Adrenal gland pathology

1. Adrenal gland pathology

2. Adrenal glands Paired endocrine organs Consists of - cortex and medulla Differ in their development, structure, and function.

6. Adrenal glands Histology – Adrenal cortex Layers: Zonaglomerulosa (narrow) Zonafasciculata (about 75% of the total cortex) Zonareticularis (narrow)

9. Adrenal cortex Synthesizes three different types of steroids: (1) Glucocorticoids (principally cortisol): Synthesized primarily in the zonafasciculata and to a lesser degree in the zonareticularis; (2) Mineralocorticoids (aldosterone): Synthesized in the zonaglomerulosa (3) Sex steroids (estrogens and androgens): Produced largely in the zonareticularis.

10. Adrenal medulla Composed of chromaffin cells Synthesize and secrete catecholamines, mainly epinephrine. Catecholamines have many effects that allow rapid adaptations to changes in the environment.

11. Adrenal diseases Diseases of the adrenal cortex can be conveniently divided into: Those associated with hyperfunction Those associated with hypofunction.

12. Adrenal diseases Diseases of the adrenal cortex can be conveniently divided into: Those associated with hyperfunction Those associated with hypofunction.

13. Adrenal hyperplasia • Hyperfunctioning – hyperplasia • Hormones are produced in excess • Cortisol- Cushing’s syndrome • Aldosterone- Aldosteronism/Conn’s disease • Androgens- Virilizingsyndrome/Adrenogenital syndrome

14. Adrenal hyperplasia • Hyperfunctioning – hyperplasia • Hormones are produced in excess • Cortisol- Cushing’s syndrome • Aldosterone- Aldosteronism • Androgens- Virilizing syndrome

15. Cushing syndrome Exogenous causes – Iatrogenic Endogenous causes

16. Cushing syndrome Endogenous causes ACTH-DEPENDENT Cushing disease (pituitary adenoma; rarely CRH-dependent pituitary hyperplasia) Ectopic corticotropin syndrome (ACTH-secreting pulmonary small-cell carcinoma, bronchial carcinoid)

17. Cushing syndrome Endogenous causes ACTH-INDEPENDENT Adrenal adenoma, Adrenal carcinoma Macronodular hyperplasia Primary pigmented nodular adrenal disease McCune-Albright syndrome

19. Morphology Adrenal glands Depending on the cause of the hypercortisolism the adrenals have one of the following abnormalities: (1) cortical atrophy- in exogenous causes (2) diffuse hyperplasia- In ACTH dependant causes (3) macronodular or micronodular hyperplasia (4) an adenoma or carcinoma.

22. Clinical features

23. Adrenal hyperplasia • Hyperfunctioning – hyperplasia • Hormones are produced in excess • Cortisol- Cushing’s syndrome • Aldosterone- Aldosteronism • Androgens- Virilizing syndrome

24. Hyperaldosteronism Generic term for a group of closely related conditions characterized by chronic excess aldosterone secretion. May be primary or secondary to an extra-adrenal cause.

25. Hyperaldosteronism Primary hyperaldosteronism stems from an autonomous overproduction of aldosterone Associated with resultant suppression of the renin-angiotensin system and decreased plasma renin activity. Blood pressure elevation is the most common manifestation of primary hyperaldosteronism, which is caused by one of three mechanisms

26. Causes Adrenocortical adenoma Bilateral adrenal hyperplasia Adrenal carcinoma

28. Secondary hyperaldosteronism Aldosterone release occurs in response to activation of the renin-angiotensin system Characterized by increased levels of plasma renin and is encountered in : Decreased renal perfusion (arteriolar nephrosclerosis, renal artery stenosis) Arterial hypovolemia and edema (congestive heart failure, cirrhosis, nephrotic syndrome) Pregnancy (due to estrogen-induced increases in plasma reninsubstrate)

29. Adrenal hyperplasia • Hyperfunctioning – hyperplasia • Hormones are produced in excess • Cortisol- Cushing’s syndrome • Aldosterone- Aldosteronism • Androgens- Virilizing syndrome

30. Adrenal diseases Diseases of the adrenal cortex can be conveniently divided into: Those associated with hyperfunction Those associated with hypofunction.

31. Adrenal virilism Adrenocorticalhyperfunction In children- Congenital adrenal hyperplasia due to congenital deficiency of a specific enzyme In adults- adrenocortical adenoma

32. Clinical features In children- distortion of external genitalia in girls and precoceous puberty in boys In adults- females will have virilization males will have feminization

33. Atrophy Atrophy- adrenal insufficiency- Primary/Secondary Primary- Acute (adrenal crisis) Secondary- Chronic (Addison’s disease) Hypoaldosteronism Hormones produced are less in quantity or nil Many causes

36. Primary Adrenal crisis: Causes- Bilateral adrenectomy Septicemia (Waterhouse-Friderichsen Syndrome) Rapid withdrawal of steroids Acute stress

37. Primary Clinical features Deficiency of mineralocorticoids- salt deficiency, hyperkalemia, dehydration Deficiency of glucocorticoids-hypoglycemia, increased insulin sensitivity, vomitings

38. Addison’s disease Addison disease, or chronic adrenocortical insufficiency, is an uncommon disorder resulting from progressive destruction of the adrenal cortex. In general, clinical manifestations of adrenocortical insufficiency do not appear until at least 90% of the adrenal cortex has been compromised. Although all races and both sexes may be affected, certain causes of Addison disease (such as autoimmune adrenalitis) are much more common in whites and in women.

39. Addison’s disease A large number of diseases may affect the adrenal cortex, including lymphomas, amyloidosis, TB, sarcoidosis, hemochromatosis, fungal infections, and adrenal hemorrhage More than 90% of all cases are attributable to one of four disorders: autoimmune adrenalitis, tuberculosis, AIDS, or metastatic cancers.

40. Addison’s disease Depend on the underlying disease. Primary autoimmune adrenalitis- characterized by irregularly shrunken glands (difficult to identify within the suprarenal adipose tissue) Histologically the cortex contains only scattered residual cortical cells in a collapsed network of connective tissue. A variable lymphoid infiltrate is present in the cortex and may extend into the adjacent medulla, although the medulla is otherwise preserved

41. Addison’s disease In cases of tuberculous and fungal disease the adrenal architecture is effaced by a granulomatous inflammatory reaction identical to that encountered in other sites of infection. When hypoadrenalism is caused by metastatic carcinoma, the adrenals are enlarged, and their normal architecture is obscured by the infiltrating neoplasm.

42. Clinical features Asthenia Hyperpigmentation Hypotension Loss of hair Hypoglycemia

43. Secondary Due to deficiency of ACTH Selective ACTH deficiency Panhypopituitarism

44. Clinical features Same except no hyperpigmentation

45. Hypoaldosternoism Isolated deficiency Due to congenital defect Prolonged administration of heparin excision of aldosterone secreting tumour Presents with renal failure and diabetes

46. Adrenal tumours

47. Adrenal adenoma Adrenocortical adenoma >2cm in size Benign slow growing Produces excess hormones Can be a part of MEN syndrome

48. Morphology Aldosterone-producing adenomas are almost always solitary, small (<2 cm in diameter), well-circumscribed lesions, more often found on the left than on the right. They tend to occur in the 30s and 40s, and in women more often than in men. Bright yellow on cut section

50. Morphology Composed of lipid-laden cortical cells that more closely resemble fasciculata cells than glomerulosa cells (the normal source of aldosterone). Cells tend to be uniform in size and shape and resemble mature cortical cells; occasionally, there is modest nuclear and cellular pleomorphism