The document summarizes the anatomy and function of the adrenal glands. It describes that the adrenal glands sit atop the kidneys and are divided into an adrenal cortex and medulla. The medulla produces catecholamines like epinephrine and norepinephrine which target various organs like the heart and lungs. The cortex produces cortisol, aldosterone, and sex hormones. Conditions of increased or decreased adrenal function are discussed like Cushing's syndrome and Addison's disease. Diagnosis and treatment of Cushing's syndrome focus on distinguishing whether it is caused by an adrenal or pituitary tumor. Treatments include surgery, medications, and adrenalectomy.

1. DR.DIPESH KR. KUSHWAHA

2.  The adrenal glands are located on top of the
kidneys;
 They are divided into an inner renal medulla and
an outer adrenal cortex.
 The adrenal cortex is located in the outer
portion, while the adrenal medulla is located in
the central portion of the adrenal glands

3. a) The adrenal medulla
 It produces the catecholamines; epinephrine and
norepinephrine.
 The hormones function in the sympathetic division
of the autonomic nervous system:
 They target: the heart (increased heart rate and
blood pressure); smooth muscle contraction (blood
vessels,); the lungs (increased breathing: rate,
rhythm, depth).

4.  Control of secretion of catecholamines in
response to physiologic or emotional stress is
through the hypothalamus and also stimulation
of the sympathetic nervous system
 Both systems support each other, hence there is
no condition attributable to hypofunction of the
adrenal medulla.
 Catecholamine-secreting tumors are attributable
to adrenal medullary hyperfunction e.g.
pheochromocytoma

5. b) The adrenal cortex
 It is located in the outer portion of the adrenal
glands.
 It produces three groups of hormones are
classified according to their function:-

6.  Glucocorticoids-(cortisol – stress hormone and
corticosterone which regulates glucose
metabolism)
 Mineralocorticoids-(aldosterone which
regulates water and electrolyte levels in the
blood regulating blood pressure.
 Sex steroids- (androgens, estrogens and
progestins that supplement those of the ovary
and testis.

7.  Aldosterone synthesis is regulated by
reninangiotensin system of the kidney.
 Increased levels of angiotensin II stimulates
adrenal cortex to secrete aldosterone which
preserves sodium thereby retaining water.

9.  Increased Adrenal Function
- Cushing's Syndrome
-Primary Aldosteronism
-Pheochromocytoma
 Decreased Adrenal Function
-Addison's(primary adrenal insufficiency)
-secondary adrenal insufficiency
 Abnormal Adrenal Function
-CAH(congenital adrenal hyperplasia)

10. Cushing syndrome is metabolic disorder
caused by overproduction of corticosteroid
hormones due to excessive activation of
glucocorticoid receptors.
 It is most commonly iatrogenic, due to
prolonged administration of synthetic
glucocorticoids such as prednisolone.

11.  Endogenous Cushing’s syndrome is
uncommon but is caused by chronic over-
production of cortisol by the adrenal glands,
either as the result of
 An adrenal tumour or because of
 Excessive production of ACTH by a pituitary
tumour or
 Ectopic ACTH production by other tumours.

13.  The manifestations of glucocorticoid excess are

14.  The large number of tests available for
Cushing’s syndrome reflects the fact that each
one has limited specificity and sensitivity.
 Testing for Cushing’s syndrome should be
avoided under conditions of stress, such as an
acute illness, because this activates the HPA
axis, causing potentially spurious results.

15.  The diagnosis of Cushing’s is a two-step
process:
1. To establish whether the patient has Cushing’s
syndrome
2. To define the cause of cushing’s syndrome

16.  Cortisol levels in blood are normally elevated
at 8 A.M. and decrease to less than 50% by
midnight except in infants and young children
in whom a diurnal rhythm is not always
established.
 In patients with Cushing syndrome this
circadian rhythm is lost, and cortisol levels at
midnight and 8A.M. are usually comparable.

