This document provides information on the adrenal gland and adrenal disorders including: 1) The adrenal gland is a paired organ that produces hormones important for stress response and electrolyte balance. Diseases include primary adrenal insufficiency (Addison's disease) and Cushing's syndrome. 2) Pheochromocytoma is a rare catecholamine-producing tumor that causes symptoms of headache, sweating, and palpitations. Preoperative management with alpha-blockade is important to prevent postoperative hypotension. 3) Adrenocortical carcinoma is a rare malignant tumor most commonly presenting as Cushing's syndrome or virilization in adults. Surgical resection is the main treatment when possible

1. ADRENAL GLAND
Dr. M.Vijay Kumar
Assistant Professor
Dept. of General Surgery

2. • Paired, Mustard-colored structures
• 4 g each.
• 2000 mL/kg/min of blood (after only the kidney
and thyroid).
• Although arterial supply is diffuse, the venous
drainage of each gland is usually solitary.
• Inferior Artery is the most prominent and is
commonly a single identifiable vessel.
• Capsule with Gerota fascia

3. • 20%
RAV>>>>ARHV or
IVC

4. • Cortex - coelomic mesodermal tissue near the
cephalic end of the mesonephros.
• Medulla - ectodermal tissues of the embryonic
neural crest > migrate ventrally to assume a para-
aortic position (paraganglioma).
• Chromaffin cells-interface b/w the nervous &
endocrine systems.
• Microvascular arrangement is essentially a portal
system between the cortex and medulla.
• Arteries>subcapsular plexus>centripetally>deep
plexus in the reticularis> phenylethanolamine & N-
MT> NE~E

5. • Primary Adrenal Insufficiency (Addison
Disease)
• Secondary adrenal insufficiency
• Adrenal Insufficiency in the Critically ill
patients
• Acute adrenal insufficiency, or adrenal crisis

6. Primary Adrenal Insufficiency
(Addison Disease)
weakness and fatigue, anorexia, nausea or
vomiting, weight loss, hyperpigmentation,
hypotension, and electrolyte disturbances
(hyponatremia and hyperkalemia)

7. Intrinsic adrenal disease
1. Congenital Adrenal dysgenesis/hypoplasia
2. Defective Steroidogenesis
3. Adrenal destruction
a. Autoimmune causes
b. Infectious adrenalitis
c. Adrenal replacement by metastatic tumor
d. Adrenal hemorrhage (WATERHOUSE-
FRIDERICHSEN SYNDROME) -septicemia-
pediatric and asplenic patients.

8. secondary adrenal insufficiency
1. ACTH deficiency
2. Panhypopituitarism caused by
a. Neoplastic or infiltrative replacement,
b. Granulomatous disease, and
c. Pituitary hemorrhage or infarction.
Pituitary infarction may occur in the setting of
severe postpartum hemorrhage (Sheehan
syndrome).

9. Pharmacologic steroid withdrawal
a. High supraphysiologic dose of
glucocorticoids->20mg prednisone daily for
>5days
b. Low supraphysiologic dose for >3weeks
are at risk for HPA axis suppresion.
Surgical cure of Cushing syndrome likewise
results in glucocorticoid withdrawal.

10. Adrenal Insufficiency in the
Critically Ill
Acute reversible dysfunction of the HPA axis
a. Adrenal ACTH resistance and
b. Decreased responsiveness of target tissues to
glucocorticoids
Inverse relationship between survival benefit and
glucorticoid dose
a.1.8% absolute risk reduction
b.Hypernatremia, hyperglycemia, weakness

11. Adrenal Crisis
• Life-threatening condition that typically occurs
in individuals with already marginal
adrenocortical function who are subjected to a
significant acute physiologic stressor, such as
infection or trauma.
• Sudden and complete loss of adrenal function,
as occurs with WaterhouseFriderichsen
syndrome and certain hypercoagulable states,
can also be manifested with adrenal crisis.

