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)
What will cause hypokalaemia with acidosis?
Hypokalaemia with acidosis
diarrhoea
renal tubular acidosis
acetazolamide
partially treated diabetic ketoacidosis
why does acetazolamide cause hypokalaemia with acidosis?
Acetazolamide is a carbonic anhydrase inhibitor that is used to treat conditions such as glaucoma, altitude sickness and certain types of oedema. It works by reducing the reabsorption of bicarbonate in the proximal tubule of the kidney, leading to metabolic acidosis. The body compensates for this acidosis by increasing potassium excretion in an attempt to retain more hydrogen ions, which can result in hypokalaemia.
what are clinical features of Bartter’s syndrome?
short stature, polydipsia, polyuria, and nocturia
patients are typically normotensive in the setting of elevated renin and aldosterone.
How do you distinguish between Bartter’s syndrome and Gitelman’s ?
Hypercalciuria in Bartter’s
What is considered acute vs chronic hyponatraemia?
acute: develops over a period of < 48 hours
chronic: develops over a period > 48 hours
how is hyponatraemia classified on severity?
mild: 130-134 mmol/L
moderate: 120-129 mmol/L
severe: < 120 mmol/L
what are the symptoms of hyponatraemia?
patients with mild hyponatraemia may be symptomatic
early symptoms may include: headache, lethargy, nausea, vomiting, dizziness, confusion, and muscle cramps
late symptoms may include: seizures, coma, and respiratory arrest
what are the causes of hyponatraemia?
hypovolemic hyponatraemia/clinically dehydrated: diuretic stage of renal failure, diuretics, Addisonian crisis
euvolemic hyponatraemia: SIADH
hypervolaemic hyponatraemia: heart failure, liver failure, nephrotic syndrome
What are the initial steps before commencing treatment for hyponatraemia ?
exclude a spurious result (e.g. blood taken from a drip arm)
review medications that may cause hyponatraemia
How is acute hyponatraemia with severe symptoms managed?
Patients with acute, severe (<120 mmol/L) or symptomatic hyponatraemia require close monitoring, preferably in an HDU or above setting.
Hypertonic saline (typically 3% NaCl) is used to correct the sodium level more quickly than would be done in patients with chronic hyponatraemia.
How is hypovolemic hyponatraemia managed?
normal, i.e. isotonic, saline (0.9% NaCl)
this may sometimes be given as a trial
if the serum sodium rises this supports a diagnosis of hypovolemic hyponatraemia
if the serum sodium falls an alternative diagnosis such as SIADH is likely
How is euvolemic hyponatraemia managed?
fluid restrict to 500-1000 mL/day
consider medications:
demeclocycline
vaptans (see below)
how is hypervolemic hyponatraemia managed?
fluid restrict to 500-1000 mL/day
consider loop diuretics
consider vaptans
what are vaptans?
Vasopressin/ADH receptor antagonists (vaptans):
these act primarily on V2 receptors - antagonism of V2 receptors results in selective water diuresis, sparing the electrolytes
They should be avoided in patients who have hypovolemic hyponatremia
Vasopression/ADH receptor antagonists can stimulate the thirst receptors leading to the desire to drink free water. They can be hepatotoxic in patients with underlying liver disease.
what are the complications of hyponatraemia treatment?
Osmotic demyelination syndrome (central pontine myelinolysis)
can occur due to over-correction of severe hyponatremia
pathophysiology:
thought to develop secondary to astrocyte (and possibly oligodendrocyte) apoptosis
astrocytes and oligodendrocytes (cells of the glial syncytium) are crucial for normal myelination
chronic hyponatraemia → loss of osmotically active organic osmolytes (such as myoinositol, glutamate, glutamine) from astrocytes. These provide protection against cerebral oedema
organic osmolytes cannot be replaced quickly enough when the brain volume begins to shrink in response to the correction of hyponatraemia
the dehydrated astrocytes and oligodendrocytes undergo apoptosis or other forms of injury → demyelination
to avoid this, Na+ levels are only raised by 4 to 6 mmol/l in a 24-hour period
symptoms usually occur after 2 days and are usually irreversible: dysarthria, dysphagia, paraparesis or quadriparesis, seizures, confusion, and coma
patients are awake but are unable to move or verbally communicate, also called ‘Locked-in syndrome’
What is Klinefelter’s syndrome and what are the features of it?
