Ad. cortical functional disorder lec 2

1. Adrenal Cortical Disorders
Lecture-27

2. Learning outcomes
Describe the clinico-pathological affects of adrenal cortical hyperfunction
Describe the clinico-pathological affects of adrenal cortical hypofunction

3. Adrenocortical Hyperfunction/ Hyperadrenalism
Cushing syndrome; ACTH-independent
Conn syndrome; Hyperaldosteronism
Adrenogenital syndrome; Excessive androgens

4. Cushing Syndrome
Disorder caused by high levels of glucocorticoids either of exogenous or endogenous origin

5. Adrenals in Cushing Syndrome
Exogenous: bilateral cortical atrophy due to
suppression of endogenous ACTH
Endogenous: adrenal cortical hyperplasia, which
may be;
Diffuse Type; (in 70%of cases)
Cortex diffusely thickened and yellow due to increase in the size and
number of lipid-rich cells in zonae fasciculata and reticularis
Nodular Type; Bilateral glands may weigh from 30- 50 gm and shows 0.5
to 2.0cm, yellow nodules scattered throughout hyperplastic cortex

6. Hyperaldosteronism
Primary or Secondary hyperaldosteronism:
Primary Hyperaldosteronism: autonomous
overproduction of aldosterone, with resultant
suppression of renin-angiotensin system and
decreased plasma renin activity, causes includes;
Aldosterone-producing unilateral adrenal
adenoma (Conn syndrome) (80%) in less than
1%, surgically curable form of hypertension
Primary adrenocortical nodular hyperplasia
(15%) in children/young adults, best managed
with medicine

7. Hyperaldosteronism
Secondary hyperaldosteronism
Aldosterone release as a consequence of any high renin state as in:
Renal ischemia due to decreased renal perfusion; e.g arteriolar
nephrosclerosis, renal artery stenosis
Arterial hypovolemia and edema; e.g congestive heart failure,
cirrhosis, nephrotic syndrome
Pregnancy; caused by estrogen-induced increases in plasma renin
substrate

8. Adrenocortical Insufficiency
Primary adrenocortical insufficiency
- Acute insufficiency (Adrenal crisis)
- Chronic insufficiency (Addison disease)
Secondary adrenocortical insufficiency
- Due to decreased stimulation of the adrenals resulting from a deficiency
of ACTH release from the pituitary gland

9. Primary Adrenocortical Insufficiency
Acute Adrenocortical Insufficiency, occurs in;
- Massive adrenal hemorrhage
- Sudden with drawls of long term corticosteroid therapy
- Stress in patient with underlying chronic adrenal insufficiency
Chronic Adrenocortical Insufficiency, causes Includes:
- Autoimmune adrenalitis
- Tuberculous adrenalitis
- Infarction
- Acquired immune deficiency syndrome (AIDS)
- Metastatic cancers

10. Primary Acute Adrenocortical Insufficiency
Massive adrenal hemorrhage:
It destroys adrenal cortex, can be seen in;
- Patients maintained on anticoagulants
- Postoperative patients who develop DIC
- Pregnancy
Waterhouse-Friderichsen syndrome
Classically associated with Neisseria
meningitidis septicemia, can be caused by
pseudomonas , pneumococci and haemophilus
influenza infection, probably due to endotoxin-
induced vascular injury with associated DIC

11. Primary Acute Adrenocortical Insufficiency
Sudden with drawal of long term corticosteroid therapy or failure
to increase its dosage in response to an acute stress;
May precipitate adrenal crisis, because of inability of the atrophic adrenals
to produce glucocorticoids
Stress in patient with chronic adrenal Insufficiency;
Such as infections, trauma, or surgical procedures may precipitate an acute
adrenal crisis, manifested by intractable vomiting, abdominal pain,
hypotension, coma, and vascular collapse
Death follows rapidly unless corticosteroids are replaced immediately

12. Primary Chronic Adrenocortical Insufficiency
Autoimmune Adrenalitis
(Addison disease) 60-70%
Autoimmune destruction of steroid producing
cells, caused by mutations in autoimmune
Regulator gene(AIRE)
Autoimmune Polyendocrinopathy
Syndrome (APS)
Coexist, Hashimoto thyroiditis, pernicious
anemia, type I DM, and idiopathic
hypoparathyroidism
Shrunken adrenals cortex
Shows scattered residual
cortical cells in a collapsed
network of connective tissue
infiltrated by lymphocytes

13. Secondary Adrenocortical Insufficiency
Secondary to disorder of hypothalamus or pituitary;
Metastatic cancer, infection, infarction or radiations that, reduces the output
of ACTH, this leads to hypoadrenalism without hyperpigmentation because
melanotropic hormone levels are low
Gross; adrenals reduced to a thin rim of uniform atrophic flat, yellow cortex
which surrounds an intact medulla
Microscopy; atrophy of cortical cells with loss of cytoplasmic lipid, in the
zonae fasciculata and reticularis

14. Pathogenesis of Hypoadrenalism
Clinical manifestation occurs when at least 90% of the adrenal cortex is
destroyed
Primary hypoadrenalism; due to primary adrenal disease;
- increased levels of ACTH precursor hormone stimulate melanocytes,
results in hyperpigmentation of skin and mucosal surfaces (not in
secondary adrenocortical insufficiency)
- decreased aldosterone activity, results in potassium retention and
sodium loss, with resultant hyperkalemia, hyponatremia, volume
depletion, and hypotension
Secondary hypoadrenalism; deficient cortisol and androgen output but
normal or near-normal aldosterone synthesis, occasionally hypoglycemia
as a result of glucocorticoid deficiency and impaired gluconeogenesis

15. References
Robbins Basic Pathology 10th edition by Kumar Abbas Aster
www.webpathology.com