Week 12 - Addison's, APKD, Cushing's Flashcards
what is adrenal insufficiency
where the adrenal glands do not produce enough steroid hormones, particularly cortisol and aldosterone
what does Addison’s disease refer specifically to
when the adrenal glands have been damaged resulting in reduced cortisol and aldosterone secretion.
what is primary adrenal insufficiency
Addison’s
what is the most common cause of Addison’s disease
autoimune
what does secondary adrenal insufficiency result from
inadequate adrenocorticotropic hormone (ACTH) and a lack of stimulation of the adrenal glands leading to low cortisol.
what is secondary adrenal insufficinecy a result of
loss or damage to the pituitary glands
what are the causes of secondary adrenal insufficinecy
Tumours (e.g., pituitary adenomas)
Surgery to the pituitary
Radiotherapy
Sheehan’s syndrome (where major post-partum haemorrhage causes avascular necrosis of the pituitary gland)
Trauma
what does tertiary adrenal insufficiency result from
corticotropin-releasing hormone (CRH) release by the hypothalamus
what is tertiary adrenal insufficiency usually caused by
patients taking long-term oral steroids causing suppression of the hypothalamus (via negative feedback)
what happens when the exogenous steroids (originating from outside the body) are suddenly withdrawn
the hypothalamus does not ‘wake up’ fast enough, and endogenous steroids (originating from inside the body) are not adequately produced.
what are the symptoms of adrenal insufficiency
Fatigue
Muscle weakness
Muscle cramps
Dizziness and fainting
Thirst and craving salt
Weight loss
Abdominal pain
Depression
Reduced libido
what are the two signs of adrenal insufficiency
Bronze hyperpigmentation of the skin, particularly in creases (ACTH stimulates melanocytes to produce melanin)
Hypotension (particularly postural hypotension – with a drop of more than 20 mmHg on standing)
what is the bronze hyperpigmentation of the skin caused by
excessive ACTH stimulating melanocytes to produce melanin.
it mainly affects skin creases, scars, lips and buccal mucosa
what is a key biochemical feature in adrenal insufficiency
hyponataemia (low sodium)
what are the other key biochemical findings that may be seen in adrenal insufficiency
Hyperkalaemia (high potassium)
Hypoglycaemia (low glucose)
Raised creatinine and urea due to dehydration
Hypercalcaemia (high calcium)
what is the test of choice for diagnosing adrenal insufficiency
the short Synacthen test
is the ACTH level high or low in primary adrenal insufficiency and why
the ACTH level is high in PAI as the pituitary is producing lots of ACTH without negative feedback in the absence of cortisol.
what does the ACTH level look like in secondary adrenal failure
the ACTH level is low
what antibodies my be present in autoimmune adrenal insufficiency
Adrenal cortex antibodies
21-hydroxylase antibodies
what can be helpful if you are suspecting structural pathology but not routinely required
CT or MRI
what does the short synacthen test involve
giving a dose of synacthen which is synthetic ACTH
the blood cortisol is checked before and 30-60 minutes after the dose
the synthetic ACTH will stimulate healthy adrenal glands to produce cortisol.
what should be levels of cortisol do in the SST
should at least double
what does a failure of cortisol to double indicate in the short synacthen test
Primary adrenal insufficiency (Addison’s disease)
or
Very significant adrenal atrophy after a prolonged absence of ACTH in secondary adrenal insufficiency
what is the mainstay of treatment in adrenal insufficiency
replacement steroids titrated to signs, symptoms and electrolytes.
