1. ADRENAL GLAND
ADRENOCORTICAL
HORMONE

3. INTRODUCTION
• The body has two adrenal ( supra renal)
glands, each located on the superior pole of
each kidney. Each adrenal gland is structurally
and functionally differentiated into two
regions or zones:
1. Adrenal cortex:
This is the outer or peripheral zone of the
adrenal gland, which makes up the bulk of
gland.
2. Adrenal medulla:
This is the inner zone of the adrenal gland.

4. ADRENAL CORTEX
• The adrenal cortex is divided into three zones.
Each zone has a different cellular arrangement
and secretes different groups of steroid
hormones.
• The layers/zones of the adrenal cortex.
Formula for remembering layers. (GFR)
1. Zona-Glomerulosa:
This is the outer most zone of the adrenal
cortex which secretes mineralocorticoids.

5. ADRENAL CORTEX
2. Zona-Fasciculata:
This is the middle zone of the adrenal cortex
which secretes glucocorticoids and adrenal
androgens.
3. Zona-Reticularis:
This is the inner most zone of the adrenal cortex
which secretes glucocorticoids and adrenal
androgen, but in a small quantities.

6. HORMONES OF THE ADRENAL CORTEX
• The adrenocortical hormones and their
functions in the body are classified into:
1. Mineralocorticoids
2. Glucocorticoids
3. Adrenal androgens

8. 1. MINERALOCORTICOIDS
• These hormones help to control the water and
electrolyte homeostasis, particularly the
concentration of Na+ and K+ ions.
Mineralocorticoids include the following
hormones:
a) Aldosterone ( principal hormone).
b) Deoxy corticsterone.
c) Corticosterone.
d) 9-alpha-Fluorocortisol.
e) Cortisol.
f) Cortisone.

9. 2. GLUCOCORTICOIDS
• The glucocorticoids are group of hormones
concerned with normal organic metabolism
and resistance to stress. Glucocorticoids
include the following hormones:
a) Cortisol.
b) Corticosterone.
c) Cortisone.
d) Prednisone.
e) Mythyl prednisone.

10. 3. ADRENAL ANDROGENS
• These are steroids which exhibit actions similar to
testosterone.
Biosynthesis of adrenocortical hormones:
Acetate
|
Cholesterol
|
Pregnenolone 17-OH-pregnenolone
| /
Progesterone Cortisol Androgen
|
Aldosterone

12. 1.ALDOSTERONE
• INTRODUCTION:
This is a hormone of the adrenal cortex,
secreted by the outermost layer called the zone
glomerulosa.
Daily secretion = 150 ug/day.
Normal plasma level : 6 ng/100 ml.

13. MCQ
• The secretion of aldosterone is caused by?
• a) angiotensin II
• b) ACTH
• c) epinephrine
• d) insulin

14. MCQ
• Aldosterone secretion is regulated by the
following except?
• a) ACTH
• b) calcium
• c) blood volume
• d) potassium

15. • HALF-LIFE:
The half-life of aldosterone is short, about 20
minutes.
• TRANSPORT:
Most of the secreted aldosterone is bound to
albumin, with a lesser amount bound to
corticosteroid binding globulin (CBG). The
transport is as follows:
I. 60% bound with plasmaproteins (mostly
albumin).
II. 40% transported in free form.

16. • METABOLISM:
Most aldosterone is converted in the liver to a
tetra hydroglucronide derivative, but some is
changed in the liver and kidneys to an 18
glucronide. The glucronide which is unlike the
breakdown products of other steroids. It is
converted to free aldosterone by hydrolysis at a
pH of 1.0 and is therefore referred to as the “
acid-labile conjugate”.

17. • METABOLISM:
Less than 1% of the secreted aldosterone
appears in the urine in free form. 5% is in
the form of “acid labile conjugate” and
upto 40% is in the form of the
tetrahydroglucronide.

20. • REGULATION OF ALDOSTERONE SECRETION:
A. Factors increasing aldosterone secretion:
a) Increased K+ ions.
b) Decreased Na+ ions.
c) Undefined pituitary factors.
d) ACTH.
e) Hypovolemia.
f) Hypotension.
g) Increased renin angiotensin.
h) Stress.
i) Adrenal adenoma (Conn’s Syndrome)
j) Idiopathic adrenal hyperplasia.

22. Factors stimulating aldosterone release from
the adrenal cortex:
Angiotensin II is the most
important trophic factor for the zona glomerulosa
and one of the two most important stimulators of
aldosterone release. Even a 0.5 mM increase in
plasma [K] stimulates aldosterone release. In turn,
aldosterone regulates plasma [K] by promoting K
secretion in the collecting ducts. Angiotensin III
has 100% aldosterone releasing activity but only
40% of the pressor activity of aldosterone. ACTH
as well as a decrease in plasma [Na] stimulate
aldosterone release but the stimulatory effects of
acute administration of pharmacologic doses of
ACTH on aldosterone release are transient if at all.

