Endocrine Flashcards
how is T3 and T4 produced?
the hypothalamus secretes thyrotropin-releasing hormone
TRH stimulates the anterior pituitary to secrete thyroid stimulating hormone
TSH stimulates the thyroid to release T3 and T4
THE THYROID:
Na+-Iodine symport transport into the epithelial cell against its concentration gradient. the epithelial cells synthesis thyroglobulin (from tyrosine) and exocytose into the follicle lumen. iodine is oxidised. iodination of the side chains of tyrosine residues in thyroglobulin form MIT and DIT.
MIT + DIT = T3, DIT + DIT = T4
what is the most common cause of hypothyroidism?
Hashimoto’s thyroiditis - autoimmune disease (gives a goitre)
anti-TPO antibodies in ~90% of patients
other causes include lithium and amiodarone
features of hypothyroidism
weight gain, cold intolerance, anhidrosis, yellowish skin (due to impaired conversion of beta-carotene to vitamin A), non-pitting oedema, constipation, menorrhagia, reduced deep tendon reflexes and carpal tunnel syndrome
medication to treat hypothyroidism
levothyroxine
MOA of levothyroxine
Levothyroxine is a synthetic form of thyroxine (T4), an endogenous hormone secreted by the thyroid gland, which is converted to its active metabolite, L-triiodothyronine (T3).
common cause of hyperthyroidism
Grave’s disease - autoimmune disease
TSH receptor antibodies in 90+% of patients
amiodarone can also cause hyperthyroidism
features of hyperthyroidism
weight loss, “manic”, restlessness, heat intolerance, palpitations, hyperhidrosis, peritibial myxoedema, Acropachy (clubbing), diarrhoea, oligomenorrhoea, anxiety, tremor
exophthalmos is the least associated feature
treatment of hyperthyroidism
carbimazole
MOA of carbimazole
is a thyroperoxidase inhibitor – prevents iodation of tyrosine so reduces T3 and T4 synthesis
what is sick euthyroid
everything (TSH, thyroxine and T3) is low
is reversible following recovery from an illness
Grave’s eye disease
severity graded using "NOSPECS" no signs or symptoms only signs e.g. upper eyelid retraction signs and symptoms (including soft tissue involvement) proptosis extra-ocular muscle involvement corneal involvement sight loss due to optic nerve involvement
thyroid storm features and management
is a life threatening condition due to undertreated hyperthyroidism
HTN, tachycardia, increased temperature, coma, agitation, diarrhoea +/- new AF
treatment:
- block synthesis (propylthiouracil or methimazole)
- block release (iodine)
- block T3 and T4 conversion (propylthiouracil, propranolol, corticosteroid +/- amiodarone)
- beta-blocker
- block enterohepatic circulation (cholestyramine)
de Quervain’s thyroiditis (aka subacture thyroiditis)
occurs following a viral infection
- hyperthyroidism (3-6 weeks, raised ESR, PAINFUL goitre)
- euthyroid (1-3 weeks)
- hypothyroidism (weeks-months)
- returns to normal
Ix: iodine-131 scan shows globally reduced uptake
does not require treatment as is self limiting, can use aspirin or NSAIDs as analgesia
primary hyperparathyroidism
raised PTH, raised Ca2+ and low PO4-
~80% due to solitary adenoma
if mild is asymptomatic but can get recurrent abdo pain, emotional and cognitive changes
secondary and tertiary hyperparathyroidism
secondary - raised PTH, reduced or normal Ca2+, high PO4-, low vitamin D (eventually get bone disease and soft tissue calcification), the PTH gland hyperplasia due to low vitamin D often due to CKD
tertiary - raised PTH, raised or normal Ca2+, low or normal PO4-, low or normal vitamin D, raised ALP (metastatic calcification, bone pain or fractures, pancreatitis, kidney stones), ongoing hyperPTH despite correction of renal disorder
hypoparathyroidism
often secondary to thyroid surgery - low PTH, low Ca2+, high PO4-
symptoms are due to hypocalcaemia –> tetany, perioral paraesthesia, Trousseasu’s sign, Chvostek’s sign, ecg prolonged QTc
treatment: alfacalcidol
MOA of alfacalcidol
Alfacalcidol is Vitamin D-hormone analog
hyperprolactinaemia causes (the P’s)
Pregnancy
Prolactinoma
Physiological (stress, exercise, sleep, post-sex)
Polycystic ovarian syndrome
