Adrenal Disease

Question 1

What is Cushings disease?

Answer 1

Cushing’s disease is due to excess ACTH secretion from the pituitary.

Most commonly caused by a ACTH excreting pituitary adenoma. But could also be due to excess CRH secretion from the hypothalamus.

Question 2

What is Cushings syndrome?

Answer 2

Cushing’s syndrome is cushing’s due any other pathology other than excess secretion of ACTH from the pituitary such as:

Adrenal Cushing’s.

An ACTH secreting ectopic tumour usually small cell carcinoma. (more associated with skin pigmentation as in ectopic tumours there are v.high levels of ACTH which controls melanin levels.)

Exogenous cortisol.

Question 3

Describe the classical features of Cushings disease/syndrome?

Answer 3

Hair thinning
Histurism 
Moon face
Buffalo Hump (intrascapular fat pad)
Central Obesity
Metabolic Syndrome
Red/purple Striae
Thin skin and easy bruising
Proximal muscle weakness
Osteoporosis

In secondary darkened skin pigmentation due to high levels of ACTH which controls melanin levels.

Note: Oestrogen becomes converted to testosterone in fat tissue, testosterone is secreted by the adrenal glands and in cushings disease the whole of the adrenals undergo hyperplasia.

Question 4

Describe how the dexamethasone suppression test works?

Answer 4

Dexamethasone is a synthetic glucocorticoid with a potency far greater than cortisol.

Administration suppresses the release of hypothalamic CRF and in turn, pituitary ACTH and cortisol from the adrenals.

Question 5

Describe how you investigate suspected Cushing’s?

Answer 5

Initially: low dose overnight dexamethasone suppression or 24 hr urinary cortisol.

If +ve low dose dexamethasone suppression and baseline ACTH levels.

If ACTH levels are low: adrenal glands are the problem

If ACTH levels are high: high dose dexamethasone suppression test.
If pituitary there will be partial suppression.
If due to an ectopic cause there won’ t be any suppression.

Question 6

What is Addison’s disease?

Answer 6

An autoimmune condition in which there is destruction of the adrenal glands therefore cortisol is not produced.

Low cortisol, High ACTH

Question 7

What other conditions cause there to be low levels of cortisol?

Answer 7

Pituitary tumour hypoadrenalism.

Low cortisol, low ACTH

Question 8

What test can be used to investigate suspected Addison’s disease?

Answer 8

Synacthen Stimulation Test. (synthetic ACTH)

In primary addison’s the stimulation test won’t increase cortisol as there is destruction of the adrenal glands.

In secondary causes it will stimulate cortisol release as the adrenal glands are functioning.*

Insulin stress test: Give IV insulin to induce a hypo which should cause a spike in cortisol

*However sometimes may have reduced stimulation due to adrenal hypoplasia.

Question 9

What are the signs and symptoms of Addison’s disease?

Answer 9

Initial symptoms of Addison's disease can include:
Fatigue 
Lethargy 
Muscle weakness
Low mood or irritability
Loss of appetite and unintentional weight loss
Polyuria
Polydipsia

Further Symptoms
Orthostatic hypotension
Nausea and vomiting
Diarrhoea
Abdominal/back pain
Muscle cramps 
Increased skin pigmentation

Note: Adrenals also produce aldosterone explaining BP and thirst symptoms

Question 10

Which metabolic derangement would be present in Addison’s disease?

Answer 10

High K+ and Low Na+

Aldosterone causes there to be reabsorption of Na+ and secretion of K+ therefore. When aldosterone is deficient such as in Addison’s K+ doesn’t get secreted causing levels to rise and Na+ isn’t reabsorbed causing levels to drop.

Question 11

Describe the treatment of Addison’s disease?

Answer 11

Hydrocortisone (glucocorticoid)
Fludrocortisone (mineralocorticoid)

Note: sick day rules continue steroids and considering increasing dose

Question 12

Describe the presentation of a patient with Addison’s crisis?

Answer 12

Preceding illness.
PMH: of adrenal insufficiency

Malaise.
Nausea/vomiting.
Abdominal pain.
Muscle cramps.

Question 13

Describe how you would treat an Addison’s crisis?

Answer 13

High dose IV hydrocortisone
Supportive care (fluids etc)

Question 14

What is Conn’s syndrome?

