Obesity/Endocrinology Flashcards
what is aldosterone
mineralocorticoid secreted by adrenal gland which stimulates absorption of sodium by kidneys and regulates water and salt balance
what is the physiology of the RAAS system
afferent arteriole: juxtaglomerular cells, sense BP
low BP = they secrete renin
liver secretes angiotensinogen and renin converts it to angiotensin 1
ACE converts it to angiotensin 2
AG 2 stimulates release of aldosterone from adrenal glands
aldosterone acts on sodium channels in collecting ducts, to increase membrane permeability = sodium reuptake increases in DCT
aldosterone also causes loss of potassium
what is the HPA axis
stress = HT release CRH
APG releases ACTH
ACTH causes release of cortisol from adrenal glands
this mobilises glucose for energy
if cortisol levels are too high = NF, receptors in hippocampus and HT recognise this and lower release of CRH and ACTH
what four regions of the adrenal gland produce what, and which conditions link to each zone?
zona glomerulosa = produces MCC (aldosterone) = conn’s syndrome
zona fasiculata = GCC eg cortisol = cushing’s syndrome
zona reticularis = androgen precursors eg DHEA and androstenedione = congenital adrenal hyperplasia
medulla = catecholamines eg adrenaline and NA (phaechromocytoma)
what is phaechromocytoma
neuroendocrine tumour of adrenal medulla
= HTN, anxiety, palpitations and weight loss
what is cushing’s?
syndrome = signs and symptoms that develop after prolonged abnormal elevation of cortisol
disease = pituitary adenoma secretes excessive ACTH
cushing’s disease causes the syndrome, but syndrome not always caused by CD
age onset is peak at 25-45
what are the features of cushing’s?
moon face, central obesity, abdominal striae, buffalo hump, muscle wasting
HTN, cardiac hypertrophy, hyperglycaemia, depression
osteoporosis, myopathy, easy bruising and poor skin healing
what electrolyte imbalances do you see in cushing’s?
hypokalameia and hypernatremia
what are the causes of cushing’s syndrome?
- Exogenous steroids (patients on long term high dose steroid medications)
- Cushing’s disease
- Adrenal adenoma
(hormone secreting tumour on adrenal gland)
Paraneoplastic cushing’s
what is paraneoplastic syndrome?
o Excess ACTH released from a cancer NOT of the pituitary, which stimulates excessive cortisol release
o ACTH from somewhere other than pituitary = ectopic ACTH
o Small cell lung cancer is the most common cause of this
when are cortisol levels highest and lowest?
Plasma cortisol is highest in the morning and very low at night and while asleep
what are the investigations for cushing’s syndrome?
dexamethasone suppression test
DMT = like cortisol = lowers the amount of ACTH released by pituitary gland which in turn lowers the amount of cortisol released by adrenal gland
how do you do the tests and what do the results mean?
low dose (1mg) if normal = not CS
if abnormal (high cortisol even after DMT) = cushing’s syndrome
if abnormal, also do high dose test
high dose test low = cushing’s disease
what is the cause if the high dose DMT test shows up as high cortisol?
ACTH low = adrenal cushing’s
ACTH high = ectopic ACTH
what other tests can you do for cushing’s syndrome?
24h urinary free cortisol
salivary cortisol
FBC (raised white cells)
electrolytes
MRI brain for pituitary
CRH test
chest and abdo CT for small cell lung cancer and adrenal tumours
how do you treat cushings syndrome?
remove underlying cause (steroids)
surgical removal of tumours or both adrenal glands and put on replacement steroids
Ketoconazole (prevents ACTH secretion), mitotane (reduces cortisol production) and metopirone (fast acting, leads to reduction in cortisol levels in just 30 minutes)
what is adrenal insufficiency
adrenal glands do NOT produce enough cortisol or aldosterone
primary = addison's secondary = inadequate ACTH stimulation on adrenals (loss or damage of pituitary, loss of blood flow or tumour removal)
tertiary = inadequate CRH release by hypothalamus (patients on long term steroids bc suppression of hypothalamus)
what is addison’s disease
specific condition where adrenal glands are DAMAGED
aka primary adrenal insufficiency, usually auto-immune cause
what happens with steroid withdrawal?
HT doesn’t activate fast enough so endogenous steroids not made fast enough = should be tapered off slowly
what are the signs and symptoms of adrenal insufficiency
Fatigue Nausea Cramps Abdo pain Reduced libido
Bronze hyperpigmentation, particularly in skin creases, bc ACTH stimulates melanocytes to produce melanin
Postural hypotension
what is the investigation of choice for addison’s?
short synacthen test
In morning: give synacthen, which is synthetic ACTH. Blood cortisol is measured at baseline, 30 and 60 minutes after
Synacthen will stimulate healthy adrenals to produce cortisol – high
Failure to rise = addison’s
what other investigations can you do for addison’s?