12. • Clinical findings
a. shock, abdominal pain, fever, nausea and
vomiting, electrolyte disturbances, and
occasionally hypoglycemia.
b. Mineralocorticoid deficiency, resulting in an
inability to maintain sodium and intravascular
volume, is the primary pathogenic mechanism,
although diminished cardiovascular
responsiveness to catecholamines caused by
glucocorticoid deficiency also plays a role.

13. • For suspected adrenal crisis should not be
delayed while awaiting the results of diagnostic
testing.
• The treatment of adrenal crisis centers around
large-volume (1–2 L) intravenous resuscitation
with isotonic saline and glucocorticoid
administration in the form of hydrocortisone (100
mg intravenous bolus followed by 75 mg every 8
hours) or dexamethasone (4 mg intravenously
every 24 hours).
Treatment -Adrenal crisis

14. • Routine and provocative biochemical testing is
necessary to confirm the diagnosis.
1. First step is to document inadequate cortisol
production, which can be done by measuring
morning levels of cortisol in serum (15mcg/dl) or
saliva (5.8ng/ml).
2. Fall below these thresholds should undergo
provocative testing.

15. High dose Cosyntropin (250mcg i.m) stimulation
test:
• Measuring serum cortisol levels 30 to 60
minutes later. A positive test result (<18mcg/dl)
is strongly suggestive of adrenal insufficiency.
• After the diagnosis made , a morning ACTH
level is determined to differentiate between
primary and secondary adrenal insufficiency.

17. Treatment -adrenal insufficiency
• Adrenal crisis
• Chronic adrenal insufficiency- replace physiologic
glucocorticoid and mineralocorticoid levels.
• Daily adult cortisol production is in the range of
10 to 20 mg, which can be replaced by the long-
acting, orally bioavailable agent prednisone at a
dosage of 5 mg/day.
• Typical mineralocorticoid replacement consists of
fludrocortisone, 0.1 mg/day

19. • Patients with secondary adrenal insufficiency
have only a 1% to 2% risk of hypotensive crisis
without perioperative glucocorticoid coverage.
• To prevent this rare but hazardous complication,
chronic glucocorticoid users should, at the least,
be maintained on their usual glucocorticoid
dosage throughout the perioperative period.
• Patients undergoing unilateral adrenalectomy should be
given supplemental glucocorticoids only if the
underlying diagnosis is Cushing syndrome.

24. Diagnosis
&
Localization

25. AVS

26. • 30% to 40% of patients being evaluated for
primary hyperaldosteronism undergo AVS
when it is applied to select patients.
• The usefulness of the test is limited by its low
success rate(40%–80%), with the most
common reason for incomplete AVS being
failure to cannulate the right adrenal vein.
• Frequently, however, sufficient lateralizing
information is provided during AVS to guide
surgical treatment, even when the study is not
bilaterally selective.

27. Surgical Management and
Outcomes
• Laparoscopic adrenalectomy is the preferred
procedure for the management of
aldosteronoma and most other adrenal tumors.

28. Clinical success is defined as
• complete (normalization of blood pressure without
antihypertensive medication),
• partial (decrease in antihypertensive medication or
reduction in blood pressure with same medication), or
• absent.
Biochemical success is defined as
• complete (correction of hypokalemia and normalization
of aldosterone to renin ratio),
• partial (correction of hypokalemia and ≥50% decrease in
plasma aldosterone but persistently elevated aldosterone
to renin ratio), or
• absent.

29. • A subset of patients with the following
preoperative features display reduced benefit
from surgical treatment and continue to
require antihypertensive medications after
operation:
• men older than 45 years, family history of
hypertension, long-standing hypertension,
requirement of more than two
antihypertensive medications, and
nonresponse to spironolactone.
• These indicate a component of essential
hypertension and, irreversible cardiovascular
alterations caused by chronic disease.

