Anatomy & Physiology

Relations
☻☻Right adrenal gland:
** Anterior surface:
Superior: "bare area" of the liver
Medial: inferior vena cava
Lateral: "bare area" of the right lobe of the liver
Inferior: peritoneum (very rarely) and first part of the duodenum
** Posterior surface:
Superior: diaphragm
Inferior: anteromedial aspect of the right kidney

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☻☻Left adrenal gland:
** Anterior surface:
Superior: peritoneum (posterior wall of the omental bursa) and stomach
Inferior: body of the pancreas
** Posterior surface:
Medial: left crus of the diaphragm
Lateral: medial aspect of the left kidney

Site & Shape

☻☻The Right Suprarenal Gland:
• It is pyramidal-shaped, capping the upper pole of the right kidney.

☻☻The left Suprarenal Gland

• It is crescentic in shape, lies along the medial border of the left kidney,
from the upper pole to the hilum

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☻☻Arterial supply:
• Superior suprarenal artery→ branch of inferior phrenic
• Middle suprarenal artery → branch of aorta.
• Inferior suprarenal artery→ branch of renal artery

☻☻Venous drainage:-
• The veins of the right gland drain into the inferior vena cava.
• The veins of the left gland drain into the left renal vein.

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☻☻Lymphatic drainage:-

Congenital anomalies
1- Agenesis of the Adrenal Glands:-
- Unilateral adrenal agenesis is almost always associated with renal
agenesis on the same side, but in 90 % of patients with unilateral
renal agenesis, the adrenal gland is present.
- Absence of the kidney is usually the result of defective ureteric bud
development, which does not affect the adrenal gland. Only a failure of
formation of the entire nephrogenic ridge results in the absence of both
the kidney and the adrenal gland.
2- Fusion of the Adrenal Glands:-
Fusion of the adrenal glands behind the aorta may accompany fusion
of the kidneys (horseshoe kidney).
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3- Hypoplasia of the Adrenal Glands:-
- Usually lethal in infancy as it usually associated with anencephalic

4- Adrenal Heterotopia:- (abnormal site)

a- beneath the capsule of the kidney → adrenorenal heterotopia
b- Beneath the capsule of the liver → adrenohepatic heterotopia
c- Near or on aorta
d- Others → see picture

5- Accessory Adrenal Tissue:-

- Small nodules of adrenal tissue may be found throughout the abdomen
- May be accessory cortical or accessory medullary tissue or both (true
accessory adrenal gland)
- They are usually found near the aorta, between the origin of the celiac
axis and that of the superior mesenteric artery

A- Accessory cortical tissue:-

* They are found under the renal capsule, in the broad ligament in the
female or in the spermatic cord of the male.
* These sites have surgical significance when the suspected lesion is not
found within the substance of the normally situated adrenal glands. All
these cortical structures are as susceptible to adenomas as is the normal
adrenal gland

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 B- Acessory Medullary (chromaffin) tissue:-
* Chromaffin tissue normally distributed around the aorta near the origin
of the inferior mesenteric artery, in the lumbar sympathetic chain, and in
and about the celiac plexus
* Such tissue represents chromaffin cells from the neural crest that were
not incorporated into the adrenal medulla.
* The largest of these are the paraaortic bodies (organs of Zuckerkandl) →
they regress in size with age.
* These structures may be sites of pheochromocytomas in childhood.
* They may also be sites of "nonfunctioning" paragangliomas with no
clinical evidence of hormonal activity.
* Medullary (chromaffin) tissue outside the normal adrenal gland is much
more frequently found than is cortical tissue, and is more frequently
associated with hyperfunction than is cortical tissue.

Medullary rests

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6- Adrenal Gland Hemorrhage:-
- It is the second most common source of hemoperitoneum in newborns.
- The right side is involved in 70% of cases, the left in 25%; the condition
is bilateral in 5%.
- This phenomenon has several etiologic factors. The large size of the
neonatal adrenal gland makes it vulnerable to traumatic injury. Involution
of the inner fetal cortical zone leaves central vessels unsupported.

7- Neuroblastoma:- see after

8- Adrenal Cyst:-
Dermoid cyst of the adrenal gland has been reported

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 HYPOADRENALISM
♣♣ Definition:
Inadequate glucocorticoid and mineralocorticoid production by the adrenals
♣♣Etiology:
I. Primary adrenal atrophy (Addison’s disease)
(Due to disease of adrenal cortex)
1. Congenital adrenal hypoplasia
2. Traumatic: bilateral adrenalectomy
3. Inflammatory: tuberculosis.
4. Neoplastic: metastases.
5. Vascular:
- Bilateral adrenal hemorrhage in septicemia and anticoagulant therapy
- Bilateral adrenal vein thrombosis.
6. Autoimmune adrenalitis (most common).
7. Metabolic: sarcoidosis, amyloidosis, and hemochromatosis.
8. Drugs: metyrapone, aminoglutethimide.

