ENDOCRINE Flashcards
modified amino acid hormones
adrenaline
thyroid hormones
steroid hormones
cortisol
progesterone
testosterone
peptide hormones
ACTH
ADH
oxytocin
protein hormones
insulin
what is autocrine signalling
signalling molecules elicit a response in the cell that produced them
what is paracrine signalling
signalling molecules elicit a response in cells adjacent to the signalling cell
what is endocrine signalling
signalling molecules elicit a response in distal cells, normally involving travel through the bloodstream
examples of hormones with complementary actions
adrenaline, cortisol, glucagon, GH, insulin (for growth), IGF-1, sex steroids
amine release is mediated by exocytosis dependent on which ion
Ca2+
how are amines transported
‘free’ in plasma (hydrophilic)
how are peptide hormones transported
‘free’ in plasma (hydrophilic)
how are steroid hormones tranpsorted
bound to plasma proteins (hydrophobic)
what is the role of carrier proteins
increase amount of hormone transported in blood
provide a reservoir of hormone
extend the half-lee of the hormone in circulation
cortisol is transported in blood bound to which carrier protein
cortisol binding globulin
thyroxine is transported in blood bound to which carrier protein
thyroxine binding globulin
testosterone and estradiol are transported in blood bound to which carrier protein
sex steroid binding globulin
examples of general carrier proteins
albumin (steroids, thyroxine)
transthyretin (thyroxine and some steroids)
bound hormones can cross the capillary wall to activate receptors in target tissues
true/false
false
only free hormone can cross the capillary wall
how do carrier proteins prevent abrupt rises in hormone concentration
they act as buffers
what are the three types of hormone receptor
GPCR
receptor kinases
nuclear kinases
class 1 nuclear receptors are activated by
steroid hormones
class 2 nuclear receptors are activated by
lipids
insulin binds to what type of hormone receptor
receptor kinase
B cells in the pancreas secrete which hormone
insulin
a cells in the pancreas secrete which hormone
glucagon
delta cells in the pancreas secrete which hormone
somatostatin
what is the name of the precursor from which insulin is derived
preproinsulin
what is insulin made up of
two polypeptide chain linked by disulphide bonds
glucose is transported into B cells brought which transporter
GLUT2 glucose transporter
insulin release is mediated by an increase in intracellular concentration of which ion
Ca2+
effect of increased ATP in beta cells (glucose metabolism)
inhibits ATP sensitive K+ channels –> depolarisation –> opens Ca2+ channels –> insulin release
why is insulin release biphasic?
a small proportion of insulin is immediately available for release, the remainder must undergo preparatory reactions to become mobilised and available for release
action of sulphonylureas
inhibit K-ATP transporter, leading to depolarisation of the cell and subsequent release of insulin
what is diazoxide used for
stimulate the K-ATP transporter to inhibit insulin secretion in hyperinsulinaemia
what is MODY
familial form of early-onset type II diabetes with primary defects in insulin secretion
what is the role of glucokinase in MODY2
glucokinase activity is impaired, leading to glucose sensing defect –> increases blood glucose threshold for insulin to be released
how does MODY differ from type 1 diabetes
MODY patients normally have some B-cell function available and so can be treated with SUs rather than with insulin
stimulatory effects of insulin
amino acid uptake in muscle DNA synthesis protein synthesis growth responses glucose uptake in muscle and adipose tissue lipogenesis in adipose tissue and liver glycogen synthesis in liver and muscle
inhibitory effects of insulin
decreased lipolysis
decreases gluconeogenesis
HbA1c diagnostic of diabetes
48 m/m or above
fasting glucose diagnostic of diabetes
7.0 mmol/L or above
2-hour glucose in OGTT diagnostic of diabetes
