Endocrine Flashcards
what is diabetes insipidus
insufficiency or failure to respond to ADH
features of diabetes insipidus
polydipsia, polyuria, thirst
hypernatraemia, dilute urine
treatment of primary diabetes insipidus?
desmopression - ADH analogue
what does primary organ dsyfunction mean?
abnormality in target organ
what is secreted in the anterior pituitary gland?
TSH ACTH GH Prolactin LH + FSH
what is secreted in the posterior pituitary gland?
stores ADH
produces oxytocin
describe the anatomy of the adrenal gland
adrenal cortex and adrenal medulla
describe the anatomy and function of the adrenal cortex
glucocorticoids - zona fasicularis
mineralcorticoids - zona glomerulosa
androgens - zona reticularis
what is the function of glucocorticoids
stress response, immune response, metabolism and other life functions
function of mineralcorticoids
electrolyte regulation
blood pressure
vascular volume
what is made in the adrenal medulla?
catecholamines like epinephrine, norepinephrine and dopamine
what happens in congenital adrenal hyperplasia?
group of conditions, causing either over or under production of mineralcorticoids or androgens, most commonly due to faulty gene for 21 hydroxylase
symptoms in over production of androgens in congenital adrenal hyperplasia?
clitoral megaly, shallow vagina, menstrual irregularity,
precocious puberty, infertility, excessive facial/pubic hair, rapid childhood growth
males - normal penis but aspermia
what is Conn’s syndrome?
hyperaldosteronism - hypernatraemia and hypokalaemia
what is phaeochromocytoma?
tumour producing too much catecholamines
which of the thyroid gland is the active hormone?
T3
why does sick euthyroidism happen?
enzyme that converts T4 to T3 is found in tissue throughout the body, when the body is under stress, it stops producing the enzyme causing increase in T4 but normal or reduced T3
what happens in Graves disease
antibodies made that bind to TSH receptors in thyroid gland, producing excess T4/T3
what happens in complete androgen insensitivity syndrome?
46XY male that has a defect in testosterone receptors, thus causing failure of male sexual characteristics to develop
what happens in turners syndrome?
45X chromosome defect, causing deficiency estrogen which results in a host of symptoms
what must be considered when measuring hormone levels?
time of day and the natural diurnal variations of hormones
how is calcium regulated?
drop in ca2+ is sensed by parathyroid, releasing PTH in response.
rise in ca2+ is sensed by thyroid gland releasing calcitonin in response
what functions does PTH have
increase osteoclast activity, increasing bone resorption
stimulating renal activation of vitamin D which leads to increased gut absorption of calcium
increase renal absorption of calcium from urine
how is vitamin D made
through sunlight in the skin it is converted from precursors and sent to the liver and finally the kidney where it is activated into calcitriol which increases gut absorption of calcium
what is bone made of?
non-organic hydroxyapatite, osteoid made of collagen and chondroitin, living cells like osteoblasts, osteoclasts, osteocytes and others
2 most common causes of hypercalcaemia
hyperparathyroidism
cancer
symptoms of hypercalcemia
thirst, polyuria, kidney pains, abdominal pains
bone pain, myalgia, weakness
constipation, vomiting, anorexia
mood change, depression, confusion
why do you get polyuria and thirst from hypercalcaemia?
high calcium in tubules impair resorption
common age/gender for primary hyperparathyroidism
elderly women, 1:1000 in population
most common cause of primary hyperparathyroidism?
benign solitary parathyroid adenoma
biochemistry in primary hyperparathyroidism?
Calcium Phosphate PTH Alk Phos Urinary calcium
calcium high phosphate low PTH high alk phos high urinary calcium high
why is alk phos raised in primary hyperparathyroidism?
due to increased bone turnover
complications of primary hyperparathyroidism?
kidney stones, renal impairment
osteoporosis at peripheral bones (wrists, hips)
erosion of periosteium
osteoclastomas
corneal calcification
management of primary hyperparathyroidism?
usually surgical if symptomatic
T or F, if primary hyperparathyroidism is asymptomatic, surgery is not indicated
T
what medical management can be used in primary hyperparathyroidism?
calcium receptor agonist - cinacalcet
when is malignant hypercalcaemia usually seen?
late stage of cancer
3 common causes of malignant hypercalcaemia
humoral hypercalcaemia of malignancy
boney erosions due to metastasis
myeloma
pathophysiology of HHM?
abnormal activation of PTHrP gene producing PTHrP proteion causing bone resorption
common cancers that cause HHM?
lung, breast, oseophagus, cervix, skin, renal, bladder, ovary, vulva
HHM patients are at an increased risk of pathological fractures due to thinning of bone - T or F?
