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1. Disorders of Adrenal Gland
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2. The Adrenal Gland
• Adrenal glands located on top each kidney
• The adrenal gland is divided into the cortex and medulla.
• The adrenal cortex secretes glucocorticoids (eg, cortisol),
mineralocorticoids (eg, aldosterone), and androgens
• The adrenal medulla secretes catecholamines (primarily epinephrine,
but also small amounts of norepinephrine and dopamine).

3. Adrenal Cortex
• Adrenocorticotropin hormone (ACTH) stimulates the adrenal cortex
to produce cortisol.
• i.e.Cortisol secretion is directly controlled by ACTH
• ACTH is synthesized/secreted by the anterior pituitary gland in
response to corticotropin-releasing hormone (CRH) from the
hypothalamus.
• Abnormal function of the adrenal cortex may render a patient unable
to respond appropriately during a period of surgical stress or critical
illness.

4. • The secretion of ACTH and CRH is governed chiefly by glucocorticoids,
the sleep–wake cycle, and stress
• Cortisol is the most potent regulator of ACTH secretion, acting by a
negative-feedback mechanism to maintain cortisol levels in a
physiologic range.
• ACTH release follows a diurnal pattern, with maximal activity
occurring soon after awakening.
• Psychological or physical stress (trauma, surgery, intense exercise)
also promotes ACTH release

5. Glucocorticoid
• Cortisol (hydrocortisone) is the most potent endogenous glucocorticoid
• The daily production of endogenous cortisol is approximately 20 mg.
• Most of the circulating hormone is bound to the α-globulin cortisol-
binding globulin.
• It is the relatively small amount of free hormone that exerts the biologic
effects.

6. Effects of Cortisol/Glucocorticoids
• Multiple effects on intermediate carbohydrate, protein, and fatty acid
metabolism
• Maintenance and regulation of immune and circulatory function.
• Enhance gluconeogenesis, elevate BP, and promote hepatic glycogen
synthesis.
• Enhance degradation of muscle tissue and negative nitrogen balance.
• Suppress growth hormone secretion and impair somatic growth

7. • The anti-inflammatory actions of cortisol relate to its effect in stabilizing
lysosomes and promoting capillary integrity.
• Reduce white cell adherence to vascular endothelium and diminish
leukocyte response to local inflammation by antagonizing leukocyte
migration inhibition factor,
• Other diverse actions include the facilitation of free water clearance,
maintenance of BP, a weak mineralocorticoid effect, promotion of
appetite, stimulation of hematopoiesis, and induction of liver enzymes.

8. Mineralocorticoid
• Aldosterone is the most potent mineralocorticoid produced by the
adrenal gland.
• This hormone binds to receptors in sweat glands, the alimentary
tract, and the distal convoluted tubule of the kidney.
• Aldosterone is a major regulator of extracellular volume and
potassium homeostasis through the resorption of sodium and the
secretion of potassium by these tissues.
• The major regulators of aldosterone release are the renin–
angiotensin system and serum potassium levels

9. • The juxtaglomerular apparatus produces renin in response to decreased
perfusion pressures and sympathetic stimulation.
• Renin splits the hepatic precursor angiotensinogen to form angiotensin
I, which is then altered enzymatically by converting enzyme (primarily in
the lung) to form angiotensin II.
• Angiotensin II is the most potent vasopressor produced in the body.
• It directly stimulates the adrenal cortex to produce aldosterone.
• The renin–angiotensin system is the body’s most important protector of
volume status.

10. • Other stimuli that increase the production of aldosterone include
hyperkalemia and, to a limited degree, hyponatremia, prostaglandin
E, and ACTH.

12. Glucocorticoid Excess/Hypercortisolism
(Cushing Syndrome)
• Cushing syndrome results from chronic exposure to excess glucocorticoids.
• It is caused either by overproduction of cortisol or exogenous
glucocorticoid therapy
• The disorder may be ACTH dependent, ACTH independent, or iatrogenic.
• ACTH-dependent etiologies include pituitary corticotrope adenomas
(known as Cushing disease) and ectopic secretion of ACTH from
nonpituitary tumors (predominantly carcinoid tumors, especially lung).
• ACTH-independent etiologies include adrenocortical adenomas and
carcinomas or adrenal hyperplasia.