U&E’s = hyponatremia and hyperkalaemia
adrenal autoantibodies
MRI/CT of adrenals and MRI of pituitary
how do you treat addison’s disease?
Hydrocortisone 10, 5mg 3x daily
OD longer-acting steroids such as prednisolone, dexamethasone given
Hydrocortisone = gcc to replace cortisol
Fludrocortisone = mineralocorticoid – replaced aldosterone
what is an addisonian crises
Acute presentation of severe addison’s, where the absence of steroid leads to life threatening situation
what are the signs and symptoms of addisonian crises
overall sick patient, hypotension, hyponatraemia
o Reduced consciousness
o Hypotension
o Hypoglycaemia, hyponatraemia, hyperkalaemia
also: abdo pain, fatigue, weight loss, aches and pains
what causes an addisonian crisis?
infection, trauma, withdrawal of steroids
how do you investigate/manage addisonian crises?
random serum cortisol and plasma ACTH but start treatment IMMEDIATELY:
high dose, stat hydrocortisone followed by 100mg iV every 6 hours
IV saline
correct hypoglycaemia
what is conn’s syndrome?
primary hyperaldosteronism
what is primary hyperadosteronism?
adrenal glands are directly responsible for producing too much aldosterone
o Serum renin will be low as it is suppressed by the high BP
Causes include:
Adrenal adenoma secreting aldosertone
Bilateral adrenal hyperplasia
Familial hyperaldosteronism
Adrenal carcinoma = rare
what is secondary hyperaldosteronism?
Excessive renin stimulating adrenal glands to produce more aldosterone
Serum renin will be high
Several causes:
occur when BP in kidneys is disproportionately lower than the blood pressure in rest of the body
Renal artery stenosis
Renal artery obstruction
Heart failure
what are the investigations you do for conn’s syndrome?
renin aldosterone ratio
high aldosterone and low renin = primary
both high = secondary
check BP, serum electrolytes (hypokalaemia), ABGs for alkalosis bc potassium and H+ exchanged for sodium and water
CT or MRI for tumour, renal doppler US and CT angio for stenosis
how do you manage hyperaldosteronism?
aldosterone antagonists eg spironolactone
treat underlying cause
what should you keep in mind that hyperaldosteronism can cause?
secondary HTN
what is water-friderichsen syndrome?
adrenal gland failure due to bleeding into the adrenal glands, commonly caused by severe bacterial infection
what is phaechromocytoma?
tumour of the chromaffin cells that secretes unregulated and excessive amounts of adrenaline
adrenaline tends to be secreted in bursts giving periods of worse symptoms followed by more settled periods
how do you diagnose phaechromocytoma?
24 hour urinary collection of metanephrines
symptoms of phaechromocytoma?
Anxiety
Sweating
Headache
Hypertension
Palpitations, tachycardia, and paroxysmal atrial fibrillation
how do you manage phaechromocytoma?
surgery
alpha or beta blockers prior to surgery
what is sheehan’s syndrome
complication of post-partum haemorrhage
necrosis of pituitary gland due to drop in circulating BV and then hypoperfusion
it ONLY affects the APG, so hormones from PPG are unaffected
what hormones are released from which part of the pituitary gland?
• The anterior pituitary releases: o Thyroid-stimulating hormone (TSH) o Adrenocorticotropic hormone (ACTH) o Follicle-stimulating hormone (FSH) o Luteinising hormone (LH) o Growth hormone (GH) o Prolactin
The posterior pituitary releases (not affected by Sheehan’s syndrome):
o Oxytocin
o Antidiuretic hormone (ADH)
what are the signs and symptoms of sheehan’s?
reduced lactatin, amenorrhea, adrenal insufficiency and adrenal crisis (low cortisol), hypothyroidism
how do you manage sheehan’s?
replacement as HRT, hydrocortisone, levothyroxine, growth hormone
what is osmolaltiy
concentration of dissolved particles of chemicals and minerals such as sodium in serum
high osmolality = more particles in serum, low means particles are diluted
where is ADH secreted from
ADH produced in hypothalamus, but released by PPG
what happens when plasma osmolality increases?
