Endocrinology Flashcards
explain the pathophysiology of type 1 diabetes
insulin deficiency, due to autoimmune destruction of insulin-secreting pancreatic beta cells
(islet cells: alpha cells = glucagon, beta cells = insulin)
explain the pathophysiology of type 2 diabetes
insulin resistance develops - body can no longer produce enough insulin to cope with the high levels of glucose entering the body so the cells become resistant to insulin’s effects.
there is hypersecretion of insulin, by a depleted number of beta cells, so the insulin levels are increased by not enough to control glucose homeostasis.
hyperglycaemia and lipid excess are toxic to beta cells so insulin secretion then drops.
what is the classical triad of symptoms for a presenting type 1 diabetic? what causes each of these
polyuria - due to osmotic diuresis from blood glucose exceeding the tubular reabsorption capacity.
polydipsia - due to fluid and electrolyte loss.
weight loss - fluid depletion and accelerated breakdown of fat and muscle.
also lethargy, DKA
give 3 complications a type 2 diabetic may present with
recurrent staphylococcus skin infections (also thrush, UTIs), retinopathy, polyneuropathy, erectile dysfunction, arterial disease e.g. MI.
sometimes just picked up on glucose testing. may get polyuria, polydipsia etc as well.
what investigation is used to measures long term glucose control? what are the normal and diagnostic values?
HbA1c - glycosylated haemoglobin - glucose is taken up by haemoglobin and remains in blood for 8-12wks - high blood glucose over that period shows up as a raised HbA1c.
diagnostic value is >48mmol/mol.
what is the WHO diagnostic criteria for diabetes mellitus ?
hyperglycaemic symptoms - polyuria, polydipsia, unexplained weight loss, visual blurring, genital thrush, lethargy AND:
fasting plasma glucose >7.0mmol/L OR.
random plasma glucose >11.1 mmol/L.
describe the general, non-pharmacological management of diabetes mellitus
risk factor management (esp. BP control!).
diabetes education, diet and exercise e.g. educate on self-adjusting doses in T1 (DAFNE).
frequent self-monitoring of blood glucose (if IDDM) and long-term monitoring of HbA1c.
maximise glucose control.
what are the steps in the pathway for managing T2DM
check this is up to date (NICE)
1) lifestyle and diet changes for 6/52, inform DVLA. low GI/dairy/fat/sugar diet, aim for 5-10% wt loss
measure HbA1c 3-6mthly initially then 6/12 (aim 48/6.5%)
2) single drug therapy - metformin ideally, increase gradually over few weeks (GI SEs). aim 6.5%/48.
3) dual therapy only if >58/7.5%: gliptin or sulfonylurea or pioglitazone, target 53/7%.
4) triple therapy if still not under 58/7.5%:
- metform + sulfonylurea + pioglitazone
- metformin + sulfonyurea + gliptin
- start insulin
5) insulin
* if metformin CI do any 1 drug –> any 2 –> insulin
how does metformin work?
biguanide.
reduces rate of gluconeogenesis, reducing hepatic glucose output.
increases insulin sensitivity (GLUT4).
CI - CKD, eGFR <30.
NO weight gain or hypos, but can cause lactic acidosis.
SEs - GI upset** 20% intolerable!
how do sulfonylureas work?
oral hypoglycaemics
binds to channels on beta
cells to increase fusion of insulin granulae with cell membrane - INCREASES PANCREATIC INSULIN SECRETION.
SEs- hypos and weight gain.
CI pregnancy
how does pioglitazone work?
increases insulin sensitivity - promotes glucose consumption by muscles.
SE - wt gain, fluid retention, osteoporosis.
CI - heart failure and osteoporosis.
what are the differences in onset between type 1 and type 2 diabetes?
type 1 - adolescent onset usual.
type 2 - onset usually >40yrs.
type 1 is linked to HLA D3 and D4, type 2 has no HLA association.
what are the differences in how type 1 and type 2 diabetes present?
type 1 will present with polydipsia, polyuria, weight loss, ketonuria etc.
type 2 presents asymptomatically (picked up on blood test), or with complications e.g. MI, recurrent infections
what lifestyle factors is type 2 diabetes associated with?
obesity, lack of exercise, calorie and alcohol excess.
list some possible causes of DM
drugs - steroids, anti-HIV drugs, antipsychotics, thiazides.
pancreatic - pancreatitis, surgery, trauma, pancreatic destruction (haemachromatosis, CF), pancreatic cancer.
Cushing’s disease.
Acromegaly.
Phaeochromocytoma.
Hyperthyroidism.
Pregnancy (gestational diabetes).
give 3 risk factors for type 2 DM
overweight/obese. central adiposity. Asian background. Age >40yrs. FHx. gestational diabetes.
what are the main different types of insulin regimes? what are the important SEs to be aware of for insulin?
1) Once-daily- ;ong or int at bedtime - only suitable T2DM
2) Twice-daily - pre breakfast/evening meal
3) Basal-bolus - long or int at bedtime with rapid/short to cover meals
4) Continuous subcut or insulin pump - if very poor control
hypos and lipodystrophy
give examples of possible injection sites for insulin. why is it important they are rotated regularly?
outer thigh, abdomen, arm.
rotating reduces risk of infection and lipohypertrophy (lipohypertrophy).
what are the main long term complications of diabetes mellitus
retinopathy, neuropathy, nephropathy, skin infections.
also increased risk of MI, stroke etc
describe the symptoms of hypoglycaemia
autonomic - sweating, anxiety, hunger, tremor, palpitations, dizziness.
neuroglycopenic - confusion, drowsiness, visual trouble, seizures, coma
how would you treat hypoglycaemia?
conscious? - 10-20g short acting carb e.g. Lucozade, x3 glucose tablets, glucogel (then some toast or something for long-acting carbs!!)
unconscious? safe airway consider glucogel, IM glucagon probs best!
what is a hypoglycaemic coma? how would you treat it?
rapid onset of hypoglycaemia preceded by aggression, sweating, high pulse, seizures - leading to loss of consciousness.
treat with IV glucose or IM glucagon - should recover promptly.
sugary drinks and a meal once conscious.
how does DKA present?
abdo pain + vomiting
polyuria, polydipsia, dehydration Kussmaul breathing (deep hyperventilation to correct acidosis) Acetone breath (pear drop - ketones)
what causes diabetic ketoacidosis?
there’s an excess glucose, but due to lack of insulin this can’t be taken up by cells to be metabolised - body pushed into starvation-like state.
ketoacidosis is the only alternative metabolic pathway.
results in severe acidosis.
does diabetic ketoacidosis generally occur in type 1 or type 2 diabetics?
type 1 - rare in type 2.
give 3 possible triggers/precipitants of DKA
missed insulin, infection, intoxication, ischaemia, infarction
what would you find on investigation of a patient presenting with DKA?
high plasma glucose (>11)
high plasma ketones >3 mmol/L
ABG - metabolic acidosis (pH <7.3)
urine dip - ketones ++ and glucose.
give 3 possible complications of DKA
cerebral oedema, aspiration pneumonia, **hypokalaemia (caused by you giving fluids and insulin wrong!!!), hypomagnesaemia, hypophosphataemia, thromboembolism
how would you manage a patient presenting with DKA?
