adrenal gland pathology

adrenal gland pathology

• hyperaldestronism
  • sodium retention
  • potassium excretion
  • resultant hypertension and hypokalemia
  • causes
    • primary
      • autonomous production of Aldosterone
        • resultant suppression of RAAS
        • decreased plasma renin activity
      • caused by
        • aldesterone producing adrenocortical neoplasm
        • primary adrenocortical hyperplasia
        • either
          • idiopathic
          • overactivity of aldostreone synthase gene CYP11B2
    • secondary
      • decreased renal perfusion
        • arteriolar nephrosclerosis
        • renal artery stenosis
      • arterial hypovolemia and edema
        • CHF
        • cirrhosis
        • nephrotic $
      • pregnancy
        • estrogen-induced increases in plasma renin substrate
  • clinical features
    • hypertension
    • hypokalemia
    • renin level
    • conn syndrome
      • unilateral aldosterone secreting adenoma
      • twice as common in females than men
      • peak onset in mid-adult life
      • >20% are normokalemic
      • important to recognize - surgically correctable hypertension
      • think of conn's in...
        • hypetension + hypokalemia
        • antihypertensive not working
        • HTN before 40years of age (esp. women)
• adrenogenital syndrome
  • causes
    • primary gonadal disorders
    • primary adrenal disorders
      • adrenal gland produces...
        • dehydroepiandrosterone
          androstenrdione
          both of which requires conversion to testesterone
          in peripheral tissues for their androgenic effects
          it is regulated by ACTH
      • also occurs as a component of Cushin's Disease
      • adrenocortical neoplasms
        • if associated with symptoms of andeogen excess,
          more likely to be carcinoma then adenomas
      • congenital adrenal hyperplasia
        • uncommon
          represent a group of autosomal recessive disorders
          enzyme dysfunction in adrenal
          steroid biiosynth, particularly cortisol
          • decreased cortisol production
            compensatory increase in ACTH
            due to absence of feedback inhibit
            resultant adrenal hyperplasia
            most affected enzyme - 21 hydroxylase Deficiency
            bilaterally enlarged adrenal gland
  • clinical features
    • depends on the specific enzyme deficiency
    • onset
      • perinatal
      • later childhood
      • adulthood
    • in 21-hydroxylase deficiency
      • masculinization
        of females
        • clitlral hypertrophy
        • psudo-hermaphroditism
        • oligomenorrhea
        • hirsutism
        • acne
        males
        • enlargement of external genitalia
        • precocious puberty
    • in CAH
      • 11B-hydroxylase deficiency
        • sodium retention
        • hypertension
      • 21-hydroxylase deficiency
        • sodium wasting
        • acute adrenal insufficiency
      • suspected in...
        • neonate with ambiguous genitalia
        • vomiting
        • dehydration
        • salt wasting
• cushing's
  • excess of cortisol
  • causes
    • exogenous
      • admin. of exogenous glucocorticoids
        • most cases in clinical practice
    • endogenous
      • primary hypothalamic-pituitary disorder
        associated with hypersecretion of ACTH
        • "cushing's disease"
          more than half of endogenous cases
          women about 5 times as frequently affected
          peak age 20-30
          vast majority
          • pituitary gland comtain ACTH producing microadenoma
          • no mass effect in brain
          remaining
          • ant. pituitary contains areas of corticotroph
            cell hyperplasia without discrete adenoma
            may be primary of arise secondary
            secondary cause
            • from excess stimulation of
              ACTH release by a hypothalamic
              Corticotropin releasing hormone-producing
              tumour.
        primary adrenocortical hyperplasia
        or neoplasia
        • responsible for about 10-20% of endognous cushing's $
        • also called
          • ACTH independent Cushing $
          • Adrenal Cushing $
        • biochemical sine qua non
          • cortisol
          • serum ACTH
        • causes
          • unilateral adrenocortical neoplasm
            • benign (adenoma)
              malignant (carcinoma)
              macronodules
              • more common
              primary pigmentednodular
              adrenocortical disease
              • familial
                associated with overactivity
                in many other organs
                e.g. pituitary, thyroid, gonads
          • bilateral adrenocortical neoplasm (rare)
        secretion of ectopic ACTH by
        nonendocrine neoplasms
        • the reminder of cases of endogenous cushing's $
        • responsible tumours
          • small-cell carcinoma
          • carcinoid tumours
          • medullary carcinoma of thyroid
          • islet cell tumour of pancreas
        • nodular cortical hyperplasia seen in adrenals
  • clinical features
    • subtle in its early stages
      • exception is cushings caused by small-cell carcinoma of lung
    • hypertension
    • weight gain
    • centripetal distribution of adipose tissue
      • teuncal obesity
      • moon facies
      • accumulation of fat in post. neck andback
    • decreased muscle mass and limb weakness
    • hyperglycemia
    • glucosuria
    • polydipsia
    • thin, fragile and easily bruised skin
      • cutanious striae
    • osteoporosis
    • increased risk to variety of infections
    • hirsutism
    • mestrual abnormalities
    • mental disturbances
      • mood swings
      • depression
      • frank psychosis
• adrenal insufficiency
  • causes
    • SECONDARY adrenocortical insufficiency
      • any disorder of hypothalamus and pituitary
        • mets cancer
        • infection
        • infarction
        • irradiation
      • reduction in output of ACTH
      ACUTE - Adrenal crisis
      • causes
        • waterhouse-fredrichsen $
          • sepsis
            most usually due to
            N. Meningitidis
            but also in;
            pseudomonas
            pneumococci
            H. influenzae
            associated with
            low BP, shock, DIC, purpura.
            
