Morning Report

Rick Hobbs
PGY – 3.4ish
 Frequency
 Endogenous Cushing syndrome –13 cases per
million individuals
 70% to Cushing disease
 15% to ectopic ACTH
 15% to a primary adrenal tumor
 Patient Characteristics
 Female-to-male ratio 5:1 for Cushing
syndrome due to adrenal or pituitary tumor
 Ectopic ACTH production is more frequent in
men than in women because of the increased
incidence of lung tumors in this population
 Clinical History
 Weight gain, skin changes, bruising, proximal
muscle weakness, menstrual irregularities,
decreased libido, depression, cognitive
dysfunction, emotional lability, HTN, diabetes,
impaired wound healing, infections,
osteoporotic fractures, headaches, vision
changes, galactorrhea, virilization
 Obesity
Physical Exam Findings
 Increased adipose tissue w/moon facies,
buffalo hump, and supraclavicular fat pads
 Central obesity w/ increased fat in mediastinum
and peritoneum, and visceral fat on CT.
 Increased waist-to-hip ratio greater than 1 in men
and 0.8 in women
 Skin
 Facial plethora
 Violaceous striae on abdomen, buttocks, lower
back, upper thighs, upper arms, and breasts
 Ecchymoses
 Telangiectasias and purpura.
 Cutaneous atrophy with exposure of subcutaneous
vasculature tissue and tenting of skin
 Increased lanugo facial hair.
 If glucocorticoid excess is accompanied by
androgen excess, as occurs in adrenocortical
carcinomas, hirsutism and male pattern balding
may be present in women. Steroid acne over the
face, chest, and back may be present
 Acanthosis nigricans, which is associated with
insulin resistance and hyperinsulinism, may be
present. Axilla, elbows, neck, and under breasts.
 Cardiovascular and renal
 Hypertension and possibly edema may be present
due to cortisol activation of the mineralocorticoid
receptor leading to sodium and water retention.
 Gastroenterologic
 Peptic ulceration particularly if patients are given
high doses of glucocorticoids (rare in endogenous
hypercortisolism).
 Endocrine
 Galactorrhea if anterior pituitary tumors compress
the pituitary stalk, leading to elevated prolactin
levels.
 Signs of hypothyroidism if anterior pituitary
tumor whose size interferes with proper TRH and
TSH function
 Decreased testicular volume due to low
testosterone levels from inhibition of LHRH and
LH/FSH function
 Skeletal/muscular
 Proximal muscle weakness
 Osteoporosis w/ fractures, kyphosis, height loss,
axial skeletal bone pain.
 Avascular necrosis of the hip is also possible from
glucocorticoid excess.
 Neuropsychological
 Emotional liability, fatigue, and depression.
 Visual-field defects, often bitemporal
hemianopsia, and blurred vision with large
ACTH-producing pituitary tumors that impinge on
the optic chiasma.
 Adrenal crisis
 May occur in patients on steroids who stop taking
their glucocorticoids or neglect to increase their
steroids during an acute illness, or in patients who
have recently undergone resection of an ACTH-
producing or cortisol-producing tumor or who are
taking adrenal steroid inhibitors.
 Hypotension, abdominal pain, vomiting, and
mental confusion (secondary to low serum sodium
or hypotension). Hypoglycemia, hyperkalemia,
hyponatremia, and metabolic acidosis.
Physical
Features
 Labs
 Leukocytosis
 Hyperglycemia
 Hypokalemic metabolic alkalosis due to
activation of the renal mineralocorticoid
receptor
Okay, that’s my patient,
how do I find the source?
 Simplify.
 Step 1: Exogenous vs Endogenous Cortisol
Excess?
 Step 2: ACTH-dependent or ACTH-
independent?
 Step 3: ACTH from pituitary or ectopic?
 Remember…
 Exogenous corticosteroids are the leading
cause of Cushing’s Syndrome
 Exogenous steroids suppress the HPA axis,
with full recovery taking as long as a year after
cessation of glucocorticoid administration.
ACTH-producing pituitary adenoma
 ACTH -> adrenal cortical hyperplasia ->
adrenal steroid overproduction
 Can also impair other anterior pituitary
hormones as well as vasopressin (galactorrhea
not uncommonly)
 Bitemporal hemianopsia
 Primary adrenal lesions
 Adrenal adenoma, adrenal carcinoma, or
macronodular or micronodular adrenal
hyperplasia
 Excess androgen secretion is suggestive of an
adrenal carcinoma rather than an adrenal
adenoma
 Ectopic ACTH
 Ectopic ACTH is sometimes secreted by oat
cell or small-cell lung tumors or by carcinoid
tumors
 Occurs later in life
 Question 1 – Endogenous?
 Endogenous overproduction of cortisol requires
the demonstration of inappropriately high serum
or urine cortisol levels
 Four Methods:
 Urinary Free Cortisol
 Low Dose Dexamethasone Suppression Test
 Evening Serum and Salivary Cortisol
 Dexamethasone-Corticotropin-Releasing hormone test
 UFC
 3-4 times the upper limit of normal are highly
suggestive of Cushing syndrome
 3 negative UFC measurements excludes
endogenous Cushing’s Syndrome
Dexamethasone Suppression Test
 Inhibit secretion of hypothalamic CRH and
pituitary ACTH but does not directly affect
adrenal cortisol production or ectopic
production
Question 2 – ACTH Dependent?
 Undetectable plasma ACTH (<5pg/ml) with
simultaneously elevated serum cortisol is
diagnostic of ACTH-independent Cushing
syndrome -> usually adrenal adenoma or
carcinoma
 Measurements of adrenal androgen production,
DHEAS and 24-hour urinary 17-ketosteroid
can confirm adrenal tumor
Question 3- Okay, too much ACTH.
But from where?
 ACTH >10-20 = dependent
 8mg overnight dex suppression test and 48hr
high-dose dex suppression test can
differentiate pituitary from ectopic ACTH
 CRH administration will increase pituitary-
driven ACTH and cortisol, but not affect
ectopic sources
 Imaging
 Wait! Not until biochemical testing performed
given 10% prevalence of incidentalomas.
 Abdominal CT to eval for primary adrenal
 Pituitary MRI
 Chest CT for lung CA w/ectopic secretion
 Octreotide scintigraphy can localize some
ectopic ACTH tumors
Inferior Petrosal Sinus Sampling
 Can identify a pituitary source of ACTH not
revealed by MRI by measuring ACTH
secretion in response to CRH in serum and
petrosal samples and comparing the values
 Bilateral sampling can actually lateralize a
microadenoma
 Treatment
 Stop exogenous glucocorticoid
 Surgery
 Medication to control hypercortisolism
 Mitotane, ketoconazole, metyrapone,
aminoglutethimide, trilostane, and etomidate
 Often fail
 Radiation if surgery not possible
 Must have stress-dose steroids pre-, intra-,
post-op