Disorders of the Adrenocortical Function Flashcards
(27 cards)
1
Q
What can adrenal overactivity be?
A
- Cushing’s syndrome
- Conn’s syndrome
- Adrenal Hyperplasia
- Phaechromaocytoma
2
Q
What can adrenal underactivity be?
A
- Addison’s Disease
- CAH
- Secondary Adrenal Failure
3
Q
How is Cushing’s disease investigated?
A
3 stages:
- Screening
- Urinary free cortisol
- Dirunal rhythm
- Over nigh dexamethasone suppression testing - Dexamethosone acts like ACTH, adminsitration can help differentiate b/w Cushing’s syndrome or disease. Cortisol should be sufficiently supressed in a normal subject, but if, for example, there’s an ectopic tumour, the negative feedback is bypassed, so cortisol lvls will still increase as the pituitary gland is not responsible. If cortisol is detectable, the patient has Cushing’s syndrome!
- Confirmation of the Diagnosis
- Differentiation of the Cause
- True Cushing’s syndrome
- Pseudocushing’s syndrome
- Depression, alcoholism, anorexia nervosa, obesity
- Exogenous steroids - Inhalers, eyedrops, nasal drops, skin creams, health food shops
4
Q
How can you differentiate between Cushing’s disease, adrenal tumour or ectopic ACTH production? What are the lab features?
A
- High dose dexamethasone suppression testing to exclude Cushing’s disease
- ACTH
- Imaging
Lab features:
- Hypokalaemia
- Metabolic alkalosis
- Hyperglycaemia
5
Q
Describe a CRH test and what it indicates
A
- 0.1 µg/kg of human CRH is given
- Blood is assayed for ACTH and cortisol at time -15, 0, 15, 30, 60, 90, 120.
- An exaggerated response indicates pituitary dependant Cushing’s Disease
- A flat response indicates ectopic ACTH production
6
Q
How can the different tumours be localised?
A
- Pituitary
- MRI
- Inferior Petrosal sinus sampling IPSS
- Adrenal
- CT or MRI
- Ectopic
- Octreotide Scan
- ACTH sampling
7
Q
How is an adrenal adenoma managed?
A
- SURGERY
- Cortisol Production Blockers
- Metyrapone
- Ketoconazole
8
Q
How is adrenal cancer managed?
A
- DXT - 3 field or gamma knife
- CXT Mitotane
9
Q
How is a pituitary tumour managed?
A
- TSS
- DXT
- Following treatment patients may require replacement of other pituitary hormones too
Patients need to have steroid replacement tablets at the time of and following surgery. The adrenal tumour suppresses the function of the normal gland. Many will not need the steroid tablets long term.
10
Q
How is adrenal insufficiency tested for?
A
- 9AM cortisol
- ACTH
- Electrolytes
- FBC
- Adrenal imaging
- Adrenal antibodies
- Investigations for other causes of adrenal failure
- Infection screen
- Imaging for cancer
- Biochemical testing enzyme deficiency
11
Q
Describe the Synacthen test in 21-hydroxylase deficiency
A
- Short Synacthen (250mcg):
- Blood taken over 1hr
- Used to diagnose primary adrenal failure
- Long Synacthen test (1mg):
- Blood taken over 24hr
- Used to diagnose secondary adrenal failure
12
Q
Describe an insulin tolerance test
A
- Gold standard for assesing adrenal reserve
- Insulin is administered to achieve hypoglycaemia with glucose less than 2.1 mmol/L
- Hypoglycaemia stimulates the stress response which is mediated by the compensatory hormones for hypoglycaemia
- Glucagon, catecholamines, growth hormone, prolactin.
- The test is contraindicated in
- Ischemic heart disease
- Epilepsy
- Severe panhypopituitarism
- The very old or very young
- Pregnancy
- Where the insulin tolerance test is contraindicated the glucagon test can be used
13
Q
What treatment is available for Addison’s disease?
A
- Hydrocortisone
- 10mg, 5mg, 5mg
- Mimicks the diurnal rhythm
- Last dose before 6pm
- Fludrocortisone
- 50-200mcg (o.d)
14
Q
How is 11beta-hydroxylase deficiency investigated?
A
- Synacthen test:
- No cortisol rise
- Increased 17-OH progesterone lvls
- Prednisolone suppression
- Androgens should fall into normal range
15
Q
How can 21-hydroxylase deficiency and 11beta-hydroxylase deficiency be treated?
