In this lecture we're going to discuss
Cushing?s syndrome and Addison's disease.
Two issues whether abnormal amount of steroids in the blood.
Remember the state of excessive circulating glucocorticoids
is really what the hallmark of Cushing?s is.
These patients have too many steroids.
Cushing?s syndrome is much more common in adults
but we do see it in children rarely.
So I want to discuss
and particularly focus on perhaps some pediatric concerns.
So let's recall the HPA axis, HPA it starts with the hypothalamus.
The hypothalamus makes corticotropin releasing hormone
which stimulates the anterior pituitary.
The anterior pituitary in turn uses ACTH to stimulate the adrenal cortex.
The adrenal cortex then makes endogenous steroids
which go back and inhibit the anterior pituitary
and the hypothalamus as a negative feedback loop.
This is our normal HPA axis.
So Cushing's syndrome can be ACTH dependent or ACTH independent.
ACTH dependent Cushing?s is Cushing?s that's cause by too much ACTH.
We see this and for example,
pituitary adenomas which is a very common cause of Cushing?s in children.
We can also see this incredibly rarely in ectopic ACTH
or carcinoid tumors such us bronchial tumors, renal or thymic tumors
these are incredibly rare in children.
ACTH independent Cushing?s by far and away
is most often caused by excessive steroid use
which is usually given to try and control for example
on an autoimmune condition,
or some problem whether it's too much inflammation.
Rarely, ACTH independent Cushing?s can be from adrenocortical tumors
that are secreting purely cortisol.
Primary adrenocortical hyperplasia is a condition
which is associated with one of the MEN syndromes.
If you can also see it in McCune-Albright?s disease.
This is a generally hyperplastic adrenal cortex
that is secreting too much cortisol.
So we're used to seeing pictures of adults with striae and moon facies
and the buffalo hump
and this can actually happen in children too.
Here is an example of a child with moon facies.
This child has too much steroid probably from the steroids
that are being administered for this child?s underline bronchopulmonary dysplasia.
Patients may have violaceous striae
they may have plethora or redness to their skin.
They may have significant weight gain as you can see in this child.
However, poor growth.
They tend to be over weight but under tall.
Short stature occurs in up to 40% of them.
They will be virilized or excessively masculine especially if they are girls.
They maybe irritable or fussy and difficult to handle children
and they may also get fatigue easily especially if they get older.
So if we suspect Cushing?s disease
we want to try and figure out what the cause may be.
And one of the first things we can do
is check a 24-hour urine cortisol level.
This is simply collecting urine for a day and then measuring the cortisol.
We do the full day because it varies from time during the day
when your urine cortisol is going to be a highest typically in the morning.
Serum cortisol levels throughout the day
also can assess this circadian rhythmicity of cortisol levels.
If we're still confuse we can do something called
the dexamethasone suppression test.
Here we provide either a low or a high dose of dexamethasone.
So the way we'll do this test is we'll check an ACTH level prior to starting.
This can give us a sense of whether this is primary
or secondary high cortisol levels
from the adrenal gland or from the brain.
Then we'll give dexamethasone for 2 days
at the doses that we describe there
and then we'll check both a cortisol and ACTH level.
What you'll see is this test is a variety of responses.
What we should typically see when we're giving dexamethasone
to a healthy patient is that we'll have a down regulation of ACTH
and cortisol in this patient.
In patients with Cushing?s disease the low dose may not reduce
the expression of ACTH but the high dose may.
Alternatively in patients with for example an ACTH
secreting tumor no suppression occurs.
So in Cushing?s disease for patients with ectopic ACTH
or a suspected tumor, imaging and chemotherapy
or surgical excision is necessary, that's very unusual.
For patients more commonly with primary Cushing?s disease
a transsphenoidal surgery may be needed to remove a pituitary adenoma.
Adrenalectomy is only necessary if that transsphenoidal surgery is impossible.
Radiation is really a second-line treatment for this children
with pituitary glands that is secreting too much ACTH.
Medical therapy can be use specifically ketoconazole, metyrapone
or other adrenal blocking agents as a temporizing measure prior to surgery.