ABCDE, catheterise, sats etc
need IV fluids, insulin to drop blood glucose - but will drop potassium so add to fluids. follow hosp. protocol, usually end up needing infusion of insulin and glucose after a bit.
IV normal saline 1L in 1hr, in 2hr, in 2, in 4, in 4, in 6 - switch to 5% dextrose when glucose is <12.
fixed rate IV insulin infusion = 0.1U/kg/hr, add glucose when drops <12
monitor K+ and add to fluids - if >5.5 nil, 3.5-5.5 add 40mmol/L to infusion solution, <3.5mmol/L senior review,
might use IV bicarb for acidaemia.
monitor - electrolytes and bicarb, pH etc every 1-2hrs. glucose hourly, fluid balance, ECG for hypokalaemia.
is hyperglycaemic hyperosmolar non-ketotic (HONK) state/coma more likely to affect a type 1 or type 2 diabetic?
type 2
how would a hyperosmolar hyperglycaemic state present?
longer history (1wk) with marked dehydration and raised glucose.
stupor/coma.
impairment of consciousness is directly related to degree of hyperosmolality.
very high blood glucose >40, v high serum osmolality.
how would you manage a HONK patient?
treat cause, ABCDE etc
safely normalise osmolality- replace fluid and electrolytes
normalise blood glucose.
what are patients with HONK at particular risk of?
cerebral oedema, central pontine myelinosis
also strokes, MI etc
how might diabetic neuropathy present? how would you manage it?
stocking and glove distribution of loss of sensation, absent ankle jerks, deformities. may develop ulcers and ischaemia if there’s accompanying peripheral vascular disease.
special foot care and diabetic shoes needed.
control pain with:
paracetamol => amitriptyline => gabapentin => baclofen
explain the disease process underlying Graves’ disease
autoimmune - serum IgG antibodies bind to TSH receptors causing thyroid growth and overstimulation of thyroid hormone
causes 75% of hyperthyroidism
associated with thyroid eye disease.
worsened by radio-iodine and smoking.
name 3 triggers for the development of Graves’ disease
stress, infections, childbirth, other autoimmune diseases
if you measures TSH and T3/T4 in Graves’ disease, what would you expect to see? other Ix?
suppressed TSH, high T3/T4.
auto-antibodies: anti-TSHR (99% in Graves!) + anti-Tg + anti-TPO.
USS if ? cancer, radioisotope uptake scan (hot = overactive, no uptake in DeQuervain’s)
what are the features of thyroid eye disease?
lid lag, lid retraction, ophthalmoplegia, exophthalmos, gritty eyes, diplopia, loss of colour vision, conjunctival oedema, papilloedema
give 4 clinical features of hyperthyroidism
weight loss diarrhoea heat intolerance increased appetite palpitations tachycardia irritability tremor hyper-reflexia lid lag oedema sweating
eye disease in Graves’
list 3 causes of hyperthyroidism, not including Graves disease
toxic multinodular goitre toxic adenoma
amiodarone
post partum thyroiditis, iodine excess (e.g. contaminated food, contrast media).
overtreatment of hypothyroidism
secondary - TSH secreting pituitary adenoma.
describe the production and general action of thyroid hormones
stimulated by TSH produced by pituitary gland.
thyroid gland secretes mostly thyroxine (T4) + some of the active triiodothyronin (T3).
most T3 is produced by peripheral conversion of T4.
gland requires iodine to produce the hormones.
act on nearly every cell, controlling metabolism - increase BMR.
what would you see on blood tests in hyperthyroidism?
TSH low - suppressed.
raised T4 and T3.
thyroid autoantibodies seen in Graves’.
outline medical management of hyperthyroidism
beta blockers (propranolol) for rapid symptom control. lubricating eye drops if Graves/eye disease
anti-thyroid drugs - carbimazole and propythiuracil.
- carb. = start 10-20mg/day and titrate based on mthly TFT
- propyl. can cause liver failure so only used in pregnancy and thyroid storm.
“block and replace” = carbimazole + thyroxine used to strike fine balance. can sometimes just carefully titrate.
usually euthyroid at 4-8wks, then can reduce till lowest dose. remission at 18mths- try stopping drugs.
WARNNG - sore throat - anti-thyroid drugs can myelosuppress –> agranulocytosis + neuropenic sepsis!!!
what does a thyroidectomy risk?
hoarseness due to damage to recurrent laryngeal nerve.
hypoparathyroidism.
name 2 possible complications of hyperthyroidism
heart failure, angina, AF, osteoporosis, ophthalmopathy, gynaecomastia
what is thyroid acropachy? give 2 features
a dermopathy associated with Graves’ disease.
CLUBBING, painful digit swelling
give 4 symptoms of hypothyroidism
weight gain decreased appetite lethargy low mood cold intolerance constipation hoarse voice decreased memory/cognition cramps and weakness
give 4 signs of hypothyroidism
BRADYCARDIC: Bradycardia. Reflexes relax slowly. Ataxia Dry thin hair/skin Yawning/drowsy/coma Cold hands ± low temp. Ascites ± non-pitting oedema ± pericardial effusion. Round puffy face/double chin/obese. Defeated demeanour Immobile CCF (congestive cardiac failure)
give 3 causes of hypothyroidism
Hashimoto’s thyroiditis (most common UK), iodine deficiency (most common worldwide), post-thyroidectomy/radioiodine treatment,
primary atrophic hypothyroidism, antithyroid drugs.
what would you find on investigation of a patient with hypothyroidism?
high TSH, low T3/free T4.
may see TSH deficiency if secondary hypothyroid (hypopituitary, hypothalamic)
how would you treat hypothyroidism?
levothyroxine (T4) - given for life, monitor TSH levels, increase dose when pregnant
initial dose = 50-100mcg, step up by 25-50 depending on TFT every 3-4/52
risk of osteoporosis and arrhythmias if overmedicate
annual TFTs once stable.
if subclinical then just monito TFT every 6-12/12 and treat is TSH >10
what is Hashimoto’s thyroiditis? what conditions are associated with it?
a primary, autoimmune thyroiditis. cause hypothyroidism (or euthyroidism), with goitre that is due to lymphocytic and plasma cell infiltration. more common in women aged 60-70yrs.