(may happen bc of increased sodium levels or body water decreases)
the receptors in the HT cause thirst to increase water intake
also signal PPG = release of vasopressin (ADH)
ADH acts on collecting ducts of kidney to increase the number of aquaporin channels allowing water to be absorbed in the blood
what is diabetes insipidus
rare condition with lack of ADH
what causes DI?
cranial: (too little production from HT) = idiopathic, brain tumours, head injuries, brain infection
kidney becomes insensitive to ADH and does not make aquaporin channels and reabsorb water from collecting ducts = nephrogenic DI
caused by drugs eg lithium, electrolyte disturbance, intrinsic kidney disease
how does DI present?
polyuria, polydipsia, dehydration, postural hypotension
hypernatremia
how do you investigate for DI?
low urine osmolality
high serum osmolality
water deprivation/desmopressin stimulation test
what is the water deprivation test
fluid deprivation for 8 hours then urine osmolality measured and synthetic ADH administered
8 hours later, measure urine osmolality again
in cranial: patient lacks ADH but kidneys still capable of responding to ADH
o Hence urine osmolality remains low bc continues to be diluted by excessive water secretion in the kidneys
o Then when synthetic ADH = UO is high
• In nephrogenic = patient unable to respond so UO will be low all the time
Primary polydipsia (drinks too much water = too much urine) = UO will be high even before ADH given = no DI
how do you manage DI
underlying cause
conservatively
desmopressin to replace ADH
what is SIADH
many stimuli can override osmolality control and cause release of inappropriately high amounts of ADH = reabsorption of water from CD of kidneys
- Causes urine = high sodium content or osmolality
- Serum sodium levels drop as water is retained
how do you diagnose SIADH
diagnosis of exclusion
euvolemia, high UO and low SO
hyponatremia on u&E’s
negative short synacthen to rule out adrenal insufficiency
what causes SIADH
lung disease = cancer, pneumonia
brain lesions = tumour, head injury and bleed, stroke
drugs = carbamezapine, SSRU;s
what are some non-specific symptoms of SIADH
headache, fatigue, muscle aches and cramps, confusion
how do you manage SIADH
fluid restriction
acute = hypertonic saline
aim for change in sodium of less than 10mmol/per 24h to prevent central pointine myelinolysis
or vaptans (ADH receptor antagonists) which acts on V1 and V2 receptors causing vasoconstriction and water diuresis
what is hyponatremia
low sodium levels
causes = excessive loss due to drugs (PPI’s, SSRIs, ACEI) or insufficient intake
symptoms include CONFUSION, headache, nausea, dizziness
may be either dehydrated or fluid overloaded so signs related to that
how do you investigate SIADH
hydration status
urinary sodium and somolality
if urine sodium is high = SIADH, it should be low bc body is conserving it
how do you manage SIADH
mild: fluid restriction less than 800ml
loop diuretics
may need hypertonic saline
what is hypernatremia?
unusual, high sodium levels only seen in association with severe dehydration
replace water deficit with iV sodium chloride 0.9%
what is hyperkalaemia?
> 5.5 serum potassium
caused by drugs like spironolactone, ARBs, ACE-I
main symptoms include fatigue, muscle weakness and confusion
Complications:
Can cause a cardiac arrhythmia and bradycardia, which is fatal
how do you treat hyperkalameia
calcium gluconate or B2 agonist nebulised
or insulin with dextrose
these increase potassium shift form plasma into cells
can also give sodium bicarbonate to reverse acidosis, given in hyperkalaemia bc most patients also have acidosis
what is obesity
classified according to BMI
o Healthy weight – 18.5-24.9 kg/m^2 o Overweight: 25-29.9 o Obesity 1: 30-34.9 o Obesity 2: 35-39.9 o Obesity 3: 40 kg/m2 or more
how would you manage obesity?
consider:
o 1. General advice on healthy weight and lifestyle
o 2. Diet and physical activity
o 3. Diet and physical activity, consider drugs
o 4. Diet and physical activity; consider drugs; consider surgery
how do you assess patients with obesity?
social
measurements eg BMI and waist circumference
RF, presenting symptoms, lipid profile, hba1c, LFTs and TFTs
comorbidities
what drugs could you give for obesity?
o Orlistat: pancreatic lipase inhibitor, leading to malabsorption of fat by in intestine
o Lorcaserin: a selective 5-HT2c serotonin receptor agonist, decreasing food intake by increasing satiety
o Phentermine/topiramate = first combination drug approved for weight loss
when is bariatric surgery considered?
if BMI is >40 or >35 and siginificant comorbidites
have tried all other measures
patient commits to need for long term follow up and is fit for surgery
