Endocrinology Flashcards
When might metformin be used in T1DM?
NICE recommend the use of metformin for patients with type 1 diabetes who are overweight with a BMI of 25kg/m² or over
What is the target HbA1c in T1DM
below 48mmol/mol
it should be checked every 3-6 months
what are sick day rules in diabetes?
- never stop insulin, continue taking insulin if they are not eating as usual they may just need to adjust the levels
- monitor CBGs more regularly
- stay hyrdrated and try to eat
- check ketones
What are the causes of hypocalcaemia?
vitamin D deficiency (osteomalacia)
chronic kidney disease
hypoparathyroidism (e.g. post thyroid/parathyroid surgery)
pseudohypoparathyroidism (target cells insensitive to PTH)
rhabdomyolysis (initial stages)
magnesium deficiency (due to end organ PTH resistance)
massive blood transfusion
acute pancreatitis
How does hypoparathyroidism cause hypocalcaemia?
.PTH plays a crucial role in regulating blood calcium levels by increasing renal calcium reabsorption, promoting conversion of vitamin D into its active form which enhances intestinal absorption of calcium and mobilising calcium from bone. Therefore, deficiency of PTH leads to hypocalcaemia.
why does pseudohypoparathyroidism lead to hypocalcaemia?
This condition involves resistance to the action of PTH often due to genetic mutations affecting signalling pathways for PTH receptor. Despite normal or high levels of PTH, its effect on target organs is blunted leading to decreased release of calcium into the bloodstream resulting in hypocalcaemia.
why does acute pancreatitis lead to hypocalcaemia?
In acute pancreatitis, there can be saponification where released fatty acids bind with calcium ions forming insoluble soaps leading to fall in serum calcium levels. Moreover, inflammation associated with pancreatitis can lead to capillary leak syndrome causing loss of protein-bound calcium into extravascular space further contributing to hypocalcaemia.
How is hypocalcaemia managed?
severe hypocalcaemia (e.g. carpopedal spasm, tetany, seizures or prolonged QT interval) requires IV calcium replacement
the preferred method is with intravenous calcium gluconate, 10ml of 10% solution over 10 minutes
intravenous calcium chloride is more likely to cause local irritation
ECG monitoring is recommended
further management depends on the underlying cause
What is Bartter’s syndrome?
an inherited disorder (AR)
it causes severe hypokalaemia due to defective chloride absorbtion at the Na+K+2CL- cotransporter in the ascending loop of hence
It causes severe hypokalaemia
Loop diuretics work by inhibiting NKCC2 - think of Bartter’s syndrome as like taking large doses of furosemide
What can cause hypokalaemia with hypertension?
Cushing’s syndrome
Conn’s syndrome (primary hyperaldosteronism)
Liddle’s syndrome
11-beta hydroxylase deficiency*
What can cause hypokalaemia without hypertension?
diuretics
GI loss (e.g. Diarrhoea, vomiting)
renal tubular acidosis (type 1 and 2**)
Bartter’s syndrome
Gitelman syndrome
What is first line treatment for patients with PCOS trying to conceive ?
Clomifene
however There is an ongoing debate as to whether metformin, clomifene or a combination should be used to stimulate ovulation
metformin is also used, either combined with clomifene or alone, particularly in patients who are obese
How can hirsutism and acne be managed in PCOS?
a COC pill may be used help manage hirsutism. Possible options include a third generation COC which has fewer androgenic effects or co-cyprindiol which has an anti-androgen action. Both of these types of COC may carry an increased risk of venous thromboembolism
if doesn’t respond to COC then topical eflornithine may be tried
spironolactone, flutamide and finasteride may be used under specialist supervision
what are secondary causes of hyperlipideamia that cause predominantly hypertriglyceridaemia ?
diabetes mellitus (types 1 and 2)
obesity
alcohol
chronic renal failure
drugs: thiazides, non-selective beta-blockers, unopposed oestrogen
liver disease
what are secondary causes of hyperlipideamia that cause predominantly hypercholesterolaemia ?
nephrotic syndrome
cholestasis
hypothyroidism
What is the mechanism of action of Sulfonyureas?
Sulfonyureas increase stimulation of insulin secretion by pancreatic B-cells and decrease hepatic clearance of insulin
What is the mechanism of action of SGLT-2 inhibitors?
e.g. dapagliflozin
Inhibits sodium-glucose co-transporter-2 in the proximal convoluted tubule of the nephron to stop glucose reabsorbtion, meaning it excrete in the urine
What is the mechanism of action of DPP-4 inhibitors?
sitagliptin, vildagliptin
Inhibits the principal enzyme that breaks down GLP-1 an incretin hormone that increases insulin secretion and suppresses glucagon secretion
What is the mechanism of action of metformin?
Reduces hepatic gluconeogenesis, increases peripheral glucose uptake and also reduces the absorption of carbohydrate in the gut
What is the mechanism of action of thiazolidinediones?
pioglitazone
upregulation of transcription of insulin responsive genes, leading to an increase in glucose transporters and insulin receptors at the surface of the cell
what are the adverse effects of sulfonylureas?
Common adverse effects
hypoglycaemic episodes (more common with long-acting preparations such as chlorpropamide)
weight gain
Rarer adverse effects
hyponatraemia secondary to syndrome of inappropriate ADH secretion
bone marrow suppression
hepatotoxicity (typically cholestatic)
peripheral neuropathy
Sulfonylureas should be avoided in breastfeeding and pregnancy.
Why does digoxin cause gynaecomastia?
Due to the similarity between the structure of digoxin and oestrogen, the drug is believed to act direct at oestrogen receptors, resulting in the hormone imbalance responsible for gynaecomastia.
What are causes of gynaecomastia?
Causes of gynaecomastia
physiological: normal in puberty
syndromes with androgen deficiency: Kallman’s, Klinefelter’s
testicular failure: e.g. mumps
liver disease
testicular cancer e.g. seminoma secreting hCG
ectopic tumour secretion
hyperthyroidism
haemodialysis
drugs: see below
Drug causes of gynaecomastia
spironolactone (most common drug cause)
cimetidine
digoxin
cannabis
finasteride
GnRH agonists e.g. goserelin, buserelin
oestrogens, anabolic steroids
Very rare drug causes of gynaecomastia
tricyclics
isoniazid
calcium channel blockers
heroin
busulfan
methyldopa
What will cause hypokalaemia with alkalosis?
Hypokalaemia with alkalosis
vomiting
thiazide and loop diuretics
Cushing’s syndrome
Conn’s syndrome (primary hyperaldosteronism)