Endocrinology Flashcards
what are the blood results for Addison’s?
Hyponatraemia
Hyperkalamiae
hypoglycaemia
metabolic acidosis
how do we manage type 2 DM?
first start lifestyle changes
if HbA1C rises to 48 on lifestyle advice, add Metformin
if HbA1C rises add a second medication from the following:
- Gliptin (DDP4 inhibitor)
- sulfonylurea
- SGLT-2 inhbitor
- pioglitazone
if, despite the 2nd med, HbA1C rises to/or remains above 58mmol/mol - add a 3rd med
triple therapy with any of the following combinations:
- metformin + sulfonylurea + pioglitazone
- metformin + sulfonylurea + SGLT-2 inhibitor
- metformin + sulfonylurea + gliptin
- metformin + pioglitazone + SGLT-2 inhibitor
or consider insulin therapy
finally, if triple therapy not working
a GLP-1 analogue can be tried in combination with metformin and a sulfonylurea if BMI>35 with obesity related problems or <35 but cant take insulin
how do we manage idiopathic adrenal hyperplasia?
aldosterone antagonists e.g. spironolactone
what are the targets in DKA treatment?
reduce ketones by 0.5 mmol/L/h
reduce glucose by 3 mmol/L/h
increase bicarb by 3 mmol/L/h
maintain potassium between 4-5.5mmol/L
what are side effects of pioglitazone?
weight gain, osteoporosis, swelling of legs/ankles, risk of liver disease, anaemia risk, fluid retention
contraindicated in previous bladder cancer patients
what usually precipitates HHS (hyperglycaemic, hyperosmolar state)?
infection, MI, stroke or other acute illness
how do DDP4 inhibitors/gliptins work?
give names of drugs
DDP-4 enzymes are involved in deactivating incretins (GLP-1). by inhibiting them - we raise the levels of GLP-1 which bind to Beta cells and increase insulin production and secretion.
e.g. sitagliptin, vildagliptin, linagliptin
how does the BD (biphasic) insulin regime work?
patient takes 2 premixed insulin doses - via disposable pens
good for a regular lifestyle
twice‑daily insulin detemir is the regime of choice.
what are the causes behind primary hyperparathyroidism?
usually - adenoma (80% cases) multifocal disease (10-15%) carcinoma (<1%)
what are side effects of sulfonylureas?
weight gain, hypoglycaemia, upset stomach, skin rash/itching
what are 3 features of Hashimoto’s thyroiditis?
hypothyroidism
goitre
anti-TPO
which thyroid cancer secretes calcitonin?
medullary cancer
when do we treat subclinical hypothyroidism?
if TSH is btwn 4-10
for <65s with symptoms - treat with a trial of levothyroxine and continue if shows improvement
if asymptomatic or older - watch and wait, repeat TFTS in 6 months
if TSH is >10
for <70s - treat with levothyroxine
watch and wait for older patients
at what HbA1C level do we add a second drug to metformin for T2DM patients?
58
what is involved in the HPA axis?
Hypothalamus secretes corticotropin releasing factor (CRF)
CRF stimulates the anterior pituitary to secrete ACTH
ACTH stimulate the adrenal cortex to secrete cortisol and androgens
which is the insulin regime of choice for adults?
multiple daily basal-bolus injections
which drugs can cause hypercalcaemia?
thiazide diuretics
calcium containing antacids
what is an important complication of fluid resuscitation in young DKA patients?
cerebral oedema
whats the most common cause of Addison’s worldwide?
Tb
tell me about ultra fast acting insulin
examples = novorapid, humalog
used to inject before a meal or just after. helps to match insulin to what is actually eaten
when do we consider transferring a DKA patient to ICU?
if there are signs of severe DKA: pH < 7 bicarb < 5 blood ketones > 7 GCS < 12 K+ < 3.5 oxygen sats <92% low BP or pulse
how do you classify BMI into normal/overweight/obese?
normal= 18.5 - 25 overweight =25-30 obese 1 =30-35 obese 2 =35-40 obese 3 =>40
what is the MoA of carbimazole?
it blocks thyroid perioxidase from iodinating the tyrosine residues on the thyroglublin - this reduces the production of thyroid hormones
what are side effects of Gliptins?
usually well tolerated
can cause hypoglycaemia, hives, fluid retention, UTI, headaches, facial swelling nasopharyngitis
how do we manage pregnancy in diabetic patients?
in advance, have a target of 48mmol/mol!
take folic acid 5mg OD
during pregnancy, have a blood glucose control assessment every 1-2 weeks throughout pregnancy
what are the TFT levels in subclinical hypothyroidism?
elevated TSH with normal T4
what is the single most useful test in determining the cause of hypocalcemia?
parathyroid hormone
which are the 2 most common thyroid cancers?
papillary (70%)
follicular (20%)
what are symptoms of hyperglycaemia?
polyuria polydypsia lethargy genital thrush weight loss visual blurring
what are the clinical features of Paget’s disease?
only 5% are symptomatic
bone pain - lumbar spine, femoral, pelvis
skull bossing, leg bowing
raised ALP, normal phosphate and calcium
skull xray - thickened vault
what is the pathophysiology of secondary hyperparathyroidism?
