the adrenal glands

Question 1

what are the layers of the adrenal glands and what does each layer produce?

Answer 1

CORTEX
Zona Glomerulosa = mineralcorticoids e.g aldosterone

Zona fasciculata = glucocorticoids e.g cortisol

zona reticularis = androgens e.g DHEA

MEDULLA

adrenal medulla = stress hormones to stimulate autonomic nervous system e.g adrenaline and noradrenaline.

Question 2

when are cortisol levels at their highest and lowest?

Answer 2

highest at 0800 and lowest at midnight.

Question 3

what is the feedback loop for cortisol secretion?

Answer 3

negative feedback

• hypothalamus reales CRH (corticotropin releasing hormone)
• anterior pituitary releases ACTH as a result (adrenocorticotropic hormone)
• this causes the adrenals to release cortisol (which in turn reduces CRH release from hypothalamus)

Question 4

where is most cortisol bound?

Answer 4

most is bound to cortisol binding globulin (CBG, 80-90%) and albumin (5-10%)

only a small portion is in the biologically active state

current immunoassays measure total bound and free cortisol

NB: conditions which stimulate CBG levels e.g oestrogen therapy may increase measured cortisol levels without affecting biologically active free levels

Question 5

what controls the secretion of adrenal androgens?

Answer 5

ACTH (adrenocorticotropic hormone)

Question 6

what is the importance of adrenal androgens?

Answer 6

important role in adult women and in both sexes pre pubertal, as adult men rely mainly on testes for androgens.

Question 7

where are androgens converted to their more potent forms?

Answer 7

DHEA and DHEA-S and androstenedione are converted to the more potent testosterone and dihydrotestosterone in peripheral tissues

have their effects of sebaceous glands, hair follicles, the prostate and external genitalia

Question 8

how is aldosterone section regulated?

Answer 8

• regulated by renin angiotensin system
• low bp/hyponatraemia/hyperkalaemia will trigger
• renin is activated to convert angiotensiongen to angiotensin 1
• ACE converts angiotensin 1 to angiotensin 2
• angiotensin 2 stimulates aldosterone release upon binding to angiotensin receptor

Question 9

where does aldosterone mainly act in the kidneys?

Answer 9

at the distal convoluted tubule on its receptor to cause sodium retention and potassium loss

Question 10

what are the clinical features of Addison’s disease (primary adrenal insufficiency)?

Answer 10

• fatigue
• weakness
• anorexia
• weight loss
• nausea
• abdominal pain
• dizziness and postural hypotension due to mineralocorticoid deficiency
• glucocorticoid loss leads to hypoglycaemia
• increased pigmentation due to ACTH excess from reduced cortisol negative feedback
• androgen deficiency in women = reduced libido and loss of axillary and pic hair

Question 11

what is primary adrenal insufficiency aka Addison’s disease and what is the most common cause?

Answer 11

this arises as result of the destruction of the adrenal gland, or genetic defects in steroids

all three zones are affected

common cause is autoimmunity, confirmed by positive adrenal autoantibodies.

other causes include infection or infiltrative processes. Unlikely, but consider if antibody test is negative.

Question 12

how do you treat an Addison’s crisis?

Answer 12

its a medical emergency

needs urgent treatment with IV fluids and hydrocortisone

Question 13

what investigations are done for Addison’s disease (primary adrenal insufficiency)?

Answer 13

hallmarks of primary adrenal failure are

• hyponatraemia
• hyperkalaemia
• raised urea
• hypoglycaemia
• mild anaemia

confirmatory test include low 9 am cortisol and simultaneously raised ACTH concentration, although synacthen test is usually needed for confirmation

Question 14

what is the syncathen test?

Answer 14

The purpose of the test is to diagnose adrenal insufficiency

stages

1) take baseline blood sample for cortisol
2) synthetic ACTH is injected into the patient
3) taker another blood for cortisol 30 mins later

if cortisol levels haven’t risen past a specific range then Addison’s disease is likely

Question 15

how is primary adrenal insufficiency aka Addison’s disease managed?

Answer 15

• lifelong glucocorticoid and mineralocorticoid replacement
• for glucocorticoids: hydrocortisone if first choice, can use low dose prednisone
• Mineralcorticoid : fludrocortisone
• patients should double glucocorticoid dose at times of illness and maintain until illness has resolved
• provide patient with steroid emergency card and medical alert jewellery, and given emergency contact details for their endocrine team

Question 16

what is secondary adrenal insufficiency (ACTH deficiency) and how is it treated?

Answer 16

due to ACTH deficiency

result from any cause of hypopituitarism

give hydrocortisone

no fludrocortisone replacement required as aldosterone is not dependant of ACTH but on the RAAS system

patients should carry a steroid card and be educated about steroid supplementation at times of illness

Question 17

why shouldn’t treatment be suddenly stopped in secondary adrenal deficiency?

Answer 17

Long-term steroids commonly cause ACTH suppression so sudden cessation may lead to adrenal crisis.

Important point: Patients taking long-term steroids should be instructed not to stop their steroids abruptly.

Question 18

what is pheochromocytoma and paraganglioma?

Answer 18

these are catecholamine secreting tumours that occur rarely in patients with hypertension

usually arise from the adrenal medulla

very few arise from extra adrenal chromaffin tissue and are called paragangliomas

Question 19

what are the clinical features of phaeochromocytomas and paragangliomas?

Answer 19

• headache
• sweating
• pallor
• palpitations
• anxiety/panic attacks
• hypertension

if left untreated, can lead to

• hypertensive crisis
• encephalopathy
• hyperglycaemia
• pulmonary oedema
• cardiac arrhythmia
• death

Question 20

what investigations can be done for phaeochromocytomas and paraganglioma’s?

Answer 20

• biochemical confirmation of elevated catecholamines or their metabolites (metanephrines)
• radiological visulisation of tumour
• 24 hr urinary catecholamines and plasma metanephrines
• CT or MRI of abdo is imaging test of choice, followed by whole body MRI if tumour isn’t localised
• MIBG scan may locate tumour not seen on MRI, and can be used to exclude multiple tumours/ metastases
• PET scan can help localise
• genetic testing in young presentation to allow for annual screening of recurrent disease

Question 21

how is a phaeochromocytoma or paraganglinoma managed?

Answer 21

• surgical excision is definitive, can be preformed laparoscopically
• at diagnosis, need alpha +/- beta blockade. Alpha with phenoxybenzamine or doxazosin and this should be done before beta blockade to avoid unopposed alpha adrenergic stimulation