Endocrinology Flashcards
Give examples of hypovolaemic hyponatraemia?
1) Diuretic use (esp thiazide diuretics and aldosterone antagonists eg spironolactone) 2) Vomiting + Diarrhoea + Sweating + Burns 3) Hypoaldosteronism (Addison’s disease / primary adrenal insufficiency) = deficiency of aldosterone which usually reabsorbs sodium and excretes potassium so you get low serum sodium and high serum potassium) 4) Pancreatitis (third space loss)
Give examples of euvolaemic hyponatraemia?
1) SIADH
2) SSRIs (especially citalopram)
3) Beer Potomania
What are the diagnostic criteria for SIADH?
1) Clinically euvolaemic 2) Low plasma osmolarity + low plasma sodium 3) Inappropriately high urine sodium (>40 mmol/L) and high urine osmolarity (>100mosmol/kg) 4) Exclusion of hypoythroidism, diuretic use and glucocorticoid deficiency, especially in those with neurosurgical conditions.
Give examples of medications that cause SIADH?
Desmopressin, SSRIs, Tricyclics, Haloperidol, Carbamazepine
List the most common underlying causes of SIADH
Malignancy (small cell lung, GI)
CNS disorders (subarachnoid haemorrhage, meningitis, encephalitis)
Drugs (desmopressin, SSRIs, tricyclics, haloperidol, carbamazepine)
Pneumonias
Stress
General Anaesthetic
Give examples of hypervolaemic hyponatraemia
CCF (reduced EJ = reduced intravascular filling = ^ ADH secretion + thirst = ^ water reabsorption/dilution) Nephrotic Syndrome (leaky glomeruli = albumin loss = hypoalbuminaemia = reduced intravascular filling = same as above) Liver cirrhosis (hypoalbuminaemia) (ALL THESE 3 CAUSES ARE ASSOCIATED WITH LOW URINE SODIUM BECAUSE KIDNEYS STILL WORK TO TRY RESORB) Chronic renal impairment - reduced eGFR = activation of R-A-A = ^ aldosterone = ^ Na + H20 reabsorption + activation of ADH = ^ H20 reabsorption (ASSOCIATED WITH HIGH URINE SODIUM AS KIDNEYS UNABLE TO RETAIN THE SODIUM)
Give examples of pseudohyponatraemia and what basic investigation would suggest pseudohyponatraemia.
Examples - hyperglycaemia, mannitol high serum triglycerides or protein (eg in myeloma)
Suspect when serum osmolarity is high (with hyperglycaemia + mannitol use) or normal (triglycerides/proteins) as in true hyponatraemia serum osmolarity is normally reduced.
What are the normal, impaired glucose tolerance and diabetic level results from the oral glucose tolerance test.
Normal: Fasting glucose <6 mmol/L, @ 2hrs post glucose challenge = <7.8 mmol/L
Impaired Glucose Tolerance: Fasting glucose 6 - 7 mmol/L.
2 hrs post challenge = 7.9 - 11 mmol/L
Diabetic = Fasting glucose >7 mmol/l. 2 hours past challenge = > 11 mmol/L
From where is TSH produced?
Anterior Pituitary
What is primary versus secondary hypothyroidism?
Primary Hypothyroidism:
Adequate stimulation from the anterior pit / hypothalamus but inadequate thyroid response =
Overt - TSH levels are high and T3 and T4
Subclinical - TSH levels are high and T3/T4 is normal
Secondary hypothyroidism: inadequate stimiulation from anterior pit / hypothalamus
What are the most common causes of primary hypothyroidism?
1) WORLDWIDE - most common cause of primary hypothyroidism = iodine deficiency
2) In UK / 1st world countries = most common cause = AUTOIMMUNE THYROIDITIS. Autoimmune thyroiditis with goitre = Hashimoto’s Thyroiditis (diffuse NON-TENDER goitre) or Subacute Thyroiditis (TENDER goitre with raised ESR, initally HYPERthyroidism then transient hypothyroidism, associated w/ viral infections). Without goitre = Atrophic thyroiditis
3) post-ablative therapy / surgery for prev hyperthyroidism
4) Treatment of hyperthyroidism with carbimazole and propylthiouracil can lead to subsequent hypothyroidism
5) Postpartum Thyroiditis (similar to subacute thyroiditis in that initially get hyperthyroidism and then transient hypothyroiditis, normally return to euthyroid within a year of postpartum -> risk factors = antithyroid antibodies before pregnancy, type I diabetes, personal or fam Hx of thyroid problems)
British guidelines on peri-operative management of diabetics: organisation of their surgery
No of meals missed should be minimised by making them 1st on the list
Day of surgery admission should be the norm - specific pre-surgery admission just because they are diabetic should be avoided.
