Disorders of Adrenal Function

Question 1

3 layers of cortex from outside going in?

Answer 1

Zona glomerulosa
Zona fasiculata
Zona reticularis

Question 2

Role of zona glomerulosa?

Answer 2

Secretes mineralocorticoids eg aldosterone

Question 3

Role of zona fasiculata?

Answer 3

Secretes glucocorticoids eg cortisol

Question 4

Role of zona reticularis?

Answer 4

Secretes the sex steroids eg testosterone

Question 5

Role of medulla?

Answer 5

releases A + NA

Question 6

Describe how is aldosterone synthesised

Answer 6

• cholesterol -> pregnenolone via P450SCC
• pregnenolone -> progesterone via 3β HSD
• progesterone -> deoxycorticosterone via 21 OH
• in zona glomerulosa
• deoxycorticosterone -> aldosterone via 11β OH

Question 7

Why is aldosterone + cortisol only produced in adrenal?

Answer 7

21 OH only expressed in adrenal

Question 8

Where are the enzymes for testosterone production produced?

Answer 8

ovaries

Question 9

How are oestrodiols synthesised?

Answer 9

in ovaries enzyme aromatase produced in high levels to aromatise testosterone -> oestradiol

Question 10

How’s progesterone synthesised in females?

Answer 10

2nd half of menstrual cycle 17α OH produced downregulates so major output is progesterone

Question 11

Actions of cortisol?

Answer 11

-Increases plasma glucose levels:
↑ gluconeogenesis
↓ glucose utilisation
↑ glycogenesis
↑ glycogen storage
-Increases lipolysis: provides energy
-Proteins are catabolised: releases AA
-Na+ and H2O retention: maintains BP
-Anti inflammatory
-Increased gastric acid production

Question 12

What’s Cushing’s syndrome?

Answer 12

Clinical features of chronic exposure to excessive levels of cortisol

Question 13

Who discovered Cushing’s syndrome?

Answer 13

Harvey Cushing in 1932

1st person to describe the association between pituitary gland tumours + signs of excess steroid hormones

Question 14

Epidemiology of Cushing’s syndrome?

Answer 14

Incidence is 2/1 000 000 population
3-15 : 1 female : male
Onset at 20-40 years old

Question 15

Epidemiology of Cushing’s syndrome?

Answer 15

Incidence is 2/1 000 000 population
3-15 : 1 female : male
Onset at 20-40 yrs

Question 16

Define Cushing’s Syndrome

Answer 16

Excess cortisol in the blood

Question 17

Define Cushing’s Disease

Answer 17

Excess cortisol in the blood due to an ACTH secreting pituitary tumour

Question 18

Clinical features of Cushing’s syndrome + why they occur?

Answer 18

High BP
Fluid retention
due to salt + water retention

Question 19

3 stages of investigation of Cushing’s disease?

Answer 19

Screening
Confirmation of the Diagnosis
Differentiation of the Cause

Question 20

Screening + Confirmation of the Diagnosis?

Answer 20

Urinary free cortisol
Diurnal Rhythm
Over night dexamethasone suppression testing

Question 21

Significance of circadian rhythm pattern?

Answer 21

endogenous pattern (innate) runs a 24/25hr cycle
so we would do a urinary free cortisol test where we test urinary cortisol over 24hrs
(highest in early morning and lowest at midnight)

Question 22

Overnight Low Dose Dexamethasone Suppression Test?

Answer 22

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

Question 23

Differential Diagnosis?

Answer 23

-True Cushing’s Syndrome
-Pseudocushing’s Syndrome:
Depression
Alcoholism
Anorexia Nervosa
Obesity
-Exogenous steroids: inhalers, eyedrops, nasal drops, skin creams, health food shops
-Cushing’s Disease:
Pituitary Adenoma
-Adrenal Tumour:
Benign
Malignant
-Ectopic ACTH production:
Benign
Malignant

Question 24

Differentiation of the Cause?

Answer 24

High dose Dexamethasone Suppression testing
ACTH
Imaging

Question 25

Dexamethasone Suppression Test?