parathyroid hyperplasia occurs in response to low calcium, almost always in a setting of chronic renal failure
what are the findings in hyperaldosteronism?
raised BP raised/normal sodium low potassium raised bicarbonate (alkalosis) raised aldosterone low renin
which steroid has high GC activity and low MC activity?
dexamethasone and betmethasone
important if we need high anti inflammatory action and low fluid retention e.g. in cranial tumours
why electrolyte deficiency is responsible for sustained hypocalcaemia despite calcium replacement therapy?
magnesium
magnesium is needed for PTH secretion and its action on target tissues
how much potassium should we give to DKA patients?
if potassium is >5.5 give nil
if potassium is 3.5-5.5 give 40mmol/L infusion
if < 3.5 - seek help
what are the symptoms of hyperaldosteronism?
can be asymptomatic
signs of hypokalaemia= cramps, weakness, paraesthesia
High BP and headaches
which hormones are reduced in the stress response?
insulin
oestrogen
testosterone
what are side effects of treatment with levothyroxine?
hyperthyroidism
reduced bone mineral density
worse angina
atrial fibrillation
what is Waterhouse - Friderichsen syndrome?
adrenal failure due to haemorrhage into the adrenal gland, commonly caused by severe infection
severe form of meningococcal sepsis
usually pre-terminal
patients present with sepsis, coagulopathy, extremities cyanosed, comatosed
whats the most important advice to give a patient being started on carbimazole?
if they get any signs of infection they should seek urgent medical review
a rare side effect = agranulocytosis
what’s sick euthyroid syndrome?
its caused by systemic disease
total and free T4 and T3 are minimally low
TSH is normal or slightly low
how do we investigate hyperaldosteronism?
1st line = renin:aldosterone ratio High serum aldosterone low serum renin adrenal vein sampling high resolution CT scan
how do we treat phaeochromocytoma?
surgery is definitive treatment
but we first stabilise the patient with alpha blockers (phenoxybenzamine) and then beta blockers (propanolol)
what is kussmauls breathing?
heavy respiration - expiring CO2 to try and compensate for metablic acidosis
what are the features of LADA?
these patients, although they have autoimmune disease, like type 1 DM, are picked up later in life.
their diabetes progresses a lot slower - and may not need insulin in the earlier stages
LADA can often be misdiagnosed at T2 DM but patients are usually younger and less obese
diagnosis may be aided by GAD autoantibody testing or other autoimmune disease
what is Cushing’s disease?
pituitary tumour secreting ACTH causing adrenal hyperplasia
what ABG results are associated with Cushings?
hypokalaemic metabolic alkalosis
give an example of a fluid replacement regime in a DKA patient?
1st hour: 0.9% saline - 1L
2nd hour: 0.9% saline + potassium chloride
what glucose ranges are diagnostic for diabetes?
fasting glucose >7
HbA1C >48
where is ADH secreted from and what does it do?
ADH is released for the posterior pituitary in response to thirst.
ADH causes more aquaporin channels to be inserted into collecting duct membranes in the kidneys. this increases water retention
what are the causes for hyperkalaemia?
AKI drugs - K sparing diuretics, ACE-I, ARBs, spironolactone metabolic acidosis massive blood transfusion addisons rhabdomyolosis
what percentage of pre-diabetic patients progress to type 2/year?
5-10%
how do we treat an adrenal tumour?
for adenoma - adrenalectomy
for carcinoma - radiotherapy and adrenolytic drugs
which mutation is associated with most cases of MODY?
mutation in the HNF1- alpha gene
known as MODY 3
how do we treat hypoparathyroidism?
with alfacalcidol
which is an analogue of vitamin D
what glucose ranges show prediabetes?
42-47 HbA1C
fasting glucose: between 6-7
what do the osteoporosis guidelines recommend regarding a postmenopausal woman who has had a fracture?
give her bisphosphonate and calcium supplements
when do you NOT have to inform the DVLA about taking insulin?
if on temporary insulin for < 3 months
or because of gestational diabetes and wont be continuing the insulin for more than 3 months postpartum
what does thyrotoxicosis alongside a singular hot nodule (on scintography) indicate?
toxic adenoma
this occurs when a single nodule grows on the thyroid gland - producing excess hormones and causing thyrotoxicosis
what are the features of type 2 DM?
associated with lack of exercise, obesity, alcohol and calorie excess
more common in asians, men and elderly
because of excess adipose tissue, there is a relative insulin insufficiency - not enough to go around
which anti diabetic drug increases insulin sensitivity?
pioglitazone
how does diabetes causes damage to the eyes? (2)
1) endothelial changes causes capillary leakage - causing intraretinal oedema which then forms hard exudates. in the macular area this can result in loss of central vision
2) capillary occlusion can cause retinal ischaemia. in the macular area this can cause visual loss. the ischaemia then causes new retinal vessels forming. the new vessels can cause - haemorrhage, fibrosis, etc
all leading to total blindness
how is Addison’s managed?
steroid replacement therapy
hydrocortisone (in 2 or 3 doses per day) and fludrocortisone
what are the features of MEN 1?
3 Ps (parathyroid, pituitary and pancreas) and adrenal and thyroid
whats the most serious potential complication of AKI?
hyperkalaemia
how do we investigate phaeochromocytoma?
