Case 16 - Obesity/GCC/ADH dysfunction Flashcards
What is Cushings?
Too many GCC in the body
Causes an over-activation of the fight or flight mechanism
Zona fasicularis is where GCC are produced in the adrenal cortex
50% 5y survival if left untreated
How can Cushings arise?
Iatrogenic - LT courses of steroids can reduce endogenous steroid production
ACTH-independent Cushings - where the problem is the adrenal glands and there is high GCC production in the absence of ACTH
ACTH-dependent - where the problem is higher up in the HPA axis
Hypothalamus makes CRH > pituitary makes ACTH > adrenal gland releases GCC
If there is a pituitary tumour for example, will produce excess ACTH and therefore more GCC will be produced
Ectopic tumours can do the same
Signs and symptoms of Cushings
Truncal obesity (central) Moonface Humpback Recent rapid weight gain HTN Myopathy Glycosuria Flushing of the face Striae Decreased libido Depression Hirsuitism Bruising
Who should be tested for Cushings?
Pituitary adenomas Adrenal adenomas PCOS Multiple or progressive Sx Features unusual for age e.g. HTN/osteoperosis
What tests can be done for Cushings?
Overnight 1 mg dexamethosone suppression test
Urinary free cortisol
Late night salivary cortisol
48 hour 2mg dexamethosone suppression test
What is late night salivary cortisol?
More accurate than random plasma testing
Should be done twice to confirm reading - done in the community, quick, cheap and non-invasive
If result is positive should do overnight dexamethosone suppression testing to confirm
Diurnal variation in cortisol will be lost in Cushings patients
Higher level than normal will be seen in Cushings
Reacts with prednisolone and cortisol
What is the overnight dexamethosone suppression test?
1mg dexomethosone given before bed, done in the community
Have BT the next morning - in normal patients, the cortisol will be suppressed in the morning due to negative ACTH feedback
In Cushing’s patients, the early morning rise in cortisol will still be seen
What is urinary free cortisol testing?
Over 24 hours, collect all urine and measure the cortisol found in the urine
Overall total of cortisol will be higher than normal patients
May have false positive in PCOS, depression and obesity
What is 48 hour dexamethosone suppression testing?
2mg dexamethosone used - 0.5mg taken every 6 hours
BT are done on day 0 and 2 to confirm rise in cortisol despite negative feedback
What physiological causes of Cushings should be tested for?
Pregnancy Stress Malnutrition Alcoholism Depression Morbidly obese Metabolic syndrome
What tests can be done to find the aetiology of Cushings?
Morning ACTH plasma level testing High dose dexamethosone suppression testing IPSS MRI head CT TAP
What is morning ACTH plasma level testing
If the patient has low ACTH, shows that the Cushings is ACTH-independent
Image adrenals to look for pathology
What is next if you have unsuppressed ACTH levels on testing?
With normal or raised ACTH levels, MRI head to look for pituitary adenoma
High dose dex suppression testing will inhibit ACTH production in pituitary tumours but not in ectopic or adrenal tumours
What is IPSS re Cushings?
For indeterminate MRI lesions, would perform inferior petrosal sinus sampling
This can detect type of ACTH-dependent Cushings
What happens if you have a negative IPSS in Cushings?
Ectopic source of ACTH
Should perform a CT TAP
How can you treat Cushings?
Metyrapone inhibits teh production of cortisol
This may be useful for preparation for surgery, but not in the LT
Surgery
Radiotherapy (often after surgery)
What types of adrenal tumours are there?
Phaechromocytoma - tumour of the medulla > increased catecholamine production
Carcinoma of the cortex - with symptoms relating to the zona affected and therefore the hormone that is being over-produced
What types of pituitary tumours are there?
Non-functioning adenoma - slow-growing and symptoms solely related to mass effect e.g. compression of the optic nerve
Prolactinoma - actively produces prolactin leading to menorrhagia, galactorrhea, amenorrhea
FUnctioning adenoma - produces hormones
ie. ACTH-secreting tumours
GH-secretign tumours
What is Addisons?
Lack of GCC production by the zona fasicularis in the cortex of the adrenal gland
Hypotension and hyponatraemia
Signs and symptoms of Addisons?
Weight loss Low BP - often postural drop Fatigue Abdo pain Hyperpigmentation (due to increased ACTH deposition) Aches and pain
What investigations for Addisons are done?
