2. ANATOMY
-The right and left adrenal glands are located
within Gerota fascia at the levels of the 11th
and 12th ribs.
- The right adrenal is bounded medially by the
inferior vena cava and anteriorly by the liver,
while the left adrenal gland is bounded
medially by the aorta and anteriorly by the
stomach, pancreas, and splenic vessels.
3. -The arterial supply of each adrenal gland may
arise from three main sources: superior
adrenal arteries (branches from the inferior
phrenic arteries), middle adrenal arteries
(direct visceral branches from the aorta), and
inferior adrenal arteries (branches from the
ipsilateral renal artery.
- The short right adrenal vein drains directly into
the vena cava. On the left, the adrenal vein is
long compared with the right and is joined by
the inferior phrenic vein prior to draining into
the left renal vein.
4. HISTOLOGY
Each adrenal gland is enclosed within a fibrous
capsule Directly beneath the capsule is the
cortex, which comprises three zones:
-zona glomerulosa.
- zona fasciculata.
-zona reticularis.
5. -The essential function of the glomerulosa is
the production of mineralocorticoids,
predominantly aldosterone.
-zona fasciculata responsible for the production
of glucocorticoids such as cortisol.
-The zona reticularis, the inner most
layer of the cortex, predominantly produces sex
steroids, such as adrenal estrogens and
androgens .
The medulla secretes epinephrine (80%),
norepinephrine(19%), and dopamine (1%).
6. ADRENAL DISORDERS
Disorders of Increased Adrenal Function
Cushing Syndrome
-Hypercortisolism secondary toexcessive production of
glucocorticoids by the adrenal cortex is defined as
Cushing syndrome.
-The zona fasciculata of the adrenal cortex secretes more than
20 mg of cortisol every day . Regulation of this secretion is
controlled through the hypothalamicpituitary-adrenal (HPA)
axis.
Causes of Cushing syndrome can be divided into
three main groups: (1) exogenous, (2) ACTH-dependent,
and (3) ACTH-independent.
7. ACTH-DEPENDENT CUSHING SYNDROME
-Most cases (80%) are due to bilateral adrenocortical
hyperplasia stimulated by overproduction of pituitary
adrenocorticotropic hormone (corticotropin, ACTH),
known as Cushing’s disease.
-10% of cases are due to the ectopic production of ACTH from
nonpituitary tumors. Ectopic ACTH production occurs most
frequently in small-cell lung carcinoma; other tumors
producing ACTH include carcinoids (lung, thymic,
gastrointestinal tract), islet cell tumors of the pancreas,
medullary thyroid carcinoma, pheochromocytoma,and small-
cell carcinoma of the prostate.
-Adrenal adenoma is the cause in 5% of cases and carcinoma
in 5%.
8. CLINICAL FINDINGS OF CUSHING SYNDROME
1. Obesity (with sparing of the extremities), moon face, and fat pads
of the supraclavicular and dorsocervical areas (buffalo
hump).
2. Striae (red and depressed) over the abdomen and thighs.
3. Hypertension (almost always present).
4. Proximal myopathy with marked weakness, especially
in the quadriceps femoris, making unaided rising from a chair
difficult.
5. Emotional lability, irritability, difficulty in sleeping,
and sometimes psychotic personality.
6. Osteoporosis (common), with back pain from
compression
fractures of the lumbar vertebrae as well as rib fractures.
7. In 80% of cases, postprandial hyperglycemia is
9. -Blood chemical analyses may show an increase in
serum Na+ and CO2 levels and a decrease in serum K+
levels. Hyperglycemia may occur.
1. Specific tests for Cushing’s syndrome
a. 24-hour urinary cortisol level—Urine cortisol is
measured in a 24-hour urine collection (normal range,
10–
50 μg/24 h). A urine cortisol value more than twofold
elevated is typical of Cushing’s syndrome. False-
positive elevations can occur in acute illness,
depression, and alcoholism.
b. Suppression of ACTH and plasma cortisol by
dexamethasone—Dexamethasone in low doses is used to
assess the feedback suppression of ACTH and cortisol
production by glucocorticoids.
