Endocrinology Flashcards
what is the step wise management of obesity
conservative: diet & exercise
medical
surgical
what is orlistat & its side effects
pancreatic lipase inhibitor used in the medical treatment of obesity
loose stool/diarrhoea
flatulence
faecal urgency/incontinence
what is the criteria for orlistat to be prescribed
BMI of 28 kg/m^2 or more with associated risk factors, or
BMI of 30 kg/m^2 or more
continued weight loss e.g. 5% at 3 months
orlistat is normally used for < 1 year
contraindications for orlistat
critical medications e.g. COCP, anti-epileptics
increased transit time through the gut caused by orlistat could reduce absorption & efficacy of vital medications
what should patients on long term steroids do to their dose when have a concurrent illness?
double hydrocortisone dose
side effects of glucocorticoids
endocrine: impaired glucose regulation, increased appetite/weight gain, hirsutism
cushing’s syndrome
MSK: osteoporosis, proximal myopathy, avascular necrosis of femoral head
immunosuppression: TB reactivation
psychiatric: insomnia, mania, depression, psychosis
GI: peptic ulceration, pancreatitis
ophthalmic: glaucoma, cataracts
suppression of growth in children
intracranial hypertension
neutrophilia
side effects of mineralocorticoids
hypertension
fluid retention
what is an Addisonian crisis/adrenal crisis
an acute presentation of severe Addison’s, where the absence of steroids leads to a life threatening presentation
can be first presentation of Addison’s
triggered by trauma, infection, or other acute illness
can happen if someone stops steroids abruptly
presentation of adrenal crisis
hypotension
hyponatremia, hyperkalaemia
hypoglycaemia
reduced consciousness
patients can be very unwell
management of adrenal crisis
Intensive monitoring if unwell
Parenteral steroids (i.e. IV hydrocortisone 100mg stat then 100mg every 6 hours)
IV fluid resuscitation
Correct hypoglycaemia
Careful monitoring of electrolytes and fluid balance
unique features of Grave’s disease
exophthalmos
ophthalmoplegia
pretibial myxoedema
thyroid acropachy:
clubbing
soft tissue swelling of hands and feet
periosteal new bone formation
** all due to TSH receptor antibodies
what is pretibial myxoedema
dermatological condition
deposits of mucin under the skin of the anterior aspect of the leg
gives a discoloured, waxy, oedematous appearance to the skin over the area
pathophysiology of hyperaldosteronism
in the afferent arterioles of the kidneys there are juxtaglomerular cells which detect BP in the vessels
if low, they secrete renin
Liver in turn release a protein called angiotensinogen, which renin converts to angiotensin I
Angiotensin I –> 2 in the lungs by ACE
Angiotensin II stimulates release of aldosterone from the adrenal glands
results in:
Increase sodium reabsorption from the distal tubule
Increase potassium secretion from the distal tubule
Increase hydrogen secretion from the collecting ducts
what type of steroid is aldosterone
mineralocorticoid
features of primary hyperaldosteronism
hypertension
hypokalemia
***muscle weakness
alkalosis
causes of primary hyperaldosteronism
adrenal glands producing too much aldosterone, resulting in low renin
bilateral adrenal hyperplasia**
adrenal adenoma
Familial hyperaldosteronism type 1 and type 2
causes of secondary hyperaldosteronism
excessive renin being produced which simultaneously produces more aldosterone
occurs when BP in the kidneys is proportionately lower to the BP in the rest of the body
renal artery stenosis
renal artery obstruction
HF
investigations for hyperaldosteronism
aldosterone/renin ratio
BP, U&Es, blood gas
Then:
high resolution CT abdomen** / MRI to look for an adrenal tumour
Renal doppler ultrasound, CT angiogram or MRA for renal artery stenosis or obstruction
management of hyperaldosteronism
adenoma:surgery
hyperplasia: aldosterone antagonists e.g. spironolactone, Eplerenone
percutaneous renal artery angioplasty via the femoral artery to treat in renal artery stenosis
drug causes of gynaecomastia
spironolactone***
cimetidine
digoxin
cannabis
finasteride
GnRH agonists e.g. goserelin, buserelin
oestrogens, anabolic steroids
pathophysiology of androgen insensitivity syndrome
x linked recessive condition
cells unable to respond to androgens due to a lack of receptor
Patients are genetically male with XY sex chromosome
However, due to no response to testosterone & excess androgens being converted to estrogen = female phenotype externally
testes in the abdomen or inguinal canal, and absence of a uterus, upper vagina, cervix, fallopian tubes and ovaries. The female internal organs do not develop because the testes produce anti-Müllerian hormone, which prevents males from developing an upper vagina, uterus, cervix and fallopian tubes
insensitivity to androgens also results in a lack of pubic hair, facial hair and male type muscle development. Patients tend to be slightly taller than the female average.