AI disease - T1DM, Addison’s, pernicious anaemia.
as it’s most common cause of hypothyroid in UK - consider these AI diseases in all hypothyroidism.
give 3 diseases associated with hypothyroidism
autoimmune hypothyroidisms are associated with other autoimmune disease - type 1 DM, Addison’s, pernicious anaemia.
Turner’s and Down’s syndromes.
CF, primary biliary cirrhosis, ovarian hyperstimulation, pregnancy problems (eclampsia, anaemia, prematurity, low birthweight etc).
how can thyroid cancer present? treatment options? what blood marker used to monitor?
thyroid nodules and cervical lymph nodes
total thyroidectomy, radioiodine to kill residual cells.
annual thyroglobulin tests to detect recurrence.
where are the common metastases sites for papillary and follicular carcinomas?
lungs and bones
how would you manage a thyroid carcinoma?
total thyroidectomy and lymph node clearance ± radioiodine ablation
what are the different types of thyroid cancer?
70% papillary - young F, good prognosis
20% follicular
5% medullary (part of MEN2)
give one physiological and one pathological cause of goitre
physiological - puberty, pregnancy.
pathological - iodine deficiency, high dose of carbimazole/propylthiouracil
if goitre became painful, what could be the cause?
bleeding, thyroiditis, malignancy
give 2 indications for surgery in goitre
malignancy, pressure symptoms, toxic nodule, cosmetic reasons
what does the adrenal cortex produce, and what do they do?
steroids.
Salt - Sugar - Sex (it gets sweeter as you go deeper)
mineralocorticoids (e.g. aldosterone) - control sodium and potassium balance.
glucocorticoids (e.g. cortisol) - affect carbohydrate, lipid and protein metabolism.
androgens - sex hormones.
how is the adrenal cortex stimulated to produce cortisol/androgens?
corticotrophin-releasing factor (CRF) from hypothalamus stimulates ACTH secretion from pituitary - stimulates cortisol and androgen production.
what is Cushing’s syndrome?
clinical state produced by prolonged glucocorticoid excess –> of normal feedback mechanisms of the hypothalamo-pituitary-adrenal axis and loss of circadian rhythm of cortisol secretion
EXCESS CORTISOL/corticosteroids
what is the main cause of Cushing’s syndrome?
oral steroids
what are the two classes of causes of Cushing’s syndrome?
increased circulating ACTH from a pituitary/ectopic tumour with glucocorticoid excess - ACTH dependent.
primary excess of cortisol secretion by an adrenal tumour or nodular hyperplasia with ACTH suppression - ACTH independent.
give 3 symptoms of Cushing’s syndrome
weight gain stretch marks red puffy, round face tanned skin - Cushing's disease muscle weakness depression tiredness
give 3 signs of Cushing’s syndrome
central obesity, moon face and buffalo hump. skin and muscle atrophy. bruising. purple abdominal striae (stretch marks). osteoporosis hypertension. pigementation, in ACTH dependent causes.
what is the specific test used for Cushing’s syndrome and what would you expect the results to be? other tests?
first line - 1mg overnight dexamethasone suppression test, measure cortisol at 8am.
second line = 48h 2mg dexamethsone test - this would normally suppress cortisol, but in Cushing’s you see normal/low ACTH and high cortisol.
failure to suppress <50nmol/L on either is +ve.
elevated serum glucose.
24h urinary free cortisol (high in 2/3 samples).
what is Cushing’s disease?
bilateral adrenal hyperplasia due to ACTH-secreting pituitary adenoma
give 2 ACTH-dependent causes of Cushing’s syndrome
Cushing’s disease, ectopic ACTH production
give 2 ACTH-independent causes of Cushing’s syndrome
adrenal adenoma/cancer, adrenal nodular hyperplasia, iatrogenic - STEROIDS.
why would you not test for Cushing’s by taking random plasma cortisols?
can be misleading - variation due to illness, time of day, and stress (e.g. venepuncture!)
how would you manage a patient with Cushing’s syndrome?
stop steroids if possible.
cushing’s disease - transphenoidal pituitary adenomectomy ± radiotherapy. last resort - bilateral adrenalectomy.
what is the main cause of acromegaly?
pituitary adenoma - secretes excess GH
give 4 symptoms of acromegaly
persistent numbness and tingling in hands and feet headache amenorrhoea sweating arthralgia increase in weight low libido, backache "my rings and shoes don't fit anymore"
give 4 signs of acromegaly
growth of hands, feet and jaw coarsening face, wide nose macroglossia darkened skin obstructive sleep apnoea goitre carpal tunnel syndrome puffy lips laryngeal dyspnoea
what cardiac disease can acromegaly cause?
hypertrophic cardiomyopathy
what would you find on blood tests in acromegaly? what’s the diff. between acromegaly and Giantism?
raised IGF-1 (main tissue mediator of GH), GH and prolactin - secreted by adenoma
acromegaly = overgrowth of all organ systems, joints, soft tissues by IGF1. Giantism = excess GH or IGF1 before closure of epiphyseal plates.
what specific test would you do to confirm a diagnosis of acromegaly? what else can be helpful when trying to diagnose acromegaly?
oral glucose tolerance test - diagnostic if GH is not suppressed by the glucose.
old photos of the patient.
what is the 1st line treatment of acromegaly?
if that is CI, what would you try?
transphenoidal surgery.
if CI - somatostatin analogues (GH is inhibited by somatostatin) - lanreotide, ocreotide.
GH antagonist - pegvisomant.
what are the metabolic actions of GH?
stimulates IGF-1 to be produced and secreted by the liver.
increases collagen and protein synthesis, opposing the action of insulin (same as glucagon).
promotes retention of calcium and nitrogen.
mainly secreted nocturnally.
explain the pathophysiology underlying Conn’s syndrome
excess aldosterone production causing sodium retention, potassium loss and less renin release - causes hypertension.
explain the renin-angiotensin-aldosterone system
renin is secreted by the kidneys in response to hypoperfusion of the kidneys, which then cleaves angiotensinogen into angiotensin I, which is an inactive form.
angiotensinogen is made in the liver, and circulates in the plasma.
angiotensin I is converted by ACE (produced in lungs) into angiotensin II in the lung and vascular endothelium.
angiotensin II causes vasoconstriction and stimulates the zona glomerulosa to increase its production of aldosterone - raises blood pressure and sodium retention - increasing blood volume.
what is Conn’s syndrome?
a cause of hyperaldosteronism - there’s an aldosterone-producing adrenal adenoma
what are the 2 main causes of primary hyperaldosteronism?
Conn’s disease (adrenal adenoma) and bilateral adrenocortical hyperplasia.
hyperaldosteronism/Conn’s is normally asymptomatic and picked up on a routine test, what test is this?
testing BP - hypertension.
before you begin to investigate hyperaldosteronism/Conn’s, what medications should you stop?
