df

1. Adrenocortical
hormones

2. Adrenal gland's Position: There are two small
triangular adrenal glands, each gland above one kidney so
it's called suprarenal glands.
Structure:
1. Medulla: synthesizes catecholamines
2. Cortex: Secretes 3 types of hormones:
• Mineralocorticoids (mainly aldosterone)
• Glucocorticoids (mainly cortisol=
hydrocortisone)
• Androgens

3. Regulation of secretion:
Hypothalamus
Anterior Pituitary
Adrenal cortex
Glucocorticoids
CRF
ACTH = Corticotropin
-
-
1. Glucocorticoids
Emotional
stress,
infection &
surgery+

4.  Long-term administration of exogenous GCs  -ve
feedback on ACTH & CRF 
Suppression of Adrenal cortices
 Too rapid withdrawal of GCs  acute adrenal
insufficiency  may lead to death!!!
Hence, GCs should be GRADUALLY withdrawn
• Diurnal rhythm: The release of
glucocorticoids is high in the early morning at 8
a.m. and low at midnight. It also increases 2
hours after meals.

5. Types of GCs
Natural
Cortisol
Synthetic
(duration of action)
Short
acting
Cortisone
Intermediate
acting
Prednisolone
Long
acting
Dexamethason
e

6. Pharmacological actions of GCs:
1. Metabolism:
 CHO metabolism: (anabolic) maintains an
adequate glucose supply to the brain during
stress.
  utilization of glucose by peripheral tissues
  gluconeogenesis
  glycogen deposition
  glucagon (anti-insulin)
So, long term administration or hyperfunction
may lead to hyperglycemia

7.  Protein metabolism: GC has catabolic effect
on protein (increase breakdown of protein in
different tissues especially muscles + synthesis
of glucose from amino acids in liver).
Hyperfuction : decrease muscle mass, thin skin,
myopathy, osteoporosis .
Osteoporosis is due to: Increased protein
catabolism in bones, ↓ Osteoblasts [Bone forming
cells] and GCs is an antagonist for Vit. D [↓Ca
absorption = -ve Ca balance]

8.  Fat metabolism: therapeutic dose of GC
causes uneven redistribution of fats  thin
extremities & central obesity (↑ fat deposition in
abdominal area & in face & back of neck &
shoulders  moon-face & buffalo hump)
2. Electrolyte balance: hydrocortisone has a weak
mineralocorticoid-like activity   Na+ & H2O
reabsorption &  K+ & H+ secretion.
In hyperfunction: hypernatremia, edema,
hypokalemia, metabolic alkalosis.

9. 3. CVS :  blood Pressure SO used in aseptic shock
4. CNS: Behavioral disturbances; mostly mood elevation,
euphoria & insomnia [Antistress effect].*
5. GIT:  PGs   HCl &  mucus formation
 predispose to peptic ulcer.(WHY?!)
6. Skeletal muscles: GCs are essential for normal muscle
work.
7. Anti-inflammatory effect .
8. Immunosuppressive effect.

10. Blocked by
GCs
PG
Kidneys Stomach
Renal Blood Flow mucus formation

11. 8. Effect on other hormones
↓ ACTH [-ve feedback] ►Adrenal gland atrophy.
↓ TSH ►↓ thyroid secretion.
↓ Melanocyte Stimulating Hormone [MSH] "The hormone
that control distribution of melanin pigments in skin“
N.B. In Cushing syndrome [Hyperfunction] ►↓Melanin ►
Uneven pigment distribution on the skin.
In Addison syndrome [Hypofunction] ►↑ Melanin ►
Hyperpigmentation.
↑ Glucagon ► Hyperglycemia.

12. Clinical disorders
Hypercorticism:
Cushing`s
syndrome
Hypocorticism:
Addison`s
disease

13. Cushing’s syndrome
 Clinical state of excess free GCs occurs due to:
1.Therapeutic administration of ACTH or
GCs for long periods.
2.Endocrine disorder
 ↑ACTH secretion(Pituitary ACTH dependent ), Known
as cushing disease .
 adrenal tumor(Pituitary ACTH independent )

14. The dexamethasone suppression test
is designed to diagnose and differentiate among the
various types of Cushing's syndrome
Test Principle:
ACTH is more sensitive to exogenous steroids
than endogenous Cortisol
Dexamethasone is given at night & plasma
cortisol is measured next morning.

