 ADRENAL CORTEX

Estrogen ( C18 )
Androgen ( C 19 ) : Testosteron
Glukocorticoid (C 21) : Cortisol
Mineralocorticoid  Aldosteron
 ADRENAL MEDULLA :
Epinephrin / norepinephrin
 Adrenocortical hyperfunction
Glucocorticoids
Aldosteronism  Mineralocorticoids Cushing’s syndrome
Virilizing tumors  Androgens
Feminizing tumors  Estrogens
Adrenocortical hypofunction
Hypopituitarism  Glucocorticoids
Hypoaldosteronism  Mineralocorticoids Addison’s disease
Hypopituitarism  Androgens
Estrogens
 Masses found incidentally during
radiographic imaging of the abdomen
 Incidence : 0.35-4.36% in general
population
In Evaluation such mass:
 Is the mass benign or malignant?
 Does the mass secrete hormones or mass
disfunction
 Benign:
Non hormone secreting (lipoma,cyst,
ganglioneuroma, adenoma)
Hormone secreting (pheochromocytoma,
aldosteronism, subclinical Cushing’s
syndrome
 Malignant
Adrenocortical carcinoma
Metastatic neoplasm
Lymphoma
 Size is important:
Adrenal masses >4cm  more likely
malignant  surgical resection should
be consideration
 The great majority (+ 89%) are benign,
non functioning masses
 A full biochemical workup should be
completed before surgery is done
 Cushing’s syndrome is a large group of
signs and symptoms that reflect excess
cortisol plasma

 Cushing’s syndrome is a rare disorder

 incidence : 2–3/million

 The female:male ratio is 3 : 1

 The prevalence rate among patients
with uncontrolled diabetes mellitus or
osteoporosis can be as high as 5%
 Cushing’s syndrome was first
described by Harvey Cushing in
1910 in a woman with :
 central obesity abdominal striae
hirsutism
 amenorrhe
 hypertension
 proximal muscle weakness
 thinning hair
 purpura

Harvey Cushing who in 1932 first described

thepresence of basophilic pituitary adenomas as a
cause of the disease.
 Cushing’s syndrome is now known to be
associated with hypercortisolism, either
endogenous or exogenous in origin

 Although several signs and symptoms are

suggestive of Cushing’s syndrome (eg, weight
gain, central obesity, moon facies, abdominal
striae, buffalo hump), no single physical finding
is pathognomonic.

 The diagnosis is confirmed through

biochemical testing, and treatment is
dependent on the cause of hypercortisolism.
 ACTH
dependent
endogen
ACTH
Cushing’s independent
syndrome :
exess cortisol
secretion

eksogen korticosteroid
 On carbohydrate
metabolism :
stimulation of
gluconeogenesis

 Protein metabolism :
decrease in cellular
protein → muscle
weakness and decrease
immunity
 Fat metabolism :
mobilization of fatty
acids
 Clinical Features of Cushing’s Syndrome

Gonadal dysfunction :
Hypertension
Skin : mellitus :
Hirsutism Diabetes
1. violaceous
Mineralocorticoid
striae Activity of
Oily skin Pituitary tumor :
Cortisol
ecchymoses
Acne hemiapnopsia bitemporalis
2. Activation
Hyperpigmentation of the Renin-
Menstrual irregilarities Parese nervus
Angiotensin aldosteron System
oily skin
Impotence in men oculomotorius, IV, VI
3. action of cortisol on peripheral
Loss of libido in both offacial
sex plethora
and systemicAcne vasculature
Skin infection

Musculoskeletal:
Atrophies the muscles
Proximal myopathy
osteoporosis
1. Recommend 2. Recommend testing
obtaining a thorough for Cushing’s
drug history to syndrome in the
exclude exogenous following groups:
glucocorticoid  Osteoporosis
exposure, physical  hypertension
examination before
conducting  Children with
biochemical testing decreasing height
percentile and
increasing weight
 Patients with adrenal
incidentaloma
compatible with
adenoma
 late night salivary cortisol
collect a saliva sample on two
separate higer
evenings between with appropriate
 Provide a complete 24-h
• 03.00 – 23.00 and 24.00 h urine Late night
collection• 23.00 –
total 04.00
volumeUFC
False AM : •is 07.00 – either by24.00 PM
potitive
 Not to drink  saliva
excessive
passive
amounts
09.00 salivary cortisol
collected
AM of fluid
Smoke
 Avoid use of anydrooling
the cigarettes into a plastic
glucocorticoid preparations,
Steroid containing tube or by placing
lotion or oral skin a cotton
gel or hemorrhoid creams,
Cortisol
including steroidcontaining
pledget (salivette) lower
in the mouth
during the collection.
Tress beforeand
collection
chewing CS for 1–2Sensitivity
min
 UFC levels in a patient with CS are variable, → two
: 92-100 %