Answer 14

Excess secretion of aldosterone.

Caused by:

• Adrenal aldosteronoma* (benign)
• Idiopathic adrenal hyperplasia

Note causes renin suppression

*Tend to have higher BP and lower K+ at presentation also more commonly presents in younger patients whereas adrenal hyperplasia is more common in older patients.

Question 15

How does Conn’s syndrome present and what biochemical markers should raise suspicion?

Answer 15

Hypertension which is refractive to treatment and hypokalaemia.

Symptoms may be that of high blood pressure:
-Headaches

Or due to he hypokalaemia:

• Fatigue
• Muscle weakness
• Cramping

Should suspect this in all patients with high blood pressure and low K+

Question 16

Describe how you would investigate Conn’s syndrome?

Answer 16

Initial screening:

• BP
• U/E’s (low K+)

Confirmative test:
-24hr urinary aldosterone excretion test

Distinguishing between adrenal adenoma and idiopathic adrenal hyperplasia:

• Postural stimulation test
• Furosemide stimulation test

Question 17

Describe how you would interpret a postural stimulation test and a furosemide stimulation test?

Answer 17

Baseline serum aldosterone and plasma renin activity (PRA) levels are taken.

The patient stands in an upright position for 2-3hrs before the serum aldosterone and PRA are retested.

Typically in healthy patients or those with idiopathic adrenal hyperplasia levels will rise by roughly 50% whereas in adrenal adenoma’s they will stay roughly the same or paradoxically fall.

Furosemide stimulation test is the same except that instead of standing the patients are given a dose of furosemide the night before. Same trends, normally baseline levels increase in adrenal hyperplasia but not in adenomas.

The 2 tests can be combined.

Question 18

If an adrenal adenoma is likely due to postural stimulation test what is the next investigation you would order?

Answer 18

High resolution CT

Question 19

Describe the treatment of Conn’s syndrome?

Answer 19

Initial treatment:
Correct electrolyte imbalance
Reduce BP

BP management:
-Tend to be particularly responsive to aldosterone antagonists (spiranolactone)

Definitive management if caused by an adrenal adenoma is surgery. (Often adenoma’s are unilateral therefore patient does not develop iatrogenic Addison’s)

Question 20

What is congenital adrenal hyperplasia?

Answer 20

It is a group of autosomal recessive congenital disorders in which there is:

• Hyperplasia of the adrenal glands
• Reduced cortisol and aldosterone secretion
• Increased secretion of testosterone

Question 21

Describe the presentation of congenital adrenal hyperplasia in boys and girls?

Answer 21

Girls: ambiguous genatalia (enlarged clitoris/fused labia majora)

Boys: if severe will present with failure to thrive, dehydration and vomiting.

Biochemical tests may show signs of lack of aldosterone: low Na+ and high K+

Question 22

How is Cushing’s treated?

Answer 22

Cushing’s disease:
Trans-phenoidal excision of pituitary adenoma

Cushing’s syndrome:
Surgical excision of adrenal gland

ACTH secreting tumour: Treatment dependent on type of tumour

Question 23

What is a Phaeochromocytoma?

Answer 23

It is a catecholamine (adrenaline, noradrenaline, dopamine) secreting tumour derived from chromaffin cells.

It is usually in the adrenal medulla but they may be extra extra adrenal.

Question 24

What is the rule of 10’s in reference to phaeochromocytoma?

Answer 24

10% malignant
10% extra medullary
10% bilateral (adrenal)
10% hereditary

Question 25

What are the hereditary conditions associated with phaeochromocytoma?

Answer 25

MEN 2 (Multiple endocrine neoplasia)
Neurofibromatosis type 1
Von Hippel-Lindau

Question 26

What are typical presenting features of a phaeochromocytoma?

Answer 26

Episodic headache
Sweating
Tachycardia

May have other adrenergic features:

• Hypertension
• Tremor
• Anxiety

Question 27

Describe how you would investigate a suspected phaeochromocytoma?

Answer 27

Plasma and urine adrenaline levels
CT abdo
Isotope scan

Question 28

Describe the treatment of a hypertensive crisis secondary to phaeochromocytoma?

Answer 28

Phentolamine 2-5mg IV (alpha-blocker) or labetalol 50mg IV