F
myeloma commonly presents with hypocalcaemia - T or F?
F, usually hypercalcaemia
why does myeloma cause chances in calcium?
diffuse osteolysis due to overproduction of local cytokines e.g. IL-6, causes erosion of bones
typical biochemistry of myeloma caused hypercalcaemia - Ca2+, Phos, alk phos
ca2+ raised, phos high, alk phos normal
why is phosphate raised in myeloma associated hypercalcaemia
myeloma produces lots of immunoglobulins causing renal damage which causes phosphate to rise
steroids are effective against treating hypercalcaemia due to myeloma - t or f
T
is phosphate usually high or low in hypercalcaemia?
usually low if PTH driven
why do focal osteolytic mets cause an increased risk of pathological fractures?
cancer invasion erodes bones and mineral structure, weakening it
pathological fractures due to boney mets usually heal with treatment - T or F
F, they are very difficult to heal due to cancer invasion
management for acute hypercalcaemia?
hydration - 6L saline over 24 hours
bisphonates once hydrated
what is the bisphosphonate of choice in hypercalcaemia?
zolendronic acid
acute rhabdomyolysis causes hypercalcaemia - T or F?
F, it causes hypocalcaemia
symptoms of hypocalcaemia?
paraesthesia of mouth and fingers
muscle twitching and leg cramps
laryngeal stridor - vocal cord cramping
seizures, hyperreflexia
chosteks sign, prolonged QTc
what is chvosteks sign
in hypocalcaemia, if u inflate a BP calf, and tap the patients parotid glands, it will cause twitching in the eye and face
common causes of hypocalcaemia?
vit D deficiency hypoparathyroidism renal failure drugs acute rhabdomyolysis acute pancreatitis
causes of hypoparathyroidism ?
iatrogenic post thyroidectomy
congenital absence of parathyroids
genetic/chromosomal abnormality
autoimmune conditions - autoimmune polyendocrinopathy
biochemistry of hypoparathyroidism?
calcium, phosphate, PTH, urinary calcium
cal - Low
phos - high
PTH - low
urinary cal - low
what is renal function like normally in primary hypoparathyroidism?
normal
why does serum magnesium affect calcium?
hypomagenisum inhibits PTH release and peripheral action of PTH
if patient is hypomagenesium, calcium will not correct until magnesium is corrected
what is secondary hyperparathyroidism?
when renal impairment causes hypocalcaemia and consequently hyperphosphataemia, stimulating PTH to be released
how is osteoporosis diagnosed?
clinically after osteoporotic fracture OR radiologically from DEXA
what is the DEXA diagnosis of osteporosis?
-2.5 SD of BMD
what are DEXA scans usually done of
wrist, femur, lumbar
risk factors for osteoporotic fractures
low BMI, tall stature smoking and alcohol medication - steroids prem menopause calcium intake fam hx
treatment for osteoporosis
calcium and vitamin D
lifestyle changes
bisphosphonates
HRT
what is osteomalacia?
vit D def causing bone abnormalities
what is different in bones in osteomalacia?
reduced mineral content - hydroxyapatite
symptoms of osteomalacia
in children - genu valrum/valgus
weakness, myalgia, bone pain, tetany
treatment of osteomalacia
vitamin D, colecalciferol, ergocalciferol
causes of osteomalacia
lack of sunlight/vitamin D
drugs - anticonvulsants
renal or hepatic disease
dietary def of calcium/phosphate
how to diagnose diabetes mellitus?
if asymptomatic, 2x random BM >=11.1
if symptomatic, one random BM over 11.1
or fasting BM over 7.0 or 2 hour after OGTT BM over 11.1
or Hba1c >= 48 mmol/mol
when should hba1c not be used for diagnosis of DM?
in children and young adults
for GDM
during pregnancy and 2 months after birth
if acutely unwell - hba1c takes 3 months to change
if on steroids or other glucose affecting drugs
renal failure
HIV
what is MODY?
maturity onset diabetes of the young - hereditary monogenic forms of DM affecting insuling production, that usually present between 20-50 years old
describe how insulin is secreted
rise in blood glucose causes influx of glucose into beta islet cells through channels, these are phosphorylated by glucokinase which is then used to produce ATP. ATP inhibits K-atp pumps which stops efflux of K from the cell. this causes depolarisation of the cell causing influx of Ca2+ ions, stimulating insulin release
clinical features of MODY
usually asymptomatic, incidental finding. or misdiagnosis of t1dm or t2dm low insulin requirement family history if DM lack of metabolic symptoms found in T2DM
describe glucokinase MODY
functional insulin production but raised set point to trigger insulin secretion. persistently raised BM, no complications associated, no treatment needed
describe hnf1a and hnf4a mody
similar symptoms
normoglycaemic in childhood, but progressively gets worse till 30s.