collections should be performed ↓ Specifisity : 93-100 %

CS : corticol
 UFC 275 nmol/dl → CS : > 145 ng/dl (4 nmol/L)l
Longer low
 Sensitivity : 89 % 1 mg overnight
 false positive : high fluid intake
cortisol(>5 L/d)
dose DST Salivary
dexametason
~ blood
False negative : creatinine clearance < 60 ml/mn
 1-mgDST
Longer low dose overnight
( 2 mgDST
selama 48 jam)
 Administration of a supraphysiological dose of glucocorticoid
results in suppression of ACTH and cortisol secretion
 Dexamethasone is given in doses of 0.5 mg for 48 h,
 In endogenous
beginning Cushing’s
at 09.00 h on dsyndrome
1, at 6-h → failure ofi.e.
intervals, thisat
suppression when low doses of the synthetic glucocorticoid
09.00, 15.00, 21.00,
dexamethasone and
are 03.00 h.
given

 Serum cortisol is measured

1 mg dexamethasone is usually at 09.00
given h, 6 h23.00
between afterand
the
last24.00
dose h, of
and cortisol is measured between 08.00 and 09.00 h
dexamethasone.
the following morning
 CS : > 1,8 µg/dl ( < 50 nmol/liter)
 Normal serum cortisol : < 5 µg/dl (< 140 nmol/liter).

 stop
 CS : >alcohol
1,8 µg/d consumtion 2 weeks :before
(50 nmol/liter ),spesifisity 80% , sensitivity : 95 %
examination
 False positive : oral contraseption, critically ill and nefrotic
and kidney disease ↑ cortisol plasma
syndroma
Liver
1. ACTH plasma
2. Loperamide test
3. High dose dexametason test
4. LDDST with CRH (1 µg/kg iv CRH, 15 second
: kortisol > 1,4 µg/dl)
5. CRH stimulation test ( 1µg/kg or 100 µg iv)
6. Desmopressin test (10 µg 1-desamino-8-D-
arginine vasopresin iv)
7. MRI
8. Bilateral inferior petrosal sinus sampling
(BIPSS)
3.

4. Pregnancy, Depression and other psychiatric

conditions, alcohol dependence, Glucocorticoid
resistance, morbid obesity, poorly controlled
diabetes mellitus
5.
6. In other individuals with normal test results (in
whom Cushing’s syndrome is very unlikely),
suggest reevaluation in 6 months if signs or
symptoms progress
 Px morning cortisol inthe 1’st
1. Cushing’s week post op
disease Kortisol :
surgical
1. < 2 µg/dl is remission
2. 2 – 5 µg/dl : can be considered
in remission
3. > 5 µg/dl for up to 6 weeks :
persistent disease and requires
further evaluation

CD
Medical management
( adrenolytic agents Radiotherapy
and neuromodulatory
agents)
Table 2.
Table 3
2. Tumour of the adrenal gland

Replacement
surgeri
hormone therapy
surgeri Chemotherapy Immunotherapy radiotherapy
• In 139 patients with nonmalignant disease, 11.1% had died during
follow-up (median, 8.1 yr; range, 3.1–14.0), yielding a standard mortality
ratio (SMR) of 3.68 [95% confidence interval (CI), 2.34–5.33].
• The SMR was partly attributable to an increased mortality within the
first year after diagnosis.
• The prognosis in patients with malignant disease was very poor.
 Cushing’s syndrome comprises a large group of
signs and symptoms that reflect prolonged and
inappropriately excess cortisol production

 Etiology cushing’s syndrome are glukokortikoid

consumption, tumour of the adrenal gland, tumour
of the pituitary gland and ectopic ACTH tumour.

 Diagnosis : anamnesis, physical examinations,

biochemical screening and radiology

 Treatment depends on the source of

hypercortisolism
 Aldosterone
 Desoxycorticosteron
 Corticosterone (slight
mineralocorticoid activity)
 9a-Fluorocortisol
 Cortisol (very slight
mineralocorticoid activity, but
large quantity secreted)
 Cortisone (synthetic, slight
mineralocorticoid
activity)
Glucocorticoids
 Cortisol (very potent,
accounts for about 95 per
cent of all glucocorticoid
activity)
 Corticosterone (provides
about 4 per cent of total
glucocorticoid activity, but
much less potent than cortisol)
 Cortisone (synthetic, almost as
potent as cortisol)
 Prednisone (synthetic, four
times as potent as cortisol)
 Methylprednisone (synthetic,
five times as potent as cortisol)
 Dexamethasone (synthetic,
30 times as potent as cortisol)
 Primary (adrenal) or secondary (hypothalamic/pituitary):
Primary (Addison’s disease): MCC: autoimmune adrenalitis;
tuberculosis, metastatic cancers ( destruction of  90% of
the cortex)  decreased cortisol & aldosterone, with feed-
back elevation of ACTH (+ MSH)  hyperpigmentation of
skin,  K+,  Na+,  BP, weakness, anorexia, N&V,
hypoglycemia

