Jack: Hi, everyone, and welcome to today's lecture
on the Epidemiology of Adrenal Cancer.
In this lecture, we have several goals.
We'll begin by reviewing the anatomy
and function of adrenal glands.
Then we'll differentiate tumors
of the adrenal cortex and medulla.
Next, we'll discuss characteristics
of adrenal cortical tumors and risk factors for those tumors
and then look at characteristics of adrenal medulla tumors
and look at some genetic syndromes.
So, to begin with, let's give a brief overview
of the anatomy of the adrenal glands.
So the adrenal glands are bilateral, triangular structures
positioned above and slightly behind the kidneys.
Each gland consists of the adrenal cortex
and the adrenal medulla.
The adrenal cortex consists of zones
of cuboidal epithelial cells
that actively synthesize and secrete steroid hormones,
and all steroid hormones are synthesized from cholesterol.
Adrenal steroids include corticosteroids like cortisol
that regulate the metabolism of protein, fat,
and carbohydrates and mineral corticoids like aldosterone
that regulates salt and water balance.
The adrenal cortex also synthesizes low levels of androgens
and estrogens that help modulate masculine
and feminine characteristics.
Adrenal masses or adrenal tumors are often
found incidentally during imaging studies
for other conditions.
Most adrenal masses are benign adenomas
and only a small fraction,
something around the 10%, prove to be malignant on biopsy.
Definitive differentiation of benign
from malignant adrenal tumors is often problematic
and requires careful evaluation of structural, clinical,
hormonal, cytologic and molecular features.
Diagnostic symptoms of adrenal tumors are often
related to hormonal imbalance due to hyper secretion
of specific hormones by dysplastic and malignant cells.
For example, Cushing's syndrome is the excessive production
of cortisol, and that influences the body's,
or cortisol influences the body's response to stress,
metabolism of fat and protein and immune function.
Another example is Conn's disease
which is the excessive production of aldosterone
which leads to increased salt retention,
potassium depletion, and elevated blood pressure.
The dominant clinical manifestation of tumors
of the adrenal medulla, which is neuroblastoma
in children and pheochromocytoma adults, is hypertension.
This is due to the excessive production
of epinephrine and norepinephrine.
Measurement of the levels of these hormones in blood
and urine aid in the differential diagnosis
of adrenal tumors.
Malignant tumors that arise from the adrenal cortex
are called adrenal cortico carcinomas.
Adrenal tumors that secrete adrenal steroids are classified
as functional, whereas non-secreting tumors are classified
as non-functional.
Most or 90% of adrenal cortical carcinomas secrete steroids
and are therefore functional.
Adrenal cortical carcinomas are rare and accurate data
on their incidents and mortality is lacking.
A review of 1,891 cases identified in the English literature
between 1952 and 1992 found that 58.6% of cases were female
with a first peak of onset in childhood
and a second peak during the fifth decade of life.
We see that in this figure on the slide
with the slightly elevated bar in the birth to 10 age range
and the high bar between 51 and 60 years.
In the US, the annual incidents estimated
from surveillance epidemiology and end results data
or SEER data is less than one case per million.
The age or diagnosis ranges from one to 91 years of age
with a small early peak during childhood
and as previously mentioned,
the larger peak in the fifth decade of life.
So in 2020, it's difficult to find accurate incidents
and mortality data.
Though the data that is available state
that adrenal cancer is very rare.
Overall, in the US incidence is estimated to be
about one per 1 million or 1.02 per 1 million overall.
To give you an idea
of how rarely this form of cancer appears,
there were only 2014 cases between 1973 and 2014.
However, it typically has a highest mortality rate
due to the typical late stage presentation.
There's several risk factors for adrenal cortical carcinomas
including tobacco smoking,
and a number of genetic syndromes.
The two principle tumors
of the adrenal medulla are neuroblastoma
and pheochromocytoma.
Both tumors arise from neuroendocrine tissues
of the adrenal medulla, and thus may secrete catecholamines
that influence the sympathetic nervous system.
There are distinct differences in the clinical
and pathological features of these tumors
and neuroblastomas are diagnosed primarily in children
while pheochromocytomas are diagnosed primarily in adults.
Risk factors for neuroblastomas include certain gestational
and maternal exposures, including opiates,
folate deficiency, and gestational diabetes.
There's also several genetic syndromes that play a role
in neuroblastoma development.
These include Turner syndrome, Hirschsprung's disease
and Neurofibromatosis Type 1.
You can read more about all of these syndromes
in your textbook.
The second main class of tumors
which affects primarily adults or pheochromocytomas
arise from chromaffin cells of the medulla
of the adrenal gland or other anatomic sites.
These are typically benign and most often detected
in adults from 20 to 50 years of age.
They cause marked elevations in blood pressure
or hypertension, and over 90% have no metastatic potential.
These are typically curable by excision.
A significant fraction of cases,
perhaps 30%, occur in familial settings
with multi-generational inheritance patterns.
The most common
of these hereditary conditions is von Hippel-Lindau disease
or VHL and the multiple endocrine neoplasia or MEN syndrome.
The first is a rare autosomal dominant genetic condition
tied to a germ line mutation
in the von Hippel-Lindau tumor suppressor gene
on the short arm of chromosome three.
In contrast, the MEN
and Sipple syndromes are a heritable syndrome
caused by mutations of the M, E, N, I, N or MENIN gene
which is the tumor suppressor gene
located on chromosome 11.