Endocrinology Flashcards
what does endocrine mean
substance released into the blood and causes an effect
what does paracrine mean
substance which acts on cells within same vicinity and causes an effect
what does autocrine mean
a cell-produced substance which acts on the cell that produced it to cause an effect
which type of hormones have slow clearance and a long half life
fat soluble/steroid
which type of hormones have fast clearance and short half life
water soluble/peptide
what is negative feedback
stimulus causes a hormone to be released which directly counteracts stimulus
what is positive feedback
stimulus causes a hormone to be released which increases the stimulus
what is an exocrine hormone
secretions secreted through a duct to site of action
where is a peptide hormone receptor located
cell membrane
where is a steroid hormone receptor located
cytoplasm
what hormones have a receptor in the nucleus
thyroid
oestrogen
vitamin D
where does ANP act
in the heart
where is IGF-1 released
liver
where is erythropoietin released
kidneys
where are gastrin and incretin released
in the GI tract
what is appetite
desire to eat food
what is hunger
need to eat
what is anorexia
lack of appetite
what is satiety
feeling of fullness/ disappearance of appetite after a meal
what are the BMI values
under 18.5 = underweight 18.5-24.9 = normal 25 - 29.9 = overweight 30 - 39.9 = obese above 40 = morbidly obese
what is the role of the hypothalamus in hunger
lateral hypothalamus = hunger centre
ventromedial hypothalamic nucleus = satiety centre
what do alpha cells of the pancreas secrete
glucagon
what do beta cells of the pancreas secrete
insulin
what is the main function of insulin
suppress hepatic glucose output = decreased gluconeogenesis and glycogenolysis
increase glucose uptake into insulin sensitive tissue
suppress lipolysis and breakdown of muscle
what are the clinical values for diabetes diagnosis
plasma glucose more than 11mmol/L
fasting glucose more than 7mmol/L
what are the clinical values for diagnosing type 2 diabetes
HbA1c of more than 48mmol/mol
what is mild hypoglycaemia
less than 4mmol/L with no symptoms
what is serious hypoglycaemia
less than 3mmol/L often symptomatic
what is severe hypoglycaemia
less than 2mmol/L symptomatic with impaired cognitive function
why does hypoglycaemia occur
increased levels of insulin usually due to insulin injections in diabetics or healthy individuals with insulinomas
how do you treat hypoglycaemia
administer 15g fast acting carb
test blood glucose 15 mins after and check its above 4mmol/L
administer long acting carb to prevent recurrence
what is whipples triad
- symptoms of hypoglycaemia
- blood glucose <50mg/dL
- relief of symptoms following ingestion of glucose
presentation of pituitary tumours - 3 key things
- pressure on local structure
- pressure on normal pituitary
- functioning tumour
cushings disease definition
increased secretion of ACTH from the anterior pituitary gland causing chronic, excessive and inappropriate elevated levels of circulating plasma glucocorticoids (cortisol)
what is cushings syndrome
increased cortisol levels
due to a cause not directly acting on the anterior pituitary
what can cause cushing syndrome
prescribed glucocorticoid drugs
excess cortisol production from:
- adrenal tumour
- hyperplastic adrenal gland
- adrenal gland with nodular adrenal hyperplasia
ACTH producing tumours e.g. small lung cell cancers
CRH producing tumours
what are the main functioning pituitary tumours
- prolactinoma
- GH producing tumour = can cause acromegaly
- ACTH producing tumour = can cause cushings
how do somatostatin analogues work
