Cushing Syndrome

Question 1

Definition of cushing syndrome

Answer 1

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.

Question 2

What are the arteries and veins of the adrenal gland?

Answer 2

The adrenal glands have a rich blood supply via three main arteries:

1. Superior adrenal artery– arises from the inferior phrenic artery
2. Middle adrenal artery– arises from the abdominal aorta.
3. Inferior adrenal artery– arises from the renal arteries.

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.

Question 2

What is the anatomy of the adrenal gland?

Answer 2

Adrenal glands, also known as suprarenal glands, are small, triangular-shaped glands located on top of both kidneys.
Adrenal glands are composed of two parts — the cortex and the medulla.
Each adrenalgland weighs about 5 grams.

Question 2

EPIDEMIOLOGY

Answer 2

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.

Question 3

Etiology of ACTH independent and ACTH dependent cushing syndrome

Answer 3

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

Question 3

Diagnosis of Cushing Syndrome

Answer 3

1. Clinical suspicion
2. 24h UFC x3: LDDST assessment of circadian rhythm
3. i) normal cushing excluded
   ii) abnormal cushing syndrome
   iii) equivocal suspicion for pseudo cushing

Question 4

Clinical features of Cushing syndrome

Answer 4

• Emotional disturbances
• Enlarged sella turcica
• Moon facies
• Osteoporosis
• Adrenal tumor or hyperplasia
• Thin, wrinkled skin
• Abdominal striae
• Amenorrhea
• Muscle weakness
• Purpura
• Skin ulcers (poor wound healing)
• HTN

Question 5

Investigations

Answer 5

• Midnight serum or salivary cortisol
• 24-hour urine free cortisol X 2
• Low dose dexamethasone suppression test
• 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 (because an adrenal adenoma is less than 4cm)

Question 6

What is the rationale for the dexamethasone suppression test?

Answer 6

• 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.

Question 7

Goal of treatment

Answer 7

Therapy should reduce the cortisol secretion to normal to reduce the risk of comorbidities associated with hypercortisolism.

Question 7

MEDICATIONS

Answer 7

1. 11-beta-hydroxylase inhibitor: Osilodrostat
2. Somatostatin analogs: Pasireotide
3. Adrenal steroid inhibitors: Metyrapone, ketoconazole, etomidate
4. Glucocorticoid receptor antagonist: Mifepristone
5. Adrenolytic agents: Mitotane
6. Pasireotide is a somatostatin analog that binds and activates human somatostatin receptors resulting in inhibition of ACTH secretion, which leads to decreased cortisol secretion.
7. It is indicated for treatment of adults with Cushing disease in whom pituitary surgery is not an option or has not been curative.

Question 8

Surgical treatment

Answer 8

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.