Endocrinology Flashcards
When would TBG be raised?
Pregnancy, oestrogen therapy (HRT, oral contraceptives), hepatitis
When would TBG be lowered?
Nephrotic syndrome, malnutrition (protein loss), drugs (androgens, corticosteroids, phenytoin), chronic liver disease, acromegaly
What thyroid function test results would you see is sick euthyroidism?
Everything is low
What would be a worrying result on an isotope scan of a thyroid?
A ‘cold’ nodule (decreased uptake of isotope) as 20% of these are malignant
What are the signs of someone with Hashimoto’s thyroiditis? Which demographic is most commonly affected?
Goitre
May be hypo or euthyroid
Commoner in women 60-70 y/o
Which antibodies are associated with Hashimoto’s thyroiditis?
Anti-TPO abs
If a patient is on amiodarone how often must you check their TFTs and why?
Every 6 months as amiodarone is like T4 so can cause hypothyroidism due to toxicity from iodine release (T4 release is inhibited)
What is the most common cause of hyperthyroidism?
Graves’
What is the pathophysiology behind Graves’ disease?
IgG autoAbs binding to and activating g-protein-coupled TSH (AKA thyrotropin) receptors
Can also react w/ orbital autoantigens
What effect does levothyroxine have on…
- T4
- T3
- Thyro-globulin
Increases T4
Decreases T3
Decreases Thyroglobulin
Subacute de Quervain’s thyroiditis:
a) What tends to precede it?
b) How would you describe the goitre?
c) Would the patient have a temperature?
d) What would be the results on an isotope scan?
e) What is the treatment?
a) A viral infection
b) Painful and diffuse
c) Yes and a raised ESR
d) Low isotope uptake on scan
e) NSAIDs
What is a major side effect of carbimazole? What advice would you give to patients on it?
Agranulocytosis (decreased neutrophils - at risk of sepsis). Warn patient to get an urgent FBC if signs of infection
Why must you not give radioiodine in a patient with active hyperthyroidism?
Risk of thyroid storm
Name 3 causes of a diffuse goitre
- Graves’
- Hashimoto’s thyroiditis
- Subacute (de Quervain’s) thyroiditis
Name 3 causes of a nodular goitre
- Multinodular goitre
- Adenoma
- Carcinoma
How would poor compliance with thyroxine show on blood tests?
High TSH and normal T4
Name the 3 autoantibodies in thyroid disease
- Anti-thyroid peroxidase (anti-TPO)
- TSH receptor abs
- Thyroglobulin abs
What is the other name for primary adrenocortical insufficiency?
Addison’s disease
What is the pathophysiology of Addison’s disease?
There is destruction of the adrenal cortex leading to glucocorticoid (cortisol) and mineralocorticoid (aldosterone) deficiency. Auto immunity is most common cause in the UK.
What is a cause of secondary adrenal insufficiency?
What happens to mineralocorticoid production?
Would the patient have hyperpigmentation and why?
Iatrogenic - due to long-term steroid therapy which suppresses the pituitary-adrenal axis
- Mineralocorticoid production remains intact.
- There is NO hyperpigmentation as ACTH is decreased
What happens to the following in Addison’s disease…
Potassium Sodium Glucose Calcium Urea Eosinophils Red blood cells
Raised potassium Decreased sodium Decreased glucose Raised calcium Raised urea Raised urea (uraemia) Raised eosinophils (Eosinophilia) Decreased red blood cells (anaemia)
Which autoantibody is found in 90% of patients with Hashimoto’s thyroiditis?
Anti-thyroid peroxidase (anti-TPO)
Which autoantibody is found in nearly all Grave’s disease patients?
TSH receptor antibodies
Which is the main test used to diagnose Addison’s disease?
Short ACTH stimulation test
What does the short ACTH stimulation test entail?
How do you interpret results?
Do plasma cortisol before and 30 minutes after Synacthen (synthetic ACTH) IM.
Cortisol would rise (>550 nmol/L) in normal individuals, but would not rise in people with Addison’s
Other than the short ACTH stimulation test, what other tests can you do in Addison’s disease?
- ACTH 9am
- 21- Hydroxylase adrenal autoantibodies in autoimmune disease
- Plasma renin and aldosterone to assess mineralocorticoid status
What would 9am ACTH in someone with Addison’s disease be compared to someone in a secondary cause of adrenal insufficiency?
ACTH 9am is inappropriately high in Addison’s but is low in secondary causes of adrenal insufficiency.
What 2 treatments should be given to those with Addison’s disease?
