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Adrenal Disorders and Anaesthesia

by Pat Neligan 1999

All tutorials located on this site are the property of Patrick Neligan and are for personal study purposes only. They are not peer reviewed and no responsibility is taken for inaccuracies. These tutorials must not be reproduced without permission or used in any other publication.

Contents:

  1. Anatomy, embryology and physiology of the adrenal glands.
  2. Pathological disorders of the adrenal galands and their anaesthetic management:
    • Phaeochromocytoma
    • Adrenal Insufficiency
    • Glucocorticoid excess
    • Mineralocorticoid excess
    • Androgen Excess

Anatomy, embryology and physiology.

The adrenal glands are endocrine organs located above each kidney.

They consist of two embryologically distinct endocrine organs:

1. The adrenal medulla.

2. The adrenal cortex.

  • The adrenal medulla is located at the centre of the gland. It is highly vascular and is of ectodermal origin. It is characterised by chromaffin cells. These cells manufacture three catecholamines: adrenaline, noradrenaline and dopamine.
  • Cortisol, which is produced in the cortex, is necessary for converting noradrenaline to adrenaline. This is carried directly in the blood from the cortex to the medulla. The adrenal medulla resembles an enormous sympathetic ganglion, without the post-ganglionic neurones. The output is approx. 80% adrenaline and 20% noradrenaline.
  • The Adrenal Cortex is located peripherally. It is of mesodermal origin and consists of three distinct zones:

Outermost - Zona Granulosa: secretes aldosterone @ 100m g per 24 hours [aldosterone is responsible for sodium balance and effectively, control of the ECF volume]

Middle - Zona Fasciculata: secretes glucocorticoids (cortisol 16-20 mg per 24 hours and corticosterone 4mg in 24 hours) [glucosorticoids are involved in controlling the stress response and also for the control of metabolism].

Inner - Zona Reticularis: secretes androgens.

The hormones secretes by the adrenal cortex are all derived from cholesterol and are under the control of other circulating factors. The release of aldosterone is controlled by the renin-angiotensin system, and, to a degree, ACTH. The production of glucocorticoids is controlled by an axis: corticotropin releasing hormone, produced by the hypothalmus) ® ACTH (corticotropin), produced by the anterior pituitary) ® cortisol. Cortisol and other corticosteroids negatively feedback onto this axis and thus production is controlled.

Pathological disorders of the adrenal glands.

Like all endocrine glands, there are three types of disorders that can occur: inadequate production of hormone, excessive production of hormone, and abnormal production of hormone.

Adrenal medulla:

  • Underproduction:
  • Overproduction: Phaeochromocytoma
  • Abnormal production:

Adrenal Cortex:

  • Underproduction: primary adrenal failure (Addison's disease)
  • Overproduction:

Glucocorticoids: Cushings disease (primary - due to adrenal adenoma, secondary - to pituitary tumour or, more commonly, to exogenous steroids).

Mineralocorticoids: Conn's syndrome (primary aldosteronism) - aldosterone secreting adenoma.

  • Abnormal production: Congenital adrenal hyperplasia.

Phaeochromocytoma

  • Rare catecholamine secreting tumours of chromaffin cells.
  • 0.75% of cases of secondary hypertension.
  • May arise from any tissue of neuroectodermal origin.
  • 10% are outside the adrenal glands.
  • 10% are bilateral.
  • 10% are malignant.

Clinical Features (all the Ps)

Pain in the chest & abdomen

Pallor

Perspiration

Polyuria (from glycosuria)

HyPertension ± diastolic / postural hyPotension

Prostration

  • Paroxysmal episodes of hypertension, headache, sweating, palpitations.
  • Cardiovascular findings: tachycardia, hypertension, congestive cardiac failure, angina, myocardial infarction and stroke.
  • The patient may also complain of weight loss, anorexia and constipation.
  • The pharmacological effects of noradrenaline are predominant in most cases.
  • The patient is in a chronic state of vasoconstriction and hyovolaemia. Cardiac dilatation and down regulation of receptors.
  • Unexpected cardiovascular crises may occur: spontaneously, due to stress / exercise, during surgery (for an unrelated disorder), handling of the tumour during surgery, during pregnancy / labour [very high maternal mortality rate].

Diagnosis of phaeochromocytoma:

1. History: hypertension in a young patient; resistant hypertension; symptoms that don't quite fit any other diagnosis (sweating, palpitations, headache etc). The differential diagnosis is thyrotoxicosis, carcinoid syndrome, pre-eclampsia and migraine.