17.  Urinary excretion of free cortisol is increased. This is
best measured in a 24-hr urine sample.

18.  Dexamethasone is an exogenous steroid that
provides negative feedback to the pituitary to
suppress the secretion of ACTH.
 This steroid is unable to pass the blood brain
barrier which allows this test to assess a
specific part of the hypothalamicpituitary-
adrenal axis.

19.  Specifically, dexamethasone binds to
glucocorticoid receptors in the pituitary gland, which
lies outside the blood brain barrier, resulting in
regulatory modulation.
 A single-dose dexamethasone suppression test is
often helpful;
 a dose of 25–30 μg/kg (maximum of 2 mg) given at
11 P.M.results in a plasma cortisol level of less than 5
μg/dL at 8 A.M.the next morning in normal
individuals but not in patients with Cushing
syndrome

20.  A normal result is decrease in cortisol levels
upon administration of low-dose dexamethasone.
 Cushing's disease involve no change in cortisol on
low-dose dexamethasone, but inhibition of cortisol
on high-dose dexamethasone
 A high dose dexamethasone exerts negative feedback
on pituitary ACTH producing cells but not on
ectopic ACTH producing cells or adrenal adenoma.

21. Establishing the presence of Cushing’s syndrome
 In patients where there is appropriate clinical
suspicion, Cushing’s syndrome is confirmed by
using two of three main tests:
1. failure to suppress serum cortisol with low doses
of oral dexamethasone.
2. loss of the normal circadian rhythm of cortisol,
with inappropriately elevated late-night serum
or salivary cortisol.
3. increased 24-hour urine free cortisol.

23.  Once the diagnosis is established, additional
evaluation is done to identify the cause of the
cushing syndrome.
 Large dose DX suppression test
◦ D.X 2mg q6h P.O 2 days
◦ Urinary free cortisol reduced 50%: Cushing’s
disease (Pituitary adenoma)
◦ Urinary free cortisol NOT reduced 50%:Adrenal
tumor, carcinoma, ectopic ACTH Syndrome

24.  ACTH stimulation test
 ACTH 25u intravenously 8h
 2-5 fold increase in urinary free cortisol in
Cushing’ s diseas
 No response in adrenal carcinoma

25.  CRH stimulation test:
Etiology diagnose (especially for pituitary
ACTH-dependent or ectopic ACTH syndrome)
 A newer approach is to combine a CRH
stimulation test with a dexamethasone
suppression test(4mg ).
method :
 1 μg / kg of CRH is administered intravenously.
 ACTH and cortisol levels are measured before
CRH injection and 15, 30, 45, 60, 90 and 120
minutes after injection.

26.  A rise in the cortisol value of 20 percent or
more above basal level or a rise in the ACTH
value of at least 50 percent above basal level is
considered evidence for an ACTH-dependent
lesion.

27.  METYRAPONE TEST:
 Etiology diagnose (especially for pituitary or
adrenal)
◦ Metyrapone (30mg/kg) P.O at midnight
◦ Urinary 17-OHCS(hydroxycorticosteroid), Plasma
ACTH,11-deoxycortisol more above basal level :
Cushing’s disease (Pituitary adenoma)
◦ No response in adrenal carcinoma , tumor, ectopic
ACTH Syndrome

28. 1. CT SCAN-
 Has a sensitivity of about 50% for identifying
microadenomas.
 High-resolution, contrast-enhanced, thin-section
computed tomography (CT) scans detect only
approximately one-third of the microadenomas,
which appear hypodense after contrast injection.

31. 2. MRI-
 MRI has increased sensitivity but is not 100%
predictive.
 Coronal projections of high-resolution MRI at 1.5
T with gadolinium enhancement reveal
microadenomas in approximately 60 percent of
patients and have replaced CT for localization.

34. 3.If diagnostic doubt need bilateral inferior
petrosal sinus sampling for ACTH.
 Inferior petrosal sinus sampling —
Measurement of ACTH gradients between the
two sinuses during inferior petrosal venous
sinus catheterization predicts the correct side of
the pituitary tumor.