Replace steroids (hydrocortisone daily): avoid giving late as can cause insomnia. Give mineralocorticoids to correct postural hypotension, low sodium and high potassium E.G. Fludrocortisone
What happens to a patient is Addisonian crisis?
They go into SHOCK! - High HR; vasoconstriction; postural hypotension; oliguria; weak; confused; coma.
Give 3 causes of Addisonian crisis?
- Steroids not being increased to cover stress
- Forgotten tablets
- Bilateral adrenal haemorrhage
What 3 biochemical tests should be ordered in Addisonian crisis?
Bloods for cortisol, ACTH & U+Es
What treatment should be given to patients who are experiencing an Addisonian crisis?
Hydrocortisone IV and an IV bolus (increases BP).
If you suspect an infection as the underlying cause in Addisonian crisis, what 2 samples should you send for culture?
Blood and urine samples.
When should you switch to oral steroids in someone being treated for an Addisonian crisis?
After 72 hours if the patient’s condition is good
What should you advise someone with Addison’s disease to do with their steroid intake if they plan to do strenuous exercise?
They should add 5-10 mg of hydrocortisone to their daily intake
What should you advise someone with Addison’s disease to do with their steroid intake if they have febrile illness, injury or stress?
They should double their steroid intake
What metabolic disturbance can Cushing’s syndrome cause?
Hypokalaemic metabolic alkalosis
Define Cushing’s syndrome
Chronic glucocorticoid XS and loss of circadian rhythms of cortisol secretion.
What is the main cause of Cushing’s syndrome?
Oral steroids
What is the most common cause of Cushing’s disease?
XS glucocorticoid due to a pituitary adenoma
How can an ACTH-secreting pituitary adenoma affect the adrenals in Cushing’s disease?
Bilateral adrenal hyperplasia
What 2 malignancies that commonly cause ectopic ACTH production?
Small cell lung cancer and carcinoid tumours
What would change in the skin of someone who has ectopic ACTH production?
Pigmentation!!
What happens to ACTH levels in ACTH-independent causes of Cushing’s syndrome?
ACTH decreases due to negative feedback.
Is McCune Albright syndrome a ACTH dependent or independent cause of Cushing’s syndrome?
ACTH-independent
List as many symptoms of Cushing’s syndrome as you can
- Increased weight
- Mood change
- Proximal weakness
- Irregular menses
- Hirsutism
- ED
- Acne
- Recurrent Achilles tendon rupture
- Central obesity
- Moon face
- Buffalo hump
- Striae
- Osteoporosis
- Increased BP
- Increased glucose
- Infection prone
What is the treatment for Cushing’s disease?
Trans-sphenoidal removal of pituitary adenoma in Cushing’s disease.
What are the 3 treatments for adrenal carcinoma?
- Adrenalectomy
- Radiotherapy
- Adrenolytic drugs (mitotane)
What is the overnight dexamethasone suppression test used for?
To diagnose Cushing’s syndrome.
How do you conduct the overnight dexamethasone suppression test and how do you interpret the results?
The patient has 1mg PO of dexamethasone then serum cortisol at 8am - there is no suppression in Cushing’s.
In which 4 circumstances may you get a false positive overnight dexamethasone suppression test?
Pseudocushing’s…
1) Depression
2) Obesity
3) Alcohol XS
4) Inducers of liver enzymes
The overnight dexamethasone suppression test has come back positive - what tests do you do next in this patient with suspected Cushing’s syndrome?
48 hr dexamethasone suppression test and midnight cortisol.
Localisation tests…
A patient with suspected Cushing’s syndrome has their plasma ACTH measured. It comes back as being undetectable - what is the next investigation you should do?
If this investigation comes back negative, what should you do next?
CT/MRI to look for an adrenal tumour.
If no mass is found, do adrenal vein sampling.
Localisation tests…
A patient with suspected Cushing’s syndrome has their plasma ACTH measured. It comes back as being detectable - what is the next test you should do?
How do you carry this test out? How can you interpret this result?
High dose suppression test/ CRH test - measure cortisol at 2 hours - cortisol is increased in pituitary disease but NOT with ectopic ACTH production.
Generally, if cortisol responds to manipulation in tests for Cushing’s syndrome/disease, which diagnosis does it point towards? Which 2 investigations should you do to investigate?
Suggests Cushing’s disease - should then do an MRI of the pituitary and consider bilateral inferior petrosal sinus blood sampling
Which investigation can you use to hunt for an ectopic source of ACTH?
IV contrast CT of chest, abdo and pelvis.
Name 5 causes of hypocalcaemia that would present with increased phosphate levels?
