Adrenal insufficiency causes, presentation, and management

1. Adrenal insufficiency

2. Mineralocorticoids
Glucocorticoids
Adrenal Androgens
Catecholamines

3. • Glucocorticoids and adrenal androgens are under control of pituitary
hypothalamic axis while mineralocorticoids are not. Thus in 2ry ,3ry AI
the mineralocorticoids is not affected less hyponatremia or
hyperkalemia.

4. Types of Adrenal Insufficiency
 Adrenal insufficiency can be:

6. Presentation
• The symptoms and signs of adrenal insufficiency depend upon:
• the rate and extent of loss of adrenal function
• whether mineralocorticoid production is preserved
• the degree of stress.

7. • The onset of adrenal insufficiency is often very gradual, and it may go
undetected until an illness or other stress precipitates adrenal crisis.
• The clinical presentation of adrenal insufficiency is variable,
depending on whether the onset is acute, leading to adrenal crisis, or
chronic, with symptoms that are more insidious and vague.
• Adrenal crisis should be considered in any patient who presents with
peripheral vascular collapse (vasodilatory shock), whether or not the
patient is known to have adrenal insufficiency.
• Likewise, isolated corticotropin (ACTH) deficiency, although rare,
should be considered in any patient who has unexplained severe
hypoglycemia or hyponatremia

8. ADRENAL CRISIS
• The predominant manifestation of adrenal crisis is shock, but the patients often
have nonspecific symptoms, such as anorexia, nausea, vomiting, abdominal pain,
weakness, fatigue, lethargy, fever, confusion, or coma.
• Situations :
• In chronic primary adrenal insufficiency, when patients experience serious infection or other
acute, major stress. Adrenal crisis may be the initial presentation in a previously undiagnosed
patient.
• It may also occur in patients with known primary or secondary adrenal insufficiency who are
under-replaced, either because of: 1) insufficient daily doses of glucocorticoid and/or
mineralocorticoid; 2) failure to take more glucocorticoid during an infection or other major
illness; or 3) persistent vomiting or diarrhea caused by viral gastroenteritis or other
gastrointestinal disorders, leading to decreased absorption.
• An acute cause of adrenal gland destruction, such as bilateral infarction or hemorrhage.
• Development of an acute cause of secondary or tertiary adrenal insufficiency, such as pituitary
infarction
• Unmasking of secondary adrenal insufficiency in patients who are abruptly withdrawn from
supraphysiologic doses of glucocorticoid. Importantly, this includes not only oral but inhaled
medications

11. Management of adrenal crisis

13. Follow up
• Adequacy of glucocorticoid dose is judged by
1. clinical wellbeing and restoration of normal, but not excessive, weight; ideally
aiming for a low dose, for example, total dose of hydrocortisone between 15
and 25 mg split in two or three divided doses throughout the day
2. measuring cortisol levels during the day while on replacement hydrocortisone
(cortisol levels cannot be used for synthetic steroids) is not recommended as an
assessment of dose adequacy.
• Adequacy of fludrocortisone replacement is assessed by:
1. restoration of serum electrolytes to normal
2. no evidence of hypertension or postural hypotension (it should not fall >10
mmHg systolic after 2 minutes’ standing)
3. suppression of plasma renin activity to high normal
• increase steroid replacement by doubling the dose for intercurrent illness

14. Regimen for maintenance of PAI

15. Management of PAI in special situations
Surgery
(minor/ major)

16.  Chronic primary adrenal insufficiency - manifestation of
glucocorticoid, mineralocorticoid and, in women, androgen
deficiency.
 Secondary adrenal insufficiency - Normal mineralocorticoid
function.
 Its onset is often insidious, with the gradual development of
symptoms, most of which are nonspecific.
Chronic Adrenal Insufficiency

17. Addison’s disease (Primary adrenal insufficiency)
Pathophysiology:
• In this condition, there is destruction of the entire adrenal cortex.
• Glucocorticoid, mineralocorticoid and sex steroid production are therefore all
reduced.
• This differs from hypothalamic–pituitary disease, in which mineralocorticoid
secretion remains largely intact, being predominantly stimulated by
angiotensin II.
• Adrenal sex steroid production is also largely independent of pituitary action.
• In Addison’s disease, reduced cortisol levels lead, through feedback, to
increased CRH and ACTH production, the latter being directly responsible for
the hyperpigmentation.

