This presentation discusses adrenocortical hypofunction, specifically focusing on primary and secondary adrenal insufficiency. It begins by outlining the learning objectives and providing definitions. It then describes the causes, signs and symptoms, diagnosis, and treatment of primary adrenal insufficiency, including Addison's disease and crisis. Secondary adrenal insufficiency is explained as resulting from hypothalamic-pituitary dysfunction. Treatment involves replacing glucocorticoids and mineralocorticoids through medications like hydrocortisone and fludrocortisone.

1. College of Health Sciences
Department of medical Physiology
Presentation on Adrenocortical
Hypofunction
robel abay
1

2. Topic out line
 Objectives
 Introduction
 Adrenal insufficiency
 Primary Adrenal insufficiency
 Secondary Adrenal insufficiency
 Addison's Crisis
 Treatment modalities
 Isolated Hypoadrenalism
Adrenal Insufficiency 2

3. learning Objectives
At the end of these presentation learners expected
to:-
 Know the pathophysiology of adrenal insufficiency.
 Identify the cause of adrenal insufficiency.
 List the clinical manifestation of adrenal
insufficiency
 Explain Addison's crisis
 Know pathophysiology of isolated hypoadrenalism
 Know the treatment modalities
Adrenal Insufficiency 3

4. Endocrine Abnormalities
 Endocrine abnormality expressed by hypersecretion or
hyposecretion of hormone.
 Primary disorder-result from the gland it self.
 Secondary disorder-the problem result from other
organ or target tissue.
Adrenal Insufficiency 4

5. Cause Of Endocrine Abnormalities
 Metabolic factors.
 Physical damage
 Congenital problems.
 Genetic abnormalities.
Adrenal Insufficiency 5

6. Adrenal Insufficiency
Definition
Adrenal insufficiency is a condition in which the
adrenal gland is not able to function well enough to
produce the amount of all corticosteroid hormones
which the body needs.
Adrenal Insufficiency 6

7. Cont’d
According the site of problem
 primary adrenal insufficiency.
 Secondary adrenal insufficiency.
- Primary Adrenal insufficiency- The gland it self is
damaged.
- Secondary adrenal insufficiency-The gland
healthy but lacks hormonal stimulation
Adrenal Insufficiency 7

8. Primary Adrenal insufficiency
Addison's disease
- it occurs when 90% of the adrenal gland is destroyed.
- is a relatively uncommon disorder that occurs in people
of all ages and both sexes.
- characterized by decreased mineralocorticoid,
glucocorticoid, and androgen secretion.
Adrenal Insufficiency 8

9. cont’d
 Cause
1. idiopathic Autoimmune Adrenalitis
 The most common type.
 Atrophy of adrenal cortex due to autoimmune
diseases, the adrenal medulla is intact.
 Accounts 70% of the Addison’ s disease.
 15% of patients with Addison's disease have an
associated autoimmune disease , graves disease being
the most common
Adrenal Insufficiency 9

10. Cont’d
 Idiopathic autoimmune Addison disease may occur in isolation
or in association with other autoimmune phenomena such as:
- Schmidt syndrome: The association of Addison disease and
Hashimoto thyroiditis.
- polyglandular autoimmune syndrome type 1:
The association of Addison disease with hypoparathyroidism and
mucocutaneouscandidiasis.
o It may have an autosomal recessive mode of inheritance. It has
no human leukocyte antigen (HLA) associations.
Adrenal Insufficiency 10

11. Cont’d
- polyglandular autoimmune syndrome type2:
The association of Addison disease with type 1
diabetes mellitus and Hashimoto thyroiditis or
Graves disease.
Adrenal Insufficiency 11

12. Primary adrenal insufficiency cont’d
2.Infections
 Tuberculosis-most common
 AIDS
 Fungal infections( histoplasmosis, Cryptococcus)
 CMV infection
Adrenal Insufficiency 12