- CKD
- Hypoparathyroidism
- Pseudohypoparathyroidism
- Acute rhabdomyolysis
- Hypomagnesaemia
What is the treatment of mild hypocalcaemia?
Give calcium
What is the treatment of hypocalcaemia in CKD?
Alfacalcidol (a vitamin D analogue)
How do you treat severe hypocalcaemia?
Calcium gluconate IV
What are the features of hypocalcaemia?
S: Spasms
P: Perioral paraesthesia
A: Anxious, irritable, irrational
S: Seizures
M: Muscle tone increases in smooth muscle
O: Orientation impaired and confusion
D: Dermatitis
I: Impetigo herpetiformis (reduced Ca2+ and pustules in pregnancy - rare and serious)
C: Chvostek’s sign; choreoathetosis (chorea and twisting); cataract (if chronic); Cardiomyopathy (long QTi on ECG)
What is Trousseau’s sign?
On inflating the cuff, the wrist and fingers flex and draw together (carpopedal spasm)
What is Chvostek’s sign?
Tapping over parotid (facial nerve) causing facial muscles to twitch
Name as many features as you can of hypercalcaemia
Bones, stones, groans, psychic moans.
Constipation, polyuria, weight loss.
What may you see on ECG of someone with hypercalcaemia?
Decreased QT interval
A patient is found to have hypercalcaemia with normal urea levels. What is the likely cause?
Cuffed specimen
A patient’s Ca2+ is >3.5 mmol/L and they are symptomatic. What treatment do you give if they are…
a) Dehydrated
b) You want something to prevent bone resorption
c) Have cancer
d) Have sarcoidosis
a) Give IV saline 0.9%
b) Bisphosphonates e.g. Zoledronic acid inhibits osteoclasts
c) Chemo
d) Steroids
Name 5 things that can affect the hypothalamus and consequently cause hypopituitarism
- Kallman’s syndrome
- Meningitis
- TB
- Tumour
- Ischaemia
Name 2 things that can affect the pituitary stalk and consequently cause hypopituitarism?
Craniopharyngioma, carotid artery aneurysm
Name 2 things that can affect the pituitary and consequently cause hypopituitarism
Pituitary apoplexy, irradiation
Name 5 effects of low growth hormone secondary to hypopituitarism
- Central obesity
- Atherosclerosis
- Decreased strength
- Osteoporosis
- Decreased glucose
Name 4 effects of low FSH/ LH secondary to hypopituitarism
Oligomenorrhoea, osteoporosis, ED, Hypogonadism
What may happen to prolactin levels in hypopituitarism?
They may be raised due to low dopamine levels
What type of anaemia may you see in someone with hypopituitarism?
Normochromic, normocytic anaemia
Name 1 test that can be used to investigate suspected hypopituitarism
How is this test conducted? What do you have to tell the patient beforehand?
Insulin tolerance test
IV insulin is given to patient which causes hypoglycaemia. This stress should increase cortisol and GH secretion in a normal person. The patient must be fasted.
What medication can you give someone experiencing low GH?
Somatotrophin (mimics GH)
Name 2 treatment options for someone who has chronic hyponatraemia and is asymptomatic?
Fluid restriction and sometimes a ADH antagonist (demeclocycline) may be needed
What treatment should you give to someone who has acute/ symptomatic/ dehydrated hyponatraemia?
Rehydrate them with 0.9% saline.
Why must you not correct hyponatraemia rapidly?
Risk of central pontine myelinolysis
What are ‘vaptans’? What do they do? Name 2 types of hyponatraemia they may be used for?
They are vasopressor (ADH) receptor antagonists which promote water excretion without loss of electrolytes.
Can be used to treat hypervolaemic and euvolaemic hyponatraemia.
What 4 criteria must be met to diagnose SIADH?
- Concentrated urine (high sodium and high osmolality)
- Hyponatraemia
- Low plasma osmolality
- Without hypovolaemia, oedema or diuretics
What is a malignant cause of SIADH?
Small cell lung cancer
What are the 4 treatment options for SIADH?
- Restrict fluid
- Salt
+/- loop diuretics if severe - Vaptans
What electrolyte abnormality can diabetes insipidus lead to? When should you suspect it? Name 2 causes of it.
Can lead to hyponatraemia
Suspect if large urine volume
May follow head injury or CNS surgery
Name 2 treatments for hypernatraemia.
Which other treatment would you give if the patient is hypovolaemic?
H2O orally.
If this doesn’t work, give glucose 5% IV slowly (guided by urine output and plasma Na+)
Use 0.9% saline IV if hypovolaemic
What would you expect to happen to the following in hyperaldosteronism…
- Sodium
- Water
- Renin release
- Increased Sodium
- Water retention
- Decreased Renin release
When should you consider hyperaldosteronism in a patient?