11.1 mmol/L or above
random glucose diagnostic of diabetes
11.1 mmol/L or above
what is gestational diabetes
any degree of glucose intolerance arising or diagnosed during pregnancy
what does HbA1c show
glucose control over the past 2-3 months
test which help determine the type of diabetes
GAD/IA2 antibodies
c-peptide
what is the ideal HbA1c range
48-58 mmol/mol
what is LADA
late autoimmune diabetes in adults (type of T1DM)
insulin is secreted into which vein
portal vein
c-peptide levels at diagnosis; type 1 vs type 2
type 1 - low
type 2 - normal or raised
children diagnosed under the age of 6 months are most likely to have which kind of diabetes
monogenic
what is Wolfram syndrome (DIDMOAD)
diabetes insipidus diabetes mellitus optic atrophy deafness neurological anomalies
aims oft therapy in type 1 diabetes
prevent hyperglycaemia
avoid hypoglycaemia
reduce chronic complications
rapid acting insulin analogues
humalog (insulin lispro), novorapid, apidra
short acting insulin
Humulin S, actrapid, Isnuman rapid
intermediate acting insulin
insulatard, Humulin I, Insuman basal
long acting insulin analogue
lantus, levemir
rapid acting analogue-intermediate mixture
Humalog Mix25/Mix50 or novomix30
short acting-intermediate mixture
Humulin M3, Isnuman Comb 15, 25, 50
how does a basal bolus insulin regime work
a long acting insulin is administered in the evening, with three rapid acting insulin boluses at meal times
how many units of insulin for 10g of carbs
1 unit
what is HbA1c a measure of
glycated haemoglobin
what is a complication that can arise if injection sites are not rotated in diabetes
lipohypertrophy
indications for IV insulin
DKA
hyperosmolar hyperglycaemic state
acute illness
fasting patients who are unable to tolerate oral intake
how does metformin help reduce hyperglycaemia
decreases hepatic gluconeogenesis
increases peripheral glucose uptake
how do sulphonylureas help reduce hyperglycaemia
blocks beta-cell K-ATP channel
increases the 1st and 2nd phase insulin secretion
side effects of SUs
weight gain
hypoglycaemia
how do SGLT-2 inhibitors reduce hyperglycaemia
inhibit glucose reabsorption in kidney tubules
how do TZDs reduce hyperglycaemia
PPARgamma activator
increase peripheral glucose uptake
side effects of TZDs
increased fracture risk
hepatotoxicity
fluid retention
what drug can be used to gain weight loss
orlistat
how does orlistat work
inhibits lipases - blocks absorption of dietary fat
microvascular complications of diabetes include
IHD
stroke
microvascular complications of diabetes include
neuropathy
nephropathy
retinopathy
what are the four types of neuropathy associated with diabetes
peripheral
autonomic
proximal
focal neuropathy
how does peripheral neuropathy present in DM
pain/loss of feeling in feet/hands
how does autonomic neuropathy present in DM
changes in bowel/bladder function, sexual response, sweating, heart rate, blood pressure
how does proximal neuropathy present in DM
pain in the thighs, hips or buttocks leading to weakness in the legs (amyotrophy)
how does focal neuropathy present in DM
sudden weakness in one nerve or a group of nerves causing muscle weakness or pain eg carpal tunnel, ulnar mono-neuropathy, foot drop, bells palsy, CN palsy
what is Charcot foot
a condition causing weakening of the bones in the pot that can occur in people who have significant nerve damage (neuropathy)
the bones are weak enough to fracture, and with continued walking, the foot eventually changes shape
treatment for painful diabetic neuropathy
amitriptyline, duloxetine, gabapentin, pregabalin
capsaicin cream if cannot tolerate oral treatment
how is diabetic neuropathy screened for
foot screening
consequences of diabetic nephropathy
development of HTN
decline in renal function
accelerated vascular disease
how to screen for diabetic nephropathy
albumin creatinine ratio
treatment for diabetic nephropathy
BP maintained <130/80 mmHg