24 hour urinary collection of metanephrines
VMA in urine is usually elevated
and serum metanephrines are elevated
what is MEN?
multiple endocrine neoplasia
autosomal dominant disorder
where is prolactin produced?
anterior pituitary gland
what is the pathophysiology of primary hyperaldosteronism?
excess aldosterone leads to Sodium reabsorption, H2O retention and K+ excretion. this leads to raised blood pressure, hypernatraemia, hypokalaemia, and alkalosis
what are side effects to long term steroid use?
endocrine - impaired glucose regulation, hyperlipidaemia, excess hair growth, increased appetite/weight gain
bones - osteoporosis, osteopaenia, avascular necrosis of the femoral head,
immunosuppression
GI - peptic ulceration and pancreatitis
psychiatric - mania, psychosis, insomnia, depression
cushings syndrome - moon face, buffalohump, stria
eyes -glaucoma, cataracts
intracranial hypertension
suppression of growth in children
how do you identify a benign incidental adrenal adenoma?
usually picked up on CT accidentally
the ademona has a rich lipid core with well circumscribed nodules
what are signs of thyrotoxicosis?
tachycardia, maybe irregular pulse, moist warm skin, fine tremors, lid lag/retraction, goitre, thin hair, thyroid nodules/bruit.
how do we manage a prediabetic patient?
encourage to make lifestyle changes - exercise and change diet (more fibre less fat)
consider 500mg OD metformin
test HbA1C regularly - annually
how do we define diabetes?
hyperglycaemia levels sufficient to cause microvascular complications
how often should a T1 DM patient check his blood glucose/day?
at least 4 times a day - before meals and before bed
what are symptoms of hyponatramea?
dizzy, nausea, headache, coma if severe, signs of dehydration or fluid overload
tell me about premixed insulins
e.g. novamix 30
30% SA and 70% LA
which glucose ranges show normal glycaemic control?
HbA1C < 42
fasting glucose < 7
what diabetic medication should we consider as first line for a patient with end-renal failure?
Gliclazide
Metformin is contraindicated (can’t be used in any patient with eGFR < 30)
is a Type 2 diabetic patient, on insulin, allowed to drive a HGV?
yes, but he must meet very strict criteria set out by the DVLA, relating to hypoglycaemia
what are the 2 main causes for hypercalcaemia?
primary hyperparathyroidism
malignancy
these 2 causes account for 90% of cases
what is MODY?
a group of genetic diseases affecting the production of insulin
maturity onset diabetes of the young
usually in those < 25 years
with a strong family history
typically autosomal dominant
number of genes identified
patients usually very sensitive to sulfonylureas
what are the 5 types of thyroid cancer?
papillary follicular medullary anaplastic lymphoma
how is HHS diagnosed?
signs of dehydration
osmolarity: >320mosmol/kg
hyperglycaemic: >30mmol/L with pH>7.3 and no ketonaemia < 3mmol/L
what are the complications of pagets disease?
deafness - CN trapping bone sarcoma skull thickening fractures high output cardiac failure
how would a patient present in phase 1 of subacute thyroiditis ?
tender goitre
hyperthyroidism
raised ESR
globally decreased uptake on iodine scan (Technetium scan)
tell me about long acting/basal insulin?
human insulin analogues
e. g. glargine - used at bedtime, to give a steady insulin baseline all night. good for those who struggle with nocturnal hypoglycaemia
e. g. detemir
what investigation should we do in a patient who’s drowsy, vomiting, dehydrated, abdo pain, polyuria, polydipsia?
CHECK BLOOD GLUCOSE
what does thyroxine interact with??
iron
iron reduces the absorption of thyroxine
take the drugs 2 hours apart
what is the mechanism of action of sitagliptin?
it is a dipeptidyl peptidase 4 inhibitor (DPP-4)
this prevents the breakdown of GLP-1, therefor increasing its levels and so increasing insulin
what rate of insulin should u prescribe for ketoacidotic patients?
0.1 unit/kg/hour
what medication can we use pre-op to decrease cortisol secretion?
metyrapone, ketocanozole, flucanazole
how do patients with hypercalcaemia present?
non specific symptoms
nausea, polydipsia, polyuria, weakness, confusion, constipation
what antibodies are associated with Graves disease?
TSH receptor stimulating antibodies
anti-thyroid peroxidase antibodies
how do we prevent diabetic retinopathy?
primary prevention - BP and glucose control
secondary - regular assessment
immediate anti VEGF treatment in diabetic macular oedema - to prevent new vessels forming e.g. ranibizumb, aflibercept
3) salvage therapy - vitrectomy
whats the best investigation to differentiate between type 1 and type 2 diabetes?
