Anatomy of the adrenal glands

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• Anatomy of the adrenal glands
• Hypothalamic Pituitary Adrenal Axis
• Renin-angiotensin system
• Steroid hormones
• Congenital adrenal hyperplasia (CAH)
• Adrenal disorders
• Adrenal insufficiency (Addisons disease and
  others)
• Adrenal hyperfunction (Cushings syndrome and
  others)
• Pheochromocytoma (adrenal medulla)

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Thomas Addison (1793-1860)
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The leading characteristic features of the
morbid state to which I direct attention are
anemia, general langour and debility, remarkable
feebleness of the hearts action, irritability of
the stomach and a peculiar change in colour of
the skin, occurring in connection with disease of
the suprarenal capsulesThomas Addison, 1855
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Clinical Presentation of Adrenal Insufficiency

• Generalized and muscular weakness
• Loss of appetite and weight
• Low blood pressure
• Hyponatremia
• Mild anemia and eosinophilia
• Symptomatic response to treatment is dramatic (1
  hour or less)
• Hypoglycemia

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Clinical Presentation of Adrenal Insufficiency

• Only in primary (Addisons disease)
• high ACTH
• Increased pigmentation
• Hyperkalemia (loss of aldosterone)
• More prominent hypotension
• Salt craving

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A Famous Patient with Addisons Disease
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Addisons Gum Hyperpigmentation
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Causes of Secondary or Tertiary Adrenal
Insufficiency(low ACTH)

• Exogenous Glucocorticoid Suppression
• Hypothalamic-pituitary disease
• Pituitary tumors
• Prior radiation therapy
• Head trauma

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Primary Adrenal Causes(ACTH increased)

• Autoimmune (most common in industrialized
  nations)
• Tuberculosis (most common in third-world)
• Adrenal Hemorrhage
• Replacement by metastatic tumor (gt90)

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Incidence of other endocrine and autoimmune
diseases in 365 patients with autoimmune adrenal
insufficiency
From UpToDate.com
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Cortrosyn (ACTH) stimulation test

• Give 1 amp(250 mcg)
• Draw a single cortisol 30 and 60 min post
• Interpretation Normal value gt18-20 mcg/dl
• Can be done at any time without regard to meals

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Hypothalamic-Pituitary-Adrenal Axis
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Causes of Cushings Syndrome(not including
iatrogenic)

• ACTH Dependent
• Pituitary dependent (Cushings Disease) 70
• Ectopic ACTH production by tumors 5
• ACTH Independent
• Adrenal Adenoma
  20
• Adrenal Carcinoma
  2
• Macronodular Hyperplasia
  2
• Surreptitious glucocorticoid use 1

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Ectopic ACTH Syndrome

• Most cases are caused by tumors of the lung,
  pancreas, or thymus
• Most common
• Bronchial Carcinoma 30
• Small Cell Carcinoma of lung 20

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Synthetic Analogues of Cortisol
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Physiological Effects of Glucocorticoids
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Glucocorticoid actions

• Acutely
• Glucose mobilized from liver, muscle, fat
• Chronically
• Elevated insulin
• Muscle atrophy
• Fat redistribution with
• Lipolysis in periphery
• Fat deposition in face, trunk
• (due to elevated insulin?)

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Common Features of Glucocorticoid Excess

• Menstrual Dysfunction
• Easy Bruisability
• Osteoporosis
• Psychological changes
• Glucose Intolerance
• Proximal Muscle Weakness

• Weight Gain
• Central obesity
• Moon Facies
• Facial Plethora
• Hypertension
• Purple Striae

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Cushings syndrome diagnostic strategy

• Confirm hypercortisolism (unless exogenous Rx
  with another steroid)
• Establish cause
• ACTH independent
• Adrenal adenoma or carcinoma
• Exogenous steroids
• ACTH dependent
• Cushings disease
• Ectopic ACTH

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Differential diagnosis of Cushings syndrome

• Dexamethasone suppression test
• ACTH levels
• Sometimes also
• Inferior petrosal sinus sampling
• (CRH testing)

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Plasma ACTH
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Cushings syndrome Treatment

• Exogenous (drug-induced) try to taper
• Primary adrenal (ACTH-independent) remove tumor
  or entire adrenal
• Ectopic ACTH try to find and remove
• Cushings disease (ACTH-producing pituitary
  tumor) try to localize and remove

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Transphenoidal Surgery
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Primary hyperaldosteronism
Autonomous adrenal aldo
Aldosterone
UNa
UK
-
Volume expansion
Renin
BDA
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Primary aldosteronism

• Suspect in hypertensive patients, especially with
  hypokalemia.
• -Up to 50 are normokalemic.
• Simultaneous plasma aldosterone to renin ratio
• Confirmatory test 24 hour urine for aldosterone
  production
• Suppression test of aldosterone IV saline
  infusion
• Imaging (CT or MRI), adrenal vein sampling

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Pathology of adrenal medulla

• Pheochromocytoma
• 10 bilateral
• 10 ectopic (extra-adrenal)
• 10 malignant

BDA
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Clinical features of pheochromocytoma

• Hypertension
• 60 sustained
• 40 paroxysmal
• Headache
• Palpitations
• Chest pain
• Diaphoresis
• Tremulousness

BDA
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Catecholamine metabolismDiagnosis of
Pheochromocytoma
vanilyl mandelic acid (VMA)
metanephrines
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Diagnosis of pheochromocytoma

• Urine metabolites
• Metanephrines
• Catecholamies
• VMA
• Blood
• Plasma Free Metanephrines
• Imaging studies
• ONLY for localization!!

BDA
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Pheo, other points

• Rare lt 0.2 of patients with hypertension
• Up to 15-20 occur as part of genetic disorder
• von Hippel-Lindau (vHL)
• MEN2 A and B (also medullary carcinoma of
  thyroid)
• Treatment surgical extirpation

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Slide credits-Steven Chessler, M.D.,
Ph.D.-George Dailey, M.D.-George Merriam, M.D.
(University of Washington)-Bradley Anawalt, M.D.
(University of Washington)
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Cushings Syndrome