Primary hypothyroidism (TSH stimulates prolactin release)
drugs: Phenothiazines, metocloPramide, domPeridone, haloPeridol
features of hyperprolactinemia
males: impotence, reduced libido, galactorrhoea
females: amenorrhoea, galactorrhoea
treatment of hyperprolactinemia
bromocriptine
MOA of bromocriptine
bromocriptine is a dopamine agonist
dopamine acts as the primary prolactin releasing inhibitory factor
gynaecomastia causes
caused by a raised oestrogen:androgen ratio
physiological (normal in puberty)
syndromes with androgen deficiency (kallman’s, Klinefelter’s)
testicular failure (e.g. due to mumps)
liver disease
testicular disease (e.g. seminoma secreting hCG)
ectopic tumour secretion
hyperthyroidism
haemodialysis
drugs: SPIRONOLACTONE, digoxin, cimetidine, anabolic steroids
Klinefelter’s syndrome
47 XXY
taller than average, lack of secondary sexual characteristics, small and firm testes, infertile, gynaecomastia and increased risk of breast cancer, mitral valve prolapse in ~55%
management –> testosterone treatment, PTOT and speech therapy
Kartagener’s syndrome (primary ciliary dyskinesia)
dynein arm defects = immobile cilia
dextrocardia/complete sinus inversus, bronchiectasis, recurrent sinusitis and subfertility
Kallmann’s syndrome
X-linked recessive
cause of delayed puberty secondary to hypogonadotropic hypogonadism - failure of GnRH-secreting neurones to migrate to hypothalamus
delayed puberty, anosmia, failure of one or both of the testes to decend
Turner’s syndrome
chromosomal disorder affecting 1 in 2500 females
either only one X or a deletion on one of the X chromosomes (45, X0 or 45, X)
features: short stature, shield chest and wide spaced nipples, bicuspid aortic valve, coarctation of the aorta, primary amenorrhoea, horse shoe kidneys
prepuberty give GH (for statue) and oestrogen (to prevent OP)
primary hyperaldosteronism (aka Conn’s syndrome - adrenal adenoma)
HTN, low potassium (and muscle weakness), alkalosis
Ix: increased aldosterone:renin ration (renin ow due to negative feedback due to high sodium as a result of aldosterone)
high resolution CT abdomen
adrenal vein sampling
Rx: if Conn’s –> sugery
of bilateral adrenocortical hyperplasia then spironolactone
acromegaly
is gigantism if growth plates are still open
increased GH secondary to a pituitary tumour (in >95% of pts), ectopic GHRH/GH from pancreas, lung or adrenal cancer
causes - HTN, DM (acanthosis nigricans), cardiomyopathy, colorectal cancer
Ix: oral glucose tolerance test (would normally suppress GH), may also have impaired glucose tolerance
R: trans-sphenoidal surgery
bromocriptine (dopamine agonist), octreotide/anreotide (somatostatin analogue) and pegvisomant SC (GH receptor antagonist)
pheochromocytoma
a rare catecholamine secreting tumour
- episodic HTN, headaches, palpitations, sweating and anxiety
investigations - 24hr urinary metanephrines
Rx: surgery is the definitive management but pt needs to be stabilised first –> phenoxybenzamine (alpha-blocker) and propranolol (beta-blocker)
polycystic ovarian syndrome
causes hirsutism, acne, female pattern alopecia, menstrual irregularities, insulin resistance (acanthosis nigricans)
raised testosterone, USS shows multiple cortical ovarian cysts and enlarged echogenic ovaries
Rx: lifestyle changes, OCP, spironolactone, metformin, clomiphene citrate for anovulation and infertility
Cushing’s syndrome
cushing’s syndrome = most commonly exogenous steroids –> overnight dexamethasone suppression test and 24hr urinary free cortisol
cushing’s disease = pituitary tumour –> high dose dexamethasone suppression test (if pituitary source then cortisol suppressed) —> trans-sphenoidal removal of tumour (complication of surgery = hypoadrenal crisis and Nelson’s syndrome - increased ACTH due to negative feedback, rapid pituitary enlargement and skin hyperpigmentation)
hypoadrenal crisis
often due to acute illness
low BP, abdo pain, vomiting, confusion, hypoglycaemia, hyperCa2+, hypoNa+, metabolic acidosis
–> double glucocorticoid dose (hydrocortisone) and keep mineralocorticoid dose the same fludrocortisone)
what is pseudo-Cushings?