30. • Patients with hyperaldosteronism have a higher
incidence of chronic kidney disease compared
to hypertensive controls. Glomerular
hyperfiltration caused by hyperaldosteronism
can artificially raise creatinine clearance and
mask renal insufficiency.
• After adrenalectomy, the decrease in
aldosterone levels can lower glomerular
filtration and unmask the true degree of chronic
kidney disease.

31. • Renal insufficiency and suppression of
aldosterone secretion from the contralateral
adrenal gland at AVS are predictors of
hyperkalemia.
• Hyperkalemia occurs within 1 to 3 weeks after
surgery; therefore, patients should be
monitored with weekly serum potassium
levels for 1 month postresection.
• Persistent hyperkalemia can be treated with
mineralocorticoid replacement therapy
(fludrocortisone).

33. • Recent next-generation sequencing on
whole exome DNA has revealed a
specific mutation of protein kinase A that
is present in cortisol producing
adenomas, particularly in patients with
overt Cushing syndrome.
• The most common cause of Cushing
syndrome is pharmacologic
glucocorticoid use for the treatment of
inflammatory disorders.

34. • Endogenous Cushing syndrome is rare,
affecting 5 to 10 individuals/million.
Of these,
A. Most affected individuals (75%) will have
Cushing disease, that is, glucocorticoid
excess caused by an ACTH-hypersecreting
pituitary adenoma.
B. Primary adrenal Cushing syndrome (15%)
C. Ectopic ACTH syndrome (<10%), (usually
is caused by neuroendocrine tumors or
bronchogenic malignant neoplasms arising
in the thorax).

36. • In the most common scenario of resection of
a solitary adrenal Cushing adenoma, steroids
can usually be tapered to physiologic
replacement levels during the course of
several weeks.
• However, a subset of patients with Cushing
syndrome of longer duration and severity will
demonstrate lasting HPA axis suppression,
requiring glucocorticoid supplementation for
longer periods, sometimes longer than 1 year.

37. • The management of patients who undergo
pituitary surgery for Cushing disease is
variable.
• In some centers, glucocorticoids are
withheld during the immediate postoperative
period to provide a window during which
early remission may be assessed.
• A subnormal morning cortisol level on
postoperative day 1 or 2 is indicative of
cure. Glucocorticoid supplementation is
then resumed until the HPA axis recovers,
usually for at least 6 months.

38. • Adrenalectomy is more than 90% effective
in the treatment of primary adrenal Cushing
syndrome.
• Failures may result from local and
occasionally distant tumor recurrence in the
case of malignant disease.
• Pituitary microsurgery for Cushing disease,
typically performed through a transnasal
transsphenoidal approach.
• Remission rates may be improved by
reoperation or pituitary irradiation.

39. • Laparoscopic bilateral adrenalectomy
should be considered for patients in whom
pituitary surgery has failed.
• Patients with Cushing syndrome are
hypercoagulable and carry a risk of
venous thromboembolism of up to 5%
after pituitary or adrenal surgery. Chemical
thromboprophylaxis should be considered,
although there are insufficient data to
determine the optimal duration and
dosage.

43. • Almost all feminizing tumors are
malignant, whereas approximately one
third of virilizing tumors are malignant.
• Of adrenocortical carcinomas, 20% cause
virilization, with most of these cases
occurring in children. An additional 24% of
adrenocortical carcinomas will display
mixed features of Cushing syndrome and
virilization.

45. • 40 to 50 years, no significant gender
predilection.
• At the time of presentation, adrenocortical
carcinomas tend to be very large (mean
tumor size, 9–13 cm) and have usually
spread beyond the confines of the adrenal
gland.

46. • More than 50% of adrenocortical carcinomas
are functional. Cushing syndrome is most
commonly seen, followed by virilization.
• Radiographic evaluation is primarily
performed with CT, which typically reveals a
heterogeneous mass with irregular or
indistinct borders, central necrosis, and
invasion of adjacent structures.
• Metastases to lymph nodes, liver, and lungs
may be found.