Can use random cortisol and ACTH
Short synacthen test (contra in recent pit gland bleeds) - should have decreased cortisol after stimulation
Can use insulin tolerance test - risky
What is the treatment for Addisons?
Primary adrenal disease - LT steroids and aldosterone
Pituitary disease - LT steroids
Should taper up until asymptomatic
Wear a steroid bracelet
Carry a steroid card
Increase requirements when ill, playing sport etc.
Pred and dexamethosone are long-acting so OD
Hydrocortisone can be given BD (lower dose in the evening)
What are the complications of Addisons treatment?
Under or over replacement
Over replacement, will leads to signs and symptoms of Cushings and osteoperosis
Under replacement will not resolve the symptoms - weight loss, hyponatraemia
What is an Addisonian crisis?
When GCC are very low Leading to almost no fight-flight mechanism DNV Tachypnoeic Dehydrated Clammy Reduced consciousness
Should treat with IV hydrocortisone 100mg and fluids
Glucose and dextrose
What do you need to do when examining and taking a history for obesity?
How long weight was gained over and how much
Pattern of weight distribution
BP
Dip urine
How do you classify obesity?
Using BMI and Wast circumference
BMI <18.5 Underweight 18.5-24.9 Normal 25-29.9 Overweight 30-34.9 Obese I 35-39.9 Obese II 40+ Morbidly obese (obese III)
Waist circumference
Male = <94|94-102|>102 cm
Female = <80|80-88|>88 cm
What are obesity interventions?
Should encourage lifestyle changes first e.g. diet, exercise and alcohol modification
When should someone be referred to a tier 3 service?
Considering surgery
Drugs unsuccessful
Complex and can’t be managed in tier 2 services
Specialist interventions needed
Underlying cause of obesity needs to be investigated
What drugs can be used for obesity?
Orlistat = Lipase
Helps to break down the fat so that it can be more easily excreted
Will have oily, foul smelling stools
Continue after 3 months only if patient has lost 5% of body weight
BMI 30+ or 28+ with RFs
When is surgery for obesity indicated?
BMI over 40
BMI over 35 and other psychological or physical comorbidities that would benefit from losing weight
When all other interventions have not resulted in significant or maintained weight loss
If patient promises to adhere to strict lifestyle changes post-surgery
Can be gastric banding/sleeve/bypass
What is the physiology of ADH?
ADH produced by the posterior pituitary gland in response to signals form teh hypothalamus
ADH inserts aquaporins in the collecting ducts of the kidney
Encourages more water reabsorption and boost BP by doing so
What is diabetes insipidus?
When the posterior pituitary gland does not produce enough ADH or kidney becomes insensitive to ADH
Leads to polyuria and polydipsia
How do you test for diabetes insipidus?
Do a water restriction test
Will become hypernatraemic and dehydrated
Decreased urine osmolality, increased serum osmolality
How do you treat diabetes insipidus?
Replace with DDAVP
Correct hypernatraemia
When can hypernatraemia occur?
When extremely dehydrated - due to desert, or due to people with cognitive disabilities etc. not remembering to drink, on ICU
What can cause SIADH?
Small cell lung cancer, pneumonia
Brain tumour, head injury
Drugs e.g. SSRIs, carbemazepine
How do you treat SIADH?
Try to treat the underlying cause if there is one
Salt administration, fluid restriction
Tolvaptan in chronic
How do you diagnose SIADH?
Urine vs plasma osmolality
The urine osmolality will be more than in the plasma, due to increased resorption of water
How do you exclude pseudohyponatraemia?
Re-test and do urine vs plasma osmolality, pseudohyponatraemia will have a normal plasma osmolality when it should be low - due to increased presence of other ions that there is an apparent hyponatraemia
What are the signs and symptoms of hyponatraemia?
Headache Dizziness Nausea Coma Signs of fluid overload Signs if fluid underload
How do you determine the cause of hyponatraemia?
If patient is dehydrated, is urine sodium higher than 20?
If yes - due to renal sodium loss, Addisons
If no - elsewhere loss due to diarrhoea, burns etc
If not dehydrated, oedematous? If yes, nephrotic syndrome, CCF, liver failure If no, is urine osmolality high? Yes=SIADH No= water overload, hypothyroidism
