8. Adrenal disease

Question 1

The zona fasciculata makes cortisol true or false?

Answer 1

True

Question 2

What is the order of the zones

Answer 2

glomerulosa (outermost), fasciculata, reticularis, medulla, capsule (innermost)

Question 3

Case 1: 31 year old presents with profound tiredness. Acutely unwell a few days. Vomiting. Na: 125, K: 6.5, U: 10, glucose 2.9mM. FT4 <5nM. TSH >50mU/l. What diagnosis does this TSH suggest?

A. A TSH producing pituitary adenoma 
B. Graves disease
C. A toxic thyroid nodule
D. Primary hypothyroidism
E. de Quervain's (viral) thyroiditis

Answer 3

D. Primary hypothyroidism - gives the highest TSH AND low T3/T4 levels (FT4 < 5nM).

Suggests thyroid failure but the hypothyroid does not explain the unusual electrolytes

Question 4

What is Schmidt’s syndrome

Answer 4

This is also known as polyglandular autoimmune syndrome type II. This patient has antibodies against their thyroid gland and their adrenal glands, thus the
co-existence of addison’s disease and primary hypothyroidism.

Question 5

What test to confirm addison’s

Answer 5

Right answer: Short synacthen test

Low dose dex - cushing’s
High dose dex - not used anymore
Glucose tolerance test - DM (2 samples), acromegaly (5 samples)
TRH simulation test

Question 6

Short synacthen test how to do it

Answer 6

1. measure cortisol + acth at start of test
2. administer 250 micrograms synthetic ACTH by IM injection
3. check cortisol at 30 and 60 minutes, normal people should be able to produce > 550nM of cortisol within 30 mins.

Question 7

Case 2: 32 year old presents with hypertension, noted to have adrenal mass, three possible differentials. What are the differential diagnoses? What does each secrete?

Answer 7

Phaeochromocytoma, (adrenal mudullary tumour secreting adrenaline), Conn’s sydrome (adrenal tumour secreting aldosterone), Cushing’s syndrome (secretes cortisol)

(NOTE: non-functioning adrenal lumps are COMMON)

Question 8

Will TB give hyponatraemic and hypoglycaemic and hyperkalaemic?

Answer 8

Yes

Question 9

Mass in adrenal medulla

Answer 9

Phaeochromocytoma

Question 10

Case 3: Hypertensive, 33 year old, Na 147, K 2.8, U 4.0, Glucose 4.0mM. Plasma aldosterone raise, plasma renin suppressed. What is the diagnosis and why?

Answer 10

Conn’s syndrome (primary hyperaldosteronism). Adrenal gland secretes high levels of aldosterone autonomously, which will cause hypertension. High levels of aldosterone will also suppress renin at the JGA.

Question 11

Case 4: 34 y/o obese woman with T2DM, presents with HTN and bruising. Na: 146, K: 2.9, U: 4.0, glucose 14.0. Aldosterone < 75 (low) and renin low. What is the likely diagnosis?

Answer 11

Cushing’s syndrome.

Question 12

What treatment for phaeochromocytoma?

Answer 12

1. URGENT alpha blockade (using phenoxybenzamine - phentolamine or doxazocin can also be used).
2. This leads to a sudden drop in blood pressure which can be dangerous, so patients are often given some fluids before the alpha blockade
3. As they are given alpha blocker, patients may experience reflex tachycardia which should be blocked using a beta-blocker
4. Whilst they are on these medications, the patients will be protected until surgery
5. During surgery, when the surgeon pokes the phaeochromoctoma it will release a massive amount of adrenaline therefore, patients need to be treated with high dose alpha-blockers and beta-blockers in the days leading up to surgery.

Question 13

Why alpha blockade and then beta blockade in phaeochromocytoma?

Answer 13

Beta blockers are used to prevent significant (reflex) tachycardia which occurs after alpha blockade. Beta blockers are not administered until adequate alpha blockade has been established, however, because unopposed alpha-adrenergic receptor stimulation can precipitate a hypertensive crisis.

Must use alpha first because suppression of beta-1 mediated cardiac sympathetic drive before adequate arteriolar dilatation can lead to acute cardiac insufficiency and pulmonary edema.

Question 14

What are the tests for cushings?

Answer 14

1. Overnight dexamethasone suppression test
2. At least two 24 hour urinary free cortisol
3. At paired midnight and waking salivary cortisol.

(9 am cortisol then 12 midnight cortisol. If their midnight cortisol level is LOW then it is definitely NOT Cushing’s. NOTE: this test is error prone and not very specific (any illness can give you a high midnight cortisol) )

Random cortisol measurements not very reliable.

Question 15

causes of cushings syndrome

Answer 15

Being on oral steroids for something else is a very common cause. Endogenous causes: pituitary-dependent Cushing’s disease (85%), ectopic ACTH (5%), adrenal adenoma (10%)

Question 16

Cushing’s disease vs cushings syndrome

Answer 16

cushing;s disease - definitely pituitary related

Question 17

Explain why Cushing’s symptoms may present in an obese patient but normal results?

