Adrenal Flashcards
Adrenal
1
Q
What are the 4 regions of the adrenal glands?
A
IN –> OUT:
1 -Adrenal medulla
Adrenal cortex:
2 -zona reticularis
3 -zona fasciculata
4 -zona glomerulosa
1) stress (adrenaline/noradrenaline)
2) sex (androgens)
3) sugar (glucocorticoids)
4) salt (mineralocorticoids- aldosterone)
2
Q
What is produced by the adrenal medulla?
A
Catecholamines (adrenaline, noradrenaline)
3
Q
What is produced by the zona reticularis?
A
Androgens (DHEA, androstenedione)
4
Q
What is produced by the zona fasciculata?
A
Glucocorticoids (cortisol, corticosterone, cortisone)
5
Q
What is produced by the zona glomerulosa?
A
Mineralocorticoids (aldosterone)
6
Q
What effect do catecholamines have on the body?
A
Increased cardiac activity, blood pressure, glycogen breakdown, blood glucose levels
7
Q
What effect do glucocorticoids have on the body?
A
Release AA from skeletal tissue, lipids from adipocytes, promote liver gluconeogenesis
8
Q
What effect do mineralocorticoids have on the body?
A
Increased renal reabsorption of Na+ and H2O, renal K+ excretion
9
Q
What is the adrenal medulla stimulated by?
A
Sympathetic preganglionic fibres
10
Q
What is the zona reticularis stimulated by?
A
ACTH
11
Q
What is the zona fasciculata stimulated by?
A
ACTH
12
Q
What is the zona glomerulosa stimulated by?
A
Angiotensin II
high K+
low Na+
inhibited by ANP/BNP
13
Q
What is the hypothalamic-pituitary-adrenal axis?
A
Hypothalamus –> CRH
Anterior pituitary –>ACTH
Adrenal cortex–> cortisol (supplies -ve feedback to the hypothalamus and anterior pituitary)
14
Q
What is adrenal insufficiency?
A
an adrenal cortex disorder where there is a decreased production of adrenocortical hormones (cortisol, aldosterone, DHEA)
15
Q
What are the causes of primary adrenal insufficiency?
A
TB – most common worldwide
Autoimmune – most common in UK
16
Q
What are the causes of secondary adrenal insufficiency?
A
HYPOPITUITARISM
- Pituitary adenoma
- Sheehan’s syndrome
- Surgery/radiotherapy
- Pituitary apoplexy
17
Q
What are the causes of tertiary adrenal insufficiency?
A
- Brain tumour
- Sudden withdrawal of long term corticosteroids
18
Q
What is the main thing you would be looking for in a Pt with glucocorticoid deficiency?
A
Hypoglycaemia
19
Q
What is the main thing you would be looking for in a Pt with mineralocorticoid deficiency?
A
Hyponatraemia
Hyperkalaemia
20
Q
What are the symptoms of adrenal insufficiency?
A
Fatigue, weakness Anorexia Weight loss Nausea and vomiting Arthralgia and myalgia Abdominal pain Depression Salt cravings
21
Q
What are the signs of adrenal insufficiency?
A
- Mucocutaneous hyperpigmentation in buccal mucosa and sun exposed areas (due to raised ACTH stimulating melanocytes)
- Postural hypotension
- Loss of body hair (in females)
22
Q
What is the investigations you should do in a Pt with adrenal insufficiency? What would you see?
A
1) Bloods – U+Es, FBC
- ↓Na+
- ↑K+
Due to ↓ aldosterone production
2) 9am cortisol = ↓
3) Short SynACTHen test (diagnostic)
4) Adrenal antibodies
5) Adrenal CT/MRI
23
Q
What is the diagnostic investigation you should do in a Pt with adrenal insufficiency?
A
synACTHen test
250mcg tetracosactide
24
Q
At what synACTHen test cortisol levels can you rule out primary adrenal insufficiency?
A
Baseline cortisol >170nmol/L
30 min cortiosl >600nmol/L
25
What is the management for adrenal insufficiency?
