Cushings Syndrome Flashcards
What is Cushing syndrome?
Cushing syndrome is a condition caused by prolonged exposure to elevated levels of either endogenous glucocorticoids or exogenous glucocorticoids causing signs and symptoms of hypercortisolism.
Exogenous use of glucocorticoids should always be considered and excluded in the etiology of Cushing syndrome.
Blood supply of the adrenal glands
The adrenal glands have a rich blood supply via three main arteries:
Superior adrenal artery– arises from the inferior phrenic artery
Middle adrenal artery– arises from the abdominal aorta.
Inferior adrenal artery– arises from the renal arteries.
Right and left adrenal veins drain the glands.
Right and left adrenal veins drain the glands. The right adrenal vein drains into theinferior vena cava,whereas the left adrenal vein drains into theleft renal vein.
Epidemiology
The annual incidence of endogenous Cushing syndrome was 1.2-1.7 per million per year according to European population based .
The female-to-male incidence ratio is approximately 5:1.
The peak incidence is in persons aged 25-40 years.
Etiology
ACTH independent cushing syndrome
Primary adrenal lesions:
Adrenal adenoma, adrenal carcinoma, macronodular or micronodular adrenal hyperplasia.
Ectopic cortisol secretion from a case of ovarian carcinoma
ACTH-dependent Cushing syndrome:
ACTH-producing pituitary adenoma
Ectopic ACTH secretion by small-cell lung tumors, carcinoid tumors, or other tumors with neuroendocrine origin.
Ectopic CRH secretion : a very rare cause.
EXOGENOUS CUSHING SYNDROME
Clinical features
Emotional disturbance
Enlarged sella turcica
Moon facies
Osseoporosis
Cardiac hypertrophy (hypertension)
Buffalo hump
Obesity
Adrenal tumor or hyperplasia
Thin, wrinkled skin
Abdominal striae
Amenorrhea
Muscle weakness
Purpura
Skin ulcers (poor wound healing)
HTN is in 80% of people
How do you diagnose Cushing syndrome
- Clinical suspicion
- 24 h UFC x3 Low dose dexamethasone suppression test assessment of circadian rhythm
- a) Normal Cushing syndrome excluded
b) Abnormal Cushing syndrome
c) Equivocal suspicion for pseudo Cushing ———> Low dose dexamethasone suppression/CRH test
Investigation
Midnight serum or salivary cortisol
24-hour urine free cortisol X 2
Low dose dexamethasone suppression test
Explain the LDDST
The rationale for the dexamethasone suppression test is based on the normal physiology of the hypothalamic-pituitary-adrenal axis; glucocorticoids inhibit secretion of hypothalamic CRH and pituitary ACTH.
The overnight 1-mg dexamethasone suppression test requires administration of 1 mg of dexamethasone at 11 PM with subsequent measurement of cortisol level at 8 am.
To enhance the sensitivity of the test, a cutoff value of less than 1.8 mcg/dL (50 nmol/L) excludes Cushing syndrome.
When is an abdominal CT recommended?
An abdominal CT scan is recommended if a primary adrenal pathology is suspected. The presence of an adrenal mass larger than 4-6 cm raises the possibility that the mass is an adrenal carcinoma.
What is the goal of treatment
Therapy should reduce the cortisol secretion to normal to reduce the risk of comorbidities associated with hypercortisolism.
Medications
11-beta-hydroxylase inhibitor: Osilodrostat
Somatostatin analogs: Pasireotide
Adrenal steroid inhibitors: Metyrapone, ketoconazole, etomidate
Glucocorticoid receptor antagonist: Mifepristone
Adrenolytic agents: Mitotane
Treatment
Pasireotide is a somatostatin analog that binds and activates human somatostatin receptors resulting in inhibition of ACTH secretion, which leads to decreased cortisol secretion.
It is indicated for treatment of adults with Cushing disease in whom pituitary surgery is not an option or has not been curative.
Surgery: The treatment of choice for endogenous Cushing syndrome is surgical resection of the causative tumor.
The primary therapy for Cushing disease is trans-sphenoidal surgery.
The primary therapy for adrenal tumors is adrenalectomy.