patients with microalbuminuria or proteinuria should be started on an ACEI or ARB
HbA1c maintained <53 mmol/mol
what eye pathologies fo people with diabetes get
diabetic retinopathy
early onset cataract
glaucoma
visual blurring due to hyperglycaemia
signs of diabetic retinopathy
haemorrhages
cotton wool spots
hard exudates
complications of diabetic retinopathy
retinal detachment
secondary glaucoma
how is diabetic retinopathy treated
laser
vitrectomy
what is DKA
a disordered metabolic state that usually occurs in the context of an absolute or relative insulin deficiency accompanied by an increase in the counter-regulatory hormones ie glucagon, adrenaline, cortisol and growth hormone
biochemical diagnosis of DKA
ketonaemia >3 mmol/L or significant ketonuria (>2+)
blood glucose >11.0 mmol/L or known diabetes
bicarbonate <15 mmol/L or venous pH <7.3
common causes of DKA are
infection intoxication infarction ischaemia insulin missed
symptoms and signs of DKA
thirst/polyuria dehydration flushed vomiting abdo pain/tenderness Kussmaul's breathing ketones on breath
causes of DKA death adults
hypokalaemia
aspiration pneumonia
ARDS
co-morbidities
causes of DKA death children n
cerebral oedema
management of DKA
replace fluid (0.9% NaCl then switch to dextrose)
insulin
potassium
manage risk factors (sepsis, aspiration)
what is the definition of HHS
hypovolaemia +
hyperglycaemia without significant acidosis or ketonaemia +
hyperosmolar
presentation of HHS
older individuals
high refined CHO intake pre-event
management of HHS
cautiously replace fluids and insulin
may require Na
screen of vascular event, sepsis
LMWH unless contraindicated
what causes type A lactic acidosis
tissue hypoxaemia
- infarcted tissue, cariogenic shock, hypovolaemic shock (sepsis, haemorrhage)
what cause type B lactic acidosis
liver disease, leukaemia states, diabetes, inherited metabolic conditions
presentation of lactic acidosis
hyperventilation
mental confusion
stupor or coma if severe
treatment of lactic acidosis
fluids
antibiotics if appropriate
treatment of alcohol induced ketoacidosis
pabrinex (high dose vitamins)
IV fluids
insulin may be required
what may cause HbA1c to be reduced
haemolytic anaemia, acute or chronic blood loss, pregnancy
immediate treatment of mild hypoglycaemia
15-20 g of glucose or simple carbohydrates
recheck blood glucose after 15 mins
eat a small snack if your next meal is more than an hour away (once BG returns to normal)
examples of carbs used in the treatment of hypoglycaemia
glucose tablets
gel tube
2 tbsps of raisins
1/2 cup juice or regular coke
treatment of severe hypoglycaemia
glucagon injection
what type of drug is metformin
biguanides
normal starting dose of metformin
500 mg od or bd
does metformin prevent microvascular and microvascular complications
yes
GI side effects of metformin
anorexia, nausea, vomiting, diarrhoea, abode pain, taste disturbance
dose changes of metformin in renal failure
avoid or stop if eGFR <30 ml/min
half dose if eGFR 30-35 ml/min
metformin and liver toxicity
discontinue if advanced cirrhosis/liver failure, or risk of lactic acidosis (encephalopathy, alcohol excess)
may be beneficial in NAFLD
examples of SUs
glicazide
glibenclamide
glimepiride
do SUs prevent microvascular and microvascular complications
microvascular - yes
microvascular - no
side effects of SUs
hypoglycaemia, weight gain, GI upset, headache
TZD mechanism of action
PPARgamma agonist (nuclear receptor) causes activation of genes that are also activated by insulin
TZD examples
pioglitazone
TZD side effects
hypoglycaemia (with an SU)
increase weight
fluid retention and heart failure
do TZDs prevent micro- and macro-vascular complication
no
GLP-1 receptor agonists examples
exanatide, expanding, liraglutide, lixisenatide
which subunits of K-ATP channel regulate the activity of the channel
SUR1 (SU receptor)
where does ATP bind on the K-ATP channel
Kir6.2 subunit
which substance binds to the K-ATP channel to close it the extracellular glucose is low
