Disorders of Adrenocortical Dysfunction Flashcards
What are the actions of cortisol?
- Glucose sparing effects
- Lipolysis
- Glyconeogenesis
- Glycogenesis
- Na and water mention
- Anti-inflammatory
- Increased gastric production
What is cushing syndrome?
Excess cortisol
What is Cushings disease?
Excess cortisol in the blood due to an ACTH secreting pituitary tumour
What are the clinical features of Cushing’s disease?
High blood pressure
Fluid retention
Due to salt and water retention
What are the 3 stages of investigating cushings disease?
- Screening
- Confirmation of the diagnosis
- Differentiation of the cause
Describe what happens in the Screening and Confirmation of the diagnosis
Urinary free cortisol
Diurnal Rhythm
Over night dexamethasone suppression testing
What happens in the Overnight Low Dose Dexamethasone Suppression Test?
Cortisol is measured at 8am
Dexamethasone 1mg is given at 11pm
Cortisol is measured at 8am the next morning
Cortisol suppression to <50nmol/l is normal
What happens in the differential diagnosis?
True Cushing’s Syndrome
Pseudocushing’s Syndrome: Depression Alcoholism Anorexia Nervosa Obesity
Exogenous steroids: Inhalers Eyedrops Nasal Drops Skin Creams Health Food Shops
What is the dosage and results of a Dexamethasone Suppression Test?
LOW DOSE
0.5 mg Dexamethasone six-hourly, 48 hrs
Result
complete suppression in normal subject
If cortisol detectable then patient has CUSHING’S SYNDROME
What does the differential diagnosis determine?
Cushing’s Disease
Pituitary Adenoma
Adrenal Tumour
Benign
Malignant
Ectopic ACTH production
Benign
Malignant
How do we differentiate between the cause?
High dose Dexamethasone Suppression testing
ACTH
Imaging
What happens at a high dose of Dexamethasone Suppression Test
HIGH DOSE
2 mg Dexamethasone six-hourly for 48 hrs
If cortisol suppresses to < 50% of baseline then the patient has Pituitary dependent Cushing’s Disease
If the Cortisol does not suppress then the patient has ectopic ACTH production or an adrenal tumour
What are the lab features of it?
Hypokalaemia
Metabolic Alkalosis
Hyperglycaemia
What happens in a CRH test?
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
What methods can be used to locate or see the problem?
Pituitary
MRI
IPSS
Adrenal
CT or MRI
Ectopic
Octreotide Scan
ACTH Sampling
What treatment is available for Cushing’s?
Cortisol Production Blockers
- Metyrapone
- Ketoconazole
DXT three field or gamma knife
Following treatment patients may require replacement of other pituitary hormones too
Adrenal source
Removal of adrenal tumour
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
Give some clinical features of additions disease
Tiredness Weakness Anorexia Weight loss Postural hypotension Myalgia Salt Craving Nausea Vomiting Hyperpigmentation Vitiligo
Hyponatraemia Hyperkalaemia Acidosis Hypercalcaemia Hypoglycaemia Increased urea and creatinine Eosinophilia
What is the cause of Addison’s disease?
Autoimmune TB Steroid Withdrawal Metastases Infiltration - Amyloid - Haemochromatosis Waterhouse- Freidrichson Apoplexy
Infection - Fungal - Viral Enzyme defect Congenital Adrenal hyperplasia - Adrenolucodystrophy - Adrenomyolneuropathy Drugs
What treatment is available for additions disease?
Hydrocortisone - 10mg 5mg 5mg - Mimicks the diurnal rhythm - Last dose before 6pm Fludrocortisone - 50-200mcg o.d.
What is 21-hydroxylase Deficiency (Classical)?
Excess sex steroids cause
virilisation, hirsutism, premature adrenarche, infertility.
No aldosterone, hence salt-losing crisis
hyperkalaemia, hypotension.
What is 11b-hydroxylase Deficiency (Non-Classical) caused by?
Excess sex steroids
virilisation, hirsutism, premature adrenarche, infertility
No aldosterone but high DOC, which is an agonist at MC receptors
hypertension and hypokalaemia
How can we investigate 11b-hydroxylase Deficiency (Non-Classical)?
Synacthen
No cortisol rise
Increased 17OH Progesterone levels
Prednisolone suppression
Androgens should fall into normal range
What is the treatment for 21-hydroxylase Deficiency (Classical) and 1b-hydroxylase Deficiency (Non-Classical)
Both entities comprise a spectrum of disease – partial deficiencies complicate matters.
Rx of 11b- and 21- hydroxylase deficiency lies mainly in the use of glucocorticoid therapy
Surgery to virilised female genitalia.
Treatment of Mother to prevent foetal Virilisation
Fludrocortisone is used only in 21-hydroxylase deficiency to replace absent mineralocorticoid activity
Describe aldosterone syndromes
Primary Excess Conn’s Syndrome Bilateral Adrenal Hyperplasia Steroid Treatable hypertension Aldosterone producing adrenal carcinoma
Secondary Excess With HT Renal artery stenosis Renin Secreting Tumour Malignant nephrosclerosis Normal BP CCF Cirrhosis Nephrotic syndrome Dehydration
What drugs treat conns syndrome?
Spironolactone
Amiloride / Triampterine
Potassium Supplementation
Treatment of the Primary Tumour
What is Phaeochromocytoma?
Tumour of the enterochromaffin cells of the adrenal medullar Produce Adrenaline ( nor adrenaline, dopamine)
What are the symptoms of Phaeochromocytoma?
Sweating Anxiety Fever Paroxysmal hypertension Palpitation (Hypotension) Angor aminii
Constipation Abdominal Pain Headache Fits Visual disturbance Pallor or Flushing
Eosinophilia Hyperglycaemia Hypercalcaemia Raised urinary Metanephrines catecholamines
How can we manage Phaeochromocytoma?
Emergency Alpha blockade Non competitive alpha antagonist Phenoxybenzamine phentolamine Beta blockade Nonselective beta blocker Propranolol Fluid Resuscitation Surgery
