Download Hypothyroidism

Thyroid gland diseases
Dr.Isazadehfar
Synthesis and Secretion
 Follicular cells arranged in clumps
 Clumps of cells contain colloid
 Colloid an iodine containing protein called
thryoglobulin. This is the precursor and storage
form of thyroid hormone
 Thyroxine (T4), Triiodothyronone (T3)
Thyroid hormone action
 T4 and T3 circulate in the blood bound to
plasma proteins.
 TBG(70%), TBPA(20%) and albumin(10%).
 T3 is the active form, 5 times more active than
T4.
 T4 is converted to T3 outside the thyroid,
mostly in liver and kidney.
 T3 binds to a nuclear receptor
Regulation of the H-P-T axis
 TRH secreted from hypothalamus controls TSH
production.
 TSH from anterior pituitary stimulates secretion
of T4 and T3 from thyroid
 Regulated by a negative feedback loop
Hypothyroidism
Prevalence of Hypothyroidism
 Prevalence is 14/1000 females and 1/1000
males
 Other autoimmune diseases
 Family history of autoimmune diseases
Primary hypothyroidism-Causes
 Autoimmune thyroiditis (Hashimoto’s)(most common
in adults)
 Radioactive iodine
 Post thyroidectomy
 Anti-thyroid drugs (CMZ PTU)
 Lithium - Amioderone
 Iodine deficiency
 Subacute thyroiditis
 Infiltrative disease
 Agenesis
Secondary hypothyroidism-causes
 Hypothalamic disease
 Pituitary disease
Clinical features
General and CVS
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Tiredness
Weight gain
Cold intolerance
Goitre
Constipation
Hair loss
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Bradycardia
Angina
Cardiac Failure
Pericardial effusion
Hypothermia
Clinical Features
Neurological and Haematological
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Aches and Pains
Carpal Tunnel
Deafness
Hoarseness
Ataxia
Depression
Psychosis
 Iron deficiency A
 Pernicious Anemia
Clinical Features
Skin and Reproduction
 Dry skin
 Erythema
 Vitiligo
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Infertility
Menorrhagia
Galactorrhoea
Amenorrhea
Laboratory Diagnosis
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T4/FT4 reduced
T3/FT3 reduced
TSH elevated
Thyroid Antibodies may indicate aetiology
If TSH is reduced or normal in the presence of
a low T4, pituitary function necessary
Additional abnormal tests
 Fasting cholesterol and triglycerides may be
raised
 AST and LDH may be raised
 CK , Chol , Triglyceride 
 Normochromic or macrocytic anemia
 ECG: Bradycardia with small QRS
complexes
Treatment
 Levothyroxine
 If no residual thyroid function 1.5 μg/kg/day
 Patients under age 60, without cardiac disease can be
started on 50 – 100 μg/day. Dose adjusted according to
TSH levels
 In elderly especially those with CAD the starting dose
should be much less 12.5 – 25 μg/day
 Compliance and adequacy of dose checked by TSH
measurements
 Try to maintain TSH in normal range
Subclinical Hypothyroidism
 Primary thyroidal failure (Hashimotos) is a
gradual process
 Non specific symptoms
 Reduced thyroid activity has been compensated
by an increase TSH output to maintain a
euthyroid state
 Normal T4/FT4 with elevated TSH
 Thyroid antibodies usually positive
Treatment
 Repeat tests after an interval
 If TSH is continuing to rise in the presence of strongly
positive antibodies, the risk of developing hypothyroidism in
the future is high. Thus treatment with thyroxin at this early
stage may be justified if symptomatic
 Beware: Thyroxine may not cure all symptoms
Myxoedema Coma
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Requires prompt treatment. Mortality of 50%.
Suspect in cases of hypothermia
T3 20μg bid IM
Steroids recommended
Glucose to correct hypoglycaemia
Rewarming
Assisted ventilation
Thyroid hormone deficiency in
Pregnancy
 Goitre is common in pregnant women
 TBG increased, thus total T4 and T3 increased.