Lifelong glucocorticoids and mineralocorticoids
eg. hydrocortisone + fludrocortisone
Raise dosage if stressed eg. trauma, surgery, infection
26
What are the complications of adrenal insufficiency?
- Addisonian crisis
- Secondary Cushing's syndrome
- Osteoporosis (long term XS glucocorticoids)
- Hypertension (long term XS glucocorticoids)
27
What is an Addisonian crisis?
Acute adrenal insufficiency with major haemodynamic collapse
28
What are the causes of an Addisonian crisis?
- Sepsis/surgery with a background of chronic insufficiency
- Steroid withdrawal
- Adrenal haemorrhage (Waterhouse-Friderichsen syndrome)
29
What is the presentation of an Addisonian crisis?
```
Hypotensive shock
Tachycardia
Abdo pain
Confusion
Lethargy
Coma
```
ELECTROLYTE ABNORMALITIES
- Hyperkalaemia
- Hypercalcaemia
- Hypoglycaemia
- Hyponatraemia
30
What is the management of a Pt with an Addisonian crisis?
- Hydrocortisone sodium succinate 50-100mg IV every 6-8 hrs
- 1L bolus IV saline followed by 2-4L over 24 hrs
- Glucose to correct hypoglycaemia, risk of worsening hyponatraemia
31
What is Cushing's syndrome?
Chronic inappropriate elevation of free circulating cortisol
32
What are the causes of Cushing's syndrome?
EXOGENOUS CUSHING'S SYNDROME
- chronic excess steroid use
ACTH-DEPENDANT
- excess ATCH from pituitary adenoma (Cushing's disease)- 85%
- excess ATCH from ectopic tumour (small cell lung cancer)- 5%
ACTH-INDEPENDANT
- excess cortisol from adrenal adenoma 10%
33
What are the symptoms of Cushing's syndrome?
```
Weight gain
Fatigue
Depression/psychosis
Insomnia
Amenorrhoea/oligomenorrhoea
Poor libido
Hirsutism/acne/balding
Thin skin
Easy bruising
Back pain
Muscle weakness
Polyuria/polydipsia
```
34
What are the signs of Cushing's syndrome?
```
Moon face
Facial plethora
Interscapular fat pad
Hirsutism/acne/balding
Thin skin
Bruising
Hypertension
Ankle oedema
Pigmentation
Proximal myopathy
Osteoporosis
Pathological fractures
Skin infections
```
35
What are the key symptoms of Cushing's syndrome?
```
Weight gain
Fatigue
Muscle weakness
Easy bruising
Menstrual irregularities
```
36
What are the key signs of Cushing's syndrome?
```
Bruising
Proximal myopathy
Purple/red striae
Facial plethora (facial rounding)
Diabetes (early-onset)
Hypertension (early-onset)
Osteoporosis (early-onset)
Pathological fractures (ribs & vertebrae)
```
37
What are the investigations for Cushing's syndrome?
1) 24hr urinary free cortisol (>50mcg)
2) Midnight salivary/plasma cortisol (exclude cushings)
3) Low dose dexamethasone suppression test
4) Plasma ACTH
38
How is the low dose dexamethasone suppression test performed? What is a positive result?
Patient is given 1 mg of dexamethasone at 11 p.m., and a plasma cortisol level is obtained the following morning at 8 a.m.
A positive test is defined as morning cortisol >50 nanomol/L (>1.8 micrograms/dL).
39
What is the management for Cushing's syndrome?
ACTH pituitary tumour:
- trans-sphenoidal pituitary adenectomy
Ectopic ACTH tumour:
- Surgical resection/ablation
Pre-surgery:
- somatostatin analogue
- steroidogenesis inhibitor
- glucocorticoid receptor antagonist
Post-surgery:
- pituitary hormone replacement therapy
40
What are the complications of Cushing's syndrome?