13. Signs and Symptoms
• Truncal obesity
• redistribution of fat in
facial, cervical, and truncal
areas.
• Hypertension
• Hyperglycemia(60%)/DM(20%)
• Increased intravascular fluid
volume
• Hypokalemia
• Fatigability,
• Abdominal striaez
• Osteoporosis, and
• Muscle weakness
• Thin extremities
• Amenorrhea,

14. • When Cushing syndrome occurs in patients older than 60 years of
age, the most likely cause is an adrenal carcinoma or ectopic ACTH
produced from a nonendocrine tumor.
• Impaired calcium absorption and a decrease in bone formation may
result in osteopenia.
• An increased susceptibility to infection reflects the
immunosuppressive effects of corticosteroids.

15. • Diagnosis is made by first excluding exogenous glucocorticoid use and
demonstrating an elevated 24-hour urinary free cortisol level.
• The laboratory diagnosis is based on a variable elevation in plasma and
urinary cortisol levels, urinary 17- hydroxycorticosteroids, and plasma
ACTH.
• Pituitary MRI, chest CT, CRH test, and high-dose dexamethasone test.
• Patients with pituitary adenomas frequently show depression in
cortisol and 17-hydroxycorticosteroid levels when a high dose of
dexamethasone is administered because the tumor retains some
negative-feedback control, and adrenal tumors do not.

16. • Treatment
• for Cushing disease: removal of the pituitary corticotrope tumor
• for ACTH-independent disease: removal of the adrenal tumor.
• Preoperative medical control of excess cortisol includes
• metyrapone (which inhibits cortisol synthesis),
• ketoconazole (which inhibits steroidogenesis),
• mitotane (which is an adrenolytic agent and reduces cortisol), and
• a low-dose IV infusion of etomidate.

17. Anesthetic Management
• Preoperative preparation of the patient include treating hypertension,
diabetes, and normalizing intravascular fluid volume and electrolyte
concentrations.
• Diuresis with the aldosterone antagonist (spironolactone) helps
mobilize fluid and normalize potassium concentration.
• Careful positioning of the osteoporosis is important
• Intraoperative monitoring depends on the patient’s cardiac reserve
and consideration of the site and extent of the proposed surgery

18. • There are no specific recommendations regarding the use of a
particular anesthetic technique or medication
• Etomidate has been used for temporizing medical treatment of severe
Cushing syndrome because of its inhibition of steroid synthesis.
• Muscle relaxants should be used cautiously when significant skeletal
muscle weakness is present.
• A pneumothorax is possible during adrenal surgery.
• Delayed wound healing and increased susceptibility to infection can
result from increased levels of glucocorticoids.

19. • A hydrocortisone replacement regimen is initiated at the time of surgery and
slowly tapered postoperatively.
• The total dosage is reduced by approximately 50% per day until a daily
maintenance dose of steroids is achieved (20 to 30 mg/day).
• Hydrocortisone given in doses of this magnitude exerts significant
mineralocorticoid activity, and additional exogenous mineralocorticoid is
usually not necessary during the perioperative period.
• but, if bilateral adrenalectomy is performed, fludrocortisone 0.05-0.1 mg/day will be
necessary in the postoperative period (usually day 3–5) dose is reduced if CHF,
hypokalemia, or hypertension develops.
• Slightly higher doses may be needed if prednisone is used for glucocorticoid
maintenance because it has little mineralocorticoid activity.

20. Management Options for Steroid Replacement in
the Perioperative Period

21. Mineralocorticoid Excess/hyperaldosteronism
(Conn syndrome)
• Hypersecretion of mineralocorticoid (aldosterone)
• Primary hyperaldosteronism, or Conn syndrome, is the most common
cause of mineralocorticoid (aldosterone) excess.
• It increases the renal tubular exchange of sodium for potassium and
hydrogen ions.
• Hypokalemic hypertension is the common presentation.
• skeletal muscle weakness, and fatigue also present
• Patients with primary hyperaldosteronism do not have edema.
• Secondary aldosteronism results from an elevation in renin production.

