Adrenal hyperactivity Flashcards
What are some causes or examples of Adrenal hyperactivity?
Primary hyperaldosteronism
Secondary hyperaldosteronism
Bilateral adrenal hyperplasia
Phaeochromocytoma
Neuroblastoma
What is meant by primary hyperaldosteronism?
This is a condition in which there is autonomous production of aldosterone, independant of its regulators (Angiotensin II and potassium)
What are some of the cardiovascular actions of aldosterone?
- Increased sympathetic outflow
- Increased cardiac collagen levels
- Cytokine and ROS synthesis
- Sodium retention
- Increased blood pressure
- Vasoconstriction
What is the most common cause of secondary hypertension?
Primary hyperaldosteronism
What are the main causes of primary hyperaldosteronism?
Adrenal adenoma (Conn’s syndrome)
Bilateral adrenal hyperplasia
Genetic
Unilateral hyperplasia
What are some clinical features of primary hyperaldosteronism?
- Significant hypertension
- Hypokalaemia
- Alkalosis
How is an aldosterone excess confirmed?
- Measure plasma aldosterone and renin and express as a ratio (ARR)
- If ratio raised, then investigate further with saline suppression test
- Failure of plasma aldosterone to suppress by >50% with 2L of normal saline confirms primary aldosteronism
How is the sub-type of primary aldosteronism confirmed?
- Adrenal CT to demonstrate adenoma (Conn’s disease)
- Sometimes adrenal vein sampling to confirm adenoma is a true source of aldosterone excess
What is the main surgical management option for primary hyperaldosteronism?
Unilateral laparoscopic adrenalectomy
What is the medical management of primary hyperaldosteronism?
Spironolactone or eplerenone
What is an adrenal adenoma (Conn’s syndrome)?
Benign neoplasm emerging from the cells of the adrenal cortex
Describe the genetics of adrenal adenoma formation
- KCNJ5 channel is a rectifying selective channel which maintains membrane hyperpolarisation
- Mutations lead to loss of ion selectivity; Na+ entry and depolarisation and therefore increased aldosterone production
Describe the histology of adrenal adenoma
- Composed of cells resembling adrenocortical cells
- Well-differentiated, small nuclei
How will adrenal adenoma present?
- Often asymptomatic
- Excess hormone secretion (E.g. Conn’s syndrome, Cushing’s)
How is adrenal adenoma investigated?
- Imaging (CT, MRI)
- Hormonal testing
How would a small adrenal lesion without biochemical abnormality be managed?
It can be safely left in situ
When would surgical excision of an adrenal adenoma be required?
Functioning lesion
Large lesion >3-5cm as this could be malignant
What is secondary hyperaldosteronism?
Increased adrenal production of aldosterone in response to nonpituitary, extra-adrenal stimuli such as renal hypoperfusion
What causes secondary hyperaldosteronism?
Reduced renal blood flow causes production of excess renin (Physiological response to low BP), causing production of angiotensin II and then aldosterone
What are some causes of reduced renal blood flow?
- Obstructive renal artery disease (eg, atheroma, stenosis)
- Renal vasoconstriction (as occurs in accelerated hypertension)
- Oedematous disorders (e.g. heart failure, cirrhosis with ascites)
What are some causes of renal artery stenosis?
Atherone
Fibromuscular dysplasia (In young females)
How will secondary hyperaldosteronism usually present?
Hypertension
What investigations are required in secondary hyperaldosteronism?
- Renin/aldosterone ratio - high aldosterone and high renin indicates secondary hyperaldosteronism
- Doppler ultrasound, CT angiogram or magnetic resonance angiography (MRA) to look for for renal artery stenosis or obstruction
How is secondary hyperaldosteronism managed?
- Aldosterone antagonists e.g. spironolactone
- Treat underlying cause e.g. percutaneous renal artery angioplasty via the femoral artery to treat in renal artery stenosis
What is a phaeochromocytoma?