13. Cont’d
 Hematogenous spread of the M.tuberculosis from
else where in the body to the adrenal gland cause-
initial enlarged with extensive epitheloid
granulomas then followed by degeneration of the
adrenal gland.
 Both cortex and adrenal medulla is affected.
 Fibrosis follows the adrenal become smaller with
calcification of 50% evident.
Adrenal Insufficiency 13

14. Cont’d
Adrenal Insufficiency 14

15. Cont’d
3. Miscellaneous-Rare causes Addison's disease
• Bilateral cancer metastasis
 Amyloidosis, hemosiderosis (rare)
 ketoconazole use, macrophage-released
cytokines are risk factors
 Intra adrenal bleeding
 Bilateral adrenoloctomy
Adrenal Insufficiency 15

16. Cont’d
Intra adrenal bleeding- cause necrosis of the
adrenal may occur in severely sick patient, with
underlying infection, trauma, or coagulopathy.
- cause of severe septicemia, particularly in children
in whom a common cause is infection with
Neisseria Meningitidis.
when caused by meningococci,the association with
adrenal insufficiency is know as the Waterhouse
Friederichsen syndrome.
Adrenal Insufficiency 16

17. WATERHOUSE-FRIDERICHSEN SYNDROME
• Acute, bilateral hemorrhagic infarction of the adrenals.
• Occurs secondary to shock and DIC, in a septicemic
infection. Endotoxic hemorrhaging.
 Tiny fibrin thrombi occlude the vessels going to the adrenal
glands ------> infarction.
 Neisseria Meningitidis is the most common agent causing
the infection.
 Also Pneumococci, Staph, Strep, Haemophilus,
Diphtheria. Herpes Virus can cause it.
 Complete and sudden collapse of cortical function
 SYMPTOMS: like symptoms of shock ,infection and DIC
(petechia, thrombocytopenia, increased PT and PTT).
Adrenal Insufficiency 17

18. Cont’d
Adrenal Insufficiency 18

19. Cont’d
4. congenital and genetic abnormalities
A. congenital Adrenal Hypoplasia (CAH)
 It is an X-linked disorder comprising congenital
adrenal insufficiency and hypogonadotrophic
hypogonadism.
 caused by mutations in the NROB1 gene.
 DAX-1 gene- a member of the nuclear receptor family
that is expressed in the adrenal cortex, gonads, and
hypothalamus.
Adrenal Insufficiency 19

20. Cont’d
 Mutations in another transcription factor
steroidogenic factor-1—may also result in
adrenal insufficiency due to lack of development
of a functional adrenal cortex.
 CAH may also occur in association with glycerol
kinase deficiency and muscular dystrophy.
Adrenal Insufficiency 20

21. Cont’d
B.Adrenoleukodystrophy
An inherited metabolic disorder resulting in
accumulation of very-long-chain fatty acids
(VLCFA) in tissues including the brain and adrenal
cortex, resulting in:
 Progressive demyelination of cerebral white matter
 Adrenal insufficiency
o Only males have the fully expressed condition and
carrier females are usually normal.
Adrenal Insufficiency 21

22. Pathogenesis
 Accumulation of VLCFA
 VLCFA esterified to
cholesterol, making
cholesterol unavailable as a
steroid/hormone precursor
 Adrenocorticalcells with
these inclusions have
decreased mitochondrial and
microsomalenzyme activity
 Over time these cells atrophy,
further deteriorating
adrenocorticalfunction
Adrenal Insufficiency 22

23. Cont’d
C.Familial glucocorticoid deficiency (FGD)
 inherited unresponsiveness to ACTH.
 It is a rare autosomal recessive cause of
hypoadrenalism .
 Usually presents in childhood.
 The renin-angiotensin-aldosterone axis is intact.
 children usually present either with neonatal hypoglycemia
or later with increasing pigmentation, often with enhanced
growth velocity.
 Two types-type 1 variant-25% of the case.
- type 2 variant .
Adrenal Insufficiency 23

24. cont’d
D. Allgrove syndrome: congenital adrenocortical
unresponsiveness to ACTH typically presents in
childhood with failure to thrive, features of
adrenocortical insufficiency and hypoglycemia.
- disease to chromosome 12q13 but the responsible gene
is unknown.
Adrenal Insufficiency
24