23. ALDOSTERONE ESCAPE
• When excess aldosterone is administered, it
causes excess Na+ and water absorption
increasing ECF volume, in turn increasing
blood volume. Increased blood volume causes
increased cardiac output and blood pressure.
Pressure diuresis and pressure natriuresis
cause a secondary loss of Na+ and water. This
process is called aldosterone escape.

24. EFFECTS OF ALDOSTERONE
• A. Effects on renal tubules:
The main action of aldosterone is to maintain
balance of the electrolyte contents of the body
fluid. The sites of action are the ascending limb,
loop of Henle, and distal and collecting tubules.
i) Aldosterone causes increased tubular
reabsorption of Na+ in exchange for K+ and H+
ions. The lack of aldosterone causes an excess
loss of Na+ in urine.

25. ii) Aldosterone increases K+ secretion into
the distal and collecting tubules of the
kidneys. This may be due to ionic exchange
with Na+ reabsorption. Excess aldosterone
causes hypokalemia and muscle paralysis.
iii) Aldosterone causes water absorption
due to the concentration gradient created
by Na+ absorption, increasing EFC volume.

26. B. General effects on:
i. Circulation: increases blood volume and
cardiac output.
ii. Blood pressure: increases blood
pressure due to increased cardiac
output, blood volume and venous
return.

27. iii. Sweat glands and salivary glands:
aldosterone causes increases Na+ and Cl-
reabsorption. And at the same time, it
increases K+ secretion.
iv. GIT: causes increased Na+ and Cl-
absorption from the intestine,
simultaneously increasing water
reabsorption from GIT.

28. CORTISOL
• INTRODUCTION:
Cortisol is also known as hydrocortisone. This
hormone is most abundunt and essential for life.
It is responsible for about 90% of glucocorticoid
activity.
• Site of formation:
Cortisol is secreted by the zona fasiculata and
zona reticularis layers of the adrenal cortex of
the adrenal gland

29. • Bio-synthesis:
This hormone is a 21 carbon atom steroid which
is synthesized from acetyl-CoA cholesterol.
Daily secretion rate = 15 mg/day
Half-life = 90 – 100 minutes
Normal plasma level = 94% bound with cortisol
binding protein, 6% in
free form.

30. • Regulation of cortisol:
The secretion of glucocorticoids is
regulated by hormone of anterior pituitary
gland called adrenocortcotropic hormone
(ACTH).
The control of glucocorticoid secretion is
under a typical negative feedback
mechanism. The two principle stimuli are
stress and low blood level of
glucocorticoids.

31. • Regulation of cortisol:
Both conditions stimulate the
hypothalamus to secrete a regulating
hormone called corticotropin releasing
hormone(CRH). This secretion initiates the
release of ACTH from the anterior pituitary
gland. ACTH is carried through blood to the
adrenal cortex where it stimulates glucocorticoid
secretion.

33. • Effects of cortisol:
A. Metabolic effects:
1. Carbohydrate metabolism:
a) Cortisol stimulates gluconeogenesis in
the liver by mobilizing amino acids from
extra hepatic tissues (muscles) and by
increasing the enzymes of
gluconeogenesis.

34. b) It decreases the utilization of glucose by
cells by decreasing oxidation of NADH2,
which is needed for glycolysis, and by
decreasing glucose transport into the cells.
c) It increases blood glucose levels due to
increased gluconeogenesis and decreases
glucose utilization. This condition is called
adrenal diabetes.

35. 2. Protein metabolism:
a) The principle effects of cortisol on the
metabolic systems of the body is reduction of
protein stores in all body cells except those of
the liver. This is caused by both decreased
protein synthesis and increases catabolism of
protein in the cells.
b) It inhibits amino acid entry into all cells
except the liver.
c) It increases amino acid concentration in
blood.
d) It increases urea level in blood.

36. 3. Fat metabolism:
a) It mobilizes fatty acids from adipose tissues.
b) It increases free fatty acid concentrations in
blood.
c) It increases utilization of free fatty acids for
energy.
d) It causes ketosis due to increased conversion
of free fatty acids into acetyls-CoA.

37. 4. Electrolyte metabolism:
a) It promotes Na+ and Cl- retention from the
renal tubules.
b) It increases excretion of K+ by kidneys.
5. Water metabolism:
It causes diuresis by suppressing ADH secretion
or by increasing destruction of ADH by the liver
cells.

38. B. General effects:
1.On C.V.S.
a) Cortisol increases blood pressure
because of increased production of
angiotensionogen.
b) Increased sensibility of vascular smooth
muscle to nor-adrenaline and
adrenaline.

39. 2. On blood cells:
a) Increases the platelet count.
b) Decreases blood clotting time.
c) Increases total WBCs.
d) Decreases lymphocytes, eosinophils and
basophils.
e) Increases neutrophils, monocytes and RBC
count.

40. 3. On C.N.S. :
a) Low cortisol levels cause restlessness,
insomnia, and inability to concentrate.
b) Causes excitation of the CNS.
4. On GIT:
a) Increases gastric acidity and may cause a
peptic ulcer.

