ADRENAL DISEASES

TYPES
AETIOLOGY
DIAGNOSIS
COMPLICATIONS
TREATMENT
 ROLE OF ADRENAL GLAND
The adrenal cortex produces three major classes of
steroids:
• (1) glucocorticoids,
• (2) mineralocorticoids, and
• (3) adrenal androgens.

Consequently, normal adrenal function is important for

• modulating intermediary metabolism and
immune responses through glucocorticoids;
• blood pressure, vascular volume, and
electrolytes through mineralocorticoids; and
• secondary sexual characteristics (in females)
through androgens
 HORMONE SYNTHESIS
• The basic structure of steroids is built upon a five-
ring nucleus .
• Adrenal steroids contain either 19 or 21 carbon
atoms.
• The C19 steroids have methyl groups at C-18 and C-
19. C19 steroids with a ketone group at C-17 are
termed 17-ketosteroids; C19 steroids have
predominantly androgenic activity.
• The C21 steroids have a 2-carbon side chain (C-20
and C-21) attached at position 17 and methyl
groups at C-18 and C-19; C21 steroids with a
hydroxyl group at position 17 are termed 17-
hydroxycorticosteroids. The C21 steroids have
either glucocorticoid or mineralocorticoid
properties.
•Cholesterol, derived from the diet and from
endogenous synthesis, is the substrate for
steroidogenesis.

•Uptake of cholesterol by the adrenal cortex is

mediated by the low-density lipoprotein
(LDL) receptor.
With long-term stimulation of the adrenal cortex by
(ACTH), the number of
adrenocorticotropic hormone
LDL receptors increases.
•The three major adrenal biosynthetic pathways lead to the
production of

glucocorticoids (cortisol),

mineralocorticoids (aldosterone), and

Separate zones of the adrenal cortex synthesize specific
hormones .

zonation is accompanied by the selective

This
expression of the genes encoding the
enzymes unique to the formation of each type of
steroid:

Aldosterone synthase is normally expressed only in

the outer (glomerulosa) cell layer,

whereas

21- and 17-hydroxylase are expressed in the

(inner) faciculata-reticularis cell layers, which
are the sites of cortisol and androgen biosynthesis,
respectively.
 ADRENAL DISEASES
• Adrenal disorders include hyperfunction
(Cushing's syndrome) and
hypofunction (adrenal insufficiency),
as well as a variety of genetic
abnormalities of steroidogenesis.

• Pheochromocytoma is the result of

hyperfunction of Adrenal medulla.
 ADRENAL FAILURE
AETIOLOGY
• PRIMARY ADRENAL FAILURE
(ADDISON’S DISEASE)

• SECONDARY ADRENAL FAILURE-

DUE TO ACTH DEFICIENCY
(MOST OFTEN DUE TO
GLUCOCORTICOID THERAPY)
 ADRENAL INSUFFICIENCY
• PRIMARY ADRENAL INSUFFICIENCY

Anatomic destruction of gland (chronic or acute)

   “Idiopathic” atrophy (autoimmune,

adrenoleukodystrophy)

    Surgical removal

    Infection (tuberculous, fungal, viral—especially in AIDS

patients)

    Hemorrhage

    Invasion: metastatic
  Metabolic failure in hormone production
    
Congenital adrenal hyperplasia

    Enzyme inhibitors (metyrapone, ketoconazole,

aminoglutethimide)
    Cytotoxic agents (mitotane)

  ACTH-blocking antibodies

  Mutation in ACTH receptor gene

 Adrenal hypoplasia congenita

•SECONDARY ADRENAL
INSUFFICIENCY
Hypopituitarism due to hypothalamic-pituitary
disease
 
 Suppression of hypothalamic-pituitary axis
    By exogenous steroid
    By endogenous steroid from tumor.
 CLINICAL FEATURES
• Clinical findings in adrenal failure are
nonspecific, and without a high index
of suspicion, the diagnosis of this
potentially lethal but readily
treatable disease is easily missed.
Symptoms include anorexia, nausea,
vomiting, weight loss, weakness, and
fatigue. Orthostatic hypotension and
hyponatremia are common.

