Transcript الشريحة 1

Follicles: the Functional Units of the
Thyroid Gland
Follicles Are the Sites
Where Key Thyroid
Elements Function:
• Thyroglobulin (Tg)
• Tyrosine
• Iodine
• Thyroxine (T4)
• Triiodotyrosine (T3)
The follicular epithelial cells
synthesise thyroid hormones by
incorporating iodine into the
amino acid tyrosine on the surface
of thyroglobulin (Tg), a protein
secreted into the colloid of the
follicle
T3 and T4 circulate in plasma almost
entirely (> 99%) bound to transport
proteins, mainly thyroxine-binding
globulin (TBG). It is the unbound or
free hormones which diffuse into
tissues and exert diverse metabolic
actions. While it is possible to measure
the concentration of total or free T3
and T4 in plasma.
Hyperthyroidism)Thyrotoxicosis)
“Hyperthyroidism” refers to overactivity 
of the thyroid gland leading to excessive
synthesis of thyroid hormones and
accelerated metabolism in the peripheral
tissues. The secretion of thyroid hormone
is no longer under the regulatory control
of the hypothalamic-pituitary center.
HORMONE EXCESS
1- Graves' disease
2- Multinodular goitre
3- Toxic adenoma
Epidemiology
Prevalence of hyperthyroidism in the
general population is 1.2%
Graves’ Disease – most common etiology
0.4%
Graves’ Disease is more common in
females (7:1 ratio)
GRAVES' DISEASE
The most common manifestation is
thyrotoxicosis
1-with or without a diffuse goitre.
2- ophthalmopathy
3- and rarely pretibial myxoedema
These features usually occur in thyrotoxic
patients,. Graves' disease can occur at any age
but is unusual before puberty and most
commonly affects women aged 30-50 years
GRAVES' DISEASE
The thyrotoxicosis results from the production 
of IgG antibodies directed against the TSH
receptor on the thyroid follicular cell, which
stimulate thyroid hormone production and, in
the majority, goitre formation. These
antibodies are termed thyroid-stimulating
immunoglobulins or TSH receptor antibodies
(TRAb)
The Classic Triad of Graves’ Disease
1-Hyperthyroidism (90%)
2-Ophthalmopathy (20-40%)
proptosis, ophthalmoplegia, conjunctival irritation
3-Dermopathy (0.5-4.3%)
localized myxedema, usually pretibial
especially common with severe ophthalmopathy
Graves’ Ophthalmopathy
Antibodies to the TSH receptor also
target retroorbital tissues
T-cell inflammatory infiltrate -> fibroblast
exophthalmus
Severe: keratopathy, diplopia, ,compressive optic neuropathy
Eyes
1) Lid lag
slowly moving point from above eye level to below
and see if eyelid smoothly follows movement of
eye -
2) Lid retraction
Lid retraction due to exophalmos (protrusion)
Pretibial myxedema
Activation of fibroblasts leads to increased 
hyaluronic acid and chondroitin sulfate
Asymmetric, raised, firm,
pink-to-purple, brown
plaques of nonpitting
edema on the anterior
leg
Features of Hyperthyroidism
Weight loss, heat intolerance
Thinning of hair, softening of nails
Stare and eyelid lag
Palpitations, symptoms of heart failure
Dyspnea, decreased exercise tolerance
Diarrhea
Frequency, nocturia
Psychosis, agitation, depression
Cardiac manifestations
Palpitations
Dyspnoea on exertion
Angina
Ankle swelling
Sinus tachycardia
Atrial fibrillation
Systolic hypertension/
increased pulse pressure
Cardiac failure
Gastroenterology
Diarrhoea, steatorrhoea, 
hyperdefecation
Vomiting
Neuromuscular
Anxiety, irritability, emotional lability,
psyachosis
Tremor
Muscle weakness
Periodic paralysis
Hyper-reflexia
sustained clonus
Proximal myopathy
Bulbar myopathy
Dermatological
Sweating
Pruritis
Alopecia
Reproductive
Amenorrhoea
Infertility
abortion
Loss of libido
impotence
Signs and Symptoms of Hyperthyroidism
Nervousness
Irritability
Difficulty Sleeping
Bulging Eyes/Unblinking
Stare
Swelling (Goiter)
Menstrual Irregularities or
Light Period
Frequent Bowel
Movements
Warm, Moist Palms
Excessive Vomiting in
Pregnancy
Hoarseness or
Deepening of Voice
Persistent
Sore or Dry Throat
Difficulty
Swallowing
Rapid or Irregular Heartbeat
Infertility
Weight Loss
Heat Intolerance
Increased
Sweating
First-Trimester Miscarriage
Family History of
Thyroid Disease
or Diabetes
investications
Thyroid function tests
1-Total T3 = 1.2 to 2.8 nmol\L
2-Total T4 = 150 nmol\L
3-TSH 0.5 to 5 mU\L.