Secondary: to hypothalamic or pituitary lesions associated with

decreased ACTH  bilateral adrenal cortical atrophy,
sparing the zona glomerulosa (skin color is pale and
aldosterone is normal, i.e. no sodium or potassium
abnormalities).
 Suppressed adrenocortical function and hormones
 May precipitate “adrenal crisis”: life-threatening
 Primary:
› Addison’s- rare, chronic disorder
› 90% gland usually destroyed before symptoms appear
 Secondary:
› Reduced ACTH secretion caused by pituitary disease or
exogenous steroid administration; more common
 Impairs stress response by reducing cortisol,
aldosterone, and androgens
 Assessments:
› Muscle weakness and fatigue (especially during stress)
› Nausea, vomiting, diarrhea, abdominal pain
› Salt craving
› Anxiety, restlessness, irritability, and confusion
› Orthostatic hypotension
› HYPOGLYCEMIA & HYPERKALEMIA
› Hyperpigmentation (ONLY PRIMARY DISEASE HAS THIS)
 Knees, elbows, nipples, palm creases, scars( bronzed, “dirty
tan”)
 Small black freckles on neck, face; bluish splotches on mucous
membranes
Clinical Presentation:
› Looks chronically ill,
weight loss, lethargy,
weakness, low libido
› Dehydration
› Creases in elbows,
knees and lips Hyperpigmentation of lip
› Nausea, vomiting,
chronic abdominal
pain
› Muscle cramps
› Hyper/hypo-
pigmentation
(unilateral, patchy)
Hyperpigmentation in Addison’s Disease
 Low levels adrenocortical hormones in blood or urine plasma
cortisol
a.m. 7-28 mcg/dl
p.m. 2-18 mcg/dl

 ACTH injection fails to cause rise in plasma cortisol

 Suggestive of disease
› hypoglycemia
› hyponatremia
› hyperkalemia
› Leukocytosis, hematicrite
› BUN elevated; hematocrit elevated
 Interventions:
› Lifelong therapy with replacement
› Drugs:
 Cortisone: twice daily, increase dose for stressful times
 Florinef: aldosterone replacement
› Salt food liberally
› Avoid fasting
› Eat high carbs and proteins
› Always wear medic alert identification
› Carry emergency kit with 100mg hydrocortisone for
injection
› Prevent acute exacerbations
› Avoid salt and fluid restriction with diuretics; may lead to
crisis
 Complications:
› Adrenal crisis: due to insufficiency; can occur
gradually or abruptly (acute adrenal
insufficiency)
› Potentially lethal
› Occurs in individuals who don’t respond to
therapy; increased stress without increased
meds; abrupt corticosteroid withdrawal
› ALWAYS WITHDRAW STEROIDS THERAPY
GRADUALLY
 Treatment:
› Restore volume with D5 or NS
› Be sure to assess fluid status frequently
› Cortisol q 6 hr. (Solu-Cortef IV): if given with
saline, proves adequate to replace
Aldosterone
› Do not give methyleprednisolone (Solu-
Medrol: lack mineralocorticoid effects)
› Reduce anxiety
 Diseases of adrenal medulla
Pheochromocytoma

Pheochromocytomas are rare (<0,2% of

hypertensive), cathecolamine-producing tumor
of neurochromaffin cells.
Extraadrenal Ph  sympathetic ganglia are
called Paraganggliomas
Incidence 3-4th decades,autosomal dominat
hereditary.
10-15% cases Malignant Hypertension is
caused by excessive plasma level epinephrine
by tumor located either or both adrenals &
anywhere along sympathetic nervus chain
(90% adrenal)
Symptoms and Signs
Usually lethal unless diagnosed and
treated severe headache, perspiration,
palpitation, anxiety, tremor, tachycardia
Attack  cyanosis, facial pallor
 Classical symptomatic triad:
headache, sweating, palpitations

 Laboratory finding
Urinary cathecolamines, metanephrine,
creatinine, Urinary VMA
Localisation
 CT scanning
› Overall accuracy 90%-95% for adrenal tumours
› Less accurate for extra adrenal tumours
 Isotope scintigraphy (MIBG scanning)
› 131I-MIBG stored in chromaffin granule
› Sensitivity 99%
› False negative 11%
› False positive 2%
Blood and Urine analysis
› Plasma catecholamine levels > 1000micrograms
› Urinary VMA and Metanephrine levels
 Treatment
• Surgery  Preoperative preparation
• To control hypertension & prevent CVS
complications.
• Alpha adrenergic blockade
– Phenoxybenzamine 10 mg qds 1-2 weeks before
surgery
– Beta blockade propanolol 10 mg qds 2-3 days
• Intraoperatively
• Phentolamine
• Sodium nitroprusside
 Treatment Laparoscopic removal of
the tumor  treatment of choice, open
laparatomy
 Prognosis
Depends early diagnosis is made