II. Secondary adrenal atrophy

(Due to failure of ACTH stimulation of adrenal cortex)
1. Hypothalamic or pituitary disease (Simmond’s disease):
- Traumatic: head trauma
- Inflammatory: tuberculosis, syphilis, and encephalitis
- Neoplastic: primary or secondary
- Vascular: Infarction due to postpartum hemorrhage
(Sheehan’s syndrome) and pituitary apoplexy
- Metabolic: sarcoidosis.
2. Hypophysectomy
3. Prolonged therapy with corticosteroid drugs.

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♣♣ Clinical features:
1. Asthenia: marked muscle weakness, and loss of weight due to:
- Decrease aldosterone (hyperkalemia & hyponatremia).
- Decrease cortisol (hypoglycemia).
- Decrease androgen (negative nitrogen balance).
2. Hypotension:
- Due to decrease aldosterone & cortisol (hyponatremia & hypovolaemia)
3. Hypoglycemia:
- Due to decrease cortisol.
→ Drowsiness, lack of concentration, hunger pain up to coma
4. Hyperpigmentation of skin and mucos membrane.
- Due to increase of ACTH (by feed back) → over production of MSH.
- Sites: →Sun exposed area: face, neck, and chest.
→Friction areas: elbows, trochanters.
→Pigmented areas: areola.
→Scars: umbilicus, operative scars.
→Mucos membrane: mouth, tongue.
5. GIT upset:
 Anorexia, nausea and vomiting.
 Vague abdominal pain.
 Diarrhea.
6. Infertility in male and amenorrhea in females:
Due to associated autoimmune gonadal failure
7. Other features:
-Polyuria due to sodium diuresis.
-Tender renal angle in TB.
-Autoimmune manifestation: vitiligo, pernicious anemia.
-Adisonian crisis

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♣♣ Investigations
I. Laboratory:
A- For diagnosis of disease:
1- Plasma cortisol level: low (N=5-20 ug%).
2- Urinary 17-oxygenic steroids: low (N= 5-20 mg/day).

B- For effect of disease:

1- Biochemical changes: ↓ Na and glucose & ↑ K.
2- Urine: high Na, low K.
3-Blood:
* Normocytic normochromic anemia, neutropenia.
* Lymphocytosis and esinophilia.

C- For cause of disease

1- Plasma ACTH level (N =10-100 pg%).
- High in 1ry adrenal failure.
- Low in 2ry adrenal failure.
2-ACTH stimulation test:
ACTH 40U IV or IM & plasma cortisol levels are estimated at 0
and 30 min.
- In 1ry failure: plasma cortisol remains low.
- In 2ry failure: plasma cortisol rises.
3- Antibodies against adrenal gland.

II. For localization

X-ray, CT and MRI: adrenal calcification in TB.

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♣♣ Treatment:
1- Treatment of cause: anti TB drug for TB.

2- Diet rich in protein, carbohydrate. Increase Na in diet but restrict K.

3- Replacement therapy:
- Oral cortisol (hydrocortisone) which is increased during
stress, trauma, operation, and infection.
- Mineralocorticoid is added if BP is still low.

4- Treatment of Addisonian crisis

a. Treatment of cause: proper management of infection.
b. Fluids:
- Infusion of 4 liters of physiological saline in 24 hours.
- Hypoglycemia treated with intravenous dextrose.
c. Drugs:
- Hydrocortisone sodium succinate IV, 20 mg immediately and 100
mg/ 6h.
- Mineralocorticoid as deoxycorticosterone, 10 mg IM should be
given.

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 ADRENAL TUMORS
A. Primary:
I. Tumors of the adrenal cortex:
A-Epithelial:
1- Adenoma
i. Non functioning adenomas
ii. Functioning adenomas producing the following→
- Cushing’s syndrome.
- Conn’s syndrome
- Adrenogenital syndrome
- Virilizing and feminizing syndrome.
2- Adrenocortical carcinoma (0.02%).

B-Connective tissue: angiofibrolipoma.

II. Tumors of the adrenal medulla (neuroendocrinal tumors):

i. Tumors of chromaffin cells → Pheochromacytoma.
ii. Tumors of the sympathetic neurons:
- Benign: neurofibroma & ganglioneuroma
- Malignant: neuroblastoma & ganglioneuroblastoma.

B. Secondary:
From carcinoma of breast (most common), lung, melanoma, lymphoma,
kidney and ovarian carcinoma

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 HYPERCOTISOLISM
(CUSHING SYNDROME)
♣♣ Definition:
It is a physiologic state of glucocorticoid excess.
♣♣ Etiology:
A. Exogenous:
Iatrogenic "Cushingoid’s syndrome": (most common) due to
chronic administration of glucocorticoids to organ transplant
recipient or patients with immune disorders.
B. Endogenous:
I. ACTH non-dependent
Adrenal Cushing’s syndrome due to primary adrenal disease as
adenoma, adenocarcinoma, or micronodular adrenal hyperplasia
II. ACTH dependent
1. Pituitary ACTH secreting adenoma or micro adenoma (Cushing’s
disease)
2. Ectopic ACTH production mainly from carcinoma of the lung
(particularly non-small cell lung carcinoma, bronchial carcinoid,
pheochromocytoma, thymoma and medullary carcinoma of the
thyroid)

♣♣Pathology
* N/E: the tumors are small, rounded and well encapsulated
* M/E:
- 90% benign adrenal adenoma
- 9% bilateral adrenal hyperplasia
- 1% adrenocortical carcinoma.