C peptide
this will be low in type 1
(because the pancreas is not producing enough insulin precursor which breaks down to give insulin and C-peptide)
and normal or high in type 2
how does the OD insulin regime work?
once a day, taking a dose of LA insulin
good started for T2 patients switching across to insulin
typical dose is around 1 unit/BMI unit/24 hours
can retain metformin etc if need for tighter control
how do we screen for acromegaly?
by testing serum Insulin-like Growth factor -1 IGF-1, which represents 24 hour GH levels
what are the features of type 1 DM?
usually presents in adolescents/young adults
at risk of ketoacidosis and weight loss
antibody destruction of pancreatic, insulin-producing beta cells (anti bodies include Glutamic acid decarboxylase (GAD) antibodies and islet cell antibodies (ICA)
associated with other autoimmune disease
treated with insulin
what is acromegaly?
excessive GH
in 95% of cases this is secondary to a pituitary adenoma
what is Paget’s disease?
a disease of excessive turnover of the bone - increased osteoclast and osteoblast activity
how do we monitor for subclinical recurrence of medullary thyroid carcinoma?
calcitonin levels
what is congenital adrenal hyperplasia?
a group of autosomal recessive diseases
in response to low cortisol, the pituitary gland produces excess ACTH which leads to increased production of androgens
leading to large build, manly hair, early menarche
what is the synacthen test?
ACTH stimulation test
ACTH is injected and the cortisol response is measured.
how do we diagnose DKA?
1) acidosis - pH <7.3 or Bicarb <15
2) hyperglycaemia - glucose>11 (or13.8) or known Diabetes
3) ketosis - ketonaemia >3 or ++ on dipstick
who’s more likely to develop diabetes: a patient with impaired fasting glycaemia or impaired glucose tolerance?
those with impaired glucose intolerance are more likely
how do we manage HHS?
rehydrate slowly - with 0.9% saline, over 48 hours
replace K+ once urine starts to flow
use insulin if glucose not falling by 5mmol/L/kg/H OR if there is ketonaemia
keep blood glucose at least 10-15mmol/L to avoid cerebral oedema
what is LADA?
latent autoimmune diabetes of adult
what features are specific to graves disease?
eye signs - exophalmus, ophalmoplegia
pretibial myxoedema
thyroid acropachy
how do we treat hyperaldosteronism?
if its due to Conn’s = laprascopic adrenalectomy
if its due to hyperplasia = treat medically with spironolactone or amiloride
what are side effects of SGLT-2 inhibitors?
UTI, weight loss, change in urination, genital yeast infections, upper resp tract infections
what causes primary hyperaldosteronism ?
idopathic adrenal hyperplasia (70% cases)
adrenal adenoma - Conn’s syndrome
adrenal carcinoma - rare
how do we treat an addisonian crisis?
100mg iv/im hydrocortisone
saline with dextrose (if hypoglycaemic)
continue steroids 6 hourly until stable
what dietary advice do we offer diabetic T2 patients?
include in your diet plenty of high fibre and low glycaemic index foods. oily fish, low fat diary products
reduce intake of high energy carbs, saturated fats, trans-fatty acids
weight loss of 5-10% fat in obese patients
what are ACTH independent causes of Cushings?
iatrogenic - steroid use
adrenal nodular hyperplasia
adrenal adenoma/cancer
how do we manage hypercalcaemia?
first - IV saline! -patient will be dehydrated
then once hydrated
can give bisphosphonates e.g. IV pamidronate
calcitonin can be given to patients who are resistant to bisphosphonates
what are the causes of primary hyperparathyroidism ?
80% cases = solitary adenoma
10-15% cases = multifocal disease
1% carcinoma
how do we treat Addison’s disease?
replace steroids
15-25 mg hydrocortisone/day
50-200mcg fludrocortisone
what population is Graves disease typically seen in?
females, aged 30-50
what does ACTH stand for?
adrenocorticotropic hormone
when should orlistat be stopped?
if the patient has lost more than 5% weight in 12 month s
what are the symptoms of hypoparathyroidism?
the symptoms are mostly secondary to hypocalcaemia
muscle spasms, twitching, cramping chvostek's sign Trousseau's sign perioral parasthesia ECG long QT
how do we diagnose asymptomatic diabetes?
random glucose >11
or fasting glucose > 7
must be demonstrated on 2 separate occasions
what is diabetes insipidus?
it can either be cranial (not enought ADH produces) or nephrogenic (kidney insensitive to ADH)
patients produce large quantities of dilute urine - polyuria and drink a lot to compensate - polydypsia
people can become dehydrated if they are unable to drink
which TFT results show poor thyroxine compliance?
High TSH and normal T4
this is because TSH takes longer to normalise, so the patient could have had low thyroxine before coming to the doctor, but taken her medication before her blood test so her T4 is normal but her TSH hasn’t corrected yet
Raised T4 with raised TSH also points towards poor compliance. the patient has taken extra tables prior to blood test causing the raised T4 but TSH hasnt had time to be suppressed (TSH levels take days to weeks to change)
if a patient with Addison’s disease is ill, should there be changes made to their medication?
yes,
hydrocortisone should be doubled (because the body would usually increase its production during illness- stress response)
fludrocortisone can be kept the same
what are the causes for galactorrhoea ?
