1. Pathology of Adrenal Cortex II

4. Adrenal cortex Hyperadrenalism
12/01/10
Adrenal cortex Hyperadrenalism
Excessive secretion of any one of the three basic types of corticosteroids gives rise to a distinct clinical syndrome:
1. Aldosterone – hyperaldosteronism (Conn’s syndrome)
2. Cortisol – Cushing’s syndrome
3. Androgens – adrenogenital syndromes

5. Aldosterone is primarily involved with fluid and electrolyte balance.
Aldosterone secretion causes sodium reabsorption in the distal renal tubule in exchange for potassium and hydrogen ions.
The net effects are, fluid retention, decrease in plasma potassium and metabolic alkalosis.

6. Primary Hyperaldosteronism
12/01/10
Hyperadrenalisms
Adrenal cortex
Primary Hyperaldosteronism
Primary hyperaldosteronism – excess aldosterone secretion which is independent of the renin-angiotensin system (Conn’s syndrome)
Causes:
Aldosterone secreting adenoma
Bilateral hyperplasia of the cortex
Rarely carcinoma
Clinical features:
Hypertension, hypokalemia, sodium retention, muscle weakness, paraesthesia, ECG changes, cardiac decompensation
renin-angiotensin system: renin, secreted by the juxtaglomerular apparatus, activates the precursor angiotensinogen. This liberates angiotensin I, then angiotensin II, a vasoconstrictor and stimulant to the secretion of aldosterone. 6

7. Aldosterone, by inducing renal distal tubular reabsorption of sodium, enhances secretion of potassium and hydrogen ions, causing hypernatremia, hypokalemia, and metabolic alkalosis.

8. Frequency:
Prevalence for Conn syndrome; % of the population.
Mortality/Morbidity:
The morbidity and mortality associated with Conn syndrome, are primarily related to;
1- Hypertension, especially if left untreated for many years, can lead to many complications, including heart disease (eg, coronary artery disease, congestive heart failure), stroke, and intracerebral hemorrhage (with very high blood pressure).

9. 2-Hypokalemia, especially if severe, causes cardiac arrhythmias, which can be fatal
Age
Peak incidence occurs in the third to sixth decades of life.
Sex
Primary hyperaldosteronism is twice as common in women as in men.

10. II- 2ry hyperaldosteronism:
There is increased renin-angiotensin with increased aldosterone secretion;
-CHF
-Liver cirrhosis and ascites
-Nephrotic syndrome
-Renal artery stenosis

11. Clinical features Clinical suspicions should be raised when
Hypertension occur with hypokalemia.
Moderate to sever hypertension
Hypokalemia
Muscle weakness
Malaise
Polyuria polydipsia

12. Investigations Blood : Hypokalemia Plasma aldosterone
Urine : Increase urinary potassium
Imaging : U S
C T
M R I
Iodocholesrerol isotope scan
Adrenal vein sampling

14. Treatment
Spironolactone
Adrenalectomy

15. Congenital Adrenal Hyperplasia (CAH)
By:
Dr. Atif Ali Bashir
Pathology Department
Faculty of Medicine
Majmaah University

16. Congenital Adrenal Hyperplasia
CAH refers to a group of disorders characterized by genital abornomalities due to deficiencies of the adrenal gland

17. Causes
Lack of an enzyme needed by the adrenal gland to make the hormones cortisol and aldosterone.
Without these hormones, the body produces more androgen which is a type of male sex hormone.
This causes male characteristics to appear early or inappropriately.

19. Congenital Adrenal Hyperplasia
The first case was described in 1865
Family of inherited disorders of adrenal steroidogenesis
Each disorder results from a deficiency of one of several enzymes necessary for steroid synthesis
Autosomal Recessive (M=F)
21-hydroxylase  is the commonest form

20. Location of Defective Gene
CAH is caused by mutations of the CYP11B1 gene.
The CYP11B1 gene is found on chromosomes 13 and 18

21. Congenital Adrenal Hyperplasia.

22. Congenital Adrenal Hyperplasia

23. CAH due to 21-Hydroxylase Deficiency
90–95% of CAH cases are caused by 21- OHD
Females affected with severe, classic 21- OHD are exposed to excess androgens prenatally and are born with virilized external genitalia

24. Symptoms Male Enlarged penis Failure to regain birth weight
Weight loss
Dehydration
Vomiting
Precocious puberty
Rapid growth during childhood, but shorter than average final height.
Female
Ambiguous genitalia
Failure to regain birth weight
Weight loss
Dehydration
Vomiting
Precocious puberty
Rapid growth during childhood, but shorter than average final height.
Infertility
Irregular or absent menstruation
Masculine characteristics

25. Presentations of 21 HCAH Ambiguous genitalia in girls Dehydration
Shock
Salt-loss presentations with electrolytes imbalance
Hyponatremia
Hyperkalaemia
Hypoglycemia
Hyperpigementations

26. .

27. Symptoms Young woman with excess hair growth
Baby girl with ambiguous genitalia.

28. BOYS WITH CAH Present early with salt wasting
Are unrecognized at birth because their genitalia are normal.
Present early with salt wasting
crisis resulting in dehydration, hypotension, hyponatremia and hyperkalemia
Or present later in childhood with early pubic hair, precocious puberty and accelerated growth

29. Non classical CAH .

30. Diagnosis Serum electrolytes & glucose
Low Na & high K
Fasting hypoglycemia
Elevated serum urea due to associated dehydration
Elevated plasma Renin & ACTH levels
Low Cortisol
High 17 – OHP
High androgens especially testosterone level
Low Aldosterone
Urinary steroid profile
Chromosomes
Pelvic US

31. Treatment
To treat CAH, children are usually referred to a pediatric endocrinologist.
Oral drugs are prescribed to boost the hormone levels
Hydrocortisone and Dexamethasone are common meds to replace cortisol
Fludrocortisone might be prescribed to replace aldosterone.

32. Pedigree Chart CAH is autosomal recessive.
This pedigree chart illustrates a child’s chances of inheriting the condition if both parents are carriers.

33. Adrenal Neoplasms Cortex: Medulla: Adenoma Carcinoma Pheochromocytoma
Usually Non-Functioning
Carcinoma
Usually Functional
Medulla:
Pheochromocytoma
Neuroblastoma

34. Adrenal Cortical Adenoma
F >> M years of age
gross: well-circumscribed encapsulated nodule
solid yellow cut surface. Some have hemorrhage/cystic degeneration.

35. Adrenal Cortical Adenoma

36. Adrenal Adenoma
Adrenal Adenoma

37. Adrenal Cortical Carcinoma
wide age spectrum
often functional associated with hyperadrenalism
large, often >100 grams
gross: foci of hemorrhage, necrosis
micro: foci of necrosis, cytologic atypia, frequent mitoses, “solid” pattern

38. Cortical Carcinoma

39. Adrenal Carcinoma

40. Pheochromocytoma a tumor of adrenal medulla 30-60 yrs.; F > M
rule of 10’s: 10% bilateral, malignant, occur in children, familial, extra-adrenal
Gross: solid, pale to light brown masses
clinical: hypertension, tachycardia, tremor, headache, sweating

41. Pheochromocytoma

42. Pheochromocytoma