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♣♣ Clinical picture:
* Type of patients: usually affects females of middle age.
* Symptoms and signs:
1. Disturbed CHO metabolism: hyperglycemia + DM (steroid diabetes)
2. Disturbed protein metabolism:
- Skin: rupture of week collagen fibers → thinning of skin, stria rubra
- Muscle: myopathy with wasting.
- Bone: osteoprosis
3. Disturbed fat metabolism:
- Face: moon face, with fish mouth.
- Interscapular area: hump at the back of neck (buffalo hump).
- Trunk: trunkal obesity→ (The limbs are thin giving the patient
appearance of a lemon on match sticks)
4. Disturbed water and electrolyte balance:
- Hypernatremia → hypertension.
- Hypokalemia with polyuria and polydipsia.
- Alkalosis & tetany.
5. Androgenic manifestation:
a. In females: amenorrhea, hirstium, and acne.
b. In males: excess body hair, boldness, later on, decrease libido
6. Anti-vitamin D:
Osteomalacia with impaired growth in children (cortisol block
ability of GH to produce somatomedin → a hepatic peptide
responsible for bone growth)
7. Erythropoiesis: polycythemia, plethoric face, which become crimson
red in hot weather and cyanosed in cold weather
8. Decrease response to stress.
9. Depression

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♣♣ Investigation
I. Laboratory:
A- For diagnosis of disease:
i. Plasma cortisol level:
- Earliest loss of circadian rhythm.
- Later, persistent high level occur (N= 5-20 ug%).
ii. Urinary free cortisol or 17-oxygenic steroids (N=5-20mg/day): ↑
iii. Low dose dexamethazone suppression test:
A dose of 1-mg dexamethazone is given orally at 11 PM and
plasma cortisol is obtained at 8 AM the following day.
- Normal individuals suppress cortisol to < 5 ug%.
- Patient with Cushing syndrome fail to suppress to < 5 ug%.
B- For effect of disease:
i. Biochemical: ↑ Na, and glucose & ↓ K
ii. Urine: ↓ Na & ↑ K.
iii. Blood:
- Polycythemia, neutrophilia,
- lymphocytopenia and esinopenia.
C- For etiology of disease:
i. Plasma ACTH by immunoradiometeric (10-100 pg%):
- Increased in pituitary Cushing and ectopic ACTH tumor.
- Decreased in adrenal tumor.
ii. High-dose dexamethazone suppression test:
A dose of 2-mg dexamethazone is given orally/ 6 hours for 2 days, and
24-hour urine collection for free cortisol is taken in the 2nd day.
- Hypercortisolism caused by pituitary adenomas are partially or
completely suppressed
- Hypercortisolism caused by ACTH secreting adenomas are not suppressed

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II. Localization of the lesion:
* Adrenal tumors
1- Ultrasonography gives details if the adrenal tumor is large.
2-CT scan detects bilateral nodular hyperplasia.
3- MRI detects small adrenal lesions and these are benign or malignant.
4- Iodocholesterol scintigraphy
5- Selective angiography
6- Selective venous sampling for cortisol from adrenal veins.

* Pituitary tumors
1-MRI: shows pituitary tumors with details of suprasellar or chiasmic extension
2- CT scans of the pituitary fossa.
3-Selective venous sampling for ACTH from veins draining pituitary
inferior petrosal veins

* Ectopic ACTH production:

X-ray, CT and MRI chest and mediastinum

♣♣ Treatment
1- Adrenal Cushing syndrome:
- Adrenalectomy of the affected side.
- Because of contralateral adrenal gland inhibition, the patient needs
postoperative administration of cortisol which is tapered gradually with
return of adequate function.

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2. Pituitary (Cushing’s Disease)
a. Transphenoidal excision of adenomas (the treatment of choice).
The operation preserves the function of the rest of the gland.

b. If the adenoma is so small to detect, implantation of radioactive

yttrium- 90 is the alternative treatment.

c. Medical adrenalectomy: Metopyrone (inhibitor of 11 -beta-hydroxylase),

aminoglutethimide (blocking the formation of pregnenolone from
cholesterol) and mitotane

d. Bilateral surgical adrenalectomy is rarely done nowadays for cases not

responding to above measures.

3- Ectopic ACTH secretion:

a. Removal of the primary tumor may be curative.
This is only usually if the tumor is a benign carcinoid or pancreatic tumor.

b. Medical adrenalectomy:

c.. Bilateral surgical adrenalectomy is rarely done nowadays for cases not
responding to above measures.