FT4 and FT3 are normal and TSH remains
unchanged.
 Hypothyroidism treated with thyroxin during
pregnancy. Dose requirements increase. A
change in dose usually needed each trimester.
Post-partum thyroiditis
 Incidence is about 9%.
 Transitory or permanent
 Early hyperthyroidism ,later hypothyroidism
,euthyroid later.
 Increased microsomal antibodies.
 Thyroxine
Elderly
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Non specific symptoms
Osteoporosis
Anemia
Heart Failure
Treatment with thyroxine
Start with small doses and titrate slowly.
(25μg).
Summary
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Suspicion
Women
Previous thyroid disease or treatment
Other autoimmune diseases
Elderly- caution with treatment
HYPERTHYROIDISM
Prevalence
Women
2%
Men
0.2%
15% of cases occur in patients older than 60 years of
age
Mechanism of Clinical Symptoms
1. Catabolism
2. Enhancement of sensitivity to catecholamines
Hyperthyroidism Symptoms
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Hyperactivity/ irritability/ dysphoria
Heat intolerance and sweating
Palpitations
Fatigue and weakness
Weight loss with increase of appetite
Diarrhoea
Polyuria
Oligomenorrhoea, loss of libido
Hyperthyroidism Signs
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Tachycardia (AF)
Tremor
Goiter
Warm moist skin
Proximal muscle weakness
Lid retraction or lag
Gynecomastia
Causes of Hyperthyroidism
Most common causes
 Graves disease
 Toxic multinodular
goiter
 Autonomously
functioning nodule
Rarer causes
 Thyroiditis or other causes
of destruction
 Thyrotoxicosis factitia
 Iodine excess (JodBasedow phenomenon)
 Struma ovarii
 Secondary causes (TSH or
ßHCG)
Graves Disease
 Autoimmune disorder
 Abs directed against TSH receptor with intrinsic
activity. Thyroid and fibroblasts
 Responsible for 60-80% of Thyrotoxicosis
 More common in women
Graves Disease Eye Signs
N - No signs or symptoms
O – Only signs (lid retraction or lag)
no symptoms
S – Soft tissue involvement (periorbital oedema)
P – Proptosis (>22 mm)(Hertl’s test)
E – Extra ocular muscle
involvement (diplopia)
C – Corneal involvement (keratitis)
S – Sight loss (compression of the
optic nerve)
Graves Disease Other
Manifestations
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Pretibial mixoedema
Thyroid acropachy
Onycholysis
Thyroid enlargement with
a bruit frequently audible
over the thyroid
Onycholysis : softening of nails and
loosening of nail beds
 Low total cholesterol
 Low HDL
 Low total cholesterol/HDL ratio
Diagnosis of Graves Disease
 TSH , free T4 
 Thyroid auto antibodies
 Nuclear thyroid
scintigraphy (I123, Te99)
Treatment of Graves Disease
 Reduce thyroid hormone production or reduce the
amount of thyroid tissue
 Antithyroid drugs: propyl-thiouracil, carbimazole
 Radioiodine
 Subtotal thyroidectomy → relapse 4-6 W after
antithyroid therapy(euthyroid), pregnancy, young
people?
