Adrenal Flashcards
Adrenal
What are the 4 regions of the adrenal glands?
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)
What is produced by the adrenal medulla?
Catecholamines (adrenaline, noradrenaline)
What is produced by the zona reticularis?
Androgens (DHEA, androstenedione)
What is produced by the zona fasciculata?
Glucocorticoids (cortisol, corticosterone, cortisone)
What is produced by the zona glomerulosa?
Mineralocorticoids (aldosterone)
What effect do catecholamines have on the body?
Increased cardiac activity, blood pressure, glycogen breakdown, blood glucose levels
What effect do glucocorticoids have on the body?
Release AA from skeletal tissue, lipids from adipocytes, promote liver gluconeogenesis
What effect do mineralocorticoids have on the body?
Increased renal reabsorption of Na+ and H2O, renal K+ excretion
What is the adrenal medulla stimulated by?
Sympathetic preganglionic fibres
What is the zona reticularis stimulated by?
ACTH
What is the zona fasciculata stimulated by?
ACTH
What is the zona glomerulosa stimulated by?
Angiotensin II
high K+
low Na+
inhibited by ANP/BNP
What is the hypothalamic-pituitary-adrenal axis?
Hypothalamus –> CRH
Anterior pituitary –>ACTH
Adrenal cortex–> cortisol (supplies -ve feedback to the hypothalamus and anterior pituitary)
What is adrenal insufficiency?
an adrenal cortex disorder where there is a decreased production of adrenocortical hormones (cortisol, aldosterone, DHEA)
What are the causes of primary adrenal insufficiency?
TB – most common worldwide
Autoimmune – most common in UK
What are the causes of secondary adrenal insufficiency?
HYPOPITUITARISM
- Pituitary adenoma
- Sheehan’s syndrome
- Surgery/radiotherapy
- Pituitary apoplexy
What are the causes of tertiary adrenal insufficiency?
- Brain tumour
- Sudden withdrawal of long term corticosteroids
What is the main thing you would be looking for in a Pt with glucocorticoid deficiency?
Hypoglycaemia
What is the main thing you would be looking for in a Pt with mineralocorticoid deficiency?
Hyponatraemia
Hyperkalaemia
What are the symptoms of adrenal insufficiency?
Fatigue, weakness Anorexia Weight loss Nausea and vomiting Arthralgia and myalgia Abdominal pain Depression Salt cravings
What are the signs of adrenal insufficiency?
- Mucocutaneous hyperpigmentation in buccal mucosa and sun exposed areas (due to raised ACTH stimulating melanocytes)
- Postural hypotension
- Loss of body hair (in females)
What is the investigations you should do in a Pt with adrenal insufficiency? What would you see?
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
What is the diagnostic investigation you should do in a Pt with adrenal insufficiency?
synACTHen test
250mcg tetracosactide
At what synACTHen test cortisol levels can you rule out primary adrenal insufficiency?
Baseline cortisol >170nmol/L
30 min cortiosl >600nmol/L
What is the management for adrenal insufficiency?
Lifelong glucocorticoids and mineralocorticoids
eg. hydrocortisone + fludrocortisone
Raise dosage if stressed eg. trauma, surgery, infection
What are the complications of adrenal insufficiency?
- Addisonian crisis
- Secondary Cushing’s syndrome
- Osteoporosis (long term XS glucocorticoids)
- Hypertension (long term XS glucocorticoids)
What is an Addisonian crisis?
Acute adrenal insufficiency with major haemodynamic collapse
What are the causes of an Addisonian crisis?
- Sepsis/surgery with a background of chronic insufficiency
- Steroid withdrawal
- Adrenal haemorrhage (Waterhouse-Friderichsen syndrome)
What is the presentation of an Addisonian crisis?
Hypotensive shock Tachycardia Abdo pain Confusion Lethargy Coma
ELECTROLYTE ABNORMALITIES
- Hyperkalaemia
- Hypercalcaemia
- Hypoglycaemia
- Hyponatraemia
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
What is Cushing’s syndrome?
Chronic inappropriate elevation of free circulating cortisol
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%
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
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
What are the key symptoms of Cushing’s syndrome?
Weight gain Fatigue Muscle weakness Easy bruising Menstrual irregularities
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)
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
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).
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
What are the complications of Cushing’s syndrome?
- Adrenal insufficiency post-treatment
- Cardiovascular disease (main cause of mortality)
- Hypertension
- Diabetes mellitus
- Osteoporosis
What is hyperaldosteronism?
Autonomous overproduction of aldosterone from the adrenal glands
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
What are the risk factors for hyperaldosteronism?
FHx of aldosteronism
Early HTN
Stroke
What are the clinical features for hyperaldosteronism?
Hypertension in YOUNG PERSON
- Usually refractory to treatment
HYPOKALAEMIA
- Polyuria, polydipsia
- Muscle weakness
- Arrhythmia
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)
What is the management for hyperaldosteronism?
If bilateral hyperplasia: ALDOSTERONE ANTAGONISTS - spironolactone - amiloride - epleronone
If aldosterone producing adenoma: ADRENALECTOMY
- post-op aldosterone agonist
What is a phaeochromocytoma?
A tumour arising from catecholamine-producing chromaffin cells of the adrenal medulla
What are the 2 origins of phaeo?
- Adrenal medullary chromaffin cells (90%)
- Extra-medullary tumour (10%)
What is the rule of 10’s for a phaeo?
10% are extra-medullary
10% are bilateral
10% are malignant
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
What are the signs of a phaeo?
- Hypertension (95%)
- Tachycardia
- Hypertensive retinopathy
- Pallor
- Impaired glucose tolerance
- Orthostatic hypotension
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
What is the management for a phaeo hypertensive crisis?
5-20mg phentolamine IV single dose
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
What is the normal range of potassium and what hormones can affect potassium levels?
3.5-5.0 mmol/L
Angiotensin II, aldosterone
What are the causes of hyperkalaemia?
Reduced excretion
- Renal - CKD
- Endocrine – Addison’s, metabolic acidosis
- Drugs – ACEi/ARBs
Release from cells
- Rhabdomyolysis
- Acidosis
At what level do Pts with hyperkalaemia become symptomatic?
> 6.0mmol/L
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
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
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
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
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
What is polycystic ovarian syndrome?
Syndrome characterised by:
- oligomenorrhoea/amenorrhoea
- hyperandrogenism
- polycystic ovarian morphology on ultrasound
Associations of PCOS?
abdominal adiposity insulin resistance obesity metabolic disorders cardiovascular risk factors
What are the symptoms of PCOS?
Irregular menstruation (75%) Oligomenorrhea/amenorrhoea Infertility Hirsutism (60%) Acne (20%) Hair loss (scalp) (5%) Oily skin Excess sweating
What are the signs of PCOS?
Hirsutism
Overweight
Hypertension
Acanthosis nigricans
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
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
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
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
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
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
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
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
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
Metabolic complications of Cushing’s
diabetes mellitus
dyslipidaemia
metabolic bone disease
hypertension
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.
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
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
RF phaeo
35% have familial link (MEN2, VHL, NF1 )
- MEN type 2
- Von Hippel-Lindau disease
Why is phaeo a medical emergency
Severe hypertension can cause myocardial infarction or stroke
High adrenaline can cause ventricular fibrillation + death
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
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
How many phaeos become malignant?
10%
What are the causes of hypokalaemia due redistribution into cells?
Insulin
Salbutamol
Metabolic alkalosis