Adrenal Disorders

							Adrenal Disorders
 Arthur S. Schneider, M.D.
 Department of Pathology
Adrenal hyperfunction
Diffuse hyperplasia of adrenal
          (bottom illustration)
         from Robbins-Cotran PBD, 8e
           Cushing syndrome
• hypercorticism regardless of cause
• medical use of exogenous adrenal corticoids –
  most frequent cause
• hyperproduction of ACTH by corticotrophs of
  the pituitary (“Cushing disease”)
• Ectopic ACTH production
• primary adrenal causes
Adrenal hypercorticism secondary
   to pituitary disease (Cushing
              Disease)
   • corticotropic adenoma (basophilic
     adenoma) hypersecretion of
     adrenocorticotropic hormone (ACTH)
     increased production of adrenal
     cortical hormones
   • also may be caused by basophilic
     microadenomas– often multiple
Other causes of Cushing syndrome
• adrenal causes
  • adrenal cortical adenoma
  • adrenal carcinoma (less common than
     adenoma)
• ectopic ACTH production
   – small cell lung carcinoma
   – various other tumors
   – Hypercorticism autonomous--not
     suppressed by exogenous adrenal steroids
     as in dexamethasone suppression tests
 Dexamethasone suppression tests
• test given at low (usually 1–2 mg) and high
  (8 mg) doses of dexamethasone
• levels of cortisol are measured
• low dose dexamethasone suppresses cortisol
  when there is no pathology in endogenous
  cortisol production
• high dose dexamethasone exerts negative retro-
  control on pituitary ACTH producing cells but not
  on ectopic ACTH producing cells or adrenal
  adenoma
        ACTH measurements in
           hypercorticism
• increased in pituitary hypercorticism and in
  ectopic ACTH production
• low when hypercorticism is of adrenal origin
       Morphologic changes
• bilateral hyperplasia of adrenal zona
  fasciculata
   • occurs when syndrome results from ACTH
     stimulation
• adrenal cortical atrophy when exogenous
  glucocorticoid medication is cause
• adrenal cortical adenoma or carcinoma:
  adenoma more common
Cushing syndrome
  from Robbins-Cotran PBD, 8e
       Cushing syndrome – clinical
             characteristics
•   round moon face
•   dorsal “buffalo hump”
•   relatively thin extremities
•   muscle wasting and weakness
•   skin atrophy
•   easy bruising and purplish striae over abdomen
•   hirsutism
•   muscle weakness
•   osteoporosis, amenorrhea, hypertension,
    hyperglycemia, psychiatric dysfunction
    Summary—Pituitary Cushing
           disease
• Increased corticotropin (ACTH)
• corticotropic (basophilic) adenoma or multiple
  corticotropic microadenomas
   Summary -- Cushing syndrome
        (hypercorticism)
• Bilateral hyperplasia of adrenal zona
  fasciculata secondary to hyperactivity of
  pituitary corticotrophs or to ectopic ACTH-like
  production by a variety of tumors; adrenal
  cortical adenoma
• May be of pituitary, adrenal, or ectopic origin;
  can also result from administration of
  exogenous hormone
From Rubin’s Pathology
From Rubin’s Pathology
    Primary aldosteronism (Conn
             syndrome)
•


• primary hyperproduction of adrenal
  mineralocorticoids.
• usual cause: adrenocortical adenoma
  (aldosteronoma)
• also can result from hyperplasia of zona
  glomerulosa
• adrenocortical carcinoma much less common
  than adenoma or hyperplasia.
    Clinical characteristics -- primary
              aldosteronism
•   hypertension
•   sodium and water retention
•   hypokalemia
•   decreased serum renin
     – negative feedback of increased blood
       pressure on renin secretion
Primary aldosteronism
     from Robbins-Cotran PBD, 8e
       Secondary aldosteronism
• secondary to renal ischemia, renal tumors,
  and profound edema of any cause such as
  cirrhosis, nephrotic syndrome, cardiac failure
• caused by stimulation of renin-angiotensin
  system
  – serum renin increased (contrast to primary
    aldosteronism)
   Serum renin in secondary
        aldosteronism
– increased (contrast to primary
  aldosteronism)
– synthesized in juxtaglomerular apparatus
– promotes conversion of angiotensinogen to
  angiotensin I
– angiotensin I converted by angiotensin-
  converting enzyme (mainly in the lung) to
  angiotensin II
– angiotensin II facilitates release of
  aldosterone
   Summary -- hyperaldosteronism
         (aldosteronism)
• primary
  – adenoma or hyperplasia of zona glomerulosa
  – serum renin decreased
• secondary
  – bilateral hyperplasia of zona glomerulosa caused
    by stimulation of renin-angiotensin system
  – serum renin increased; frequently secondary to
    edema, regardless of the cause
   Adrenal virilism (adrenogenital
             syndrome)
• congenital enzyme defects lead to diminished
  cortisol production
• compensatory increased ACTH adrenal
  hyperplasia androgenic steroid production
• 21-hydroxylase deficiency most common. in
  most severe “salt-wasting” form  salt loss
  and hypotension
• 11-hydroxylase deficiency, much less common
  salt retention and hypertension.
         Adrenogenital syndrome
          clinical characteristics
• virilism in females
• precocious puberty in males
21-hydroxylase deficiency
       from Robbins-Cotran PBD, 8e
       Summary--adrenal virilism