If they are hypertensive (not always!), hypokalaemic (not always!) or alkalotic but not on diuretics.
What is the most common cause of hyperaldosteronism? What is another name for this?
What is the 2nd most common cause?
Solitary aldosterone-producing adenoma AKA Conn’s syndrome
Bilateral adrenocortical hyperplasia
In which 3 cases should you consider Conn’s syndrome?
1) HTN w/ low potassium
2) Refractory hypertension
3) Hypertension before 40 years old
What must you be wary of if you are doing an MRI to find a cause for hyperaldosteronism?
You might find adrenal incidentalomas that are common but not the actual cause
What should you do if you find a unilateral adenoma of the adrenals on MRI? What is a positive result? What is the treatment?
Do adrenal vein sampling. If 1 side reveals increased aldosterone production then it is an adenoma and it should be surgically excised.
Name a differential diagnoses other than adenoma and bilateral adrenal hyperplasia that could cause hyperaldosteronism with no nodules found on MRI?
Renal artery stenosis
What are the treatment options for adrenal hyperplasia?
Spironolactone, amiloride or eplerenone (new selective aldosterone receptor antagonist that does NOT cause gynaecomastia
What surgery is used in the treatment of Conn’s? What treatment must you give to the patient beforehand and why?
Laparoscopic adrenalectomy
Give spironolactone for 4 weeks pre-op to control BP and potassium.
What are the 4 ‘10%’ rules in phaechromocytoma?
- 10% malignant
- 10% bilateral
- 10% familial
- 10% extra-adrenal
What is the triad in phaechromocytoma?
Sweating
Episodic headache
Tachycardia
Where do phaechromocytomas arise from normally?
Arise from sympathetic paraganglia cells found within the adrenal medulla.
Name 5 things that can lead to acute hypertensive crisis in someone with a phaechromocytoma?
- Stress
- Abdo palpation
- Parturition
- GA
- Contrast media
Name 5 symptoms of an acute hypertensive crisis in someone with a phaechromocytoma?
- Pallor
- Pulsating headache
- HTN
- Feels ‘about to die’
- Pyrexia
List 4 things you may see on the ECG of someone with phaechromocytoma
1) Signs of LVF
2) Increased ST elevation
3) VT
4) Cardiogenic shock
What medications must you give to someone prior to the surgery needed to treat their phaechromocytoma and why?
a blocker THEN b blocker to avoid crisis from unopposed a-adrenergic blockade.
What 2 things must you monitor post-op in someone with phaechromocytoma? How long must you follow up these patients?
1) 24 hr urine metadrenalines 2 weeks post-op
2) Monitor BP as there is a risk of this dropping
Life-long follow up as malignant recurrence may present late.
What tests should you do in someone with a phaechromocytoma?
Plasma + x3 24 hour urines for free metadrenaline and normetadrenaline +/- clonidine suppression test if borderline.
List 5 symptoms of PCOS
- Secondary oligo- or amenorrhoea
- Infertility
- Obesity
- Acne
- Hirsutism
What imaging would you do in someone with suspected PCOS? What may you find?
An ultrasound scan - bilateral polycystic ovaries.
What would happen to the following in someone with PCOS…
- Testosterone
- Sex hormone binding globulin
- LH : FSH ratio
- TSH
- Lipids
- High Testosterone
- Low Sex hormone binding globulin
- High LH : FSH ratio
- TSH: could be low as hypothyroidism is common in PCOS
- Dyslipidaemia
What 4 medications can be used for PCOS and why?
- Metformin: may restore cycles and fertility and helps insulin resistance
- COCP: can cause ovarian androgen suppression
- Can add spironolactone if not working: An androgen receptor blocker
- Co-cyprindicol can be used to treat hirsutism and acne (combo of oestrogen and anti-androgen)
What is pituitary apoplexy?
Sudden endocrine crisis due to haemorrhage/ ischaemic infarction of gland.
Name 4 potential symptoms of pituitary apoplexy
- Sudden, severe headache
- Visual field defects
- III/ IV/ VI CN palsies
- +/- meningeal irritation
What treatment is necessary for pituitary apoplexy and which treatment may be required?
IV hydrocortisone ASAP
May need decompressive surgery
What is the criteria for diagnosing PCOS? How many of the criteria needs to be met?
2/3 needed for diagnosis:
- Oligo/ amenorrhea
- Hyperandrogenism (clinical or biochemical)
- Polycystic ovaries on US + exclusion of other disorders