- Adrenal insufficiency post-treatment
- Cardiovascular disease (main cause of mortality)
- Hypertension
- Diabetes mellitus
- Osteoporosis
41
What is hyperaldosteronism?
Autonomous overproduction of aldosterone from the adrenal glands
42
What are the causes of hyperaldosteronism?
PRIMARY
1) adrenal adenoma (Conn's syndrome) 70%
2) adrenal cortex hyperplasia 30%
SECONDARY
1) glucocorticoid-supressible hyperaldosteronism (FHx)
2) aldosterone producing adrenal carcinoma
43
What are the risk factors for hyperaldosteronism?
FHx of aldosteronism
Early HTN
Stroke
44
What are the clinical features for hyperaldosteronism?
Hypertension in YOUNG PERSON
- Usually refractory to treatment
HYPOKALAEMIA
- Polyuria, polydipsia
- Muscle weakness
- Arrhythmia
45
What are the investigations for hyperaldosteronism?
1) PLASMA POTASSIUM
- low
2) ALDOSTERONE:RENIN RATIO (best initial)
- increased
2) FLUDROCORTISONE SUPPRESSION TEST (best diagnostic)
- 4 days of fludrocortisone, plasma aldosterone should be suppressed
- Saline infusion test
- Adrenal CT/MRI
- Adrenal venous sampling (to determine unilateral/bilateral Dx)
46
What is the management for hyperaldosteronism?
```
If bilateral hyperplasia:
ALDOSTERONE ANTAGONISTS
- spironolactone
- amiloride
- epleronone
```
If aldosterone producing adenoma: ADRENALECTOMY
- post-op aldosterone agonist
47
What is a phaeochromocytoma?
A tumour arising from catecholamine-producing chromaffin cells of the adrenal medulla
48
What are the 2 origins of phaeo?
- Adrenal medullary chromaffin cells (90%)
| - Extra-medullary tumour (10%)
49
What is the rule of 10's for a phaeo?
10% are extra-medullary
10% are bilateral
10% are malignant
50
What are the symptoms of a phaeo?
```
Paroxysmal episodes of:
Headache (90%)
Palpitations (60%)
Diaphoresis (65%)
Chest pain
Dyspnoea
Epigastric pain and nausea
Diarrhoea
Tremor
Anxiety
```
51
What are the signs of a phaeo?
- Hypertension (95%)
- Tachycardia
- Hypertensive retinopathy
- Pallor
- Impaired glucose tolerance
- Orthostatic hypotension
52
What are the investigations for a phaeo?
24 hour urine collection for catecholamines (+metanephrines, normetanephrines)
If clinical suspicion is high: Serum free metanephrines, normetanephrines
Genetic testing
CT/MRI adrenals
53
What is the management for a phaeo hypertensive crisis?
5-20mg phentolamine IV single dose
54
What is the management for a phaeo?
IV fluids if dehydrated
1) Alpha blockers (eg. phenoxybenzamine)
2) Beta blockers (eg. atenolol, propanolol)
- once alpha blockade is sufficient
- prevents reflex tachycardia (due to a2 blockade)
3) Surgical excision of tumour
55
What is the normal range of potassium and what hormones can affect potassium levels?
3.5-5.0 mmol/L
| Angiotensin II, aldosterone
56
What are the causes of hyperkalaemia?
Reduced excretion
- Renal - CKD
- Endocrine – Addison's, metabolic acidosis
- Drugs – ACEi/ARBs
Release from cells
- Rhabdomyolysis
- Acidosis
57
At what level do Pts with hyperkalaemia become symptomatic?
>6.0mmol/L
58
What are the symptoms/signs of a Pt with hyperkalaemia?
Muscle weakness
ECG changes
- Loss of p waves
- Tall tented T waves
- Widened QRS complex
59
What is the management for hyperkalaemia?
- 10ml 10% IV calcium gluconate (cardio-protective)
- 100ml 20% dextrose + 10 units of insulin (drives K+ into cells)
- Nebulised salbutamol
60
What are the causes of hypokalaemia due to excretion?
