CUSHING SYNDROME

 01 BACKGROUND
 02 SIGNS AND SYMPTOMS
TABLE OF  03 ETIOLOGY
CONTENTS  04 DIAGNOSIS
 05 TREATMENT
Hypersecretion by the adrenal cortex causes a complex cascade of
hormone effects called Cushing's syndrome. It’s also known as
hypercortisolism. Cortisol comes from your adrenal glands, which
sit on top of your kidneys. It helps your body:
 Maintain blood pressure
 Regulate blood sugar
 Lower inflammation
 Turn the food you eat into energy
But when you have too much cortisol, it can throw off your body's
other systems
When Cushing’s syndrome is secondary to excess secretion of ACTH
by the anterior pituitary, this condition is referred to as Cushing's
disease.
 Administration of large doses of dexamethasone, a synthetic
glucocorticoid, can be used to distinguish between ACTH-
dependent and ACTH-independent Cushing’s syndrome.
 In patients who have overproduction of ACTH due to an ACTH-
secreting pituitary adenoma or to hypothalamic-pituitary
dysfunction, low doses of dexamethasone usually do not suppress
ACTH secretion normally. By increasing the dose of
dexamethasone to very high levels, ACTH eventually can be
suppressed in most patients with Cushing’s disease.
 In contrast, patients with primary adrenal overproduction of
cortisol (ACTH independent Cushing’s syndrome) usually have low
or undetectable levels of ACTH.
Exogenous  Cushing syndrome can develop from taking oral corticosteroid
medications, such as prednisone, in high doses over time.
Cushing  Oral corticosteroids may be necessary to treat inflammatory
Syndrome diseases, such as rheumatoid arthritis, lupus and asthma. They
may also be used to prevent your body from rejecting a
transplanted organ.
 The condition can be due to your body producing either too much
cortisol or too much adrenocorticotropic hormone (ACTH), which
Endogenous regulates cortisol production. In these cases, Cushing syndrome
may be related to:
Cushing 1. A pituitary gland tumor (pituitary adenoma)
Syndrome 2. An ACTH-secreting tumor
3. A primary adrenal gland disease
4. Familial Cushing syndrome
 A special characteristic of Cushing’s syndrome is
mobilization of fat from the lower part of the body,
with concomitant extra deposition of fat in the
thoracic and upper abdominal regions, giving rise to a
buffalo-like torso.
 The excess secretion of steroids also leads to an
edematous appearance of the face, and the
androgenic potency of some of the hormones
sometimes causes acne and hirsutism (excess growth
of facial hair).
 The appearance of the face is frequently described as
a “moon face,” as demonstrated in the untreated
patient with Cushing’s syndrome to the left in figure.
 About 80% of patients have hypertension, presumably
because of the mineralocorticoid effects of cortisol.
 Individuals with Cushing syndrome can develop
 moon facies
SIGNS AND  facial plethora
SYMPTOMS  supraclavicular fat pads
 buffalo hump
 truncal obesity
 purple striae.
Individuals often complain of proximal muscle weakness, easy
bruising, weight gain, hirsutism, and, in children, growth retardation.
Hypertension, osteopenia, diabetes mellitus, and impaired immune
function may occur.
 In a European population-based study, the annual incidence of
endogenous Cushing syndrome was reported to be 1.2-1.7 per
million per year (Cushing disease), 0.6 per million per year (adrenal
adenoma), and 0.2 per million per year (adrenal carcinoma). The
female-to-male incidence ratio is approximately 5:1 for Cushing
INCIDENCE syndrome due to an adrenal or pituitary tumor. Ectopic ACTH
production is more frequent in men than in women because of the
higher incidence of lung tumors in this population. The peak
incidence of Cushing syndrome due to either an adrenal or pituitary
adenoma is in persons aged 25-40 years. Ectopic ACTH production
due to lung cancer occurs later in life.
 1. 24-hour urinary free cortisol test
2. Salivary cortisol measurement
3. Low-dose dexamethasone suppression test
4. Blood adrenocorticotropin hormone (ACTH) test
5. Corticotropin-releasing hormone (CRH) stimulation test
DIAGNOSIS 6. High-dose dexamethasone suppression test
7. Corticotropin-releasing hormone (CRH) stimulation test
8. High-dose dexamethasone suppression test
9. Petrosal sinus sampling
10. Imaging studies
  Treatment of people with Cushing’s syndrome consists of
removing an adrenal tumor if this is the cause or decreasing the
secretion of ACTH, if possible.
 Hypertrophied pituitary glands or even small tumors in the
pituitary that oversecrete ACTH can sometimes be surgically
removed or destroyed by radiation.

TREATMENT  Drugs that block steroidogenesis, such as metyrapone,

ketoconazole, and aminoglutethimide, or that inhibit ACTH
secretion, such as serotonin antagonists and GABA transaminase
inhibitors, can also be used when surgery is not feasible.
 If ACTH secretion cannot easily be decreased, the only satisfactory
treatment is usually bilateral partial (or even total) adrenalectomy,
followed by administration of adrenal steroids to make up for any
insufficiency that develops.
 Medications used in the management of Cushing syndrome include
the following:
 11-beta-hydroxylase inhibitor: Osilodrostat

PHARMACO  Somatostatin analogs: Pasireotide

 Adrenal steroid inhibitors: Metyrapone, ketoconazole, etomidate
THERAPY  Glucocorticoid receptor antagonist: Mifepristone
 Adrenolytic agents: Mitotane
 The treatment of choice for endogenous Cushing syndrome is
surgical resection of the causative tumor. The primary therapy for
CONTENTS Cushing disease is transsphenoidal surgery, and the primary therapy
SURGICAL for adrenal tumors is adrenalectomy. Other surgical interventions
include the following:
THERAPY  Bilateral adrenalectomy
 Unilateral adrenalectomy
 Resection of carcinomas
 Without treatment, complications of Cushing syndrome may
include:
 Bone loss (osteoporosis), which can result in unusual bone
fractures, such as rib fractures and fractures of the bones in the
feet
 High blood pressure (hypertension)

COMPLICATIONS  Type 2 diabetes

 Frequent or unusual infections
 Even the protein collagen fibers in the subcutaneous tissue are
diminished so that the subcutaneous tissues tear easily, resulting
in development of large purplish striae where they have torn
apart.
 Loss of muscle mass and strength
CUSHING  Monitor your calorie intake
 Try to avoid drinking alcohol
SYNDROME  Watch your blood sugar
DIET  Cut back on sodium
 Make sure to get enough calcium and vitamin D
  Taking care to avoid long term use of cortisol-containing
medications may help to prevent some cases of Cushing's
PREVENTION syndrome.
  (Guyton Physiology) John Hall, Michael Hall - Guyton and Hall Text
book of Medical Physiology-Elsevier (2020)
 https://emedicine.medscape.com/article/2233083-overview
REFERENCES  https://www.healthline.com/health/cushings-syndrome#diagnosi
s
 https://www.mayoclinic.org/diseases-conditions/cushing-syndrom
e/symptoms -causes/syc-20351310
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