15. Cortisol ACTH Interpretation
is not
suppressed by
low doses
Undetectable or
low
Adrenal CS (i.e.
the
hypercortisolism is
not driven by
ACTH
hypersecretion)
is not
suppressed by
low doses, but is
suppressed by
high doses
Normal to
elevated but not
in hundreds
Pitutary CS,
pituitary still retains
some feedback
control. A pituitary
MRI would be
needed to confirm.
is not
suppressed by Elevated in
Probably Lung
tumor. (Ectopic

16. Features of Cushing`s syndrome :

17. Red stria

18. ☺ Treatment of Cushing’s syndrome:
  or stop exogenous GC gradually
(risk vs benefit)
 Surgical removal of the tumor
 Using inhibitors of biosynthesis, e.g.:
Aminoglutethimide
 Trilostane
 Metyrapone (S.E. salt & water retention, hirsutism
in females)
 Using GCs receptor antagonists , e.g.:
 Mifepristone
Ketocanazole: antifungal which inhibits all
steroid synthesis.

19. Addison’s disease occurs when the adrenal cortex is
damaged and the adrenal glands do not produce enough of
the steroid hormones cortisol.
Causes of Addison’s disease :
1. Primary Adrenal Insufficiency:
occurs when the adrenal glands are damaged so severely
that they can no longer produce hormones.
autoimmune disease : when immune system attacks the
adrenal glands.
2. Secondary Adrenal Insufficiency :
 occurs when the pituitary gland (located in your brain) can’t
produce adrenocorticotropic hormone (ACTH).

20. Features of Addison`s disease :


22. Treatment of addison’s disease
Medications :
• a combination of glucocorticoids medications
• Hormone replacements may be prescribed to replace
hormones that your adrenal glands are not making.
Alternative Therapies :
• It’s important to keep your stress level down.
 If Addison’s disease goes untreated for too long, it can become an
Addisonian crisis. An Addisonian crisis is a life threatening medical
emergency. It can lead to shock and death.
 mental status changes (confusion, fear, or restlessness)
 loss of consciousness
 high fever
 sudden pain in the lower back, belly, or legs

23. Diagnosis:
 Physical examination
 Laboratory tests:

24. Actions:
- ↑ Na+ & H2O reabsorption and ↑ K+ & H+
secretion.
- Regulation of aldosterone secretion:
 ↓ plasma Na+ , ↑ K+  ↑ aldosterone.
 ↓ Na+ , ↓ BP  ↑ renin  ↑ Ang II  ↑ aldosterone.
 ACTH also stimulates secretion but to a much
smaller extent.
2. Mineralocorticoids

25.  Hypertension
 Hypernatremia
 Hypokalemia
 Alkalosis
Clinical disorders
Hyperfunction:
1ry hyperaldosteronism
(CONN`s disease)
Hypofunction:
Hypoaldosteronism
• Hypotension
• Hyponatremia
• Hyperkalemia
• Acidosis
ttt: Aldosterone antagonist
e.g. Spironolactone
ttt: RT with
fludorocortisone

26. Case 1

27. A twenty four-year-old unmarried female presented with a
seven-month history of puffiness of the face that progressed
to generalized swelling of the body. She had noticed striae
over the lower limbs, abdomen and lower back at the same
time. Besides, she had complaints of amenorrhoea,
progressively increasing weakness of the proximal
muscles(osteoporosis) , frontal headaches, polyuria and poor
performance over the past six months.
On examination, the patient had moon face, truncal obesity,
puffiness of the face and eyes, purple striae over breasts,
abdomen and thighs, and edema. Her blood pressure was
160/100 mmHg. Her blood glucose level was very high .

28. High dose dexamethasone suppression test was done Basal
serum cortisol was 530 nmol/l and failed to suppress after 48
hours, remaining raised at 525 nmol/l .
Abdominal examination revealed a lump in the right upper
abdomen extending to the right flank of size 10 x 8 cms. An
ultrasound of the abdomen showed a large heterogenous
mass 13 x 12 x 7.6 cms anterolateral to the upper pole of
right kidney. scan of the abdomen
revealed a 20cm x 18 cm sized soft tissue mass with
mixed densities in the right suprarenal region.

29. 1.What is the most likely diagnosis in this case ?
and What is the main cause of your diagnosis ?
 Cushing’s syndrome.
 The main cause is adrenal tumor.

30. 2.What are the signs and symptoms that aided your
decision ?
• puffiness of the face (moon face) and eyes.
• generalized swelling of the body.
• striae over the lower limbs, abdomen and lower back.
• Amenorrhoea
• progressively increasing weakness of the proximal
muscles(osteoporosis)
• frontal headaches,
• polyuria.
• truncal obesity.
• edema.
• High blood pressure was and blood glucose.

