Adrenal Gland Flashcards
Cushing’s is…
Excess cortisol
What are the causes of Cushing’s syndrome?
- 65% = pituitary
- 25% = adrenals
- 10% = ectopic source (small cell lung ca), non-pituitary, ACTH producing tumour
Cushing’s Symptoms?
SWEDISH
Differentials of Cushings:
- Chronic severe anxiety and/or depression
- Prolonged excess alcohol consumption
- Obesity
- Poorly controlled diabetes
- HIV infection
How is Cushing’s diagnosed?
- Perform at least two first-line biochemical tests to obtain the diagnosis:
- Urine free cortisol (UFC) (at least two measurements)
- 1-mg overnight Dexamethasone Suppression Test (ODST)
- Longer low-dose Dexamethasone Suppression Test (LDDST) (2 mg/d for 48 h).
- CT/MRI of Pituitary and Adrenal
Treatment of Cushings:
• Metyrapone, ketoconazole, and mitotane can all be used to lower cortisol by directly inhibiting synthesis and secretion in the adrenal gland.
What are the complications of Cushings?
Premature death in untreated Cushing’s syndrome are caused by vascular disease (MI/CVA), uncontrolled DM and infections.
Secondary vs Primary adrenal insufficiency:
Can also be caused by:
- TB (most common worldwide)
- Infections – AIDS, fungal
- Adrenal haemorrhage (caused by sepsis, meningitis)
- Metastatic spread to adrenals
- Amyloidosis
- Adrenalectomy
- Genetic/congenital defects
What is Addison’s Disease?
Addison’s Disease refers to the specific condition where the adrenal glands have been damaged, resulting in a reduction in the secretion of cortisol and aldosterone. This is also called Primary Adrenal Insufficiency. The most common cause is autoimmune.
Primary Auto-immune Addison’s:
- True Addison’s:
- Affects 1 in 10000 in UK – rare
- Common presentation between 30 and 50
- Affects women more
- 70-90% have autoimmune basis – cytotoxic T cells
- Clinical and biochemical insufficiency only occurs once >90% of the gland is destroyed.
Symptoms and signs of Addisons and adrenal insufficiency:
Hyperpigmentation
Weight loss
Low BP
Nausea and GI problems
What are the symptoms of Adrenal crisis?
- Fever
- Syncope
- Severe vomitting and diarrhoea
- Convulsions
- Hypoglycemia
- Hyponatremia
Investigations of Adrenal insufficiency:
Blood tests:
- Low Na, low cortisol
- Low aldosterone causing high K
- High adrenocorticotrophic hormone (ACTH)
- Low glucose
- CXR and CT/MRI of adrenals
Why is a chest xray done in cases of adrenal insufficiency?
To check for TB.
Causes of adrenal insufficiency?
Auto-immune destruction
TB (most common worldwide)
Infections – AIDS, fungal
Adrenal haemorrhage (caused by sepsis, meningitis)
Metastatic spread to adrenals
Amyloidosis
Adrenalectomy
Genetic/congenital defects
Amyloidosis
Abnormal protein, called amyloid, builds up in your organs and interferes with their normal function.
Treatment of adrenal insufficiency
Treat cause.
Replace steroids.
Symptoms of an Addisonian Crisis:
Treatment of Addisonian crisis
- Medical emergency
- Bloods, large bore cannula
- Seek help if you suspect
- Iv Hydrocortisone
- Iv fluids
- Iv glucose if needed
Mineralcorticoid =
= Aldosterone produced by zona glomerulosa
What are the actions of Aldosterone?
- Sodium retention.
- Excretion of Potassium
- Increase blood volume and pressure.
- H+ excretion.
Aldosterone acts where?
On the DCT (distal convuluted tubule)
What are the primary causes of hyperaldosteronism?
- Idiopathic most common.
- Conn syndrome - Adenoma secretes to much aldosterone.
- Familial - where aldosterone is produced in repsonse to ACTH aswell as angiotensinogen 2.
What are the secondary causes of hyperaldosteronism?
Usually due to excess renin - can result from chronic low blood pressure in cases of congestive heart failure / cirrhosis.
- Decreased renal perfusion (arteriolar nephrosclerosis, renal artery stenosis)
- Arterial hypovolemia and edema (congestive heart failure, cirrhosis, nephrotic syndrome)
- Pregnancy (due to estrogen-induced increases in plasma renin substrate)
Metabolic profile of hyperaldosteronism:
High Na+
Low K+
Alkalosis due to H+ loss.
Symptoms of Hyperaldosteronism:
Raised blood pressure.
Resistant raised BP big sign.
How is hyperaldosteronism diagnosed?
Measuring levels of renin and aldosterone.
Plasma:
- Hypokalemia
- Aldosterone:renin ratio (ARR): Plasma renin/aldosterone
Urine :
• Increase urinary potassium
Imaging :
- CT/ MRI
- Adrenal vein sampling
- Functional imaging
How is hyperaldosteronism treated?
Spironolactone (potassium sparing diuretic).
- spironolactone competitively binds to aldosterone receptors on the principal and intercalated cells of the DCT - blocks aldosterone.
Removal of tumour in Conn’s syndrome.
Management of congestive heart failure and cirrhosis.
Hyperaldosteronism affects what population most commonly?
Women aged 30-60
11C-metomidate, a potent steroidogenic enzyme inhibitor, is a PET CT radiotracer that is selectively accumulated by Conn’s adenomas.
11C-metomidate, a potent steroidogenic enzyme inhibitor, is a PET CT radiotracer that is selectively accumulated by Conn’s adenomas.
Diagnosis of Adrenal Incidentaliomas:
• Functioning vs. Nonfunctioning (producing hormones).
- functioning requires surgery.
Benign or malignant
- more than 4-6cm requires surgery due to risk of malignancy.