2. Urinary tests: metabolic products of adrenaline and noradrenaline - VMA, HMMA, *urinary catecholamines, metanephrines & normetanephrines.

3. Blood tests: plasma catecholamine levels.

4. Radiology: ultrasound may demonstrate large adrenal / intrabdominal tumours. CT scanning will pick up 90% of tumours >1cm. If not located on CT, but suspected (CT is poor for non adrenal tumours) then an MIBG scan is indicated).

Why is it important to anaesthetists?

  • These patients may become extremely unstable haemodynamically perioperatively, and untreated would incur a high mortality rate.
  • The prime objective of anaesthesia management is proper preoperative preparation, and rapid diagnosis and treatment in the previously undiagnosed patient.

The preoperative visit

History: look for the symptoms above

Examination: hypertension, weak pulse, pallor, sweating etc.

Investigations: standard bloods: FBC, Renal, Liver, Bone profiles, T4 & TSH, Coag, X-match,

ecg, x-ray of chest (cardiomegaly and pulmonary oedema), special investigations: phaeo work up plus echocardiogram

Perioperative care plan

Preoperative medical preparation

This is the essential component of preparing these patients. Preoperative a -adrenergic blockade is essential using phenoxybenzamine 10mg BD increasing daily until blood pressure is controlled (postural hypotension and resolution of adrenergic symptoms). If a tachycardia develops, propranolol, a b -blocker, is added (40-80mg/daily). Patients should be given plenty of fluids as a relative hypovolaemia is exposed. A minimal of 7 to 10 days treatment is required for most patients; longer for severe disease or if there is a cardiomyopathy.

Never ever commence beta blockage before alpha blockade, as this will precipitate a hypertensive crisis (this includes labetalol which has greater b than a effect).

Pre-medication:

  • Oral phenoxybenzamine and propranolol.
  • Anxiolytic: diazepam or temazepam.
  • Enoxparin or minihep.

Vascular access

  • Large bore iv access (14G) ± swan-ganz introducer.
  • Perioperative monitoring
  • ECG / SpO2 / EtCO2 / Gases etc.
  • Arterial line.
  • CVP line (3-lumen)
  • Pulmonary artery catheter (differences in right and left sided filling pressures, changes in cardiac output and SVR), with continuous cardiac output monitoring (if available).
  • Core and peripheral temperatures.

 

Conduct of anaesthesia

Preparation: avoid atropine (® tachycardia), phentolamine infusion, sodium nitroprusside infusion for control of hypertensive surges (eg. handling of the tumour), propranolol iv for control of tachycardia, noradrenaline infusion for control of post resection hypotension.

An epidural is inserted prior to induction: this is for augmentation of a blockade and for perioperative analgesia.

Induction: Induction agent (little difference between them), vecuronium or cis-atracurium, fentanyl/alfentanyl, isoflurane.

Airway: endotracheal tube

Positioning: the lateral position is preferred by most surgeons. The theatre temperature should be 21 degrees, and use of a bair hugger / warming blanket / warmed fluids is indicated.

Maintenance: there may be huge swings in blood pressure during the procedure, best treated with propranolol (esmolol has not been shown to be as effective). Volume loading is usually necessary. Following ligation of the venous drainage, there is usually a fall in the blood pressure due to vasoplegia (high output, low SVR, resembling septic shock), requiring noradrenaline infusion.

Recovery: in most cases cardiovascular stability returns within a few hours of completion of surgery. At this stage vasoactive agents are withdrawn.

Post-operative care

  1. Venue : ICU
  2. Monitoring: ECG, SpO2, ABP, CVP, continuous cardiac output.
  3. Analgesia: epidural
  4. Fluid and nutrition: as normal
  5. General care [DVT / stress ulcer prophylaxis etc].

Drugs that should be avoided: opioids (may cause release of NAD from the tumour), tricyclic antidepressants, dopamine antagonists (e.g. metoclopramide)

Adrenal Insufficiency

Inadequate glucocorticoids and mineralocorticoids

  • Adrenal insufficiency may be primary or secondary (to hypopituitarism or withdrawl of exogenous steroids).
  • Primary adrenal insufficiency is most commonly Addison's disease: an autoimmune disease whereby circulating autoantibodies progressively destroy adrenal tissue (other causes are infiltration [tumour], infection [TB] or surgical removal).
  • There is a strong association with other autoimmune disorders such as thyroid disease, diabetes and myasthenia gravis.
  • Main problem is cortisol deficiency.

