Instructor: Hi all.
In this lecture will be discussing the epidemiology
of thyroid cancer.
So we've several goals.
We'll begin by describing the anatomy
and function of the thyroid gland,
looking at diseases of the thyroid gland,
and then looking at hyperthyroidism and Graves' disease.
We'll also discuss Hashimoto's thyroiditis,
hypothyroidism and goiter.
Finally, we'll look at studies of iodine supplementation.
So to begin with,
let's look at the anatomy of the thyroid gland.
So the thyroid gland produces iodine-containing
thyroid hormones like triiodothyronine or T3
and thyroxine or T4.
These circulating hormones are essential
in regulating the rate of metabolism in the body.
Inside the cell, T3 and T4 stimulate energy production
by the mitochondria
and promote glucose metabolism, protein synthesis,
lipolysis, and excretion of cholesterol.
Thyroid hormones also influence growth
and development in early life
and help maintain normal cardiac rhythm, muscle tone
and neuronal function in the sympathetic nervous system.
Biosynthesis of thyroid hormones is regulated
by peptide hormones secreted by the hypothalamus
and the anterior pituitary gland
in response to low blood levels of thyroid hormones
or neurological signals.
Special cells of the thyroid gland called C cells
produce a polypeptide hormone called calcitonin
which helps regulate calcium homeostasis
throughout the body.
Relatively small parathyroid glands,
usually four in number,
are located at the periphery of the thyroid gland.
The parathyroid glands synthesize parathyroid hormone,
or PTH, which together with calcitonin
and the active form of vitamin D, regulate levels of calcium
and phosphorus in the blood, the bones,
and most other tissues.
So there's several kinds of neoplasms of the thyroid gland.
To begin with, benign thyroid adenomas are relatively common
and are detected approximately three times more often
in women than men.
Approximately 90 to 95%
of solitary thyroid nodules are benign
and are treated by simple excision.
Treatment by simple excision is curative.
Careful histological examination of tissue is always
necessary to rule out malignant transformation.
Malignant tumors of the thyroid gland are rare,
but all thyroid nodules must be carefully examined
under the microscope to distinguish benign
from malignant tumors.
Thyroid carcinomas arise from the cuboidal epithelium
that lines the thyroid follicles.
During 2000 and 2020 or during 2000 and 2012,
the annual number of incident cases
of thyroid cancer detected in the world population
has increased dramatically,
whereas the number of deaths has changed very little.
Age-adjusted incidents
and mortality rates actually show inverse trends.
During 2002 to 2012, the incidents doubled among women,
whereas the mortality declined by 25%.
The inverse trends of incidents and mortality
may largely reflect the increased early detection
of small papillary thyroid tumors
that are treated by complete surgical resection.
During 2012, almost 300,000 new cases were diagnosed
in the world population,
and almost 40,000 people died from thyroid cancer.
Of these, 77% of cases and 68% of deaths occurred in women.
The annual age-adjusted incidence rate in 2012
among women was 60.1 cases per 100,000
compared to 1.9 per 100,000 in men,
Incidence rates are markedly higher
in high income countries
than low and middle income countries.
For example, the incidence in American
and Canadian women is 10 to 20 times higher
than the incidence rates among women living in India
and sub-Saharan Africa.
In contrast, mortality rates
of thyroid cancer are markedly higher
in less-developed regions of the world.
For example, the mortality rates range from one
to three deaths per 100,000 among women
in sub-Saharan Africa,
compared to 0.3 deaths per 100,000 among women
in Canada and the US.
In 2020, the overall age-standardized incidence
of thyroid cancer was 6.6 per 100,000.
Though as previously mentioned,
the rate is much higher in women than men.
The age-standardized mortality rate is 0.43
per 100,000 people overall globally,
but the mortality rate is slightly higher
than women than in men.
The annual incidence of thyroid cancer in the US
during 1996 to 2000 was 68 cases per million.
The female to male ratio
of thyroid cancer is approximately three to one,
and the annual incidence rates are highest in Hawaii
where rates are one point or 119 per million in women
and 45 per million,
119 per million in women, and 45 per million in men.
