The document discusses the thyroid gland and thyroid hormones. It covers the importance of thyroid hormones in growth, development and physiological processes. It describes the morphology of the thyroid gland including its location, structure, blood supply and functional units. It explains thyroid hormone biosynthesis and secretion, the effects of thyroid hormones, and the regulation of thyroid function by TSH. It discusses causes, signs and symptoms, and treatment of both hypothyroidism and hyperthyroidism.

1. Thyroid Gland
Dr. May Galal

2. Dr. M. Alzaharna (2014)
Importance
• In the adult human, normal operation of a wide
variety of physiological processes affecting
virtually every organ system requires appropriate
amounts of thyroid hormone
• Governing all these processes, thyroid hormone
acts as a modulator, or gain control, rather than
an all-or-none signal that turns the process on or
off
• In the immature individual, thyroid hormone
plays an indispensable role in growth and
development
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3. Dr. M. Alzaharna (2014)
Morphology
• The human thyroid gland is
located at the base of the neck
and wraps around the trachea
just below the cricoid cartilage
• The two large lateral lobes that
comprise the bulk of the gland
lie on either side of the
trachea and are connected by
a thin isthmus
• A third structure, the
pyramidal lobe, is sometimes
also seen as a finger-like
projection extending
headward from the isthmus
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4. Dr. M. Alzaharna (2014)
Morphology
• The thyroid gland in the normal human being
weighs about 20 g but is capable of enormous
growth, sometimes achieving a weight of
several hundred grams when stimulated
intensely over a long period of time
• Relative to its weight, the thyroid gland
receives a greater flow of blood than most
other tissues of the body
• The thyroid gland also has an abundant supply
of sympathetic and parasympathetic nerves
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5. Dr. M. Alzaharna (2014)
Morphology
• The functional unit of the
thyroid gland is the follicle
• It is composed of epithelial
cells arranged as hollow
vesicles of various shapes
ranging in size from 0.02 to 0.3
mm in diameter
• It is filled with a glycoprotein
colloid called thyroglobulin
• Groups of densely packed
follicles are bound together by
connective tissue septa to
form lobules
• Single layer of epithelial cells (red arrow)
• Parafollicular cell (white arrow)
• Connective tissue septum separating two
lobules (green arrow)
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6. Dr. M. Alzaharna (2014)
• Secretory cells of the thyroid gland are of two
types:
– Follicular cells, which produce the classical thyroid
hormones, thyroxine and triiodothyronine
– Parafollicular, or C cells, are located between the
follicles and produce the polypeptide hormone
calcitonin
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7. Dr. M. Alzaharna (2014)
Thyroid Hormones
• The thyroid hormones are α-amino
acid derivatives of tyrosine
• Thyroxine & Triiodothyronine are
exceptionally rich in iodine, which
comprises more than half of their
molecular weight
• Thyroxine contains four atoms of
iodine and is abbreviated as T4
• Triiodothyronine, which has three
atoms of iodine, is abbreviated as
T3
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8. Dr. M. Alzaharna (2014)
Thyroid Hormone Biosynthesis & Secretion
• Iodide (I-) is transported into the
thyroid follicular cell by the
sodium/iodide symporter (NIS)
• Thyroglobulin (TG) is synthesized
by microsomes on the rough
endoplasmic reticulum (ER)
• Iodide reacts with tyrosine
residues in TG in the follicular
lumen to produce
monoiodotyrosyl (MIT) and
diiodotyrosyl (DIT) within the
peptide chain
• The TPO reaction also catalyzes
the coupling of iodotyrosines to
form thyroxine (T4) and some
triiodothyronine
• Iodide channel called pendrin (P)
• Thyroid oxidase ( TO)
• Thyroid peroxidase ( TPO)
• Iodotyrosine deiodinase ( ITDI) 8

