The Adrenal Gland

Question 1

What is the structure of the adrenal cortex in terms of what it produces?

Answer 1

Outer:mineralocorticoids (aldosterone) which control Na+ and K+ balance
Middle:glucocorticoids (cortisol) which affect carbs, lipid and protein metabolism
Inner: androgens, have a weak effect until conversion to testosterone and dihydrotestosterones

Salt, Sugar, Sex

Question 2

How is the adrenal cortex stimulated to realise cortisol and androgens?

Answer 2

Corticotropin-releasing hormone (CrH) is released from hypothalamus. This stimulates release of Adrenocorticotrophic hormone (ACTH) from the pituitary, which stimulates the adrenal cortex

Question 3

What is Cushing’s syndrome?

Answer 3

Clinical state produced by chronic glucocorticoid excess and loss of the normal feedback mechanisms of the HPA axis as well as loss of the circadian rhythm of cortisol secretion

Question 4

What are some causes of Cushing’s?

Answer 4

1. ACTH dependent (raised)
   - Cushing’s disease-ACTH secreting pituitary adenoma resulting in bilateral adrenal hyperplasia
   - Ectopic ACTH production: small cell lung cancers and carcinoid tumours
2. ACTH independent (reduced levels due to -ve feedback)
   - Iatrogenic: oral steroids (common)
   - Adrenal adenoma/cancer
   - Adrenal modular hyperplasia

Question 5

What is a Dexamethasone suppression test?

Answer 5

Dexamethasone is a potent synthetic steroid that, when given orally would normally suppress (by feedback inhibition) the secretion of ACTH and thus cortisol. Dexamethasone suppression of plasma cortisol by >50% is characteristic of Cushing’s disease because for the diseased pituitary, even though it is relatively insensitive to cortisol, it does retain some sensitivity to potent synthetic steroids. Suppression does not normally occur in adrenal tumours or ectopic ACTH production.

Question 6

What would be the result of a dexamethasone suppression test with an adrenal tumour?

Answer 6

No cortisol suppression because the adrenal gland is unaffected by dexamethasone

Question 7

What would be the result of a dexamethasone suppression test with a pituitary adenoma (Cushing’s disease)?

Answer 7

A low dose test may lead to no changes in cortisol but a higher dose should reduce cortisol levels

Question 8

What would be the result of a dexamethasone suppression test with ACTH/CRH secreting ectopic tumour?

Answer 8

No cortisol suppression even at higher doses

Question 9

What would be the result of a dexamethasone suppression test with adrenal modular hyperplasia?

Answer 9

No cortisol suppression

Question 10

What are the symptoms of Cushing’s syndrome?

Answer 10

Weight gain
Mood change (depression, lethargy, irritability)
Proximal weakness
Gonadal dysfunction (irregular menses, ED)
Acne
Recurrent Achilles’ tendon rupture

Question 11

What are the signs of Cushing’s syndrome?

Answer 11

Central obesity 
Plethora, moon face
Buffalo hump
Skin and muscle atrophy
Bruises
Purple abdominal striae 
HTN
hyperglycaemia
Infection prone
Poor healing

Question 12

What is the treatment for steroid caused Cushing’s?

Answer 12

Stop medications

Question 13

What is the treatment for Cushing’s caused by Cushing’s disease?

Answer 13

Selective removal of pituitary adenoma (trans-sphenoidally) and potentially also bilateral adrenalocetomy if source unlocatable

Question 14

What is the treatment of Cushing’s syndrome caused by an adrenal adenoma

Answer 14

Adrenalectomy (but doesnt resolve cancer- may need radiotherapy and adrenolytic drugs)

Question 15

What is the treatment for Cushing’s syndrome due to an ectopic ACTH source?

Answer 15

Surgery if tumour can be located and hasn’t spread

Lower cortisol pre-op with metyrapone/ketoconazole/fluconazole

Question 16

What is the prognosis of untreated Cushing’s?

Answer 16

Increased vascular mortality

Treatment reduces mortality but symptoms largely remain so follow up carefully

Question 17

How do you investigate suspected Cushing’s syndrome?

