Thyroid endocrinology

Thyroid hormones are extremely important and have

diverse actions. They act on virtually every cell in the body
to alter gene transcription : under- or over- production of
these hormones has potent effects. Disorders associated
with altered thyroid hormone secretion are common and
.affect about 5% women and 0.5% men
Like the catecholamines epinephrine and
norepinephrine, thyroid hormones are synthesized from
the amino acid tyrosine. The synthesis of thyroid
hormones requires the iodination of tyrosine molecules
and the combination of two iodinated tyrosine residues.
The thyroid gland has evolved not only to trap this
element avidly from dietary sources but also to maintain a
large store of the iodinated tyrosines to maintain the
secretion of thyroid hormones during periods of relatively
.iodine deficiency
Iodine intake
The normal daily intake of iodine is about 150 g, of
which 125 g is taken up by the thyroid gland and used for
.hormone synthesis
Iodine (as the iodide) is relatively abundant in seawater
and seafood is a rich dietary source. Fruits and vegetables
also contain significant concentrations of iodine, although
the amount depends on the soil and growing region. The
term cretinism, used to define the severe impairment of
physical and neurological development resulting from
.iodine deficiency during fatal and post-natal development
Increased iodine intake or a deficiency of dietary iodine
can both induce goiter formation. The former results
from increased thyroid hormone synthesis and storage.
Goiter formation in regions of dietary deficiency ( the most
common cause of goiter) is due to reduced thyroid
hormone synthesis and the compensatory increased

secretion of the pituitary hormone thyrotrophin as a result

.of the loss of negative feedback

Anatomical features of the thyroid gland

The thyroid gland consists of 2 lobes lying on either
side of the ventral aspect of the trachea. Each lobe is
about 4cm in length and 2cm thickness connected
together by a thin band of connective tissue called the
isthmus. Weighing approximately 20g, it is largest
classical endocrine glands in the body and receives a high
blood flow from the superior thyroid arteries and the
.inferior thyroid arteries
The functional unit of the thyroid gland is the follicle, a
roughly spherical group of cells arranges around a protein.rich storage material called colloid
Synthesis of thyroid hormones
Thyroxin (T4) and Tri-iodothyronin (T3) are together
known as the Thyroid hormones. They are synthesized by
thyroid gland by iodination and decoupling of two tyrosine
molecules. T4 has four attached iodine atoms while T 3 has
.three
Approximately 100 g thyroid hormones are secreted from
the gland each day, mostly in the form of T 4 with a about
10% as T3. 80% of the T4 undergoes peripheral conversion
to the more active T3 on the liver and kidney (T3 is 10
times more active than T4) or to reverse T3 (rT3) that has
. little or no biological activity
Control of thyroid hormone synthesis and secretion
Like the adrenal cortex and the gonads, the thyroid gland
is controlled by hormone secretions from the
hypothalamo-pituitary axis. The synthesis and

secretion of TSH from the thyrotrophs is stimulated by the

tripeptide, thyrotrophin-releasing hormone (TRH). TSH
secretion is inhibited by other hormones (including
.somatostatin and dopamine) and also cytokines
Hyperthyroidism- Graves disease
An autoimmune disease resulting in the production of
autoantibodies that stimulate the TSH receptor. This highly
unusual action of an antibody not only stimulated thyroid
.hormone synthesis and secretion but also thyroid growth
Incidence and diagnosis of Graves disease
Graves disease is the most common cause of
hyperthyroidism and other causes are uncommon or,
indeed rare. For reasons remain unknown, it is much
commoner in women, particularly those aged 30-50. It
.affects 3% women and 0.3% men
Causes of hyperthyroidism
Common
Graves disease (80%)- autoimmune with stimulating .antibodies to the TSH receptor
Toxic multinodular goiter (15%) Uncommon
-Toxic adenoma (2%)
- Thyroiditis (1%)
Rare
TSH secreting pituitary tumor (<0.01%) -Trophoblastic tumors (<0.001%)
-Thyrotoxicosis factitia (<1%)
-Thyroid follicular carcinoma (<0.01%)

Treatment of hyperthyroidism
There are 3 methods of treating hyperthyroidism- drugs,
surgery and radioisotopes. none is ideal; each has its
own advantages and disadvantages; none is exclusive
.and; not infrequently, a combination of therapies is used

Drugs
Thiocarbamides e.g. carbimazole
-adrenergic receptor blockers e.g. propranolol
glucocorticoids e.g. prednisolone
iodine e.g. Lugol's solution (no longer widely used)
percholate (no longer used routinely)
lithium
surgical
partial or total thyroidectomy
radioisotope
iodine131
primary hypothyroidism- Hashimoto's disease and
myxedema
most common causes of hypothyroidism are autoimmune
in etiology. Like Graves disease they may have a number
of autoimmune markers, including the presence of
autoantibodies. However, unlike Graves disease, T-cell
mediated actions result in thyroid gland destruction rather
.than stimulation
Causes of hypothyroidism

Primary disorders
Common (95%)
- Hashimoto's disease-autoimmune thyroid destruction
Primary (atrophic) hypothyroidism (probably endstage Hashimoto's disease)
-Post-radioiodine therapy which destroys thyroid tissue
Post- surgery of the gland-

Uncommon (5%)
-Thyroiditis (non-lymphocytic)
-Impaired T4 synthesis due to genetic defect
-Antithyroid drugs
Rare (<1%)
-Loss of function TSH receptor mutations
-Thyroid hormone resistance
Secondary (or pituitary, 1%) disorder
Hypopituitarism caused e.g. tumors, surgery, radiotherapy
-Impaired TSH synthesis
Tertiary (or hypothalamic,<1%) disorder
Hypothalamic damage due to tumors, radiotherapy or
trauma
Diagnosis of hypothyroidism
The diagnosis of Hashimoto's disease is usually easy,
based on the presence of goiter (enlargement of the
thyroid gland), circulating thyroid autoantibodies and low

circulating concentrations of thyroid hormones with high

.TSH concentrations
Treatment of primary hypothyroidism
Use of the prohormone thyroxine in the treatment of
.primary hypothyroidism is cheap and easy to monitor