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 HYPERALDOSTERONISM
♣♣ Definition:
It is a physiologic state of aldosterone excess

♣♣ Etiology:
1. Primary hyperaldosteronism with suppressed renin (Conn’s syndrome):
Due to presence of a functioning adrenal cortical hyperplasia,
adenoma and carcinoma
2. Secondary hyperaldosteronism with increased renin:
a. Renal diseases: renal artery stenosis, renin-secreting renal tumor
(Bartter’s syndrome)
b. Liver disease: cirrhosis
c. Cardiac disease: CHF.
d. Drugs: loop diuretics, purgatives (hypokalemia)

♣♣ Pathology
** N/E
- The tumors are small, rounded and well encapsulated
- The cut surface is golden yellow in color.
** M/E :
- 60% a benign adrenal adenoma
- 40% bilateral hyperplasia
- Very rarely an adrenocortical carcinoma is present.

♣♣ Clinical picture
* Type of patients: usually affects females of middle age.

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* Symptoms & signs:
1-Hypertension (the main feature):
- Is due to salt and water retention.
- It may be mild (asymptomatic) or severe (malignant hypertension).
- It is associated with hypokalaemia and not responding to
antihypertensives.
2-Hypokalaemic alkalosis → muscle weakness, tetany, polyuria & polydypsia

♣♣ Investigations
I. Laboratory:
A- For diagnosis of disease
a. Elevated levels of plasma aldosterone (> 20 ng% is diagnostic)
b. Elevated levels of urinary aldosterone.
B- For effect of disease
a. Biochemical: Na may be ↑ or normal and hypokalaemia (98%)
b. Urine: High urinary excretion of potassium
C- For cause of disease:
Elevated plasma aldosterone concentration /plasma renin activity > 30
is diagnostic of 1ry hyperaldosteronism.

II. Localization
a. Ultrasonography
b. CT scanning (the best test)
c. MRI → solid or cystic - benign or malignant
d. 131lodine-6-beta-iodomethyl-19-nor-cholesterol (NP59) scintigraphy →
localization & distinguish between adenoma and hyperplasia.
e. Selective angiography.

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f. Selective venous sampling for aldosterone determination.
♣♣ Treatment
A- Adrenal adenoma:
i. Preoperative control of the blood pressure and hypokalaemia using:
- Aldosterone antagonists: spironolactone.
- Non aldosterone antagonists: amiloride.
- ACE inhibitor: captopril which blocks aldosterone synthesis.
- Metopyrone (11-beta hydroxylase blocker): ↓ aldosterone synthesis.

ii. Surgical adrenalectomy.

B- Adrenal hyperplasia:
Medical treatment because < 20%-30% of patients with this disease
are cured by adrenalectomy

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 Congenital Adrenal Hyperplasia
♣♣ Definition:
It is an autosomal recessive disease due to inherited defects of one
or more of the enzymes necessary for cortisol biosynthesis.
♣♣ Etiology:
** Cortisol deficiency → ACTH over production → 2ry hyperplasia of adrenal
cortex with shunting of cortisol precursors into adrenal androgen pathway.
** Peripheral tissues convert the excess adrenal androgens to testosterone,
which causes virilisation of the patient.

A- > 90% of congenital adrenal hyperplasia is due to deficiency of 21-

hydroxylase enzyme due to mutation of the gene on the short arm of
chromosome 6.
** 2 forms 21-hydroxylase enzyme deficiency are recognized:
a. Complete form:- which is characterized by androgen excess at
birth, with virilisation, hypovolemia, hyponatremia, hyperkalemia,
and hyperpigmentation.
b. Partial form:- which is characterized by androgen excess at
adolescence or adulthood with virilisation only.

B- < 10% of congenital adrenal hyperplasia is due to deficiency of 11-beta

hydroxylase enzyme, 17-hydroxylase and 3-beta-hydroxydehydrogenase enz.

♣♣ Pathology:
** N/E:
Enlargement of the adrenals, which reach 10-20 times their normal weight
** M/E:
Simple hyperplasia, adenoma and less commonly adenocarcinoma
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 ♣♣ Clinical picture:
It depends according to the age and sex of the patient:

Age
Male
Prenatal Premature enlargement of sex
Female > organs (Macrogenitoroma precox) born baby is genetically a
male
Prepubertal Precocious puberty (the child
Male > show rapid appearance of 2ry sex
female characters by the age of 2-3 years,
increased potency, muscle
strength “infant Hercules”
premature closure of epiphysis
and testicle is small because its
size depends on G.H. “false
puberty” → infertility
Postpubertal Feminization and obesity
Female >
male
Sex
female
Pseudohermaphroditism (the
female, has fallopian tube,
ovaries and uterus but the
external genitalia resembles
those of a male e.g. big clitoris
like penis and big 2 labia
majora like scrotum.
Primary amenorrhea with
delayed or no puberty
Virilism , 2ry amenorrhea,
polycystic ovaries,
psychological trouble and sex
aberration

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♣♣ Investigations
1. Laboratory:
a. Elevated levels of plasma 17-hydroxyprogesterone.
b. High urinary excretion of its metabolite “pregnanetriol”.
c. Plasma cortisol and 24 hour free urinary cortisol excretion: reduced

2. Localization: as Conn’s syndrome

♣♣ Treatment
- Hyperplasia: glucocorticoid and mineralocorticoid replacement.
- Correct abnormalities of the external genitalia.