A
- Both entities comprise spectrum of disease - partial deficiencies complicate matters
- Rx of 11B and 21 - hydroxylase deficiency lies mainly in use of glucocorticoid therapy
- Replace cortisol
- Inhibit ACTH production, reducing adrenal testosterone production
- Surgery to virlised female genitalia
- Treatment of mother to prevent foetal virilisation
- Fludriocortisone is used to replace absent mineralocorticoid activity
16
Q
How is Conn’s disease treated?
A
- Mineralocorticoid receptor blockade
- Spironolactone/eperelone
- Potassium sparing diuretics
- Amiloride/Traimpterine
- Potassium supplementation
- Treatment of the Primary Tumour
- Surgery
17
Q
What are the actions of cortisol?
A
- Increases plasma glucose lvls
- Increases gluconeogenesis, glycogenesis, glycogen storage
- Decreases glucose utilisation
- Increases lipolysis
- Provides energy
- Proteins catabolised
- Releases amino acids
- Na+ and H2O retention
- Maintains BP
- Anti-inflammatory
- Increased gastric acid production
18
Q
What is Cushing’s syndrome?
A
- Excess cortisol in the blood caused by ectopic ACTH production from tumour not located in pituitary gland
- Can be benign or malignant
19
Q
What is Cushing’s disease?
A
- Excess cortisol in the blood due to an ACTH secreting pituitary tumour (adenoma)
- Adrenal tumours can be benign or malignant
20
Q
What are the clinical features of Cushing’s syndrome?
A
- High BP and fluid retention - Due to salt and water retention
- Depression and anxiety
21
Q
What is Addison’s disease?
A
Insufficiency of Cortisol
22
Q
What are the clinical features of Addison’s disease?
A
- Tiredness
- Weakness
- Anorexia
- Hyponatraemia
- Hyperkalaemia
- Acidosis
- Hypoglycaemia
- Increased urea and creatinine
- Hyperpigmentation
- Vitiligo
23
Q
What are the causes of Addisons syndrome?
A
- Autoimmune
- TB
- Steroid Withdrawal
- Metastases
- Infiltration
- Amyloid
- Haemochromatosis
- Waterhouse-Freidrichson
- Apoplexy
- Infection
- Fungal histoplasmosis
- Viral HIV
- Bacteerial TB
- Enzyme
- Congenital Adrenal hyperplasia
- Adrenolucodystrophy
- Adrenomyolneuropathy
- Drugs
24
Q
Describe 21-hydroxylase deficiency (classical) CAH and its features
A
- Commonest form of Congenital Adrenal Hyperplasia
- Autosomal recessive
- HLA linked
- HLA-A3, Bw47, DR7
- Increased incidence in Yupik Eskimos
- Excess sex steroids cause:
- Virilisation, hirsutism, premature adrenarche, infertility
- No aldosterone, hence salt-losing crisis - Hyperkalaemia, hypotension
25
Describe 11beta-hydroxylase deficiency (Non-classical) and its features
- Approx 5% of reported CAH
- Autosomal recessive
- Increased incidence in Moroccan Jews
- HLA linked
- HLA-B14, DR1
- Excess sex steroids
- Virilisation, hirsutism, premature adrenarche, infertility
- No aldosterone but high DOC, which is an agonist at MC receptors
- Hypertension and hypokalaemia
26
Where is aldosterone produced and how does it acts on the kidneys? Describe renal control of aldosterone
- Produced in zona glomerulosa of the adrenal cortex
- Acts on kidney via receptor, binds glucocorticoids with equal affinity
- A decrease in NaCl load at the macula densa or decrease in renal afferent perfusion pressure can activate RAAS. Or increase SNS or plasma K+
- Renin is released from JG cells, acts with angiotensinogen from liver, produces Ang I
- Ang I converted into Ang II by ACE
- Ang II does lots of things, but specific to this, binds to AT1 receptors on the adrenal cortex, inducing aldosterone secretion
- Intranuclear receptor (type 1)
27
Describe the 2 types of aldosterone syndromes
Primary excess:
- High aldosterone
- Low renin
- Conn’s syndrome
- Bilateral adrenal hyperplasia
- Steroid treatable hypertension
- Aldosterone producing adrenal carcinoma
Secondary excess:
- High aldosterone
- High renin
- With hypertension
- Renal artery stenosis
- Renin secreting tumour
- Malignant nephrosclerosis
- Normal BP
- CCF
- Cirrhosis
- Nephrotic syndrome
- Dehydration