6 Ps pregnancy physiological primary hypothyroidism prolactinoma polycystic ovarian syndrome phenothiazines, domperidone, metaclopramide
what is phaeochromocytoma?
a rare catecholamine secreting tumour
in regards to insulin, how do we manage a patient with DKA?
start him on a fixed IV insulin of 0.1 units/kg/hour
how does SIADH present?
solitary hyponatraemia, water retention
what are common precipitating factors for DKA?
missed insulin dose
infection
myocardial infarction
what are the features of DKA?
dehydration, polyuria, polydipsia
abdominal pain , vomiting , drowsiness
kussmauls respiration - deep hyperventilation
sweet smelling breath - acetone
which blood cells might increase with corticosteroid use?
neutrophils
CS are thought to cause neutrophilia via 3 mechanisms.
what type of drug is gliclazide?
sulfonylurea
what are the signs of thyroid eye disease? (as seen in almost 50% cases of Graves disease)
exophthalmus - protruding eye appearance proptosis - eye protudes beyond orbit othalmoplegia conjuntival oedema papillodeama corneal ulceration
what are contraindications for radioiodine treatment?
pregnancy - should be avoided for 4-6 months after as well
thyroid eye disease is a relative CI- can be made worse
how are thyroid hormones synthesised?
thyroid follicular cells produce thyroglobulin (Tg)
iodine is transported and trapped in the colloid
Thyroid perioxidase (TPO) on the luminal surface of TFCs iodinates the tyrosine residues on the Tg (this is known as organification)
the iodinated Tg are endocytosed by the follicular cells and are hydrolised there to produce thyroid hormones. (mostly T4)
they are then secreted into the blood - bound to globulins.
in peripheral tissues, T4 is deionised to produce T3
where is iodine deficiency most common?
africa, asia, himalayas
when should you refer a patient to the diabetic foot clinic?
if they have any foot problems besides for simple calluses
what are symptoms of a prolactinoma in female?
infertility
oligomenorrhoea
galactorea
what risk factor modification medication should diabetic patients be on?
ACE-I if BP>140/80
statins if 10-year CVD risk is >10%
anti-platelets
what are the levels in secondary hyperparathyroidism?
Raises PTH
low or normal Calcium
High Phosphate
Low Vit D
how does the QDS insulin regime work?
this regimen is useful for those with a flexible/changing lifestyle.
patient takes ultra fast acting insulin before meals/exercise and then a LA analogue at night
how do we treat symptomatic prolactinoma?
with dopamine agonists which inhibit the release of prolactin from the pituitary gland
e.g. Bromocriptine
if the DAs are not tolerated, surgery is the next option. trans-sphenoidal hypophysectomy
why does potassium fall in DKA treatment?
insulin makes the cells take up potassium
what are the symptoms of Addison’s disease??
lethargy, weakness, anorexia, nausea, weight loss, vomiting, salt craving
hyperpigmentation, vitilgo, loss of pubic hair in females
hypotension
crisis = collapse, shock, pyrexia
what are the features of acromegaly?
coarse facial features, spade like hands, bigger feat
oily skin, excessive sweating
prognathism, large tongue, interdental spaces
symptoms of intracranial mass- headaches, bitemporal hemianopia
raised prolactin in 1/3 of cases - galactorrhoe
what are the features of addisonian crisis?
hyponatraemia
hyperkalaemia
hypoglycaemia
hypovolaemia
what is an important worry in HHS and how do we prevent it?
occlusive events (DIC, chorea, focal CNS signs, leg ischaemia/rhabdomyolosis) give prophylactic LMWH
how is osteoporosis linked to graves disease?
excess T3 causes increased osteoclast activity leading to excess bone resorption - causing osteoporosis
in patients admitted with hypercalcaemia, when is IV bisphosphonate indicated?
when calicum is over 3
how do we treat painful diabetic neuropathy?
the same way as we treat any neuropathic pain
1) first line treatment = amitryptaline, pregablin, gabapentin, duloxetine
2) if the medication doesnt work, try another of the 4 drugs
tramadol can be used as rescue therapy
topical capsaicin can be used for topical pain
how do we confirm a diagnosis of acromegaly ?
with an OGTT
normally, hyperglycaemia leads to suppression of GH - but this doesnt happen in acromegaly
we perform the OGTT with series of GH tests after
what is ketogenesis?
its an alternative metabolic pathway - to provide energy to cells. its inefficient and produces acetone
without insulin, glucose can’t enter the cells, so the body thinks it is ‘starving’ - and ketogenesis kicks in, as a last resort
what are the symptoms of hypothyroidism?
lethargy, tired, weak, cramps, cold intolerance, weight gain, cramps, hoarse voice, constipation, menhorragea, myalgia
what is a grand mal seizure?
its a tonic clonic seizure
loss of consciousness with strong muscle contractions
what is primary hyperaldosteronism ?
excessive production of aldosterone, independent of the RAA axis
what are the ‘sick-day rules’ for diabetic patients?
try drink 3L/24hour
maintain normal insulin regime
if dehydrated- possible stop metoformin
check ketones regularly - every 3-4 hours
check glucose levels more frequently - every 4 hours
if ketones are raised take a corrective insulin dose (usually normal dose divided by 6 - not more than 15 units)
have sugary drinks if struggling to eat
how does pioglitazone work?
helps to decrease insulin resistance (aka increase insulin sensitivity) in peripheral tissues and liver
decreases gluconeogenesis and levels of glucose/glycated Hb in bloodstream
what are hormone levels in primary hyperparathyroidism?
raised PTH, raised calcium, low phosphate
what are important side effects of SGLT2 inhibitors
genital infections
diabetic ketoacidosis
what is Addison’s disease?
primary adrenocortical insufficiency
destruction of the adrenal cortex leading to corticosteroid and aldosterone deficiency
what are complications of DKA and its treatment?
hypoglycaemia hypo/hyperkalaemia - can cause arrhythmias cerebral oedema thromboembolism AKI gastric stasis respiratory destress
what % of thyrotoxicosis cases are due to graves?