presentation of androgen insensitivity syndrome
often presents in infancy with inguinal hernias containing testes
or at puberty with primary amennorhoea
Raised LH
Normal or raised FSH
Normal or raised testosterone levels (for a male)
Raised oestrogen levels (for a male)
what is there an increased risk of in androgen insensitivity syndrome
testicular cancer
requires a bilateral orchidectomy
management of androgen insensitivity syndrome
Bilateral orchidectomy (removal of the testes) to avoid testicular tumours
Oestrogen therapy
Vaginal dilators or vaginal surgery can be used to create an adequate vaginal length
side effects of SGLT2-I
urinary & genital infections
normoglycaemic ketoacidosis
increased risk of lower limb amputation
** patients often lose weight which can be beneficial in T2DM
how to monitor & adapt levothyroxine dose in pregnancy
increase dose by up to 50% as early as 4-6 weeks
serum TSH measured in each trimester and 6-8 weeks post partum
what is transient gestational hyperthyroidism
activation of the TSH receptor by HCG may also occur
HCG levels will fall in the second and third trimester
management of hyperthyroidism in pregnancy
propylthiouracil in the 1st trimester (carbimazole associated with congenital abnormalities)
at the start of the 2nd trimester, should be transferred back to carbimazole
maternal free thyroxine levels should be kept in the upper third of the normal reference range to avoid fetal hypothyroidism
thyrotrophin receptor stimulating antibodies should be checked at 30-36 weeks gestation - helps to determine the risk of neonatal thyroid problems
features of subclinical hypothyroidism
TSH raised but T3, T4 normal
no obvious symptoms
management of subclinical hypothyroidism
if TSH 4-10
if <65yrs and have symptoms, trial levothyroxine
>80 yrs, watch and wait
if no symptoms, repeat TFTs in 6 months
TSH >10
<70yrs start treatment even if asymptomatic
in older people follow a watch & wait approach
should patients with T2DM be offered a statin?
only if QRISK >10%
then start atorvastatin 20mg
BP targets for those with T2DM
same as those without T2DM
<80 yrs
clinic: 140/90
home: 135/85
> 80 yrs
clinic: 150/90
home: 145/85
MOA of DPP-4 inhibitors
prevent the breakdown of incretins
**hormones produced by the GI tract in response to large meals, reducing the blood sugar levels
Increase insulin secretions
Inhibit glucagon production
Slow absorption by the GI tract
side effects of DPP-4 inhibitors
GI tract upset
Symptoms of upper respiratory tract infection
Pancreatitis
what is the range for impaired fasting glucose
6.1-6.9mmol/L
what is the range for impaired glucose tolerance
plasma glucose at 2 hours 7.8 – 11.1 mmol/l on an OGTT
MOA of TZD
agonists to the PPAR-gamma intracellular receptor
increase insulin sensitivity & decreases production of glucose from the liver
side effects of TZD
weight gain
liver impairment: monitor LFTs
fluid retention: contraindicated in heart failure
increased risk of fractures
bladder cancer
what is Grave’s disease
an autoimmune condition where TSH receptor antibodies cause a primary hyperthyroidism
These are abnormal antibodies produced by the immune system
Most common cause of hyperthyroidism
management of Grave’s disease
propranolol = controls symptoms
NICE recommend referring these patients to secondary care for ongoing treatment
1) carbimazole
leaving them with normal thyroid function after 4-8 weeks
- the dose is carefully titrated to maintain normal levels (known as “titration-block”)
- or the dose is sufficient to block all production and the patient takes levothyroxine titrated to effect (known as “block and replace”)
2) propylthiouracil
3) radioiodine treatment
side effects of hyperthyroidism management
carbimazole - agranulocytosis
propylthiouracil - severe hepatic reactions
radioiodine - hypothyroidism
contraindications for radioiodine
pregnancy (should be avoided for 4-6 months after)
<16 years
thyroid eye disease
management of prediabetes
weight loss
exercise
change in diet
how often should you monitor HbA1C for those with prediabetes
annually
what are GLP-1 mimetics?
increase insulin secretion and inhibit glucagon secretion - mimic incretins
examples include exenatide & liraglutide
can cause weight loss
key difference between exenatide & liraglutide
exenatide: subcut injection 60 mins before morning & evening meals
liraglutide: once daily subcut injection
side effects of GLP-1 mimetics
nausea & vomiting
can cause pancreatitis
when to consider giving GLP-1 mimetics?
