a hormone concerned with calcium
homeostasis
 Thyroxine (T4) is generally converted to triiodothyronine(T3) by
enzymes known as deionases in target cells.
 T4 is the major secretory product of the thyroid and the total T4
concentrations are higher in the blood.
 However T3 is the major thyroid hormone
 BIOSYNTHESIS OF THYROID
HORMONES
 Iodine is essential for the synthesis of thyroid hormones.
 More than half of the body’s total iodine content is found in the thyroid
gland
 Iodine is found in seafood, dairy products, iodine-enriched breads, and
iodated salt
 The thyroid gland is composed of numerous follicles each made up of an
enclosed sphere of highly specialized cells surrounding a core containing
a protein rich material called colloid
 Synthesis of thyroid hormones
 Step 1: uptake of iodide
 Synthesis begins when circulating iodide is cotransported with sodium
ions across the follicular cell plasma membrane.
 Iodide uptake is primarily controlled by TSH (thyroid-stimulating
hormone which is produced by the anterior pituitary gland)
 N.B. Iodine cannot diffuse back into the interstitial fluid once it is in the
cell. This is called iodide trapping.
 Synthesis of thyroid hormones
Step 2: formation of active iodine
 The iodide is oxidised to iodine by the enzyme thyroperoxidase
 Oxidation of iodide permits its binding to the amino acid tyrosine
 TSH promotes the oxidation of iodide to active iodine
 The major component of colloid, thyroglobulin, is a glycoprotein
manufactured exclusively by thyroid follicular cells and rich in the
amino acid tyrosine
 Step 3: Thyroglobulin and synthesis of T3 and T4

 Synthesis of hormone takes place in thyroglobulin, a glycoprotein, which

is produced in the thyroid cell and extruded into the colloid
 Thyroglobulin contains about 140 tyrosine residues which can serve as
substrates for iodine for the formation of thyroid hormone
 Iodine combines with tyrosine in thyroglobulin to form monoiodotyrosine
(MIT) and diiodotyrosine (DIT)
 The binding of one atom of iodine to the tyrosine residues results in the
formation of monoiodothyrosine (MIT),
 whilst the binding of two iodine atoms to tyrosine residues results in the
formation of diiodothyrosine (DIT)
 Two molecules of DIT couple to form thyroxine (T4).
 One molecule of MIT, when coupled with one molecule of DIT,
triiodothyronine (T3)
 These are the two active forms of thyroid hormone.
 The thyroglobulin matrix, with branches now holding T4 and T3, is
stored in the core of the thyroid follicle
 Thyroglobulin containing T4 and T3 can be stored for several months
in the thyroid gland
 The ratio of T3 to T4 in thyroglobulin is usually around 1 : 10 (thus
10% is T3, and about 90% is T4)
 Thyroglobulin is digested by lysosomal proteolytic enzymes in the
thyroid gland.
 The free hormones thyroxine (90%) and triiodothyronine (10%) are
released into the blood, a process stimulated by TSH
 Transport of thyroid hormones
 Since T4 and T3 are lipid-soluble, they diffuse across the plasma membrane and
enter the circulation.
 only 0.04% of T4 and 0.4% of T3 are unbound by proteins and available for
hormonal activity
 They are lipophilic, thus can only be transported through by carrier proteins
 The three major binding proteins, in order of significance, are
o thyroxine-binding globulin (TBG) (about 99%)
o thyroxine-binding prealbumin (TBPA)
o Albumin
o Alterations to
 The concentrations of these binding proteins significantly affect circulating
quantities of T4 and T3.
 The unbound or free T4 and T3 are considered to be the biologically active
fraction
 They enter cells, bind to specific receptors, and initiate the physiological
response and cause the negative feedback regulation of thyroid hormone
secretion.
 The approximate reference ranges for serum concentrations of total and
free thyroid hormones are:
HORMONE TOTAL FREE

T4 60 – 160 nmol/L 10–25 pmol/L

T3 1.2 - 2.3 nmol/L 4.0 – 6.5 pmol/L
 Thyroxine (T4) is released from the thyroid gland in greater amounts than
T3,
 However, T3 is the more biologically active than T4.
 Thyroxine enters cells and is deiodinated (removal of one I atom) to form
T3.
 Thyroxine is the major hormone secreted by the thyroid gland, which is
converted by specific de-iodinase enzymes, particularly in the liver and
kidney, to form T3, the biologically active hormone.
 The peripheral deiodination of T4 provides approximately 80% of plasma
T3, the remainder being derived from thyroid gland secretion
 Control of Thyroid Function