31. 3. What is the reason that cause this patient to
have osteoporosis & muscle weakness?
 GC has catabolic effect on protein.
 Osteoporosis is due to: Increased protein catabolism
in bones, ↓ Osteoblasts [Bone forming cells] and GCs
is an antagonist for Vit. D [↓Ca absorption = -ve Ca
balance]

32. 4. What is the reasons that cause this patient to
have hyperglycemia ?
 GC has anabolic effect so, it maintains an adequate
glucose supply to the brain during stress.
 utilization of glucose by peripheral tissues
 gluconeogenesis
 glycogen deposition
 glucagon (anti-insulin)
So, long term administration or hyperfunction may lead to
hyperglycemia

33. 5. What diagnostic tests should be performed to
confirm the patient’s diagnosis ?
 Physical examination
 Laboratory tests:
1. Serum cortisol
2. Serum ACTH
3. Na+
4. K+
5. Fasting blood glucose level
Dexamethasone suppression test.

34. 6. Explain the dexamethasone suppression test ?
Dexamethasone is given at night & plasma cortisol
is measured next morning

35. Cortisol ACTH Interpretation
is not
suppressed by
low doses
Undetectable or
low
Adrenal CS (i.e.
the
hypercortisolism is
not driven by
ACTH
hypersecretion)
is not
suppressed by
low doses, but is
suppressed by
high doses
Normal to
elevated but not
in hundreds
Pitutary CS,
pituitary still retains
some feedback
control. A pituitary
MRI would be
needed to confirm.
is not
suppressed by
high or low
Elevated in
hundreds
Probably Lung
tumour. (Ectopic
ACTH

36. 7. What is the treatment for this patient ?
 Surgical removal of the tumor
 Using inhibitors of biosynthesis, e.g.:
 Aminoglutethimide
 Trilostane
 Metyrapone (S.E. salt & water retention, hirsutism in
females)
 Using GCs receptor antagonists , e.g.: Mifepristone
 Ketocanazole: antifungal which inhibits all steroid
synthesis.

37. Case 2

38. A 37-year-old male soldier was presented with fatigue,
nausea, vomiting, weight loss, malaise and dizziness. On
examination, marked skin and buccal hyperpigmentation,
hyponatremia was diagnosed. There was no relevant family
history. He had a low cortisol level and his response to the
adrenocorticotrophic hormone in a Synacthen test was poor.
X-ray of his abdomen showed no calcified areas in either
adrenal gland, and his serum contained antibodies to
adrenal cortex,consistent with a diagnosis of autoimmune
adrenalitis.

39. Laboratory investigations showed a hemoglobin of 14.2 g/dl,
a total leukocyte count of 5.7 × 103/µL, differential and
platelet counts were normal. The patient was hyponatremic
with a serum sodium of 128 meq/L (130-142 meq/L)
and potassium of 5.9 meq/L (3.5-5.5 meq/L) on the higher
side. Renal function tests were essentially normal.
Fasting blood sugar of 106 mg/dL (80-110 mg/dL) and
postprandial sugars of 136 mg/dL (110-140 mg/dL) were
in the normal range.

40. 1.What is the most likely diagnosis in this case ?
and justify your answer?
 Addison’s syndrome
 The main cause is the presence of
autoimmune adrenalitis

41. 2.What are the signs and symptoms that aided
your decision ?
• Fatigue and dizziness
• Nausea &vomiting,
• weight loss.
• marked skin and buccal hyperpigmentation
• orthostatic hypotension
• hyponatremia.
• low cortisol level and his response to the
adrenocorticotrophic hormone in a Synacthen test was
poor.
• serum contained antibodies to adrenal cortex,consistent
with a diagnosis of autoimmune adrenalitis.

42. 3.What is the reason for patient’s-associated
hyponatremia?
• due to aldosterone deficiency
• The disease is autoimmune so it affects all the
corticosteroids ( glucocorticosteroids,
mineralocorticosteroids and androgens )

43. 4. What is the reason that cause this patient to
have buccal hyperpigmentation ?
 ACTH is derived from a bigger precursor
molecule(POMC).
 POMC is also a precursor for melanocyte stimulating
hormone (MSH).
 so, In Addison syndrome [Hypofunction] Cortisol .
ACTH ↑ , Melanin ► Hyperpigmentation.

44. 4. What are the complications that could be
present if this disease goes untreated ?
 Addisonian crisis
 Hypoglycemia
 hypotension

45. 5. What is the treatment for this patient ?
 Medications :
 a combination of glucocorticoids medications and
mineralocorticoids replacements.

46. The End