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 Virilizing and feminizing adrenal tumors

1. Virilizing adrenal tumors

♣♣ Etiology:
Excess production of adrenal androgens by an adrenal adenoma or
carcinoma can produce virilizing features + Cushing syndrome.
♣♣ Clinical picture:
A- Women → Virilism
1. Hirsutism: excessive growth of hair in women outside the sites usually
associated with female hair growth. (The cheeks, upper lip, chin, chest,
breast areolar, limbs & the linea alba)
2. Musculanization
3. Male pattern of hair loss from the head
4. Deepening of the voice
5. Acne
6. Enlargement of the clitoris.
B- Man → abdominal pain, mass, and distant metastases.

♣♣ Investigations:
1. Laboratory:
Plasma testosterone and de-hydro-epi-androsterone (DHEA) are elevated.
2. Localization: as Conn’s syndrome.

♣♣ Treatment:
A- Localized, resectable→ excision
B- Metastatic, resectable→ tumor debulking and excision of metastases.

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C- Metastatic, non resectable→ aminoglutethimide or mitotane.
2. Feminizing adrenal tumors
- Feminizing tumors are very rare and are almost always malignant.
-In men they are present with gynecomastia and impotence before they
have metastasized and curative resection may be possible but in women
they tend to be advanced when 1st detected.

Adrenocortical Carcinoma
♣♣ Etiology:
Mutation of tumor suppressor gene p53 (Li-Fraumeni syndrome)

♣♣ Pathology
** N/E:
-The tumor has a very large size (>20 cm), lobulated and encapsulated
- Cut section: areas of hemorrhagic necrosis.

** M/E:
It is difficult to differentiate between a benign adenoma and a well
differentiated carcinoma on the basis of cellular characteristics alone but it
depends on:
1. Size of tumor > 6 cm. 2. Presence of capsular invasion.
3. Mitosis > 1/10HPF 4. Presence of vascular invasion.
5. DNA aneuoploidy.

** Spread:
1. Local: Intrinsic or Extrinsic → invade local structures such as the pancreas,
kidney, and bowel
2. Lymphatic: to the local lymph nodes.
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3. Blood: liver, lungs, or less commonly bone
♣♣ Clinical Picture:
* Type of patients: female > male, 50-70 years (no age is immune)
* Symptoms & signs:
1. The non-functioning tumors (40%):
a. Abdominal mass.
b. Abdominal pain, fever, and weight loss.
2. Functioning tumors (60%)
a. Symptoms and signs of hypercortisolism.
b. Symptoms and signs of aldosterone excess is rare.
c. Symptoms and signs of virilizing and feminizing adrenal tumor in
adult.

♣♣ Investigations:
I. Laboratory:
I. Functioning carcinoma:
To detect excess of cortisol, aldosterone, androgen and estrogen (see before)
II. Non-functioning carcinoma: → no hormonal excess.

II. Localization:
a. Ultrasonography
b. CT scanning (the best test): large mass > 6 cm adrenal mass that extends
to nearby structures is considered malignant until proved otherwise.
c. MRI to differentiate between benign or malignant lesions.
d. Biopsy of adrenal lesions suspected of being adrenocortical carcinoma
is unnecessary and should be avoided.
- The risk of seeding and the inability of HPE to distinguish between
adenoma or carcinoma underlie this approach.

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- Biopsy of extra adrenal lesions is performed to confirm metastatic disease.
♣♣ Treatment:
A- Localized, resectable → excision of tumor
B- Metastatic, resectable → tumor debulking and excision of metastases.
C- Metastatic, non resectable →
* Aminoglutethimide or mitotane.
* Chemotherapy:
Mitotane produces selective necrosis of the zona fasciculate
and, zona reticularis.
* Radiotherapy: effective for relief of pain from bony metastases.

♣♣ Prognosis:
Usually highly aggressive and has poor prognosis.

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 PHEOCHROMOCYTOMA

♣♣ Etiology:
* Neoplasm arising from neuroectodermal cells (chromaffin cells).
* It may occur as:
a. Sporadic 90%
b. Familial 10% (associated with MEN-II and von Hippel-Linddau syndrome)

♣♣ Pathology:
** Sites:
- Adrenal: 90% are found in the adrenal medulla.
- Extra adrenal: 10% are found in the sympathetic chain from neck
to pelvis.
- The tumor may be unilateral 90% or Bilateral 10%

** N/E
-The tumor is variable in size (from small nodules to very large
masses), lobulated and well encapsulated.
-The cut surface is red-brown and sometimes hemorrhagic.
- The tumor may be solitary in 90% or multicentric 10%

** M/E
- Cell: polygonal or spheroidal chromaffin cells.
- Stroma: vascularized fibrous stroma.
- The tumor may be benign 90% or malignant in 10%

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♣♣ Clinical Picture:
* Type of patients:
Male = female. It occurs in middle age 90% and in children 10%.
* Symptoms & signs:

I. Functioning tumor:
1. Hypertension in 50% of patients.
- Due to increased secretion of catecholamine → characterized by:
1- Associated with vasomotor manifestations.
2- Early onset hypertension (in young).
3- Paroxysmal or continuously elevated with superimposed crisis.
4- Postural (orthostatic) hypotension due to diminished plasma
volume and blunted autonomic reflexes.
2. Headache, sweating, and tachycardia (characteristic triad).
3. CVS symptoms: palpitation, arrhythmia, MI and stroke.
4. Metabolic symptoms similar to those of hyperglycemia or hyperthyroidism
due to metabolic effects of epinephrine.