ADP-Mg2+
when should SUs be used
first line if intolerant to metformin
second line if diabetes is not controlled with metformin
examples of glinides
repaglinide and nateglinide
mechanism of glinides
bind to SUR1 to close the K-ATP channel and trigger insulin release
why is insulin response greater to oral glucose than IV glucose
incretin effect
- ingestion of food stimulate GLP-1 and GIP from cells in the small intestine
- they enter the portal blood
- they enhance insulin release and enhance glucose uptake
- GLP-1 decreases glucagon release from pancreas
DPP-4 inhibitors are also known as
gliptins
mechanism of action DPP-4 inhibitors
inhibit the action of DPP-4 which terminated the action of GLP-1 and GIP
side effects of DPP-4 inhibitors
nausea
mechanism of action of incretin analogues
mimic action of GLP-1 but last longer due to resistance to DPP-4
side effects of incretin analogues
modest weight loss nausea
pancreatitis (rare)
administration of increasingly analogues
SC
action of alpha-gluosidase
breaks down starch and disaccharides to absorbable glucose at the brush border in the small intestine
action of alpha-glucosidase inhibitors
inhibit the action of alpha-glucosidase therefore preventing the breakdown of complex carbs to glucose
side effects of alpha-glucosidase inhibitors
flatulence, loose stools, diarrhoea, abdominal pain, bloating (due to increase population of colonic bacteria)
examples of SGLT-2 inhibitors
dapagliflozin, canagliflozin and empagliflozin
what is the difference between primary and secondary thyroid disease
primary disease affects the gland itself
secondary disease is caused by hypothalamic or pituitary disease
TSH is also known as
thyrotropin
TSH is released by which cells in which aspect of the pituitary
thyrotroph cells in the anterior pituitary
biochemical presentation of primary hypothyroidism
low free T3/4
TSH high
biochemical presentation of primary hyperthyroidism
high free T3/4
low TSH
causes of goitrous primary hypothyroidism
chronic thyroiditis (Hashimoto's thyroiditis) iodine deficiency
causes of non-goitrous primary hypothyroidism
atrophic thyroiditis
what is the most common cause of hypothyroidism in the western world
Hashimoto’s thyroiditis
what antibody is associated with Hashimoto’s thyroiditis
thyroid peroxidase (TPO) antibodies
microscopic appearance of hashimoto’s thyroiditis
T-cell infiltrate and inflammation
clinical features of hypothyroidism
coarse, sparse hair dull, expressionless face periorbital puffiness pale cool skin that feels doughy to touch vitiligo hypercarotenaemia cold intolerance pitting oedema
management of hypothyroidism
levothyroxine
50-100 ug young patients
25-50 ug older patients
what is primary hypogonadism (female)
problem with ovaries
high LH/FSH
what is secondary hypogonadism (female)
problem with hypothalamus or pituitary
low LH/FSH
signs of premature ovarian failure
amenorrhoea
oestrogen deficiency
elevated gonadotrophins
diagnosis of premature ovarian failure
FSH >30 on two separate occasions
what is idiopathic hypogonadotrophic hypogonadism
absent of delayed sexual development associated with inappropriate low levels of gonadotrophin and sex hormone levels in absence of anatomical/functional defects of HPG axis
what phenotypic features are associated with idiopathic hypogonadotrophic hypogonadism
anosmia
what is the function of kisspeptin
stimulator of GnRH
what is Kallman’s syndrome
a genetic disorder characterised by loss of GnRH secretion and anosmia/hyposmia
in which condition is the absence of olfactory bulbs on MRI
Kallman’s syndrome
diagnosis of PCOS
2 of;
menstrual irregularity
hyperandrogenism
polycystic ovaries
treatment of PCOS
oral contraceptive pill
anti-androgens
local anti-antiandrogens
cosmesis
karyptype of turner’s syndrome
XO - only one X chromosome
signs of turner’s syndrome
short stature, webbed neck, shield chest with wide spaced nipples, cubitus valgus, lymphedema