10. The procedure is to give 1 mg of dexamethasone by
mouth at 11 pm and to draw blood at 8–9:00 am for
measurement of plasma cortisol. If the level is <5
μg/dL (normal is 5–20 mg/dL), Cushing’s syndrome
can be ruled out. If the value is >10 μg/dL,
Cushing’s syndrome is present.
2. Specific tests for differentiation of causes of
Cushing’s syndrome
a. Plasma ACTH level b. Plasma androgen levels
11. TREATMENT
A. CUSHING’S DISEASE
A pituitary microadenoma, which is the most
common cause of bilateral adrenocortical
hyperplasia, must be located and removed
surgically. Transsphenoidal resection.
12. THE HYPERTENSIVE, HYPOKALEMIC
SYNDROME (PRIMARY
ALDOSTERONISM)
Etiology:
A- benign unilateral adrenal adenoma
(Conn’s Syndrome) [Most Common
Cause].
B-Unilateral or Bilateral hyperplasia of
adrenals.
C-Adrenal carcinoma (rare).
Signs and symptoms :Hypertension
(typically moderate and diastolic)
Hypokalemia Polyuria Muscle weakness
Fatigue Headache
13. LABORATORY FINDINGS
Aldosterone to Plasma Renin Assay ratio:
# If ratio < 24 – excludes primary
aldosteronism.
# If ratio >30 Order 24-hour urine collection
which is assayed for aldosterone, free
cortisol,
and creatinine.
#Low PRA (< 5mcg/L/h) with an elevated urine
aldosterone (>20 mcg/24h) indicates primary
aldosteronism .
14. LOCALIZATION
CT scan is the initial procedure and will
localize an adenoma in approximately 90% of
patients. If no adenoma is visualized,
adrenal vein sampling of aldosterone and
cortisol will correctly differentiate adenoma
from hyperplasia in virtually all cases.
15. TREATMENT
#Unilateral Adenoma – laparoscopic surgical
excision.
#Bilateral hyperplasia (and pt who don’t want
surgery for adenoma):
A-Dietary sodium restriction.
B-Spironolactone (aldosterone antag).
16. PHEOCHROMOCYTOMA
DEFINITION: catecholamine-producing tumor
derived from the sympathetic and
parasympathetic nervous system, usually
located in the adrenal gland .
Pheo = Dusky Chromo = Color Cytoma = Cell
Tumor
The name refers to the color the tumor cells
acquire when stained with chromium salts
17. EPIDEMIOLOGY
-Rare Occurs in 2-8 out of 1 million persons/ yr
-< 0.1% of hypertensive patients harbor a
pheochromocytoma.
-Mean age at diagnosis is 40 years
18. SIGNS AND SYMPTOMS
#Classic triad Episodes of headache, profuse
perspiration, and palpitations.
#Hypertension in is the dominant sign May be
sustained or episodic.
#MEN 2
LOCALIZATION :
ADRENAL 90% EXTRAADRNAL 10%
20. PHEOCHROMOCYTOMA IMAGING STUDIES
CT SCAN
MRI( METHOED OF CHIOC TO LOCALAIZ
PHEOCHROMOCYTOMA)
MIBG (metaiodobenzylguanidine):-
(1) small lesions, (2) extraadrenal
lesions, (3) bilateral lesions, and (4)
metastatic
deposits in patients with malignant tumors.
21. DIAGNOSTIC STRATEGY
#Patients in whom there is a high index of clinical suspicion
and those who have a greater than twofold elevation of
urine catechols should undergo an adrenal CT scan.
#If the CT scan reveals a unilateral tumor and the
contralateral adrenal is normal, the diagnosis is established.
#Patients with familial syndromes and those in whom cancer
is suspected should undergo MIBG scanning to determine
the extent of disease.
#If the adrenal CT is negative, MIBG scanning or MRI of the
chest and abdomen is indicated to localize the tumor. This
approach localizes virtually all tumors.
#If the clinical suspicion is low and urine catechols are
normal, imaging procedures are not indicated.
22. THERAPY
A. PREOPERATIVE MANAGEMENT
#Once the diagnosis of pheochromocytoma is established,the patient sho
be prepared for surgery to reduce the incidence of intraoperative
complications and postoperative hypotension.
#alpha-adrenergic blocker phenoxybenzamine, and
its use has minimized surgical mortality and morbidity, The initial dosage i
mg twice daily.