Klinefelter’s syndrome is associated with karyotype 47, XXY.
Features
often taller than average
lack of secondary sexual characteristics
small, firm testes
infertile
gynaecomastia - increased incidence of breast cancer
elevated gonadotrophin levels but low testosterone
What would you see in the hormones of a patients with Klinefelter’s syndrome?
hypergonadotrophic hypogonadism, in which FSH and LH concentrations are elevated and serum testosterone concentrations are low. Gonadal dysgenesis secondary to Klinefelter’s syndrome impairs spermatogenesis, with semen analysis commonly showing azoospermia.
Why is thyroid storm?
Thyroid storm is a rare but life-threatening complication of thyrotoxicosis. It is typically seen in patients with established thyrotoxicosis and is rarely seen as the presenting feature. Iatrogenic thyroxine excess does not usually result in thyroid storm.
What may precipitate a thyroid storm?
thyroid or non-thyroidal surgery
trauma
infection
acute iodine load e.g. CT contrast media
what are the clinical features of thyroid storm?
fever > 38.5ºC
tachycardia
confusion and agitation
nausea and vomiting
hypertension
heart failure
abnormal liver function test - jaundice may be seen clinically
How do you manage a thyroid storm?
symptomatic treatment e.g. paracetamol
treatment of underlying precipitating event
beta-blockers: typically IV propranolol to counteract the peripheral effects of thyroid hormone
anti-thyroid drugs: e.g. methimazole or propylthiouracil and Lugol’s iodine to inhibit further function of thyroid hormone synthesis
dexamethasone - e.g. 4mg IV qds - blocks the conversion of T4 to T3
what is subacute thyroiditis?
Subacute thyroiditis (also known as De Quervain’s thyroiditis and subacute granulomatous thyroiditis) is thought to occur following viral infection and typically presents with hyperthyroidism.
What are the features of subacute thyroiditis?
There are typically 4 phases;
phase 1 (lasts 3-6 weeks): hyperthyroidism, painful goitre, raised ESR
phase 2 (1-3 weeks): euthyroid
phase 3 (weeks - months): hypothyroidism
phase 4: thyroid structure and function goes back to normal
what are the investigations of subacute thyroiditis?
TFTs
thyroid scintigraphy: globally reduced uptake of iodine-131
How is subacute thyroiditis managed?
usually self-limiting - most patients do not require treatment
thyroid pain may respond to aspirin or other NSAIDs
in more severe cases steroids are used, particularly if hypothyroidism develops
What is remnant hyperlipidaemia ?
rare cause of mixed hyperlipidaemia (raised cholesterol and triglyceride levels)
also known as Fredrickson type III hyperlipidaemia, broad-beta disease and dysbetalipoproteinaemia
associated with apo-e2 homozygosity
high incidence of ischaemic heart disease and peripheral vascular disease
thought to be caused by impaired removal of intermediate density lipoprotein from the circulation by the liver
what are the features of remnant hyperlipidaemia and how is it managed?
Features
yellow palmar creases
palmer xanthomas
tuberous xanthomas
Management
fibrates are first line treatment
What is multiple endocrine neoplasia?
Multiple endocrine neoplasia causes overgrowth or tumors on one or more endocrine glands.
what is MEN type I
3ps
Parathyroid (95%): hyperparathyroidism due to parathyroid hyperplasia
Pituitary (70%)
Pancreas (50%): e.g. insulinoma, gastrinoma (leading to recurrent peptic ulceration)
Also: adrenal and thyroid
MEN1 gene