may be misdiagnosed as t1dm. usually notobese, poor control leads to complications. responds to sulphonylureas. do not use insulin
describe MODY 5
AKA HNF-1b. causes renal complications - cysts and impaired function. associated with pancreatic and genitourinary abnormalities. require insulin
where (within healthcare) is MODY commonly diagnsed
incidental finding
OGTT during pregnancy
renal clinic
after hypoglycaemia
T1DM is not possible before 6 months old - t or F
True, called neonatal diabetes mellitus before 6 months
what is c peptide
part of proinsulin that is cleaved off to form active insulin. used to measure insulin production, more reliable than measuring insulin because c peptide is not broken down by the liver
when should hba1c not be used for diabetes
young people if pregnant or ?GDM if acute onset of symptoms anyone on glycemic affecting drugs HIV renal failure
what is neonatal diabetes?
diabetes presenting before 6 months of age
how does neonatal diabetes present
hyperglycaemia or DKA
low birth weight
low c peptide
is c peptide high low or normal in neonatal diabetes
low
neonatal diabetes is usually life long - t or f
false, can be transient or permanent
what medication is used in neonatal diabetes
sulphonylurea
what are some endocrinopathies that can cause secondary diabetes?
cushings acromegaly phaeochromocytoma hyperthyroidism glucoagonoma
Down’s syndrome is associated with diabetes - t or F
T
what is lipodystrophy
condition where body is unable to produce and maintain fat tissue due to lack of leptin. associated with insulin resistance and other metabolic syndromes
what are some drugs that can cause diabetes
long term steroid use HIV HAART antipsychotics beta blockers statins
name the hormones secreted or regulated by the anterior and posterior pituitary
anterior - GHRH, TRH, ACTH, LH/FSH, prolactin,
posterior: oxytocin, adh
what is pituitary apoplexy
infarction/haemorrhage of the pituitary
describe the adrenal-pituitary axis
CRH produced by hypothalamus stimulates pituitary to produce ACTH which stimulates adrenal glands to make cortisol/steroids
symptoms of hypoadrenalism
fatigue, weight loss, nausea and vomiting, abdominal pain, postural hypotension, hypoglycaemia, hyponatraemia, hyperkalaemia, acidosis
what is primary hypoadrenalism called and caused by
failure of adrenal glands to produce steroids, addison’s disease
difference between primary and secondary hypoadrenalism
pri - adrenal glands not working, low glucocorticoids, mineralcorticoids, and sex steroids
secondary - pituitary not making acth, low glucocorticoids, but normal mineralcorticoids
clinical features of addison’s disease
same as those of hypoadrenalism, but also pigmentation due to high ACTH, and salt craving due to low mineralcorticoids
investigations in someone suspected of primary hypoadrenalism
pituitary panel test to find out extent of hormone deficiency
ACTH test - synacthen test
what is the ACTH test
measure baseline cortisol and give acth, measure after 30 mins and 60 mins and see if cortison goes up. differentiates primary from secondary.
management in hypoadrenalism
cortisol replacement, hydrocrotison, prednisolone, or dexamethasone, and fludrocrotisone.
what to monitor in someone treated for hypoadrenalism
weight, postural bp, signs of excess, renin.
biochemical markers of someone with primary hypoadrenalism
ACTH: cortisol: renin: sodium: potassium:
ACTH: high
cortisol: low
renin: high
sodium: low
potassium: high
biochemical markers of someone with secondary hypoadrenalism
ACTH: cortisol: renin: sodium: potassium:
acth: low
cortisol: low
renin: normal
aldosterone: normal
sodium and potassium: normal
causes of addison’s crisis
illness, injury, missed medication
surgery, burns, MI, pregnancy
usually in someone with known addison’s or hypoadrenalism
clinical features of addison’s crisis
abdominal pains fatigue n&v low grade fever muscle pains/cramps dehydration
signs of addison’s crisis (electrolytes, biochemical markers)
hyponatraemia hyperkalaemia hypoglycaemia hypotension dehydration
management of someone with addison’s crisis - dose and route, monitoring,
hydrocortisone 100mg IM/IV
IV fluids - 0.9% nacl
treat underlying cause
cardiac and electrolyte monitoring
what is cushing’s syndrome
hypercortisolism
causes of cushing’s syndrome
exogenous cortisol
cortisol producing adrenal tumour
pituitary tumour producing acth
ectopic tumour producing acth
what is a pituitary tumour producing acth called?