And the lowest in Poland
where the rates are 14 per million in women
and four per million in men.
As shown in this figure, the annual incidence
of thyroid cancer in the US increased 142%
during 1973 to 2000,
from 3.6 per 100,000 to 8.7 per 100,000.
This increase was almost entirely attributed
to the corresponding 185% increase
in the incidence of papillary thyroid carcinoma
from 2.7 per 100,000 to 7.7 per 100,000.
In contrast,
the incidence of follicular thyroid carcinoma did not change
during the study period, and the mortality rates
of thyroid cancer actually declined
from 0.57 per 100,000 to, in 1973,
to 0.47 per 100,000 in 2003.
The observed trends are explainable
by the increased early detection
of small papillary thyroid tumors that were treated
by complete surgical removal.
Thyroid cancer, as well as other thyroid disorders,
are more prominent in women.
Since women seek medical attention more often than men,
they may be more likely than men to undergo screening
and diagnostic procedures that can detect thyroid nodules
and other disorders of the thyroid gland.
The incidence
of thyroid malignancies is significantly increased
in populations exposed to excessive radioactive fallout
in Japan, following the atomic bombing in World War II
and in Russia after the Chernobyl nuclear reactor accident.
Longitudinal studies of populations exposed
to radiation fallout indicate
that diets deficient in iodine potentiate the risk
of radiation-induced thyroid cancer
and suggest that iodine supplementation
has a protective effect against carcinogenesis.
One study, a case control study looking
at thyroid cancer and exposure to radioactive fallout
from the Chernobyl nuclear reactor accident,
in combination with dietary intake
of iodine supplements,
found that the overall risk of thyroid cancer increased
with increasing doses of radioactivity.
But subjects with low iodine intake had high,
a higher odds ratio of developing cancer
than those with similar radiation exposures
and increased potassium iodine supplementation.
Another potential risk factor is obesity.
So, one case control study conducted in Hawaii
found the risk of thyroid cancer increased
with increasing body weight in both men and women.
However, additional investigations are needed
in order to clarify the impact of radiation, iodine,
body mass, female reproduction,
and other risk factors
on thyroid carcinogenesis in different populations.
The most commonly encountered diseases
of the thyroid gland include either,
involve either an overactive gland known as hyperthyroidism
or an underactive gland known as hypothyroidism.
The most prevalent thyroid condition is enlargement
of the thyroid gland, which is called a goiter.
Thyroid adenomas or nodules occasionally arise
within the thyroid gland,
and on pathologic examination,
the vast majority of thyroid nodules turn out to be benign.
Several non-malignant thyroid disorders
have been found to be associated with thyroid cancer.
The most prominent of these associations
involve autoimmune conditions
and auto-antibodies against thyroglobulin
and other thyroid-specific factors.
Thyroiditis refers to an inflammatory condition
of a thyroid gland.
Thyroiditis can lead to hyperthyroidism
as in Graves' disease
or hypothyroidism like in Hashimoto's thyroiditis.
These inflammatory conditions are believed
to have an autoimmune basis, and both have been linked
to the development of thyroid adenomas and thyroid cancer.
Hyperthyroidism refers to an overactive thyroid.
Symptoms of this are due to the overproductive
of thyroid hormones T3 and T4 by the thyroid gland.
The most common cause
of hyperthyroidism is a condition called Graves' disease.
Graves' disease, also called diffuse toxic goiter,
is believed to arise
as a consequence of autoimmune reactions.
This disease affects approximately 0.5%
of the US population and is the underlying cause
of up to 80% of all cases of hyperthyroidism.
The clinical signs and symptoms
of this condition result from excess stimulation
of the thyroid gland by auto-antibodies,
resulting in overproduction of T3 and T4 hormones.
The peak incidence of Graves' disease is between 20
and 40 years of age and symptoms include enlargement
of the thyroid gland, protruding eyes, palpitations,
excess sweating, diarrhea, weight loss, muscle weakness,
and unusual sensitivity to heat.
And it's five to 10 times more commonly diagnosed in women
than in men.
Genetic studies suggest
that Graves' disease has a significant heredity component.
An association between Graves disease
and the development of thyroid cancer was reported
more than 60 years ago in a 1948 article.