#The dose may then be titrated upward every 2–3 days over several week
until the blood pressure is <160/90 mm Hg and symptoms are abolishe
#Metyrosine (alpha-methylparatyrosine), an inhibitor of catecholamine
synthesis, is also useful for preoperative management although current
experience is limited. Initial dosage is 250 mg every 6 hours, and total d
dosages of 2–4 g are required. Preoperative treatment for 1–2 weeks
appears to be sufficient to prevent operative complications.
23. B. SURGERY
#Intraoperatively, hypertension is controlled with
nitroprusside, and antiarrhythmics are used as needed.
#If CT and MIBG show only a solitary adrenal lesion in
patients with sporadic disease, a unilateral
laparoscopic approach may be used.
#Bilateral or malignant disease may require a
transabdominal approach, and even if total resection
is not feasible, debulking of tumor mass facilitates
subsequent medical management of catecholamine
excess.
24. MALIGNANT PHEOCHROMOCYTOMA
#All patients should undergo serial follow-up to
detect early recurrences.
#Despite encouraging reports of chemotherapy
or 131I-MIBG therapy, it appears that only a
minority of patients have sustained
remissions.
25. INCIDENTALOMA
#The most common presentation of adrenal masses is incidental observation
on cross-sectional imaging performed for other reasons.
Differential Diagnosis of Adrenal Incidentaloma:
-Adenoma
-Metastasis
-Lymphoma
-Pheochromocytoma
-Neuroblastoma
-Adrenocortical carcinoma
-Hematoma
-Myelolipoma
-Adrenal hyperplasia
-Adrenal cyst
-Granulomatous disease.
#systematic approach is required to differentiate functional adrenal masses
that deserve removal and those lesions with a significant risk of carcinoma
from the more common benign nonfunctional adenoma.
26. IMAGING
#Lesions that are primarily cystic on CT or MRI are typically
benign and can be followed with serial imaging.
#Benign adrenal cysts are characterized by thin
nonenhancing walls; fluid attenuation on CT and thin
calcifications may be present peripherally in about 50%.
#Characteristics suspicious for malignancy include solid
masses that are large, hemorrhagic, or necrotic. MRI is
usually heterogeneous on T1- and T2-weighted images
due to internal bleeding.
#Masses with gross fat on CT (Hounsfield unit [HU]
<30) are myelolipomas , benign nonfunctional
adrenal lesions with lipid and myeloid components.
Myelolipomas are usually asymptomatic or present with
pain if they bleed.
27. DIAGNOSTIC ALGORITHM
#Percutaneous CT-guided biopsy may be
appropriate for adrenal masses with imaging
characteristics suspicious for metastasis or in
patients with known malignancy.
#All functional adrenal masses and those >5 cm
should be removed.
#Laparoscopic adrenalectomy is the preferred
technique andis used in most cases except
very large masses suspicious for malignancy
or with evidence of local extension.
28. #Nonfunctional adrenal masses <5 cm should
be assessed for radiographic features
concerning for malignancy and removed if
they are irregular or hemorrhagic or have
demonstrated growth.
#Those <3 cm can generally be followed up with
serial CTs every 6 months initially, then yearly
if
stable.
29. DISORDERS OF DECREASED
ADRENAL FUNCTION
Adrenal insufficiency (addisonian state)
Causes of adrenal insufficiency.:
Primary:
-Infectious adrenalitis (e.g., tuberculosis)
-Autoimmune adrenalitis.
-Adrenal infiltration (e.g., metastasis,sarcoidosis)
-Bilateral or pharmacologic adrenalectomy
-Bilateral adrenal infarction/hemorrhage.
Secondary:
-Congenital ACTH deficiency.
-Pituitary abnormality.
-Hypothalamic abnormality.
30. CLINICAL CHARACTERISTICS
#Clinical signs and symptoms of Addison
disease are generally nonspecific.
#pt may co fatigue and anorexia.
#Hyperpigmentation, a hallmark of primary
adrenal insufficiency, results from high serum
concentrations of ACTH in response to
increased hypothalamic release of
proopiomelanocortin (POMC)-derived
peptides that stimulate the
melanocortin (MC-1) receptor of the skin.