CBG should be measured hourly during the procedure and the immediate post-operative period
British guidelines on peri-operative management of diabetics: the use of sliding scale in the peri-operative period
- If short starvation period (missing only 1 meal) should avoid sliding scale and manage by modifying their normal diabetic meds
- If missing more than one meal but their diabetes is managed by lifestyle or 1x metformin dose/day then only start sliding scale is CBG >12 on 2x consecutive occasions
Blood glucose targets in the peri-operative patient
If sedated / anaethetised / on/received insulin / sulphonylurea (ie hypoglycaemic causing agents) then target = 6-10 (upto 12 is acceptable)
If pt AWAKE and NOT on any hypoglycaemic causing agents then a lower threshold of 3.5 is acceptable.
Percentage of UK population with diabetes
~ 7%
Peri-operative management of insulin regime in type I diabetics
Insulin should NEVER be stopped in type I diabetics as this can leads to ketoacidosis.
If missing more than 1 meal = start sliding scale and continue long-acting insulin (the dose of the long-acting insulin should be reduced by 20% of their normal dose when they are in hospital)
The optimum pre-operative HbA1C to optimise wound healing / recovery
= <6.9 / 8.5%
How should patients with a continuous subcutaneous insulin pump be managed peri-operatively?
If short starvation period (1 or less meals missed) then continue basal rate of subcut pump with mealtime boluses resumed once eating and drinking normally.
If more than 1 meal missed, then remove the pump and start sliding scale instead.
What is stress hypergylcaemia and how should it be managed after the peri-operative period?
Stress hyperglycaemia = can occur in severe illness + trauma, inflammatory cytokines = ^ peripheral insulin resistance.
Mx - treat aggressively in the acute phase as per diabetic hyperglycaemia. If blood glucose then returns to normal, then arrange oral glucose tolerance test or fasting blood glucose in 6 wks. If blood glucose remains high in the acute phase then can diagnose as diabetic without formal testing.
Peri-operative management of patients on metformin?
If only 1 meal missed and @ low risk of AKI = can continue metformin
For those missing >1 meal or @ high risk of AKI = suspend metformin peri-operatively and resume once E+D / renal function known to be stable
What are risk factors for peri-operative AKI?
- CKD or Hx of prev AKI
- Heart Failure
- Liver disease
- Neurological / cognitive impairment / disability due to risk of not drinking fluids
- Hypovolaemia / Hypotension
- Nephrotoxic drugs - NSAIDs, ARBs, ACEi, diuretics, aminoglycosides ie gentamicin
- Use of contrast in the past week
- Urological obstruction / symptoms of
- Haematological malignancy
- Age > 65
At what renal function should metformin be stopped?
Don’t initiate if eGFR <45. Stop when eGFR <30.
How should insulin regimes be modified peri-operatively.
OD long-acting insulins taken in AM -> reduce dose by 20% the day before AND the day of surgery
OD long-acting insulin taken in the evening -> reduce dose by 20% the day before and then review post-surgery dose depending on BMs
BD mixed or long-acting insulins -> normal dose the day before, half the morning dose the day of surgery, leave the evening dose after surgery the same
BD separate injections of short and intermediate acting insulins -> no dose change the day before, calculate the total dose of the morning insulins and give half of that as INTERMEDIATE insulin only. Leave the evening dose the same post-surgery.
TDS/QDS/5X/day regimens (of either basal-bolus or mixed insulin preparations -> dose before is unchanged, if basal bolus regime, omit morning and lunch bolus insulin if surgery is AM (or just lunch dose if PM) and give basal insulin at 20% reduction. If premixed regime, half the morning dose and omit the lunchtime dose if surgery is AM or give morning dose as normal and omit lunchtime dose if surgery is PM.
How should the various oral diabetic agents be taken peri-operatively?
Metformin: normal dose the day before surgery, on the day of surgery max 2 doses (AM + PM) so omit lunchtime dose if on TDS. STOP METFORMIN IF STARTED ON SLIDING SCALE.
Sulphonylureas (gliclazide, glipizide) -> normal dose the day before, omit the dose in the morning before surgery, resume post-surgery. STOP SULPHONYLUREAS WHILE ON A SLIDING SCALE
Meglitidine (repeglinide, nateglinide) -> normal dose the day before, omit morning dose day of if NBM, can give morning dose if still eating. STOP WHEN ON SLIDING SCALE
Acarbose - normal dose the day before, omit morning dose if NBM. STOP WHILE ON SLIDING SCALE.