35. 4. Somatostatin scintigraphy :-to identify
sites of ectopic hormone production

36.  Identify the cause of the cushing syndrome.

37. GOALS
Ideal therapy of Cushing's syndrome would achieve the
following goals.
●Reverse the clinical manifestations by reducing cortisol
secretion to normal
●Eradicate any tumor threatening the health of the patient
●Avoid permanent dependence upon medications
●Avoid permanent hormone deficiency

38.  Exogenous Cushing's syndrome —
 Stop the glucocorticoid.
 Most patients who have taken enough
glucocorticoid for a long enough time to cause
Cushing's syndrome will have a period of
hypothalamic-pituitary adrenal insufficiency
when therapy is discontinued. Thus, gradual
withdrawal is necessary.

39.  Cushing’s disease
◦ Transsphenoidal microadenomectomy
◦ Pituitary radiation
◦ Bilateral total adrenolectomy
◦ Drugs
 Adrenal adenoma and carcinoma
◦ Surgical removal
◦ Drugs ( mitotane, metyrapone, ketoconazole )
for nonresectable or metastatic carcinoma.

40.  Ectopic ACTH Syndrome
◦ Surgical removal of the ectopic tumor
◦ Chemotherapy, radiotherapy
◦ Drugs ( mitotane, metyrapone, ketoconazloe )

41.  CUSHING'S DISEASE:-
The approach to the treatment of Cushing's
disease

42. TRANSSPHENOIDAL SURGERY:-
 The treatment of choice for Cushing's disease
(ACTH-producing pituitary tumor) is
transsphenoidal microadenomectomy when a
clearly circumscribed microadenoma can be
identified at surgery .
 In the remaining patients, subtotal (85 to 90
percent) resection of the anterior pituitary may
be indicated if future fertility is not desired.

43.  Approach — The operative approach varies.
Traditionally, the procedure involved
transsphenoidal exploration through either a
sublabial or endonasal approach, followed by
use of a high-powered microscope

44.  Extent of surgery — The extent of surgery varies.
- Ideally, the entire tumor is removed while normal
pituitary tissue is left behind.
-However, in adult patients in whom a microadenoma
cannot be identified at the time of surgery and for
whom fertility is not an issue, 80 to 90 percent of the
pituitary should be resected, leaving a small island
attached to the stalk.

45.  Preoperative localization — In general, tumors
are localized by the preoperative MRI scan or
by intraoperative exploration and observation
by the surgeon.
 The decision to operate should not depend
upon radiographic demonstration of the tumor.
 High-resolution, contrast-enhanced, thin-
section computed tomography (CT) scans
detect only approximately one-third of the
microadenomas, which appear hypodense after
contrast injection

47.  Perioperative glucocorticoids
-Before surgery – Preoperative glucocorticoid
replacement is not necessary unless cortisol
production has been blocked by adrenal enzyme
inhibitors.
- After surgery – Glucocorticoids must be stopped for
24 hours before serum cortisol can be measured to
assess cure. Glucocorticoid replacement can be held
for a few days, with careful observation for the
development of adrenal insufficiency.

48. For patients with clear persistent disease after
transsphenoidal surgery or later recurrence, there
are five therapeutic options:
●Repeat surgery of residual corticotroph adenoma,
particularly if residual tumor is visible on magnetic
resonance imaging (MRI).
●Irradiation of the pituitary gland. Radiation therapy
may decrease the occurrence of Nelson syndrome in
patients not cured by irradiation for whom
adrenalectomy becomes necessary.

49. Nelson syndrome — Patients who have had
bilateral adrenalectomy for Cushing's disease
may develop corticotroph tumor progression,
defined as an enlarging pituitary tumor (new
mass, or an increase of at least 2 mm in
diameter) on magnetic resonance imaging
(MRI).

50. ●Medical therapy with adrenal enzyme inhibitors or
other agents.
●Medical adrenalectomy with mitotane, an
adrenolytic agent, may be used during or after
pituitary irradiation in patients with Cushing's
disease.
●Surgical adrenalectomy.

