Sindrom Cushing

Donnie Lumban Gaol

Departemen Ilmu Penyakit Dalam
FKUKI
 Case.
Seorang wanita, 21 tahun datang ke
rumah sakit dengan keluhan utama
bengkak seluruh tubuh. Keluhan
tambahan, pada lipat paha, perut
dan pantat terdapat garis-garus tebal
berwarna merah keunguan. Pasien
mengeluh timbul jerawat yang
banyak di muka hingga di dada.
 About Cushing
Cushings syndrome was first
described by Harvey Cushing in 1910
in a woman with central obesity,
abdominal striae, hirsutism,
amenorrhea, hypertension, proximal
muscle weak- ness, thinning hair,
and purpura.
About Cortisol..
 The distinction between Cushings
syndrome and Cushings disease is
important.
Cushings Syndrome: syndrome is
the constellation of signs associated
with hypercortisolism
Cushings disease is specific to an
ACTH-secreting pituitary tumor that
results in Cushings syndrome.
 Cushing
Pseudo-Cushings syndrome. In
pseudo-Cushings syn- drome,
patients have all or some of the
clinical features of true Cushings
syndrome, but hypercortisolism is
due to activation of the
hypothalamic-pituitary-adrenal axis
by an underlying illness.
Hypothalmus-Pituitary-Adrenal
Axis
 CRH
Hypothalmus-
Pituitary-Adrenal Axis (+) (-)

ACTH (-)
(+) Cortisol
Cortisol Circadian Rhythm
Clinical findings I

Central obesity with insulin resistance, & Weight

gain.
Diabetes mellitus or Impaired glucose tolerance
and their sequelae of atherosclerosis and
cardiovascular disease.
Dyslipidemia
Osteoporosis
Nephrolithiasis
Neuropsychiatric problems
Polycystic ovary syndrome is common in women
with the Cushing syndrome.
Pt. with PCOD should be tested to exclude
endogenous hypercortisolism
Clinical findings II

Hypertension
Coetaneous wasting
Cervical (dorsal) fat pad fat pads.
Facial rounding with plethora
Supra-clavicular fullness
Proximal myopathy
Striae
Thin skin
 About Cushing

Cushings
Hypercortisolism
syndrome
Cushings Syndrome
Etiology
 Cushings Syndrome Causes

ACTH-dependent (bilateral adrenal hyperplasia)

Pituitary ACTH-dependent Cushings syndrome
(Cushings disease)
Ectopic ACTH syndrome
Ectopic CRH syndrome

ACTH-independent
Adrenal Adenoma or Carcinoma
Adrenal hyperplasia (Micro- and macro-)
Glucocorticoids administration
Causes of Cushing's
syndrome
The most common cause of
hypercortisolism is ingestion of prescribed
medication, usually for Non-Endocrine
disease.
Oral
Injected
Topical
Inhaled glucocorticoids
 Exogenous
Iatrogenic CRH Hydrocortiso
Cushings ne
Syndrome (+)

(-)

ACTH (-)
(-) Cortisol
 ACTH-
CRH
dependent (+)
Cushings
disease

tonomous ACTH secreting tumour

ACTH (-)
(+) Cortisol
 CRH
Adrenocortical tumour
(+)

ACTH (-) (+)

Cortisol
Autonomous cortisol secreting tumour
 CRH
Ectopic ACTH
syndrome (+)

