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Transcript
Dr: Wael H.Mansy, MD
Assistant Professor
College of Pharmacy
King Saud University
1
Function of the thyroid gland
 There are two main hormones produced by the thyroid
gland:
1. Thyroxin (T4) and
2. Triiodothyronine (T3).
 Both hormones are derived from the amino acid
Tyrosine and contain Iodine that is extracted from the
blood.
 The release of thyroid hormones from the thyroid is
regulated by TRH secreted from the anterior pituitary
gland.
2
T4 versus T3
• T3 ~5X as active as T4
• T4 secreted solely form thyroid gland
• <20% T3 secreted from the thyroid
gland
• Majority of T3 from breakdown of T4
(de-iodination) in peripheral tissue
• Mostly liver and kidneys
3
The main actions of T3 and T4
1. Increased basal metabolic rate
2. Maintenance of normal metabolic function.
3. Normal physical, mental and sexual development.
4. Development of the nervous system in the fetus
5
Thyroid Diseases
Definitions
• Goiter
– Enlargement of the thyroid gland
• Hypothyroidism
– Inadequate thyroid hormone production
• Thyroiditis
– Inflammation of the thyroid gland
• Thyrotoxicosis
a term that is used to describe the “toxic” effects of excess thyroid
hormones on the body.
– State resulting from excess production/exposure to thyroid
hormone
• Hyperthyroidism
– Thyrotoxicosis caused by a hyperfunctioning thyroid gland
– Excludes thyroiditis or excessive exogenous thyroid hormone
6
Hypothyroidism
Common causes of Hypothyroidism
• Thyroiditis: Hashimoto’s thyroiditis in which
antibodies are produced against the tissue of the thyroid.
Although the exact etiology of this autoimmune disorder
is unknown, it can lead to progressive destruction of the
thyroid gland and loss of thyroid function.
• Thyroid Surgery or Irradiation
• Iodine deficiency (Goiter)
–Most common cause of hypothyroidism worldwide
7
Hashimoto’s Thyroiditis
• Most common cause of hypothyroidism
• Women 30-50 years of age
• HLA-DR5 +
• Autoimmune thyroiditis
– Antimicrosomal antibodies
• Against peroxidase
– Antithyroglobulin antibodies
• Against thyroglobulin
– Autoantibodies against TSH receptor
• Net effect is prevent TSH stimulation of gland
8
Goiter
Nontoxic goiter:
1. Hypertrophy of the thyroid gland that is not accompanied by
excess secretion of thyroid hormones.
2. May occur as a result of dietary iodine deficiency, during
pregnancy and at puberty.
3. Symptoms are those of hypothyroidism.
Toxic goiter :
1. Hypertrophy of the thyroid that is accompanied by excess thyroid
production.
2. May be associated with Graves’ disease.
3. Symptoms are those of hyperthyroidism.
9
GOITER
10
Hypothyroidism
Cretinism
Hypothyroidism that occurs during
fetal development
 May occur as a result of a
congenital
defect
in
thyroid
development
Severe mental retardation due to
poor development of the brain
Poor
overall
development
and
growth retardation
11
Hypothyroidism
Myxedema
 Hypothyroidism in the adult
 May result from autoimmune destruction of the thyroid or
thyroid injury or removal
 Presents with signs of hypometabolism including:
 Cold intolerance
 Weight gain
 Fatigue
 Bradycardia
 Cool, dry skin
 Anorexia
 Constipation
 Edema of the face (swelling around the eyes), hands
and ankles; drooping eyelids.
12
Hypothyroidism
Possible
long-term
complications
of
untreated
hypothyroidism:
cardiac hypertrophy, heart failure, and myxedema coma,
which
presents
with
hypothermia,
seizures
and
respiratory depression.
Treatment
Thyroid hormone replacement therapy. A variety of
synthetic and natural T3/T4 preparations are available for
use orally.
13
Hyperthyroidism
Increased synthesis and release of T3 and T4, Hyperthyroidism is
also referred to as Thyrotoxicosis.
Hyperthyroidism may be
1. A primary condition that results from an overactive thyroid
gland.
2. Secondary to excessive stimulation of the thyroid by TSH from
the pituitary.
3. Grave’s disease: the most common causes of hyperthyroidism
4. Plummer’s disease: toxic goiter not associated with Grave’s
disease.
5. a tumor of the thyroid. In rare cases carcinomas arising outside
of the thyroid may produce thyroid hormone or TSH.
14
Hyperthyroidism
Graves’ disease
*Patients with Graves’ disease produce (Thyroid
Stimulating Immunoglobulin) antibodies that bind
TSH receptors on the thyroid and mimic the actions
of TSH leading to excess production of thyroid
hormones.
*Classic Triad (15-20%):
Diffuse goiter, Hyperthyroidism, and
Ophthalmopathy (exophthalmos)
15
Hyperthyroidism
Manifestations
The manifestations of hyperthyroidism are essentially the same
regardless of the cause of the hyperthyroidism:
1. Increased basal metabolic rate
2. Increased heat production, patient always feels “hot”
3. Tachycardia
4. Increased catecholamine sensitivity; patients are at risk for
cardiac arrhythmias
5.
Increased appetite
6.
Weight loss
7.
Enhanced bowel activity
8.
Behavioral changes : nervousness and hyperactivity
16
Laboratory tests to evaluate thyroid function
• Serum total thyroxine (total)
• Unbound or serum free thyroxine
• Serum total triiodothyronine
• Serum TSH
• Serum thyroglobulin
• Antibodies
Thyroid Antibodies
• Antithyroglobulin and Antiperoxidase
– Markers for Hashimoto’s but not specific
• Thyroid stimulating immunoglobulin—TSI
– Against the TSH receptor
– The cause of Graves’ disease
– Predict neonatal hyperthyroidism
Thyroid Scan
Hyperthyroidism
Treatment
β-Blocking drugs
to blunt the effects of excess adrenergic
stimulation.
Antithyroid drugs
(propylthiouracil, carbimazole, methimazole)
that block production of thyroid hormone.
Surgical ablation
of a portion of the thyroid may be used.
Following surgery, patients may likewise become hypothyroid and require
thyroid hormone replacement therapy.
20
Hyperthyroidism
Treatment
Radioiodine: Given orally and taken up by hormone-producing
cells of the thyroid as if it were normal iodine. The cytotoxic actions
of the β and γ radiation destroy the hormone-producing cells of the
thyroid. After treatment the patient usually becomes hypothyroid and
must be managed with thyroid hormone replacement therapy.
Radioactive iodine should not be used in patients of childbearing age
due to the possible effects on offspring.
21
Hyperthyroid emergencies
Thyroid Storm
• Rare complication of hyperthyroidism
where manifestations of thyrotoxicosis
become life threatening. Also may be
termed Thyrotoxic Crisis.
Precipitating factors:
• Infection
• Trauma/Surgery
• Parturition
• DKA
• MI
• CVA
• PE
• Withdrawal of thyroid meds
• 20-25% cases no precipitant found
• Fever >38.5
• Sinus tachycardia out of proportion to
fever.
• SVT or dysrhythmias with or without CHF
• GI symptoms (nausea, vomiting,
diarrhea, rarely jaundice)
• Volume depletion.
• CNS dysfunction (agitation, confusion,
delirium, stupor, coma, seizure)
25