Endocrinology Flashcards
Difference between proptosis and exophthalmos?
Exophthalmos is forward protrusion of eyeball related to Graves
Proptosis - forward protrusion related to any cause:
Malignancy
Inflammation
Traumatic
Signs of Cushing’s syndrome?
ACTH/cortisol
Moon face Buffalo hump Supraclavicular fat pads Central obesity Wasted limbs
Signs of hyperandrogenism
Hirsutism
Temporal balding
Acne
What are the micro and macro problems of diabetes?
Micro:
Retinopathy
Nephropathy
Neuropathy
Macro:
Stroke
Renovascular disease
Limb ischaemia
What are the three ways diabetes may be diagnosed?
- Symptoms + 1 BM
- 2 BMs
- HbA1c ≥48 (6.5%)
BM: fasting ≥7 or random > 11
What signs indicate thyrotoxicosis?
Hair loss
Bulging eyes (proptosis/exophthalmus)
Onycholysis- nail separation from nail bed
Pretibial myxoedema
What measurements suggest impaired fasting glucose?
Fasting glucose of 6.1-7mmol/L
Impaired glucose tolerance is defined as?
Fasting plasma glucose
What HbA1c indicates prediabetes?
42-47mmol
6-6.4%
What is the target blood glucose if on metformin?
6.5%
48mmol
How is Atorvastin dosed differently depending on whether someone has a QRISK above 10% or has existing IHD?
Primary prevention (QRISK)- 20mg Secondary prevention (IHD)- 80mg
What values after 2 hours indicate impaired glucose tolerance on an OGTT?
7.8-11mmol/L
Which drugs can cause diabetes mellitus?
Steroids
Anti-HIV drugs
Thiazides
Atypical antipsychotics
What features define metabolic syndrome?
Central obesity (BMI>30) with 2 of:
BP >130/85
Triglycerides >1.6
HDL 5.6 or diabetes
Functions of PTH?
In the kidney:
Increases Calcium reabsorption
Lowers Phosphate reabsorption
Vit D synthesis
Osteoclast activity
Vit D functions?
Acts mostly on the guts:
Calcium and phosphate reabsorption
Increases osteoclast activity
How does tertiary hyperparathyroidism arise in CKD?
Failure of the kidney to activate vit D reduces Ca2+ absorption from the gut, chronic overproduction of hyperparathyroidism leads to it’s autonomous activation (tertiary hyperparathyroidism)
Patient has high PTH, but low Ca and high PO4 and short fourth and fifth metcarpals.
What’s the syndrome?
Pseudo-hypoparathyroidism
Target organs don’t react to PTH (due to genetic insensitivity) so kidney’s don’t absorb more calcium, low Ca drives PTH secretion
In what circumstances does post-prandial hypoglycaemia typically occur?
IHX:
After bariatric surgery
In type 2 diabetics
IHx: prolonged Oral Glucose Tolerance Test
Which endocrine tumour syndrome is insulinoma associated with?
Men1
Parathyroid tumours, pancreatic endocrine tumours, pituitary prolactinoma
IHx for suspected insulinoma?
Screening: Prolonged fast leads to high insulin (unusual) and low glucose
Suppression test: IV insulin and measure C-peptide (in normal people C peptide is suppressed by exogenous insulin)
If you suspect hyperthyroidism is due to abuse of levothyroxine, what IHx can be used to confirm?
Low Serum thyroglobulin
- may be used to monitor carcinoma also
Which illnesses warrant screening for thyroid dysfunction?
Those with: AF, hyperlipidaemia DM, or type 1 DM in 1st trimester of pregnancy, or Addison's (yearly screen) DHx: amiodarone or lithium PMH: Down's, Turner's disease
IHx that is useful for detecting retrosternal goitre or ectopic thyroid tissue?
Isotope scan with 123-iodine or 99-technetium
What type of Ig antibodies occur in Grave’s disease?
IgG- TSH receptor antibodies
How do you test to differentiate a toxic multinodular goitre from a toxic adenoma in thyroid disease?