ACEi, beta-blockers, spironolactone, ARBs
what are the sodium and potassium levels seen in patients with hyperaldosteronism/Conn’s, and how does this present?
high serum sodium, low serum potassium.
features - headaches, polyuria (compensatory), muscle weakness, tetany, nocturia.
how would you treat primary hyperaldosteronism?
Conn’s (adrenal adenoma) - surgery ± post-op spironolactone.
benign adrenal hyperplasia - spironolactone.
what causes secondary hyperaldosteronism?
excess renin stimulation of zona glomerulosa due to decreased renal perfusion - accelerated hypertension, renal artery stenosis
Addison’s disease is describe as adrenal insufficiency - which part of the adrenal gland is destroyed and therefore what hormones are affected?
aka primary hypoaldosteronism
the adrenal cortex - decreased production of mineralocorticoids (aldosterone), sex steroids and glucocorticoids (cortisol).
how might a patient present in an Addisonian crisis?
severe hypotension and dehydration, abdominal pain and vomiting, skin pigmentation (increased ACTH).
precipitated by major or minor infections, injury, surgery, pregnancy.
list some causes of adrenal insufficiency
Primary = autoimmune Addison’s disease - 80% of UK cases. also surgical, metabolic failure (CAH e.g.g21-hydroxylase deficiency)
Secondary = inadequate pituitary stimulation of adrenal glands, exogenous steroids (steroids suppress the axis), CRH (corticotrophin releasing hormone) deficiency
how might Addison’s disease present?
mild, non-specific symptoms:
lean, tanned, tired and tearful
± weakness, anorexia, dizzy, faints, flu-like illness.
depression, psychosis, low self-esteem.
GI - nausea/vomiting, abdo pain, diarrhoea/constipation.
what is Addison’s disease commonly misdiagnosed as?
viral infection or anorexia nervosa
what specific investigation would you perform to confirm a diagnosis of Addison’s disease? other tests
short ACTH stimulation (Synacthen) test - measure cortisol, give IV/IM synthetic ACTH and measure cortisol again - its positive if the cortisol decreases - Addison’s is excluded if cortisol after is >550nmol/L
auto-antibody = anti-21 hydroxylase
Na low, K+ high. glucose low in children.
imaging bilateral CT adrenals.
what happens to serum sodium and potassium levels in Addison’s disease?
sodium is decreased and potassium is increased - due to decreased mineralocorticoid
how would you test for autoimmune Addison’s disease?
21-hydroxylase adrenal autoantibodies will be +ve
long-term treatment of Addison’s?
- patient education
- medical emergency bracelet/steroid card
- hormone replacement: hydrocortisone (TDS, highest dose in AM) and fludrocortisone
monitor symps/signs and BP, electrolytes.
screen annually for TFT, glucose/HbA1c, coeliac.
what causes secondary adrenal insufficiency?
long-term steroid therapy suppressing the pituitary-adrenal axis - becomes apparent when steroids are withdrawn.
what is diabetes insipidus?
passage of large volumes (>3L/day) of dilute urine due to impaired water resorption by kidney
what is the difference between cranial and nephrogenic DI?
cranial is due to reduced ADH secretion from posterior pituitary.
nephrogenic is due to impaired response of the kidney to ADH.
give 3 causes of cranial DI
idiopathic, congenital, tumour (craniopharyngioma, metastases, pituitary tumour), trauma, hypophysectomy, autoimmune hypophysitis, infiltration (histiocytosis, sarcoidosis), haemorrhage, infection (meningoencephalitis).
give 3 causes of nephrogenic DI
inherited. metabolic - low potassium, high calcium. drugs - lithium, demeclocycline. chronic renal disease. post-obstructive uropathy.
give 3 symptoms of diabetes insipidus
polyuria, nocturia, polydipsia, hypernatraemia
give 3 signs of diabetes insipidus
dehydration, enlarged and palpable bladder, no weight loss
what specific test can you do to confirm a diagnosis of diabetes insipidus, and what result would you expect?
fluid deprivation test - failure of urine concentration despite fluid restriction.
can give desmopressin - cranial DI will show an increase in urine osmolality.
how would you treat cranial diabetes insipidus?
desmopressin - synthetic ADH analogue.
MRI head to find cause.
why would treatment for cranial DI not work for nephrogenic and what would you use instead?
nephrogenic DI is a defect in channels rendering the kidneys insensitive to vasopressin - so desmopressin will have no effect.
treat cause.
if persists - bendroflumethiazide, and NSAIDs to lower the urine volume and plasma sodium.
explain the effect of vasopressin on the body
vasopressin is synthesised in the hypothalamus and migrates to the posterior pituitary where it is released into the circulation.
stimulates V2 receptors in kidney, making the collecting ducts more permeable to water via aquaporin 2 channels - decreasing diuresis and promoting water retention.
what types of malignancy can cause the syndrome of inappropriate ADH secretion?
small cell lung cancer, pancreas, prostate, thymus, lymphoma
list some causes of the syndrome of inappropriate ADH secretion
malignancies.
neuro - stroke, SAH, Guillain-Barre, SLE, vasculitis, meningoencephalitis.
resp - TB, pneumonia, abscess.
endocrine - hypothyroidism.
drugs - opiates, psychotropics, SSRIs, cytotoxics.
what is the main metabolic abnormality in the syndrome of inappropriate ADH secretion?
hyponatraemia
despite water retention, what is NOT a feature of the syndrome of inappropriate ADH secretion?
oedema
describe the urine of a patient with the syndrome of inappropriate ADH secretion
concentrated urine with hyponatraemia and a low plasma osmolality
what clinical features might you see in the syndrome of inappropriate ADH secretion?
hyponatraemia features - anorexia, nausea and malaise.
then headache, irritability, confusion, weakness, decreased GCS and seizures.
how would you treat the syndrome of inappropriate ADH secretion?
restrict fluid intake + treat cause.
give salt ± a loop diuretic if severe.
describe the usual function of parathyroid hormone
secreted in response to low ionised calcium levels (-ve feedback).
acts by increasing osteoclastic activity - releases calcium/phosphate from bones.
increases calcium reabsorption in kidney.
decreases phosphate reabsorption in kidney.
increases active 1,25-dihydroxy-vitamin D3 production.
overall effect = increases calcium, decreases phosphate.
name a primary, secondary and tertiary cause of hyperparathyroidism
primary - solitary parathyroid adenoma (85% - usually occurs in postmenopausal women), malignancy (lung small cell, breast, renal), hyperplasia of parathyroid gland.
secondary - compensatory hypertrophy of gland in response to low calcium from KIDNEY FAILURE.
tertiary - long term hyperparathyroidism - KIDNEYS again
in hypercalcaemia, you can classify the clinical features as bones, stones, psychic moans and abdo groans- give an example of each of these
bones - pain, cysts, tumours.
psychic moans - depression, psychosis.
stones - renal colic, polyuria, nocturia, haematuria, hypertension.
abdo groans - abdo pain, nausea, vomiting, constipation, anorexia.
what metabolic state usually accompanies hyperparathyroidism?
hypercalcaemia - hyperPTH is most frequent cause of hypercalcaemia!
what biochemical tests and what imaging tests would you perform in assessing hyperparathyroidism?
what are the hormone profiles of the different types of hyperparathyroidism?
high calcium and PTH, low phosphate, high calcium excretion (24h urinary calcium).