51. Choice of procedure —
 Bilateral total surgical adrenalectomy is the
definitive treatment for patients in whom rapid
cure of hypercortisolism is necessary or when
all other therapies have failed .
 Bilateral adrenalectomy has also been
successfully used in several pregnant women
with Cushing's syndrome.

52. Surgical approach —
 The laparoscopic approach, which can be done
via either the anterior or posterior approaches,
has become standard, as
 hospital stays appear to be shorter (usually one to five
days) and
 complications fewer, as compared with open surgery .
 Regardless of the approach used, the glands
must be removed en bloc.

53.  Care also must be taken to ensure that the
fragile capsule is not broken because cells
spilled locally can become hyperplastic and
cause recurrent disease; they are then not
usually amenable to surgical removal.

54. Patient positioning —
 The patient is placed on an inflatable beanbag in the
lateral decubitus position, with all bony
prominences padded and the area between the iliac
crest and 11th rib overlying the kidney exposed.
 The patient is rotated backward approximately 15°,
and the beanbag is inflated to secure this position.

56. Port and extraction sites —
 Prior to making any incision for port placement,
the skin is infiltrated with a 1% lidocaine and
0.4% bupivacaine (50:50 mixture) solution.
 The ports should be placed approximately 9 to 12
cm apart, with the most lateral port placed
through the flank.

57.  For right adrenal gland resections, four trocars
(three 5 mm and one 12 mm) are placed in the right
subcostal area and midline .

58.  For left adrenal gland resections, three ports
are usually sufficient.
 CO2 is insufflated to a pressure of 13 to 15
mmHg using a Veress needle or open (Hasson)
technique .
 The peritoneal cavity is initially inspected with
a 0° laparoscope and then with a 30°
laparoscope.

59. Mobilization and resection —
Mobilization, dissection, and resection
techniques are dependent upon the anatomic
location of the gland to be resected.

60.  The general principles for resecting the right
adrenal gland are as follows

61.  Incise the peritoneal reflection of the right hepatic
triangular ligament and retract the liver and colon
medially.
 The second portion of the duodenum can also be
mobilized if needed to facilitate exposure of the right
adrenal gland.

62.  Incise the anterior renal fascia (Gerota's fascia), a
thin fascial layer encompassing the kidney and
adrenal gland, vertically over the upper portion of
the right kidney.
 Dissect superiorly to the diaphragm, approximately
4 to 6 cm above the superior pole of the kidney

64.  Dissect the medial perirenal adipose tissue medially
until the lateral border of the inferior vena cava (IVC)
is identified.
 Dissect cephalad along the lateral wall of the IVC
superiorly to the level of the right diaphragmatic
crus.

65.  The right adrenal vein is identified along the lateral
border of the IVC.

66.  The vein is meticulously dissected and ligated
with Hem-o-lok polymer clips or metal clips,
linear vascular stapler, or suture ligatures.
 Identify and ligate any accessory adrenal veins
that drain into the IVC or liver.

67.  Identify and ligate or cauterize the multiple small
adrenal arteries that arise from the aorta,
phrenic, and/or renal arteries.
( as they are encountered to minimize the risk of
hemorrhagic rupture of the tumor or bleeding from
the adrenal gland)

69.  Dissect the lateral periadrenal adipose tissue
containing the adrenal gland from the diaphragm
and the superior pole of the kidney en bloc, using
electrocautery or another energy device.
 When dissecting in the groove between the adrenal
gland and kidney, use caution in the inferomedial
area to avoid injury to the superior pole renal
vasculature.

70.  Avoid disrupting the capsule of the tumor by
grasping the adipose and areolar tissues, rather
than directly grasping the adrenal gland and
tumor.
 Rotate the adrenal gland laterally and divide
the remaining areolar tissue circumferentially
between the superomedial border of the gland
and the IVC.

71.  Place the adrenal gland in an endoscopic
retrieval bag and remove it through the larger
port, without rupture of the tumor.
 The port site may be enlarged, as needed, to
accommodate the specimen.

