Endocrinology Flashcards
What is the pathophysiology of DKA
There is excessive glucose but cannot be taken up by the cells due to a lack of insulin
so the body metabolises proteins and fats into ketones for energy.
Ketones then cause a metabolic acidosis due to an excessive concentration of ketone anions in the blood
How may DKA present?
Gradual drowsiness vomiting and dehydration Polyuria Polydipsia Lethargy Anorexia non-specific abdominal pain Ketotic breath Coma Deep breathing - Kussmaul breathing
What are the triggers for DKA
Infection MI Pancreatitis Chemo antipsychotics Non-compliance Wrong Insulin dose
What are the three criteria needed for diagnosis of DKA
- Acidaemia (pH<7.3)
- Hyperglycemia
- Ketonaemia
What investigations are done in suspected DKA?
Bedside: Capillary blood glucose, urine dipstick, ECG
Bloods: blood glucose, FBC, U+Es, amylase, blood culture (if signs of infection), ketones
Imaging: CXR (may be considered)
ABG - for anion gap and pH
What type of anion gap will someone with DKA have?
High anion gap
How is the anion gap calculated?
(Na + K) - (Cl + HCO3)
shows if acidosis is metabolic
When would a patient with DKA be transferred to ICU?
high blood ketones low bicarb a pH lower than 7.1 Potassium lower than 3.5 GCS <12 Sats <92 Systolic <90 Tachy or Brady Anion gap above 36
Why may potassium drop when insulin is given?
because insulin forces potassium back in the cells by increasing the sodium-potassium channel activity, therefore there is less within the blood causing hypokalaemia
When can ketonuria also occur?
After an overnight fast
Alcohol (if glucose is normal)
how is DKA managed?
if BP is low - 500ml bolus
Find out blood gases for pH, keones, glucose, bicarb, U+Es
50units of actrarapid into 49.5ml of 0.9% saline. Infuse at 0.1unit/kg/hr
Stat dose if infusion is delayed
Assess need for potassium replacement (if potassium falls below 5.5)
Catheterise
Consider NG tube if vomiting or drowsy
What should be considered once insulin is being administered
Glucose level AVOID HYPOGLYCAEMIA once glucose drops below 14, start 10% glucose at 125ml/hr Potassium level 3.5-5.5 - Add 40mmol per litre of fluid <3,5 - Seek help from HDU/ICU
What is the typical fluid deficit in DKA?
100ml/kg
What are the complications of DKA?
Cerebral oedema (if sudden CNS decline get help) - if fluid and insulin given rapidly
Aspiration Pneumonia (drowsy/unconscious and vomiting)
Hypokalaemia - if potassium not replaced once insulin is given
Hypomagnesaemia
Hypophophataemia
Thromboembolism
Why is cerebral oedema a complication of DKA?
The high glucose content of the blood causes fluid to move from ICF to ECF therefore the cells in the brain shrink. If insulin and fluid is given to a patient in DKA too rapidly it cause a rapid reversal of osmolarity and fluid moves into the cells and causes cerebral oedema,
How does a hypoglycaemia present?
Rapid onset
Autonomic - sweating. anxiety, hunger, tremor, palpitations, dizziness
Neuroglycopenic - confusion, drowsiness, visual trouble, seizures, coma
What are the causes of hypoglycaemia?
EXPLAIN
Ex ogenous drugs e.g. insulin, oral hypoglycaemics, alcohol (binge without food) and aspirin poisoning
P ituitary insufficiency
L iver failure
A ddisons disease
I slet cell tumours
N on pancreatic neoplasms, e.g. fibrosarcomas
How is hypoglycaemia investigated?
BM
Bloods: glucose, FBC, U+Es, cortisol, insulin, c-peptide, plasma ketones
Drug history
What are the causes of hypoglycaemic hyperinsulinaemia?
Sulfonylureas, insulinoma, insulin injection (no detectable C peptide - only released with endogenous insulin)
If the insulin is low and the plasma ketones are increased what are the differentials
Addisons disease
Pituitary insufficiency
Alcohol
How is a hypoglycaemic episode treated?
Oral sugar and long acting starch
If cannot swallow - 25-50ml 50% glucose with 0.9%saline flush
Glucagon 1mg IM if not IV access (repeat after 20mins and follow with oral carb)
What is Cushings Syndrome
Chronic state caused by excess glucocorticoids and loss of normal feedback mechanisms of HPA axis
exogenous - oral steroids
endogenous - increased secretion of cortisol (very rare)
How is cortisol excreted
in the urine
What are the causes of Cushings DISEASE?
