Adrenal Insufficiency

Sub-section: Adrenal Section: Endocrine

Types of Adrenal Insufficiency

• Primary Adrenal Insufficiency
  • Addison’s Disease
  • Caused by the Adrenal gland
• Secondary
  • Caused by the interference with ϲοrtiϲοtropin (ΑCTН) secretion by the pituitary gland
• Tertiary
  • Caused by interference with ϲοrtiϲοtrοpin-releasing hormone (СRΗ) secretion by the hypothalamus

Primary Adrenal Insufficiency

• Addison’s Disease
  • Rare
• Symptoms
  • Weakness and fatigue, anorexia, nausea or vomiting, weight loss, hyperpigmentation, hypotension, and electrolyte disturbances (hyponatremia and hyperkalemia)
  • Hyperpigmentation caused by ACTH-induced melanogenesis
• Three general causes
  • Congenital adrenal dysgenesis/hypoplasia
  • Defective steroidogenesis
  • Adrenal destruction
    • Autoimmune (most common cause)
    • Infectious (TB, Fungal, Viral)
    • Adrenal replacement by metastatic tumor
    • Adrenal hemorrhage (Waterhouse-Friderichsen syndrome)
      • Occurs in the setting of septicemia caused by meningococcal or other organisms and is more common in pediatric and asplenic patients

Secondary Adrenal Insufficiency

• Relatively common
• Cause
  • Any process that involves the pituitary and interferes with ϲοrtiϲоtrοpin (ΑCТH) secretion can cause secondary adrenal insufficiency. The ΑСΤH deficiency may be isolated or occur in conjunction with other pituitary hormone deficiencies (раոhурοрituitarism)
  • Isolated ACTH deficiency
  • Panhypopituitarism
  • Autoimmune
  • Drugs
  • Neoplastic or infiltrative replacement of pituitary glands
  • Granulomatous disease
  • Pituitary haemorrhage
  • Pituitary infarction may occur in the setting of severe PPH (Sheehan Syndrome)

Tertiary Adrenal Insufficiency

Tertiary adrenal insufficiency refers to hypothalamic abnormalities that reduce ϲοrtiϲоtrοрiո-releasing hormone (СRН) secretion.

• The most common causes of tertiary adrenal insufficiency suppress ϲοrtiϲοtroрin (ΑCТH) secretion:
  • Abrupt cessation of high-dose glucocorticoid therapy
  • Correction (cure) of hуреrϲоrtiѕοliѕm (Cushing syndrome)
• Other interfere hypothalamus CRН secretion
  • Tumors
  • Infiltrative diseases
    • Sarcoidosis
  • Cranial radiation

Diagnosis

• Clinical suspicion
  • Confirm with lab work
• Early am cortisol
  • If high or normal, insufficiency unlikely
  • If low do ACTH stimulation test
• Early ACTH stimulating test
  • If cortisol high, insufficiency unlikely
  • If cortisol low/normal, likely
    • The physiologic basis of the test is that adrenocortical destruction (in primary adrenal insufficiency) or adrenocortical atrophy (due to loss of the trophic action of endogenous ACTH) will lead to a subnormal cortisol response to a pharmacologic dose of synthetic ACTH.
• Distinguishing between primary and central
  • Early morning cortisol and ACTH
    • Cortisol - should be low
    • ACTH
      • High - primary
      • Low - central

Treatment

• Acute crisis
  • Large volume resus and steroids
• Chronic insufficiency
  • Goal to replace physiologic glucocorticoid and mineralocorticoid levels
  • E.g. Prednisone 5mg/day, Fludrocortisone 0.1mg/day
• Increase glucocorticoid doses in times of stress
  • Infections
  • Trauma
  • Burns
  • Surgery

Peri-op Management of Adrenal Insufficiency

• Pts with Addison’s
  • Increased risk of adrenal crisis
  • Generally require peri-op hydrocort
• Pts on long-term steroids (secondary insufficiency)
  • Risk of adrenal crisis low (1-2%)
  • Generally just continue on regular dose of steroids
  • If large stress consider short course increased dose
• Patients undergoing unilateral adrenalectomy
  • Only need supplemental steroids if procedure is done for Cushing syndrome

Adrenal Insufficiency in Critically Ill

• Acute reversible dysfunction of the HPA axis
  • Seen in ~ 30% of critically ill patients
  • May be higher in septic shock
• Mechanism
  • ? Adrenal ACTH resistance
  • ? Decreased responsiveness of target tissues to glucocorticoids
  • Steroid supplementation
• Studies show inverse relationship between survival benefit and glucocorticoid dose
  • Physiologic (replacement) doses yielding a relative survival benefit of 1.2
  • High supraphysiologic doses demonstrating significant harm
  • Data controversial
• Pts with septic shock, esp. those requiring vasopressors, may benefit from 5-7 day courses of glucocorticoids in the dosage range of 300 mg/day or less of hydrocortisone or equivalent

Adrenal Crisis

• Life threatening condition
  • Usually occurs in those with marginal adrenal function who then get significant stress
• Clinical findings
  • Shock
  • Abdominal pain
  • Fever
  • Nausea
  • Vomiting
  • Electrolyte disturbance
  • Hypoglycaemia
  • Mineralocorticoid deficiency is the main mechanism
    • Inability to maintain sodium and intravascular volume
  • Also get decreased cardiac responsiveness to catecholamines
    • Result of low glucocorticoids
• Treatment
  • Large volume resus with isotonic saline, and glucocorticoid administration
  • Hydrocort 100mg IV Q6H, or Dex 4mg IV Q24H (longer acting)
  • Mineralocorticoid not early priority
    • Don’t see effect of Fludrocortisone for days