‫بسم هللا الرحمن الرحيم‬
Disorders of the adrenal glands
Disorders of the adrenal glands result in classic
endocrine syndromes such as
-cushing syndrome,
-hyperaldosteronism, &
-catechol excess from pheochromocytoma.
The diagnosis of these disorders requires
careful endocrine evaluation &
imaging with CT or MRI.
Diseases of the adrenal cortex.
Cushing syndrome.
Clinical condition caused by overproduction of
cortisol.
If we exclude exogenous causes
-80% bilateral adrenocortical hyperplasia stimulated
by overproduction of adrenocorticotropic hormone
(ACTH).
-10% of cases are due to ectopic production of ACTH
from non pituitary tumors,
-5% due to adrenal adenoma, &
-5% adrenal carcinoma.
Pathophysiology.
Overproduction of cortisol by adrenocortical tissue
leads to catabolic state.
This cause liberation of amino acid from muscle
tissue which are transformed into glucose & glycogen
in the liver by gluconeogenesis.
The resulting weakened protein structures
(muscle & elastic tissue) cause protuberant abdomen
& poor wound healing, generalized muscle weakness,
& marked osteoporosis, which is made worse by
excessive loss of calcium in the urine.
In addition, glucose is transformed largely into fat &
appear in characteristic site such as the abdomen,
supraclavicular fat pads, & cheeks.
There is tendency to diabetes & hypertension.
The cortisol excess also suppresses the immune
mechanisms, which make the patient susceptible to
repeated infection.
Clinical findings.
-Central obesity,
-striae,
-hypertension,
-emotional lability, &
-osteoporosis.
Laboratory finding.
-Polycythemia is present in over half of the cases, but
-anemia may occur in pt with malignant tumor
ectopically secreting ACTH.
-Increase serum sodium & CO2 levels &
-decrease in serum potassium levels.
-Hyperglycemia may occur.
Specific tests for cushing syndrome.
a.24-h urinary cortisol.
(normal range 10-50 microgram/24 h),
a value > 2-fold elevated is typical of cushing
syndrome.
False positive elevations can occur in
acute illness, depression, & alcoholism.
b. suppression of ACTH & plasma cortisol by
dexamethasone.
If dexamethasone is given at 11 PM, ACTH is
suppressed in normal persons but not in those with
cushing syndrome.
CT &MRI of both the pituitary & abdomen may help
to localize the site of pathology.
Treatment.
Medical treatment is indicated in pt who cannot
undergo surgery.
Surgical therapy.
-Transsphenoidal resection of pituitary adenoma,
or
total bilateral adrenalectomy (in pt with
unresectable
pituitary tumor & radiotherapy & chemotherapy fail
to control cortisol excess).
-removal of primary tumor in cases of ectopic
ACTH.
Congenital adrenal hyperplasia (CAH)
A congenital defect in certain adrenal enzymes result
in the production of abnormal steroids, causing
pseudohermaphroditism in female &
macrogenitosomia in males.
The enzyme defect is associated with excess
androgen production in utero.
In female the mullerian duct structures ( e.g. ovaries,
uterus, & vagina) develop normally,
but the excess androgen exerts a masculinizing effect
on the urogenital sinus & genital tubercle.
So that externally, the appearance is that of severe
hypospadias with cryptorchidism.
Clinical finding.
-In the newborn girls, the appearance of external
genitalia resembles severe hypospadias with
cryptorchidism.
-Infant boys appear normal at birth.
*The earlier the intrauterine life the fetus has been
exposed to excess androgen, the more marked the
anomalies.
-In untreated cases, hirsutism, excess muscle mass,
and eventually, amenorrhea are the rule.
-Breast development is poor.
In males growth of phallus is excessive.
The testes are often atrophic because of inhibition of
gonadotropins secretion by the elevated androgens.
Laboratory findings.
Urinary 17-ketosteroid levels are higher than normal
for sex & age.
Plasma testosterone also elevated.
CT may show hypertrophied adrenals.