II. Non functioning tumor:

Abdominal mass and pain in large pheochromocytoma
90% 10%

‫األحسن في كل حاجه‬ ‫األوحش‬

1- Sporadic Familial
2- Adrenal Extra adrenal
3- unilateral Bilateral
4- solitary multicentric
5- benign malignant
6- middle age children

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♣♣ Investigations:
1. Laboratory:
a. Plasma level of epinephrine, norepinephrine and dopamine.
- Benign pheochromocytoma secrets mainly epinephrine
- Malignant Pheochromocytoma secrets mainly nor-epinephrine

b. 24 hours Urinary Vanyl mandelic acid (VMA): increased

c. Clonidine suppression test:

An oral 0.3 mg dose of Clonidine is given:
** In normotensive or mildly hypertensive with elevated catecholamine →
Suppresses centrally mediated release of catecholamine to <
500 pg/mL within 3 hours
** In pheochromocytoma → does not suppress release of catecholamine

2. Localization:
a. IVU
b. Ultrasound → accuracy of 80-90%.
c. CT scan → accuracy up to 100%.
d. MRI: also help in diagnosis of the pathological nature
e. Whole body scan with 131I methyl iodobenzyl guanidine (MIBG)
scintigraphy is very helpful and detect occult metastasis
f. Selective angiography
g. Venous catheterization and selective sampling at sites along the inferior
and superior vena cava.

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♣♣ Treatment:
** Approaches:
1. The anterior transperitoneal approach (midline or subcostal)
→ favorable as it allows a proper search, and minimal handling before
ligation of adrenal veins.
2. The thoracoabdominal approach → used for large and malignant tumors
3. Laparoscopic.

** Technique:
Important principals of operation:-
1- Minimal handling of the tumor
2- Early isolation and ligation of the adrenal vein
3- Avoidance of capsular rupture

A- Localized, resectable → excision of tumor

B- Metastatic, resectable → tumor debulking and excision of metastases.
C- Metastatic, non resectable→
* Ablative therapy with I131 methyl iodobenzyl guanidine (MIBG).
* Chemotherapy:
* Radiotherapy: effective for relief of pain from bony metastases.
* Radiofrequency

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 NEUROBLASTOMA
(The most common abdominal malignancy in childhood)
♣♣ Etiology:
Highly malignant tumor, which arises from sympathetic neurones
♣♣ Pathology:
** Site:
1. Abdomen (68%) → adrenal 38% and sympathetic chain 30%.
2. Chest 20%
3. Pelvis 3.5%
4. Uncertain 8.5%

** N/E
- They are variable in size (from 3-4 cm to massive retroperitoneal
masses), irregular or nodular and capsulated.
- The cut section shows reddish purple (they are very vascular), with
areas of hemorrhage, necrosis, and calcifications.

** M/E
* Cells: small rounded cells with hyper chromatic nuclei arranged
diffusely or in Homer-Wright pseudorosettes consisting of dark stained
neuroblasts surrounding an eosinophilic core of neutrophil
* Stroma: highly vascularized stroma.
** Spread
1. Direct: either intrinsic or extrinsic
2. Lymphatic spread to prevertebral lymph nodes
3. Blood spread to bone marrow. The bony orbit is frequently involved
and produce proptosis and bruising around eye due to rupture of vein in the
periorbital skin (Panda or raccoon eye)

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** Staging
Stage I → Confined to tissue of origin.
Stage II → Local spread not crossing the midline, with or without
ipsilateral regional lymph node involvement.
Stage III → Local spread cross midline OR involvement of regional L.N.
on both sides.
Stage IV → distant metastases
Stage IVS→ As for stages I and II with metastases in skin, liver and bone
marrow but not in any other sites.

♣♣ Clinical Picture:
* Type of patients:
Male = female
> 80% of neuroblastoma present in children < 5 year
& about 1/3 of patients are < 2 years of age.
* Symptoms & signs:
I. General:
Change in personality with misery irritability, fatigue and anorexia.
II. Specific:
1- Abdominal tumors:
1. Abdominal mass may be palpable or visible.
2. Abdominal pain, fevers and weight loss.
3. Obstructive manifestations:-
a. Obstructive GI symptoms: intestinal obstruction & chronic constipation.
b. Obstructive urological symptoms: UTI, hydronephrosis.
c. Vascular compression:
IVC: Edema & varicosity in the lower limbs.
Portal vein: ascites.

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4. Cord compression in the posterior mediastinum tumors because there is
almost always a dumb-bell protrusion within the spinal canal.

