Adrenal Disease Flashcards
1
Q
Which hormones does the adrenal gland produce?
A
-
CORTEX (out to in):
- Zona glomerulosa → mineralocorticoids (eg. aldosterone)
- Zona fasciculata → glucocorticoids (eg. cortisol)
- Zona reticularis → androgens
-
MEDULLA (catecholamines):
- Noradrenaline
- Adrenaline
- Dopamine
2
Q
Cushing’s syndrome is caused by prolonged exposure to an excess of glucocorticoids.
For causes of Cushing’s sydrome, what is meant by exogenous versus endogenous, and which is more common?
A
- Exogenous → derived externally, occurs due to administration of glucocorticoids either as medication or misuse - this is by far most common cause
- Endogenous → derived internally, occurs due to excess production of glucocorticoids by body itself - very rare
3
Q
What is Cushing’s disease?
A
- Endogenous type of Cushing’s syndrome
- Refers to cases caused by pituitary adenoma
- Responsible for majority of endogenous cases
4
Q
Cushing’s syndrome is defined based upon its aetiology - whether the cortisol excess is ACTH dependent or independent.
What is meant by ACTH-dependent?
A
- This is when cortisol excess is driven by ACTH, either from pituitary or ectopic sources
- Cushing’s disease (80%) → bilateral adrenal hyperplasia from ACTH-secreting pituitary adenoma; peak age 30-55yrs
- Ectopic ACTH production (5-10%) → small cell lung cancer; carcinoid tumours
- Ectopic CRH production → rarely produced by malignant tissue
5
Q
What is meant by ACTH-independent?
A
- Cortisol excess is independent of ACTH
- Includes exogenous causes (consumption of cortisol)
- Also adrenal lesions (adenomas, carcinomas)
- McCune-Albright syndrome (rarer cause)
6
Q
What role does the HPA axis have in controlling cortisol secretion?
A
- Corticotropin-releasing hormone (CRH) → released by hypothalamus, transported via hypophyseal portal system to anterior pituitary, stimulating ACTH release
- Adrenocorticotropic hormone (ACTH) → released from corticotrophs of anterior pituitary, stimulates release of cortisol; XS is a feature of both Addison’s and ACTH-dependent Cushing’s syndrome
- Cortisol → released from adrenal cortisol in response to ACTH; exerts negative feedback on release of both ACTH and CRH; exhibits diurnal variation - highest around 8am
7
Q
Pseudo-Cushing’s mimics cushing’s. What are causes for this?
A
- Alcohol excess or severe depression
- Causes false positive dexamethasone suppression test or 24hr urinary free cortisol
- Insulin stress test may be used to differentiate
8
Q
The clinical features asssociated with Cushing’s syndrome are related to the effects of excess cortisol.
What are the symptoms (not signs) of Cushing’s syndrome?
A
- Tiredness
- Depression
- Weight gain
- Easy bruising
- Amenorrhoea
- Reduced libido
- Striae
9
Q
What are the clinical signs of Cushing’s syndrome?
A
- Acne
- Moon facies
- Plethora (facial redness)
- Buffalo hump
- Hypertension
- Proximal muscle weakness
- Hyperpigmentation (in ACTH-dependent causes)
10
Q
The work-up for Cushing’s syndrome follows two stages, establishing a diagnosis and establishing a cause.
For exogenous disease, there should be a clear history of prolonged glucocorticoid use.
Which tests are performed for endogenous cases?
A
- 24hr urinary cortisol → initial test; 3+ collections needed; levels 3-4x normal are highly suggestive of cushing’s syndrome; measure creatinine levels too as variation in levels between samples (>10%) indicates repeat for test
- Midnight cortisol → demonstrates loss of normal circadial pattern; can be salivary or blood based; if blood, take samples from indwelling cannula
- Low-dose dexamethasone suppression → demonstrates loss of normal negative feedback on pituitary and hypothalamus; 1mg of dex given at 11pm and serum cortisol measured at 8am; normally, dex should suppress morning rise in serum cortisol but in pts w/ cushing’s there’s a lack of suppression
- Dexamethasone-CRH test → less common; can help distinguish between Cushing’s and HPA axis dysregulation in severe depression
11
Q
After diagnosing cortisol excess we must identify the underlying aetiology.
What tests can be done to identify causes?
