Disorders of the Adrenal Gland Anesthetic Implications

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Disorders of the Adrenal GlandAnesthetic
Implications

• Rajeshwari Subramaniam
• Professor, Anesthesiology
• All India Institute of Medical Sciences

www.anaesthesia.co.in anaesthesia.co.in_at_gmail.c
om
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Disorders to be discussed

• Hypercortisolism-Cushings syndrome
• Addisons Disease
• Pheochromocytoma
• Conns Syndrome

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What is Cushings Syndrome?

• A multisystem disorder resulting from chronic
  exposure to high levels of glucocorticoids

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What is Cushings Disease?

• Cushing syndrome secondary to pituitary ACTH
  overproduction

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What are the clinical features of Cushings
syndrome?

1. Moon facies
2. Truncal obesity, supraclavicular fat
3. Buffalo hump
4. Abdominal striae, bruising
5. Fungal infections
6. Susceptibility to TB

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Other findings

• Hirsuitism, frontal baldness
• Depression, lethargy
• Proximal myopathy-inability to climb stairs,
  arise from sitting
• Menstrual irregularities
• Backache, vertebral fractures
• Psychiatric disorders

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What is the cause of abdominal striae and
bruising?

• Altered collagen synthesis? weakened elastin
  fibers,capillary fragility, thin skin
• Stretching by obese abdomen? bruising, ecchymosis

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What are the metabolic disturbances?

• Hypertension,
• Diabetes mellitus
• Sodium retention
• Hypokalemia
• High cholesterol

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How is biochemical evaluation of a patient with
Cushings syndrome done?

• Establish cortisol excess
• 24 hour urinary free cortisol
• LDDST
• HDDST

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What is the principle of Dexamethasone
suppression tests?

• Requires intact HPA
• Low dose dexamethasone will not suppress ACTH or
  adenoma
• Confirms hypercortisolism if positive
• High dose will suppress pituitary-originated ACTH
  but not ectopic ACTH

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How is the LDDST done?

• Overnight-1 mg dexamethasone at 11 PM
• Measure serum cortisol at 8 AM
• Levels should be lt 2-3 mg/dl
• Levels less than 1.8 mg/dl exclude Cushings
• 3-DAY-ACTH, Cortisol at 9 AM 0.5 mg dexa 6-hrly
  for 8 dosesACTH, Cortisol at 9 AM

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What is the HDDST?

• 8mg at midnight/2mg 6hrly for 2 days? sample at 8
  am
• Corticotrophs of pituitary origin get
  suppressed, not ectopic ACTH
• VE test- suppression of cortisol by gt50
• High false positives

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Interpretation

• Complete suppression of cortisol to lt 50 nmol/L
  by LDDST-no hypercortisolism
• Non-suppression- indicates hypercortisolism
• HDDSTIf suppresses cortisol, pituitary source
  responsible if not, adrenal adenoma/ectopic ACTH

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CRH test

• Discriminates between causes of ACTH-dependent
  Cushings
• Pituitary adenomas have CRH receptors
• Ectopic ACTH tumors dont
• After CRH stimulation ACTH levels rise by
  gt35-50, cortisol by 15 in Cushings disease
• High sensitivity and specificity

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Inferior Petrosal Sinus Sampling

• Catheters placed in B/L inferior petrosal sinuses
• Simultaneous peripheral and catheter sampling
• ACTH ratiogt21, or gt31 after CRH is diagnostic
• 100 sensitive and specific for Cushings disease

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Name four agents that inhibit steroid genesis

• Ketoconazole
• Etomidate
• Metyrapone
• Aminoglutethimide

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Pre operative evaluation in Cushings syndrome

1. Airway
2. Difficulty in vascular access including central
   venous access
3. Hypertension
4. Presence of fractures (especially vertebral)-xray
   spine
5. Fungal infection in neck, groins
6. Presence of proximal myopathy
7. Hyperglycemia, hypokalemia

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Preoperative preparation

• Optimize blood sugar levels
• Control hypertension
• Treat fungal infection
• Normalize intravascular volume electrolyte
  status (spironolactone)
• Prepare for a difficult airway
• Plan analgesic technique-pros and cons of EA
• Plan for elective ventilation

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Premedication

• Routine antihypertensives
• Proton pump/H2 inhibitor
• Metoclopramide

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What monitoring would be appropriate for a 52
year old, 82 kg patient with Cushings syndrome
scheduled for laparotomy and bilateral
adrenalectomy?
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• ECG, SpO2, Capnography
• Central Venous Pressure
• Invasive Arterial Pressure
• Neuromuscular Junction Monitoring
• Urine Output
• Temperature

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What are the surgical approaches to the adrenal
gland?