USS: cystic vs solid
+ fine needle aspiration in a multinodular goitre
Isotope scan: cold nodules (more likely to be malignant), hot nodules (more likely to be adenoma producing thyroid hormone)
If a goitre is painful what does that make it likely to be?
Subacute de Quervain’s thyroiditis
Thyrotocosis Rx?
Propranolol
Carbimazole (titrated to TFTs) or carbimazole + levothyroxine
For 12-18 months
Carbimazole SE: agranulocytosis
Main RF for eye involvement in Grave’s disease?
Smoking
Occurs in 25%-50% of those with Grave’s disease
Rx for eye disease in Graves?
Mild- symptomatic (artificial tears, sunglasses etc)
Severe- methylprednisolone if opthalmoplegia or gross oedema
Why do those with hashimoto’s get a goitre?
Lymphocytic and plasma cell infiltration of the thyroid, with autoantibodies against it
60 year old woman has high TSH and normal T3 and T4
Management?
Subclinical hypothyroidism:
Repeat in 2-4 months to check it’s persistent
Rx if symptomatic, TSH >10, thyroid autoantibodies, previous Graves
Or Rx trial for 6 months if TSH 4-10
Which types of cancer may produce ectopic PTH?
Lung
Breast
Kidney
Risk reducing Rx for patients with MEN-2 and test to determine if someone is applicable?
Test for ret-oncogene before age 3
Do a thyroidectomy (as 100% get medullary thyroid cancer- of the parafollicular C cells making calcitonin)
What are the 3 types of thyroid cancer?
70% papillary thyroid cancer (fingerlike)
15% follicular thyroid cancer
10% medullary thyroid cancer (parafollicular C cells- calcitonin)
3 causes of primary hyperaldosteronism?
And Rx?
- Conn’s (solitary adenoma)- laparoscopic adrenalectomy + spironolactone 4 weeks pre-op
- Adrenocortical hyperplasia. Rx: aldosterone R antagonist (spironolactone or eplerenone)
- Rarely glucocorticoid-remediable aldosteronism, where ACTH controls aldosterone expression. Rx: dexamethasone
Causes of secondary aldosteronism?
Due to high renin from reduced kidney perfusion:
Renal artery stenosis
Accelerated hypertension
Diuretics
CCF or hepatic failure
Features of Bartter’s syndrome:
Leaky sodium and chloride channel in the Loop of Henle means children become hypovolaemic, hypokalaemic and alkalotic (without much K+ to swap for Na+ they rely on H+ instead)
Rx: ACEi, K+ supplements, NSAIDs (reduces renal perfusion pressure)
What type of cell forms phaeochromocytomas?
Sympathetic cells (chromaffin cells), often in the adrenal medulla
IHx for suspected phaeochromocytoma?
Plasma and 3x24 hour urines for:
Free metadrenaline + normetadrenaline
If borderline: clonidine supression test
Localising: MIBG chromaffin-seeking isotope
Rx pre-op for phaeochromocytoma?
A blocker (phenoxybenzamine) then b-blocker if tachycardic/heart disease
Surgical removal
A 30 year old woman with hypertension, low K+ that has been resistant to antihypertensives has her renin:angiotensin checked. Angiotensin is raised. What further tests are warranted?
- CT/MRI of adrenals
- Adrenal vein sampling
If no nodules, consider adrenal hyperplasia or glucocorticoid-remediable aldosteronism
Drug causes of gynaecomastia?
Digoxin Isoniazid Spironolactone Cimetidine Oestrogen
CIs to phosphodiesterase 5? (Sildenafil)
CVS: unstable angina, concurrent nitrate use
MI 3 months ago, stroke 6 months ago
High BP, arrhythmia
Retina degeneration, renal or liver failure
Low FSH + LH, lack of smell and colour blind = which syndrome?
Kallman’s Syndrome:
Isolated lack of GnRH from the hypothalamus = secondary hypogonadism
NB lack of smell and colour blindness do not necessarily occur
Rx of male hypogonadism?
Rx is for symptoms and to prevent osteoporosis:
Testosterone enanthate IM every 3 weeks
2 hormones of the posterior pituitary?
ADH
GH
Rx for short stature in childhood?