22. • The diagnosis of primary or secondary hyperaldosteronism should be
entertained in the nonedematous hypertensive patient with
persistent hypokalemia who is not receiving potassium-wasting
diuretics.
• The diagnosis is made by demonstrating an elevated level of plasma
aldosterone and low plasma renin (renin secretion is inhibited by the
high aldosterone levels).
• A specific aldosterone-renin ratio (ARR) confirms the diagnosis.

23. Anesthetic Considerations
• Anesthetic management requires preoperative restoration of
intravascular volume, electrolyte levels, renal function, and control of
hypertension.
• Hypertension and hypokalemia may be controlled by restricting sodium
intake and administration of the aldosterone antagonist spironolactone.
• Administering potassium (significant total deficit)may be necessary.
• The usual complications of chronic hypertension need to be assessed.
• A preoperative echocardiogram is useful
• Excess preoperative diuresis may render the patient hypovolemic.

24. • No specific anesthetic technique or medications are recommended
for these cases.
• An arterial line should be used, and other invasive monitors should be
determined on a case-by-case basis.
• Patients with Conn syndrome have a high incidence of ischemic heart
disease.

25. Adrenal Insufficiency (Addison Disease)
• The undersecretion of adrenal steroid hormones may develop as the
result of a
• Primary inability of the adrenal gland to elaborate sufficient quantities
of hormone or
• Secondary Deficiency in the production of ACTH.
• Clinically, primary adrenal insufficiency is usually not apparent until at
least 90% of the adrenal cortex has been destroyed.

26. • The predominant cause of primary adrenal insufficiency used to be
tuberculosis;
• however, today, the most frequent cause of Addison disease is
idiopathic adrenal insufficiency secondary to autoimmune destruction
of the gland.
• Autoimmune destruction of the adrenal cortex causes both a
glucocorticoid and a mineralocorticoid deficiency.
• Other possible causes of adrenal gland destruction include
• certain bacterial, fungal, and advanced HIV infections; metastatic
cancer; sepsis; and hemorrhage.

27. • Secondary adrenal insufficiency occurs when the anterior pituitary
fails to secrete sufficient quantities of ACTH.
• may result from tumor, infection, surgical ablation, or radiation
therapy.
• Patients receiving chronic corticosteroid therapy may develop acute
adrenal insufficiency during the stress of the perioperative period.
• Relative adrenal insufficiency is a common finding in critically ill
surgical patients with hypotension requiring vasopressors.

28. Clinical Presentation
• The cardinal symptoms of idiopathic Addison disease include
• chronic fatigue, muscle weakness, anorexia, weight loss, nausea,
vomiting, and diarrhea.
• Hypovolemia, hyponatremia, and hyperkalemia.
• Hypotension is almost always encountered in the disease process.
• Diffuse hyperpigmentation
• Adrenal insufficiency secondary to pituitary disease is not associated with
cutaneous hyperpigmentation or mineralocorticoid deficiency.
• Decreased axillary and pubic hair growth in female patients
• An acute crisis can present as abdominal pain, severe vomiting and
diarrhea, hypotension, decreased consciousness, and shock.

29. Diagnosis
• The classic definition of AI includes a baseline plasma cortisol
concentration of <20 μg/dL and a cortisol level of <20 μg/dL after
ACTH stimulation.
• Plasma cortisol levels are measured before and 30 and 60 minutes
after the IV administration of 250 μg of synthetic ACTH.
• A normal ACTH stimulation test result is a plasma cortisol level
greater than 25 μg/dL.
• Patients with adrenal insufficiency usually demonstrate little or no
adrenal response.

30. Treatment and Anesthetic Considerations
• Glucocorticoid therapy is usually given twice daily in sufficient dosage
to meet physiologic requirements.
• A typical regimen in the unstressed patient may consist of
• Prednisone, 5 mg in the morning and 2.5 mg in the evening, or
• Hydrocortisone, 20 mg in the morning and 10 mg in the evening.
• The daily glucocorticoid dosage is typically 50% higher than basal
adrenal output to cover the patient for mild stress.

31. • Mineralocorticoid replacement is also administered on a daily basis;
most patients require 0.05 to 0.1 mg/day of fludrocortisone.
• The mineralocorticoid dose may be reduced if severe hypokalemia,
hypertension, or congestive heart failure develops, or it may be
increased if postural hypotension is demonstrated.