48. • Particular care must be taken in dealing with
right-sided adrenocortical carcinomas larger
than 9 cm because direct tumor extension
into the inferior vena cava and sometimes the
right side of the heart may be observed.
• Tumors demonstrating intravascular
extension may need to be resected while the
patient is on cardiopulmonary bypass to
reduce the likelihood of lethal intraoperative
tumor embolization.

51. • The principal chemotherapeutic agent for the
treatment of adrenocortical carcinoma is
mitotane [o,p-DDD, or 1,1-dichloro-2-(o-
chlorophenyl)-2-(p-chlorophenyl)ethane], a
derivative of the insecticide DDT that is a direct
adrenocortical toxin.
• Mitotane has been used clinically as an adjuvant
to surgery and as primary therapy in individuals
with unresectable or metastatic disease.
• The use of mitotane is limited by significant,
dose-dependent gastrointestinal and neurologic
toxicity.

53. Pheochromocytoma
• Felix Frankel
• Dusky-colored tumor, from the Greek
• César Roux and Charles Mayo

55. • Pheochromocytoma affects approximately
0.2% of hypertensive individuals.
• Men and women are affected equally.
• The peak incidence in sporadic cases is
between the ages of 40 and 50 years,
whereas familial cases tend to be
manifested earlier.
• classic triad of headache, diaphoresis, and
palpitations.

56. • In fact, only 0.5% of patients with
hypertension and suggestive features will
ultimately prove to have the disease.
• hyperthyroidism,
• hypoglycemia,
• coronary artery disease,
• heart failure,
• stroke,
• drug-related effects, and panic disorder.

65. • Postoperative hypotension may be
profound. It results from a state of
hypovolemia created by the presence of
excess circulating catecholamines.
• Sudden withdrawal of this stimulus after
tumor removal leads to peripheral
arteriolar vasodilatation and a dramatic
increase in venous capacitance, which
together may precipitate cardiovascular
collapse.

66. • As soon as the biochemical diagnosis of
pheochromocytoma has been confirmed,
α-adrenergic blockade should be initiated
to protect against hemodynamic lability.
• The period of preoperative conditioning
should last at least 2 weeks to allow
adequate reversal of α-adrenergic receptor
downregulation. This restores sensitivity to
vasopressor agents, which can then be
used to treat the patient postoperatively.

67. • Phenoxybenzamine is a nonspecific,
noncompetitive (irreversible), long-acting
(half-life of 24 hours) α-adrenergic
antagonist.
• Although its use is associated with the
side effects of postural hypotension and
significant nasal congestion, it is generally
favored over α1-adrenergic selective
agents, such as prazosin and doxazosin.
• Nasal congestion can actually serve as a
useful indicator of adequate blockade.

69. • Beta blockers may be administered after
adequate alpha blockade has been
achieved for the subset of patients with
persistent tachycardia, who often have
predominantly epinephrine secreting
tumors.
• Beta blockers should never be the first
agent administered because a decrease in
peripheral vasodilatory beta receptor
stimulation results in unopposed α-
adrenergic tone, which may exacerbate
hypertension.

70. • Clinical suspicion for hypovolemia should
remain high in the postoperative period,
and patients should be resuscitated
aggressively if they become hypotensive
or oliguric.
• Some patients may require vasopressors
after tumor removal, especially if
preoperative alpha blockade is incomplete.

72. • Laparoscopic resection is contraindicated
when preoperative imaging demonstrates
local invasion.
• Open resection should be considered for
larger (>6 cm) pheochromocytomas
depending on surgeon experience to
prevent tumor rupture, which can lead to
local recurrence even in benign cases.

75. • Succinate dehydrogenase, which is made
up of four subunits, is localized to the
mitochondria and catalyzes essential
steps in oxidative phosphorylation.
• Germline mutations in the B and D
subunits, inherited in an autosomal
dominant fashion, have been identified in
approximately 10% of apparently sporadic
pheochromocytoma cases.

