Disorders of adrenocortical dysfunction

Question 1

What are the actions of Cortisol?

Answer 1

Increases plasma glucose levels
Increases lipolysis
Proteins are catabolized 
Na+ and H2O retention 
Anti-inflammatory
Increased gastric acid production

Question 2

Cushing’s syndrome

Answer 2

High levels of the steroid hormone cortisol

Question 3

Who first discovered Cushing’s?

Answer 3

Harvey Cushing’s in 1932 and he made the link between pituitary gland tumors and signs of excess steroid hormones

Question 4

Epidemiology of Cushing’s

Answer 4

2/1 000 000
onset 20-40 years
3:1 or 15:1 female: male

Question 5

Definition of Cushing’s syndrome and Cushing’s disease

Answer 5

Syndrome - Excess cortisol in the blood

Disease - excess cortisol in the blood due to an ACTH secreting pituitary tumor

Question 6

Clinical features of Cushing’s

Answer 6

High Blood Pressure
Fluid retention
Caused by Salt and water retention

Question 7

How do you investigate Cushing’s

Answer 7

Screening
Confirmation of the diagnosis
Differentiation of the Cause

Question 8

Screening and confirmation for Cushing’s

Answer 8

Urinary Free cortisol
Diurnal rhythm
Overnight dexamethasone suppression testing

Question 9

Overnight low dose dexamethasone suppression test

Answer 9

Cortisol is measured at 8 am
Dexamethasone 1mg is given at 11 am
Cortisol is measured at 8 am the next morning
Cortisol suppression to <50mmol/l is normal

Question 10

Differential diagnosis

Answer 10

True Cushing's syndrome 
Pseudo Cushing's syndrome
Depression 
Alcoholism 
Anorexia Nervosa 
Obesity 
Exogenous steroids

Question 11

Dexamethasone suppression test

Answer 11

Low dose
0.5 mg dexamethasone six-hourly, 48 hrs
Results
Complete suppression in a normal subject
If cortisol detectable then the patient has Cushing’s Syndrome

Question 12

Differential diagnosis carried on

Answer 12

Cushing’s disease - Pituitary Adenoma
Adrenal Tumour - Benign, Malignant
Ectopic ACTH production - Benign, Malignant

Question 13

What happens if cortisol is less than 50% in a high dexamethasone test?

Answer 13

Pituitary dependent Cushing’s Disease

If cortisol does not suppress then the patient has ectopic ACTH production or an adrenal tumor

Question 14

High Dexamethasone Suppression test?

Answer 14

2 mg dexamethasone 6-hourly for 48 hours

Question 15

Difference between Adrenal tumor and Ectopic ACTH production

Answer 15

Low ACTH

High ACTH

Question 16

CRH test

Answer 16

0.1 ug/kg of human CRH is given
Blood is assayed for ACTH and cortisol at timed intervals
An exaggerated response indicates pituitary-dependent Cushing’s disease
The flat response indicates ectopic ACTH production

Question 17

How do you find the tumors?

Answer 17

Pituitary - MRI, IPSS
Adrenal - CT or MRI
Ectopic - Octreotide scan ACTH sampling

Question 18

What is IPSS?

Answer 18

Inferior petrosal sinus sampling to measure ACTH from the veins from the pituitary gland and the ACTH from peripheral blood.

Question 19

Octreotide scan

Answer 19

also known as somatostatin receptor scintigraphy, is a test used to check the body for the presence of neuroendocrine tumor cells.

Question 20

Treatment of Cushing’s

Answer 20

Cortisol production blockers
DXT three field or gamma knife
Adrenal source - remove the tumor source
Steroid replacement tablets

Question 21

Addison’s clinical Features Part 2

Answer 21

Hyponatraemia
Hyperkalaemia
Acidosis
Hypercalcemia

Question 22

Addison’s clinical Features Part 1

Answer 22

Hyponatremia 
Hyperkalaemia 
Acidosis 
Hypercalcemia 
Hypoglycemia 
Increased urea and creatinine 
Eosinophilia
Lymphocytosis

Question 23

Causes of Addison’s syndrome part 1

Answer 23

Autoimmune
TB
Steroid withdrawal 
Metastases 
Infiltration 
Amyloid 
Hemochromatosis 
Waterhouse - Freidrichson 
Apoplexy

Question 24

Causes of Addison’s syndrome part 2

Answer 24

Infection 
fungal 
Viral 
Enzyme defect
Drugs

Question 25

Treatment of Addison’s

Answer 25

Hydrocortisone  
- 10 mg, 5mg
Mimicks the diurnal rhythm 
last dose before 6 pm 
Fludrocortisone

Question 26

21- hydroxylase deficiency classical CAH

Answer 26

A common form of CAH 
1:10 000 live births
Autosomal recessive 
HLA linked 
HLA-A3, Bw 47, DR7
Increased incidence in Yupik Eskimos

Question 27

What is the result of 21- hydroxylase deficiency?

Answer 27

Excess sex steroid
Hirsutism, virilization, premature adrenarche, infertility
No aldosterone, hence the salt-losing crisis
Hyperkalaemia. hypotension

Question 28

11 beta-hydroxylase deficiency (nonclassical)

Answer 28

Accounts for approx 5% of reported CAH
0.5:100 000 live births 
autosomal recessive
Increased in Moroccan jews (1:6000 live) 
HLA linked 
HLA-B14, DR1

Question 29

What is CAH?

Answer 29

Congenital adrenal hyperplasia

A group of rare and inherited disorders that leads to the inability to make specific hormones

Question 30

What is the result of 11 beta-hydroxylase deficiency?

Answer 30

Excess sex steroids
virilization, hirsutism, premature adrenarche, infertility
No aldosterone but DOC which is an agonist at MC receptors - hypertension and hypokalemia

Question 31

Aldosterone

Answer 31

Produced in the zona glomerulosa of the adrenal cortex
Acts on the kidney via receptor binds glucocorticoids with equal affinity
Intranuclear receptor

Question 32

Aldosterone syndromes

Answer 32

Primary Excess
Conn's syndrome 
Bilateral adrenal hyperplasia 
Steroid treatable - hypertension
Aldosterone producing adrenal carcinoma

Question 33

Phaeochromocytomas

Answer 33

Tumor of the enterochromaffin cells of the adrenal medullar

Produce adrenaline

Question 34

What is the role of ten?

Answer 34

10% Bilateral
10% Malignant
10% extra-adrenal
10% inherited

Question 35

Conn’s treatment

Answer 35

Spironolactone
Amiloride/ triampterine
Potassium supplementation
Treatment of the primary tumor