Cushing syndrome arises from excessive cortisol production, either due to the body's malfunction or prolonged use of corticosteroids, leading to symptoms like weight gain, high blood pressure, and bone loss. Diagnosis involves reviewing medical history, physical exams, and various lab tests, while treatment may include tapering off medications, surgery, or medications like mifepristone for non-surgical patients. Dietary changes can help manage symptoms but are not a cure, highlighting the complexity of diagnosing and treating this condition.

1. Memoona Arshad
Group 11 – 6th Sem
ISM – IUK
Presented to: Uvaidulaeva F.T

2.  Cushing syndrome occurs when your body has too much of
the hormone cortisol over time. This can result from taking
oral corticosteroid medication. Or your body might
produce too much cortisol.
 Too much cortisol can cause some of the hallmark signs of
Cushing syndrome — a fatty hump between your
shoulders, a rounded face, and pink or purple stretch
marks on your skin. Cushing syndrome can also result in
high blood pressure, bone loss and, on occasion, type 2
diabetes.
 Treatments for Cushing syndrome can return your body's
cortisol levels to normal and improve your symptoms. The
earlier treatment begins, the better your chances for
recovery.

4.  There are two main etiologies of Cushing syndrome:
 Endogenous hypercortisolism
 Endogenous Cushing syndrome results from excessive production
of cortisol by adrenal glands and can be ACTH-dependent and
ACTH-independent.
 exogenous hypercortisolism.
 Exogenous hypercortisolism, the most common cause of Cushing
syndrome, is mostly iatrogenic and results from the prolonged use
of glucocorticoids.
 ACTH-secreting pituitary adenomas (Cushing disease) and
ectopic ACTH secretion by neoplasms are responsible for
ACTH-dependent Cushing. Adrenal hyperplasia, adenoma,
and carcinoma are major causes of ACTH-independent
Cushing syndrome.

5.  When stimulated by ACTH, the adrenal gland secretes cortisol
and other steroid hormones.
 ACTH is produced by the pituitary gland and released into the
petrosal venous sinuses in response to stimulation by
corticotropin-releasing hormone (CRH) from the
hypothalamus (according to image on next slide).
 ACTH is released in a diurnal pattern that is independent of
circulating cortisol levels: peak release occurs just before
awakening, and ACTH levels then decline throughout the day.
 Control of CRH and ACTH release is maintained through
negative feedback by cortisol at the hypothalamic and pituitary
levels.
 Neuronal input at the hypothalamic level can also stimulate CRH
release.

7.  Although the adenomas of Cushing's disease secrete
excessive amounts of ACTH, they generally retain some
negative feedback responsiveness to high doses of
glucocorticoids.
 Ectopic sources of ACTH, usually in the form of
extracranial neoplasms, are generally not responsive to
negative feedback with high doses of glucocorticoids.
 However, some overlap exists in the response to negative
feedback between pituitary and ectopic sources of excessive
ACTH.
 Cushing's syndrome is categorized as ACTH dependent or
ACTH independent (according to table on next slide).
 This division is convenient for organizing the work-up of
patients with suspected hypercortisolism.

8. ACTH Dependent ACTH Independent
Cushing's disease Iatrogenic
Ectopic ACTH syndrome Adrenal adenoma
Ectopic corticotropin-releasing
hormone syndrome*
Micronodular hyperplasia*
Macronodular hyperplasia*
ACTH = adrenocorticotropin hormone.
*—Accounts for 1 percent or less of cases.

9.  Depression, alcoholism, medications, eating disorders
and other conditions can cause mild clinical and
laboratory findings, similar to those in Cushing's
syndrome, termed “pseudo-Cushing's syndrome.”
 The laboratory and clinical findings of
hypercortisolism disappear if the primary process is
successfully treated.
 Dexamethasone, an exogenous glucocorticoid, is used
to test for Cushing's syndrome.
 This gluococorticoid does not interfere with cortisol
assays but induces similar physiologic responses.

10.  The most common symptoms of this condition are:
 weight gain
 fatty deposits, especially in the midsection, the face
(causing a round, moon-shaped face), and between the
shoulders and the upper back (causing a buffalo hump)
 purple stretch marks on the breasts, arms, abdomen,
and thighs
 thinning skin that bruises easily
 skin injuries that are slow to heal
 acne
 Fatigue
 muscle weakness

13.  In addition to the common symptoms above, there are other
symptoms that may sometimes be observed in people with
Cushing’s syndrome.
 These can include:
 high blood sugar
 increased thirst
 increased urination
 osteoporosis
 high blood pressure (hypertension)
 a headache
 mood swings
 anxiety
 irritability
 depression
 an increased incidence of infections

15.  Cushing’s syndrome can be particularly difficult to
diagnose. This is because many of the symptoms, like
weight gain or fatigue, can have other causes.
Additionally, Cushing’s syndrome itself can have many
different causes.
 Your healthcare provider will review your medical
history. They’ll ask questions about symptoms, any
health conditions you may have, and any medications
you may be prescribed.
 They’ll also perform a physical exam where they’ll look
for signs like buffalo hump, and stretch marks and
bruises.