2- Chest: mediastinal syndrome

3- Pelvic tumors:
1. Pelvic mass may be palpable or visible.
2. Pelvic pain, fevers and weight loss.
3. Obstructive manifestations:-
a. Obstructive GI symptoms: chronic constipation.
b. Obstructive urological symptoms: UTI, hydronephrosis.
c. Obstructive vascular compression:
Common iliac veins: Edema & varicosity in the lower limbs.
4. Epidural extension to the sacrum → somatic motor and sphincter
dysfunction

4- Cervical tumors:
1. Lateral neck mass may be palpable or visible.
2. Neck pain, fevers and weight loss.
3. Obstructive manifestations:-
a. Obstructive GI symptoms: Dysphagia.
b. Obstructive vascular compression: edema of the face
c. Airway obstruction.
4. Horner's syndrome

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♣♣ Investigations:
1. Laboratory:
a. Plasma level of epinephrine, norepinephrine and dopamine.
b. Urinary Vanyl mandelic acid (VMA): increased
c. Serum tumor markers:
- Neuron-specific enolase (NSE): elevated in metastatic disease.
- Ganglioside (Gd2): elevated in active and advanced disease.
d. Bone marrow aspiration: deposits in about two-thirds of patients.

II. Localization:
1- Plain X ray (diffuse calcification)
2- IVU: kidney is pushed downward and laterally → Lilly flower appearance
3- US, CT and MRI are obviously preferable in children.
4- 123 OR 131IMIBG scintigraphy help in detecting extent of spread.
5- Biopsy of 1ry or 2ries by needle core biopsy is achieved
6- PET scan.

♣♣ Differential diagnosis:
1. From childhood tumors:
1- Neuroblastoma
2- Wilm's tumor
3- Rhabdomyosarcoma & other STS
4- Ewing's sarcoma
5- Hepatoblastoma
6- HCC
7- Germ cell tumors.

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2. From round cell tumors: (MR MOLTEN)+P
- Melanoma - Rhabdomyosarcoma
- Multiple myeloma - Osteoclastoma
- Lymphoma (non Hodgkin) - Testicular tumors
- Ewing sarcoma. -Neuroblastoma
- Primitive neuroectodermal tumor (peripheral neuroepithelioma, Askin's
tumor, peripheral neuroblastoma)

3. From neuroendocrinal tumors:

1- Neuroblastoma 2- Ganglioneuroblastoma
3- Gangliononeuroma 4- Pheochromacytoma
5- Medullary thyroid carcinoma 6- Carcinoid tumors
7- Parathyroid tumors 8- Pancreatic endocrinal tumors.
9- Pituitary tumors

4. From neuroectodermal tumors:

(They arise from neural crest)
1- Glial cells: gliomas.
2- Meninges: meningioma.
3- Medulloblastoma
4- Nerve cells: neuroblastoma and ganglioneuroblastoma.
5- Nerve sheath: neurofibroma, schwannoma, and neurofibrosarcoma.
6- Melanocytes: benign melanoma and malignant melanoma.
7- C-cells of thyroid: medullary carcinoma.
8- Four soft tissue sarcomas:
* 2 pediatric tumors: Extraskeletal Ewing and neuroblastoma.
* 2 adult tumors: malignant paraganglioma and neurosarcoma.

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 ♣♣ Treatment:
A- In localized disease: excision with safety margin.
B- In disseminated disease: neoadjuvant chemotherapy and radiotherapy

followed by excision of residual tumor (it is highly radiosensitive).

♣♣ Prognosis: Prognostic factors in neuroblastoma.

Factor Good prognosis Poor prognosis
1- Age < l year > l year
2- Site Extra adrenal Adrenal
3- Histology Differentiated Undifferentiated
4- Stage I and II all ages III if > 1 year
III, if < 1 year IV all ages
5- HVA/VMA Low High
6- NSE Low level < 100 High level > 100
7- Ferritin < 143 ng/ml > 143 ng/ml
8- N-myc oncogene Single copy Amplified
9- N- myc proteins None detected High levels
10- DNA content Hyperploidy Euploidy (diploidy)

** HVA (Homovanilic acid)

N.B.
It is well documented that small tumors presenting during the first year of
life have a fairly high incidence of spontaneous regression or maturation
into a benign ganglioneuroma.

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 Ganglioneuroma
♣♣ Etiology:
Benign tumor, which arises from sympathetic neurones

♣♣ Pathology:
**Site:
It arises from the sympathetic chain or adrenal medulla.

**N/E:
- The Tumor is variable in size (from that a pea to that of a large
melon), rounded or lobulated and well encapsulated.
- Cut section shows areas of hemorrhage and necrosis.

**M/E:
- It is composed of unipolar or multipolar ganglion cells scattered
among non-medullated nerve fibers.

♣♣ Clinical picture:
**Type of patients: The tumor occurs in childhood
** Symptoms and signs:
Soft abdominal swelling which attracts attention by its size or
pressure effects.

♣♣ Investigations: US, CT or MRI.

♣♣ Treatment: The tumor is well encapsulated and can be enucleated

easily.