Clinical Features (symptoms and signs):

Asthenia - progressive fatigue and weakness

Pigmentation of the skin and mucus membranes (not seen with hypopituitarism).

Weight loss, anorexia, diarrhoea, vomiting, abdominal pain.

Main Problems:

1. Poor stress response.

2. Hypovolaemia, hypotension and intolerance of fluid loading.

3. Hypoglycaemia [particularly "reactive hypoglycamai" after a meal]

4. Hyperkalaemia: risk of cardiac arrhythmias, particularly with suxamethonium.

5. Problems associated with chronic steroid therapy.

Diagnosis:

­ K, ¯ Na, ­ urea, ¯ glucose, ­ Ca

Random serum cortisol >140nmol/l

Short synachten test: 250m g of ACTH is given and cortisol measured at 0 and 30 mins. Addison's is excluded if second cortisol is >500nmol/l and >200nmol/l greater than baseline. If this does not excude Addison's, an ACTh level should be measured (low cortisol and ACTH>300 = Addison's).

Treatment:

Hydrocortisone 20mg mane and 10mg tarde (adjusted to symptoms).

Fludrocortisone up to 150m g once daily.

Follow up:

Patients must carry a steroid card or a medi-alert bracelet. For surgery the morning dose should be doubled. For serious illness, the total daily dose should be doubled.

Addisonian Crisis

Acute Adrenal Insufficiency

Acute withdrawl of corticosteroids in patients with Addison's disease or exogenous steroids. May also be precipitated by infection, surgery or trauma [insufficient hormonal response to meet the stress requirements]. Sudden destruction of the gland may occur in severe sepsis, DIC, burns, trauma.

The patient presents in shock, usually with an antecedent history of malaise, tiredness, weakness, anorexia, abdominal pain.

Severe dehydration, hypotension and peripheral circulatory failure are refractory to treatment without steroid administration. Shock refractory to conventional treatment should always make you think of an Addisonian crisis.

Treatment:

1. ABC

2. iv fluids (gelofusin or Hartmann's/NaCl).

3. Steroids are given without delay: if adrenal insufficiency is known give Hydrocortisone 100mg stat, if unknown, give Dexamethasone 10mg iv and do a short ACTH stimulation test (Dexamethasone does not interfere with the hypothalmo-pituitary axis).

Why is Adrenocortical Insuficiency it important?

Patients with unsuspected adrenocortical insufficiency may present for surgery. Alternatively, patients taking exogenous steroids may have inadequate reserves to meet the demands of perioperative stress.

What are the anaesthesia implications?

Patients may develop an acute adrenal crisis intraoperatively. What is important is that during these crises, the patient may become hypotensive, and this ¯ BP is unresponsive to fluids and adrenaline. With the administration of hydrocortisone (100mg iv) this situation resolves rapidly.

Perioperative care plan

Preoperative medication: how much steroid do you give?

  • Under normal conditions, an individual requires approx 30mg of hydrocortisone per 24 hours.
  • Minor surgical stress: cortisol output increases to 50mg / 24 hours.
  • Major surgical stress: cortisol output increases to 150 mg / 24 hours.
  • After even major surgical stress, serum cortisol levels return to normal within 48 hours.
  • There is no advantage in giving more steroid than is necessary. In fact, the contrary is probably true: steroids have adverse effects on wound healing and immune function.

Suggested regime:

Minor surgery (dental extractions): hydrocortisone 25mg mane and 25mg tarde. Normal dose day 2.

Moderate surgery (hernia repair): hydrocortisone 25mg TID x 2/7. Normal dose day 3.

Major surgery (bowel resection): hydrocortisone 50mg TID x 3/7. Normal dose day 4.

Equivalent doses: hydrocortisone 100mg = prednisolone 25mg = methylprednisolone 20 mg = triamcinolone 20mg = dexamethasone 4mg

Conduct of anaesthesia

For the most part the conduct of anaesthesia should not be any different from your usual practise. Nonetheless, one should endeavor to minimise the stress response by ensuring good quality analgesia and using "blunting" techniques (fentanyl or lignocaine for induction, incision etc). Epidural analgesia may be particularly useful in this regard.