DEXA scan to show any skeletal involvement, abdo XR for renal stones
primary = high PTH, high Ca, low phosphate - can be asympt. secondary = high PTH, low Ca, high phosphate, low vit D (kidney) tertiary = high PTH, high Ca, high phosphate, normal vit D, high alk phos
what classical sign is seen on imaging a patient with hyperparathyroidism?
pepper pot skull
how would you treat hyperparathyroidism?
curative (for primary adenoma or gland hyperplasia) = partial/total parathyroidectomy
if mild hypercalcaemia and minimal kidney stones - surveillance (yearly DEXA, check Cr and Ca 6/12)
treat symptomatic hypercalcaemia.
bisphosphonates and cinacalcet (increases sensitivity of parathyroid cells to calcium) can help.
avoid thiazide diuretics, low calcium/vit D diet.
explain how high parathyroid levels can lead to high calcium levels
PTH causes increased release of calcium from bone matrix, increased calcium reabsorption by kidney, increased phosphate excretion, increased renal production of calcitriol (leads to increased intestinal absorption of calcium)
what would biochemical tests show in a patient with hypoparathyroidism?
low calcium, low/normal phosphate
main concern is the hypocalcaemia
how would you treat hypoparathyroidism?
treat the hypocalcaemia - calcium supplements and calcitriol, vit D.
from what malignancies do you most commonly get hypercalcaemia?
squamous cell lung, breast, bone mets, myeloma, GI cancer
how does hypercalcaemia of malignancy occur in myeloma?
stimulation of osteoclasts by IL-1 and TNF promotes calcium loss from bones
give 3 symptoms of hypercalcaemia of malignancy
lethargy, anorexia, nausea, polydipsia, polyuria, constipation, dehydration, confusion, weakness
what are the clinical features of hypocalcaemia?
SPASMODIC:
Spasms (carpopedal spasm triggered by inflating BP cuff over systolic BP - Trousseau’s sign)
Perioral paraesthesiae.
Anxious, irritable, irrational.
Seizures.
Muscle tone increased in smooth muscle - colic, wheeze, dysphagia.
Orientation impaired (time, place and person) and confusion.
Dermatitis.
Impetigo herpetiformis.
Chvostek’s sign (latent tetany - tap facial nerve), choreasthetosis, cataract, cardiomyopathy.
what is Chvostek’s sign and what does it indicate?
when facial nerve is tapped at the angle of the jaw, facial muscles on the same side of the face contract - indicates nerve hyperexcitability due to hypocalcaemia.
give 2 causes of hypocalcaemia with high PTH
CKD, pseudohypoparathyroidism, acute rhabdomyolysis, vitamin D deficiency/resistance, hypomagnesaemia
give 2 causes of hypocalcaemia with normal/low PTH
what are the most common causes of hypocalcaemia? what are the important causes to rule out?
parathyroid agenesis (DiGeorge), destruction (surgery, radiotherapy)
most common = CKD, hypoPTH, pseudohypoPTH, vit D deficiency or malabsorption.
rule out/important = acute pancreatitis, hyperventilation, rhabdomyolysis
how would you investigate hypocalcaemia?
what would you see on the ECG of a patient with hypocalcaemia?
- adjusted calciu,
- exclude CKD (U&E), acute pancreatitis (amylase), rhabdo (check CK)
- serum: Mg, PO4, PTH
- evaluate vit D metabolism
ECG = prolonged QT interval.
how would you treat chronic hypocalcaemia?
calcium supplements + alfacalcidol (derivative of vitamin D).
what makes hyperkalaemia a medical emergency?
causes cardiac hyperexcitability, leading to ventricular fibrillation and cardiac arrest.
give 3 possible causes of hyperkalaemia
Addison's disease AKI/CKD potassium-sparing diuretics (spironolactone) metabolic acidosis burns/rhabdo ACEi, ARB, NSAIDs, heparin, ciclosporin DKA digoxin, beta-blockers
artefact - long tourniquet time, clenched fist
give 3 changes you would see on an ECG of a patient with hyperkalaemia
tall tented T waves, reduced P waves, widened QRS complexes.
give 2 possible clinical features of hyperkalaemia
fast irregular pulse, chest pain, weakness, palpitations, light-headedness, ECG changes
how would you manage a patient with hyperkalaemia?
ABCDE, 12 lead ECG (>7 or ECG change or symptomatic = URGENT).
- reduce potassium - stop any potassium supps/fluids, stop digoxin/beta-blockers if poss.
- protect heart - 10ml 10% calcium gluconate IV (can repeat every 10mins up to 50ml if no ECG changes.)
- shift K+ into cells - IV infusion of insulin + glucose: 10U insulin + 25g glucose. keep an eye on their BM.
- salbutamol nebs also shifts potassium into cells.
- remove potassium from body - calcium resonium
- haemodialysis if none of the above work
there will be a hospital protocol.
give a chronic and an acute cause of hypokalaemia
acute - IV fluid without potassium, vomiting/diarrhoea.
chronic - diuretics, Conn’s.
list 2 clinical features of hypokalaemia
muscle weakness, hypotonia, hyporeflexia, cramps, tetany, palpitations, light-headedness, constipation.
what ECG changes might be seen in a patient with hypokalaemia?
small/inverted T waves.
prominent U waves.
long PR interval.
depressed ST segments.
how would you treat hypokalaemia
mild - oral potassium supplement.
severe - IV potassium NEVER bolus as can cause fatal arrhythmia! never exceed 10mmol/hr. cardiac monitoring + bloods every 1-3 hrs.
what are carcinoid tumours and where are they most commonly found?
diverse group of tumours of enterochromaffin cell (neural crest) origin, capable of producing 5HT.
appendix, ileum, rectum, elsewhere in GI tract, ovary, testis, bronchi.
what is carcinoid syndrome?
only occurs if there are liver metastases.
spontaneous red-blue flushing mainly on face and neck (kinis), pulmonary stenosis/tricuspid incompetence (5-HT), hepatomegaly.
tumours secrete serotonin, kinin, histamine, prostaglandins.
how would you treat carcinoid syndrome?
somatostatin analogues - ocreotide and lanreotide.
resection of primary tumour.
somatostatin analogues are used in which pituitary disease and how do they work?
acromegaly, they inhibit the release of growth hormone from the anterior pituitary
what renal drug can you use to treat Conn’s?