what is used to replace cortisol
hydrocortisone (glucocorticoid)
what is used to replace aldosterone
fludrocortisone (a mineralcorticoid)
what happens to steroid doses during an acute illness in an adrenal insufficient patient
doubled
what is given in an emergency in adrenal insufficiency
IM hydrocortisone
what is an adrenal crisis
describes an acute presentation of severe adrenal insufficiency where the absence of steroid hormones leads to a life-threatening emergency
how do people in adrenal crisis present
Reduced consciousness
Hypotension
Hypoglycaemia
Hyponatraemia and hyperkalaemia
what should you do before starting treatment in suspected adrenal crisis
not wait to perform investigations and establish a definitive diagnosis
what does management for adrenal crisis patients involve
- ABCDE approach to initial assessment and arrange transfer to hospital
- Intramuscular or intravenous hydrocortisone (the initial dose is 100mg, followed by an infusion or 6 hourly doses)
- Intravenous fluids
- Correct hypoglycaemia (e.g., IV dextrose)
- Careful monitoring of electrolytes and fluid balance
what is polycystic kidney disease
a genetic condition where the healthy kidney tissue is replaced with many fluid filled cysts
what are the affected genes in autosomal dominant polycystic kidney disease
PKD1 gene on chromosome 16 (85% of cases)
PKD2 gene on chromosome 4 (15% of cases)
what are the extra-renal manifestations of polycystic kidney disease
Cerebral aneurysms
Hepatic, splenic, pancreatic, ovarian and prostatic cysts
Mitral regurgitation
Colonic diverticula
what are the complications of polycystic kidney disease
Chronic loin/flank pain
Hypertension
Gross haematuria can occur with cyst rupture (usually resolves within a few days)
Recurrent urinary tract infections
Renal stones
End-stage renal failure occurs at a mean age of 50 years
what is oligohydramnios
reduced amniotic fluid volume due to reduced urine output
what does oligohydramnios lead to
underdevelopment of the fetal lungs and respiratory failure shortly after birth
what is used for diagnosis of polycystic kidney disease
ultrasound and genetic testing
what can be used to slow the development of cysts and the progression of renal failure in autosomal dominant polycystic kidney disease
tolvaptan (a vasopressin receptor antagonist)
what other management may be needed in autosomal dominant polycystic kidney disease
Antihypertensives for hypertension (e.g., ACE inhibitors)
Analgesia for acute pain
Antibiotics for infections (e.g., UTIs or cyst infections)
Drainage of symptomatic can be performed by aspiration or surgery
Dialysis for end-stage renal failure
Renal transplant for end-stage renal failure
what does chronic kidney disease describe
a chronic reduction in kidney function sustained over three months. it tends to be permanent and progressive
what are the factors that can speed up the decline of the kidneys and cause CKD
Diabetes
Hypertension
Medications (e.g., NSAIDs or lithium)
Glomerulonephritis
Polycystic kidney disease
what is the estimated glomerular filtration rate based on
the serum creatinine, age and gender.
what does the eGFR estimate
the glomerular filtration rate - the rate at which fluid is filtered from the blood into the Bowman’s capsule)
what is proteinuria quantified with
urine albumin:creatinine ratio (ACR)
what will renal ultrasound help to identify
obstructions and polycystic kidney disease
what are the other investigations done to identify risk factors
Blood pressure (for hypertension)
HbA1c (for diabetes)
Lipid profile (for hypercholesterolaemia)
when can a diagnosis of CKD be made
when there are consistent results over three months of either:
- eGFR sustained below 60ml/min/1.73m2
OR
- Urine albumin:creatinine ratio (ACR) sustained above 3mg/mmol
what is the G score based of
the eGFR
what is the A score based of
the albumin:creatinine ratio
what is accelerated progression of CKD classed as
Accelerated progression is a sustained decline in the eGFR within one year of either 25% or 15 mL/min/1.73 m2.
what can be used to estimate the 5 year risk of kidney failure requiring dialysis
The Kidney Failure Risk Equation can be used to estimate the 5-year risk of kidney failure requiring dialysis.
what is the blood pressure target in patients under 80 with CKD and an ACR above 70mg/mmol
The blood pressure target is less than 130/80 in patients under 80 with CKD and an ACR above 70 mg/mmol.
what medications help slow disease progression of CKD
ACE inhibitors (or angiotensin II receptor blockers)
SGLT-2 inhibitors (specifically dapagliflozin)
what is the SGLT-2 inhibitor licensed for CKD
Dapagliflozin is the SGLT-2 inhibitor licensed for CKD. It is offered to patients with:
Diabetes plus a urine ACR above 30 mg/mmol
why does CKD result in a low erythropoietin
Healthy kidneys produce erythropoietin, a hormone that stimulates the production of red blood cells. CKD results in lower erythropoietin and a drop in red blood cell production. It causes a normocytic (normal sized) normochromic (normal colour) anaemia.
Anaemia may be treated with erythropoiesis-stimulating agents, such as recombinant human erythropoietin. Blood transfusions can sensitise the immune system (allosensitization), increasing the risk of future transplant rejection.
Iron deficiency is treated before using erythropoietin. Intravenous iron is usually given, particularly in dialysis patients.
what does renal bone disease involve
High serum phosphate
Low vitamin D activity
Low serum calcium
what is Cushing’s syndrome
refers to the features of prolonged high levels of gucocorticoids in the body
what are the two groups of corticosteroid hormones found in the body
Glucocorticoids (e.g., cortisol)
Mineralocorticoids (e.g., aldosterone)
what is the primary natural glucocorticoid hormone produced by the adrenal glands
cortisol
what does Cushing’s disease refer to
a pituitary adenoma secreting excessive adrenocorticotropic hormone (ACTH)
what does this excessive ACTH do
stimulates excessive cortisol release from the adrenal glands.