TZDs / Pioglitazone = take as normal on the day before AND the day of surgery. STOP WHILE ON SLIDING SCALE
DPP4 inhibitors (linagliptin/sitagliptin) = take as normal on the day before AND the day of surgery. STOP WHILE ON SLIDING SCALE
SGLT2 Inhibitors = take as normal day before. omit day of surgery. STOP WHILE ON SLIDING SCALE UNTIL E+D NORMALLY
GLP-1 Agonists (exenetide, dulaglutide) = take as normal on the day before and day of surgery AND CAN CONTINUE THEM WHILE ON SLIDING SCALE
What is the triad of DKA?
Hyperglycaemia + Acidosis + Ketosis
Why do you get ketosis / acidosis in DKA?
Need insulin in order to build up glycogen stores in the liver.
In the deficiency of insulin, high circulating blood glucose but no intracellular glucose = stimulates glucagon release = no glycogen stores to breakdown so instead stimulates lipolysis = breakdown of triglycerides into fatty acids = generates ketosis -> 1st ketone to be produce in acetylacetate, then you get acetone which is secreted by the lungs (pear-drop smell). Ketone bodies generate hydrogen ions and ketone ions. Bicarb is used as a buffer so gets used up.
Bicarb + hydrogen ions = C02 = hyperventilation
High glucose = osmotic diuresis = dehydration and hyponatraemia and hypokalaemia and hypomagnesium and hypocalcaemia
What are markers of SEVERE DKA?
Blood ketones > 6mmol/L Bicarb < 5 mmol/L pH <7 Hypokalaemia on admission (<3.5) GCS < 12 SP02 < 92% on air SBP < 90 mmHg Pulse > 100 or < 60 Anion gap > 16 (Cations [hydrogen, sodium, potassium] - anions [chloride + bicarb] - tend to be high in DKA because of the increased H+
If any of these markers then should be reviewed by a consultant and considered for admission to HDU.
Management of DKA
0-60 mins: 1) IV rehydration - * Bolus of 0.9% NaCl -> 1L over 15 mins if BP < 90 or over an hour if BP ok * then 1L over next 2 hrs * then 1L over next 2 hrs K+ is added in according to the potassium level Tight monitoring of urine output VBG at 60 mins then 2 hrly then 2 hrly
2) Alongside the IVI = fixed rate insulin infusion through a separate cannula = 50 units short-acting insulin (Actrapid/Humulin S) in 50 mls 0.9% Nacl infused at 0.1 units/ kg/hr
AND continue their usual long-acting insulin
Be cautious of inducing cerebral oedema in young adults with aggressive fluid resus (concern if develops headache, reducing GCS, seizures etc)
60 mins - 6 hrs:
If blood ketones not falling by 0.5 mmol/L/hr
OR
If blood glucose not falling by 3 mmol/l/hr
THEN need to increase the insulin infusion rate by 1 unit/hour until ketones/glucose falling at the appropriate amount.
If blood glucose drops below 14 mmol/L - then must start 10% glucose alongside the NaCl.
What is the gold standard diagnostic test for acromegaly?
acromegaly = excess growth hormone, normally due to tumour
2hr oral glucose tolerance test + growth hormone
no drop in growth hormone with glucose load in true acromegaly
Diagnostic test for Cushing’s test?
Dexamethasone suppression test
-> cortisol stays high
Diagnostic test for Addison’s disease?
Synacthen (synthetic ACTH) -> don’t see a rise in cortisol in response to the Synacthen
Diagnostic test for diabetes insipidus?
Water deprivation test -> then measure urine and serum osmolarity over 24 hrs
Diagnostic test for myaesthenia gravis?
Tensilon test -> ask them to repeat the phrase as many times as they can until they fatigue then give tensilon and get them to repeat and it improves
Cushing’s syndrome v cushing’s disease?
Cushing’s syndrome = high cortisol levels 2ndary to drugs (exogenous steroids) -> no suppression to either low or high dose dexamethasone
Cushing’s disease = high cortisol levels 2ndary to pituitary adenoma - low dose dex supression test = no suppression, high dose dex supression test = suppression
Side effects of propranolol?
cold fingers and toes
disturbed sleep
Thiazide diuretic side effects?
can ^ blood glucose! and ^ serum lipids and serum uric acid
Tx of graves opthalmopathy ?
high dose steroids
orbital decompression if resistant to treatment and eyesight is threatened
in treating hypthyroidism in pregnancy, what is the target?
to keep TSH in the normal range
What is the most common type of thyroid cancer?
PAPILLARY
which drug is VERY COMMONLY associated with gallstone formation?
OCTREOTIDE
which diagnosis to suspect in a child <3 presenting with pubic/axillary hair / precocious puberty?
Hamartoma of the posterior hypothalamus!!!
typical presentation of kallman syndrome?
delayed puberty due to hypothalamic gonadotrophin deficiency + anosmia +/ cleft palate
Which eye signs are specific to Grave’s disease (hyperthyroidism due to TSH-receptor antibodies)?
