2. Andrenogenital Syndromes
• Adrenogenital syndromes - caused by:
– Androgen excess:
• Primary gonadal disorders
• Primary adrenal disorders.
• The adrenal cortex secretes two compounds—
– Dehydroepiandrosterone
– Androstenedione—which require conversion to
testosterone in peripheral tissues for their
androgenic effects.
3. Adrenogenital Syndrome
• ACTH regulates adrenal androgen formation -
excessive secretion can present:
– An isolated syndrome
– Combined with Cushing disease.
• Congenital Adrenal Hyperplasia (CAH):
– Autosomal recessive disorder – hereditary defect in an
enzyme needed in adrenal synthesis particularly
cortisol.
– Decreased cortisol – Increased ACTH secretion – due
to absence of negative feedback – Adrenal hyperplasia
– increased production of cortisol precursor steroids –
synthesis of androgen – virilizing activities.
4. Congenital Adrenal Hyperplasia (CAH)
• Most common enzyme defect - 21-hydroxylase
deficiency – 90% of cases
• Range from total lack to mild loss – depending on the
mutation
• In adrenal glands cortisol, aldosterone and sex
steroids are synthesized from cholesterol through
various intermediates – 21 – hydroxylase is required
for synthesis of cortisol and aldosterone but not sex
steroids – thus its deficiency reduces cortisol and
aldosterone synthesis – hence shunts the common
precursors into sex steroid precursors.
5. CAH - Morphology
• Adrenal gland: Hyperplastic (10 – 15 times
the normal)
• Adrenal cortex – thickened and nodular
• Cut section: Brown color
7. Adrenal Insufficiency (Addison disease)
• Adrenocortical insufficiency, or hypofunction, may
be caused by:
– Primary adrenal disease (primary hypoadrenalism)
– Secondary hypoadrenalism: Decreased stimulation of the
adrenals resulting from ACTH deficiency
• Primary adrenocortical insufficiency may be:
– Acute (Adrenal crisis)
– Chronic (Addison disease)
8. Causes of Adrenal Insufficiency
• Acute
– Waterhouse-Friderichsen syndrome:
• N.meningitidis sepsis
– Sudden withdrawal of long-term corticosteroid
– Massive adrenal haemorrhage:
• Anti-coagulant therapy
• DIC
• Pregnancy
– Stress in patients with underlying chronic adrenal
insufficiency
9. Adrenal crisis
• Stresses such as infections, trauma, or surgical
procedures in affected patients may precipitate an
acute adrenal crisis:
– Profound asthenia (weakness)
– Severe pain in the abdomen, lower back, or legs
– Peripheral vascular collapse
– Renal shutdown with azotemia
In adrenal crisis, a delay in instituting corticosteroid
therapy, particularly if there is hypoglycemia and
hypotension, may be fatal.
12. Adrenocortical adenomas
• Mostly incidental findings during Autopsy or
radiological imaging
• Cut section: yellow to yellow brown - presence
of lipid within the neoplastic cells
• 1 to 2 cm in diameter
13. Adrenocortical neoplasms
Adrenocortical carcinoma
• Li-Fraumeni syndrome
• Beckwith-Wiedemann
syndrome
• Invades the adrenal vein, vena cava, and lymphatics
• Metastases to regional/periaortic nodes are common
• Hematogenous spread to the lungs and other viscera
• Bone metastases are unusual
• The median patient survival is about 2 years.
• Carcinomas metastatic to the adrenal cortex are significantly
more frequent than a primary adrenocortical carcinoma.