Increased potassium excretion:
RENAL
- renal tubular acidosis
- thiazide diuretics (+hyponatraemia)
- elevated mineralocorticoids (Conn's)
- elevated cortisol (Cushing's)
GI TRACT
- N+V
- villous adenoma
SKIN
- eczema
- burns
- psoriasis
61
what are the signs of hypokalaemia?
Muscle weakness
ECG changes
- ST depression
- reduced T wave amplitude
- increased U wave amplitude
Polyuria/polydipsia (nephrogenic DI due to hypokalaemia)
Rhabdomyolysis, renal abnormalities, cardiac arrhythmias
62
What is the management for hypokalaemia?
Reduce K+ loss
-stop diuretics/laxatives etc
Replenish K+ stores
-oral replacement, IV if ECG changes/severe symptoms
Monitor for complications eg. ECG
63
What is polycystic ovarian syndrome?
Syndrome characterised by:
- oligomenorrhoea/amenorrhoea
- hyperandrogenism
- polycystic ovarian morphology on ultrasound
64
Associations of PCOS?
```
abdominal adiposity
insulin resistance
obesity
metabolic disorders
cardiovascular risk factors
```
65
What are the symptoms of PCOS?
```
Irregular menstruation (75%)
Oligomenorrhea/amenorrhoea
Infertility
Hirsutism (60%)
Acne (20%)
Hair loss (scalp) (5%)
Oily skin
Excess sweating
```
66
What are the signs of PCOS?
Hirsutism
Overweight
Hypertension
Acanthosis nigricans
67
What is the criteria used to diagnose PCOS?
Rotterdam criteria (2/3 needed for diagnosis)
1) Amenorrhoea/Oligomenorrhoea
2) Clinical or biochemical hyperandrogenism
3) Polycystic ovaries on USS
68
What are the investigations for PCOS?
TRANSVAGINAL USS
- Tests to exclude other causes (prolactin, TFT etc)
Testosterone studies
- LH/FSH ratio >3
- Serum total/free testosterone (elevated)
- Serum DHEAS elevated
Oral glucose tolerance test- diabetes
Fasting lipid profile- dyslipidaemia
69
A 40 year old female presents to the GP with chronic fatigue, myalgia and depressive type symptoms. On examination you notice hyperpigmentation of the buccal membrane. Routine blood tests reveal a hyponatraemia and hyperkalaemia.
Which of the following investigations should be done?
A. Low dose dexamethasone suppression test
B. High dose dexamethasone suppression test
C. Short SynACTHen test
D. TRH stimulation test
E. Glucose tolerance test
C. Short SynACTHen test
70
A patient with Addison's disease is found unconscious on the bus. She is brought to the A+E where is she found to be hypotensive and slightly feverish. Routine blood tests are sent off which are normal except for the U+E’s.
Na+ = 130 mmol/L
K+ = 5.4 mmol/L
Urea = 9 mmol/L
Creatinine = 80 mcmol/L
What is the most appropriate immediate therapy?
```
A. IV hydrocortisone and fludrocortisone
B. IV hydrocortisone
C. IV fludrocortisone
D. Start sepsis 6
E. Give IV fluid bolus
```
A. IV hydrocortisone and fludrocortisone
?not severe enough to be classified as an Addisonian crisis, where the management would be B. IV hydrocortisone
71
A 58 year old man attends the GP concerns about the stretch marks on his stomach. On examination, there are purple striae on his abdomen and you notice he is overweight with adipose tissue predominantly centrally and subscapular. You send for a dexamethasone supression test with come back with the following:
Initial 9am cortisol = 600 nM. 48 hours later: cortisol = <50 nM.
What of the following is the most likely cause?
```
A. Cushing’s syndrome
B. Alcohol excess
C. Cushing’s disease
D. Hypothyroidism
E. Addison's disease
```
B. Alcohol excess
72
A 38 year old female has a routine blood test for health insurance. She is referred to her GP after a mild hypokalaemia was detected. She reports some fatigue and lethargy but no other symptoms. Her examination is normal except for a blood pressure of 150/90.