mimics cushingoid features etc, often due to alcohol excess or severe depression
causes a false positive dexamethasone suppression test or 24hr urinary cortisol
insulin stress test used to differentiate
Addison’s disease
80% of cases are due to autoimmune destruction of adrenal glands
- lethargy, weakness, anorexia, N&V, weight loss, hyperpigmentation (as ACTH is precursor for MSH), low BP, loss of pubic hair in women
Ix: short synACTHen test
Rx: hydrocortisone (double dose if ill) and fludrocortisone
Addisonian crisis
collapse, shock and pyrexia
due to surgery or sepsis, adrenal haemorrhage (waterhouse-friderichsen syndrome)
Rx: hydrocortisone 100mg IV?IM (continue 6-hourly)
1L NaCl over 30-60mins (or dextrose if hypoglycaemic)
oral replacement at 24hrs and reduce dose to maintenance over 3-4 days
Metabolic Syndrome
central obesity (BMI >30 or increased waist circumference, ethnic specific) plus two of:
- BP >130/85 or on HTN treatment
- triglycerides >1.7mmol/L, HDL <1.03 (M) or <1.29 (F)mmol/L
- fasting glucose >5.6mmol/L or T2DM
Rx: exercise, lose weight, treat individual components
T1DM
autoimmune destruction of beta cells of the islets of langerhan in the pancreas that produce insulin
= absolute insulin deficiency so hyperglycaemia
presents in childhood/early adulthood - very unwell, possibly in DKA
HbA1c target is 48mmol/L (6.5%) or lower
may experience a ‘honeymoon’ period when starting insulin, can last 3-5 years
T2DM
polydipsia, polyuria and weight loss
if symptomatic need either fasting glucose >7.0mmol?l or random glucose >11.1mmol/L
if asymptomatic need two abnormal results on 2 separate occasions
gestational DM
increased glucose due to physiological insulin resistance due to extra oestrogen
complications include macrosomia, pre-eclampsia
risk factors: BMI >30kg/m2, previous baby >4.5kg, 1st degree relative with DM, south Asian/black Caribbean/middle eastern
screened with OGTT
may need insulin: if BM 6-6,0mmol/L and complications or >7mmol/L
maturity onset diabetes of the young
inherited genetic disorder (HNF-1alpha or glucokinase gene)
younger patients with symptoms similar to T2DM but at risk DKA
latent autoimmune diabetes of adults
autoimmune DM that presents later in life, often mistaken for T2DM
metformin
max dose is 1g BD
increases insulin sensitivity, reduces hepatic gluconeogenesis, increases peripheral glucose use and reduced LDL and VLDL
ADR:
GI upset
lactic acidosis if severe liver disease or renal failure
possible weight loss, cannot cause hypos
CI: dose reduced if eGFR <45, stopped if <30, stopped if using contrast (1 day before and restarted 2 days after)
has a short half life so give 2 times a day with food (helps with the GI upset. if patient can’t tolerate try a modified release.
sulphonylureas
e.g. gliclazide
max dose is 160mg BD
increases pancreatic insulin secretion - binds to ATP dependent K+ channels on beta-cells
ADR: hypoglycaemia weight gain due to increased appetite (don't give to obese pts) SIADH myelosuppression
CI: pregnant and breast feeding, severe liver or renal disease, if obese, caution if elderly or frail
DDP-4 inhibitors (gliptins)
e.g. sitagliptin
prevents breakdown of endogenous GLP-1 - so increases insulin secretion and sensitisation
ADR: possible hypoglycaemia GI upset weight neutral (can use alogliptin in CKD)
SGLT2 inhibitors
e.g. dapagliflozin
reversibly inhibits SGLT2 in the PCT to reduce glucose reabsorption and increase urine glucose excretion
ADR:
genitourinary infections secondary to glycosuria
DKA
weight loss
(don’t use dapagliflozin with a loop diuretic)
meglitinides
e.g. repaglinide insulin secretagogues block hyperpolarising K+ channels often used for patients with erratic lifestyles short acting so taken before a meal
ADR:
hypoglycaemia and weight gain (less so than SU)
intestinal alpha-glucosidase inhibitors
e.g. acarbose
delays carbohydrate absorption so reduced post-prandial spikes in blood sugar
has little effect on fasting glucose
ADR:
flatulence, diarrhoea, abdo pain and bloating
CI: IBD, liver disease (monitor LFTs)
is not used much as has very little effect on HbA1c and has unpleasant side effects
GLP1 analogue
SC administration
e.g. exenatide
criteria for use: BMI >35kg/m2 and psychological or medical problems associated with weight or BMI <35kg/m2 where insulin has significant occupational implications
increases insulin secretion and sensitisation
ADR: hypoglycaemia weight loss (THE BEST DRUG) GI upset risk of pancreatitis and pancreatic carcinoma
Insulin
aim to emulate endogenous insulin