Answer 25

- HIGH DOSE:2 mg Dexamethasone six-hourly for 48hrs - If cortisol suppresses to < 50% of baseline then the patient has Pituitary dependent Cushing’s Disease - If cortisol does not suppress then the patient has ectopic ACTH production or an adrenal tumour

Question 26

Adrenocorticotropic hormone (ACTH) levels in adrenal tumour?

Answer 26

low ACTH

Question 27

Adrenocorticotropic hormone (ACTH) levels in ectopic ACTH production?

Answer 27

high ACTH

Question 28

Laboratory Features?

Answer 28

Hypokalaemia Metabolic Alkalosis Hyperglycaemia

Question 29

CRH test?

Answer 29

- 0.1 µg/kg of human CRH is given - Blood is assayed for ACTH and cortisol at time -15, 0, 15, 30, 60, 90, 120. - An exaggerated response indicates pituitary dependant Cushing’s Disease - A flat response indicates ectopic ACTH production

Question 30

Localisation?

Answer 30

``` -Pituitary MRI IPSS -Adrenal CT or MRI -Ectopic Octreotide Scan ACTH Sampling ```

Question 31

Treatment?

Answer 31

- SURGERY - Cortisol Production Blockers: metyrapone, ketoconazole - DXT three field or gamma knife - Following treatment patients may require replacement of other pituitary hormones too - Pituitary : Transsphenoidal Hypophysectomy - Adrenal source : Removal of adrenal tumour - Patients need to have steroid replacement tablets at the time of and following surgery - The adrenal tumour suppresses the function of the normal gland - Many will not need the steroid tablets long term - Hydrocortisone :10mg 5mg 5mg, mimicks the diurnal rhythm, last dose before 6pm - Fludrocortisone : 50-200mcg o.d.

Question 32

Addison’s Clinical Features?

Answer 32

``` Tiredness Weakness Anorexia Weight loss Postural hypotension Myalgia Salt Craving Nausea Vomiting Hyperpigmentation Vitiligo Hyponatraemia Hyperkalaemia Acidosis Hypercalcaemia Hypoglycaemia Increased urea + creatinine Eosinophilia Lymphocytosis ```

Question 33

Causes of Addison’s Syndrome?

Answer 33

``` Autoimmune TB Steroid Withdrawal Metastases Infiltration : amyloid, haemochromatosis Waterhouse- Freidrichson Apoplexy Infection : fungal, viral Enzyme defect : Congenital Adrenal hyperplasia, Adrenolucodystrophy, Adrenomyolneuropathy Drugs ```

Question 34

21-hydroxylase Deficiency (Classical) congenital adrenal hyperplasia?

Answer 34

``` Commonest form of CAH Incidence 1:10 000 live births Autosomal recessive HLA linked HLA-A3, Bw47,DR7 Increased incidence in Yupik Eskimos ```

Question 35

21-hydroxylase Deficiency (Classical)?

Answer 35

-Excess sex steroids cause virilisation, hirsutism, premature adrenarche, infertility. -No aldosterone, hence salt-losing crisis hyperkalaemia, hypotension.

Question 36

11β-hydroxylase Deficiency (Non-Classical)?

Answer 36

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

Question 37

11β-hydroxylase Deficiency (Non-Classical)?

Answer 37

- Excess sex steroids : virilisation, hirsutism, premature adrenarche, infertility - No aldosterone but high DOC, which is an agonist at MC receptors : hypertension and hypokalaemia

Question 38

Investigation?

Answer 38

- Synacthen : no cortisol rise, increased 17OH Progesterone levels - Prednisolone suppression : androgens should fall into normal range

Question 39

Treatment?

Answer 39

Both entities comprise a spectrum of disease – partial deficiencies complicate matters. Rx of 11b- and 21- hydroxylase deficiency lies mainly in the use of glucocorticoid therapy Surgery to virilised female genitalia. Treatment of Mother to prevent foetal Virilisation Fludrocortisone is used only in 21-hydroxylase deficiency to replace absent mineralocorticoid activity