60-70%
what is considered hypoglycaemic?
glucose < 4
what causes secondary hypothyroidism? how is it detected?
TFT results of low TSH and low T4 suggests pituitary insufficiency
pituitary disease will cause secondary hypothyroidism - rare
MRI pituitary should be ordered to investigate further
how does phaeochromocytoma present?
typically episodes of: hypertension headaches sweating anxiety palpitations
how do we treat pagets disease?
bisphosphonates
oral Risedronate or IV zoledronate
what is the first line insulin regime offered to adults with T1 DM?
basel-bolus regime with twice daily detemir
why does diabetic foot disease occur?
1) neuropathy - loss of protective sensation, charcots arthropathy
2) peripheral arterial disease -macro/microvascular ischaemia
what is hashimoto’s thyroiditis?
an autoimmune thyroid disease, associated with hypothyroidism
10 times more common in women
features include anti-TPO antibodies and anti - Tg antibodies
non-tender goitre
tell me about short acting insulin
isophane
it has a variable peak at 4-12 hours
cheap - favoured by NICE
what does OGGT stand for?
oral glucose tolerance test
what are causes of thyrotoxicosis?
graves disease toxic nodular goitre acute phase of subacute thyroiditis acute phase of hashimoto's htyroiditis acute phase of post-partum thyroiditis amiodarone therapy
what is the cushing’s triad?
3 clinical signs resulting from raised ICP
1) irregular breathing
2) bradycardia
3) systolic hypertension
how do we manage thyrotoxicosis?
carbimazole - either via titration or block and replace method
titration: start on carbimazole 40 mg and titrate down until euthyroid state is reached. continued for 12-18 months.
titration results in less side effects than block and replace.
block and replace: give carbimazole 40mg and then thyroxine is added when the patient reaches euthyroid. treatment usually lasts 6-9 months.
radio-iodine and surgery are also options
which hormones are produced by the anterior pituitary?
TSH GH LH/FSH Prolactin Endorphins ACTH
what are daily blood glucose targets for T1 DM patients?
5-7 on waking
4-7 before meals
what are the symptoms of HHS?
signs of dehydration, polydypsia, weakness, leg cramps, altered mental states, trouble sleeping
how do sulfonylureas work?
give names of drugs
they increase Beta cell activity and insulin release (by binding to, and closing potassium channels - they lead to raised calcium levels and fusion of insulin granules with cell membrane)
e.g. gliclazide, glipizide, glibenclamide
how do we narrow down the cause of hyponatraemia?
1) we first assess if the patient is in a state of fluid overload or dehydrated
2) if the patient is dehydrated - we check the urinary sodium. if the urinary sodium is high (>20mmol/L)- we know the sodium is being lossed in the urine. causes can include: addisons, renal failure, diuretics
3) if the urinary sodium is low, the sodium is being lossed elsewhere - perhapes in burns/vomit/diarrhoea etc
4) if the patient is not dehydrated, we check to see if they are oedematous, if they aren’t - we look at urine osmolarity. if it is high,causes = SIADH
if it is low = water overload
5) if the patient is oedematous - causes can include = CF, renal failure, cirrhosis, nephrotic syndrome
how do WHO define diabetes?
fasting glucose > 7
levels 2H post glucose load >11.1
HbA1C > 48
what is Trousseau’s sign?
carpal spasm of the hand when BP cuff is inflated to higher than systolic pressure
it is a sign of hypocalcaemia
whats the best investigation for suspected Addison’s disease?
ACTH stimulation test
if not available- can do a 9am cortisol test. if >500 it rules out Addison’s. if <100 it’s an abnormal result.
between 100-500, an ACTH stimulation test is indicated
how do we manage primary hyperparathyroidism and nephrolithiasis (kidney stones)??
exploration and parathyroidectomy
how do we assess treatment response in hypothyroidism patients?
TSH levels
aim of treatment is to normalise the TSH levels
how is paget’s disease defined?
isolated raise of ALP with x-ray changes
what are the features of MEN 2a?