• Open approach-supine, lateral, prone
• Laparoscopic- transperitoneal, retroperitoneal

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How is peri operative steroid replacement planned
for bilateral adrenalectomy?
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• 25 mg hydrocortisone IV followed by 100mg over 24
  hours
• Hydrocortisone 100mg IV before, during and after
  surgery

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What are the common sources of ectopic ACTH?

• Bronchial carcinoid
• Small-cell carcinoma
• Medullary Ca thyroid
• Pancreatic carcinoid

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Features of Ectopic ACTH Syndrome

• Hyperpigmentation
• Profound weakness
• Severe hypokalemia
• Little or no weight gain
• Absence of Cushingoid features

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What are the pharmacological agents used to treat
hypercortisolism?

• Metyrapone
• Ketoconazole
• Etomidate
• Mitotane

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How much is the normal cortisol production?

• 20-30 mg/day.
• What is the recommended dosage for surgery in a
  patient on steroid therapy?
• Minor- 25 mg hydrocortisone Moderate- 25 mg IV
  intraoperatively and 100 mg IV infusion/24 hrs
  Major-200-300mg/70 kg in divided doses

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How much IV hydrocortisone should be ordered for
a patient who is taking oral prednisolone 10 mg
twice a day?

• Hydrocortisone 20 mg is equivalent to 5 mg
  prednisolone for glucocorticoid activity. Hence
  the patient will require 20 mg hydrocortisone IV
  every 6 hours.

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Quiz

• This patient reports to the emergency department
  with history of fever (1030) and vomiting for 2
  days. On examination, he is drowsy, has a
  tachycardia of 120/min and BP of 84/52 mm Hg.
  Rapid infusion of 1.5 liters saline does not
  improve his condition.
• What could be the diagnosis?

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Adrenal or Addisonian crisis

• Vomiting
• Abdominal pain
• Hypovolemic shock refractory to fluids pressors
  
• Hyperthermia / hypothermia

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Which are the drugs that can cause adrenal
crisis?

• Ketoconazole
• Rifampicin
• Phenytoin

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What are the laboratory findings in adrenal
crisis?

• Hyponatremia
• Hyperkalemia
• Metabolic acidosis
• Hypoglycemia
• Anemia, eosinophilia

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What is the treatment of adrenal crisis?

• Hydrocortisone 100 mg 6 hourly
• Aggressive fluid replacement with 5 or 10
  dextrose and saline
• Treatment of hyperkalemia
• Look for underlying cause.
• Inotropic support if needed.

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What is Nelson Syndrome?

• Large ACTH producing locally invasive pituitary
  tumor which develops after bilateral
  adrenalectomy, associated with hyper
  pigmentation.
• Due to absence of negative feedback to pituitary
  does not occur if pituitary is irradiated after
  adrenalectomy.
• Incidence approximately 20-25

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Pheochromocytoma
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What are the types of presentation?

• Headache,sweating,palpitations
• Difficult hypertension
• Hypertension, dysrhythmias during unrelated
  surgery, parturition
• Adrenal mass on incidental abdominal screening
• Screening for suspicion in MEN-II/other familial
  disorders

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What are the syndromes associated with
pheochromocytoma?

• MEN-IIA (Sipple syndrome)
• MEN-IIB(MCT, Pheo, mucosal neuromas)
• Von-Hippel-Lindau disease
• Neurofibromatosis

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What are the implications of these syndromes?