41. 5. On bone:
a) Excess cortisol may cause a defect in the
synthesis of protein matrix.
b) It decreases the deposition of calcium.
c) It increases the loss of calcium in urine.
d) It decreases absorption of calcium from
the GIT.

42. 6. On infection, inflammation, and trauma:
a) Large doses of cortisol decrease the
formation of antibodies due to its destructive
effect on lymphoid tissues.
b) It decreases tissue response to bacteria.
c) It is anti- inflammatory.
d) It is anti- allergic.
e) It delays wound healing.

43. COMMON THERAPUTIC USES OF
GLUCOCORTICOIDS
• Bronchial asthma.
• Chronic bronchitis.
• Emphysema.
• Sarcoidosis.
• Ulcerative colitis.
• Crohn’s disease.
• SLE, cerebral edema.
• Skin diseases.
• Hodgkin’s disease.

44. SUMMARY OF ADVERSE EFFECTS OF
GLUCOCORTCOIDS
• Hypertension.
• Peptic ulcer, pancreatitis.
• Nocturia, polyurea.
• Insomnia, depression and psychosis.
• Amenorrhea.
• Hyperglycemia.
• Osteoporosis.
• Pathological fractures.
• Cataract.

45. PATHOLOGY OF ADRENAL CORTEX
• ADDISON’S DISEASE:
This disease results from failure of adrenal cortex to
produce adrenocortical hormones.
Causes:
1. Atrophy of the adrenal cortex.
2. Tuberculosis.
3. Surgical removal of adrenal gland.
4. Tumor.
5. Deficiency of enzymes (responsible for the formation
of aldosterone).
6. Hemorrhage and infarction.
7. Meningococal septicaemia.
8. Amyloidosis.
9. Schilder’s disease.

46. Clinical features of Addison's disease:
a) Symptoms:
Weight loss, anorexia, malaise, fever,
depression, impotence, abdominal pain, nausea,
vomiting, diarrhoea, syncope, constipation etc.
b) Signs:
General wasting, loss of weight, loss of body
hair, buccal pigmentation, postural hypotension,
dehydration, vitiligo etc.

47. Investigations:
• Blood cortisol level.
• The short ACTH stimulation test.
• Plasma ACTH level.
• Electrolytes and urea ( classically shows
hyponatremia, hyperkalemia and high
urea levels).
• Blood glucose levels may be low.

48. Investigations:
• Adrenal antibodies are present.
• Chest X-rays may show evidence of
tuberculosis.
• Serum aldosterone level is increased.
• Hypercalcemia.
Treatment:
Long term treatment is replacement with
glucocorticoids and mineralcorticoids.

49. MCQ
• In Addison’s disease, the following is
seen?
• a) hyperkalemia
• b) increase in ECF volume
• c) hyperglycemia
• d) high blood pressure

51. CUSHING’S SYNDROME
• Introduction:
This syndrome is characterized by a clinical state
of increased free circulating glucocortcoid.
• Causes:
 Adrenal cortex tumor that secretes excess
cortisol. (20%)
 Anterior pituitary gland tumor that secretes
excess ACTH.(80%)

52. • Causes:
 Abdominal tumor that secretes excess ectopic
ACTH.(0.5%)
 ACTH administration.
 Adrenal carcinoma.
 Cortisol administration.
 Alcohol induced pseudo Cushing’s syndrome.

53. • Clinical features of Cushing’s syndrome:
A. Symptoms:
 Central obesity.
 Fat accumulates the face, neck and trunk.
 Depression, insomnia, psychosis.
 Amenorrhea, oligomenorrhoea.
 Decreased libido.
 Thin skin, easy bruising.
 Hair growth on face, acne.
 Muscular weakness.
 Back pain.
 Polyurea and polydipsia.

54. B. Signs :
 Acne, thin skin, bruising, hirsutism, striae (purple),
pigmentation.
 Moon face, buffalo hump, central obesity
(pendulous abdomen, tomato head, potato body
and four match stick limbs).
 Kyphosis, rib fractures.
 Poor wound healing.
 Hypertension, glucosuria.
 Proximal muscle wasting, proximal myopathy.
 Edema.

55. • Diagnosis: ( diagnosis of Cushing’s syndrome
is based on the following investigations).
 Clinical features = buffalo hump, moon face,
masculinizing effect.
 Blood glucose level increases.
 Blood cortisol level increases.
 Urinary secretion of the 17 hydroxysteroids
increases.

56. • Diagnosis:
 Over night dexamethasone suppression test
+Ve.
 Low dose dexamethasone test.
 Insulin tolerance test.
 Corticotropic releasing hormone test.
 Adrenal CT- scan.
 Chest x-ray.

57. • Treatment:
 Removal of adrenal tumors.
 Suppression of ACTH secretion.
 Bilateral adrenalectomy.

58. MCQ
• All are seen in Cushing’s syndrome
except?
• a) truncal obesity
• b) hypertension
• c) hypoglycemia
• d) hirsutism

60. THE END