inhibit multiple hormones and shrink tumours
may have side effects
not available orally
e.g. LANREOTIDE
how are dopamine agonists useful
useful for prolactinoma (and GH secreting tumour) no damage to pituitary work quickly orally available relatively ineffective e.g. CABERGOLINE, BROMOCRITINE
how do GH receptor antagonists work
act as competative antagonists to GH
doesnt change GH levels but blocks receptors so less IGF1 produced
daily subcutaneous injection
e.g. PEGVISOMANT
what is the circadian rhythm
changes in hormone levels through the day
hormone levels peak just after waking then decrease after this until sleep where they rise again
e.g. cortisol
what is primary adrenal insufficiency (addisons)
due to impairment at adrenal glands
= destruction of adrenal cortex
= low cortisol but high ACTH (feedback)
what is secondary adrenal insufficiency
due to impairment at pituitary and/or hypothalamus
= reduced adrenal cortex stimulation
= low ACTH therefore low cortisol
what is tertiary adrenal insufficiency
due to hypothalamic disease and decrease in CRH
what is thyroid peroxidases TPOs
antibody found in almost all individuals with autoimmune hypothyroidism
also associated with graves disease = hyperthyroidism
marker in healthy individuals for increased chance of developing autoimmune thyroid diseases
what is the mechanism of thyroid destruction in autoimmune disease
cytotoxic T lymphycyte mediated
thyroglobulin and TPO antibodies may cause secondary damage but alone = no effect
rare = antibodies against TSH receptors block effect of TSH
what causes predisposition to autoimmune thyroid disease
- female
- HDL-DR3 and other immunoregulatory genes
- environmental factors = stress
- high iodine intake
- smoking
what autoimmune disease are related to autoimmune thyroid disease
type 1 diabetes Addisons disease vitiligo coeliac disease pernicious anaemia
what is hyperthyroidism
abnormally high T4 and T3 levels
what are the main pituitary mass legions (?)
craniopharyngioma
rathke’s cysts
meningioma
lymphocytic hypophysitis
what are the definitive signs of puberty
females = menarche, breast bud presence (depend on oestrogen) males = first ejaculation, testes over 3mL large
what are the female secondary sexual characteristics
breast/genitalia growth
pubic/auxiliary hair growth
what are the male secondary sexual characteristics
external genitalia/auxiliary hair growth
larynx/laryngeal enlargement
what is thelarche
breast development = first visible change of puberty induced by oestrogen = ductal proliferation site specific adipose deposition enlargement of areola and nipple
what is adrenarche
developmental process where specialised subset of cells arise forming the zona reticulata
occurs at 2/3 end at 9/10
caused by increased in DHEA and DHEA-s
what is pubarche
most pronounced clinical result of adrenarche
= appearance of pubic hair
what are the indications for late puberty in women
lack of breast development by 13
more than 5 years between breast development and menarche
lack of pubic hair by 14
absent menarche by 15-16
what are the indications for late puberty in men
lack of testicular enlargement by 14
lack of pubic hair by 15
more than 5 years to complete genital enlargement
what are the hormone levels in a male with primary hypogonadism
raised LH/FSH
low testosterone
what is the effect of anabolic steroid use in men
low testosterone and suppressed LH
what are the hormone levels in primary ovarian failure in women
high LH and FSH
FSH is greater than LH
low oestrogen
what are the effects of metformin on glucose control
- increase peripheral insulin sensitivity (?)