• Genetic origin
• May be familial
• Require screening (eg MCT)
• Incidence of malignancy

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Association of malignancy

• Syndrome Malignancy
• Von Hippel-Lindau 5
• MEN II 3
• Von Recklinghausen 11
• Familial Paraganglioma, pheo 50

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Frequency of common signs and symptoms
Sign/symptom Frequency
Headache 60-90
Palpitations,sustained HT 50-70
Sweating 50-75
Pallor 40-45
Hyperglycemia 40
Paroxysmal HT 30
Nausea, anxiety, panic, wt loss 20-45
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What is the rule of 10 for pheos?

• 10 Extra adrenal
• 10in children
• 10 Familial
• 10 recurrent
• 10 malignant
• 10 bilateral
• 10incidental

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Factors precipitating crisis

• Opiates
• Dopamine antagonists
• Cold medications
• Childbirth
• Radiographic contrast
• Exercise, incidental surgery

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What are the types of a-adrenergic receptors?

• a-1 vasoconstriction,intestinal
  relaxation,uterine contraction, pupillary
  dilatation
• a -2?presynaptic NE (clonidine),
  vasoconstriction, ?insulin secretion

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What is phenoxybenzamine?

• A non-selective a-blocker
• Covalent, non-competitive binding
• Duration of action?24-48 hours
• Block of presynaptic a-2 receptor? NE release,
  tachyphylaxis
• Orthostatic hypotension
• Tachycardia
• Fluid retention, nasal stuffiness, pedal edema
• Non-compliance and difficulty in titration

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Specific a1 blockers

• Act selectively at post-junctional a1 receptors
• I dose may produce profound hypotension(1st dose
  syndrome)
• Prazosin, Terazosin short acting(4h)
• Doxazosin longer acting (12-36 hours)
• Main advantageslack of tachycardia, dosage
  flexibility

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What are the criteria for adequacy of pre
operative control?

• BPlt160/90
• Orthostatic hypotension
• Resolution of ST-T changes on ECG
• VPCslt 5/ minute

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How is the preoperative preparation done?

• Start a blocker
• Ensure fluid(2-3l) and salt intake
• BP and pulse charting
• Postural hypotension
• Nasal stuffiness
• Start ß-blocker

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What are the preoperative investigations?

• ECHO-myocardial performance, RWMA
• Blood glucose
• Fundus examination
• Renal and Hepatic function

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What are the indications of pre-operative
ß-blockade?

• Tachycardia after a-blockade
• Supraventricular tachydysrhythmias
• Multiple VPCs
• Predominant EPI or dopamine pheos/association
  with carcinoid

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Which common pre-medicant drug can precipitate a
crisis?

• Metoclopramide

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How is the diagnosis of pheo established?

• Catecholamine excess
• Radiological localization
• Why not localization first?

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Biochemical diagnosis-which test is best?
Parameter Sensitivity Specificity
Plasma free metanephrines 99 89
Plasma catecholamines 84 81
Urine catecholamines 86 88
Urine total metanephrines 77 93
Urine free metanephrines 97 69
Urine VMA 64 95
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What are metanephrines and why are they more
sensitive?

• Derived from catecholamine metabolism
• Produced by intra cellular COMT
• Continuously produced regardless of paroxysm
  (silent pheo) and released into bloodstream
• Do not get affected by collection technique or
  storage

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Sensitivities of Tests

• Urinary normetanephrine 96.9
• Platelet norepinephrine 93.8
• 131I-MIBG 83.7
• 131I-MIBG Platelet NE 100
• 131I-MIBG Plasma NE 97.1
• 131I-MIBG Urine normetanephrine 96.6
• 131I-MIBG Urine NE 95.3

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Normalized product of urinary metanephrine and
normetanephrine has a sensitivity of 100 and
specificity of 99.1
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Clonidine Suppression

• Differentiates sympathetic stimulation from
  pheochromocytoma
• Failure to reduce levels by gt50 of consistent
  elevation predictive of pheochromocytoma(97)
  negative predictive value 75
• If plasma metanephrine used predictive values
  100 and 96 respectively
• (Lenders et al. Lancet 2005366665-675)

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Tumor Localization

• CT scan with contrast- protect from crisis
• Iohexol-reported to have no effect
• MRI with Gadolinium enhancement for extra
  adrenal/ pregnancy/children/allergy
• Similar sensitivities for CT and MRI