32. Management of Acute Adrenal Insufficiency
• Immediate therapy of acute adrenal insufficiency is mandatory,
regardless of the etiology
• It consists of fluid/electrolyte resuscitation and steroid replacement
• Hydrocortisone 100 mg of IV bolus then 100mg IV every 6 hours for
24hrs.
• If the patient is stable, the steroid dose is reduced starting on the
second day.
• After adequate fluid resuscitation, if the patient continues to be
hemodynamically unstable, inotropic support may be necessary.

33. Steroid Replacement during the Perioperative
Period
• Perioperatively, patients with adrenal insufficiency and those with
HPA suppression from chronic steroid use require additional
corticosteroids to mimic the increased output of the normal adrenal
gland during stress.
• The degree of adrenal responsiveness has been correlated with the
duration of surgery and the extent of surgical trauma.
• Adrenal activity may also be affected by the anesthetic technique
used.
• RA and Deep GA suppress the elevation of stress hormones

34. Management Options for Steroid Replacement in
the Perioperative Period
• There is no proven optimal regimen for perioperative steroid
replacement
• A low dose cortisol replacement program is recommended:
• Hydrocortisone 25 mg IV before the induction of anesthesia, followed
by a continuous infusion of cortisol (100 mg) in the next 24 hours
• A popular regimen calls for the administration of 200-300 mg of
hydrocortisone in divided doses on the day of surgery.

35. • Etomidate transiently inhibits cortisol synthesis and should be
avoided in this patient population.
• Patients with untreated AI undergoing emergency surgery should be
managed aggressively with
• invasive monitoring, IV corticosteroids, and fluid and electrolyte resuscitation.
• Minimal doses of anesthetic agents and drugs are recommended,
since myocardial depression and skeletal muscle weakness are
frequently part of the clinical presentation.
• Hemodynamic support with vasopressors may be necessary.

36. Addisonian crisis
• Adrenal crisis is a life-threatening condition which can be induced by
stress during surgery in patients with adrenal insufficiency.
• Exogenous replacement should be considered in such cases, this
includes all patients on long term steroids as they will also display
iatrogenic adrenal suppression

37. Pheochromocytoma (Catecholamine Excess)
• A phaeochromocytoma is a tumour that arises in the adrenal medulla
and secretes catecholamines.
• It is a neuroendocrine tumours that arise from the chromaffin cells of
the sympathoadrenal system.
• This tumor accounts for 0.1% of all cases of hypertension.
• It is known as “the 10% tumour” because:
• 10% are bilateral
• 10% arise outside the adrenals
• 10% are malignant
• 10% are familial

38. • Uncontrolled catecholamine release can result in malignant
hypertension, cerebrovascular accident, and myocardial infarction

39. Diagnosis
• 24-hour urine collection for measurement of metanephrines and Free
catecholamine level
• MRI and CT

40. Clinical Features
• The cardinal manifestations of pheochromocytoma are paroxysmal
hypertension, headache, sweating, and palpitations.
• Pallor, flushing, Anxiety
• Abdominal pain, nausea and/or vomiting
• Weight loss
• Constipation or diarrhoea
• Glucose intolerance

41. • The pathophysiology, diagnosis, and treatment of these tumors
require an understanding of catecholamine metabolism and of the
pharmacology of adrenergic agonists and antagonists.

42. Preoperative investigations
• A clinical evaluation of the cardiac status of the patient,
• especially if a catecholamine induced cardiomyopathy is suspected
• CBC:
• normalisation of the haematocrit is indicative of the adequacy of α blockade
as the intravascular volume is corrected.
• Occult anaemia might be revealed on correction of the vascular tone.
• Blood sugar: Hyperglycaemia is common.
• ECG: ST and T changes secondary to myocardial ischemia, ventricular
hypertrophy, arrhythmias. Most changes are reversible on treatment.
• Echo: to estimate myocardial function if cardiomyopathy is suspected

43. Anesthetic Considerations
• Preoperative assessment should focus on the adequacy of α-
adrenergic blockade and volume replacement.
• Specifically, resting arterial BP, orthostatic BP and HR, ventricular
ectopy, and ECG evidence of ischemia should be evaluated.
• A decrease in plasma volume and red cell mass contributes to the
severe chronic hypovolemia seen in these patients.
• The hematocrit may be normal or elevated, depending on the relative
contribution of hypovolemia and anemia

44. • Preoperative α-adrenergic blockade with phenoxybenzamine helps
correct the volume deficit, in addition to correcting hypertension.
• β Blockade should not be initiated prior to initiation of α blockade but
may be added if there is a need to control heart rate and to reduce
arrhythmias provoked by excess catecholamine concentrations.
• A more selective approach using doxazosin (alpha 1 blockade) has the benefit
of not requiring the beta blockade.
• A drop in hematocrit should accompany the expansion of circulatory
volume, sometimes unmasking an underlying anemia.