These are rare tumours affecting the adrenal medulla
What are some possible complications of phaeochromocytoma?
Arrhythmia
Ischaemia
Cerebral haemorrhage
Death
How can phaeochromocytoma cause complications?
They can produce high levels of adrenaline and noradrenaline
How may phaeochromocytoma affect the sympathetic chain?
They can form extra-adrenal tumours (Paragangliomas)
What are some factors that increase the risk of phaeochromocytoma?
Surgery
Pregnancy
What are some causative syndromes of phaeochromocytoma?
- MEN2
- Von Hippel Lindau (VHL)
- Succinate dehydrogenase mutations
- Neurofibromatosis
- Tuberose sclerosis
What is the main triad of symptoms in phaeochromocytoma?
- Labile hypertension (On and off)
- Headache
- Paroxysmal sweating
What are some other symptoms of phaeochromocytoma?
- Pallor
- Palpitations
- Constipation
- Anxiety
- Weight loss
What are some clinical signs of phaeochromocytoma?
- Postural hypotension
- Bradycardia and tachycardia
- Pyrexia
What are some investigations required in diagnosis of phaeochromocytoma?
- Urine or plasma catecholamine excess
- MRI scanning
- MIBG scanning (Meta-iodobenzylguanidine)
- Biochemistry
- PET scanning
- Gallium-Dotate scan
What will biochemistry show in phaeochromocytoma?
- Hyperglycaemia - Adrenaline secreting tumours
- Possible hypokalaemia
- High haematocrit
- Mild hypercalcaemia
- Lactic acidosis in absence of shock
What are some conditions that can elevate urinary metanephrines?
Phaeochromocytoma
Heart failure
Hypertension
Drugs
On which body region would MRI scanning be performed in phaeochromocytoma?
MRI scanning is usually performed on the abdomen or pelvis, unless a paraganglioma is suspected, in which a whole body scan is performed
Who is screened for phaeochromocytoma?
Those will family history
Those with resistant hypertension
Those under 50 with hypertension
Those with classical symptoms of phaeochromocytoma
Why is phaeochromocytoma known as the 10% tumour?
10% Malignant
10% Extra-adrenal (probably 20-30%)
10% bilateral
10% associated with hyperglycaemia
10% in children
10% familial (Probably 25-40%)
What is the management plan in phaeochromocytoma?
- Full alpha and beta blockade (Alpha before Beta)
- Fluid and/or blood replacement (High salt diet as well)
- Careful anaesthetic assessment
- Stop blockade before surgery
- Surgical recision (If possible)
- Chemotherapy if malignant
- Radio-labelled MIBG
- Long term follow-up (10 years - lifelong)
- Genetic testing and family tracing
What alpha blocker is used in phaeochromocytoma?
Phenoxybenzamine
What ß-blockers can be used in phaeochromocytoma?
Propranolol
Atenolol
Metoprolol
What is a neuroblastoma?
Malignant neuroendocrine tumour of the sympathetic nervous system that originates from neural crest cells
Where can neuroblastoma occur?
40% arise in the adrenal medulla, remainder mostly occur along the sympathetic chain
Describe the histology of neuroblastoma
Composed of primitive appearing cells but can show maturation and differentiation towards ganglioid cells
What are some features of the tumour that predict a poor outcome?
Amplification fo N-myc and expression of telomerase
What are some symptoms of neuroblastoma?
Late onset:
- Loss of appetite
- Vomiting
- Weight loss
- Fatigue
- Bone pain
What are some investigations required in neuroblastoma?
- Bloods - FBC may detect anaemia, raised inflammatory markers, abnormal coagulation tests
- CT
- Biopsy
How is a low risk patient with neuroblastoma managed?
Low risk patients are simply observed for spontaneous resolution or are treated with local resection
How is a high risk patient with neuroblastoma managed?
High risk patients are given multi-agent chemotherapy, surgery and radiotherapy