A
- Plasma ACTH done first, points to whether ACTH independent or dependent
- ?ACTH independent → CT or MRI
- ?ACTH dependent → High dose dex test:
- pituitary adenoma (ACTH suppressed)
- ectopic (ACTH continued production)
12
Q
What is the management of exogenous Cushing’s syndrome?
A
- Withdrawal of glucocorticoid
- Should not abruptly stop (risk of Addisonian crisis)
- Instead, gradual tapering regimen
- Close safety netting + monitoring
13
Q
What is the gold standard management of Cushing’s disease?
A
Transsphenoidal surgery :
- Microadenomectomy → identifiable adenoma found + resected
- Subtotal resection of anterior pituitary → used where no identifiable adenoma + no desire for fertility after counselling - risk of hypopituitarism
14
Q
What is the medical therapy for Cushing’s disease?
A
- Most commonly used as bridge to definitive surgical rx
- Or when surgery not possible / fails
- Metyrapone used (inhibitor of 11B-hydroxylase) → reduction in corticol synthesis
- Children + young people → pituitary irradiation
15
Q
When is adrenalectomy performed, for Cushing’s?
A
- For those where all other therapies have failed
- Bilateral adrenalectomy
- Mandates lifelong glucocorticoid + mineralocorticoid replacement
16
Q
How is unilateral adrenal adenoma treated?
A
- Unilateral adrenalectomy (curative)
- Laparoscopic > open surgery
- Follow-up tapering of exogenous steroids for period of time as endogenous CRH/ACTH suppressed
17
Q
How is bilateral adrenal hyperplasia treated?
A
- Bilateral adrenalectomy
- In pts w/ overt Cushing’s
- Require replacement of glucocorticoids and mineralocorticoids
18
Q
How is adrenal carcinoma treated?
A
- Appropriate staging
- Resection is mainstay of treatment
- Adjuvant chemo, radio or mitotane may be given
19
Q
What is Addison’s disease?
A
- Primary adrenal insufficiency
- Caused by destruction or dysfunction of adrenal cortex
- Hence low glucocorticoids and mineralocorticoids (mainly)
- In women, loss of androgens → axilla/pubic hair loss and loss of libido
- Men have testes to make androgens so few problems there
- Lots of symptoms mediated by lack of normal glucocorticoids and mineralocorticoids
- Profound and acute losses → addisonian crisis
20
Q
What is the function of aldosterone?
A
- Reduced in Addison’s
- A mineralocorticoid released from zona glomerulosa
- Released in response to Ang II, ACTH and K+
- Primary action = increase sodium and water reabsorption, potassium excretion
21
Q
What are common causes of Addison’s?
A
- Western world → Autoimmune
- Worldwide → Tuberculosis
22
Q
Addison’s disease is often diagnosed late due to its non-specific presentation.
What are clinical features of chronic Addison’s?
A
- Chronic, insidious onset
- Fatigue / Anorexia / Abdo pain
- Androgen deficiency in women
- Muscle wasting
- Postural hypotension
- Hyperpigmentation
23
Q
Addisonian crisis is a potentially life-threatening presentation of Addison’s disease. It is most commonly seen in tertiary adrenal insufficiency (termed an ‘adrenal crisis’) as a result of the sudden withdrawal of exogenous steroids. Occurs following an acute decompensation where an additional stress (e.g. infection) results in an exacerbation of a pre-existing deficiency. Bilateral adrenal gland haemorrhage can also result in a crisis.
What are clinical features of an addisonian crisis?
A
- Dehydration
- Hypotension
- Confusion
- Hyponatraemia / Hyperkalaemia / Hypoglycaemia
24
Q
The diagnosis of Addison’s may utilise both blood tests and stimulation tests.
What do blood tests show?
A
- U+Es → hyponatraemia and hyperkalaemia
- BM → hypoglycaemia
- FBC → anaemia and eosinophilia
- 21-hydroxylase adrenal autoantibodies → positive in autoimmune disease
25
What is the **Synacthen** test?
* IV administration of 250 mcg of tetracosactide (synthetic ACTH)
* Cortisol measured 3 times: **0** (immediately before), **30 mins** + **60 mins** following administration
* Serum cortisol **\> 500-550 nanomol/L** either before or following the ACTH is considered _normal_
26
What is the **management** of Addison's disease?
