THYROTOXICOSIS
-Thyrotoxicosis is defined as the state of thyroid hormone
excess and is not synonymous with hyperthyroidism, which
is the result of excessive thyroid function.
-However, the major etiologies of thyrotoxicosis are
hyperthyroidism caused by Graves' disease, toxic
multinodular goiter, and toxic adenomas
Causes of thyrotoxicosis
A.Primary hyperthyroidism
1) Graves' disease
2) Toxic multinodular goiter
3) Toxic adenoma
4) Functioning thyroid carcinoma metastases
5) Activating mutation of the TSH receptor
6) Activating mutation of Gsα (McCune-Albright
syndrome)
7) Struma ovarii
8) Drugs: iodine excess (Jod-Basedow phenomenon)
B. Secondary hyperthyroidism
1) TSH-secreting pituitary adenoma
2) Thyroid hormone resistance syndrome:
occasional patients may have features of
thyrotoxicosis
3) HCG-secreting tumors
4) Gestational thyrotoxicosis
C. Thyrotoxicosis without hyperthyroidism
1) Sub acute thyroiditis
2) Silent thyroiditis
3) Other causes of thyroid destruction: amiodarone,
radiation, infarction of adenoma
4) Ingestion of excess thyroid hormone
(thyrotoxicosis factitia)
GRAVES DISEASE
Introduction
-Is an autoimmune disease characterized by
hyperthyroidism due to circulating autoantibodies.
-Thyroid-stimulating immunoglobulins (TSIs) bind to and
activate thyrotropin receptors, causing the thyroid gland to
grow and the thyroid follicles to increase synthesis of
thyroid hormone.
-Graves disease, along with Hashimoto thyroiditis, is
classified as an autoimmune thyroid disorder.
-In some patients, Graves disease represents part of a more
extensive autoimmune process called autoimmune
polyglandular syndrome, which is also associated with
 Pernicious anemia
 Vitiligo
 DM type 1
 Autoimmune Adrenal insufficiency
 SLE
Race
-Susceptibility is influenced by genes in the human
leukocyte antigen (HLA) region on chromosome 6 and in
CTLA4 on band 2q33
Sex
-F;M ratio 7-8:1.
-The female-to-male ratio for pretibial myxedema is 3.5:1.
-Only 7% of patients with localized myxedema have
thyroid acropachy.
-Unlike the other manifestations of Graves’s disease, the
female-to-male ratio for thyroid acropachy is 1:1.
Age
-Typically, Graves’s disease is a disease of young women,
Pathophysiology
-B and T lymphocyte–mediated autoimmunity are known to
be directed at 4 well-known thyroid antigens:
 Thyrotropin receptor.(TSH receptor) -primary
autoantigen of Graves disease responsible for the
manifestation of hyperthyroidism
 Thyroglobulin
 Thyroid peroxidase
 Sodium-iodide symporter
-Direct proof of an autoimmune disorder is the development
of hyperthyroidism in healthy subjects by transferring
thyrotropin receptor antibodies from serum of patients with
Graves disease
-Also the passive transfer of thyrotropin receptor antibodies
to the fetus in pregnant women.
-The thyroid gland is under continuous stimulation by
circulating autoantibodies against the thyrotropin receptor,
and pituitary thyrotropin secretion is suppressed because of
the increased production of thyroid hormones.
-The stimulating activity of thyrotropin receptor antibodies
is found mostly in the immunoglobulin G1 subclass. These
thyroid-stimulating antibodies cause release of thyroid
hormone and thyroglobulin that is mediated by adenosine
3,'5'-cyclic phosphate and they also stimulate iodine uptake,
protein synthesis, and thyroid gland growth.
-The anti–sodium-iodide symporter, antithyroglobulin, and
antithyroid peroxidase antibodies appear to have little role
in the etiology of hyperthyroidism
-.However, they are markers of autoimmune disease against
the thyroid.
-Intrathyroidal lymphocytic infiltration is the initial
histologic abnormality in persons with autoimmune thyroid
disease and can be correlated with the titer of thyroid
antibodies.
Prevalence
-Among the causes of spontaneous thyrotoxicosis, Graves
disease is the most common.
-Graves disease represents 60-90% of all causes of
thyrotoxicosis in different regions of the world
80 cases per 100,000 women per year.
Mortality/Morbidity
-If left untreated, life-threatening thyrotoxic crisis (ie,
thyroid storm) can occur.
- Long-standing severe thyrotoxicosis leads to severe
weight loss with catabolism of bone and muscle.
-Cardiac complications and psychocognitive complications
can cause significant morbidity.
- Graves disease is also associated with ophthalmopathy and
acropachy.
-Long-term excess of thyroid hormone can lead to
osteoporosis in men and women.
- Maternal Graves disease can lead to neonatal
hyperthyroidism by transplacental transfer of thyroid-
stimulating antibodies.
Usually, the TSI titer falls during pregnancy.
-Severe acropachy can be disabling and can lead to total
loss of hand function.
-Progression of ophthalmopathy can lead to compromised
vision and blindness. Visual loss due to corneal lesions or
optic nerve compression can be seen in severe Graves
ophthalmopathy.
Lipid metabolism - Decreased total cholesterol levels,
decreased triglyceride levels
Physical
Common physical findings associated with thyrotoxicosis
include
 Widening of the palpebral fissures
 Tachycardia
 Hand tremor (fine and usually bilateral)
 Proximal muscle weakness
 Brisk deep tendon reflexes
 Fidgetiness
 Warm velvety skin.
 Upon careful examination, the thyroid gland