measuring of:
1- freeT4=10-30nmol\L
2- freeT3=0.3-3.3nmol\L
3- TSH = 0.5 to 5 mU\L which is the most
sensitive and specific test for the diagnosis
of hyper- and hypothyroidism
4- Autoantibody assessment: include TPH
(thyroid peroxidase), and anti thyroglobulin
anti body.
Diagnostic Imaging
Radioactive Iodine Uptake
Shows distribution of uptake
Technetium-99 Pertechnetate Uptake
Distinguishes high-uptake from low-uptake
Thyroid ultrasonography
Identifies nodules
Doppler can distinguish high from low-uptake
Thyroid scanning: iodine 123 (123I)
and iodine 131 (131I) Technetium Tc
99m
pertechnetate (99mTc).The images
obtained by these studies provide the
size and shape of the gland and the
distribution of functional activity.
Guide in thyrotoxicosis treatment
The choice of therapy depends on:
1-Age of the patient
2-Size of the thyroid
3-Type of thyroxicosis
Guide in thyrotoxicosis treatment
1-Graves below 45 year
anti thyroid drug
2-No response or large goiter or recurrence
surgery
3-Graves above 45 year
RAI
4-Toxic multinoduler
surgery
5-Toxic nodule
surgery. if not fit
RAI
6-Recurrent after surgery above 45 year
RAI
Pregnancy
surgery in the first and second trimester
Antithyroid (propylthiuracil) in the third trimester in low
doses.
Antithyroid drugs
carbimazole 40-60 mg daily
prophylthiouracil 400-600 mg daily. There is
subjective improvement within 10-14 days
and the patient is usually clinically and
biochemically euthyroid at 3-4 weeks, when
the dose can be reduced. The maintenance
dose is determined by measurement of T4 and
TSH, attempting to keep both hormones
within their respective reference ranges...
Adverse effects
Rash 
Arthralgias 
Urticaria 
GI symptoms 
Agranulocytosis 
β-adrenoceptor antagonist (β-blocker), such 
as propranolol (160 mg daily) or nadolol
(40-80 mg daily), will alleviate but not
abolish symptoms within 24-48 hours.
Beta-blockers cannot be recommended for
long-term treatment, but they are extremely
useful in the short term, e.g. for patients
awaiting hospital consultation or following
131I therapy.
Radioactive iodine
131I is administered orally as a 
single dose and is trapped and
organified in the thyroid .Although
it will decay within the thyroid in a
few weeks, the effects of its
radiation are long-lasting, with
cumulative effects on follicular
cell survival and replication.
Subtotal thyroidectomy
Patients must be rendered euthyroid 
with antithyroid drugs before
operation. Potassium iodide, 60 mg 8hourly orally, is often added for 2
weeks before surgery to inhibit thyroid
hormone release and reduce the size
and vascularity of the gland, making
surgery technically easier.
Complications of surgery are rare.
Treatment of Ophthalmopathy
Mild Symptoms 
Eye shades, artificial tears 
Progressive symptoms (injection, pain) 
Oral steroids – typical dosage from 30-40mg/day 
for 4 weeks
Impending corneal ulceration, loss of vision 
Oral versus IV steroids 
Orbital Decompression surgery 