* Glucocorticoid replacement → **hydrocortisone** **15-30mg/day**
* Mineralocorticoid replacement → **fludrocortisone** **50-300 mcg/day**
* **Patient** **education** + sick day rules (double dose)
* Carry steroid card and MediAlert identification
27
How is an **Addisonian** **crisis** managed?
* _Medical emergency_ → prompt recognition + treatment
* **IV hydrocortisone 100mg**
* **IV fluid rehydration**
* Cardiac, electrolyte + blood sugar monitoring
* Following initial resus → hydrocortisone/dextrose infusion, target of 400mg of hydrocortisone / 24 hours
* Specialist input should be sought
28
What is **primary** **hyperaldosteronism**?
* Excess production of aldosterone, independent of RAS
* **Hypernatraemia** + **water** **retention**
* Reduced renin release
* **Hypokalaemia**
29
What are **clinical** **features** of primary hyperaldosteronism?
* Often asymptomatic
* **Hypokalaemia signs** → weakness / cramps / paraesthesia / polyuria / polydipsia
* Hypertension _sometimes_
30
What are **causes** of primary hyperaldosteronism?
* **Conn's syndrome** → solitary aldosterone-producing adenoma
* **Bilateral adrenocortical hyperplasia**
Rarer causes → adrenal carcinoma / glucocorticoid-remediable aldosteronism (GRA)
31
What **investigations** are done for **hyperaldosteronism**?
* 1st-line → **aldosterone:renin ratio** - in suspected primary hyperaldosteronism, shows high aldosterone levels alongside low renin levels
* CT Abdo + adrenal vein sampling → used to differentiate between unilateral and bilateral sources of aldosterone XS
32
What is the **management** for **Conn's** **syndrome**?
* **Laparoscopic** **adrenalectomy**
* **Spironolactone** for 4wks pre-op controls BP + potassium
33
What is the mangement for **bilateral** **adrenocortical** **hyperplasia**?
* Medically treated w/ **spironolactone** or **amiloride**
34
What is **secondary** **hyperaldosteronism**?
* Due to high renin from **decreased renal perfusion**
* Causes:
* **renal artery stenosis**
* **accelerated hypertension**
* **diuretics**
* **CCF**
* **hepatic fialure**
35
What is **Bartter's** **syndrome**?
* Inherited cause (autosomal recessive)
* _**Severe** **hypokalaemia**_
* Defective chloride absorption at NKCC2 in ascending loop of Henle
* Associated w/ normal BP
## Footnote
*Loop diuretics work by inhibiting NKCC2 - think of Bartter's syndrome as like taking large doses of furosemide*
36
What are **clinical** **features** of **Bartter's** **syndrome**?
* Usually presents in childhood (failure to thrive)
* Polyuria. polydipsia
* Hypokalaemia
* Normal BP
* Weakness
37
What is the **management** of Bartter's syndrome?
* **Potassium replacement**
* NSAIDs to inhibit prostaglandins
* ACEi
38
What is **phaeochromocytoma**?
* **Rare catecholamine secreting tumour**
* Arise from sympathetic paraganglia cells
* Found in adrenal **medulla**
* Extra-adrenal tumours rarer + often found by aortic bifurcation
* 90% are **sporadic** and 10% part of **hereditary** cancer syndromes (Thyroid, MEN II, neurofibromatosis, Von-Hippel-Lindau)
39
What are the **clinical** **features** (typically episodic) of **phaeochromocytoma**?
* **CVS** → tachycardia / palps / dyspnoea / angina / MI / LVF / cardiomyopathy
* **Psych** → anxiety / hyperactivity / confusion / episodic psychosis
* **Neuro** → headache / visual disorder / dizziness / tremor / numbness
* **Gut** → D+V / abdo pain
* **Other** → sweats / heat intolerance / backache
40
What **investigations** are done for phaeochromocytoma?
* **24hr urinary collection of metanephrines**
* Localisation by abdominal CT / MRI or meta-iodobenzylguanidine scan
41
What is the **management** for phaeochromocytoma?
* Pre-op → **alpha-blockade** (eg. phenoxybenzamine) before beta-blocker to avoid crisis from unopposed alpha adrenergic stimulation
* Post-op → 24hr urine metanephrine 2ks post-op + monitor BP