31. #Acute adrenal insufficiency, or adrenal crisis,
is a lifethreatening condition often preceded
by hypotension unresponsive to fluid
resuscitation. Patients are easily and often
misdiagnosed with an acute abdomen,
whereas abdominal pain, nausea, vomiting,
and fever frequently
accompany hypovolemia in these individuals.
Pediatric patients can exhibit hypoglycemic
seizures.
#Adrenal insufficiency (an addisonian state)
following
adrenalectomy in the setting of a normally
functioning contralateral adrenal gland is
unlikely, but possible.
32. TREATMENT
The treatment of Addison disease involves
adrenal hormonal repletion. Cortisol is
replaced with hydrocortisone (15 to 25 mg
per day) or with cortisone acetate (25 to 37.5
mg per day).
33. CONGENITAL ADRENAL HYPERPLASIA
disorder that is characterized by low cortisol
production due to a metabolic enzymatic
abnormality in the cholesterol-steroid biosynthesis
pathway.
#The disorder is autosomal recessive and
associated with a deficiency in the enzyme 21-
hydroxylase in over 95% of cases.
#In the absence of negative feedback, ACTH
production by the pituitary is increased, resulting
in hyperplasia of the adrenal cortex and
overproduction of adrenal androgens.
#high propensity for developing benign adrenal
cortical adenomas.
34. ADRENAL LESIONS
:Malignant
Adrenal Carcinoma
Epidemiology:
#is a rare malignancy with an incidence of 0.5
to 2 per million.
#peaks in children in the first decade of life and
adults in the fourth to fifth decades of life.
#slight female predominance.
#The majority of ACCs are sporadic and
unilateral.
35. PATHOPHYSIOLOGY
Two hereditary disorders, Li-Fraumeni
and Beckwith-Wiedemann syndrome, have
provided valuable insight into the
tumorigenesis of sporadic ACC.
#squamous cell carcinoma–related oncogene
(SCCRO),
#Inhibin or activin,epidermal growth factor
receptor,
# vascular endothelial growth factor (VEGF).
36. CLINICAL CHARACTERISTICS
Incidental detection of adrenal cortical carcinoma has
increased with the routine use of cross-sectional imaging.
#The majority of patients still present with
advanced disease and tumor-related symptoms.
#The most common hormone secreted by adrenal cortical
carcinoma is cortisol, resulting in the clinical
manifestations of Cushing syndrome.
#Androgen-secreting tumors in women can lead to
virilization.
#hypersecretion of aldosterone is rarely associated with
ACC, when present, it is associated with profound
hypertension and hypokalemia.
#Nonfunctional ACC may present with more generalized
tumor related symptoms, such as abdominal fullness, back
pain, nausea, vomiting….
37. DIAGNOSTIC TESTS#When considering the functional status of a tumor suspicious for adrenal cortical
carcinomas, glucocorticoid, mineralocorticoid,
catecholamine, sexual steroid, and steroid precursor excesses should be evaluated.
#Functional Evaluation of Adrenal Tumors Suspicious for Adrenal Cortical Carcinoma
TYPE OF ADRENAL
HYPERSECRETION FUNCTIONAL EVALUATION
Glucocorticoid excess Low-dose dexamethasone suppression test Or
Late night salivary
or 24-hour urine cortisol
Sexual steroids and
steroid precursors
DHEA-S 17-OH-progesterone
Androstenedione
Testosterone 17β-estradiol (only in men and
postmenopausal
women)
Catecholamine excess Serum or urinary metanephrines
Mineralocorticoid excess
Aldosterone to renin ratio (only in patients
with hypertension or hypokalemia
38. #On cross-sectional imaging, adrenal cortical
carcinomas tend to be larger than benign adrenal
tumors with an average size of 10 to 12 cm on
presentation. Indeed over 90% of ACCs are greater
than 5 cm.
#Common radiographic characteristics of adrenal
carcinomas on CT imaging include the presence
of irregular borders, irregular
enhancement,calcifications,
and necrotic areas with cystic degeneration.
Mean attenuation on noncontrast CT scan in ACC is
significantly higher (39 HU) compared with
adenomas
(8 HU).
39. MRI provides valuable information when
evaluating adrenal tumors. ACCs appear
isointense relative to the liver or spleen on
T1-weighted images.
detecting the presence of a tumor clot and
delineating its extent.