        • hemorrhage into adrenal
        • post-op ptn with DIC
        • in ptn with anticoagulant therapy
        • Sudden withdrawal of long-term corticosteroid therapy
        • stress in ptn with Addison's.
        • pregnancy
      CHRONIC - Addison's
      • causes & pathophysio
        • autoimmune adrenalitis
          • 60-70%
            most common cause of primary adrenal insufficiency
            autoimmune destruction of steroid producing cells
            • 
            half of patients, antibody restricted to adrenal
            remaining of patients,
            other autoimmune diseases
            (autoimmune polyendocrinopathy $)
            • hashimoto
            • pernicious anemia
            • type1 DM
            • idiopathic hypothyroidism
            • AIRE 1 gene on ch 21q22
        • infections
          • TB
            • associated with active
              infection in other areas
              • lungs
              • GU tract
          • AIDs
            • CMV
            • MAI
            • Kaposi Sarcoma
          • H. Capsulatum
          • Coccidioides immitis
        • Metastatic Cancer
          • disseminated carcinoma
          • lung and breast most common source
          • others
            • GI carcinoma
            • Malignant melanoma
            • hematopoietic neoplasms
        pathophysio
        • chronic  progressive destruction of adrenal cortex
        • autoimmune
  • clinical features
    • addison's disease
      • very vague
      • lean, tired, tanned, tearful
      • weakness, anorexia, dizzy, flu-like myalgias/arthralgia
      • mood disorder
        • depression
        • psychosis
      • GI
        • abd pain
        • diarrhea
        • constipation
      • pigmented
        • palmer creases
        • mucosa
        • face
  • tests
    • Na
    • K
    • glucose
      • due to cortisol
    • uremia
    • ca
    • eosinophilia
    • anemia
    • diagnosis by...
      • short ACTH stimulation test
• Adrenal medulla pathology
  • pheochromocytoma
    • neoplasms composed to chromaffin cells
      sunthesize and release catecholamines
      gives rise to a surgically correctable form of Hypertension
      rule of 10s - (10% will...)
      • arise in children
      • arise in association with familial $
        • von hippel-lindau
        • sturge weber
        • MEN2A
        • MEN2B
        • type 1 neurofibromatosis
      • extra adrenal
        • organ of zuckerkandl
        • carotid body
      • bilateral
      • malignant
      • calcify
      5 p symptoms
      • pressure
        • hypertension
          • increased risk of MI, HF, renal injury, CVA
            Sudden Cardiac Death may occur due to
            catecholamine-induced myocardial irritability
            and ventricular arrythmia
          abrupt, precipitous elevation in 1/3
          chronic, sustained elevation in 2/3
      • palpitation
        • tachycardia
      • pain
        • headache
        • abdominal / chest pain
        • nausea, vomiting
      • pallor
      • perspiration
      • tremour
      • sense of apprehension
  • neuroblastoma
    • most common extracranial tumour of childhood
    • most commonly during first 5 years of life
    • may occur anywhere in sympathetic nervous system
      • most common in abdomen
        most cases arise in adrenal medulla
         / retroperitoneal symphathetic ganglia
        occasionally in brain
    • most are sporadic - some familial