(+)
Ectopic ACTH secreting tumour
Cortisol

ACTH (+)
 CRH Ectopic CRH
Ectopic CRH secreting tumour
(+)
producing tumour

ACTH (+)
(+) Cortisol
 Cushings Syndrome
Clinical features
General
Central obesity
Proximal muscle weakness
HTN
Headaches
Dermatologic
Wide purple striae
Spontaneous ecchymoses
Facial plethora
Hyperpigmentation
Acne, hirsutism
Fungal skin infections
Endocrine/Metabolic
Hypokalemic alkalosis
Hypokalemia
Osteopenia
Hypogonadism
Glucose intolerance
Hyperlipidemia
Hyperhomocysteinemia
Kidney stones
Polyuria
Hypercoagulability
Neuropsychiatric
Insomnia
Depression, frank psychosis
Impaired cognition and short-
term memory
Cushings Syndrome
Clinical features
 Cushing Syndrome AND
Skin
Dermatologic manifestations of
Cushings syndrome include violaceous
striae, ecchymoses, hyperpigmenta-
tion, oily skin, acne, and facial plethora.
Striae are the result of scarring from
dermal tears, and they appear purple
because the underlying vasculature be-
comes apparent as the skin becomes
increasingly thin.
 Cushing AND skin
Violaceous striae and ecchymoses
are caused by deficient colla- gen
synthesis, resulting in thin and fragile
skin.
Patients often report easy bruising,
which is caused by weakness of
vessel walls and the surrounding con-
nective tissue.
ACTH binds to melanocyte-
stimulating hormone, causing
 Diagnosis of Cushing
syndrome
Does the patient have Cushing's
syndrome?
Determining if the Cushing's
syndrome is corticotropin (ACTH)-
dependent or (ACTH)-independent.
Determining the source of the ACTH
in ACTH-dependent Cushing's
syndrome.
 Cushing AND
musculoskeletal
Musculoskeletal
Excess glucocorticoids can suppress muscle
protein synthesis, which atrophies the
muscles.
Osteoporosis can also develop with long-
standing Cushings syndrome, and fractures,
including vertebral fractures, may result.
Osteoporosis results from inhibition of bone
formation and suppression of calcium
absorption from the intestine, both of which
are effects of excess glucocorticoids
Cushing AND Gonadal Dysfunction..

Hypogonadism results from the inhibitory

ef- fect of cortisol on gonadotropin-
releasing hormone, follicle stimulating
hormone, and luteinizing hormone.
Increased androgen production causes
hirsut- ism, oily skin, acne, and menstrual
irregularities (eg, amenorrhea,
oligomenorrhea) in women, impotence in
men, and loss of libido in both sexes.
 Cushing AND Psychiatric

Confusion and psychosis are

possible.
Depression is the most common
psychiatric complication of
endogenous Cushings syndrome,
whereas mania is more common with
exogenous Cushings syndrome
 Cushing
The most common cause of ACTH-
independent Cushings syndrome is
long-term exogenous glucocorticoid
administration.
 DIAGNOSTIC EVALUATION
Confirming Hypercortisolism
The presence of hypercortisolism
must first be determined using 1 of 3
available screening tests:
the overnight (1-mg) dexamethasone
suppression test
24-hour urinary free cortisol (UFC)
measurement, and
or a midnight salivary cortisol
measurement.
 Cushing
The 24-hour UFC measurement is the
most widely used screening test for
Cushings syndrome and is considered the
gold standard test for evaluating the
presence of hypercortisolism.
Normal urinary cortisol excretion is 20 to
100 g per 24 hours, whereas most
patients with Cushings syndrome excrete
more than 250 g of urinary cortisol per
24 hours.
 DIAGNOSTIC EVALUATION
Localizing the Cause

To localize the cause, the serum ACTH level

should be measured.
Normal ACTH levels range from 9 to 52
pg/mL.
An elevated or normal ACTH level in the
presence of elevated serum cortisol
indicates a pituitary or ectopic source.
Low ACTH levels indi- cate an adrenal
source (ie, ACTH-independent Cushings
SYNDROME)
EVALUATION..
 TREATMENT

Treatment depends on the source of

hypercortisolism.
Surgical resection of the tumor is often
cu- rative
Metyrapone and ketoconazole block
cortisol synthesis, and aminoglutethimide
inhibits pro- duction of adrenal
glucocorticoids, mineralocorticoids,
aldosterone, estrogens, and androgens.