Cushing's syndrome

Excess Glucocorticoids

Coticosteroid excess may be primary, due to an adrenal adenoma / hyperplasia, or secondary, to an ACTH secreting tumour, pituitary (Cushing's disease) or "ectopic", or to exogenous steroid usage.

Clinical Features:

Coarsening of the features: moon faced, buffalo humped, central obesity, hirsuitism. Atrophy of the skin, osteoporosis, easy bruising, diabetes, proximal myopathy, aseptic necrosis of the hip, diabetes, euphoria, pancreatitis etc.

Main problems:

1. Hyperglycaemia.

2. Hypokalaemia.

3. Hypertension.

4. Polycytaemia.

5. Congestive cardiac failure.

6. Atrophic skin - breaks down easily.

7. Osteoporosis - risk of fractures, vertebral compression.

Diagnosis of Cushing's syndrome:

1. Midnight and 9am cortisol: loss of diurnal variation.

2. Metyrapone test: this inhibits 11b -hydroxylation, this inhibits cortisol synthesis and leads to the ­ presence of metabolites in pituitary adenoma and in normal patients.

3. ACTH assay; very high in ectopic ACTH, high in Pituitary adenoma, very low in adrenal adenoma.

4. Dexamethasone supression test: low dose supresses the ­ cortisol associated with alcohol and depression, a high dose suppresses a pituitary cause.

5. CT of the adrenals.

Why is it Cushing's syndrome important?

These patients have a multitude of problems. Of importance: obesity, diabetes, coronary heart disease, hypertension etc. Increased anaesthetic risk.

What are the anaesthesia implications?

  • Pre-op: if iatrogenic (commonest), must have double dose steroids as premed.
  • Intra-op: difficult airways, difficult venous access, skin breaks down or tears easily (care fixing down tubes and iv lines), care with positioning - obesity® difficult to lift, osteoporosis® fractures occur easily, difficult to insert a spinal / epidural. Obesity often mandates rapid sequence induction. Hypertension ® volume loading necessary to prevent "roller coaster" anaesthetic
  • Post-op: poor ventilatory performance (¯ FRC), poor mobilisation, pressure sores etc.

The preoperative visit

History: *steroid dosage and duration, identification of associated disorders.

Examination: cardiovascular, respiratory, abdomen, airway.

Investigations: standard bloods / glucose, HbA1C/ ECG / CXR / PFTs

*Steroid

Glucocorticoid effect

Mineralocorticoid effect

Cortisol (hydrocortisone)

1

1

Prednisolone

4

0.7

Dexamethasone

40

2

Aldosterone

0.1

400

Fludrocortisone

10

400

Perioperative care plan

This really depends on what type of operation the patient is having. Below is what would be required for a standard / simple case:

Preoperative medication: anxiolytic, double dose of steroids

Vascular access: as appropriate

Perioperative monitoring: ECG, SpO2, NiBP (art line if necessary), EtCO2, gases

Conduct of anaesthesia

Induction: Rapid sequence induction.

Airway: endotracheal tube.

Positioning: with care as described above.

Maintenance: avoid large doses of opioids, as post-op respiratory depression may cause difficulty with extubation.

Recovery: extubate awake

Post-operative care

Venue [ward / HDU / ICU] as appropriate.

Hyperaldosteronism (Conn's syndrome)

This is caused by an aldosterone secreting tumour, adenoma (60%) or carcinoma or bilateral adrenal hyperplasia (30%).

Clinical Features:

Weakness, polyuria, polydipsia, tetany (all due to ¯ K+).

Hypokalaemic metabolic alkylosis

Hypertension

­ plasma aldosterone, ¯ plasma renin, ­ urinary K+ in spite of low plasma levels.

Differential diagnosis:

  • Barrter's syndrome (hyperplasia of the juxta-glomerular apparatus): normotensive, high renin levels.
  • Diuretic abuse: dehydrated - hypernatraemia
  • Diarrhoea / laxatives: history.
  • Ectopic ACTH: acidotic (not alkylotic), hyperglycaemic
  • Cushing's syndrome: other features are evident.
  • Type IV Renal Tubular Acidosis: hyperkalaemia

Congenital adrenal hyperplasia

Deficiency of 21b -hydroxylase in 95% ® insufficient cortisol, excessive precursors leading to the accumulation of androgens ® virilism in females, precocious puberty in males. Deficiency of 11 hydroxylase ® hypertension.

It is extremely unlikely that you will be asked about this in anaesthetics exams.

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