Endo2 Flashcards
Adrenal
What are the 4 regions of the adrenal glands?
Adrenal medulla Adrenal cortex: -zona reticularis -zona fasciculata -zona glomerulosa
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 formation of glucose and glycogen
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 Corticotrophin releasing hormona (CRH) Anterior pituitary Adrenocorticotrophic hormone (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?
Addison’s disease (80%, autoimmune, common in females)
Tuberculosis (commonest cause in endemic countries)
What are the causes of secondary adrenal insufficiency?
Pituitary adenoma
Sheehan’s syndrome
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 Anorexia Weight loss Nausea and vomiting Arthralgia and myalgia Abdominal pain Depression Salt cravings
What are the signs of adrenal insufficiency?
Hyperpigmentation in buccal mucosa and sun exposed areas (due to raised ACTH stimulating melanocytes)
Hypotension
Loss of body hair (in females)
What is the first line investigation you should do in a Pt with adrenal insufficiency?
9am cortisol (will be low)
What is the diagnostic investigation you should do in a Pt with adrenal insufficiency?
synACTHen test
250mcg tetracosactide
At what cortisol levels can you rule out adrenal insufficiency?
Baseline cortisol >170nmol/L
30 min cortiosl >600nmol/L
What other investigations can be done in a Pt with adrenal insufficiency?
Long synACTHen test (1mg tetracosactide, check at 1, 2, 3, 4, 5, 8, 24 hrs)
Adrenal antibodies
Adrenal CT/MRI
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 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 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) -excess ATCH from ectopic tumour ACTH-independant: -excess cortisol from adrenal adenoma
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?
24hr urinary free cortisol (>50mcg)
Late night salivary/plasma cortisol
48hr low dose dexamethasone suppression test
How is the 48 hour low dose dexamethasone suppression test performed?
Measure 9am plasma cortisol
Administer 0.5mg dexamethasone orally at 6hr intervals for 48hrs
Measure 9am plasma cortisol again
What are the investigations for Cushing’s syndrome?
High dose dexamethasone suppression test -slight suppression if pituitary tumour Inferior petrosal sinus sampling -measure ACTH from pituitary Adrenal CT/MRI -adrenal adenoma/hyperplasia/tumour Pituitary MRI CT CAP -ectopic sources
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:
- adrenal adenoma (Conn’s syndrome) 70%
- adrenal cortex hyperplasia 30%
Secondary:
- glucocorticoid-supressible hyperaldosteronism
- aldosterone producing adrenal carcinoma
What are the risk factors for hyperaldosteronism?
FHx of aldosteronism/early HTN/stroke
What are the clinical features for hyperaldosteronism?
Asymptomatic unless hypokalaemic Hypokalaemia: -lethargy -polyuria/polydipsia --nephrogenic diabetes insipidus secondary to hypokalaemia -muscle weakness -paraesthesia -tetany
Key signs: HTN
What are the investigations for hyperaldosteronism?
Plasma potassium
-low
Aldosterone/renin ratio (best initial)
-increased
Fludrocortisone suppression test (best diagnostic)
-4 days of fludrocortisone, plasma cortisol 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 antagonist if ongoing hyperaldosteronism
What is a phaeochromocytoma?
Catecholamine producing tumour
What are the causes of a phaeo?
Adrenal medullary chromaffin cells (90%)
Extra-medullary tumour (10%)
35% have familial link (MEN2, VHL, NF1 etc)
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?
24hr urinary catecholamines, metanephrines, normetanephrines, and creatinine
Plasma metanephrines and normetanephrines (will be continuously elevated unlike catecholamines)
Genetic testing
CT/MRI AP
I-123 metaiodobenzylguanidine (MIBG) scintigraphy
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 Alpha blockers (eg. phenoxybenzamine) Beta blockers (eg. atenolol, propanolol) -once alpha blockade is sufficient -prevents reflex tachycardia (due to a2 blockade) 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?
Renal impairment- decreased GFR Decreased renin production ACEi Ang II receptor blockers Addison's Aldosterone antagonists Rhabdomyolysis Blood acidosis
At what level do Pts with hyperkalaemia become symptomatic?
> 6.0mmol/L
What are the symptoms of a Pt with hyperkalaemia?
Muscle weakness
ECG changes
-tall tented T waves
-loss of P waves
What is the management for hyperkalaemia?
10ml 10% calcium gluconate
100ml 20% dextrose and 10 units of insulin (drives K+ into cells)
Nebulised salbutamol
What are the causes of hypokalaemia?
Gastrointestinal loss (D+V) Renal loss -diuretics: loop/thiazide diuretics -genetic defects -hyperaldosteronism -excess cortisol (binds to mineralocorticoid receptors) -osmotic diuresis Redistribution of K+ into cells (insulin, beta agonist, blood alkalosis)
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 ovaries
What is the cause of PCOS?
Unknown cause
Associated with obesity, insulin resistance, T2DM, dyslipidaemia
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)
- menstrual irregularity
- clinical/biochemical evidence of hyperandrogenism
- polycystic ovaries on US
What are the investigations for PCOS?
Tests to exclude other causes (prolactin, TFT etc) LH/FSH ratio >3 Serum total/free testosterone (elevated) Serum DHEAS elevated Oral glucose tolerance test- diabetes Fasting lipid profile- dyslipidaemia Pelvic ultrasound
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