Answer 17

: obesity can change your metabolism of Cortisol and produce a clinical picture that looks like Cushing’s (this is called Pseudo-Cushing’s syndrome)

Question 18

Why IPSS/pituitary sampling and not MRI for pituitary?***

Answer 18

More efficient??? Results of IPSS confirm or exclude the diagnosis of Cushing’s disease with 80%–100% sensitivity and over 95% specificity.***

Question 19

What shape do adrenals have?

Answer 19

three-pronged shape

Question 20

What are some of the causes of wasted adrenal glands?

Answer 20

Addison’s disease or long-term steroid treatment

Question 21

What are some causes of hyperplastic adrenal glands?

Answer 21

Cushing’s disease or ectopic ACTH

Question 22

What do the adrenal glands make more of - aldosterone or cortisol? By how much?

Answer 22

If you look at the concentrations of the adrenal hormones, aldosterone is measured in picomoles and cortisol is measured in nanomoles i.e. you make 1000 times more cortisol than aldosterone

Question 23

Describe the blood supply to the adrenal glands.

Answer 23

The adrenal gland has an extensive arterial supply. 57 small arteries but only 1 vein. To get a blood sample to test adrenal output, you will need to put a cannula through the IVC and into the adrenal vein. Each adrenal gland drains via a different route: LEFT - into the left renal vein; RIGHT - directly into the IVC.

Question 24

Case 1: 31 year old presents with profound tiredness. Acutely unwell a few days. Vomiting. Na: 125, K: 6.5, U: 10, glucose 2.9mM. FT4 <5nM. TSH >50mU/l. Likely diagnosis is primary hypothyroidism.

Suggests thyroid failure but the hypothyroid does not explain the unusual electrolytes. What could be going on?

Answer 24

Hyponatraemia + hyperkalaemia -> deficiency of mineralocorticoid.
Hypoglycaemia -> deficiency of glucocorticoid.
This combination is suggestive of Addison’s disease. Co-existence of Primary Hypothyroidism and Addison’s Disease is known as SHMIDT’s SYNDROME.

Question 25

Case 1 results after Addison’s disease investigations:

ACTH > 100 ng/gl
Cortisol < 10 nM
Check cortisol at 30 and 60 minutes
Both times, cortisol < 10nM

Which findings are suggestive of Addison’s?

Answer 25

Short synacthen test results show low cortisol despite high ACTH, suggestive of Addison’s disease.

Question 26

Case 2: 32 year old presents with hypertension, noted to have adrenal mass, three possible differentials. Further investigation reveals that this patient has high urine catecholamines. What is the diagnosis?

Answer 26

Phaeochromocytoma

Question 27

What is phaeochromocytoma and what can it cause?

Answer 27

• Adrenal medullary tumour that secretes adrenaline, and can cause severe hypertension, arrhythmias and death. MEDICAL EMERGENCY.

Question 28

Phaeochromocytomas have some very specific genetic links, what are they?

Answer 28

MEN2, Von Hippel Lindau syndrome, neurofibromatosis type I

Question 29

Phaeochromocytomas are associated with MEN2, how may pts present?

Answer 29

Parathyroid tumours, medullary thyroid cancer, phaeochromocytomas. (NOTE: MEN2b is associated with a Marfanoid appearance and neuromas of the GI tract)

Question 30

Phaeochromocytomas are associated with Von Hippel Lindau syndrome, how may pts present?

Answer 30

Phaeochromocytomas, renal cell carcinoma, renal cysts, retinal/CNS haemangioblastomas

Question 31

Phaeochromocytomas are associated with neurofibromatosis type I, how may pts present?

Answer 31

Peripheral and spinal neurofibromas, multiple café au lait spots, freckling (axillary/inguinal), optic nerve glioma, Lisch nodules (on iris), skeletal deformities, phaeochromocytomas, renal artery stenosis

Question 32

How does the dexamethasone suppression test work to indicate Cushings syndrome?

Answer 32

Dexamethasone is a potent steroid so your pituitary should be able to detect its presence and reduce its secretion of ACTH resulting in a drop in cortisol. In Cushing’s syndrome, you will keep making cortisol irrespective of dexamethasone.

Question 33

In a dexamethasone suppression test, a low-dose test is done by measuring the cortisol and ACTH at the start, then giving 0.5 mg dexamethasone every 6 hours for 48 hours. What is a NORMAL Result?

Answer 33

1. 9am cortisol (Monday): 650 nM.
2. Given 0.5 mg dexamethasone every 6 hours for 48 hours.
3. 9am cortisol (Wednesday) < 50nM

Question 34

If the patient fails to suppress their cortisol after a low-dose dexamethasone suppression test, what’s the next thing you do? Why?

Answer 34

Sampling the pituitary (inferior petrosal sinus sampling). This is because 85% of the time, the cause of endogenous Cushing’s syndrome IS Cushing’s disease. On the other hand, a high-dose dexamethasone suppression test has a false positive rate of around 20%. Therefore, guessing and going straight for IPSS is better.

Question 35

What is the basis of high-dose dexamethasone test?

Answer 35

When you give a patient a massive dose of dexamethasone, even a pituitary tumour will respond and slightly reduce secretion of ACTH. However, even 20% of patients with ectopic ACTH causing Cushing’s syndrome will show some decrease in cortisol production.