This document discusses hypoadrenalism, including primary and secondary adrenal insufficiency. It notes that the adrenal cortex produces glucocorticoids, mineralocorticoids, and androgen precursors. Primary adrenal insufficiency can be caused by autoimmune adrenalitis, congenital adrenal hyperplasia, infections, tumors, or drugs. Secondary adrenal insufficiency results from hypothalamic-pituitary dysfunction. Symptoms include fatigue, low blood pressure, and electrolyte abnormalities. Treatment involves glucocorticoid and mineralocorticoid replacement therapy.
2.  Adrenal cortex produces 3 classes of corticosteroid hormones-
glucocorticoid,mineralocorticoid and androgen precursors.
 Glucocorticoids and mineralocorticoids act through specific nuclear
receptors –regulate stress responses ,blood pressure and electrolyte
homeostasis.
 Androgen precursors are converted in the gonads and peripheral target
cells to sex steroids that act via nuclear androgen and estrogen
receptors.
3.  Production of glucocorticoids and adrenal androgens is under control of
hypothalamic pituitary adrenal axis, whereas mineralocorticoids are
regulated by RAAS system.
4.
5.  Prevelance of permanent adrenal insufficiency is 5 in 10000
 Primary adrenal insufficiency-2 in 10000
 Hypothalamo-pituitary origin of disease- 3 in 10000
8. CLINICAL FEATURES
 primary adrenal insufficiency(Addison’s disease)-loss of both
mineralocorticoid and glucocorticoid secretion.
 In secondary adrenal insufficiency,only glucocorticoid deficiency is
present.
11. Adrenal androgen deficiency:
 Lack of energy
 Dry and itchy skin
 Loss of libido
 Loss of axillary and pubic hair
Other signs:
 Hyperpigmentation in skin areas exposed to increased friction,shear
stress
12. ADRENAL CRISIS:
 Prolonged periods of non-specific symptoms
 Seen in primary adrenal insufficiency
 Postural hypotension- hypovolemic shock
 Abdominal tenderness,nause,vomiting,fever
 Trigger:-intercurrent illness, surgical or other stress, increased
glucocorticoid inactivation
13. DIAGNOSIS
 made by cosyntropin test-excellent predictive diagnostic value.
 Failure:-cortisol level<450-500nmol/L(16-18microgram/dl)sampled 30-60
minutes after ACTH stimulation.
 Random serum cortisol level-limited value- baseline cortisol levels will be
coincidentally low due to physiological diurnal rhythm of cortisol
secretion.
 Secondary adrenal insufficiency have normal baseline cortisol levels but
fail to mount an appropraite cortisol response to ACTH, which can only
be revealed by stimulation testing.
17. TREATMENT
 ACUTE ADRENAL INSUFFICIENCY:immediate initiation of rehydration-
saline infusion- 1L/hr with continous cardiac monitoring.
 Glucocorticoid replacement- bolus injection of 100 mg hydrocortisone
followed by administration of 200 mg hydrocortisone over 24 hours
continous infusionor by bolus iv/im injections.
 Mineralocorticoid replacement- initiated once the daily hydrocortisone
has been reduced to <50 mg because at higher doses hydrocortisone
provides sufficient stimulation of mineralocorticoid receptor.
18.  CHRONIC ADRENAL INSUFFICIENCY:-
Glucocorticoid replacement– administered at a dose that replaces the
physiologic daily cortisol production- oral administration of 15-25 mg
hydrocortisone in two-three divided doses.
 Pregnancy- increase in hydrocortisone dose by 50% during the last
trimister.
 Atleast one half of the daily dose is administered in the morning
 Long acting glucocorticoid such as prednisolone and dexamethasone are
not preferred – increased glucocrticoid exposure due to extended GR
activation at times of low cortisol secretion.
19.  1 mg hydrocortisone = 1.6 mg cortisone acetate = 0.2 mg prednisolone =
0.25 mg prednisone = 0.025 mg dexamethasone.
 Monitoring:- history and examination of signs and symptoms suggestive
of glucocorticoid over or under replacement- assessment of body weight
and blood pressure.
 Plasma ACTH , 24 hr urinary free cortisol or serum cortisol-
hydrocortisone has been taken or not, don’t convey information on
replacement quality.
20.  Supraphysiologic glucocorticoid treatment(dose of hydrocortisone-30 mg)
affect bone metaboism – regular bone mineral density evaluation
 In case of intercurrent illness with fever – double dose of routine oral
glucocorticoid.
 In case of prolonged vomiting, surgery , trauma – iv hydrocortisone
injection at dose of 100mg daily
21. Mineralocorticoid replacement:
 At dose of 100-150 microgm fludrocortisone
 Monitoring:-
1. Bp-postural hypotension-hypovolemia
2. Serum Na, K, plasma renin(upper limit of normal)
 Adjust dose in pregnancy- antimineralocorticoid activity of progesterone
22. Adrenal androgen replacement:
INDICATIONS:
 Despite optimized mineralocorticoid and glucocorticoid replacement-
complaints of Lack of energy
 Women with features of androgen deficiency-loss of libido
Once daily administration of 25-50 mg DHEA.
MONITORING:
 Measure DHEAS, androstenedione, testosterone,sex hormone binding
globulin 24 hours after the last DHEA dose
23. CONGENITAL ADRENAL HYPERPLASIA
 most common cause is 21 hydroxylase deficiency.
 Disrupts glucocorticoid and mineralocorticoid synthesis,
resulting in diminished negative feedback via HPA axis.
 Increased ACTH release ---causes increased synthesis of
adrenal androgen precursors ----androgen release.
 Classic CAH- combined glucocorticoid and mineralocorticoid
deficiency--- neonatal presentation.
 Simple virilizing CAH- neonatal and early childhood
presentation—glucocorticoid synthesis
24.  Androgen excess- non classic
1. severe virilization of external genetalia in neonatal girls
2. Hirsuitism
3. Oligomenorrhoea
 Boys with classic CAH- adrenal crisis- first few weeks of life.
 Simple virilizing genotype- precocious puberty,advanced bone age
25. TREATMENT
 children: hydrocortisone is given in divided dosesat 1-1.5 times the
normal cortisol production rate
 Adults: intermediate acting glucocorticoids-prednisone in the lowest dose
needed to suppress excess androgen production.
 Fertility: dexamethasone.
 Monitoring- androstenedione and testosterone in normal sex specific
reference range.
26.  Children with CAH should receive mineralocorticoid and salt
replacement.
 Plasma renin should be regularly monitored and kept within upper half of
normal range.