76. • Succinate dehydrogenase B mutation
carriers have high rates of extra-adrenal
(abdominal or thoracic)
pheochromocytomas and malignant
disease.
• succinate dehydrogenase D carriers tend
to present with multiple tumors and
hormonally inactive paragangliomas of the
head and neck.
• The lifetime penetrance of succinate
dehydrogenase mutations is estimated at
more than 75%.

77. • Genetic counseling should be considered
in all patients, particularly those
• younger than 45 years and
• those with multiple tumors,
• extra-adrenal location, and
• previous head and neck paraganglioma.

78. • Cortical-sparing adrenalectomy should be
considered in cases of familial
pheochromocytoma where the risk of
contralateral pheochromocytoma is high.
• Preservation of at least one third of one
adrenal gland is necessary to allow for
adequate cortical function without the
need for exogenous steroids.

79. • No histopathologic criteria for determining
malignancy.
• Thus, malignancy is defined by the
development of metastases (i.e., tumor
implants distant from the primary mass in
locations in which neuroectodermal tissues
are not normally found). The latter criterion
distinguishes metastatic disease from
possible multifocal primary disease.
• The most common sites of metastasis are
the axial skeleton, lymph nodes, liver, lung,
and kidney.

82. Incidentally Discovered Adrenal
Mass (Incidentaloma)

84. • In patients with a history of malignant
disease, metastatic disease is the most
likely cause of adrenal masses,particularly
when they are bilateral.
• In those without a clear history of
malignant disease, at least 80% of
incidentalomas will turn out to be
nonfunctioning cortical adenomas or other
benign lesions that do not require surgical
management.

85. Management
• The workup of the adrenal incidentaloma
integrates hormonal evaluation with size
criteria.
• Evaluation begins with history taking, with a
focus on prior malignant disease,
hypertension, and symptoms of
glucocorticoid or sex steroid excess.
• Biochemical investigations for hormonally
active tumors are followed by consideration
of size criteria.

90. • The diagnosis of primary adrenal
malignancy cannot reliably be made on the
basis of cytologic criteria alone.
• Therefore, the use of fine-needle aspiration
is generally confined to patients with a
history of extra-adrenal malignancy in whom
the clinician seeks to establish the
diagnosis of metastatic disease.
• In all cases, pheochromocytoma must be
excluded before attempting such a
procedure to avoid precipitating potentially
fatal hypertensive crisis.

94. • Evaluation of patients presenting with
isolated adrenal metastases must involve
1. careful exclusion of extra-adrenal disease
with CT or MRI (including the head in
cases of breast cancer or melanoma, and
triphasic contrast-enhanced CT evaluation
of the liver plus 3-mm slices through the
lungs for gastrointestinal malignant
neoplasms)
2. as well as bone and PET scans, when
appropriate.

95. • Patients presenting with isolated bilateral
adrenal metastasesmust be evaluated for
adrenal insufficiency because of replacement
of all normal adrenal tissue with tumor, which
may occur in up to 30% of these patients.
• This is best performed with measurement of
morning cortisol and ACTH levels.
• Cortical insufficiency should be adequately
treated before operation to avoid
perioperative adrenal crisis.

99. • More challenging in older, obese male
patients because of increased
retroperitoneal fat, making initial entry and
orientation more difficult.
• Severe obesity (body mass index >35)
results in compression of the
retroperitoneum by the abdominal viscera
when the patient is in the prone position
and is a relative contraindication to the
retroperitoneoscopic approach,
depending on the surgeon’s experience.

100. • The Gagner’s lateral transabdominal
technique offers a wider operative field
and greater versatility, and it is well suited
for larger tumors and obese patients.
• The overall conversion rate to open
adrenalectomy is less than 5% with either
technique.

102. • The placement of an orogastric or
nasogastric tube for gastric
decompression is frequently helpful,
particularly in treating left-sided lesions.
• CVP, Arterial lines, Cardiac monitors
Secured.
• The patient is then turned on his or her
side (80-degree lateral decubitus position),
with the side of the lesion facing upward.