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Control of Thyroid Function
• The principal regulator of thyroid function is the
thyroid-stimulating hormone (TSH), which is
secreted by thyrotropes in the pituitary gland
• Binding of TSH to the G-protein coupled receptor
results in its activation and production of c-AMP
• Each step of hormone biosynthesis, storage, and
secretion appears to be directly stimulated by a c-
AMP-dependent process
• This lead finally to phosphorylation of proteins
including transcription factors and protein
production
• TSH also increases blood flow to the thyroid
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14. Dr. M. Alzaharna (2014)
Physiological Effects of Thyroid Hormones
• Growth and maturation
– Skeletal system
– C.N.S. DEVELOPMENT & FUNTION
• “ESSENTIAL” in the newborn to prevent
development of “CRETINISMS” & to a normal “IQ”
• normal development of the brain
• Modulation of brain cerebration
• Mood modulation
• Metabolism
– Oxidative metabolism and thermogenesis
– Carbohydrate metabolism
• increases glucose absorption from the digestive tract,
glycogenolysis and gluconeogenesis
• and glucose oxidation in liver, fat, and muscle cells 14

15. Dr. M. Alzaharna (2014)
– CHO METABOLISM
• Increases:
– Glucose absorption of the GI tract
– Glucose consumption by peripheral tissues
– Glucose uptake by the cells
– Glycolysis
– Gluconeogenesis
– Insulin secretion
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16. Dr. M. Alzaharna (2014)
Physiological Effects of Thyroid Hormones
– Lipid metabolism
• The primary determinant of lipogenesis is not T3
– Nitrogen metabolism
• Cardiovascular system
– Cardiac output is increased in hyperthyroidism
and decreased in thyroid deficiency
• Autonomic nervous system
– Thyroid hormones increase the abundance of
receptors for epinephrine and norepinephrine in
the myocardium and some other tissues
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• Brain----growth & development of nervous system
• Bone & tissue growth– linear growth & maturation of
bones
• CVS-- increased contractility, heart rate & cardiac
output
• GUT—increased absorption of nutrients, increased
motility
• Liver -increased gluconeogenesis & glycogenolysis

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• Adipose tissue –increased lipolysis
• Muscle –increased protein catabolism in skeletal
muscle
• Kidney -increased erythropoietin synthesis
• Respiration- increased central stimulation of
respiration
• Energy metabolism -increased BMR, increased
oxygen consumption, increased heat production
stimulation of Na-K-ATP ase

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– ELECTROLYTE BALANCE
• Low Thyroid hormones could induce
hyponatremia
– VITAMIN METABOLISM
• Modulates vitamin consumption
– HEMATOPOIETIC SYSTEM
• Could induce anemia
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20. Dr. M. Alzaharna (2014)
Regulation of Thyroid Hormone
Secretion
• Secretion of thyroid hormones depends on stimulation of
thyroid follicular cells by TSH
– TSH absence: quiescent and atrophy of thyroid cells
– administration of TSH increases both synthesis and
secretion of T4 and T3
• TSH bears primary responsibility for integrating thyroid
function with bodily needs
• Secretion of TSH by the pituitary gland is governed by:
– positive input from the hypothalamus by way of
thyrotropin releasing hormone (TRH)
– and negative input from the thyroid gland by way of T3
and T4
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24. Dr. M. Alzaharna (2014)
Primary hypothyroidism
– Iodine deficiency- most common cause worldwide
– Congenital
– Autoimmune mediated
• Hashimoto’s thyroiditis- B lymphocytes invade thyroid
– Iatrogenic- post-thyroidectomy or radio-iodine
treatment
– Drug-induced – Anti-thyroid, lithium, amiodarone
– Severe infection
– Trauma to thyroid/pituitary/hypothalamus
– Absent or ectopic thyroid gland
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26. Dr. M. Alzaharna (2014)
• CONGENITAL HYPOTHYROIDISM
• Prevalence: 1 in 3000 to 4000
newborns
– Cause: Dysgenesis 85%
– Dx: Blood screning (TSH &/or
T4)
• Hypofunction in childhood - cretinism
• Growth inhibition
• Unproportional body development
• Disorders of mental development
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Treatment:
Supplemental Tx. With Levothyroxine
is “essential” for a normal C.N.S.
Development and prevention of
mental retardation

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Hypothyroidism Symptoms
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Hypothyroidism Signs

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• underproduction of thyroid hormones
slows metabolism, leading to fluid
retention and swollen tissues that can
exert pressure on peripheral nerves
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Chronic Autoimmune Thyroiditis
(Hashimoto Thyroiditis)
• Occurs when there is a severe defect in thyroid hormone
synthesis
– Is a chronic inflammatory autoimmune disease characterized by
destruction of the thyroid gland by autoantibodies against
thyroglobulin, thyroperoxidase, and other thyroid tissue
components
– Patients present with hypothyroidism, painless goiter, and other
overt signs
• Persons with autoimmune thyroid disease may have other
concomitant autoimmune disorders
– Most commonly associated with type 1 diabetes mellitus
• Will often have significantly elevated anti-TPO ab