 This is achieved through the hypothalamic–pituitary–thyroid axis (HPT-

axis)
 This axis is central to the regulation of thyroid hormone production
 The hypothalamus secretes thyrotropin-releasing hormone (TRH)
 TRH stimulates cells in the anterior pituitary gland to produce thyroid-
stimulating hormone (TSH).
 TSH stimulates the thyroid gland to produce and secrete mainly T4 and
smaller quantities of T3.
 T4 that is released by the thyroid gland is mostly converted to T3 by the
liver and kidney.
 Control of Thyroid Function
 When the hypothalamus and pituitary sense that there is an
inadequate amount of thyroid hormone in circulation, TRH
and TSH secretion increases and stimulates increased
thyroid hormone production.
 If thyroid hormone levels are high, TRH and TSH release
will be inhibited, leading to lower levels of thyroid hormone
production.
 This feedback loop requires a normally functioning
hypothalamus, pituitary, and thyroid gland, as well as an
absence of any interfering agents or agents that mimic TSH
action
 Biological functions of thyroid hormones
 Thyroid hormones have widespread function effecting metabolism,
growth and maturation, and other organ-specific effects
 They increase protein catabolism, promote gluconeogenesis, increase
the utilization of glucose and promote lipid metabolism
 influence cardiac function by increasing heart rate, myocardial
contractility, blood volume, and cardiac output while decreasing
peripheral vascular volume.
 Biological functions of thyroid hormones
 They stimulate the production of cytokines, growth factors and
other factors to stimulate bone development and growth
 Thyroid hormones also promote increased motility in the
gastrointestinal system and increase adrenergic activity and sensitivity
in the central nervous system

 Because they also promote cell differentiation, growth and maturation

thyroid hormones are essential in early fetal life to promote normal
growth and brain development
 THYROID FUNCTION TEST (TFT)
 Is a test used to quantify thyroid stimulating hormone (TSH) and
circulating thyroid hormones in serum
 TFTs are used for diagnosis and to monitor treatment of common
thyroid gland disorders.

Thyroid Stimulating Hormone (TSH)

 Is the most useful test for assessing thyroid function
 TSH is a sensitive marker of thyroid dysfunction, since small changes
in fT4 create large changes in TSH
 High TSH implies hypothyroidism,
 Low TSH levels implies hyperthyroidism
 THYROID FUNCTION TEST (TFT)
 When TSH levels are out of the reference range, but concentrations of
free thyroxine (fT4) fall within the reference range, this is referred to as
subclinical thyroid dysfunction.(mild degree of thyroid
dysfunction)

 Thus if TSH is slightly increased but fT4 is normal then it is termed

subclinical hypothyroidism

 If TSH is slightly reduced but fT4 is normal, then it is termed

subclinical hyperthyroidism
 Interpretation of TFT results
TSH Free T4 Free T3 Condition
Normal Normal Normal
Low High High Hyperthyroidism
Low Normal Normal Sub-clinical hyperthyroidism
Low Normal High T3 toxicosis
Low High Normal Thyroiditis
T4 ingestion
Hyperthyroidism in the elderly or with
comorbidity
Low Low Low Sick euthyroid syndrome
Secondary (Central) hypothyroidism

High Normal Normal Subclinical hypothyroidism

Recovery from Sick euthyroid syndrome

High Low Low Primary hypothyroidism

High High High TSH producing pituitary adenoma
TFT Result Pattern

 Low TSH and high FT4 (and FT3)

 primary hyperthyroidism
 Common causes include Graves disease and goitre
TFT Result Pattern

 High TSH and low FT4 (and FT3)

 suggests primary hypothyroidism
 autoimmune thyroiditis (Hashimoto’s disease or atrophic
thyroiditis)
 follows radioiodine or thyroidectomy
TFT Result Pattern

 Low TSH and normal FT4 and/or FT3

 Subclinical hyperthyroidism
 Characterized by normal thyroid hormones but low TSH
TFT Result Pattern

 High TSH and normal FT4 (and FT3)