cushing’s disease
symptoms of cushings syndrome
truncal obesity - buffalo hump, weight gain facial fullness/moon face proximal muscle wasting diabetes/impaired glucose tolerance gondal dysfunction hypertension kidney stones skin/hair changes - acne, hirsutism, striae, pigmentation psychological changes osteoporosis irregular periods thirst/polydipsia,polyuria impaired immune function
how to investigate cushings syndrome
midnight cortisol
overnight dexamethasone suppression
low dose dexamethasone suppresion
high dose dexamethasone suppresion
what do the dexamethasone suppresion tests tell you
low dose dex - if cortisol unsuppresed, diagnosis of cushings syndrome
high dose dex - measure ACTH and cortisol
if acth is low and cortisol high - adrenal tumour producing cortisol
if acth is low and cortisol is low - pituitary tumour producing acth
if acth is high and cortisol is high - ectopic tumour producing acth
do you get metabolic acidosis or alkalosis in addisons disease?
acidosis - due to lack of aldosterone and failure of Na/H+ pumps to work, causing sodium to be secreted and h+ to be retained
what further investigations to do after dexamethasone suppresion tests
imaging to find source of tumour
what time of the day should ACTH be measured?
8-9am as they would be the highest.
what an ACTH test, what levels of cortisol is considered normal??
> 580nmol/L
what is the drug used in ACTH test, dose and route
250microgram tetracosactide IM or IV
antibodies found in gRaves disease
TRAb
what is the antibody found in autoimmune hypothyroidism
anti TPO
when is goitre ultrasound indicated?
when the goitre is non-functional
what is usually done to confirm after a thyroid ultrasound
FNA +/- histology
what can be used to investigate a functional goitre?
radioisotope uptake scan
clinical features of hypothyroidism
tiredness weight gain depression dry skin and brittle hair constipation menorrhagia
dose of levothyroxine given to patients with hypothyroidism?
75-100mcg, if old start at 25-50mcg
what blood markers are used to monitor in hypothyroidism management
if primary - TSH
if secondary - t4/t3
causes of hyperthyroidism
graves disease
toxic nodule +/- multi
management of primary hyperthyroidism
antithyroid medication
surgery
radioiodine ablation
2 medical regimes used in hyperthyroidism
block and replace - carbimazole or PTU, then levothyroxine
or dose titration of carbimazole or PTU
what usually causes 2ndary hyperthyroidism
TSHoma
symptoms of hyperthyroidism
anxiety sleeplessness weight loss heat intolerance tremors diarrhea graves -> exopthalmos, tibial myxodema, thyroid acropatchy
physiology of gonado-pituitary axis
hypothalamus makes GNRH which stimulates pituitary to make fsh/lh, whcih stimulates gonads to make testosterone or estrogen
causes of primary hypogonadism
congenital, chromosomal or genetic abnormality
acquired - infection, autoimmune, iatrogennic, drugs
drug that can cause hypognoadism
ketoconazole
what kind of hypogonadism would anabolic steroid use exhibit
secondary
what would hyperprolactinaemia cause in terms of gondotrophic hormone balance
secondary hypogonadism, prolactin inhibits GnRH from hypothalamus
investigations in suspected hypogonadism
male - testosterone, sperm count
female - ovary ultrasound, estrogen, progesterone
both - basal lh/fsh
male features of hypogonadism
loss of hair acne, hirsutism loss of muscle mass loss of libido osteoporosis central obesity low sperm count shrunen testes erectile dysfunction
female features of hypogonadism
none/irregular periods
osteoporosis
infertility
loss of libido
treatment for hypogonadism
testosterone replacement - gel patch or IM
estrogen/progesterone replacement (HRT)
what is treatment in secondary hypogonadism?
fsh/lh replacement
what controls prolactin production
TRH from hypothalamus stimulates prolactin, dopamine inhibits, extrogen also stimulates
pathological causes of hyperprolactinaemia
drugs - antidopamine/antipsychotics
prolactin secreting adenomas
hypothyroidism (primary)
why does hypothyroidism cause hyperprolactinaemia?
primary hypothyroidism causes TRH levels to rise, thus stimulating prolactin as well
male features of hyperprolactinaemia
galactorrhea erectile dysfunction headaches osteoporosis visual field defects
why does hyperprolactinaemia cause erectile dysfunction
prolactin inhibits fsh/lh production
features of acromegaly
large hands, face organs, soft tissue overgrowth, increase interdental space carpal tunnel syndrome hypertension cardiovascular disease diabetes
investigations for acromegaly
IGF-1 levels (elevated)
imaging
management for acromegaly
transphenoidal surgery to remove tumour
or medical options
what are 2 possible endocrine causes of hypertension?