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Endemic goiter
(occurs in the
deficit of iodine in
water, soil and air)
Connective tissue is
enlarged in gland and
it is increased in size
markedly

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Hypothyroidism Treatment Goal
Euthyroidism
• The goal of hypothyroidism therapy is to
replace thyroxine to mimic normal,
physiologic levels and alleviate signs,
symptoms, and biochemical abnormalities

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Therapy Initiation and Titration
• Therapy with levothyroxine sodium products requires
individualized patient dosing
– Careful titration: use a formulation with consistent doses
– Clinical evaluation: symptoms resolve more slowly than TSH
response
– Laboratory monitoring: need consistent, sensitive TSH
measurements
• Individualized patient dosing is influenced by
– Age and weight
– Cardiovascular health
– Severity and duration of hypothyroidism
– Concomitant disease states and treatment

35. Dr. M. Alzaharna (2014)
• Levothyroxine sodium is the treatment of choice for the
routine management of hypothyroidism
– Adults: about 1.7 g/kg of body weight/d
– Children up to 4.0 g/kg of body weight/d
– Elderly <1.0 g/kg of body weight/d
• Clinical and biochemical evaluations at 6- to 8-week
intervals until the serum TSH concentration is normalized
• Given the narrow and precise treatment range for
levothyroxine therapy, it is preferable to maintain the
patient on the same brand throughout treatment
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Primary Hypothyroidism Treatment
Algorithm
TSH >3.0 IU/mL TSH <0.5 IU/mL
Initial Levothyroxine Dose
Increase
Levothyroxine
Dose by
12.5 to 25 g/d
Repeat TSH Test
6-8 Weeks
TSH 0.5- 2.0 IU/mL
Symptoms Resolved
Measure TSH at 6 Months,
Then Annually or
When Symptomatic
Continue Dose Decrease
Levothyroxine
Dose by
12.5 to 25 g/d

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Caution in Patients With Underlying
Cardiac Disease
• Using LT4 in those with ischemic heart disease increases the risk
of MI, aggravation of angina, or cardiac arrhythmias
• For patients <50 years of age with underlying cardiac disease,
initiate LT4 at 25-50 g/d with gradual dose increments at 6- to
8-week intervals
• For elderly patients with cardiac disease, start LT4 at 12.5-25
g/d, with gradual dose increments at 4- to 6-week intervals
• The LT4 dose is generally adjusted in 12.5-25 g increments

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Hypothyroidism - Management
• Conservative
– Lifestyle - smoking cessation, weight loss
• Medical
– Levothyroxine (T4)
• Repeat TSH in 6/52
• Adjust dose according to clinical response and
normalisation of TSH
• Caution in patients with IHD- risk of exacerbation of MI
• Clinical improvement may not begin for 2/52
• Symptom resolution 6/12 if not consider +T3

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Hyperthyroidism (thyrotoxicosis) is excess thyroid hormone
– Autoimmune
• Graves Disease (76%)
– F>M, age 20-40
– IgG auto antibodies bind TSH receptors T3 & T4
– Leads to gland hyper function
– Toxic adenoma and toxic multinodular goitre
– Viral Thyroiditis (de Quervain’s)
• Fever and ESR- self limiting
– Exogenous Iodine
– Neonatal thyrotoxicosis
– Drugs- Amiodarone
– TSH secreting pituitary adenoma (rare)
– HCG producing tumour
Hyperthyroidism Causes

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Hyperthyroid Symptoms

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Hyperthyroid Signs
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accumulation of hyaloronic acid in
dermis- manifestation of graves

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Hyperthyroidism – Eye Disease
• Associated with Graves’ disease
– Inflammation of retro-orbital tissues
– Optic nerve compression atrophy
• Symptoms
– Eye discomfort, grittiness
– Excess tear production
– Photophobia
– Diplopia
– Decreased acuity
• Signs
– Exopthalmos- Graves
– Proptosis
– Opthalmoplegia
– Oedema