If triple therapy is not effective or tolerated
BMI ≥ 35 kg/m² and specific psychological or other medical problems associated with obesity or
BMI < 35 kg/m² and for whom insulin therapy would have significant occupational implications or weight loss would benefit other significant obesity-related comorbidities
only continue if there is a reduction of at least 11 mmol/mol [1.0%] in HbA1c and a weight loss of at least 3% of initial body weight in 6 months
when & how often should patients with diabetes monitor their BM when driving?
Patients on medication for diabetes with potential to cause hypoglycaemia eg. insulin, sulphonylureas, are required to check their BM prior to driving and every 2 hours of the journey
presentation of hypoglycaemia depending on blood sugar level
<3.3mmol/L:
autonomic symptoms due to release of glucagon & adrenaline:
sweating
shaking
anxiety
nausea
hunger
<2.8
neuroglycopenic symptoms due to inadequate glucose supply to the brain
weakness
vision changes
confusion
dizziness
severe:
convulsion
coma
if a patient is asymptomatic, how many sets of tests need to be done to confirm diabetes
2 on separate occasions if asymptomatic
what reduces hypoglycaemic awareness
frequent episodes of hypoglycaemia
beta-blockers
complication of lipodystrophy
may cause erratic insulin absorption
associated features of metabolic syndrome
PCOS
raised uric acid levels
non-alcoholic fatty liver disease
symptoms of T2DM
polyuria & polydipsia
fatigue
opportunistic infections
slow healing
glucose in urine
what is De Quervain’s thyroiditis
thought to occur following viral infection, presenting with fever, neck pain & tenderness, dysphagia, and features of hyperthyroidism
phases of De Quervain’s thyroiditis
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
management of De Quervain’s thyroiditis
self-limiting condition
NSAIDS/aspirin for the pain
beta blockers for symptomatic relief
what is a thyroid storm/thyroid crisis?
more severe presentation of hyperthyroidism with pyrexia, tachycardia, and delirium
management of a thyroid storm
admission for monitoring
fluid resuscitation
anti-arrhythmic medication
beta blockers
features of hyperthyroidism
sweating
anxiety/irritability
diarrhoea
fatigue
weight loss
tachycardia
causes of hyperthyroidism
Grave’s disease
toxic multi-nodular goitre (2nd most common cause)
Solitary toxic thyroid nodule (benign adenoma)
thyroiditis e.g. de Quervain’s
role of parathyroid gland & PTH
4 parathyroid glands of the thyroid, where the chief cells release PTH in response to hypocalcemia
PTH increases calcium levels in the blood by:
- increasing osteoclast activity
- increasing vitamin D activity
- increasing calcium absorption from the gut & kidneys
main cause of primary hyperparathyroidism
solitary adenoma
**treated with surgical excision
symptoms of hyperparathyroidism
**bones, stones, abdominal groans, and psychic moans
polyuria, polydipsia
abdominal groans - nausea and vomiting, constipation
bone pain
renal stones
depression, fatigue, psychosis
characteristic xray finding of hyperparathyroidism
pepperpot skull
symptoms of hypocalcaemia
paraesthesia in fingertips, toes, and lips
facial twitching
depression, fatigue
muscle pains or cramps
cause of secondary hyperparathyroidism
insufficient vitamin D or chronic renal failure
low calcium leads to raised PTH, results in hyperplasia of the glands
tertiary hyperparathyroidism
happens when the cause of secondary hyperparathyroidism is treated, but PTH remains high due to the hyperplasia of the glands
***treated by surgically removing part of the parathyroid gland to return to normal functioning
autoantibodies associated with hashimoto’s thyroiditis
anti-thyroid peroxidase
anti-thyroglobulin
Hashimoto’s thyroiditis is associated with an increased risk of what?