- increased glucose uptake and use by skeletal muscle
- decreased hepatic gluconeogenesis
- decreased intestinal glucose absorption
what are the side effects of metformin
GI disturbances nausea vomiting lactic acidosis weight neutral or loss
describe the action of sulphonylureas E.G. GLICLAZIDE
block potassium channels on pancreatic beta cells = stimulating insulin secretion
what are the side effects of sulphonylureas
GI disturbances
hypoglyceamia
weight gain
describe the action of a DPP4 inhibitor
DPP4 = enzyme in vascular endothelial lining which INactivates incretin hormones = DPP4 inhibitor = competitive agonist of DP44 enzyme = result in enhanced incretin effect= more insulin secreted
what are the side effects of DPP4 inhibitors
GI disturbances
acute pancreatitis
describe the action of a GLP-1 receptor agonist
GLP1 agonists activate GLP1
GLP1 acts to increase concentration of incretin
also cause delay in gastric emptying
what are the side effects of GLP1 agonists
GRUPH GI disturbances Respiratory tract infection UTI Peripheral oedema Hepatotoxicity
describe the action of thiazolidinediones (TZD) e.g. pioglitazone
acts to increase bodies response to own insulin
act to decrease glucose and FFA levels
what are the side effects of TZDs
weight gain
hypoglycaemia (low risk though)
heptatomegaly
fracture risk
describe the action of SGLT2 inhibitors
act to inhibit SGLT2 transporter
prevents glucose reabsorption in the PCT of the nephron
= results in increased glucose loss in urine = decrease blood glucose levels
what is bariatric surgery
acts to decrease stomach size or bypass sections to promote weight loss
where is leptin expressed most
in white fat cells
what is the role of leptin
switch off appetite + immunostimulation
lack of leptin = constant appetite
what is peptide YY
secreted by neuroendocrine cells in the ileum/pancreas/colon in response to food
hormone that binds to neuropeptide Y (NPY) receptor
inhibit gastric motility and therefore reduce appetite
what is the role of cholycystokinin CCK in appetite
released in response to meal and increased duodenal pH
delays gastric emptying
cause gall bladder contraction
stimulates insulin secretion
stimulates vagus nerve = feeling of satiety
what secretes CCK
secreted by enteroendocrine cells in the duodenum
what is the role of ghrelin
cause an increased in growth hormone release
stimulates appetite
increases food intake
promotes fat storage
what produces ghrelin
stomach
name 3 hormones/receptors that suppress your appetite
leptin
peptide YY
CCK
name a hormone that stimulates appetite
ghrelin
what is the role of incretins
augment insulin secretion from beta cells
(some) inhibit glucagon release from alpha cells
= decrease blood glucose levels
DPP4 = inactivates incretins
how does hyperglycaemia stimulate insulin secretion (in 4 steps)
- hyperglycaemia leads to increase glucose uptake in cells
- glucose metabolism = increase ATP = K+ channels close
- causes depolarisation of cell membrane = Ca2+ channels open and Ca2+ enter
- increased Ca2+ in cell = exocytosis of insulin vesicles
= insulin released by pancreatic beta cells
describe short acting soluble insulins
start working within 30-60mins
last for 4-6 hrs
describe short acting insulin analogues
faster onset and shorter duration of action than soluble
routinely used in DMT1
describe longer acting insulin
insulin + protamine/zinc
intermediate lasting 12-24hrs
long acting lasting >24hrs
when should you avoid doing an HbA1c test
type 1 DM
pregnant
children
haemoglobinopathies
what is used to treat hypothyroidism
levo-thyroxine lifelong treatment
aim = TSH levels >0.5
what is used to treat hyperthyroidism
- betablockers for rapid attacks/tachycardia
- carbimazole = antithyroid drug = blocks T3/T4 synthesis (may need levothyroxine to replace lost T3/4)
- radioiodine therapy = shrink thryoid gland + decrease number of T3/4 producing cells
* radioiodine = risk of hypothyroidism
what drugs can cause hyperthyroidism/hyperthyroidism
amioderone
lithium (rare)
iodine
ipilimumab
what 3 things characterise diabetic ketoacidosis DKA
- hyperglycaemia
- raised plasma ketones
- metabolic acidosis
what investigations are done in DKA
- blood glucose test >11.0mmol/L
- blood ketones = finger prick near patient test
- blood pH/carbonate = acidaemia
- urine dipstick = heavy glycosuria and ketonuria
- Cr and Urea high due to dehydration
how is DKA managed
fluids