How do you test is a adrenal mass if functional or non-functional?
Overnight dexamethasone suppression test.
Normal summary of adrenal tumours:
Pheochromocytoma produces what hormones to excess?
Epinephrine and norepinephrine.
Conn’s results in what hormone abnormality?
Excess aldosterone
When is it important to consider hyperaldosteronism?
In patients with hypertension and hypokalemia.
What can cause phaecytochromatoma’s to form?
- Arise sporadically
- MEN Type 2a and 2b
- Von Hippel Lindau disease (mutation in VHL tumour supressor).
- Neurofibromatosis
What can phaecytochromatoma’s lead to?
Hypertensive urgency which can burst small blood vessels in the heart, eye, brain and kidneys.
- this can result in congestive heart failure / ischaemic and haemorrhagic stroke.
Where do pheochromocytoma’s commonly metastasize to?
Liver
Lymph nodes
Bones
Lungs
What are the symptoms of pheochromocytoma’s?
High blood pressure
Sweating
Anxiety
Palpitations
Headaches
How are pheochromocytoma’s diagnosed?
Increase catecholamines in blood / urine.
Metanephrine in urine.
Ultrasound and CT of adrenal gland.
What is the treatment for pheochromocytoma?
Medications to lower BP.
Surgery to remove the tumour.
Pheochromocytoma is a tumour of what?
Chromaffin cells in the adrenal medulla.
MEN
Mutliple endocrine neoplasia - an inherited disorder where tumours grow in the endocrine glands of the body.
Paragangliomas
Paragangliomas are rare tumors that form near the carotid artery, along nerve pathways in the head and neck, and in other parts of the body. Some paragangliomas make extra catecholamines called adrenaline and noradrenaline. The release of these extra catecholamines into the blood may cause signs or symptoms of disease.
They are pheochromocytoma’s that form outsid of the adrenal gland.
What organs are affected in MEN?
Pancreas
Adrenal gland
Thyroid gland
Parathyroid gland
Pituitary
What is the genetic cause of MEN?
Inheritance of mutation in either MEN1 or RET.
- both are autosomal dominant.
MEN1 gene is found on what chromosome and does what?
Chromosome 11 and is a tumour supressor.
MEN1 affects what organ?
Pancreas - insulinoma, glucagonoma, and gastrinoma.
Parathyroid - excess PTH.
Pituitary - prolactinoma, acromegaly.
MEN2a causes what cancer?
Thyroid medullary cancer - from the c cells.
Pheocytochromotoma
Parathyroid tumours.
MEN 2b difference from MEN2a?
MEN2b also causes thyroid medullary cancers and pheocytochromocytoma however also causes multiple neuromas.
Multiple neuroma
Tumours of the nerve tissue, skin and mouth.
MEN type 2 summary:
What is the treatment for MEN?
Diagnosed with genetic testing to find mutation.
Surgery for tumours.
In MEN type 2 thyroidectomy’s are carried out as thyroid cancer is guaranteed in this condition.
MEN summary:
Neurofibromatosis:
Neurofibromatosis is a genetic disorder that causes tumors to form on nerve tissue. These tumors can develop anywhere in your nervous system, including your brain, spinal cord and nerves. Neurofibromatosis is usually diagnosed in childhood or early adulthood.
What are the causes of Cushing’s
Exogenous steroids (in patients on long term high dose steroid medications)
Cushing’s Disease (a pituitary adenoma releasing excessive ACTH)
Adrenal Adenoma (a hormone secreting adrenal tumour)
Paraneoplastic Cushing’s
What is used to diagnose Cushing’s?
Dexamethasone suppression test
How does a dexamethasome suppression test detect Cushing’s?
Dexamethasone suppresses the release of ACTH from the anterior pituitary.
- if cortisol is low after the test this indicates Cushing’s.
Dexamethasone suppression test:
low cortisol =
Cushing’s
Dexamethasone suppression test:
High cortisol low ACTH
Adrenal tumour secreting excess cortisol
Dexamethasone suppression test:
High cortisol high ACTH
Paraneoplastic syndrome secreting ACTH e.g lung cancer
What other investigations should be carried out in suspected Cushing’s?
- FBC (raised white cells) and electrolytes (potassium may be low if aldosterone is also secreted by an adrenal adenoma)
- MRI brain for pituitary adenoma
- Chest CT for small cell lung cancer
- Abdominal CT for adrenal tumours
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What test is used to diagnose adrenal insufficiency?
A short synacthen test is the test of choice to diagnose adrenal insufficiency.
In Cushing’s how are cortisol levels normalised?
• Metyrapone, ketoconazole, and mitotane can all be used to lower cortisol by directly inhibiting synthesis and secretion in the adrenal gland.
Addison’s =
Adrenal insufficiency
What are the functions of aldosterone?
Reabsorption of sodium and water in the kidneys.
Excretion of potassium.
Maintenance of blood pressure.
Causes of Addison’s:
Auto-immune adrenalitis
Infections e.g tuberculosis
Adrenal infarction - occurs in SLE and APS
Drugs
Metastasis
Trauma
Adrenal haemorrhage e.g waterhouse frederichsen syndrome.
Clinical features:
Due to cortisol deficiency:
Fatigue
anorexia
weight loss
muscle weaknesses
abdo pain
diarrhoea
hypoglycemia = sweating +headache
Hyperpigmentation (hands + buccal mucosa).
Management of phaecytochromatoma
Alpha blockers (i.e. phenoxybenzamine)
Beta blockers once established on alpha blockers
Adrenalectomy to remove tumour is the definitive management
What is the first-line investigation in suspected primary hyperaldosteronism?
A plasma aldosterone/renin ratio is the first-line investigation in suspected primary hyperaldosteronism.