Answer 17

1. Overnight dexamethasone suppression test (1mg at midnight and a 8am cortisol level)/ 24hr urinary free cortisol is an alternative.
2. (If 1. Was abnormal) 48 hr dexamethasone suppression test (measure cortisol at hours 0 and 48)

Question 18

How do you localise the cause of Cushing’s syndrome once it is confirmed?

Answer 18

1. ACTH levels

2. Imaging: CT/MRI (Adrenal glands), MRI (pituitary), IV contrast CT chest,abdo,pelvis +_ MRI (ectopic causes)

Question 19

What is another word for primary adrenocortical insufficiency?

Answer 19

Addison’s disease

Question 20

What are the causes of Addison’s disease? (6)

Answer 20

80% autoimmune (in the UK)
TB (Commonest world wide)
Adrenal metastases (lung, breast and renal primaries)
Lymphoma 
Opportunistic infections in HIV
Adrenal haemorrhage

Question 21

What is secondary adrenal insufficiency?

Answer 21

Suppression of cortisol secretion most commonly due to chronic steroid use which suppresses the HPA axis.

Will become apparent upon withdrawal of steroids

Question 22

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

Answer 22

Lean
Tanned (w/ pigmented palmar creases, and buccal mucosa)
Tired
Tearful +_ weakness,
Dizzy/faints,  postural hypotension 
Flu like aches and pains 
Low mood
NV

Question 23

What test would you do to confirm/explore Addison’s disease and what results would you be expecting?

Answer 23

Na low, K+ high (due to reduced mineralocorticoids)
Glucose low (due to low cortisol)

Short ACTH stimulation test (plasma cortisol level, give tetracosactide, measure cortisol 1/2h after)

Plasma renin and aldosterone (to assess mineralocorticoid levels)

CXR/AXR: for cause ie TB

Question 24

In what situations would you expect cortisol to be falsely high?

Answer 24

Pregnancy
Oral contraceptive pill

Due to increased cortisol binding globulin

Question 25

What is the treatment for Addison’s disease?

Answer 25

Replace steroids (hydrocortisone daily)
Mineralocorticoids to correct postural hypotension, low Na+ and high K+ (fludrocortisone daily)

Question 26

If a pt has a poor response to Addison’s treatment what would you need to think about?

Answer 26

Associated autoimmune disease: check thyroid, do coeliac serology

Question 27

What are the recommendations for those using steroids long term?

Answer 27

Wear a bracelet
Use them prior to strenuous activity
Double dose in febrile illness, injury or stress (Adrenal insufficiency can cause fatal hypovolaemic shock)
Inject self with hydrocortisone if vomiting prevents oral intake

Question 28

What is the prognosis for pt with Addison’s disease?

Answer 28

Good, but death from infections and adrenal crises do occur

Question 29

What are the signs and symptoms of an addisonian crisis?

Answer 29

Shock: high HR, vasoconstriction, postural hypotension, oliguria, weak, confused, comatose

Question 30

Who is at most risk of going into an addisonian crisis?

Answer 30

Someone with known Addison’s (who’s steroids haven’t been increased to deal with new stress ie pneumonia)
Someone on long term steroids who has forgotten to take tablets

*bilateral Adrenal haemorrhage is another cause (ie meningococcaemia)

Question 31

What are the precipitating factors for an addisonian crisis?

Answer 31

Increased stress on the bod: Infection, Trauma, Surgery

Missed medication

Question 32

What is the management of a pt in an addisonian crisis?

Answer 32

Bloods:

• cortisol and ACTH (straight to lab!!),
• U+E: high K+ (give calcium gluconate), low Na+ (should resolve with rehydration and steroids)
• BM- watch out for hypoglycaemia (give glucose IV)
• blood, urine, sputum for culture, then Abx if infection is suspected

Give:

• hydrocortisone IV stat 100mg (then continue 100mg/8hrs IM/IV)
• IV fluid

*if there is clinical suspicion for this then treat without lab results