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Endocrine Flashcards

1
Q

how is T3 and T4 produced?

A

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

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2
Q

what is the most common cause of hypothyroidism?

A

Hashimoto’s thyroiditis - autoimmune disease (gives a goitre)
anti-TPO antibodies in ~90% of patients

other causes include lithium and amiodarone

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3
Q

features of hypothyroidism

A

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

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4
Q

medication to treat hypothyroidism

A

levothyroxine

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5
Q

MOA of levothyroxine

A

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).

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6
Q

common cause of hyperthyroidism

A

Grave’s disease - autoimmune disease
TSH receptor antibodies in 90+% of patients

amiodarone can also cause hyperthyroidism

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7
Q

features of hyperthyroidism

A

weight loss, “manic”, restlessness, heat intolerance, palpitations, hyperhidrosis, peritibial myxoedema, Acropachy (clubbing), diarrhoea, oligomenorrhoea, anxiety, tremor

exophthalmos is the least associated feature

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8
Q

treatment of hyperthyroidism

A

carbimazole

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9
Q

MOA of carbimazole

A

is a thyroperoxidase inhibitor – prevents iodation of tyrosine so reduces T3 and T4 synthesis

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10
Q

what is sick euthyroid

A

everything (TSH, thyroxine and T3) is low

is reversible following recovery from an illness

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11
Q

Grave’s eye disease

A 
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
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12
Q

thyroid storm features and management

A

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)
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13
Q

de Quervain’s thyroiditis (aka subacture thyroiditis)

A

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

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14
Q

primary hyperparathyroidism

A

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

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15
Q

secondary and tertiary hyperparathyroidism

A

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

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16
Q

hypoparathyroidism

A

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

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17
Q

MOA of alfacalcidol

A

Alfacalcidol is Vitamin D-hormone analog

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18
Q

hyperprolactinaemia causes (the P’s)

A

Pregnancy
Prolactinoma
Physiological (stress, exercise, sleep, post-sex)
Polycystic ovarian syndrome
Primary hypothyroidism (TSH stimulates prolactin release)
drugs: Phenothiazines, metocloPramide, domPeridone, haloPeridol

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19
Q

features of hyperprolactinemia

A

males: impotence, reduced libido, galactorrhoea
females: amenorrhoea, galactorrhoea

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20
Q

treatment of hyperprolactinemia

A

bromocriptine

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21
Q

MOA of bromocriptine

A

bromocriptine is a dopamine agonist

dopamine acts as the primary prolactin releasing inhibitory factor

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22
Q

gynaecomastia causes

A

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

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23
Q

Klinefelter’s syndrome

A

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

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24
Q

Kartagener’s syndrome (primary ciliary dyskinesia)

A

dynein arm defects = immobile cilia

dextrocardia/complete sinus inversus, bronchiectasis, recurrent sinusitis and subfertility

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25
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
26
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)
27
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
28
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)
29
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)
30
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
31
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)
32
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)
33
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
34
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
35
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
36
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
37
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
38
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
39
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
40
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
41
latent autoimmune diabetes of adults
autoimmune DM that presents later in life, often mistaken for T2DM
42
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.
43
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
44
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) ```
45
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)
46
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)
47
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
48
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 ```
49
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
50
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
51
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
52
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 ```
53
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
54
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)
55
diabetes insipidus
cranial DI = deficiency of ADH nephrogenic DI = insensitivity to ADH investigations --> high plasma osmolality and low urine osmolality, water deprivation test
56
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
57
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
58
Trousseaus sign
blood pressure cuff inflation above systolic pressure causes carpal spasm - seen in hypocalcaemia
59
Chvostek's sign
tapping over the parotid causes facial muscle twitch - seen in hypocalcaemia
60
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+)
61
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
62
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
63
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
64
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

EOY3 (20 decks)

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