Treatment.
It is imperative to make the diagnosis early.
Treatment of the underlying cause is medical, with
the goal of suppressing excessive ACTH secretion.
thus minimizing excess androgenicity.
This is accomplished by adrenal replacement with
cortisol or prednisone in doses sufficient to suppress
adrenal androgen production & therefore prevent
virilization & rapid skeletal growth.
Adrenocortical tumors
Adrenocortical tumors producing androgens are most
frequently carcinomas, however, few benign
adenomas have been reported.
Most of the carcinomas also hypersecrete other
hormones (i.e. cortisol) & thus the clinical
presentation is variable.
Female patients present with androgen excess, which
may be severe enough to cause virilization.
Many of these patients also have cushing syndrome
&
mineralocorticoid excess (hypertension &
hypokalemia).
In adult male
-excess androgen may cause no clinical
manifestation,
& diagnosis in these patient may be delayed until
there is abdominal pain or an abdominal mass
-These patient may also present with cushing
The tumor can be located by CT scan, which is also
used to define the extent of tumor spread.
Local invasion & distant spread to the liver & lungs
are common at the time of diagnosis.
The primary therapy is surgical resection of the
adrenal tumor.
Primary aldosteronism
Excessive production of aldosterone, due mostly to
aldosteronoma or to spontaneous bilateral
hyperplasia of the zona glomerulosa of the adrenal
cortex, leads to combination of
hypertension, hypokalemia,
nocturia, & polyuria.
A syndrome resembling nephrogenic diabetes
insipidus may occur as a result of reversible damage
to the renal collecting tubules.
The alkalosis may produce tetany.
Clinical finding
-Hypertension is usually the presenting symptoms &
the accompanying hypokalemia suggest
mineralocorticoid excess.
-Headache are common, nocturia is invariably
present, & rare episodes of paralysis occur with very
low serum potassium levels.
-Numbness & tingling of the extremities are related
to alkalosis that may lead to tetany.
Laboratory finding.
High serum sodium & CO2 + low serum potassium
& increase urinary potassium.
Definite diagnosis by measuring elevated serum &
urine aldosterone with suppression of plasma renin
to be differentiated from renal hypertension with
also elevated aldosterone & renin levels.
Localization.
-CT scan will localize adenoma in 90% of cases.
-If no adenoma visualized adrenal vein sampling of
aldosterone & cortisol will correctly differentiate
adenoma from hyperplasia in virtually all cases.
Treatment
If the site of the tumor has been established only the
affected adrenal need to be removed.
The procedure of choice is laparoscopic unilateral
adrenalectomy.
Medical treatment is recommended for
-bilateral hyperplasia
-mild hypertension in older person.
Spironolactone ( aldactone) 25-50 mg orally 4-times
daily.
Or Amiloride potassium sparing diuretic may be
given in dose up to 20-40 mg /day.
Other antihypertensive may also be necessary.
Disease of the adrenal medulla
Pheochromocytoma
derived from the neural crest, it is one of the
surgically curable hypertensive syndrome,
there is no sex predilection.
It account 1% of hypertension, but it is readily
diagnosed if the possibility is kept in mind.
It usually occur spontaneously
10% associated with other disorders like
neurofibromatosis,
10% bilateral,
10% extra-adrenal,
10% malignant.
Clinical findings
-Hypertension is both systolic & diastolic.
May either sustained or paroxysmal
(coming on for variable length of time & then
subsiding to normal level).
Trigger mechanisms is emotional stress, or straining
at stool.
-Headache, increase sweating without appropriate
cause,
-tachycardia with palpitations, &
-postural hypotension is frequent finding.
-Profound weakness may occur after an attack of
hypertension.
-Weight loss is common.
-Decrease gastrointestinal motility occurs, leading to
nausea, vomiting & constipation.
-Episodes of emotional instability.
Biochemical diagnosis.
Elevated plasma & urinary catecholamine
(Epinephrine norepinephrine) or metabolites
(Vanillylmandelic acid) during the attack is usually
diagnostic.