spironolactone - it is an aldosterone antagonist, so increases potassium reabsorption.
carbimazole is used to treat hyperthyroidism, what is the mechanism of action?
stops coupling and iodination of thyroglobulin to TPO (thyroid peroxidase)
why do you give nebulised salbutamol, insulin and calcium gluconate to treat hyperkalaemia?
calcium gluconate increases the threshold potential and restores normal gradient between that and the resting membrane potential - protects heart, but doesn’t change K+ levels.
insulin forces potassium back into cells - give with glucose.
salbutamol lowers serum potassium levels by promoting movement of potassium back into cells.
how do levothyroxine and liothyronine work as treatments for hypothyroidism?
levothyroxine is a synthetic T4, so gets converted into T3.
liothyronin is synthetic T3 - quicker onset, used in emergencies.
name 2 antithyroid drugs, describe how they work.
carbimazole, methimazole.
prevent thyroid peroxidase enzyme from coupling and iodinating the tyrosine residues on thyroglobulin - so reduces the production of the thyroid hormones T3 and T4.
name 2 calcitonin drugs, and what they treat
miacalcin, fortical.
postmenopausal osteoporosis, hypercalcaemia
how do calcitonin drugs work?
calcitonin is produced in thyroid gland by C cells and increases deposition of calcium and phosphate in bone, lowering circulating levels.
calcitonin drugs inhibit calcium resorption by intestine, inhibit osteoclast activity in bones, stimulate osteoblast activity and inhibit renal reabsorption of calcium.
what class of drug is pegvisomant and what is it used to treat?
growth hormone receptor antagonist.
acromegaly, if pituitary tumour can’t be controlled with surgery/irradiation
how does pegvisomant work?
blocks action of GH at the GH receptor to reduce production of insulin-like growth factor-1 (responsible for most of the symptoms of acromegaly).
what generally causes a patient to go into hyperosmolar, hyperglycaemic state?
very high glucose levels develop due to combination of:
illness e.g. infection (pneumonia!)
dehydration
inability to take normal diabetes meds due to illness (so poor control).
how does sitagliptin, a DPP-4 inhibitor, work?
inhibits DPP-4, which results in increased insulin secretion in response to meals, and decreased glucagon secretion by alpha cells of pancreas.
brings glucose levels nearer to normal, without any risk of hypos.
what are phaeochromocytomas? where are they usually found?
rare catecholamine-producing tumours.
arise from sympathetic paraganglia cells - collections of chromaffin cells.
usually found in adrenal medulla.
what is the 10% rule of phaeochromocytomas?
10% are malignant, 10% are extra-adrenal, 10% are bilateral and 10% familial.
what is the main problem caused by phaeochromocytomas?
hypertension
what is the classic triad of clinical features of phaeochromocytomas?
episodic headache, sweating and tachycardia
how might a phaeochromocytoma be treated?
surgery - alpha blockade pre-op, then beta blockade.
explain pathway of insulin release in pancreas
glucose enters beta cell via GLUT-2 –> increases ATP –> ATP closes K+ channels which depolarise cells –> VgCa channels open –> Ca moves into cell –> insulin released.
explain the action of insulin on peripheral muscle cells? what happens with insulin/glucose in the body after eating.
binds insulin receptor on peripheral muscle cells
mobilises GLUT-4 to membrane - glucose then able to enter cell.
increase glucose –> increased insulin:
increased uptake in liver (200g) and muscles (150g) as glycogen.
this suppresses gluconeogenesis, lipolysis, proteolysis, ketogenesis
explain how diabetic NEURopathy works?
hyperglycaemia –> oxidative stress –> lipid peroxidation of myelin –> glove and stocking sensory changes
explain how diabetic NEPHropathy works
hyperglycaemia –> mesangial expansion + thickening of glomerular basement membrane.
narrowing of efferent renal artery –> increased pressure in glomerulus –> glomerular sclerosis + thickened BM –> increased gaps between podocytes (more permeable) –> hyperfiltration
proteinurine and < GFR leads to HTN
treat with ACEi or ARB!
give some basic info on diabetic foot
occurs in 10% - most common cause of amputation.
RF - ulcers, PAD, peripheral neuropathy
PAD + neuropathy + infection - end up with ulcers (neuropathic - painless, punched out- or arterial), loss of pulses.
basically patient can’t feel their foot so they let it get v grim
what are the different types of diabetic eye problems? what’s the mechanism?
cataracts, retinopathy, maculopathy, glaucoma
microvascular occlusion –> retinal ischaemia –> AV shunts + neovascularisation.
pericyte loss –> leakage –> haemorrhages or diffuse oedema
what are the possible fundoscopy features in a diabetic eye?
- microaneurysms - physical weakness
- hard exudates - lipoproteins from leakage
- haemorrhages - rupture of weakened capillaries - small dots, blots or flame.
- cotton wool spots - build up of axonal debris
- neovascularisation
need slit lamp Ix!
how are diabetic eye problems classified?
- Background - one microaneurysm
- Mod - microaneurysms, IR haem ± cotton wool spots, venous beading + IRMAs (intra-retinal micro vasular abnormalities)
- Severe/pre-prolif - see ophth, depends on number and quadrants
- Proliferative (non-high risk) new vessels on disc (or <1 diam) or NV everywhere
Proliferative (high risk) large NVD or NVE
how do diabetic eye problems present? who requires an emergency referral?
painless, gradual reduction of central vision.
haemorrhage may present with sudden onset dark, painless floater.
emergency refer - sudden LOV, red eye, retinal detachment (see opthamology)
list some management options for diabetic eye problems
- optimise glycaemic control (obvs)
- BP, lipid control
- laser photocoagulation or intravitreal steroids, anti-VEGF
what should be included in an annual diabetic review?
Educate + modifiable RFs
- Check BMI
- Check complications: hypos, HOHS, DKA
- Assess CVS: BP, pulses, bruits
- Inspect injection sites - lipodystrophy
- Foot check - neuropathy and pulses
- Urine dip - protein, nitrites, ketones
- Check eyes - acuity and ophthalmoscopy -> refer opthalmology
- Ask erectile dysfunction
- Bloods: HbA1c and home capillary monitoring results, random lipids
how do gliptins work?
DPP-4 inhibitors (DPP-4 destroys incretin - more incretin means can produce more insulin when needed)
SEs - GI upset and flu-like symptoms
what’s the NICE recommended insulin regime for T1DM?
MDI (multiple daily injections) basal-bolus regimen:
- twice daily detemir (long acting) +
- rapid acting insulin analogue before meals (Humalog or Novorapid)
what’s the NICE recommended insulin regime for T2DM?