72.  Typically, three 5 mm ports in the left subcostal
region are adequate for a laparoscopic
transabdominal left adrenalectomy.
 However, a fourth port may be required for
retraction of an enlarged spleen or pancreas.

74.  Mobilize the splenic flexure of the colon by dividing
its attachments to the kidney and Gerota's fascia .

75.  Mobilize the spleen by dividing the lienophrenic
ligament to the level of the gastric fundus.
 The spleen, pancreas, anterior surface of the Gerota's
fascia, and medial edge of the adrenal gland can be
fully visualized with this maneuver.

76.  Dissect en bloc in the avascular plane between the
posterior surface of the pancreas, with the splenic
artery and vein intact, and the anterior surface of
Gerota's fascia.
 For smaller adrenal tumors, an alternative approach
is to incise the fascia along the inferior border of the
pancreas and mobilize the body and tail of the
pancreas superiorly.

78.  The left renal vein and the adrenal gland are
now exposed.

79.  Identify the left adrenal vein as it courses from the
inferior pole of the adrenal gland to the midportion of
the renal vein.
 Once identified, the left adrenal vein can be divided
with methods similar to those used to divide the right
adrenal vein.

80.  Divide and ligate the small-caliber adrenal
branches of the left suprarenal and phrenic
arteries as they are encountered with
electrocautery or another energy device.
 Dissect the medial edge of the adrenal gland
from the diaphragm en bloc, and divide and
ligate small vessels with electrocautery as
described for a right adrenalectomy.

81.  Place the adrenal gland in an endoscopic
retrieval bag and remove through the larger
port.
 The port site may be enlarged, as needed, to
accommodate the specimen to avoid rupture or
morcellation of the tumor.

82. When conversion is required, a subcostal
incision can be created expeditiously by
connecting the two or three most medial trocar
incisions.

83. Hormone replacement —
 On the day of adrenalectomy, most surgeons
administer glucocorticoids (50 to 100
mg hydrocortisone, intravenous eight hours.
 Generally, the dose is tapered rapidly to 50 and then
25 mg IV every eight hours over the next two days.
 This agent and dose provide both glucocorticoid
and mineralocorticoid coverage.

84. Postoperative management —
 After adrenalectomy in Cushing's disease, one
should not wait for the occurrence of Nelson
syndrome; modern imaging allows early detection
and management of corticotroph tumor
progression.
 Monitoring — Between three days and two weeks
after adrenalectomy (or possibly later), if clinical
features of Cushing's syndrome recur, a morning
blood sample should be drawn before the
replacement glucocorticoid dose is taken to confirm
that serum cortisol is undetectable.

85.  In addition, because of the potential risk of
corticotroph tumor progression (Nelson
syndrome)
 Adrenalectomized pt. be followed with MRI of
the pituitary and plasma ACTH measurements,
annually for seven years, and then
intermittently if there has been no tumor
progression.

86. Purpose
◦ Correct metabolic abnormalities before
attempted surgical cure
◦ Palliate surgically noncurable disease
◦ Achieve remission in patients for whom surgery
is unlikely to achieve satisfactory long term
results.

87. Steroidogenic inhibition
◦ Mitotane
◦ Metyrapone
◦ Aminoglutethimide
◦ Ketoconazole
Neuromodulatory treatment
◦ Bromocriptine
◦ Cyproheptadin
◦ Valproic acid
◦ Octreotide
Glucocorticoid receptor antagonist
◦ RU486

89.  Addison’s disease, or primary adrenal
insufficiency, was first described by Addison in
1855 as follows:
- the characteristic features... are general languor
and debility, remarkable feebleness of the
heart’s action, irritability of the stomach, and a
peculiar change of colour in the skin.

92.  Acute primary adrenal insufficiency(adrenal
crisis)

93.  The presenting symptoms and signs of bilateral
adrenal hemorrhage include:-
-Hypotension or shock (>90 percent)
-Abdominal, flank, back, or lower chest pain (86 percent)
-Fever (66 percent, presumably a response to inflammation)
-Anorexia, nausea, or vomiting (47 percent)
-Neuropsychiatric symptoms such as confusion or disorientation (42
percent)
-Abdominal rigidity or rebound tenderness (22 percent)

94.  Chronic primary adrenal insufficiency

96.  (A) A 57-year-old
woman presented
with symptoms of
primary adrenal
insufficiency
secondary to
autoimmune
Addison's disease.
Diffuse skin
hyperpigmentation
had developed during
the last year, as
illustrated by her facial
appearance.