Localization.
CT scan is the initial imaging procedure of choice
&MRI or radionuclide scanning may be used in
certain cases.
Pheochromocytoma 98% intra-abdominal &
90% intra-adrenal.
Treatment
Usually surgical the use of long acting alphaadrenergic blocker has minimize surgical mortality &
morbidity.
Incidentaloma
The most common presentation of adrenal masses is
incidental observation on cross-sectional imaging
performed for other reasons.
D.Dx quite broad & include
-benign adenoma,
-functional adrenal tumors,
-metastases, &
-benign adrenal lesion such as myelolipoma &
neurofibroma.
A systemic approach is required to differentiate
functional adrenal masses that deserve removal &
those lesions with significant risk of carcinoma from
the more common benign nonfunctional adenoma.
Metabolic evaluation.
A careful history & physical examination with focus
on
-obesity pattern,
-virilization,
-glucose intolerance &
-hypertension is warranted.
Laboratory examination
serum electrolytes including glucose & potassium
should be done.
If hypokalemia is present then other testes for
aldosterone are indicated.
A 24 hr urinary free cortisol to rule out cushing &
urinary metanephrines & normetanephrines to rule
out
pheochromocytoma are recommended.
If the test that identified adrenal mass ultrasound or
CT then MRI may be indicated if needed.
*Lesions that are primarily cystic on CT or MRI are
typically benign & can be followed with serial
imaging.
*All functional adrenal masses & those over 5 cm
should be removed .
laparoscopic adrenalectomy is the preferred
technique
except in very large masses.
*Nonfunctional adrenal masses < 5cm removed if
they have feature of malignancy irregular,
hemorrhagic or demonstrated growth.
*Those <3 cm generally be followed up with serial
CT every 6 months.
Neuroblastoma
Are of neural crest origin & may develop from any
sympathetic chain.
*Most arise in the retroperitoneum,
- 45% involve adrenal gland.( poorest prognosis)
*in childhood neuroblastoma is the third most
common neoplastic disease after leukemia
and brain tumors.
*most are encountered in the First 2.5 years of life,
but a few are seen as late as the sixth decade,
when they seem to be lees aggressive.
*Abnormalities of muscle and heart and
hemihypertrophy have been observed in association
with neuroblastoma.
*Metastases spread through both the bloodstream &
lymphatic. Common sites include skull & long bone,
regional LN, liver & lung.
*Best prognosis if metastasis limited to the liver &
subcutaneous fat.
Staging of neuroblastoma
Stage1- confined to the structure of origin.
Stage2- beyond the organ but not crossing midline.
Stage3- beyond the midline.
Stage4- remote. Involving skeletal, soft tissue or
distant LN
Stage5- stage 1 or 2 with remote spread confined to
one of the following liver, skin, & bone marrow.
Clinical findings
*Abdominal mass usually noted by parent, physician
or patient usually palpable may be visible.
*70% of pt have metastasis when 1st seen.
*Symptoms related to metastases include fever,
malaise, bone pain, failure to thrive & constipation or
diarrhea.
*Ocular proptosis from metastases to skull
*Hypertension is often noted
Laboratory finding
* 70% elaborate norepinephrine & epinephrine
*Urinary VMA level should be measured.
Can be used as tumor markers for diagnosis,
response to therapy & prognosis.
Bone marrow aspiration may reveal tumor cells.
CT used for diagnosis & staging.
DDX.
-wilms tumor,
-hydronephrosis,
-polycystic renal disease,
-neonatal adrenal hemorrhage.
Treatment
-surgical excision.
-For stage 4 & high risk stage 3 chemotherapy
typically given followed by surgery & radiation
therapy for residual disease.
Best prognosis
-Stage 1 & 2 disease (have 80% survival rate)
-Infant
-tumor confined to the primary site
High risk including
-age >1 yr.
-Metastasis
-amplification of the MYCN oncogene
-Particular histologic finding.