ACTH secreting pituitary adenoma causing bilateral adrenal hyperplasia
A low dose dexamethasone test leads to no change in cortisol but 8mg may be enough to halve morning cortisol
What are some other causes of ACTH dependent causes of Cushing’s syndrome
Ectopic ACTH production
- small cell lung cancers (may also secrete ADH)
- Carcinoid tumours
Ectopic CRF production - medullary thyroid cancer and prostate cancer
What are the specific features of ectopic ACTH production
Increased ACTH production causes hyperpigmentation
Hypokalaemia
Metabolic alkalosis - increased mineralocorticoid activity - more odium retained and potassium excreted
Weight loss
Hyperglycaemia
Classical features of Cushing’s not usually present
What are some ACTH independent causes (decreased ACTH due to negative feedback)
Adrenal adenoma/cancer - tumour is autonomous so dexamethasone suppression will have no effect
Adrenal nodular hyperplasia - no dexamethasone suppression
Iatrogenic - steroid use (common)
How does Cushing’s syndrome present
Weight gain and central obesity
Moon face
buffalo neck hump
Acne
Mood change - depression, lethargy, irritability and psychosis
Proximal weakness
gonadal dysfunction - irregular menses, hirutisim, erectile dysfunction
MSK: recurrent achilles tendon rupture, osteoporosis
Skin: bruises, purple abdominal striae, poor healing
Infection-prone
What tests can be done for suspected cushings syndrome
Random cortisol levels can be misleading due to time of day taken, stress and illness
24hr urinary cortisol secretion - increased cortisol
Overnight dexamethasone suppression test 1mg PO at midnight and serum cortisol done at 8am - no suppression Cushing’s syndrome
In Cushing’s disease there is 50% suppression in high dose (8mg) dexamethsone suppression
No suppression at high doses in ectopic disease
If the above normal
- 48hr dexamethasone suppression test - give 0.5mg PO 6hrly for 2 days - measure cortisol at 0 and 48hrs
How is Cushing’s syndrome treated
Depends on cause
Iatrogenic: Stop steroids if possible, lower dose slowly
Cushing’s disease: selective removal of pituitary adenoma or bilateral adrenalectomy if source undetectable
Adrenal adenoma or carcinoma: adrenalectomy rarely cures cancer, radiotherapy and drugs follow if carcinoma
Ectopic ACTH: Surgery if tuour is located and hasnt spread
What are the complications of an adrenalectomy
Nelsons syndrome - increase in skin pigmentation due to increase in ACTH from an enlarging pituitary tumour
Adrenals removed –> no negative feedback
Responds to pituitary radiation
Which drugs can be given to lower cortisol levels before surgery for Cushing’s syndrome
Metyrapone (blocks cortisol synthesis)
Ketoconazole (inhibits cytochrome p450 enzyme) and Fluconazole
What is Addison’s disease
Adrenal insufficiency - adrenal glands are unable to make enough cortisol for the body due to destruction of the adrenal cortex
Both glucocorticoid and mineralocorticoid deficiency
What are some of the causes of Addison’s disease
Autoimmunity
TB - most common worldwide
Adrenal mets - from breast, lung and renal cell carcinoma
Lymphoma
Opportunistic infections in HIV - CMV, mycobacterium avium
Adrenal haemorrhage - Waterhour-Friderichsen syndrome, SLE, Antiphospholipid syndrome
How would Addisons disease present
Very vague Often diagnosed late - lean -tanned - tired - weakness - anorexia - Dizzy, faints, postural hypotension - flu like myalgias/arthralgia GI: nausea/vomiting, abdo pain, diarrhoea/constipation Think of Addisons in unexplained abdominal pain or vomiting Skin: pigmented palmar creases/buccal mucosa, vitiligo
What would tests show in addisons disease
Low sodium High potassium - due to decrease mineralocorticoid hypoglycaemia - due to reduced cortisol Also - uraemia - increased calcium - eosinophilia - anaemia
Short Synacthen test: Do plasma cortisol before and 30mins after
Addisons excluded if 30mins cortisol is >550nmol/L
Plasma renin:aldosterone - asses mineralocorticoid status
21-hydroylase adrenal autoantibodies - positive in autoimmune disease >80%
Imaging
AXR/CXR - previous TB, calcification of adrenal glands
In which situations may cortisol levels be falsely positive
Pregnancy and COCP - due to increase cortisol-binding globulin
How is Addison’s disease treated
Replace steroids
- 15-25mg hydrocortisone daily in 2-3 doses
- Avoid giving late - may cause insomnia
- mineralocorticoids to stop postural hypotension and electrolytes
What other management is involved in Addison’s disease
Steroid Card
medic ID bracelet
Make doctors/surgeons/dentists aware if having treatment
Steroids need to be doubled in febrile illness, injury or stress
Give IM hydrocortisone and how to inject if vomiting prevents oral intake - seek medical help and admit for IV fluids if dehydrated
What is secondary adrenal insufficiency caused by
Iatrogenic - long term steroid use leading to suppression of HPA axis
only becomes apparent on withdrawal of steroids
What is primary hyperaldosteronism
excess production of aldosterone independent of the RAAS
Causing increased sodium and water retention and decreased renin release
How does primary hyperaldosteronism present
Often asymptomatic Sign of hypokalaemia - weakness - cramps - paraesthesiae - polyuria - polydipsia - BP increased - not always
What are the causes of Primary hyperaldosteronism
Solitary aldosterone producing adenoma - Conn’s syndrome
Bilateral adrencorticol hyperplasia
How would you investigate a patient with suspected primary hyperaldosteronism
Bloods
- FBC
- U+Es - high sodium low potassium however not all pts have low K
- Renin - low
- Aldosterone - high
When should Conn’s syndrome be suspected
Refractory hypertension e.g. despite 3 hypertensive drugs
Hypertension with associated hypokalaemi
Hypertension occurring before 40yrs of age esp in women
How is Conn’s syndrome treated
Laparoscopic adrenalectomy and Spironolactone for 4 weeks pre op to control BP and K+
What causes secondary hyperaldosteronism
Due to high renin from reduced renal perfusion e.g. in renal artery stenosis, accelerated hypertension, diuretics, CCF or hepatic failure