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• Symptoms:
– Hyperactivity
– Irritability
– Dysphoria
– Heat intolerance &
sweating
– Palpitations
– Fatigue & weakness
– Weight loss with
increased appetite
– Diarrhea
– Polyuria
– Sexual dysfunction
• Signs:
– Tachycardia
– Atrial fibrillation
– Tremor
– Goiter
– Warm, moist skin
– Muscle weakness,
myopathy
– Lid retraction or lag
– Gynecomastia
– * Exophtalmus
– * Pretibial
myxedema

46. Dr. M. Alzaharna (2014)
• Investigating Thyroid Disease
• TSH- first thing you assess
– Normal range 0.5-5 U/ml
– Supressed= Hyperthyroid
– Elevated= Hypothyroid
If TSH abnormal request Free T4
– Elevated= Hyperthyroid
– Suppressed= Hypothyroid
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TSH
T3, T4
TSH
T3, T4 T3, T4
TSH
Hypothyroidism Hyperthyroidism Hypopituitarism TSH secreting
tumour
↑TSH; ↓T4,T3 ↓TSH; ↑T4,T3 ↓TSH; ↓T4,T3 ↑TSH; ↑T4,T3
TSH
T3, T4

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Hyperthyroidism - Management
• Conservative
– Smoking cessation – especially with Graves’s
ophthalmology, associated with worse prognosis
• Medical
– Symptomatic – β-blockers
– Carbimazole, propylthiouracil (50% relapse)
• Risk of agranulocytosis
– Radio-iodine treatment –avoid contact with
pregnant women and small children
• Long term likely to become hypothyroid

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• Anti-thyroid drugs:
• Inhibit the iodination of tyrosyl residues in
thyroglobulin. They inhibit TPO catalysed
oxidation reaction.
• Propylthiouracil reduce the de-iodination of
T4 into T3 in peripheral tissues.
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• Surgical
– Subtotal/total thyroidectomy
– Orbital decompression if thyroid eye disease causing
compression of optic nerve
• Complications of thyroid surgery
– Immediate
• Haemorrhage
– Short term
• Infection
– Long term
• Damage to laryngeal nerve
• Hypothyroidism
• Transient hypocalcaemia
• Hypoparathyroidism

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Adjunctive Therapy of
Hyperthyroidism
• Beta blockers
• Corticosteroid therapy
• Bile acid sequestrants
• Iodide

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• Treatment:
– Reducing thyroid hormone synthesis:
• Antithyroid drugs (Methimazole, Propylthyouracil)
• Radioiodine (131I)
• Subtotal thyroidectomy
– Reducing Thyroid hormone effects:
• Propranolol
• Glucocorticoids
• Benzodiazepines
– Reducing peripheral conversion of T4 to T3
• Propylthyouracil
• Glucocorticoids
• Iodide (Large oral or IV dosage) (Wolf-Chaikoff effect)
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Which Treatment to choose?
Depends on:
• Patient preference
• Severity of hyperthyroidism
• Evidence of complications of
hyperthyroidism
• Pregnancy
• The cause of hyperthyroidism

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Complications of Thyroid Disease
• Myxoedema
• Severe hypothyroidism (TSH T4 )
– Accumulation of mucopolysaccaride in subcutaneous
tissues
– Presents with
• Hyponatraemia
• Hypoglycaemia
• Hypotension
• Hypothermia
• Coma
• Confusion
• HF
• Anaemia
HIGH MORTALITY

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Thyroid Storm
• Life threatening emergency (rare) – 30% mortality even with early
recognition and management
• Exacerbation of thyrotoxicosis precipitated by stress i.e.
– Surgery
– Infection
– Trauma
• Signs
– Fever
– Agitation and confusion
– Tachycardia +/- AF
• Management
• IV fluids
• Broad spectrum antibiotics
• Propanolol, digoxin
• Antithyroid drugs – sodium ipodate, Lugol’s solution, carbimazole

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Thyroid Cancers
Type of tumour Frequency (%) Age at
presentation
(years)
20 year survival
(%)
Papillary 70 20-40 95
Follicular 20 40-60 60
Anaplastic 5 >60 <1
Medullary 5 >40 50
Lymphoma 2 >60 10