FDG PET SCAN.
40. PATHOLOGIC EVALUATION
Weiss Pathologic Criteria for Differentiating
Benign and Malignant Adrenal Tumors
High nuclear grade (Furman grade 3 to 4)
High mitotic rate (greater than 5 mitoses per HPF)
Presence of atypical mitoses
Character of cytoplasm (low percentage of clear cells)
Diffuse architecture of tumor cells
Presence of necrosis
Invasion of venous structures
Invasion of sinusoidal structures
Invasion of tumor capsule
41. STAGING
Staging of Adrenocortical Carcinoma Including
Stage at Diagnosis and 5-Year Survival Data
STAGE WHO AT DIAGNOSIS 5-
YEAR SURVIVAL
1 T1N0M0 3%-4%
33%-66%
2 T2N0M0 29%-46% 20%-
58%
3 T1-2N1M0
T3N0M0 11%-19%
18%-24%
4 T1-4N0-1M1
T3N1M0
T4N0-1M0 39%-49%
<5%
42. MANAGEMENT.
#Despite aggressive surgical resection, adrenal
carcinoma is associated with a high rate (60% to 80%)
of recurrent disease.
#radiation therapy remains the treatment of choice in the
management of bone and CNS metastasis.
#Adjuvant radiation has been noted to decrease local
recurrence rates following complete tumor resection.
MEDICAL THERAPY: Mitotane is an oral synthetic
derivative of
the insecticide dichlorodiphenyltrichloroethane (DDT)
and is the most commonly used chemotherapeutic
agent in the treatment of adrenal cortical carcinoma.
43. METASTASES
over 25% of patients with melanoma and
lung carcinoma have metastases to their
adrenals.
44. BENIGN
Adenoma
Epidemiology:
Adenomas are the most common
neoplasms arising from the adrenal gland and are
most often associated with the cortex.
-The incidence of adenomas rises with age.
-The essential evaluation of the small adrenal mass
requires differentiating the nonfunctional benign
adenoma from functional or malignant lesions.
45. PATHOPHYSIOLOGY AND CLINICAL
CHARACTERISTICS.
-Adrenal adenomas are by definition benign and the
vast majority are metabolically silent.
-pathologists use a set of criteria proposed by Weiss
along with modern immunohistochemical methods to
differentiate the two clinical entities
46. DIAGNOSTIC TESTS.
The goal in evaluating any adrenal lesion is twofold:
(1) rule out the possibility of malignancy and
(2) document metabolic inactivity of the lesion in
question.
#Noncontrast CT scan is arguably the most
valuable
imaging study for the diagnosis of an adrenal
adenoma.<10 HU.
#incidentalomas are evaluated for excess cortisol
and catecholamine secretion. In patients with
history of hypertension, hyperaldosteronemia also
47. TREATMENT
#Adenomas that are metabolically active should
undergo resection in acceptable surgical
candidates.
#In patients with nonfunctional adenomas, the size
of
lesion and its growth characteristics dictate
management.
48. ONCOCYTOMA
-It’s a very rare tumor.
-histologically oncocytic adrenal lesions are
characterized by mitochondria-rich, large,
eosinophilic cells with abundant granulations.
- Most lesions that are are metabolically
inactive.
- proportion of lesions can exhibit malignant
potential.
49. MYELOLIPOMA
-Myelolipoma is a rare lesion of the adrenal
gland that contains hematopoietic elements
and
mature adipose tissues.
-Surgery is indicated only for
extremely large or symptomatic lesions.
51. ADRENAL CYSTS
Epidemiology
-account for 1% to 5%.
- Cystic adrenal lesions can be diagnosed
throughout
life and as early as the prenatal period.
-range from mm to greater than 20 cm.
- majority of adrenal cysts are unilateral.
-women > men .
52. PATHOPHYSIOLOGY.
Four histologic types of adrenal cysts:
-pseudocysts: the most common and result from
previous intra-adrenal hemorrhage or infarction.
-endothelial: lymphangiomatous and angiomatous
subtypes.
-epithelial: characterized as glandular and embryonal cysts.
- parasitic cysts:associtd with Echinococcus infections.