Medullary thyroid carcinoma and 2Ps - Pheochromocytoma and parathyroid
what is Nelsons syndrome?
rapid enlargement of pituitary corticothroph adenoma (ACTH secreting tumour). this occurs post bilateral adrenalectomy (an old popular treatment for cushings disease/syndrome)- so there is no negative feedback by cortisol on ACTH production - leading to proliferation of any pre-existing pituitary adenoma.
the growth leads to physical compression affects such as headaches and visual distrubances. the high levels of ACTH can cause MSH (melanocyte stimulating hormone) production and hyperpigmentation
how do we manage thyroid cancer?
total thyroidectomy
radioiodine treatment to remove residual cells
thyroglobulin monitoring to detect early recurrent disease
what are the signs/symptoms of diabetic autonomic neuropathy?
impaired pupil adaptation,
dry skin, tachycardia, orthostatic hypotension, silent myocardial ischaemia, exercise intolerance
gastroperisis, constipation/diarrhoea, oesophageal dysmobility,
genitourinary dysfunction - erectile dysfunction, retrograde ejaculation, female sexual dysfunction
what are signs of hypothyroidism?
bradycardia, thin hair and skin, drowsy, yawning, cold hands, decreased temp, fluid overload, goitre
what is the best way to treat MODY 3?
sulfonylureas (glicazide) are optimal treatment for HNF1-a mutations
what causes secondary hyperaldosteronism?
increased renin due to decreased kidney perfusion. this can result from renal artery stenosis, diuretics, CCF, hepatic failure
which thyroid carcinoma is associated with genetic inheritance?
medullary carcinoma
it can be inherited in an autosomal dominant pattern
may also be alongside a pheocromocytoma
what is the most common cause of thyrotoxicosis?
Graves disease
what is the most common cause of secondary adrenal insufficiency?
iatrogenic - steroids lead to suppression of the HPA axis. when steroids are withdrawn, addison’s is apparent
what are other names for subacute thyroiditis?
De Quervains thyroiditis
subacute granulomatous thyroiditis
how do we manage hypoglycaemia?
if patient conscious and cooperative -give quick acting 20g carb
if uncooperative - squeeze glucagel into mouth
if unconscious - IV/IM glucose 1mg
once glucose >4, give long acting carb e.g. toast
what are glucose targets for T2 Diabetic patients?
on lifestyle advice or lifestyle advice + metformin - the target is 48mmol/mol
with a second medication added, target is 53mmol/mol
what are side effects of metformin?
upset stomach, sickness with alcohol, kidney complications, dizziness, tiredness, metal taste
what are levels in secondary hyperparathyroidism?
raised PTH, low calcium, raised phosphate, low Vit D
how do patients with primary hyperparathyroidism present?
bones renal stones abdominal groans psychic moans - depression hypertension polyuria polydypsia
how do we manage DKA?
1) fluid resuscitation. isotonic saline used at first
2) insulin -IV. (0.1 unit/kg/hour)
3) once insulin is < 15 mmol/mol then 5% dextrose infusion should be started (to prevent hypoglycaemia)
4) continue normal LA insulin regime
5) treat hyperkalaemia (calcium and then potassium)
what are causes of primary hypothyroidism?
hashimoto’s thyroiditis - most common, autoimmune disease
subacute thyroitis
hyperthyroid treatment - ATD, radioiodine, surgery
iodine deficiency (leading cause worldwide)
drugs - amiodarone, lithium
riedel thyroiditis - inflammatory condition of the thyroid, replacing the tissue with fibrosed tissue
what are the phases for subacute thyroiditis?
usually post viral infection
phase 1 - hyperthyroidism, painful goitre, raised ESR (3-6 weeks)
phase 2 - euthyroid (1-3 weeks)
phase 3 - hypothyroidism (weeks to months)
phase 4 - thyroid structure and function returns to normal
which drugs can cause SIADH?
sulfonylureas SSRIs, triclyclics carbamazapine vincristine cyclophosphamide
how often do we check HbA1C in diabetic patients?
3-6 monthly until stable
and then every 6 months
what percentage of diabetic patients have type 2?
90%
what are names for pre-diabetes syndromes?
impaired glucose tolerance (IGT)
impaired fasting glucose (IFG)
what levels are raised in congenital adrenal hyperplasia?
raised 21 deoxycortisol
raised 17 deoxyprogesterone
raised urinary adrenocorticosteroid metabolites
why are Free T3/4 measurements more reliable than Total T4/3?
total T4 / T3 measurements rely on TBG (thyroid binding globulin).
TBG goes up in pregnancy, hepatitis and oestrogen therapy
TBG goes down in malnutrition, nephrotic syndrome, CLD, acromegaly
how do patients with diabetic foot disease present?
neuropathy - loss of sensation
ischaemia - absent foot pulses, reduced ankle brachial index pressure, claudication
complications - ulceration, gangrene, charcots arthropathy, osteomyelitis, calluses, cellulitis
what are the symptoms of thyrotoxicosis?
diarrhoea, palpitations, sweat, overactive, irritable, weight loss, increased appetite, oligomenorrhea, labile emotions, heat intolerance, tremors,
a patient presents with hypercalcaemia, recurrent peptic ulcerations and milky nipple discharge, what do you suspect?
MEN type 1
causing parathyroid, pancreas and pituitary tumours (3Ps)
which group of people is papillary cancer most commonly observed?
young females
what are the layers of the adrenal gland and what hormones do they produce?
there is the cortex and the medulla
the cortex is divided into 3 layers:
1) zona glomerulosa - produces mineralcorticoids - aldosterone
2) zona fasciculata - produces glucocorticoids - cortisol etc
3) zona reticularis - produces androgens
the medulla produces catecholamines e.g. E and NE
what can cause ectopic ACTH production?
small cell lund cancer
carcinoid tumour
how do SGLT-2 inhibitors work?
give names of drugs
they inhibit the sodium-glucose cotransporter in the in the kidney. mainly expressed in the PCT.
prevents glucose being absorbed by the kideys - so passed out in urine
e.g.’ -gliflozin’ dapagliflozin, empagliflozin
how do we diagnose diabetes?