What is the most appropriate 1st investigation?
```
A. Fludrocortisone suppression test
B. Thyroid function tests
C. Aldosterone/Renin Ratio
D. Renal duplex ultrasound
E. Low dose dexamethasone suppression test
```
C. Aldosterone/Renin Ratio
73
A 35 year old man has headache, palpitations, and sweating. Examination reveals hypertension, which is paroxysmal in nature. Additionally, there are café au lait spots. A diagnosis of phaeochromocytoma is suspected. Which investigation would provide confirmation?
A. thyroid stimulating immunoglobulin antibody levels
B. TFTs
C. 24-hour urinary catecholamine and metanephrine Levels
D. aldosterone/renin ratio
C. 24-hour urinary catecholamine and metanephrine Levels
Phaeochromocytoma secondary to NF1
74
A nurse bleeps you (the on-call SHO) at 7pm as a patients blood tests have come back showing a severe hyperkalaemia of 7.4 mmol/l. You burst into the ward and find the patient. He responds cheerily to you and asks how you are doing.
What is the best appropriate next step?
```
A. Ask the nurse to do an ECG on him
B. Do a venous blood gas
C. Repeat the blood test
D. Give 10ml 10% calcium gluconate
E. Warm up the defibrillator
```
C. Repeat the blood test
75
A 22 year old female presents to the GP with excessive hair growth along persistent acne. She mentions that’s she’s been having painful irregular periods for many years and would also like treatment for that.
What is the most likely diagnosis?
```
A. Physiologically normal
B. PCOS
C. Hypothyroidism
D. Delayed puberty
E. Hyperthyroidism
```
B. PCOS
76
Metabolic complications of Cushing’s
diabetes mellitus
dyslipidaemia
metabolic bone disease
hypertension
77
Explain the different outcomes of the low dose dexamethasone test
ELEVATED MORNING CORTISOL >50 = CUSHINGS
Then, measure plasma ACTH..
1) low plasma ACTH = ACTH-independent = adrenal tumour
2) high plasma ACTH = ACTH-dependent = pituitary tumour/ectopic
NOTE- ACTH can be high OR inappropriately normal.. it should be completely suppressed.
78
Further investigation to discern whether ACTH-dependent Cushing's is due to a pituitary adenoma or an ectopic
Inferior petrosal sinus sampling (IPSS) – an invasive procedure in which ACTH levels are sampled from the veins that drain the pituitary gland
1) ↑ACTH = pituitary adenoma
2) Normal ACTH = ectopic
Disadvantages = need good angiography, not readily available
79
Briefly explain the effect of Aldosterone on the kidneys
1) causes an increase in the number of open Na+ channels in luminal membrane of principal cells in the collecting duct of the nephron = Na+ reabsorption
2) Makes the lumen electronegative & creates an electrical gradient
K+ is secreted into lumen = hypokalaemia
80
RF phaeo
35% have familial link (MEN2, VHL, NF1 )
- MEN type 2
- Von Hippel-Lindau disease
81
Why is phaeo a medical emergency
Severe hypertension can cause myocardial infarction or stroke
High adrenaline can cause ventricular fibrillation + death
82
Von Hippel-Lindau syndrome (VHL)
Hereditary condition associated with tumors arising in multiple organs.
- hemangioblastomas
- clear cell renal cell carcinoma (ccRCC),
- pancreatic neuroendocrine tumor (pNET)
- phaeo
- retinal angiomas
83
Why do you alpha and beta blockade someone with a phaeo before surgery?
Alpha blockade leads to unopposed stimulation of beta-adrenoreceptors = reflex tachycardia and arrythmias
Added BB means patient is fully protected from adverse effects of high adrenaline
84
How many phaeos become malignant?
10%
85
What are the causes of hypokalaemia due redistribution into cells?
Insulin
Salbutamol
Metabolic alkalosis