IV insulin - 6 units per hr starting dose
electrolytes (K+)
what is hyperglycaemic hyperosmolar state
- marked hyperglycaemia
- hyperosmolality
- milds/no ketosis
most common cause is INFECTION (particularly pneumonia)
= dehydration
= decreased consciousness
= polyuria
how is hyperglycaemic hyperosmolar state managed
same as for DKA
fluids
insulin 3 units/hour, only if severe
LMWH because hyperosmolality causes blood viscosity to increase = clots, MI, stroke
what is a thyroid storm
rare/life-threatening = rapid deterioration of thyrotoxicosis high fever tachycardia extreme restlessness delirium/coma/death
how is a thryoid storm managed
- propranolol
- large doses of carbimazole
- potassium iodide = block release of T3/4 from gland
- hydrocortisone = inhibit conversion of T4 to T3
whats the most common cause of hyperthryoidism
graves disease
what does IGF1 do
stimulate growth by protein synth
increase lipolysis
stimulate hypertrophy and hyperplasia of bone, skeletal muscle
decrease blood glucose
symptoms of cushings
Cataracts Ulcers Striae Hypertension and hyperglycaemia Increase risk infection Necrosis Glucosuria
what is the first line treatment for acromegaly
transphenoidal surgical resection to remove adenoma from pituitary
describe the ECG features in hypokalaemia
U have no Pot (K+) and no Tea but a long PR and a long QT
- flat T waves
- ST depression
- long PR and QT
- pathological U waves
describe the Tx fro Conns syndrome
laproscopic adrenalectomy
aldosterone antagonist = spironolactone
what is the commonest cause of primary adrenal insufficiency (addisons) worldwide and in UK
UK = addisons worldwide = TB
what is the Tx for adrenal insufficiency (addisons)
glucocorticoids = hydrocortisone/prednisolone mineralocorticoids = fludrocortisone
describe the pathophysiology of SIADH
too much ADH = insertion aquaporin 2 = water retention = blood dilution = hyponatraemia
too much ADH = decreased RAAS-aldosterone = secretion of Na+ = excess water removed WITH Na+ =
hyponatraemia with NORMOVOLAEMIA
what drug is used in the Tx of SIADH
demeclocycline = inhibit action of ADH on kidney
what drugs can cause hyperkalaemia
NSAIDs ACEi = block aldosterone binding spironolactone ciclosporin heparin
what is the blood plasma value for hyperkalaemic and hypokalaemic
over 5.5mmol/L
emergency = over 6.5mmol/L
under 3.5mmol/L
emergency = under 2.5mmol/L
what is the blood plasma values for hypercalcaemia and hypocalcaemia
> 2.6mmpl/L on 2 or more occasions
<2.1mmol/L
what is chvosteks sign and what condition would you see it in
tapping over facial nerve in parotid gland region = ipsilateral twitch
= hypocalcaemia
what is trousseaus sign and what condition would you see it in
carpopedal spasm induced by inflation of BP cuff to 20 above systolic
= hypocalcaemia
what ECG changes would you see in hyper and hypocalcaemia
hyper = short QT, tented T hypo = long QT
how to work out plasma osmolality
(Na x 2) + glucose + urea
what antibodies are present in DMT1
anti-GAD
pancreatic islet autoantibodies
islet antigen 2 antibodies
what drugs are used to lower cortisol
metyrapone
ketoconazole
what disease causes bulging eyes and why
graves disease
swelling and oedema of extra-occular muscles
what is kallmans syndrome
decreased GnRH causes anaemia
genetic
failure to start or finish puberty
what is a pheochromocytoma
catecholamine secreting tumour = adrenaline
diagnosed by blood conc of hormones
treat with surgery and alpha blocker then beta blocker
what is a prolactinoma
prolactin secreting tumour
cause headaches + period changes
check prolactin levels
treat with dopamine agonists (cabergoline)
what is hyperparathyroidism
increase PTH caused by parathyroid adenoma/hyperplasia primary secondary or tertiary bones, groans, stones, psychic moans primary = high Ca secondary = low Ca treat by surgical removal of cancer calcium correction treat underlying possible bisphosphonates for osteoporosis
name a calcium mimetic
cinacalcet
what is hypoparathyroidism
low PTH = rare
symptoms same as hypocalcaemia (chovstek + trousseau)
high phosphate and low calcium
treat with IV calcium + vitamin D analogue
name a vitamin D analogue
alfacalcidol
what is a carcinoid tumour
seratonin secreting tumour
pain/weight loss/palpable mass
causes carcinoid syndrome
diagnose with serum 5-Hydroxyindoleacetic acid (seratonin bkd/n product) + liver ultrasound
treat with somatostatin analogue = octreotide