97.  (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.

98.  Lips and gums of a 32-year-
old man demonstrating
hyperpigmentation of the
buccal mucosa along the line
of dental occlusion (an area
of repeated trauma) and of
the gums (in the area of
chronic inflammatory
periodontal disease).
 The high plasma ACTH
concentrations responsible
for the hyperpigmentation
were due, in this case, to
primary adrenal
insufficiency; similar
changes can be seen in
patients with ACTH-
dependent Cushing's
syndrome or Nelson
syndrome.

99.  Fingers of a 28-year-old white
woman with Addison's disease
(underneath) compared with
those of a normal woman (top).
 There is hyperpigmentation of
the skin and increased
pigmentation of the distal half
of the nails that occurred during
the period of adrenal
insufficiency.
 The proximal half of the nails
are hypopigmented, a reflection
of the reduction in corticotropin
(ACTH) secretion after the
institution of glucocorticoid
therapy.

101. The diagnosis of adrenal insufficiency of any cause
depends entirely upon the demonstration of
inappropriately low cortisol production.

102.  Morning serum cortisol concentration —
 In normal subjects, serum cortisol concentrations
are higher in the early morning (about 8AM),
ranging from 10 to 20 mcg/dL (275 to
555 nmol/L), than at other times of the day.
 An early morning low serum cortisol
concentration (less than 3 mcg/dL [80 nmol/L]) is
strongly suggestive of adrenal insufficiency.

103.  Morning salivary cortisol concentration —
A salivary cortisol concentration at 8 AM above
5.8 ng/mL (16 nmol/L)excludes adrenal
insufficiency, whereas a value below about
1.8 ng/mL (5 nmol/L) makes the probability of
adrenal insufficiency high.

104.  Afternoon serum cortisol; measurements:-
 At 4 PM, normal serum cortisol concentrations
range from 3 to 10 mcg/dL (85 to
275 nmol/L); concentrations are at their lowest
(less than 5 mcg/dL [140 nmol/L]) one hour after
the usual time of sleep.
 As a result, serum cortisol measurements at these
times are of no value in establishing the diagnosis
of adrenal insufficiency.

105.  Urinary cortisol measurements —
 As with morning serum cortisol
concentrations, basal urinary cortisol excretion
is low in patients with severe adrenal
insufficiency, but may be low-normal in
patients with partial adrenal insufficiency.
 Thus, they cannot be used as a screening test
for adrenal insufficiency.

106.  Short ACTH stimulation tests —
 A short ACTH stimulation test should be performed
in virtually all patients in whom the diagnosis of
adrenal insufficiency is being considered.
 A standard high dose and a low dose test are
available.
- For both tests, a subnormal response confirms the
diagnosis of adrenal insufficiency

107. 1)Standard high-dose test (250 mcg) —
 A normal response to the high-dose (250 mcg as
an intravenous [IV] bolus) ACTH stimulation test
is a rise in serum cortisol concentration after either
30 or 60 minutes to a peak of ≥18 to
20 mcg/dL (500 to 550 nmol/L).
 A normal response to the high-dose (250 mcg)
ACTH stimulation test excludes primary adrenal
insufficiency and most patients with secondary
adrenal insufficiency.

108. 2)Low-dose test (1 mcg) —
 The low-dose (1 mcg as an IV bolus) result in
the peak serum cortisol concentrations at 20 to
30 minutes. in healthy individuals.

110.  Basal plasma ACTH, renin, and aldosterone
concentration:-
• In primary adrenal insufficiency, the 8 AM plasma
ACTH concentration is high, sometimes as high as
or higher than 4000 pg/mL (880 pmol/L);
• These patients have mineralocorticoid deficiency in
addition to cortisol deficiency, plasma renin
concentration or activity will be elevated, while
aldosterone levels will be low, with increased serum
potassium and decreased serum sodium levels.