MALT lymphoma
other autoimmune conditions
when to consider stopping/stopping metformin?
metformin dose should be reviewed if the creatinine is > 130 µmol/l (or eGFR < 45 ml/min)
AND stopped if the creatinine is > 150 µmol/l (or eGFR < 30 ml/min)
what is the importance in recognising subclinical hyperthyroidism
effects on the cardiovascular system - supraventricular arrhythmias, AF
bone metabolism - osteoporosis
cause & management of subclinical hyperthyroidism
cause - multinodular goitre, especially in elderly women
management - TSH levels usually revert to normal, so need a persistently low TSH
can try a low dose of anti-thyroid medication for approx 6 months to induce remission
role of dexamethasone in cerebral metastases
reduce cerebral oedema
reduce the risk of seizures
side effects of thyroxine therapy
hyperthyroidism
worsening of angina
AF
osteoporosis - reduced bone mineral density
different criteria for starting levothyroxine therapy
those suffering from cardiac disease, severe hypothyroidism, >50 yrs - started on 25mcg with dose slowly titrated
others should start on 50-100mcg
following a change in dose, TFTs should be checked after 8-12 weeks
causes of hypothyroidism
hashimoto’s thyroiditis (autoimmune)
iodine deficiency
hyperthyroidism medication e.g. carbimazole, propylthiouracil, radioactive iodine, surgery
drugs - lithium, amiodarone
secondary cause: dysfunction of the pituitary gland due to tumour, infection, vascular cause (Sheehan syndrome)
symptoms of hypothyroidism
weight gain
fatigue
cold intolerance
depression
constipation
dry skin, coarse hair
fluid retention
heavy/irregular periods
use of radioactive isotope when diagnosing thyroid conditions e.g. diffuse, focal, and cold areas
Diffuse high uptake is found in Grave’s Disease
Focal high uptake is found in toxic multinodular goitre and adenomas
“Cold” areas (i.e. abnormally low uptake) can indicate thyroid cancer
pathophysiology of DKA
as cells have no fuel and think they are starving, lipolysis starts and ketogenesis occurs
initially the body produces enough bicarbonate to counteract the ketone acids, but eventually it is used up –> ketoacidosis
due to hyperglycaemia, more glucose is excreted in the urine, water follows due to osmotic diuresis leading to polyuria and dehydration
insulin normally drives potassium into cells, serum potassium is high or normal, total body potassium is low as none is being stored in the cells
common causes of DKA
infection, MI, missed insulin doses
features of DKA
hyperglycaemia
dehydration
ketosis
metabolic acidosis
potassium imbalance
polyuria, polydipsia
dehydration & subsequent hypotension
abdominal pain
nausea & vomiting
acetone smell to breath
diagnosing DKA
Hyperglycaemia (i.e. blood glucose > 11 mmol/l)
Ketosis (i.e. blood ketones > 3 mmol/l or urine ketones ++ on dipstick)
Acidosis (i.e. pH < 7.3)
diagnosing DKA
Hyperglycaemia (i.e. blood glucose > 11 mmol/l)
Ketosis (i.e. blood ketones > 3 mmol/l or urine ketones ++ on dipstick)
Acidosis (i.e. pH < 7.3)
management of DKA
IV fluids
insulin (add dextrose infusion if blood sugars go below a certain level)
potassium supplementation
** if the rate of potassium infusion is greater than 20 mmol/hour then cardiac monitoring may be required
what is important in the prevention of thyroid eye disease
stopping smoking
radioiodine therapy is a contraindication
features of thyroid eye disease
*** patient may be hypo-, eu-, or hyperthyroid at point of presentation
exophthalmos
conjunctival oedema
optic disc swelling
ophthalmoplegia
inability to close lids may lead to sore, dry eyes —> exposure keratopathy
features of thyroid eye disease
*** patient may be hypo-, eu-, or hyperthyroid at point of presentation
exophthalmos
conjunctival oedema
optic disc swelling
ophthalmoplegia
inability to close lids may lead to sore, dry eyes —> exposure keratopathy
why are GLP-1 mimetics sometimes used in combination with insulin
minimise insulin related weight gain
management of Addison’s disease in concurrent illness
double hydrocortisone dose
*** during illness the body usually increases cortisol levels as a stress response
keep fludrocortisone dose the same