Somatotropin (synthetic GH)
Child’s growth has dramatically halted in the last few months and they’ve been complaining of headache, thirst and visual changes. Most likely tumour cause?
Craniopharyngioma > hypopituitarism
Lack of ADH- thirst and frequency, lack of GH- short stature
IHx for acromegaly?
If serum GH >0.4 and IGF-1 is raised
Oral glucose tolerance test (GH should normally reduce with higher glucose levels)
False +ve: anorexia, pregnancy, DM, liver/kidney disease
What are somatotropin and somatostatin used as Rx for?
Somatotropin is synthetic GH used when there is deficiency
Somatostatin is GH-inhibiting hormone used in acromegaly (2nd line after surgery)
How is serum osmolality measured?
2 x (Na + K) + urea + glucose
Normal is 285-295mOsmol/kg
What urine to plasma osmolality ratio excludes significant diabetes insipidis?
2:1
As long as plasma osmolality is > 295
Shows urine is concentrating
IHx for diabetes insipidis
Water deprivation test (providing urine output is >3L/d)
Stage 1: 8 hours
>3% weight loss + serum osmolality >300 at any point go to stage 2
Stage 2: Desmopressin (if concentrates = cranial DI)
How is primary polydipsia differentiated with diabetes insipidis on water deprivation tests?
Primary polydipsia- urine concentrates but less than normal
DI- cranial or nephrogenic, urine doesn’t concentrate > 600
What are the two main types of hypoglycaemia and the tests for them?
- Check drugs (diabetes, quinine, malnourished)
- Post-prandial (big influx of carbs causes large insulin release)- mixed meal test
Fasting (more serious)- 72 hour fast
Check urine sulphonylurea for C-peptide (if taking artificial insulin it won’t have C-peptide)
Which familial syndrome might be associated with insulinoma?
Men1- pancreas, parathyroid, pituitary
Medical treatment of insulinoma?
Diazoxide
Hyperpolarises islet cells (acting the opposite way to sulphonylurea)
Or Octreotide (somatostatin blocks pancreatic hormone production)
On which diabetes drug can you get a euglycaemic DKA?
Ie normal BMs
SGLT2s (dapagliflozin) makes you pee out glucose
A patient has a high blood glucose, 1 unit of insulin will roughly reduce blood glucose by how many?
3
How do you calculate serum osmolarity?
2 (sodium + potassium) + urea + glucose
Patient has low sodium, what is the first step to find a diagnosis?
Check plasma osmolality:
Isotonic- lipids or proteins are masking true value so Na is not really low. Check on ABG machine instead.
Hypertonic- if given mannitol, high glucose/urea causes blood dilution
Hypotonic- what you expect with low Na, check fluid status next
Low Na and hypovolaemic, causes?
Burns
Vomiting
Diuretics
Sepsis- 3rd space losses leads to intravascular depletion so increase ADH, more dilute sodium
Low Na and euvolaemic, causes?
SIADH- more water kept than sodium
Psychogenic polydipsia
Addison’s
Beer Potomania- per litre of urine need enough solute/salts
Low Na and hypervolaemic, causes?
Failures
What is the difference between osmolality and tonicity?
Osmolality is an absolute concentration
Tonicity is a relative concentration that is more useful clinically, ie how is the RBC size affected by the concentration of fluid
Per day, if someone has high sodium how much should you try and reduce the concentration?
6mmol/L change of Na per day
Otherwise demyelination may occur up to 6 days later
Which two hormones if missing, means patient’s can’t pee out free water into urine so sodium drops?
Thyroid and cortisol (ie addison’s)
Mimics SIADH (ADH = like a bath plug)
What two things have to be checked before diagnosing SIADH?
Low sodium, hypotonic serum, euvolaemic
ADH is like a plug in a bath with the tap running
- If they are on diuretics
- Cortisol or thyroid hormone levels
Causes of SIADH?
Like putting a plug in the bath when the tap is running
Post-op Hypovolaemia- bleeding, dehydration Drugs- opiates, SSRIs, CNS drugs, PPIs Pulmonary disease- neoplastic (small cell lung cancer) or pneumonia CNS disease Tumours
What are the two main types of hypoglycaemia and the tests for them?