hyperaldosteronism
phaeochromocytoma
difference between primary and secondary hyperaldosteronism
primary produces excess aldosterone
secondary is triggered by underperfusion to stimulate increased aldosterone secretion
how to tell if primary or secondary hyperaldosteronism
aldosterone:renin ratio
primary will have more aldosterone than renin, secondary will have high renin as well
clinical features and biochemical markers of primary hyperaldosteronism
hypertension hypernatraemia hypokalaemia alkalosis low renin high aldosterone
causes of secondary hyperaldosteronism
things that cause RAAS activation/renal underpfusion
cardiac failure renal stenosis nephrotic syndrome liver failure diuretics
treatment of primary hyperaldosteronism
spironolactone then surgery
reference range for serum sodium
135-144 mmol/L
causes of hypernatraemia
low volume - not drinking water, excess urinary loss, extreme sweating or diarrhea
normal volume - diabetes insipidus
high volume - conn’s syndrome, too much hypertonic intake
management of hypernatraemia
careful fluid resuscitation, avoid too rapid due to cerebral edema risk
broad causes of hyponatraemia?
gaining too much water, loosing too much salt, or retaining too much water
what is pseudohypontraemia
when other solutes in the serum decrease the relative concentration of sodium and water e.g. hypertriglyceridaemia, hyperglycaemia,
causes of sodium depletion causing hyponatraemia?
renal loss - diuretics, salt wasting, nephropathy
gut sodium loss
causes of reduced renal free water clearance (not excreting enough urine)
drugs, renail failure, portal hypotension and ascites, sepsis,
cardiac failure, nephrotic syndrome, siadh, hypoadrenalism
symptoms of hypontraemia
often asymptomatic
headache, n&v, muscle cramps, lethargy
signs of severe hyponatraemia
disorientation, seizures, coma, cerebral edema
investigations in hyponatraemia?
urine tests - osomolality, sodium
plasma tests - lfts, bone panel, tfts, cortisol
radiology
in hyponatraemia, what does low urine osmolality indicate ?
too much water intake - dipsogenic polydipsia, IVT
in hyponatraemia, what does high urine osmolality indicate ?
not enough free water clearance, proceed to test urine sodium
in hyponatraemia, what does high urine osmolality and low urine sodium indicate?
body is retaining sodium and fluids, e,g, heart failure, nephrotic syndrome, hypotensive shock
in hyponatraemia, what does high urine osmolality and high urine sodium indicate?
body is concentrating urine inappropriately - SIADH, hypoadrenalism
management of hyponatraemia
if acute and severe - hypertonic saline infusion
if chronic or mild, reduce non-essential fluids and treat cause, stop interacting medications
where is potassium stored in the body
mostly intracellularly
what affects serum potassium
potassium influx into cells caused by alkalosis, insulin and beta adrenergic agonist
potassium efflux caused by acidosis, a-adrenergic agonist and strenuous exercise
where in the kidney is potassium regulated
DCT - 10%
ECG changes in hypokalaemia
flattened T waves and inversion prolonged PR interval ST depression U waves SVT torsade de pointes
neuromuscular clinical features of hypokalaemia
neuromuscular symptoms - tetany, cramps, weakness, constipation, paralysis
ECG features of hyperkalaemia
peaked T waves lengthening PR segment disappearing P waves wide QRS sinus bradycardia or slow AF sine wave
causes of hyperkalaemia
hypoaldosternoism ACEI, ARBS renal failure acidosis tissue damage increased intake
management of hyperkalaemia
urgent ECG calcium gluconate insuline, dextrose salbutamol dialysis
what is SIADH
syndrome of inappropriate antidiuretic hormone secretion
how to diagnose siadh
hyponatraemia, low serum osmolality, high urine osmolality and sodium. with no other possible causes
causes of SIADH
drug induced
CNS infection/inflammation/tumour
neoplasms
pulmonary disease
drugs that can cause SIADH
na valproate, carbamazepine,
clofibrate, chlorpropamide
SSRIs
morphine, oxytocin
what are some broad categories of strong cyp3a4 inhibitors
antibiotics - clarythromycin
antifungals - ketoconazole
antivirals - ritonavir
clinical features of phaeochromocytoma
anxiety, tremors, palpitations, tachycardia, hypertension, headaches, weight loss, hyperglycaemia,