• adenoma, carcinoma, or hyperplasia of zona
  reticularis
• Can be due to hyperplasia resulting from
  congenital enzyme deficiencies such as 21-
  hydroxylase and 11-hydroxylase deficiencies
Adrenal hypofunction
      Deficiency of pituitary ACTH
• adrenal failure is secondary
• no hyperpigmentation of the skin
   – lack of b-melanocyte-stimulating hormone
     (β-MSH ) as well as ACTH
   – contrasts with primary adrenal failure
     (Addison disease) in which ACTH and β-
     MSH is increased and hyperpigmentation is
     the rule
        Hypocorticism (adrenal
           hypofunction)
• cause is primary in adrenal or secondary to
  hypothalamic or pituitary dysfunction
• deficiency of glucocorticoids (primarily
  cortisol), often with associated
  mineralocorticoid deficiency
          Addison disease
 (primary adrenocortical deficiency)
• idiopathic adrenal atrophy (autoimmune
  lymphocytic adrenalitis) most common
  cause
• tuberculosis (former most common cause)
• metastatic tumor, and various infections
 Addison disease -- characteristics
• hypotension
• increased pigmentation of skin
• decreased serum sodium, chloride, glucose,
  and bicarbonate
• increased serum potassium
Addison disease secondary to
        tuberculosis
Addison disease secondary to
        tuberculosis
Waterhouse-Friderichsen syndrome
• catastrophic adrenal insufficiency and vascular
  collapse
• due to hemorrhagic necrosis of the adrenal
  cortex.often associated with disseminated
  intravascular coagulation (DIC)
• classically due to meningococcemia, most
  often in association with meningococcal
  meningitis
Waterhouse-Friderichsen syndrome
          from Robbins-Cotran PBD, 8e
Waterhouse-Friderichsen syndrome
Waterhouse-Friderichsen syndrome
          from Robbins-Cotran PBD, 8e
Autoimmune adrenalitis
     from Robbins-Cotran PBD, 8e
Tumors of adrenal medulla
Adrenal cortical adenoma
       from Robbins-Cotran PBD, 8e
Adrenal cortical adenoma
      from Robbins-Cotran PBD, 8e
from Robbins-Cotran PBD, 8e
Adrenal cortical carcinoma (left)
           from Robbins-Cotran PBD, 8e
          Pheochromocytoma
• derived from chromaffin cells of the adrenal
  medulla;
   – when derived from extra-adrenal
     chromaffin cells, called paraganglioma
• most often benign; 10% malignant.
• surgically correctable hypertension
          Pheochromocytoma
• hypertension usually paroxysmal (episodic)
  • may be persistent
  • results from hyperproduction of
    catecholamines (epinephrine and
    norepinephrine)
  • increased urinary excretion of
    catecholamines and their metabolites
    (metanephrine, normetanephrine,
    vanillylmandelic acid)
          Pheochromocytoma
• tumor can also cause hyperglycemia
• can be part of MEN IIa or MEN IIb (III)
      Pheochromocytoma other
            associations
•  von Hipple-Lindau disease
  • renal, hepatic and pancreatic cysts
  • renal cell carcinomas
  • cerebellar hemangioblastomas
• von Recklinghausen disease
  • neurofibromatosis
  • schwannomas, gliomas
• Sturge-Weber
  • cavernous hemangiomas
Pheochromocytoma
   from Robbins-Cotran PBD, 8e
Pheochromocytoma
   from Robbins-Cotran PBD, 8e
Pheochromocytoma
   from Robbins-Cotran PBD, 8e
Neurosecretory granules in a
   pheochromocytoma
            Neuroblastoma
• highly malignant catecholamine-producing
  tumor
• occurs in early childhood
• urinary catecholamines and catecholamine
  metabolites are same as in
  pheochromocytoma
• tumor causes hypertension
• usually originates in adrenal medulla
• often presents as large abdominal mass
             Neuroblastoma
• amplification of N-myc oncogene
   – thousands of gene copies per cell
   – characteristic karyotypic changes
     (homogeneously staining regions or double
     minute chromosomes)
   – number of N-myc gene copies related to
     aggressiveness of the tumor.
• occasionally converts into more differentiated
  form – ganglioneuroma
   – change reflected by marked reduction in
     number of gene copies
   Summary – adrenal medullary
            tumors
• pheochromocytoma
   – chromaffin cell tumor; benign or malignant
   – tumor secretes catecholamines
     (epinephrine and norepinephrine) and
     causes secondary hypertension
• neuroblastoma
   – malignant “small blue cell” tumor of
     adrenal medulla
   – catecholamine-secreting malignancy of
     early childhood; hypertension