Obesity/Endocrinology

Question 1

what is aldosterone

Answer 1

mineralocorticoid secreted by adrenal gland which stimulates absorption of sodium by kidneys and regulates water and salt balance

Question 2

what is the physiology of the RAAS system

Answer 2

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

Question 3

what is the HPA axis

Answer 3

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

Question 4

what four regions of the adrenal gland produce what, and which conditions link to each zone?

Answer 4

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)

Question 5

what is phaechromocytoma

Answer 5

neuroendocrine tumour of adrenal medulla

= HTN, anxiety, palpitations and weight loss

Question 6

what is cushing’s?

Answer 6

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

Question 7

what are the features of cushing’s?

Answer 7

moon face, central obesity, abdominal striae, buffalo hump, muscle wasting

HTN, cardiac hypertrophy, hyperglycaemia, depression

osteoporosis, myopathy, easy bruising and poor skin healing

Question 8

what electrolyte imbalances do you see in cushing’s?

Answer 8

hypokalameia and hypernatremia

Question 9

what are the causes of cushing’s syndrome?

Answer 9

• Exogenous steroids (patients on long term high dose steroid medications)
• Cushing’s disease
• Adrenal adenoma

(hormone secreting tumour on adrenal gland)

Paraneoplastic cushing’s

Question 10

what is paraneoplastic syndrome?

Answer 10

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

Question 11

when are cortisol levels highest and lowest?

Answer 11

Plasma cortisol is highest in the morning and very low at night and while asleep

Question 12

what are the investigations for cushing’s syndrome?

Answer 12

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

Question 13

how do you do the tests and what do the results mean?

Answer 13

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

Question 14

what is the cause if the high dose DMT test shows up as high cortisol?

Answer 14

ACTH low = adrenal cushing’s

ACTH high = ectopic ACTH

Question 15

what other tests can you do for cushing’s syndrome?

Answer 15

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

Question 16

how do you treat cushings syndrome?

Answer 16

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)

Question 17

what is adrenal insufficiency

Answer 17

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)

Question 18

what is addison’s disease

Answer 18

specific condition where adrenal glands are DAMAGED

aka primary adrenal insufficiency, usually auto-immune cause

Question 19

what happens with steroid withdrawal?

Answer 19

HT doesn’t activate fast enough so endogenous steroids not made fast enough = should be tapered off slowly

Question 20

what are the signs and symptoms of adrenal insufficiency

Answer 20

Fatigue 
Nausea 
Cramps 
Abdo pain 
Reduced libido 

Bronze hyperpigmentation, particularly in skin creases, bc ACTH stimulates melanocytes to produce melanin

Postural hypotension

Question 21

what is the investigation of choice for addison’s?

Answer 21

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

Question 22

what other investigations can you do for addison’s?

Answer 22

U&E’s = hyponatremia and hyperkalaemia

adrenal autoantibodies
MRI/CT of adrenals and MRI of pituitary

Question 23

how do you treat addison’s disease?

Answer 23

Hydrocortisone 10, 5mg 3x daily

OD longer-acting steroids such as prednisolone, dexamethasone given

Hydrocortisone = gcc to replace cortisol

Fludrocortisone = mineralocorticoid – replaced aldosterone

Question 24

what is an addisonian crises

Answer 24

Acute presentation of severe addison’s, where the absence of steroid leads to life threatening situation

Question 25

what are the signs and symptoms of addisonian crises

Answer 25

overall sick patient, hypotension, hyponatraemia o Reduced consciousness o Hypotension o Hypoglycaemia, hyponatraemia, hyperkalaemia also: abdo pain, fatigue, weight loss, aches and pains

Question 26

what causes an addisonian crisis?

Answer 26

infection, trauma, withdrawal of steroids

Question 27

how do you investigate/manage addisonian crises?

Answer 27

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

Question 28

what is conn's syndrome?

Answer 28

primary hyperaldosteronism

Question 29

what is primary hyperadosteronism?

Answer 29

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

Question 30

what is secondary hyperaldosteronism?