106. • Palmer point
• Generally use three radially dilating trocars,
and a fourth may be added in cases in
which the spleen and pancreatic tail require
additional retraction.
• The ports are equally distributed along the
costal margin, with the posterior port placed
as far lateralposterior as permitted by the
position of the colon.

113. • The left adrenal vein is carefully dissected
out, aggressively coagulated or clipped,
and divided.
• The inferior tip of the left adrenal gland
may extend low, approaching the renal
hilum within millimeters.
• However, because the left adrenal vein is
rather long (2 cm), it is generally not
necessary to expose the renal vasculature
during left adrenalectomy.

118. • The right adrenal vein is a potentially
perilous structure to manage because it is
short, wide, variable, and confluent with
thin-walled, large-capacitance vessels.
• That can bleed briskly if directly injured
(e.g., by the cautery), lacerated from
undue traction on adjacent structures, or
sheared by clips. A significant second
adrenal vein may be found in up to 10% of
patients.

122. Posterior Retroperitoneoscopic
Adrenalectomy

123. • Advantages, including avoidance of
mobilization of the solid organs that is
necessary with transabdominal approaches,
elimination of the need for repositioning
during bilateral adrenalectomy, and
avoidance of anterior adhesions in patients
with extensive prior abdominal surgery.
• One disadvantage is the relatively small
working space, which makes the
retroperitoneal technique best suited for
tumors smaller than 7 cm in diameter.

126. • Mobilization of the adrenal gland begins
near the paraspinous muscles, at the
inferomedial aspect of the gland. This is
where the left adrenal vein is almost
always encountered early in the
procedure.
• On the right side, the vein is encountered
slightly later as dissection proceeds
superiorly.

132. • open adrenalectomy should be performed
for primary adrenal tumors demonstrating
features suggestive of malignancy, such
as large size (>8 cm), clinical feminization,
hypersecretion of multiple steroid
hormones, or any of the following imaging
attributes: local or vascular invasion,
regional adenopathy, and metastases.
• For open adrenalectomy, prefer a
transabdominal approach, which is
performed through a subcostal incision.

134. Patient Preparation and Positioning
• Neuraxial blockade
• The patient is positioned supine, with the
ipsilateral side slightly elevated on a bolster.
• urinary catheter, orogastric or nasogastric
tube, and intermittent pneumatic
compression devices are placed. The
surgical preparation is carried from the nipple
line to the pubis and down to the table on
either side.

136. • The splenic flexure of the colon is
mobilized inferiorly, and the plane medial
to the adrenal gland is developed.
• The adrenal vein is isolated, tied in
continuity, and divided.
• The small adrenal arteries can be ligated
or electrocoagulated and the specimen
removed after circumferential dissection is
completed.

138. • The retroperitoneum is entered by
performing a Kocher maneuver and the
inferior vena cava is exposed by medial
reflection of the duodenum.
• The plane between the adrenal gland and
inferior vena cava is developed first.
• Downward traction to right kidney
improves the exposure.

139. • Vascular structures, which may be
numerous in highly angiogenic tumors, are
ligated sequentially.
• The adrenal vein is isolated, securely tied,
and divided.
• Loss of control of the adrenal vein stump
may be managed with the application of a
side-biting (Satinsky) vascular clamp.

140. • Open adrenalectomy is generally
performed in cases of suspected or known
malignant disease.
• Locally invasive right-sided adrenal tumors
can be challenging to manage, given their
frequent invasion of adjacent venous
structures.

141. • Locally invaded organs, most commonly
the kidney, should be resected en bloc
with the primary mass.
• Complete radical resection is a critical
determinant of survival in patients with
malignant adrenal tumors; in some cases,
this can be achieved only if immediate
venous reconstruction is performed.

142. • Technical complications
a. venous hemorrhage,
b. tumor embolization in cases with
intravascular tumor extension, and
c. solid-organ injury
d. pleura injury
Postoperative complications are similar to
those associated with other major abdominal
procedures.