- Check drugs (diabetes, quinine, malnourished)
- Post-prandial (big influx of carbs causes large insulin release)- mixed meal test
Fasting (more serious)- 72 hour fast
Check urine sulphonylurea for C-peptide (if taking artificial insulin it won’t have C-peptide)
Which familial syndrome might be associated with insulinoma?
Men1- pancreas, parathyroid, pituitary
Medical treatment of insulinoma?
Diazoxide
Hyperpolarises islet cells (acting the opposite way to sulphonylurea)
Or Octreotide (somatostatin blocks pancreatic hormone production)
On which diabetes drug can you get a euglycaemic DKA?
Ie normal BMs
SGLT2s (dapagliflozin) makes you pee out glucose
A patient has a high blood glucose, 1 unit of insulin will roughly reduce blood glucose by how many?
3
How do you calculate serum osmolarity?
2 (sodium + potassium) + urea + glucose
Patient has low sodium, what is the first step to find a diagnosis?
Check plasma osmolality:
Isotonic- lipids or proteins are masking true value so Na is not really low. Check on ABG machine instead.
Hypertonic- if given mannitol, high glucose/urea causes blood dilution
Hypotonic- what you expect with low Na, check fluid status next
Low Na and hypovolaemic, causes?
Burns
Vomiting
Diuretics
Sepsis- 3rd space losses leads to intravascular depletion so increase ADH, more dilute sodium
Low Na and euvolaemic, causes?
SIADH- more water kept than sodium
Psychogenic polydipsia
Addison’s
Beer Potomania- per litre of urine need enough solute/salts
Low Na and hypervolaemic, causes?
Failures
What is the difference between osmolality and tonicity?
Osmolality is an absolute concentration
Tonicity is a relative concentration that is more useful clinically, ie how is the RBC size affected by the concentration of fluid
Per day, if someone has high sodium how much should you try and reduce the concentration?
6mmol/L change of Na per day
Otherwise demyelination may occur up to 6 days later
Which two hormones if missing, means patient’s can’t pee out free water into urine so sodium drops?
Thyroid and cortisol (ie addison’s)
Mimics SIADH (ADH = like a bath plug)
What two things have to be checked before diagnosing SIADH?
Low sodium, hypotonic serum, euvolaemic
ADH is like a plug in a bath with the tap running
- If they are on diuretics
- Cortisol or thyroid hormone levels
Causes of SIADH?
Like putting a plug in the bath when the tap is running
Post-op Hypovolaemia- bleeding, dehydration Drugs- opiates, SSRIs, CNS drugs, PPIs Pulmonary disease- neoplastic (small cell lung cancer) or pneumonia CNS disease Tumours
What are the two types of auto-antibodies in thyroid disease identified by fluorescence?
Anti-Thyroid Peroxidase (TPO): against the membranes
Anti-Thyroglobulin: against the colloid in the middle of the circles.
If a patient is dehydrated, what pattern of urea and creatinine would suggest this?
High urea compared to creatinine.
Urea is reabsorbed to try to rebalance electrolytes whereas creatinine is not
What changes on bloods can indicate dehydration?
High urea, compared to creatinine
High albumin
High haematocrit (RBCs vs blood volume)
Why is the anion gap needed?
Many lab tests do not measure every cation (+ve charge) or anion (-ve) in the blood, but plasma is neutral.
The unmeasured ions tend to be anions.
If acid has been added that is not measured on lab tests, ie ketoacids or lactate it will be buffered by HCO3, lowering concentration of this and increasing the anion gap
How would bone mets look different to primary hyperparathyroidism on bloods?
Both cause high calcium
In mets the potassium would be normal or raised (as PO4 gets released from bone)
In primary hyperPTH potassium would be low or normal as PTH inhibits PO4 absorption from kidney (but note vit D increases phosphate absorption from intestine)
Why is Po4 high in hypoparathyroidism?
Normally PTH prevents P04 reabsorption from the kidney, so if levels are low P04 will rise.
Which two blood findings suggest excess alcohol intake?
