Adrenal
Cushing's Disease
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Cushing's Disease
, Cushing's Syndrome, Cushing Disease, Cushing Syndrome
See Also
Addisons Disease
Definitions
Cushings Syndrome
Chronic
Glucocorticoid
excess
Cushing Disease
ACTH
Secretin
g pituitary tumors
Named for Harvey Cushing, who first described the condition in 1932
Hypercortisolism
Glucocorticoid
excess
May represent up to 2 to 5% of poorly controlled type diabetes cases with
Hypertension
Functional hypercortisolism also occurs in pregnancy
Epidemiology
Incidence
: 1-3 cases per million/year
Prevalence
: 40 cases per million
Gender: More common in women (3:1)
Peak age
Women: 50 to 60 years old
Causes
ACTH
Dependent Cushings Syndrome (80%)
Central Cause
Pituitary Adenoma
Adrenal Cause
Adrenal Adenoma
Bilateral Adrenal Hyperplasia
Adrenal Malignancy (15%)
Ectopic Source
Malignancy (Small Cell Carcinoma of the lung: 15%)
ACTH
Independent Cushings Syndrome (20%)
Iatrogenic
Corticosteroid
therapy (most common cause)
Pseudo-Cushings Syndrome
Obesity
Major Depression
Alcoholism
Precautions
Delayed diagnosis is common (often 3 to 6 years after initial symptoms)
Symptoms
Mood changes (depression, anxiety, irritability)
Easy
Bruising
Weakness
Weight gain
Amenorrhea
Back pain
Signs
Gene
ral
Truncal
Obesity
(90%)
Glucose Intolerance
(80%)
Moon facies
Plethoric face
Protein
wasting
Thin skin
Wide, purple abdominal and thigh striae (65%)
Easy
Bruising
and slow healing
Muscle
wasting (esp. leg atrophy)
Musculoskeletal
Osteoporosis
(55%)
Supraclavicular fat pad development
Buffalo hump (Thoracic kyphosis)
Myopathy
Cardiovascular
Hypertension
(85% when Cushing Disease is caused by tumors, 20% when iatrogenic)
Peripheral Edema
Hyperandrogenism
Hirsutism
(70%)
Hypertrichosis
Irregular
Menses
(e.g.
Amenorrhea
)
Diagnosis
Screening Test
24-hour Urinary free cortisol level
(preferred, performed at least twice)
Urine 17-Ketosteroid excretion
Urine 17-Hydroxysteroid excretion
Serum Cortisol
Low dose
Dexamethasone Suppression Test
Dexamethasone
1 mg at 11pm
Plasma
Cortisol
in following 8 AM
Night-time
Saliva
ry
Cortisol
testing
Distinguish between pituitary, adrenal or ectopic cause
Plasma
ACTH
High dose
Dexamethasone Suppression Test
(8 mg)
Differential Diagnosis
See Causes above
Imaging
CT or MRI Cone down Sella Turcica
Pituitary Adenoma
CT Abdomen
Adrenal Adenoma
Management
Exogenous Cushing Syndrome (Iatrogenic Cushing Syndrome, most common cause)
Stop
Corticosteroid
s or decrease dose
Change steroid dosing to every other day with drug holiday
Endogenous Cushing Syndrome
Transphenoidal surgery to excise adenoma (in pituitary or adrenal)
Preferred first-line management
Associated with 65 to 90% remission rate for microadenomas (65% for macroadenomas)
Alternatives to Surgical Management (and adjunctive in refractory cases)
Pituitary
Radiation Therapy
Risk of
Hypopituitarism
Bilateral adrenalectomy for Cushing Disease
Requires subsequent lifelong adrenal replacement therapy
Medications
Central Inhibition of
ACTH
Secretion (e.g. pasireotide,
Cabergoline
)
Adrenal Steroidogenesis Inhibition (e.g.
Ketoconazole
, metyrapone,
Mitotane
, osilodrostat)
Glucocorticoid
Receptor Blockade (e.g.
Mifepristone
)
Complications
Hypertension
Mood Disorder
s (e.g.
Major Depression
)
Muscle
atrophy
Osteoporosis
Type 2 Diabetes Mellitus
Prognosis
Untreated cases are ultimately fatal
Overall mortality rate 10%
Resources
Cushings Disease (StatPearls)
https://www.ncbi.nlm.nih.gov/books/NBK448184/
References
Castinetti (2012) Orphanet J Rare Dis 7:41 +PMID: 22710101 [PubMed]
Magiakou (2006) Best Pract Res Clin Endocrinol Metab 20(3): 467-82 [PubMed]
Orth (1995) N Engl J Med 332:791-803 [PubMed]
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