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Meta iodo benzyl guanidine (MIBG) scan

• Specificity 95-100
• 123I preferable-131I second choice
• MIBG specifically indicated for
• Extra adrenal tumors
• Tumors gt 5 cm
• High risk of malignancy
• High possibility of multifocal disease
• Labetalol, TCAs, Ca channel blockers? false
  negatives

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Other Imaging Techniques

• 111 In- octreotide scanning
• Intra operative ?-detector probe
• PET scan with 18F-fluorodopamine, 18F-
  fluorodeoxyglucose
• 18F-fluorodopamine can localise more foci than
  131 I-MIBG in metastatic pheochromocytoma

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What will you prepare in the OT?

• Vasodilator(SNP, NTG) infusions
• Invasive pressure monitoring setup
• Warming of IV fluids
• Large bore IV access
• Rapid infusors for vascular involvement
• Norepinephrine infusion
• Esmolol
• Induction agents, muscle relaxants,
  narcotics

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Role of MgSO4

• Action
• Inhibits catecholamine release from adrenal
  medulla
• Reduces catecholamine sensitivity of peripheral
  adrenergic receptors
• Dosage
• 40mg/kg at induction,1-2 g/hr as infusion
• Uses
• Preinduction hypertension despite a,ß blockade
• Extra adrenal pheochromocytoma
• Acute preoperative preparation
• Concomitant coronary artery disease

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What is the monitoring used for pheochromocytoma?

• ECG, SpO2,ETCO2
• Invasive arterial pressure
• Central venous pressure
• Temperature
• Urine output
• Pulmonary artery catheter?

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What are the common causes of peri operative
hypertensive episodes?

• Intubation
• Incision
• Insertion of N/G tube/urinary cath
• Insufflation
• Instrumentation(manipulation)

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How is intra operative hypertension managed?

• Increase anesthetic depth
• NTG infusion 2-8µ/kg/min
• SNP 0.01 solution titrated to effect
• Diltiazem 0.1 mg/kg IV
• Labetalol 5-10 mg boluses IV
• Esmolol 0.5 mg/kg to counter tachycardia after
  SNP
• Nicardipine, fenoldopam

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What are the causes of post-resection hypotension?

• Catecholamine withdrawal
• Residual a-blockade
• Residual vasodilators(SNP, NTG)
• Downregulation of a receptors
• ?Suppression of contralateral adrenal
• Steroid withdrawal

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How is it managed?

• Discontinue vasodilators and inhalational agents
• Raise CVP to 13-15 cm H2O
• Dopamine, dobutamine usually ineffective
• Norepinephrine best physiological pressor
• 4-8µg/min
• Phenylephrine, vasopressin for refractory
  hypotension
• Vasopressin-bolus 10-20units, infusion 0.05-0.1
  unit/min

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What are other post operative issues?

• Fall in HCT as vasodilation and intravascular
  volume increase occur? may need transfusion
• Prolonged pressor support
• HYPOGLYCEMIA
• Aggressive fluid therapy to treat hypotension?CHF
  in patients with cardiomyopathy
• Persistent post operative hypertension-residual
  tumor

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What is Conns syndrome?

• Excess secretion of aldosterone from
  adrenals-Hyperaldosteronism

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What are the biochemical effects?

• Distal tubular sodium exchanged for potassium and
  hydrogen ions
• Sodium and water retention
• Hydrogen ion excretion
• Hypertension
• Hypokalemia
• Metabolic alkalosis

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What are the clinical implications?

• Diastolic hypertension
• Headache
• Muscle weakness, cramps, fatigue
• Cardiac arrhythmias
• Hyporeflexia
• Increased duration of action of non depolarising
  relaxants

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Pre operative preparation

• Control of hypertension
• Correction of hypokalemia
• Oral potassium
• Spironolactone

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Intra operative concerns

• Cardiac arrhythmias- ECG monitoring
• Lignocaine, defibrillator
• Neuromuscular function monitoring
• Monitoring of acid-base balance
• Serial potassium estimations

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