Raised MCV and y-GT
What happens to plasma and urine osmolality in diabetes insipidis?
ADH is like the bath plug, in this condition there is no ADH/bath plug but the taps are running so:
Salt gets deposited in the bath (high plasma osmolality)
Water runs down the plug hole (low urine osmolality)
What is 5% dextrose useful for, hydration or fluid resuscitation?
Hydration- the sugar in the fluid gets quickly metabolised by the liver leaving pure water, the water will equilibrate into cells so little volume is left in the intravascular compartment to upkeep BP
What volume of saline is appropriate for fluid resuscitation in the elderly or those with heart failure?
250mL
In which scenarios should you consider increasing K+ replacement above the normal maintenance?
GI losses are rich in K+ so if someone has diarrhoea, vomiting or an NG tube
Which other pathway does angiotensin converting enzyme input into?
It metabolises bradykinin, so ACEi lead to raised levels of bradykinin and might explain why some people get a cough
What effect does ANP and BNP have on sodium in the kidney?
They reduce Na+ absorption from the DCT and inhibit renin (which means there’s less AT-II and thus aldosterone and therefore salt uptake)
Name 4 causes of a metabolic acidosis with an increased anion gap:
More unmeasured anions= negatively charged (the acid donates it’s H+ to HC03- buffer, leaving behind it’s conjugate base)
- Lactic acid
- Urate (renal failure)
- Keto acids (diabetes or alcohol)
- Drugs (salicylates, methanol, metformin)
Metabolic acidosis, anion gap 16
Normal anion gap:
If acidosis is caused by a loss of bicarbonate then chloride replaces it.
GI losses- diarrhoea, pancreatic fistula
Renal dysfunction- renal tubular acidosis type 1 or 2 (HCO3 loss)
Renal hypoaldosterone- Addison’s disease (Na absorption by aldosterone in DCT leads to H+ secretion), drugs (ACEi, diuretics)
3 causes of metabolic alkalosis
Loss of acid:
GI- vomiting
Renal- K+ depletion from diuretics
Burns- unclear why
In which conditions would respiratory acidosis prompt you to get an urgent ITU review?
CO2 is high, so it is a sign of exhaustion in
Asthma
Pneumonia
Pulmonary oedema
How can tonicity/osmolality help to determine whether a low sodium is a true result?
Osmolality = 2(Na+ + K+) + urea + glucose
Isotonic- pseudohyponatraemia from high lipids or proteins
Hypertonic- high glucose pushing sodium out of vessels
Hypotonic- consistent with low Na+
If a patient is found to have a K+ of 6.7, what symptoms should you ask about?
Chest pain
Palpitations
Light headedness
Weakness
Worrying ECG changes in hyperkalaemia?
Flattened P waves
Broad bizarre QRS
Upsweeping ST
Tall tented T’s
Also VF
Causes of hyperkalaemia?
Drugs: ACEi, suxamethonium (nAChR inhibitor anaesthetics), K+ sparing diuretics
Kidney: renal failure, metabolic acidosis, Addison’s
Cell destruction: Rhabdomyolysis, massive blood transfusion, burns
Digoxin toxicity is made worse by which metabolite abnormality?
Hypokalaemia
(As digoxin inhibits myocardial Na/K/ATPase, increasing Na in cell and preventing Na/Ca exchanger)
Na/K/ATPase pumps Na out of cell, Na/Ca exchanger allows sodium in
ECG changes that are a worry in cases of hypokalaemia?
Everything is down or sluggish
Small/inverted T waves
Long PR
Depressed ST
Only up is that U wave!
Which metabolic imbalance is hard to correct until Mg levels have normalised?
Hypokalaemia
Endocrine causes of hypokalaemia?
Conns (aldosteronism- high BP)
Cushing’s
Which food can cause hypokalaemia?
Liquorice
Management of asymptomatic patient with K+ of 2.6mmol, no ECG changes?
If mild (>2.5, asymptomatic) Oral K+ supplements like Sando-K
What is the fastest that K+ can be given if severe hypokalaemia (<2.5mmol ± dangerous symptoms)?
No more than 20mmol/hour
Not more concentrated than 40mmol per litre