Exophthalmos
Ophthalmoplegia
Thyroid acropachy
pretibial myxoedema
what are the indications for islet cell transplant?
Type I diabetic with 2 or more SEVERE HYPOS in the last year with IMPAIRED HYPO AWARENESS
Most common causes of hypo and hyperthyroidism and the antibodies involved?
HYPO -> 1st world = Hashimoto’s thyroiditis (anti TPO and anti thyroglobulin antibodies). worldwide = iodine deficiency
HYPER -> Grave’s disease (Anti TSH receptor antibodies)
Other’s toxic multinodular goitre, single toxic nodule / adenoma / de quervain’s thyroiditis (after a viral infection), postpartum thyroiditis
Primary versus secondary versus tertiary hyperparathyoidism?
Primary hyperparathyroidism -> parathyroid adenoma or parathyroid gland overproduction
= high PTH with normal or high calcium and low phosphate
Secondary hyperparathyroidism > APPROPRIATELY ^ PTH due to LOW CALCIUM (normally due to either vitamin D deficiency or chronic kidney disease commonly)
= high PTH with LOW calcium
Tertiary hyperparathyroidism -> autonomous production of PTH usually due to chronic secondary hyperparathyroidism
Primary versus secondary hyPOparathyroidism?
Primary hypoparathyroidism ->
Low calcium, high phosphate, low or inappropriately normal PTH
Secondary hypoparathyroidism ->
Low PTH, low calcium, high phosphate -> normally due to either surgery on the parathyroid glands OR low magnesium
(Mg is needed for PTH production!!)
Typical presentation of Addison’s disease and the preferred method of diagnosis?
Buccal pigmentation, palmar creases, postural hypotension
= primary adrenal insufficiency = low cortisol + low aldosterone
Low aldosterone = low serum sodium, low BP and high potassium
Low cortisol - low glucose
Dx = short synacthen test
Typical presentation + most common cause of Conn’s syndrome?
Conn’s = primary hyperaldesteronism
= hypernatraemia, high BP, low potassium
Most common cause = an adrenal aldosterone-producing adenoma
Typical presentation of pheochromocytoma and which syndromes is it associated with?
Tumour of the adrenal medulla = ^ adrenaline + noradrenaline secretion
= ^ BP + headache + palpitations
90% are sporadic, 10% are linked to syndromes: Von-Hippel-Lindeau, Multiple Endocrine Neoplasia (MEN), neurofibromatosis
What are the most common types of hormone-secreting pituitary tumours in adults and children respectively?
in adults most common = growth hormone secreting adenoma (acromegaly / gigantism)
In children = prolactinoma
Which pituitary tumours do NOT produce hormones?
MOST COMMON = a non-functioning pituitary adenoma = only produces symptoms when large enough to compress the optic chiasm (bitemporal hemianopia) or other surrounding structures
Others (more rare) = Craniopharnygoma + Rathke’s cleft cysts
Which neurotransmitter INHIBITS prolactin release from the hypothalamus?
Dopamine
hence dopamine antagonists cause ^ prolactin = galactorrhoea
Drug causes of ^ prolactin / galactorrhoea?
DOPAMINE ANTAGONISTS:
Metoclopramide, Chlorpromazine, Domperidone + Haloperidol + Risperidone
Which drugs are used to TREAT hyperprolactinaemia / galactorrhoea?
Dopamine agonists!!
Bromocriptine + Cabergoline
How does hyperprolactinaemia present in men?
Hypogonadism + reduced libido + erectile dysfunction
Different type of prolactinoma?
Microprolactinoma = MOST COMMON = 90%
Macroprolactinoma = less common, larger in size
Malignant prolactinoma = rare
What is macroprolactinaemia?
Macroprolactin = a biologically inactive molecule that can result in a false positive high prolactin level
Typical presentation of acromegaly?
Hand + feet swelling High blood glucose + diabetes Hypertension Excessive sweating Obstructive sleep apnoea Hepatosplenomegaly Hoarse voice
What is wolfram syndrome?
genetic disorder with diabetes mellitus + optic atrophy (colour blindness) + deafness
Types of oesophageal cancer?
Majority (>90%) = SCC of the UPPER THIRD (due to smoking)
10% adenocarcinoma in the LOWER THIRD due to Barret’s oesophagus (metaplasia from Squamous to columnar)
Hypothyroidism can cause a MACROCYTIC ANAEMIA - true or false
True!!
What is congenital adrenal hyperplasia?
Excessive ACTH release = hyperplasia of the adrenal gland - HIGH ANDROGENS but LOW CORTISOL RELEASE
Tx - Hydrocortisone replacement
typical presentation of pituitary apoplexy?
Sudden bleed into a pituitary tumour
Presents with sudden-onset headache then a rapid decline in GCS in someone with a known/suspected pituitary tumour