45. Preoperative adrenergic blockade achieves the following objectives:
• Lowers blood pressure,
• Increases intravascular volume,
• Reduces the chance of hypertensive crises during induction and
tumour manipulation,
• Allows resensitisation of adrenergic receptors
• Reduces myocardial dysfunction in the perioperative period.

46. Criteria for optimal control include:
• Blood pressure readings consistently less than 160/90
• Presence of orthostatic hypotension (not less than 80/45)
• ECG should be free of ST-T changes
• No more than one PVC every 5 minutes

47. Intraoperative Management
• Close communication amongst team members is important to
anticipate and treat periods of instability.
• The choice of surgery can be either an open (retroperitoneal or
transperitoneal) approach or laparoscopic.
• Gas insufflation during laparoscopy can produce a hypertensive crisis
due to the increased intra-abdominal pressure

48. Periods of instability include:
• Induction and intubation
• Surgical incision
• Pneumoperitoneum during laparoscopic approach
• Abdominal exploration and tumour manipulation
• Ligation of venous drainage

49. The intraoperative goals are to:
• Avoid drugs or manoeuvres which produce a catecholamine surge
• Maintain cardiovascular stability with short acting drugs
• Maintain normovolemia and hemodynamics after tumour resection

50. • Intubation should not be attempted until a deep level of general
anesthesia has been established.
• Avoid drugs or techniques that
• Indirectly stimulate or promote the release of catecholamines (eg,
ephedrine, hypoventilation, or large bolus doses of ketamine),
• Potentiate the arrhythmic effects of catecholamines (classically
halothane), or
• Consistently release histamine (eg, large doses of atracurium or
morphine sulfate)

51. • Invasive arterial pressure monitoring and adequate IV access:
• Because of potentially life-threatening variations in BP—
particularly during induction and manipulation of the tumor
• Patients with evidence of cardiac disease (or in whom cardiac
disease is suspected) may benefit

52. • handling these tumours can cause a surge of catecholamaine release,
severe hypertension and end organ damage.
• Unexpected intraoperative hypertension and tachycardia during
manipulation of abdominal structures may occasionally be the first
indications of an undiagnosed pheochromocytoma.

53. • Intraoperative hypertension can be treated with phentolamine,
nitroprusside, nicardipine, or clevidipine.
• Phentolamine specifically blocks α-adrenergic receptors and blocks
the effects of excessive circulating catecholamines.
• Nitroprusside has a rapid onset of action, a short duration of action,
and can be effective in cases where calcium channel blockers are
ineffective.
• Nicardipine and clevidipine are being used more frequently
preoperatively and intraoperatively.

54. • After ligation of the tumor’s venous supply, the primary problem
frequently becomes hypotension from
• hypovolemia, persistent adrenergic blockade, and tolerance to the high levels
of endogenous catecholamines that have been abruptly withdrawn.
• Appropriate fluid resuscitation should reflect surgical bleeding and
other sources of fluid loss.
• Assessment of intravascular volume can be guided by
echocardiographic assessment of left ventricular filling using TEE or
other noninvasive measures of cardiac output and stroke volume.
• Infusions of adrenergic agonists, such as phenylephrine or
norepinephrine, often prove necessary.

55. Postoperative Management
• These patients, ideally, are managed post operatively in an ICU/HDU.
• Anticipated problems include refractory hypotension ,and hypoglycaemia
• Consider steroid supplementation if bilateral adrenalectomy is carried
out or if hypoadrenalism is suspected.
• Provide adequate postoperative analgesia
• Postoperative hypertension is rare and may indicate the presence of
residual tumour, renal ischemia or underlying essential hypertension