This document discusses various adrenal gland disorders including androgenital syndromes, congenital adrenal hyperplasia, Addison's disease, adrenal adenomas, and adrenocortical carcinoma. Congenital adrenal hyperplasia is described as the most common cause of androgenital syndromes and is usually due to a 21-hydroxylase deficiency which results in masculinization of females. Addison's disease represents chronic adrenal insufficiency and presents with weakness, fatigue, and hyperpigmentation. Adrenocortical carcinomas are aggressive tumors that commonly metastasize to regional lymph nodes and lungs.

1. Androgenital syndrome
Addison’s disease
Adrenal adenoma
Cortical carcinoma
Dr. Reetu Baral MD (Pathology) (KU)
Department of Pathology
Nobel Medical College

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

6. CAH Clinical Features
• 21-hydroxylase deficiency: Excessive androgenic
activity:
• Females:
– Masculinization in females
– Clitoral hypertrophy
– Pseudohormaphroditism
– Oligomenorrhea
– Hirsutism
– Acne
• Males:
– Precocious puberty
– Enlargement of external genitalia
– Oligospermia

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.

10. Chronic Adrenocortical Insufficiency: Addison disease
• Chronic (Progressive destruction of adrenal cortex)
– Autoimmune adrenalitis (60 – 70%)
– Infections
• Tuberculosis
• Acquired immunodeficiency syndrome
• Fungal infections
– Hemochromatosis
– Sarcoidosis
– Systemic amyloidosis
– Metastatic disease

11. Clinical features – Addison's disease
• Progressive weakness
• Easy fatigability
• Gastrointestinal disturbances :
– Anorexia
– Nausea
– Vomiting
– Weight loss
– Diarrhea
• Hyperpigmentation: Increased levels of ACTH
precursor hormone stimulates melanocytes: face,
axillae, nipples, areolae, and perineum

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.

14. Next Class
• Multiple Endocrine Neoplasia (MEN)
• Neuroblastoma
• Pheochromocytoma