18. Causes
• Addison’s disease is rare, shows a
marked female preponderance and
is usually caused by autoimmune
disease (autoantibodies against 21-
hydroxylase)
• HIV/AIDS
• tuberculosis
• Adrenal hage or infarction: The
major risk factors for adrenal
hemorrhage or infarction are
anticoagulant therapy or an
underlying coagulopathy
• Other causes are rare

19. Bilateral adrenal hemorrhage can inhibit adrenal
function. This usually occurs in specific settings:
• Disseminated infection (meningococcus, Pseudomonas aeruginosa, Streptococcus
pneumoniae, Neisseria gonorrhoeae, Escherichia coli, Haemophilus influenzae, and
Staphylococcus aureus).
• Clotting abnormalities (anticoagulant drug or heparin therapy or coagulopathy,
thromboembolic disease, hypercoagulable states such as antiphospholipid
syndrome).
• Other associations include physical trauma, the postoperative state, sepsis, and
severe stress.

20. other autoimmune conditions in polyglandular autoimmune syndromes types I and II (e.g. type 1
diabetes mellitus, pernicious anaemia, thyroiditis, hypoparathyroidism, premature ovarian insufficiency

21.  Weakness, tiredness, fatigue 100%
 Anorexia 100%
 Gastrointestinal symptoms 92%
 Nausea 86%
 Vomiting 75%
 Constipation 33%
 Abdominal pain 31%
 Diarrhea 16%
 Salt craving 16%
 Postural dizziness 12%
 Muscle or joint pains 6-13%
How common are the Symptoms

22.  Weight loss 100%
 Hyperpigmentation 94%
 Hypotension (systolic BP <110 mmHg) 88-94%
 Vitiligo 10-20%
 Electrolyte disturbances 92%
 Hyponatremia 88%
 Hyperkalemia 64%
 Hypercalcemia 6%
 Azotemia 55%
 Anemia 40%
 Eosinophilia 17%
Signs and Lab. abnormalities

26. A) A 57-year-old woman presented with symptoms of primary adrenal insufficiency
secondary to autoimmune Addison's disease. Diffuse skin hyerpigmentation had developed
during the last year, as illustrated by her facial appearance.
(B) The hands demonstrate increased pigmentation of the palmar creases and wrists
compared to a normal female control (far right).
(C) With long-term glucocorticoid and mineralocorticoid therapy, her hyperpigmentation
resolved, as shown by the normal palmar skin pigmentation in the patient at age 83.
- Of note, she wears a medical bracelet indicating her requirement for glucocorticoids in
case of severe illness
In fair skin

27. Investigations
• Once Addison’s disease is suspected, investigation is urgent.
• If the patient is seriously ill or hypotensive, hydrocortisone 100 mg should
be given intravenously or intramuscularly, together with intravenous 0.9%
saline, immediately after a blood sample is taken for later measurement of
plasma cortisol.
• Single cortisol measurements are of little value, although a random cortisol
below 100 nmol/L during the day is highly suggestive, and a random cortisol
higher than 550 nmol/L makes the diagnosis unlikely.
• The short ACTH stimulation test
• A 09:00-hours plasma ACTH level
• Adrenal antibodies are present in approximately 90% of cases of autoimmune
adrenalitis.

28. The short ACTH stimulation test

29. • Chest and abdominal X-rays or cross-sectional
imaging of the abdomen (CT or MRI) may show
evidence of tuberculosis and/or calcified adrenals
• Plasma renin activity is high due to low serum
aldosterone.
• Serum creatinine and electrolytes classically show
hyponatraemia,hyperkalaemia and a high urea,
but they can be normal.
• Blood glucose may be low, with hypoglycaemia.
• Hypercalcaemia and anaemia (after rehydration)
are sometimes seen.

30. Secondary hypoadrenalism
This may arise from:
1. hypothalamic–pituitary disease (inadequate ACTH production)
2. long-term steroid therapy leading to ACTH suppression
Most people with hypothalamic–pituitary disease have
panhypopituitarism and need T4 replacement, as well as cortisol; in
this case, hydrocortisone must be started before T4.
• ACTH levels are low in secondary hypoadrenalism.

31. 2ry adrenal insufficiency criteria
 Hyperpigmentation is not present.
 Dehydration is not present, and hypotension is less prominent.
 Hyponatremia may be present.
 Hyperkalemia is not present.
 Gastrointestinal symptoms are less common.
 Hypoglycemia is more common in secondary adrenal insufficiency.
 Manifestations of a pituitary or hypothalamic tumor.