Cushing's Syndrome Flashcards
Define Cushing’s Syndrome?
Syndrome associated with chronic inappropriate elevation of free circulating cortisol
How can Cushing’s Syndrome be divided?
ACTH Dependent (80%) ACTH Independent (20%)
What are some of the ACTH Dependent Cushing’s Syndromes?
Excess ACTH froma a pituitary adenoma (Cushing's Disease) Ectopic ACTH (e.g. lung cancer, pulmonary carcinoid tumours)
What are some of the ACTH Independent Cushing’s Syndromes?
Benign Adrenal Adenoma
Adrenal Carcinoma
What is the epidemiology of Cushing’s Syndrome?
Incidence: 2-4/1,000,000 per year
Peak incidence: 20-40 yrs
What are the presenting symptoms of Cushing’s Syndrome?
Increasing Weight Fatigue Muscle Weakness Myalgia Thin Skin Easy Bruising Poor Wound Healing Fractures Hirsuitism Acne Frontal Balding Oligomenorrhoea/amenorrhoea Depression or psychosis
What are the signs of Cushing’s Syndrome on physical examination?
Moon Face Facial Plethora Interscapular Fat pad Proximal Muscle Weakness Central Obesity Pink/Purple striae on abdomen/breast/thighs Kyphosis Hypertension Ankle Oedema Pigmentation in ACTH dependent cases
What is Kyphosis due to in Cushing’s Syndrome?
Vertebral Fracture
What is Ankle Oedema due to in Cushing’s Syndrome?
Salt and water retention from the mineralocorticoid effect of excess cortisol
On which patients are investigations performed in Cushing’s Syndrome?
On patients with a high pre-test probability
What bloods do you do for Cushing’s Syndrome and what might you expect?
U&Es - hypokalaemia due to mineralocorticoid effect
BM - High Glucose
What Initial High-Sensitivity Tests do you do for Cushing’s Syndrome?
Urinary free cortisol
Late-night salivary cortisol
Overnight dexamethasone suppression test
Low dose dexamethasone suppression test (LDDST)
How does the Low Dose Dexamethasone Suppression Test work?
Give 0.5 mg dexamethasone orally every 6 hrs for 48 hrs
In Cushing’s Syndrome, serum cortisol measured 48 hrs after the first dose of dexamethasone fails to suppress below 50 nmol/L
What test would you do to determine the underlying cause of an ACTH-independent Cushing’s Syndrome (Adrenal Adenoma/Carcinoma)?
Low plasma ACTH
CT or MRI of adrenals
What tests would you do to determine the cause of an ACTH-dependent Cushing’s Syndrome (pituitary adenoma)?
High plasma ACTH
Pituitary MRI
High-Dose dexamethasone SuppressionTest
Inferior Petrosal Sinus sampling (superior to high-dose dexamethasone suppression test)
What might you see on Inferior petrosal sinus sampling for ACTH-dependent Cushing’s Syndrome (Pituitary Adenoma)?
Central : peripheral ratio of venous ACTH > 2:1 (or > 3:1 after CRH administration) in Cushing’s Disease
What tests would you do for ACTH-Dependent Cushing’s Syndrome (Ectopic)?
If lung cancer suspected: CXR, sputum cytology, bronchoscopy, CT scan
Radiolabelled octreotide scans can detect carcinoid tumours because they express somatostatin receptors
What is the management plan for Cushing’s Syndrome if iatrogenic?
Discontinue steroids, use lower dose or use a steroid-sparing agent
What is the medical management plan for Cushing’s Syndrome?
Used pre-operatively or if unfit for surgery
Inhibit cortisol synthesis with metyrapone or ketoconazole
Treat osteoporosis
Physiotherapy for muscle weakness
What is the surgical management plan for Cushing’s Syndrome?
Pituitary Adenomas: trans-sphenoidal adenoma resection
Adrenal Adenoma/Carcinoma - surgical removal of tumour
Ectopic ACTH - treatment directed at the tumour
When would you do Radiotherapy in Cushing’s Syndrome?
Performed in those who are not cured and have persistent high cortisol after trans-sphenoidal resection of the tumour
When can Bilateral Adrenalectomy be performed?
May be performed in refractory Cushing’s Disease
What are the possible complications of Cushing’s Syndrome?
Diabetes
Osteoporosis
Hypertension
Pre-disposition to infections
What are the complications of surgery in Cushing’s Syndrome treatment?
CSF leakage
Meningitis
Sphenoid Sinusitis
Hypopituitarism
What are the complications of Radiotherapy in Cushing’s Syndrome treatment?
Hypopituitarism
Radionecrosis
Increased risk of second intracranial tumours and stroke
How can Bilateral Adrenalectomy be complicated?
By the development of Nelson’s Syndrome (locally aggressive pituitary tumour causing skin pigmentation due to ACTH secretion)
What is the prognosis for patients with Cushing’s Syndrome?
Untreated - 5 yr survival = 50%
Depression persists for many years following treatment