NPH insulin twice daily intermediate = Humulin N or Novolin N
briefly explain ‘sick day rules’ for diabetics
rules used if unwell - 4hrly monitoring + beware DKA (may monitor ketones).
aim for 3l fluids/24hrs - take sugary drinks if can’t eat.
meds - continue oral hypoglycaemics, continue normal insulin regime but increase monitoring.
if on oral meds - seek help if glucose >13mmol/L
if on insulin = seek help if signs of DKA or glucose >25mmol/L despite increasing insulin
why do diabetics need sick day rules?
stress response to illness –> increased cortisol
cortisol increases blood sugars and decreases insulin
ECG findings for hypokalaemia?
PRSTTU: PR prolonged ST depression Flattened/inverted T wave Prominent U wave after T
what are the criteria for metabolic syndrome? define it?
- Truncal obesity: men ≥ 94cm, women ≥ 80cm or -BMI > 30
- BP: Systolic ≥130 diastolic ≥ 85 or prev Dx HTN
- Reduced HDL: <1.03mmol/l (men), <1.29mmol/l (women)
- High triglycerides: ≥ 1.7mmol/l
- Fasting glucose ≥6.1mmol/l (prediabetes)
def = cluster of common abnormalities including insulin resistance, impaired glucose tol, reduced HDL, elevated triglycerides and HTN
what are the cut offs for different categories of obesity?
≤18.5 underweight 18.5-24.9 optimal 25-29.9 overweight 30-34.9 obese I 35-39.9 obese II ≥40 obese III - weight is imminent threat
list some medications that can cause/contribute to obesity
Glitazone, sulfonylurea Anticonvulsants Antidepressants: tricyclics and mirtazapine Lithium Progesterone only contraception Beta blockers Corticosteroids
list some conditions that can cause obesity
hypothyroid, PCOS, Cushing’s hypogonadism.
poss. genetic link = KRS2 (severe insulin resistances and reduced metabolic rate)
how would you investigate and manage obesity according to weight class?
Ix = hormone profile, esp. sex hormones, cortisol, TFT.
According to weight class:
Overweight: structured advice diet + ex, if comorbid consider drug post lifestyle
Obese I: structured advice diet + ex, if comorbid consider drug post lifestyle
Obese II: structured advice ± drug, consider referring for surgery
Obese III: structured advice ± drug, consider referring for surgery
what does NICE say about diet and exercise advice for obesity?
diet - recommend 600kcal deficit, reduce fat consumption.
in some consider low cal (800-1600) or very low cal (<800 - not for more than 12/52)
exercise - need realistic expectations! helps increase BMR. aim for 30 mins moderate exercise x5/week
drug/surgical management for obesity?
orlistat - only after diet/behaviour/exercise. continue for 3/12, only if lose 5% wt. take 1 tablet 1hr after each meal - lipase inhibitor (reduces absorption of dietary fat).
CI in cholestasis.
surgery - bariatric surgery:
indications = BMI >40 or >35 w/signif co-morbidity and all non surgical measures tried.
types:
- restrictive - gastric banding
- malabsorptive - biliopancreatic diversion
- both = gastric bypass
describe the pathophysiology of gynaecomastia
oestrogens stimulate, androgens inhibit - so ratio is important
conditions raising oestrogen vs dropping testosterone/androgen resistance.
conditions causing increased conversion of androgrens to oestrogen - aromatase (in increased adiposity)
aetiology of gynaecomastia? split according to different pathology
1) physiological @ 14 (unilateral + tender) - assoc delayed testosterone, aging - low testosterone
2) low testosterone - androgen resistance, Klinefelter’s, viral orchitis (mumps), renal disease
3) high oestrogren- neoplasms secreting HCG (e.g. seminoma) or ectopic BCG lung, RCC, adrenal tumour (oestrogen), CAH, *liver disease - increased prod androstenedione and aromatisation to oestrogen), obesity, hyperThyroid
4) high prolactin - prolactinoma
*Medication (25%)
what medications can cause gynaecomastia?
DISCO: digoxin, isoniazid. spironolactone, cimetidine, oestrogen
- Spironolactone - inhibits testosterone synthesis
- Digoxin - oestrogen like effect (enhanced with liver failure)
- Finasteride - inhibit testosterone action
- Anabolic steroids - androgens cause high oestrogens
- Increase prolactin - antipsychotics, TCA, metoclopramide
what different hormone profiles might you see in a patient with gynaecomastia? what other investigations would you do?
- LH high + test low = testicular failure
- LH low + test low = increased oestrogens
- LH high + test high = androgen resistance or neoplasm
- renal function, LFT, TFT, oestradiol, testosterone, prolactin, bHCG, AFP, LH
- imaging - USS or mammography if suspicious or unilateral (+/- needle core biopsy).
try and learn HPA axis/thyroid hormone physiology
maybe watch a video?
what is myxoedema? how do you manage a myxoedema coma?
mucopolysaccharides accumulate under skin and tissue in hypothyroid - thickening of facial features.
expressionless face with peri-orbital fullness, pale cool skin w/rough/doughy texture.
enlarged heart, megacolon, cerebellar aataxia
psychosis, encephalopathy –> myxoedema coma (occurs in elderly, usually precipitated by infection) - get seizures, hypothermia, decreased consciousness, hypoventilation.
Rx = IV levothyroxine + Iv hydrocortisone (test blood cortisone first) + resp support
what kind of goitre do you see in Hashimoto’s thyroiditis?
painless, diffuse, varying in size, rubbery, irregular surface.
atrophic AI hypothyroidism is other end of spectrum to Hashimoto’s - overtly hypothyroid and have NO goitre.
what will investigations show in autoimmune hypothyroidism?
TFT:
primary = high TSH, low T3/T4
secondary = low TSH, low T3/T4
autoantiboidies = anti-TPO, anti-Tg (anti-thyroglobulin)
what non-drug treatment options are there for hyperthyroidism?
radioactive iodine (CI pregnancy/breast feeding) - but can worsen eye disease in Graves’.
Surgery - only once euthyroid. subtotal thyroidectomy.
complciations - hypoparathyroidism + damage to recurrent laryngeal nerve (*hoarse voice post-op)
how does a thyroid storm (aka thyrotoxic crisis) present?
occurs in Graves or toxic multinodular goitre.
hyperpyrexia (>41)
CVS: HR > 140, hypotension, AF, CHF
GI: Nausea, jaundice, vomiting, diarrhoea, abdominal pain
NEURO: Confusion, agitation, delirium
precipitated by infection
management of a thyrotoxic crisis patient?