the prolonged use of what can also cause Cushing’s
the prolonged use of exogenous corticosteroids such as prednisolone or dexamethasone
what are the features on inspection of Cushing’s
Round face (known as a “moon face”)
Central obesity
Abdominal striae (stretch marks)
Enlarged fat pad on the upper back (known as a “buffalo hump”)
Proximal limb muscle wasting (with difficulty standing from a sitting position without using their arms)
Male pattern facial hair in women (hirsutism)
Easy bruising and poor skin healing
Hyperpigmentation of the skin in patients with Cushing’s disease (due to high ACTH levels)
what are the metabolic effects of Cushing’s
Hypertension
Cardiac hypertrophy
Type 2 diabetes
Dyslipidaemia (raised cholesterol and triglycerides)
Osteoporosis
what is the mneumonic to remember the causes of Cushing’s syndrome
C – Cushing’s disease (a pituitary adenoma releasing excessive ACTH)
A – Adrenal adenoma (an adrenal tumour secreting excess cortisol)
P – Paraneoplastic syndrome
E – Exogenous steroids (patients taking long-term corticosteroids)
when does paraneoplastic Cushing’s syndrome occur
when ACTH is released from a tumour somewhere other than the pituitary gland
small cell lung cancer is the most common cause of this
A high level of ACTH causes skin pigmentation by stimulating melanocytes in the skin to produce melanin, similar to melanocyte-stimulating hormone. This is an important sign of Cushing’s disease (where excess ACTH comes from a pituitary adenoma) and also primary adrenal insufficiency (where there is inadequate cortisol from the adrenals with a lack of negative feedback to the pituitary). In a patient with Cushing’s syndrome, the pigmentation allows you to determine the cause as excess ACTH, either from Cushing’s disease or ectopic ACTH. This sign is absent in an adrenal adenoma or exogenous steroids.
what test is used to diagnose Cushing’s syndrome caused by a problem inside the body
the dexamethasone suppression test
what is the normal response to dexamethasone
suppressed cortisol due to negative feedback
how does dexamethasone normally work on the hypothalamus and what does this lead to
causes negative feedback on the hypothalamus, reducing the corticotropin releasing hormone output.
it causes negative feedback on the pituitary reducing the ACTH output
the lower CRH and ACTH levels result in a low cortisol output by the adrenal glands. a lack of cortisol suppression in response to dexamethasone suggests Cushing’s syndrome
what are the three types of dexamethasone suppression tests
Low-dose overnight test
Low-dose 48-hour test
High-dose 48-hour test
what is the low dose overnight test used as
a screening test to exclude Cushing’s syndrome
what is the low dose 48 hour test used in
suspected Cushing’s syndrome
what is the high dose 48 hour test used to
determine the cause in patients with confirmed Cushing’s syndrome
explain and describe the low dose over night test
For the low-dose overnight test, dexamethasone (1mg) is given at night (usually 10 or 11 pm), and the cortisol is checked at 9 am the following morning. A normal result is that the cortisol level is suppressed. Failure of the dexamethasone to suppress the morning cortisol could indicate Cushing’s syndrome, and further assessment is required.
explain and describe the low dose 48 hour test
For the low-dose 48-hour test, dexamethasone (0.5mg) is taken every 6 hours for 8 doses, starting at 9 am on the first day. Cortisol is checked at 9 am on day 1 (before the first dose) and 9 am on day 3 (after the last dose). A normal result is that the cortisol level on day 3 is suppressed. Failure of the dexamethasone to suppress the day 3 cortisol could indicate Cushing’s syndrome, and further assessment is required.
explain and describe the high dose 48 hour test
The high-dose 48-hour test is carried out the same way as the low-dose test, other than using 2mg per dose (rather than 0.5mg). This higher dose is enough to suppress the cortisol in Cushing’s syndrome caused by a pituitary adenoma (Cushing’s disease), but not when it is caused by an adrenal adenoma or ectopic ACTH.
LOOK ON ZERO TO FINALS FOR TABLE ON CUSHINGS
what is an alternative test used instead of the dexamethasone test
A 24-hour urinary free cortisol is an alternative to the dexamethasone suppression test. However, it is cumbersome to carry out and does not indicate the underlying cause.
what is the treatment of Cushing’s syndrome
Trans-sphenoidal (through the nose) removal of pituitary adenoma
Surgical removal of adrenal tumour
Surgical removal of the tumour producing ectopic ACTH (e.g., small cell lung cancer), if possible
what is Nelson’s syndrome
Nelson’s syndrome involves the development of an ACTH-producing pituitary tumour after the surgical removal of both adrenal glands due to a lack of cortisol and negative feedback. It causes skin pigmentation (high ACTH), bitemporal hemianopia and a lack of other pituitary hormones.
what does metyrapone do
reduces the production of cortisol in the adrenals and occasionally used in treating of Cushing’s