25. Secondary Adrenal insufficiency
 Loss of hypothalamic-pituitary function and deficiency
of ACTH.
 Will usually have deficiencies of other gland regulated
by hypothalamic-pituitary system.
 Aldosterone secretion may continue intact.
Adrenal Insufficiency 25

26. Cont’d
 Problems in hypothalamus or pituitary
⇓
 plasma levels of ACTH low.
⇓
 unable to stimulate the zona fasiculate and zona
reticularies of adrenal cortex.
⇓
 cortisol levels low.
 Adrenal cortices do response to exogenous ACTH.
Adrenal Insufficiency 26

27. Cont’d
 Cause
1. Sudden cessation of exogenous glucocorticoid
therapy.
 Abrupt withdrawal of corticosteroids is a very common
cause of secondary acute adrenal insufficiency.
 chronic exogenous glucocorticoid
⇓
 Suppresses diurnal CRH/ACTH release
 both time- and dose-related
 reversible
 recovery may take up to long time
Adrenal Insufficiency 27

28. STEROID THERAPY
STEROID LEVELS
PITUITARY GLAND IS INHIBITED TO REALEASE
ACTH
ENDOGENOUS CORTISOL
PRODUCTION & ADRENAL ATROPHY
RELEASE BY ADRENAL CORTEX
Adrenal Insufficiency 28

29. Cont’d
2. Pan- Hypopituitarism
reflect inadequate ACTH production from the anterior
pituitary gland.
 In many of these, other pituitary hormones are
deficient in addition to ACTH, so that the patient
presents with partial or complete hypopituitarism.
Adrenal Insufficiency 29

30. Cont’d
3.Surgical cause
- Selective removal of ACTH-secreting pituitary
adenoma
-pituitary surgery.
4. Postpartum pituitary infarction (Sheehan's syndrome)
Adrenal Insufficiency 30

31. Signs & Symptoms
1. Hyper Pigmentation of skin & mucous membrane
due to excess ACTH secretion because of cortisol
deficiency.
- ACTH causes pigmentation by its melanocyte
stimulating action. on the sun exposed areas of the skin,
extensor surface,knuckles,elbows and knees.
2.Vitiligo is also common in auto Immune Addison's
disease due to destruction of melanocyte.
31
Adrenal Insufficiency

32. Hyperpigmentation
Adrenal Insufficiency 32

33. Cont’d
2.Electroliyte and acid – base balance
abnormalities.
 Hyponatremia.
 Hyperkalemia and metabolic acidosis
 Hypercalcemia.
Adrenal Insufficiency 33

34. Cont’d
3.Dehydretion with loss of sodium
- As ECF becomes depleted.
- plasma volume fall.
- COP decreased.
4.Muscle weakness.
Adrenal Insufficiency 34

35. Cont’d
 5. Decreased cardiac output & decreased workload of the
heart leading to decrease in size of the heart.
 6. Hypoglycemia.
 7. Inability to withstand any type of stress like physical,
mental, even exposure to mild stress, trauma.
 8.Decreased pubic and axillary hair in women.
 9.Nausea,vomiting and diarrhea.
Adrenal Insufficiency 35

36. Cont’d
Adrenal Insufficiency 36

37. Cont’d
 Primary vs. secondary adrenal hypo function
primary secondary
Site=adrenal site=hypothalamus-pituitary
↑ACTH ↓ACTH
↑pigmentation ↓pigmentation
weight loss weight change vary
No change in GH and ↓GH and gonadotropins
Gonadotropins.
Deficient in all corticosteroids other adrenal hormones normal or
slightly↓
No response to exogenous ACTH sluggish response to
exogenousACTH.
37
Adrenal Insufficiency

38. Diagnosis
1.ACTH stimulation test
A. Blood and/or urine cortisol levels are measured.
B. Administration of synthetic ACTH.
C. Cortisol measurement in blood is repeated 30 to 60
minutes after an IV ACTH injection.
In healthy person rise in blood and urine cortisol levels
In adrenal insufficiency respond poorly or do not
respond at all.
Adrenal Insufficiency 38