A review of the malignancy rate in multiple studies
of surgically resected thyroid nodules suggests
that it's approximately 1.7 to 2.5% of nodules
from Graves' disease patients manifest thyroid cancer,
compared to only 0.25% nodules from other patients,
reflecting a seven to 10 fold increased risk
of thyroid cancer among patients with Graves' disease.
Next, return to Hashimoto's thyroiditis,
we see that it's a chronic autoimmune disease
in which the thyroid gland is gradually destroyed
by auto-antibodies against thyroglobulin
or other cellular components of the thyroid gland.
Patients often have a family history of thyroid disorders
including Graves' disease
and other autoimmune conditions
such as type one diabetes, celiac disease
pernicious anemia, Addison's disease,
and Sjogren's syndrome.
Hashimoto's thyroiditis is typically diagnosed
between the ages of 45 and 65 years
and occurs 10 to 20 times more often in women than in men.
Patients are at increased risk
of developing thyroid cancer
compared to patients with thyroid nodules.
In a metaanalysis of 38 studies,
pathologic evidence of Hashimotos thyroiditis was present
in 40.5% of the cases with thyroid cancer
compared to only 21% of the controls
with benign thyroid nodules.
Next to turn to human leukocyte antigen or HLA,
we see that genes of HLA play a major role
in the immune response to foreign antigens
as well as to the recognition of self versus non-self
in immune reactions.
The two classical forms of thyroiditis are known
to have an autoimmune basis,
Graves' disease and Hashimoto's thyroiditis.
And genetic variants at the HLA locus appear
to increase susceptibility to both conditions.
Hypothyroidism refers to an underactive thyroid gland
that results in a deficiency of thyroid hormones T3 and T4.
Hypothyroid disorders occur
when the thyroid gland is inactive or underactive
as a result of improper formation from birth,
lack of iodine or removal,
and iatrogenic inactivation of the thyroid gland.
Symptoms of hypothyroidism include abnormal weight gain,
fatigue, baldness, temperature intolerance,
and in some cases thyroid enlargement.
Cretinism is an anomaly that is caused by iodine deficiency
in the developing fetus.
This devastating condition typically manifests at birth
or during infancy and is characterized by hypothyroidism,
goiter, intellectual developmental disabilities,
deaf-mutism, stunted growth, and other anomalies.
Endemic cretinism was once common
in the Alpine populations of Southern Europe
due to lack of iodine in their diets.
And populations living in those areas
without outside food sources are therefore at high risk
for the development of iodine deficiency diseases.
The addition of iodine to table salt
has virtually eliminated cretinism in developed countries.
Early detection of thyroid insufficiency in newborns
and administration of thyroxine or T4 can often be effective
in reinstating thyroid function
and normal growth and development.
Nevertheless, in lower middle income countries
without such programs,
the lack of dietary iodine remains the leading cause
of preventable mental disability
in babies and small children.
In the US, iodized table salt
containing 100 milligrams per kilogram of potassium iodine
has been available since 1924.
The US Food and Drug Administration recommends
150 micrograms of iodine per day for both men and women.
So supplementing the diet with iodized salt is a simple,
cost effective method of ensuring adequate iodine intake.
Goitrogens are dietary agents that suppress thyroid function
and induce the formation of goiters,
particularly in children.
There also are some studies that suggest
that high dietary intake of iodine may be associated
with the development of thyroiditis,
papillary thyroid carcinoma, and thyroid lymphoma.
There also are some genetic characteristics
to medullary thyroid cancer.
Another rare form of cancer is parathyroid cancer,
and it is approximately 1% of all cases
of parathyroidism and about 0.005% of all cancers.
Key steps to take for prevention of thyroid cancer
are total avoidance of radiation exposure
to the head and neck,
maintenance of normal thyroid function by intaking iodine,
avoiding goitrogens in the diet, like soy products,
and regular checkups by ultrasonography to detect nodules
and other abnormalities of the thyroid gland.
Finally, a therapy for thyroid cancer
includes early detection coupled with complete excision.
There's a greater than 95% five year survival rate
for patients with stage one disease.