111. • In contrast, plasma ACTH concentrations are
low or low normal in secondary or tertiary
adrenal insufficiency.

112. PAI: primary adrenal insufficiency;
21-OH-Abs: 21-hydroxylase antibodies;
VLCFA: very-long-chain fatty acids;

113. 1) Acute adrenal insufficiency
(adrenal crisis)
2) Chronic adrenal insuffiency

114.  Emergency measures
1. Establish intravenous access with a large-gauge needle.
2. Draw blood for immediate serum electrolytes and glucose
and routine measurement of plasma cortisol and ACTH. Do
not wait for lab results.
3. Infuse 2 to 3 liters of isotonic saline or 5 percent dextrose in
isotonic saline as quickly as possible. Frequent hemodynamic
monitoring and measurement of serum electrolytes should be
performed to avoid iatrogenic fluid overload.

115. 4. Give 4 mg dexamethasone as intravenous bolus over
one to five minutes and every 12 hours thereafter.
Dexamethasone is the drug of choice because it does
not interfere with the measurement of plasma
cortisol.
 If dexamethasone is unavailable, intravenous
hydrocortisone, 100 mg immediately and every six
hours thereafter, may be used.
5. Use supportive measures as needed.*

116.  Subacute measures after stabilization
of the patient
1. Continue intravenous isotonic saline at a slower rate
for next 24 to 48 hours.
2. Search for and treat possible infectious precipitating
causes of the adrenal crisis.
3. Perform a short ACTH stimulation test to confirm the
diagnosis of adrenal insufficiency, if patient does not
have known adrenal insufficiency.
4. Determine the type of adrenal insufficiency and its
cause if not already known.

117. 5. Taper parenteral glucocorticoid over one to
three days, if precipitating or complicating
illness permits, to oral glucocorticoid
maintenance dose.
6. Begin mineralocorticoid replacement with
fludrocortisone, 0.1 mg by mouth daily, when
saline infusion is stopped.

118. A.Glucocorticoid replacement

Hydrocortisone 15 to 25 mg orally in two or three divided
doses (largest dose in morning upon awakening; typically 10
mg upon arising in morning, 5 mg early afternoon, 2.5 mg
late afternoon) or
 Prednisone 5 mg (range: 2.5 to 7.5 mg) orally at bedtime;or
 Dexamethasone 0.75 mg (range: 0.25 to 0.75 mg) orally at
bedtime.
 Monitor clinical symptoms and morning plasma ACTH

119. B. Mineralocorticoid replacement*
 Fludrocortisone 0.1 mg (range: 0.05 to 0.2 mg) orally.
 Salt intake.
 Monitor lying and standing blood pressure and
pulse, edema, serum potassium, and plasma renin
activity.

120. C. Androgen Replacement
Dehydroepiandrosterone (DHEA) initially 25 to
50 mg orally (only in women with impaired
mood or sense of well-being despite optimal
glucocorticoid and mineralocorticoid
replacement).

121. D. Treatment of minor febrile illness or stress
 Increase glucocorticoid dose two- to threefold for the
few days of illness.
 Do not change mineralocorticoid dose.
 Patient is instructed to contact clinician if illness
worsens or persists for more than three days.
 No extra supplementation is needed for most
uncomplicated, outpatient dental procedures under
local anesthesia.

122.  Glucocorticoid supplement for surgical stress:
 Minor (eg, herniorrhaphy): hydrocortisone 25 mg IV (or
equivalent) on day of procedure.
 Moderate (eg, orthopedic surgery): hydrocortisone 50 to 75
mg IV (or equivalent) on day of surgery and postoperative
day 1.
 Major (eg, cardiac bypass): hydrocortisone 100 to 150 mg IV
(or equivalent) in two or three divided doses on day of
surgery and postoperative days 1 and 2.
 Then return to usual daily glucocorticoid dose.