1) symptoms AND random glucose>11.1/fasting glucose>7
2) asymptomatic AND random glucose>11.1/fasting glucose>7 on 2 separate occasions
3) HbA1C >48 mmol/mol
what causes Addison’s disease?
80% of cases are autoimmune in the UK
world wide- the main cause is Tb
other causes = haemorrhage, congenital, lymphoma, opportunistic infections in HIV
how do we diagnose diabetes insipidus?
water restriction test
how do hypoglycaemic patients present?
sweaty, increased pulse, seizures, odd behaviour (maybe aggression), decreased mental state
how do we stratify diabetic foot according to risk ?
low risk - no risk factors present
moderate risk - 1 risk factor present e.g. neuropathy/ischaemia/deformity
high risk - previous amputation/ulceration
or on renal replacement therapy
or >1 risk factor present e.g. loss of sensation/ signs of PAD
how do we initially treat hyperkalaemia?
calcium gluconate or calcium chloride - stabilises the myocardial membrane potential
what are the features of MEN 2b?
Medullary thyroid carcinoma and 1P -pheochromocytoma
and marfinoid body habitus and neuromas
what should initial starting dose of levothyroxine be?
50-100mcg OD
this should be lower in elderly patients and those with ischaemic heart disease
what is Chvostek’s sign?
tapping over the parotid (CN7) causes facial muscles to twitch
a sign of hypocalcaemia
when should we add metformin for T1 DM?
if BMI >25
how do we confirm a diagnosis of cushings syndrome?
using the dexamethasone suppression test
1) we give 1 mg dexamethasone at 10 pm at night and then take serum cortisol levels at 9 am the next day. if the cortisol level is not suppressed by negative feedback from this extra steroid - we can confirm excess steroids and cushings syndrome
2) we then do the high dose (8 mg) dexamethasone suppression test to differentiate between cushings disease (pituitary adenoma) or another source. if the cortisol is suppressed - we know it is cushings disease.
if it is NOT suppressed, the raised cortisol will either be due to 1) an ectopic ACTH source or 2) an adrenal cushings which is independent of ACTH
to differentiate between these 2 options, we measure the ACTH. if the ACTH is low then it is an adrenal cushings (independent of ACTH), and if it is high, the cortisol level is due to an ectopic ACTH producing tumour
what is the best way to decrease the risk of thyroid eye disease?
stop smoking
what types of insulins are there?
ultra-fast acting , short acting, long acting and mixed
should we alter thyroxine doses in pregnant women?
yes, by 25-50mcg - because of the increased demand
what are the criteria for prescription of Orlistat?
BMI >28 with risk factors
or BMI >30
with continued weight loss e.g. 5% at 3 months
use for <1 year
what are causes for an addisonian crisis?
surgery/sepsis exacerbating a chronic deficiency
adrenal haemorrhage
steroid withdrawal
is hyperpigmentation seen in primary or secondary adrenal insufficiency ?
primary
this is because lower cortisol production from adrenal glands leads to positive feedback of ACTH production. more ACTH leads to more MSH, causing pigmentation
how do we manage gastroperesis?
with prokinetic agents including erythromycin methoclopramide domperidone
what are the levels in primary hyperparathyroidism ?
High PTH
High Calcium
Low phosphate
how is SIADH treated?
fluid restriction
when do we feel thirst?
if plasma osmolarity increases - either due to decreased water or increased electrolytes (mainly sodium)
what are considerations when prescribing pioglitazone?
its contraindicated with history of bladder cancer (it can increase the risk of bladder cancer), heart failure (because can cause fluid retention),
in obese patients may increase weight
when is bariatric surgery indicated?
BMI > 40 or >35 with significant disease
tried all other medical/lifestyle treatment
fit and well for surgery
committed to long term follow up
whilst awaiting brain imaging, how do we treat a patient with suspected brain metastases?
high dose dexamethasone
will reduce cerebral oedema
what is Sheehan’s syndrome?
secondary hypothyroidism due to pituitary infarction post-partum (due to big haemorrhage during labour)
patients will also probably be low in other pituitary hormones - prolactin, ACTH, gonadotropins
what are the symptoms of hypercalcaemia?
bones - pain stones - renal groans - abdo, nausea, vomiting thrones - polyuria pshyc overtones - confusion, cognitive impairment
what age does Cushings disease most commonly occur?
30-50s
what does a combination of hypothyroidism and a goitre point towards?
hashimoto’s thyroiditis
how do you investigate subacute thyroiditis?
globally low uptake on iodine - 131 scan
which anti-diabetic medication causes weight gain?
sulfonylurea
which anti-diabetic drug can cause gastroperesis?
GLP-1 agonists e.g.
liraglutide
what is suspected in a young patient with asymptomatic hyperglycaemia?
MODY
MODY3 being the most common - mutation in HNF1alpha gene
what are MODY3 patients more at risk of?
hepatocellular carcinoma
what is a rare complication of steroid therapy?
steroid psychosis