patients have their own regimens e.g. basal bolus
administer SC - is important to rotate injection sites to prevent lipodystrophy
is administer IV if acutely unwell or having surgery
hyperosmolar hyperglycaemic state
seen in unwell patients with T2DM
longer history (e.g. 1 week) with marked dehydration (typically 200ml/kg), glucose .30mmol/l. no ketone metabolism so ketonemia stays <3mmol/l and pH >7.3 and osmolality >320mosmol/kg
occlusive events are a danger - e.g. focal CNS signs, chorea, DIC, leg ischaemia and rhabdomyolysis
Rx:
LMWH prophylaxis
rehydrate slowly with 0.9 NaCl IVI over 48hrs
replace K+ when patient starts passing urine
only give insulin (0.05U/kg/hr) if BM is not falling by 5mmol/l/h with rehydration
keep BM between 10-15 for the first 24hrs to avoid cerebral oedema
DKA
may be a complication of or a first presentation of T1DM
common ppt factors include infection, missed insulin and MI
features: abdo pain, polyuria, polydipsia and dehydration, gradual drowsiness, Kussmaul respiration, acetone breath smell
diagnosis: pH <7.3, hyperglycaemia >11.0mmol/l (or known DM), ketonemia (> 3mmol/l) or significant ketouria (+2 on dipstick)
Rx:
IVF
IV insulin (0.1U/kg/hr)
correct low potassium
consider ITU admission if severe
thiazolidinediones
e.g. pioglitazone
reduces peripheral insulin resistance and upregulates genes for insulin signalling
ADR: weight gain liver impairment (monitor LFTs) fluid retention - worse if taken with insulin (contraindicated in heart failure) risk of fracture (CI if post-menopausal) risk of bladder cancer (CI if history) also CI if pregnant
what may cause a HbA1c to be unreliable?
if RBC lifespan is reduced (e.g. HbS) it underestimates
if RBS lifespan is increased (e.g. splenectomy) it overestimates
hypoglycaemia
BM <4
usually rapid onset, usually accompanied with odd behaviour - agitation, sweating, tachycardia and seizures
Rx: if able - quick acting carb (200ml orange juice). if conscious - glucose gel, if unconscious - IVI glucose or IV/IM glucagon (doesn’t work if patient is malnourished)
once BM >4 give a long acting carbohydrate (slice of toast)
diabetes insipidus
cranial DI = deficiency of ADH
nephrogenic DI = insensitivity to ADH
investigations –> high plasma osmolality and low urine osmolality, water deprivation test
hypercalcaemia
features: bone pain, fractures, renal stones, fatigue, depression, constipation, shortened QTc
causes: primary hyperparathyroidism, malignancy, dehydration
Rx: rehydration with normal saline 3-4L/day, bisphosphonates, calcitonin
possible HDU admission for a central line to prevent overload
hypocalcaemia
features (SPASMODICS) - spasms (Trousseaus sign), perioral paraesthesia, anxiety, spasms (tetany), muscle tone increased, orientation impaired, dermatitis, impetigo herpetiformis, Chvostek’s sign
causes: CKD, osteomalacia, rhabdomyolysis
Rx: IV calcium gluconate, ECG monitoring, correct cause
Trousseaus sign
blood pressure cuff inflation above systolic pressure causes carpal spasm - seen in hypocalcaemia
Chvostek’s sign
tapping over the parotid causes facial muscle twitch - seen in hypocalcaemia
hyperkalaemia
features: metabolic acidosis, ECG (tall tented t waves, small p waves, widened QRS)
causes; AKI, potassium sparing diuretics, ACEi, ARK, spironolactone, addinson’s, rhabdomyolysis
Rx: IV calcium gluconate (stabilises cardiac membrane (moves K+ from extracellular to intracellular), calcium resonium, loop diuretics and dialysis (remove K+)
hypokalaemia
features: muscle weakness, hypotonia, ECG (u waves, small/no t waves, prolonged pr, st depression#0
causes:
- if with alkalosis (vomiting, Conn’s, Cushing’s)
- if with acidosis (diarrhoea, partially treated DKA)
Rx: ECG monitoring, treat cause, dietary supplements
hypomagnesaemia
causes: diuretics, TPN, diarrhoea, alcohol, low K+/Ca2+, crohn’s
features: paraesthesia, tetany, seizures, arrhythmias, ECG (u waves, small/no t waves, prolonged pr and st depression)
Rx: <0.4mmol/l - IV magnesium sulphate, if >0.4mmol/l - oral magnesium salts
hypernatremia
features: thirst, weakness, nausea and anorexia, if severe - confusion, muscle twitching, intracranial/intracerebellar bleeds
causes: dehydration, osmotic diuresis, DI, excess IV saline
Rx: (high to low, brain might blow) slow correction, no more than 12mmol over 24hrs as risk of cerebral oedema
hyponatraemia
causes: diuretics, diarrhoea, vomiting, sweating, SIADH
Rx: (low to high, pons might die) slow correction, no more than 12mmol over 24hrs as risk of central pontine myelinolysis
