6: Adrenal disease Flashcards
Adrenal microanatomy
Going from outside inwards:
- Glomerulosa: makes aldosterone
- Fasciculata: makes cortisol
- Reticularis: makes androgen precursors
- Medulla: makes adrenaline/noradrenaline
- All surrounded by a capsule
The adrenal glands have a three-pronged shape
Wasted adrenal glands likely to be caused by Addison’s disease or long-term steroid treatment
_Hyperplastic adrenal gland_s may result from Cushing’s disease or ectopic ACTH
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
Adrenal blood supply
The adrenal gland has an extensive arterial supply with 57 small arteries
However, they have only one central vein
The blood picks up the hormones as it goes through the gland, which is carried out of the gland via the central vein
To get a blood sample to test adrenal output, you need to put a cannula through the IVC and into the adrenal vein
Each adrenal gland drains via different routes:
LEFT: into the left renal vein,
RIGHT - directly into the IVC
Case 1: A 31-year-old presents with profound tiredness. They are acutely unwell for a few days and are vomiting.
Sodium: 125
Potassium: 6.5
Urea: 10
Glucose: 2.9
FT4 < 5nM (low) and TSH > 50mU/l (high)
What is going on?
This is suggestive of thyroid failure as hypothyroidism can cause profound tiredness
Primary hypothyroidism would produce a low FT4 and a high TSH
However, hypothyroidism does NOT explain the unusual electrolytes
Hyponatraemia and hyperkalaemia suggest that there is a deficiency of mineralocorticoid
Similarly, hypoglycaemia suggests that there is a deficiency of glucocorticoid
This combination is suggestive of Addison’s disease
The co-existence of Primary Hypothyroidism and Addison’s Disease is known as SCHMIDT’s SYNDROME.
What is Schmidt’s syndrome
The co-existence of Primary Hypothyroidism and Addison’s Disease
This is also known as polyglandular autoimmune syndrome type II (PAST II)
This patient has antibodies against their thyroid gland and their adrenal glands
Addison’s disease and primary hypothyroidism occur together more commonly than by chance
This is because they are of autoimmune nature
- Autoimmune addisons = most common cause UK
- Tubeculosis addisons = outside of UK
Schmidt syndrome: combination of autoimmune adrenal insufficiency (Addison’s disease) with autoimmune hypothyroidism and/or type 1 diabetes mellitus (T1DM) and is part of a larger syndrome known as autoimmune polyendocrine syndrome type II or polyglandular autoimmune syndrome type II (PAS II).
Addison’s disease investigation
SHORT SYNACTHEN TEST
Measure cortisol + ACTH at the start of the test
Administer 250 µg of synthetic ACTH by IM injection
Check cortisol at 30 and 60 mins: normal people should be able to produce > 550 nM of cortisol within 30 mins (if there is no increase in cortisol, the patient has adrenal failure)
This is the diagnostic test for autoimmune or tuberculous adrenal failure
SHORT SYNACTHEN TEST result in case 1
ACTH > 100 ng/dl
Cortisol < 10 nM (before and after the test, at 30 minutes and 60 minutes post synACTHen)
The low cortisol despite high ACTH is suggestive of Addison’s disease
The patient also has hypothyroidism and is from the UK – most likely autoimmune
Crisis in adrenal failure is much worse than what is seen in pituitary failure
(in adrenal failure, you do not have any aldosterone either). These patients die if not treated acutely.
In pituitary failure (i.e. ACTH not released), the patient has aldosterone (release controlled by RAAS) – bit more time.
Case 2: A 32-year-old presents with hypertension. He is noted to have an adrenal mass. There are three possible differentials:
high catecholamines -> what is the diagnosis?
