Management of Cushing’s syndrome, what do
you want to do?
Why do want to treat the underlying cause?
If it’s iatrogenic, stop giving the Cushing…
I mean, stop giving the prednisone.
If it’s the adrenal source, adrenalectomy
If it’s Cushing’s disease, where is this?
In the anterior pituitary, perhaps you have
Therefore, transsphenoidal resection is usually
the first line of treatment.
Next, there is something called pituitary
radiation therapy, XRT.
Sometimes used when tumour is not found or
not surgically cured.
It may decrease risk of what’s known as
Nelson’s syndrome, the rapid tumour enlargement
causing mass effect and hyperpigmentation
after loss of negative feedback in patients
for whom adrenalectomy becomes necessary.
Okay, so, here, you’re thinking about what’s
known as pituitary radiation.
I need you to be familiar with what’s known
as Nelson’s syndrome, a rapidly tumour enlarging
and compression, meaning to say that now,
you’re worried about maybe visual defects
and the hyperpigmentation more so because
of increased POMC… radiation.
Bilateral adrenalectomy, Adx it stands for,
removal of adrenalectomy with lifelong glucocorticoid
and mineralocorticoid replacement is definitive
treatment for Cushing’s disease.
Interesting enough, if it’s Cushing’s
disease, what does that mean?
It means that your excess cortisol is being
caused by ACTH from the anterior pituitary,
So, therefore, both adrenals are affected,
so bilateral adrenalectomy with lifelong glucocorticoid
and mineralocorticoid replacement; without
the glucocorticoid, you’re dead.
Without the mineralocorticoid, your blood
pressure is depressed severely.
Adrenalectomy, usually performed after pituitary
radiation to decrease the risk of, once again,
Nelson’s, Nelson’s, Nelson’s…
Clinically, that is a very important point.
If you missed that discussion, go back to
the previous section where we just finished
For ectopic Cushing’s, where are you looking?
Surgery or other treatment.
Here, you might be looking at chemo or radiotherapy
of the inciting tumour, maybe perhaps coming
from a small cell lung cancer of the lung.
Medical therapy for when surgery is contraindicated
For example, post Cushing’s disease and
Adrenal enzyme inhibitors, 17-20 desmolase
inhibitors; in the US-ketoconazole; in UK-metyrapone
which inhibits 11-beta-hydroxylase.
You want to know about ketoconazole and desmolase…
We talked about the patho-physiology.
Desmolase is responsible for the first step
of converting cholesterol into pregnenolone
as you move down through your adrenocortical
Adrenolytics, these are mitochondrial inhibitors
of adrenal cortical cells mitotane.
Neuro agents, things that you want to keep
in mind, understand the concept first.
What are we trying to take care of?
Cushing’s… too much cortisol.