 subclinical hypothyroidism
TFT Result Pattern

 High FT4 (±FT3) with inappropriately normal or high

TSH
 DISORDERS OF THE THYROID
HYPOTHYROIDISM
 Hypothyroidism results when the thyroid gland provides insufficient amounts
of thyroid hormone for the needs of peripheral tissues
 This leads to impaired synthesis of T3 and T4
 Hypothyroidism is majorly divided into two categories, primary and
secondary (central) hypothyroidism.
 In primary hypothyroidism, thyroid gland itself is not able to produce
adequate amounts of thyroid hormone
 This is characterized by high TSH and low T3 and T4.
 Secondary (central) hypothyroidism
 Occurs when the thyroid gland itself is normal, and the pathology is
related to the pituitary gland or hypothalamus, producing a deficiency of
TSH or TRH or both.
 Generally, secondary hypothyroidism is associated with low TSH and
low T3 and T4.
 However, TSH levels may also be normal or even slightly elevated.
 For this reason, TSH is often an unreliable measure of secondary
hypothyroidism and should not be used to assess the adequacy of thyroid
replacement in these patients
 HYPOTHYROIDISM
Causes
 Iodine deficiency (globally the most common cause)
 Autoimmune disease (Hashimoto’s disease, where autoantibodies cause
progressive destruction of the individual’s own thyroid gland.
Hashimoto’s disease is the most commonest cause of hypothyroidism in
developed countries))
 Atrophic hypothyroidism
 Enzyme defect in thyroxine synthesis
 Hypopituitarism caused by e.g. tumors, surgery, radiotherapy
 Hypothalamic damage due to tumors, radiotherapy or trauma
 Drugs like amiodarone
 Symptoms Signs
 lethargy, tiredness  Periorbital and facial
 cold intolerance oedema
 Pale dry skin
 dryness and coarsening of skin & hair
 Goitre
 weight gain
 Cool peripheries
 slow relaxation of muscles and tendon reflexes
 Bradycardia
 depression, dementia, psychosis
 constipation  Median nerve compression

 bradycardia, angina pericardial effusions  Delayed relaxation of

reflexes
 muscle stiffness
 carpal tunnel syndrome
 menorrhagia, infertility, galactorrhoea
 Symptoms
 Hypothyroidism in children is associated with physical and mental
retardation, collectively known as cretinism
 Hypothyroidism in adult causes myxoedema, characterized by bagginess
under the eyes, puffiness of face, slowness in physical and mental
activities
 any unexplained hypercholesterolaemia or elevated creatine kinase
should raise the suspicion of hypothyroidism
 Thyroiditis

 is the inflammation of the thyroid gland, usually on a viral or

autoimmune basis
 Results from an antibody attack on the thyroid gland as a result of
autoimmune disease, bacteria or viral infection or drugs like interferon
and amiodarone
 Causes include Hashimoto’s disease (autoimmune attack of the thyroid
gland), postpartum thyroiditis )occurs after the delivery of a baby),
Drug-Induced and Radiation Thyroiditis and acute thyroiditis caused by
infectious organisms
 Goitre
 Simply refers to the abnormal enlargement of the thyroid gland
 The presence of a goitre does not necessarily indicate a malfunctioning
thyroid gland, but rather a condition causing the thyroid gland to grow
abnormally
 It can occur in hypothyroidism, hyperthyroidism or euthyroidism
 One of the most common causes of goiter formation worldwide is iodine
deficiency
 Other causes include Hashimoto’s disease (causes hypothyroidism) and
Grave’s disease (causes hyperthyroidism)

 Congenital hypothyroidism
 occurs in newborn children with a defect in the development of the thyroid
gland, resulting in either its absence or an undeveloped gland
 Untreated children develop a condition referred to as cretinism.
 Children with cretinism present with growth failure, developmental delay,
and are often deaf and mute
 Congenital hypothyroidism is caused by a deficiency of thyroid hormones at
birth, usually due to an absent thyroid gland or by an ectopic gland, which
means the thyroid gland is not in the correct anatomical position in the neck
 HYPERTHYROIDISM
 Hyperthyroidism is a condition characterised by increased thyroid
hormone synthesis and secretion from the thyroid gland
 Any condition in which there is too much thyroid hormone produced in
the body
 Hyperthyroidism (overactive thyroid gland) is different from
thyrotoxicosis
 Thyrotoxicosis refers to the clinical syndrome of excess circulating
thyroid hormones, irrespective of the source
 Clinical features
 Weight loss despite increased appetite
 heat-related symptoms (sweating, and polydipsia, heat intolerance
 Tremor; nervousness; anxiety; fatigue; weakness; disturbed sleep; poor
concentration
 Tachycardia; systolic hypertension; irregular heartbeat (atrial fibrillation)
 Diarrhoea, oligomenorrhoea, infertility, goiter
 Causes of hyperthyroidism

 Grave’s disease
 Toxic multinodular goitre
 Painful thyroiditis
 Iodine containing drugs
 Excessive T4 or T3 intake
 TSH secreting tumor
 Post-partum thyroiditis
 Grave’s disease

 Is an autoimmune condition, in which antibodies to the TSH receptor

bind it in such a way as to mimic TSH and lock the receptor in its
active conformation.
 This causes constant stimulation of the gland to grow and produce
thyroxine
 Pituitary TSH secretion is suppressed.
 A unique feature of Graves’ (as opposed to other causes of toxicosis)
is the presence of proptosis (bulging eyes, due to thickening of
retroorbital muscles, and swelling of soft tissue in the legs and feet
(pre-tibial myxoedema)
 Neonatal hyperthyroidism

 occurs in infants born to mothers who have or have had Graves’

disease
 It is due to thyroid stimulating antibodies (IgG) crossing the placenta
and stimulating the fetal thyroid.
 It is transient since these immunoglobulins are gradually cleared, but
may need short term treatment