16.  The doctor may order laboratory tests, including:
 24-hour urinary free cortisol test
 For this test, you’ll be asked to collect your urine over a 24-hour
period. The levels of cortisol will then be tested.
 Salivary cortisol measurement
 In people without Cushing’s syndrome, cortisol levels drop in the
evening. This test measures the level of cortisol in a saliva sample
that’s been collected late at night to see if cortisol levels are too
high.
 Low-dose dexamethasone suppression test
 For this test, you’ll be given a dose of dexamethasone late in the
evening. Your blood will be tested for cortisol levels in the morning.
Normally, dexamethasone causes cortisol levels to drop. If you have
Cushing’s syndrome, this won’t occur.

17.  Imaging tests
 CT or MRI scans can provide images of your pituitary and adrenal
glands to detect abnormalities, such as tumors.
 Petrosal sinus sampling
 This test can help determine whether the cause of Cushing
syndrome is rooted in the pituitary or somewhere else. For the test,
blood samples are taken from the veins that drain the pituitary
gland (petrosal sinuses).
 A thin tube is inserted into your upper thigh or groin area while
you're sedated and is threaded to the petrosal sinuses. Levels
of ACTH are measured from the petrosal sinuses and from a blood
sample taken from the forearm.
 If the ACTH level is higher in the sinus sample, the problem stems
from the pituitary. If the ACTH levels are similar between the
sinuses and forearm, the root of the problem lies outside of the
pituitary gland.

18.  Most cases of Cushingoid symptoms are caused by corticosteroid
medications, such as those used for asthma, arthritis, eczema and other
inflammatory conditions.
 Consequently, most patients are effectively treated by carefully
tapering off (and eventually stopping) the medication that causes the
symptoms.
 If an adrenal adenoma is identified, it may be removed by surgery.
 An ACTH-secreting corticotrophic pituitary adenoma should be
removed after diagnosis.
 Regardless of the adenoma's location, most patients require steroid
replacement postoperatively at least in the interim, as long-term
suppression of pituitary ACTH and normal adrenal tissue does not
recover immediately.
 Clearly, if both adrenals are removed, replacement with hydrocortisone
or prednisolone is imperative.

19.  In those patients not suited for or unwilling to undergo surgery, several drugs have been
found to inhibit cortisol synthesis (e.g. ketoconazole, metyrapone) but they are of
limited efficacy.
 Mifepristone is a powerful glucocorticoid type II receptor antagonist and, since it does
not interfere with normal cortisol homeostasis type I receptor transmission, may be
especially useful for treating the cognitive effects of Cushing's syndrome.
 However, the medication faces considerable controversy due to its use as an abortifacient.
 In February 2012, the FDA approved mifepristone to control high blood sugar levels
(hyperglycemia) in adult patients who are not candidates for surgery, or who did not
respond to prior surgery, with the warning that mifepristone should never be used by
pregnant women.
 In March 2020, Isturisa (osilodrostat) oral tablets a 11-beta-hydroxylase enzyme inhibitor
was approved by FDA for treating those patients who cannot undergo pituitary surgery or
for patients who underwent surgery but continue to have the disease.
 Removal of the adrenals in the absence of a known tumor is occasionally performed to
eliminate the production of excess cortisol.
 In some occasions, this removes negative feedback from a previously occult pituitary
adenoma, which starts growing rapidly and produces extreme levels of ACTH, leading to
hyperpigmentation.
 This clinical situation is known as Nelson's syndrome.

20. Before After

21.  Diet
 Although dietary changes won’t cure your condition, they can help to keep
your cortisol levels from rising even more or help to prevent some
complications.

22.  Some dietary tips for those with Cushing’s syndrome include:
 Monitor your calorie intake
 Keeping track of your calorie intake is important since weight gain is one of the
main symptoms of Cushing’s syndrome.
 Try to avoid drinking alcohol.
 Alcohol consumption has been linked with a rise in cortisol levels, particularly in
heavy drinkersTrusted Source, according to a 2007 study.
 Watch your blood sugar.
 Cushing’s syndrome can lead to high blood glucose, so try not to eat foods that
can cause a rise in blood sugar. Examples of foods to focus on eating include
vegetables, fruits, whole grains, and fish.
 Cut back on sodium.
 Cushing’s syndrome is also associated with high blood pressure (hypertension).
Because of this, try to limit your sodium intake. Some easy ways to do this
include not adding salt to food and carefully reading food labels to check sodium
content.
 Make sure to get enough calcium and vitamin D.
 Cushing’s syndrome can weaken your bones, making you prone to fractures.
Both calcium and vitamin D can help to strengthen your bones.

23.  Cushing’s Syndrome: Signs, Causes, and Treatment
(healthline.com)
 Cushing's Disease: Clinical Manifestations and Diagnostic
Evaluation - American Family Physician (aafp.org)
 Cushing’s Syndrome/Disease – Causes, Symptoms,
Diagnosis and Treatments (aans.org)
 Cushing syndrome - Symptoms and causes - Mayo Clinic
 Cushing Syndrome - StatPearls - NCBI Bookshelf (nih.gov)
 Diagnostic Approach to Cushing Disease (medscape.com)