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 Ganglioneuroblastoma
Foci of neuroblasts within ganglioneuroma (nodular, intermixed, and
borderline)

Neurofibroma
♣♣ Pathology:
Very rarely, neurofibroma may develop in the adrenal medulla.
♣♣ Clinical picture:
1. Retroperitoneal mass.
2. Spinal cord compression (dumb-bell tumor).
3. Manifestations of Von Recklinghausen’s disease may be present.
♣♣ Treatment:
Surgical excision is indicated for this benign tumor.

Adrenal Incidentaloma
** It is clinically inapparent adrenal masses.
** It is discovered accidentally during US, CT and MRI for abdominal pain.
** Epidemiologic data indicate that up to 7% produces aldosterone, 0.035%
produces cortisol, 6.5% produces catecholamine, and 0.06% is carcinoma.
** Is it functioning or not?
We do laboratory tests for functioning adrenal tumors (Cushing
syndrome, Conn's syndrome, and Pheochromocytoma).
** Is it malignant or not?
a. Ultrasonography: cystic or solid.
b. CT confirm presence of mass.
c. MRI: distinguish between benign and malignant lesion.

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 d. Ultrasonographic or CT scan-guided fine needle biopsy for metastases
♣♣ Treatment:
I. Functioning tumors:
Resection
II. Non functioning:
a. ≥ 6 cm and suspicious imaging features → resection.
b. 4-6 cm and no suspicious imaging features → resection if patient < 60 years
or observation by CT.
c. < 4 cm and no suspicious imaging features → observation.

III. Metastatic carcinoma from another site: adrenalectomy since

many of these lesions become symptomatic and resection of metastatic disease
can be associated with survival for more than 5 years.

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 Hirsutism and Virilism X X
♣♣ Hirsutism:
Excessive growth of hair in women outside the sites usually associated with
female hair growth. (The cheeks, upper lip, chin, chest, breast areolar, limbs
and the linea alba)
♣♣ Virilism
Hirsutism, with other features of marked androgen excess occur, such as male
pattern of hair loss from the head, deepening of the voice, acne, male body
habitus and skeletal muscle development and enlargement of the clitoris.
♣♣ Etiology:
1. Constitutional or idiopathic hirsutism
2. Iatrogenic: Androgens, anabolic steroids, diazoxide, and phenytoin
3. Adrenal disorders:
Cushing’s syndrome, adrenal tumor, and congenital adrenal hyperplasia
4. Ovarian disorders:
Polycystic ovaries (Stein-Leventhal syndrome) and ovarian tumor
♣♣ Clinical picture:
In addition to the feature of hirsutism and virilism discussed above,
amenorrhea and anovulation is usual when there is a virilizing adrenal
tumour.
♣♣ Investigations:
1. Laboratory:
-Plasma testosterone and urinary 17-oxysteroids, dehydroepiandrosterone
(DHEA) are elevated where there is a virilizing adrenal tumor.
2. Localization: as Conn’s syndrome.
♣♣ Treatment:
- Benign adrenal tumors: excision -Malignant tumors: chemotherapy.

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 Methods of exploration of adrenal gland
A- Anterior approach
B- Posterior approach
C- Lateral approach

A- Anterior approach

1- Incision:-

2- Exposure of adrenal gland:-

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By three approaches:-

1- Incision of the posterior parietal peritoneum lateral to the left colon:-

* The incision is carried upward, dividing the splenorenal ligament
* Care must be taken to avoid injury to the spleen, the splenic capsule, or the
splenic vessels and the tail of the pancreas.

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2- Opening the lesser sac through the gastrocolic omentum:-
* In this approach, care must be taken to avoid traction on the spleen or the
splenocolic ligament.
* The ligament may contain tortuous or aberrant inferior polar renal vessels
or a left gastroepiploic artery

3- Oblique incision of the left mesocolon:-

* Useful in patients whose left adrenal lesion is anterior
* The arcuate vessels can be divided and the marginal artery can be
sectioned, but the major branches of the middle and left colic arteries must
be preserved.

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3- Devascularization of the gland:-
** Left gland:

** Right gland:

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 B- Posterior Approach

C- Thoracoabdominal Approach

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 Complications:-

Posterior Thoraco-
Anterior approach
approach abdominal
Left adrenal Right adrenal Left Right approach

1- Inferior Mesenteric 1- Hepatic Veins 1- 1- Right

Vein 2- IVC Superior Hepatic
2- Middle and Left 3- Superior Renal Renal Vein
Colic Arteries Polar Artery Polar 2- IVC
Vascular As in anterior
3- Superior Renal 4- Arteries 3-
injury approach
Polar Arteries Gastroduodenal 2- Left Superior
4- Renal Artery and Artery Adrenal Renal
Vein Vein Polar
Arteries
1- Splenic Capsule 1- Liver 1- Pleura As in anterior
and Spleen 2- Duodenum 2- 12th Subcostal approach
Organ
2- Pancreas Nerve +
injury
3- Renal Capsule 3- Renal Capsule 1- Lung
4- Left Colon 4- Pancreas 2- phrenic nerve

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