- Phaeochromocytoma – adrenaline (tend to be large tumours – may be > 3 cm)
- Conn’s syndrome – aldosterone (tend to be smaller tumours – often < 1 cm)
- Cushing’s syndrome – cortisol
Non-functioning adrenal lumps – very common (in 10% of patients)
Note: functioning tumours are rare (first three differentials)
Note: difficult to operate on adrenals for tumour removal
Further investigation reveals that this patient has high urine catecholamines
Therefore, phaeochromocytoma is diagnosed
Phaechromocytoma
diagnosis other than high catecholamines
complications
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Phaeochromocytomas are adrenal medullary tumours that secrete adrenaline
- Not to be confused with Conn’s syndrome (adrenal tumour secreting aldosterone)
- Not to be confused with zona fasciculata tumours producing Cushing’s syndrome
They are surprisingly common – diagnosed on history and examination
- Also diagnosed on scanning
- Anyone with an acute stomach pain will likely receive an abdominal CT scan
We therefore pick these tumours up before the patient has symptoms
They can cause severe hypertension, arrhythmias and death (MEDICAL EMERGENCY)
These patients need URGENT alpha blockade (using phenoxybenzamine) with saline (stabilises)
- Phentolamine or doxazocin can also be used
- You do not operate on the patient until the alpha blockade is given
- This is because touching the phaeochromocytoma releases lots of adrenaline
Alpha blockade in phaeochromocytoma management
Fluids -> alpha blockade + beta blocker (high dose leading up to surgery)
Alpha blockade is the first treatment for a patient who has got a phaeochromocytoma
- This leads to a sudden drop in blood pressure, which can be dangerous
Patients are often given some fluids before the alpha blockade to prevent complications
Patients may experience a reflex tachycardia, which should be blocked using a beta-blocker
Whilst they are on these medications, the patients will be protected until surgery
During surgery, if the surgeon pokes the phaeochromocytoma it will release a surge of adrenaline
Patients need to be treated with high dose alpha-blockers and beta-blockers in the days leading up to surgery
Phaeochromocytoma genetic links
MEN2
- Parathyroid tumours
- Medullary thyroid cancer
- Phaeochromocytomas
- NOTE: MEN2b is associated with a Marfanoid appearance and neuromas of the GI tract
Von Hippel Lindau Syndrome (PRRR)
- Phaeochromocytomas
- Renal cell carcinoma
- Renal cysts
- Retinal/CNS haemangioblastomas
Neurofibromatosis Type 1
- 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
Case 3: A hypertensive 33-year-old presents. On taking their bloods:
Sodium: 147
Potassium: 2.8
Urea: 4.0
Glucose: 4.0 mM
Plasma aldosterone raised; plasma renin suppressed
Conn’s Syndrome (primary hyperaldosteronisms) = tumour of the zona glomerulosa
- The adrenal gland secretes high levels of aldosterone autonomously
- This will cause hypertension
- High levels of aldosterone will also suppress renin at the JGA
Case 4: A 34-year-old obese woman with type 2 diabetes presents with hypertension and bruising.
Sodium: 146
Potassium: 2.9
Urea: 4.0
Glucose: 14.0 mM
Plasma aldosterone: < 75 (low)
Plasma renin low
This is likely to be Cushing’s syndrome.
Cushing’s Disease Investigations: the one you take in the morning
9 am cortisol will always be high in any patient (this is normal) – diurnal rhythm
Midnight cortisol: zero if the patient is asleep (can be disturbed in shift workers etc.)
Midnight cortisol is easiest, but it involves hospital admission and venepuncture during sleep
12 midnight cortisol: if their midnight cortisol level is LOW then it is definitely NOT Cushing’s
NOTE: this test is error prone and it is not very specific (any illness can give you a high midnight cortisol)
Pituitary sampling
85% of the time, the cause of endogenous Cushing’s syndrome is Cushing’s disease
A high-dose dexamethasone suppression test has a false positive rate of around 20%
Therefore, guessing and going straight for IPSS is better
IPSS: sampling blood for ACTH in the pituitary veins (invasive) – CRH used to stimulate corticotrophs
NOTE: if you do this test in a normal obese person, you’ll diagnose Cushing’s (where ACTH comes from)