 Smptomatic treatment
 Propranolol
Neoplastic Thyroid Disease
 Thyroid Nodules
 Goiter
 Multinodular
 Diffuse
 Endemic
 Thyroid Cancer
 Well differentiated and poorly differentiated
Thyroid Nodular Disease
 Thyroid gland nodules are common in the general
population
 Mainly in women
 Most thyroid nodules are benign
 Less than 5% are malignant
 Only 8% to 10% of patients with thyroid nodules have
thyroid cancer
Multinodular Goiter (MNG)
 MNG is an enlarged thyroid gland containing
multiple nodules
 The thyroid gland becomes more nodular with increasing
age
 In MNG, nodules typically vary in size
 Most MNGs are asymptomatic
 MNG may be toxic or nontoxic
 Toxic MNG occurs when multiple sites of autonomous
nodule hyperfunction develop, resulting in thyrotoxicosis
 Toxic MNG is more common in the elderly
Endemic Goiter
 No longer a problem in the
developed world
 Still a serious health
concern in parts of the
world with iodine
deficiency including
mountainous areas or areas
with high rainfall/flooding
Kaplan, E. et al. Thyroid Disease Manager “Surgery of the Thyroid Gland” Chapter 21, May 9
Thyroid Carcinoma
 Incidence
 Thyroid carcinoma occurs relatively infrequently compared
to the common occurrence of benign thyroid disease
 Thyroid carcinomas
 Papillary (70%)
 Follicular (15%)
 Medullary thyroid (5%)
 Anaplastic carcinoma (5%)
 Primary thyroid lymphomas (5%)
 Metastatic from other primary sites (rare)
Risk factors for Malignancy
 Solitary thyroid nodules in patients >60 or
<30 years of age
 Irradiation of the neck or face during infancy
or teenage years
 Symptoms of pain or pressure (especially a
change in voice)
 Male sex
 Large Nodules (>3 or 4 cm)
 Growth of nodule
Evaluating Thyroid Nodules
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TSH measurement
Ultrasound of the thyroid
Fine needle aspiration
Radioactive iodine imaging
Thyroid Ultrasonography
 Excellent for
characterizing
size and other
features of nodule
 Useful in localizing
nodule for FNA
 Cannot distinguish
between benign vs.
malignant
Thyroid FNA
 Now considered the
most cost effective
and
sensitive/specific
diagnostic test of
thyroid nodules
 The use of US has
expanded the role of
FNA in evaluating
nodules and
improved the
validity of the results
Typical Presentation of
Thyroid Cancer
 Painless lump
 Normal thyroid function tests
 Found on routine examination or by the
patient
 Slow growth or no growth over several
months
Types of Thyroid Cancer
 Papillary :develops from thyroid follicle cells in 1 or
both lobes; grows slowly but can spread
 Follicular :common in countries with insufficient
iodine consumption; lymph node metastases are
uncommon
 Medullary: develops from C-cells, can spread
quickly; sporadic and familial types
 Anaplastic: develops from existing papillary or
follicular cancers; aggressive, usually fatal
 Lymphoma: develops from lymphocytes;
uncommon
Papillary Thyroid Cancer
 Most common type
 Makes up about 70% of all
thyroid carcinomas
 Females outnumber males
3:1
 Highest incidence in women
in midlife
Papillary Thyroid Cancer
Characteristics
 Unencapsulated tumor nodule with ill-defined
margins
 Tumor typically firm and solid
 May present as nodal enlargement
 Commonly metastasizes to neck and mediastinal
lymph nodes
 40% to 60% in adults and 90% in children
 <5% of patients have distant metastases at time
of diagnosis
 Lung is most common site
Follicular Thyroid Cancer
 Second most common
type of thyroid cancer
 Solid invasive tumors,
usually solitary and
encapsulated
 Usually stays in the
thyroid gland, but can
spread to the bones,
lungs, and central
nervous system
 Usually does not spread
to the lymph nodes
Follicular Thyroid
Cancer
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Medullary Thyroid Cancer
 Tumor arising from the
calcitonin-secreting C-cells
of the thyroid gland
 Mortality rate of 10% to
20% at 10 years
 20% to 30% are part of 3
familial autosomal
dominant syndromes
(MEN-2A, MEN-2B, or
familial non-MEN medullary
thyroid cancer [median
age=21 years])
Medullary (C-cell)
Carcinoma
Treatment of Thyroid Cancer
Summary
 Papillary and follicular thyroid cancer
 Generally excellent prognosis
 Risk for recurrence for as long as 30 years
 Initial management
 Surgery and radioactive iodine
 LT4 suppressive therapy
 Follow-up
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Physical examination
Radioactive iodine scans
Serum Tg
TSH and T4