Answer 30

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

Question 31

what are the investigations you do for conn's syndrome?

Answer 31

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

Question 32

how do you manage hyperaldosteronism?

Answer 32

aldosterone antagonists eg spironolactone treat underlying cause

Question 33

what should you keep in mind that hyperaldosteronism can cause?

Answer 33

secondary HTN

Question 34

what is water-friderichsen syndrome?

Answer 34

adrenal gland failure due to bleeding into the adrenal glands, commonly caused by severe bacterial infection

Question 35

what is phaechromocytoma?

Answer 35

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

Question 36

how do you diagnose phaechromocytoma?

Answer 36

24 hour urinary collection of metanephrines

Question 37

symptoms of phaechromocytoma?

Answer 37

Anxiety Sweating Headache Hypertension Palpitations, tachycardia, and paroxysmal atrial fibrillation  

Question 38

how do you manage phaechromocytoma?

Answer 38

surgery alpha or beta blockers prior to surgery

Question 39

what is sheehan's syndrome

Answer 39

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

Question 40

what hormones are released from which part of the pituitary gland?

Answer 40

``` • 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)

Question 41

what are the signs and symptoms of sheehan's?

Answer 41

reduced lactatin, amenorrhea, adrenal insufficiency and adrenal crisis (low cortisol), hypothyroidism

Question 42

how do you manage sheehan's?

Answer 42

replacement as HRT, hydrocortisone, levothyroxine, growth hormone

Question 43

what is osmolaltiy

Answer 43

concentration of dissolved particles of chemicals and minerals such as sodium in serum high osmolality = more particles in serum, low means particles are diluted

Question 44

where is ADH secreted from

Answer 44

ADH produced in hypothalamus, but released by PPG

Question 45

what happens when plasma osmolality increases?

Answer 45

(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

Question 46

what is diabetes insipidus

Answer 46

rare condition with lack of ADH

Question 47

what causes DI?

Answer 47

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

Question 48

how does DI present?

Answer 48

polyuria, polydipsia, dehydration, postural hypotension hypernatremia

Question 49

how do you investigate for DI?

Answer 49

low urine osmolality high serum osmolality water deprivation/desmopressin stimulation test

Question 50

what is the water deprivation test

Answer 50

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

Question 51

how do you manage DI

Answer 51

underlying cause conservatively desmopressin to replace ADH

Question 52

what is SIADH

Answer 52

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

Question 53

how do you diagnose SIADH

Answer 53

diagnosis of exclusion euvolemia, high UO and low SO hyponatremia on u&E's negative short synacthen to rule out adrenal insufficiency

Question 54

what causes SIADH

Answer 54

lung disease = cancer, pneumonia brain lesions = tumour, head injury and bleed, stroke drugs = carbamezapine, SSRU;s

Question 55

what are some non-specific symptoms of SIADH

Answer 55

headache, fatigue, muscle aches and cramps, confusion

Question 56

how do you manage SIADH

Answer 56

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

Question 57

what is hyponatremia

Answer 57

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

Question 58

how do you investigate SIADH

Answer 58

hydration status urinary sodium and somolality if urine sodium is high = SIADH, it should be low bc body is conserving it

Question 59

how do you manage SIADH

Answer 59

mild: fluid restriction less than 800ml loop diuretics may need hypertonic saline

Question 60

what is hypernatremia?

Answer 60

unusual, high sodium levels only seen in association with severe dehydration replace water deficit with iV sodium chloride 0.9%

Question 61

what is hyperkalaemia?

Answer 61

>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

Question 62

how do you treat hyperkalameia

Answer 62

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

Question 63

what is obesity

Answer 63

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 ```

Question 64

how would you manage obesity?

Answer 64

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

Question 65

how do you assess patients with obesity?

Answer 65

social measurements eg BMI and waist circumference RF, presenting symptoms, lipid profile, hba1c, LFTs and TFTs comorbidities

Question 66

what drugs could you give for obesity?

Answer 66

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

Question 67

when is bariatric surgery considered?

Answer 67

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