Lecture 11: Clinical Aspects of the Adrenal Gland Clinical Case & Discussion

Question 1

what other autoimmune disease are associated with Addison’s disease?

Answer 1

• thyroid disease (20%)
• type 1 diabetes mellitus (15%)
• premature ovarian failure (15%)

Question 2

what are common symptoms associated with primary adrenal failure?

Answer 2

• weakness, fatigue, anorexia, weight loss
• skin pigmentation or vitiligo
• hypotension
• unexplained vomiting or diarrhoea
• salt craving
• postural symptoms

Question 3

diagnosis of adrenal insufficiency involved which investigations?

Answer 3

• routine bloods: U&E, glucose, FBC
• random cortisol: > 450nmol/l (not Addison’s), < 450nmol/l (adrenal status uncertain)
• synacthen test (and basal ACTH)
• if suspicion high and patient is unwell, treat with steroids and do synacthen test later

Question 4

in the case of secondary adrenocortical insufficiency, is plasma ACTH suppressed or elevated?

Answer 4

suppressed

Question 5

in the case of primary adrenocortical insufficiency, is plasma ACTH suppressed or elevated?

Answer 5

elevated

Question 6

list the glucocorticoid replacement drugs used in adrenal insufficiency

Answer 6

• hydrocortisone 20-30mg
• prednisolone 2.5mg
• dexamethasone 0.75mg
• given in divided doses to mimic normal diurnal variation

Question 7

describe mineralocorticoid replacement therapy used for adrenal insufficiency

Answer 7

• synthetic steroid, fludrocortisone
• binds to mineralocorticoid receptors
• 50-300 mg daily
• adjust dose according to clinical status, U&E, plasma renin level

Question 8

what are the three important ‘self-care’ rules for patients on steroids?

Answer 8

• never miss steroid doses
• double the hydrocortisone dose in event of intercurrent illness (e.g. flu, UTI)
• if severe vomiting or diarrhoea, call for help without delay

Question 9

what % of Cushing’s syndrome is caused by a pituitary tumour (Cushing’s disease)?

ACTH-dependent

Answer 9

75%

Question 10

what % of Cushing’s syndrome is caused by ectopic ACTH secretion (e.g. lung carcinoid)?

ACTH dependent

Answer 10

5%

Question 11

what % of Cushing’s syndrome is caused by an adrenal tumour (adenoma or carcinoma)?

ACTH-independent

Answer 11

20%

Question 12

list the screening tests for Cushing’s syndrome

Answer 12

• 24hr urinary free cortisol (normal 14-135nmol/24h)
• 1mg overnight dexamethasone suppression test taken

Question 13

treatment for Cushing’s disease

Answer 13

Surgery is treatment of choice to remove causative tumour.

Medical:
- adrenal hormone synthesis inhibitors: ketoconazole, metyrapone, aminoglutethimide, etomidate
- destroy adrenocortical cells: mitotane

• radiotherapy
• bilateral adrenalectomy

Question 14

what does a PAC/PRA ratio > 20 indicate?

PAC = primary aldosterone concentration PRA= plasma renin activity

Answer 14

primary hyperaldosteronism e.g. Conn’s syndrome caused by an adrenal adenoma or bilateral hyperplasia)
- elevated plasma aldosterone concentration
- suppressed plasma renin activity

Question 15

what does an elevated PRA and PAC indicate? (PAC/PRA ratio <20)

PRA= plasma renin activ

Answer 15

• secondary hyperaldosteronism
• essential hypertension

Question 16

what screening tests are performed when there is clinical suspicion of hyperaldosteronism?

Answer 16

• plasma renin activity (PRA)
• plasma aldosterone concentration (PAC)
• PAC/PRA > 20 with concomitant serum aldosterone > 10ng/dl

Question 17

which confirmatory test is performed when there is clinical suspicion of hyperaldosteronism after positive screening tests?

Answer 17

24-hr urine aldosterone > 12 ug/day and urinary sodium > 200 mEq/day during 4 days of salt loading

Question 18

give an example of a hypersecretion disorder affecting the adrenal medulla?

Answer 18

• phaeochromocytoma (excess catecholamines e.g. epinephrine)

Question 19

clinical features of phaeochromocytoma

Answer 19

• hypertension (persistent in 70%)
• paroxysmal attacks: headache, sweating, palpitations, tremor, pallor, anxiety/fear

Question 20

what causes congenital adrenal hyperplasia?

Answer 20

• > 90% cases due to 21-hydroxylase deficiency (cannot produce cortisol, aldosterone)

Question 21

features of congenital adrenal hyperplasia

Answer 21

Severe cases:
- neonatal salt-losing crisis
- ambiguous genitalia (girls)

Incomplete defects:
- pseudo-precocious puberty (boys)
- hirsutism (women)