39. Cont’d
2.insulin-induced hypoglycemia test
A. Blood measure of glucose and cortisol level.
B. An injection of fast acting insulin.
C. Blood glucose and cortisol levels are measured at
30,45 and 90 minutes after the insulin injection.
 The normal response is -↓blood glucose level
-↑cortisol level.
Adrenal Insufficiency 39

40. Addison’s crisis
 A life treating emergency of exacerbate adrenal
insufficiency of undiagnosed patient during facing
stress full conditions.
 symptoms are intensified. Nausea, vomiting, and
abdominal pain may become intractable.
 In all patients in addisonian’s crisis, a precipitating
cause should be identify.
Adrenal Insufficiency 40

41. Addison's Crisis
Clinical Presentation
 Life-threatening emergency
 May be primary or secondary
 HYPOTENSION
 Typically resistant to catecholamine and IVF
resuscitation
Adrenal Insufficiency 41

42. cont’d
Abrupt adrenal failure usually from gland
hemorrhage or thrombosis
 Anticoagulation
 DIC
 Sepsis
 Usually have abdominal and flank pain
Adrenal Insufficiency 42

43. Cont’d
Catastrophic HPA axis failure
 Head injury
 Hemorrhage of pituitary adenoma
 Post-partum herniation (Sheehan syndrome)
 Usually neurological deficits, headaches, visual field
cuts and diabetes insipidus.
Adrenal Insufficiency 43

44. Treatment Modalities
 Different treatment regimes.
 Emergency treatments
 maintenance therapy.
 Replacement of glucocorticoids and mineralo
corticoids.
Adrenal Insufficiency 44

45. Treatment of Addison's crisis
 hydrocortisone 50-100 mg every 6-8 hours
 intravenous fluids
 dextrose
 search for precipitating cause
Adrenal Insufficiency 45

46. Treatment
 Patients with symptomatic adrenal insufficiency, should be
treated with hydrocortisone or cortisone therapy.
 The usual initial dose is 25 mg of hydrocortisone (divided
into doses of 15 and 10 mg)
 37.5 mg of cortisone (divided into doses of 25 and 12.5 mg)
 The daily dose may be decreased to 20 or 15 mg of
hydrocortisone as long as the patient remains
asymptomatic.
Adrenal Insufficiency 46

47. Treatment chronic AI
 hydrocortisone 12-15 mg in one or divided doses
 titrate to lowest tolerated dose
 consider mineralocorticoid ( fludrocortisone ) if
primary AI. in a single daily dose of 50 to 200 µg, as
a substitute for aldosterone.
Adrenal Insufficiency 47

48. Cont’d
o The dose can be guided by measurements of blood
pressure, serum potassium, and plasma renin
activity, which should be in the upper-normal .
 double or triple the dose of hydrocortisone
temporarily whenever they have any febrile illness
or injury.
Adrenal Insufficiency 48

49. Hypoaldosteronism
Secondary hypoaldosteronism (hyporeninism
hypoaldosteronism)
Inadequate stimulation of the zona gromulesa of the
adrenal cortex despite intact adrenal cortex.
CAUSE
 Hyporeninism, as an inherited biosynthetic defect.
 postoperatively following removal of aldosterone-
secreting adenomas.
 during protracted heparin administration.
 Renal insufficiency .
Adrenal Insufficiency 49

50. pseudohypoaldosteronism
An inherited disease characterized by severe neonatal
salt wasting, hyperkalemia, metabolic acidosis, and
unresponsiveness to mineralocorticoid hormone
action.
The disease can be due to a loss-of-function mutation in
the mineralocorticoid receptor .
Adrenal Insufficiency 50

51. References
1.Williams text book of endocrinology,11th Edition
2.Ganong’s review of medical physiology,23th
Edition.
3. Harrison’s principles of internal medicine.16th
edition.
4. Guyton Text book of medical physiology,11th
edition
5. Internet websites.
Adrenal Insufficiency 51

52. Adrenal Insufficiency 52