Ix - sepsis screen, TFT, ECG, CXR, ABG
Management - ABCDE, fluid resus, NG tube if vomiting, treat infection.
antithyroid Rx:
- oral carbimazole or propylthiouracil
- Lugol’s solution at 4hrs (aqueous iodine)
- IV propranolol
- IV hydrocortisone (for possible relative adrenal insufficiency).
keep cool with tepid sponging (NOT paracetamol)
how does hyperparathyroidism tend to present?
usually asymptomatic and diagnosed when hypercalcaemia is found!
give some causes for the different types of hypoparathyroidism
Primary hypoparathyroidism:
- Congenital - DiGeorge (defect in PTH gene –> defective Ca sensing)
- Acquired - neck surgery/irradiation, iron deposition (haemochromatosis), Wilson’s (copper), alcohol, Mg deficiency or excess
T2 = pseudohypoparathyroidism - defective PTH action:
- characteristic morphology (low IQ, short stature, short 4th/5th metacarpals)
- low Ca, high PO4, high PTH (but end organ resistance so it doesn’t do anything)
T3 = pseudopseudohypoparathyroidism
- I wish this was a joke
- similar phenotype to T2 but normal biochem.
explain calcium correction
normal calcium range 2.2.5-2.5mmol/L
in hyperCa, half circulation Ca is protein bound so need to adjust for albumin - cos we only care about the unbound, ionised Ca.
correction:
+ 0.1 for every 4g/L albumin is <40g/L
- 0.1 for every 4g/L albumin is above 40g/L
what’s the most common cause of hypercalcaemia?
secondary to hyperparathyroidism in a post menopausal woman
what symptoms of hypercalcaemia do you get at what degree of severity?
- mild = <2.8 = polyuria + polydipsia, dyspepsia (calcium release gastrin), depression, mild cognitive impairment
- moderate = <3.5 = muscle weakness, fatigue, constipation, anorexia and nausea
- severe = >3.5 = abdo pain, vomiting, dehydration, arrhythmia + short QT, coma, pancreatitis
what investigations might you run in hypercalcaemia and what might they show?
- High corrected Ca (<3 = PHPT, >3 = malignancy)
- Albumin - high -> with high urea = dehydration
- Alk phos - normal in myeloma, raised in bony mets
- Calcitonin - B cell lymphoma
- PTH - high = primary hyperPTH, low = granulomatous or adrenal
*XR - bone abnormalities, cysts, pathological fractures etc
acute management of hypercalcaemia >3.5
- IV 0.9% saline - hydrates, increases urinary excretion
- loop diuretic (furosemide) for fluid overload
- post-rehydration = IV bisphosphonates (pamidronate or zolendronic acid)
- If vit D toxicity, sarcoid, lymphoma - glucocorticoids
- If secondary hyperPTH = cinacalcet
- If underlying kidney disease - haemodialysis
acute management of hypocalcaemia?
if seizures/tetany or <1.9
- 10ml 10% calcium gluconate slow IV infusion, repeat as necessary
- oral calcium
- monitor calcium
- if hypomagnesaemia - correct otherwise Ca will not respond.
what hormones are produced in the anterior pituitary gland?
GH: stimulates liver to produce IGF-1 and counteracts insulin
Prolactin: promotes growth of mammary glands and reproductive organs
FSH: stimulates release of sex steroids
LH: stimulates release of sex steroids
ACTH: adrenocorticotropic hormone: stimulates adrenal cortex to release glucocorticoids and androgens
TSH
what hormones are produced in the posterior pituitary gland?
supraoptic nucleus = vasopressin
paraventricular nucleus = oxytocin
describe the local effects of a pituitary tumour
cavernous sinus contains CN 3, 4, 5a/b, 6 and the optic chiasm.
get headaches - retro-orbital and bilateral, worse on waking
visual field defect = bitemporal hemianopia
ocular nerve palsies = squint
what are the most common types of pituitary tumour?
usually benign non-functioning adenoma.
then:
prolactinoma > GH > ACTH > TSH > LH/FSH
how might a pituitary tumour be managed?
- transphenoidal surgery (can lead to further pituitary dysfunction –> adrenal insufficiency, DI, SIADH)
- radiation for recurrence
- drugs:
- prolactinoma - bromocriptine
- GH - somatostatin analogues
- hormone replacement (make sure you give steroids before levothyroxine as this can precipitate adrenal crisis)
main worry = pituitary apoplexy = rapid enlargement of gland due to bleed into tumour - mass effect, CV collapse, acute hypopituitarism
what are the effects of a prolactinoma (–> hyperprolactinaemia) in men vs women?
NB - you get physiological hyperPRL in pregnancy, puerperium and stress.
women: inhibits GNRH -> reduced gonadotropin (FSH + LH) secretion -> menstrual dysfunction + galactorrhoea -> low oestrogen
men: direct reversible response on hypothalamus -> secondary hypogonadism -> decreased libido and ED
give some non-prolactinoma causes of hyperprolactinaemia
- hypothyroid - raises TSH which raised PRL
- Cushing’s synd.
- *antipsychotics (block dopamine –> raised PRL)
e. g:
- Dopamine receptor antag: domperidone, metoclopramide, neuroleptics
- Dopamine depleting: methyldopa
- Antidepressants: e.g. TCA, MAOI, SRI
how does hyperprolactinaemia present in women and in men
Women: oligomenorrhoea, amenorrhoea, galactorrhoea, infertility, hirsutism
Men: slower pres, reduced libido, reduced beard growth, ED
Children: growth failure and delayed puberty
If macroprolactinoma
Headache, vis disturb, bitemporal hemianopia or upper temporal quadrantanopia
investigation and management of hyperprolactinaemia?
Ix:
- PRL: normal < 400, if mild el = 400-1000 - repeat before referral
> 5000 = true prolactinoma
- TFT, exclude pregnancy, assess other pituitary function
- MRI pituitary
Rx if effect of size or adverse effect of hyperPRL
- dopamine agonist e.g. cabergoline or bromocriptine (SEs - sleepiness, hypotension, cardiac/pulmonary fibrosis (monitor))
which bits of the adrenals produce what hormones?
GFR - salt, sugar, sex - the deeper you go the sweeter it gets
zona Glomerulosa - mineralocorticoids - aldosterone
zona Fasciculata - glucocorticoids - cortisol
zona Reticularis - androgens
what are the effects of cortisol?
RIDGE: Suppression of reproduction Suppression of immunity Suppression of digestion Suppression of growth mobilisation of Energy -> elevated sugars - insulin is ineffective
diurnal variation - highest at morning, lowest at midnight.
acute management of Addisionian crisis?
IV/IM hydrocortisone (100mg if adult)
rehydration w/ IV fluids.
further hydrocortisone + glucose: 100mg in 5% over 24hrs.
continuous cardiac and electrolyte monitoring.
treat infection/precipitant.
how does different sodium levels affect the brain?
Na 130-135 = headaches
Na 125-130 = weakness + lethargy
Na <125 = agitation + coma
acute hyponatraemia can cause cerebral oedema due to low serum osmolality (water moves into brain)
rapid correction causes rapid movement of water out of brain –> osmotic demyelination!