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Investigating Thyroid cancers
• Serum calcitonin & CEA in Medullary cancer
• Radioactive iodine scan
• Ultrasound
• FNA
• CT scan- detects metastases
• MRI and PET scans- distant metastases
Treatment: Total thyroidectomy & wide LN clearance
RAI ablation for papillary & follicular

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Definition of Subclinical
Hypothyroidism
• An isolated elevated TSH level in the
setting of normal T3 and T4 levels
• Symptoms may be present or absent

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Thyroid function tests
Estimation of thyroid
hormones
• Total T4
• Total T3
Estimation of free
hormone fraction
• Free T4 fraction %FT4
• Free T3 fraction %FT3
• THBR
Estimates of free
hormone
concentration
• FT4E (T4 X %FT4)
• FT3E (T3 X % FT3)
• FT4I (T4 X THBR)
• FT3I (T3 X THBR)
• T4: TBG ratio

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Serum binding proteins
• Thyroxine binding
globulin
• Thyroxine binding
prealbumin
Tests for autoimmune
thyroid disease
• Anti thyroglobulin
Abs
• Anti microsomal Abs
• Anti TPO antibodies
• TSH receptor anti
bodies
Other hormones &
thyroid related
proteins
• TRH
• Thyroglobulin
• calcitonin

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Measurement of T4,T3 &rT3
• METHOD
• Immunoassay
• Chemiluminiscence
• The major clinical role for T3 measurements are
in the diagnosis & monitoring of hyperthyroid pts
with suppressed TSH & normal FT4
• r T3 test is not always elevated with illness. It is
seldom used in pts with euthyroid sick syndrome
• Specifially, renal failure is associated with low r T3
conc.

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FT4 index
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• Unlike direct free T4 methods , index methods
measure both the serum total T4 & the free T4
fraction
• They have an advtantage that they can define
whether an abnormal FT4 estimate is due to
abnormal hormone production or due to
abnormal protein binding
• An FT4 index is sometimes directly calculated
using the percentage T-uptake
• FT4I =total T4(µg/dl) x % thyroid uptake/ 100

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Plasma TSH
Method- Immunoassay
-chemiluminiscence
Secretion of TSH occurs in a circadian fashion
Primary Hypothyroidism-TSH increased
Secondary hypothyroidism-TSH ,T3 ,T4 are low
Primary hyper thyroidism –TSH decreased
Secondary hyperthyroidism-TSH,T3,T4 high

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TSH stimulation test
Measurement of serum T4 after TSH injection
• No response - primary
• Increase of T4- secondary
• Useful for distinguishing primary from
secondary hypothyroidism

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• TRH administration will stimulate the production of TSH
• Useful for differentiating hypothalamic from a pituitary
hypotyroidism
• There is increase of TSH after TRH in hypothalamic disorder
If the hypothalamo pituitary axis is normal .the T3 and T4
secretions will be increased
An abnormal response is seen in
Hyperthyroidism – T4 elevated
• Hypopituitarism- T4 Levels subnormal
• Primary hypothyroidism-exaggerated response
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TRH response test

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• TBG is the thyroid binding globulin with the
greatest affinity for T4
• TBG is very important for regulating the conc.
And availability of the FT4 hormone.
• Method - immunoassay
- commercial kit methods available
- chemiluminiscence
• Estrogen induced TBG excess and congenital
TBG deficiency are important abnormalities
that affect the test results
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Determination of thyroid binding
globulin

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• Thyroglobulin is used primarily as tumor marker in pts
carrying a diagnosis of differentiated thyroid carcinoma
Tg levels are elevated in
Thyroid follicular &papillary carcinoma
Certain non neoplastic conditions like..,
• Thyroid adenoma
• Subacute thyroiditis
• hashimoto’s thyroiditis
• Grave’s disease
• Tg determination is used as an adjunct to ultrasound and
radio iodine scanning
• Assessment of serum Tg also aids in management of infants
with congenital hypo thyroidism
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71. Dr. M. Alzaharna (2014)
Normal ranges
• T3 :120-190 ng/dl
• r T3 : 10-25 ng/dl
• T4 : 5-12 µg/dl
• Thyroglobulin:3-5 µg/dl
• TRH :5-60 ng/L
• TSH :0.5-5 µU/ L
• Thyroxine binding globulin :1-2 mg/dl
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