Usually, symptoms are chronic, but shock

may develop suddenly, and is fatal unless
promptly treated. Often, this adrenal crisis
is triggered by illness, injury, or surgery. All
these symptoms are due to cortisol deficiency
and occur in both primary and secondary adrenal
failure.

Hyperpigmentation (due to marked

ACTH excess) and hyperkalemia and volume
depletion (due to aldosterone deficiency) occur
only in primary adrenal failure.
 COMPLICATIONS
• HYPONATREMIA
• HYPERKALEMIA
• VOLUME DEPLETION
• ORTHOSTATIC HYPOTENSION
• SHOCK
• ADRENAL CRISIS
• DEATH
 DIAGNOSIS
• The cosyntropin (Cortrosyn) stimulation test
is used for diagnosis.
• Cosyntropin, 250 mcg, is given IV or IM, and
plasma cortisol is measured 30 minutes
later.
• The normal response is a stimulated plasma
cortisol >20 mcg/dL. This test detects primary
and secondary adrenal failure, except within a
few weeks of onset of pituitary dysfunction (e.g.,
shortly after pituitary surgery)
The distinction between primary and secondary adrenal failure is
usually clear.
1. Hyperkalemia, hyperpigmentation, or other
autoimmune endocrine deficits indicate primary
adrenal failure, whereas deficits of other pituitary
hormones, symptoms of a pituitary mass (e.g.,
headache, visual field loss), or known pituitary or
hypothalamic disease indicate secondary adrenal failure

2. If the cause is unclear, the plasma ACTH level

distinguishes primary adrenal failure (in which it
is markedly elevated) from secondary adrenal failure.

3. Most cases of primary adrenal failure are due to

autoimmune adrenalitis, but other causes should be
considered. Radiographic evidence of adrenal
enlargement or calcification indicates that the
cause is infection or hemorrhage.

4. Patients with secondary adrenal failure should be

tested for other pituitary hormone deficiencies and
should be evaluated for a pituitary or hypothalamic
tumor .
 TREATMENT
• Adrenal crisis with hypotension must be treated
immediately. Patients should be evaluated for an
underlying illness that precipitated the crisis
• If the diagnosis of adrenal failure is known,
hydrocortisone, 100 mg IV q8h, should be given, and
0.9% saline with 5% dextrose should be infused rapidly
until hypotension is corrected.
• The dose of hydrocortisone is decreased gradually
over several days as symptoms and any precipitating
illness resolve, then changed to oral maintenance therapy.
Mineralocorticoid replacement is not needed until the
dose of hydrocortisone is <100 mg/d.
 TREATMENT CONTD.
• If the diagnosis of adrenal failure has not been
established, a single dose of dexamethasone, 10 mg
IV, should be given, and a rapid infusion of 0.9%
saline with 5% dextrose should be started.

• A Cortrosyn stimulation test should be performed.

Dexamethasone is used because it does not
interfere with measurement of plasma cortisol.

• After the 30-minute plasma cortisol measurement,

hydrocortisone, 100 mg IV q8h, should be given until
the test result is known.
 TREATMENT CONTD.
• Maintenance therapy-
All patients with adrenal failure requires cortisol replacement
with prednisone.
Most patients with primary adrenal failure also require
replacement of aldosterone with fludrocortisone.
Prednisone, 5 mg PO every morning, should be started.
The dose is then adjusted with the goal being the lowest
dose that relieves the patient's symptoms, to prevent
osteoporosis and other signs of Cushing syndrome. Most
patients require doses between 4 mg PO every morning
and 5 mg PO every morning and 2.5 mg every evening.
Concomitant therapy with rifampin, phenytoin, or
phenobarbital accelerates glucocorticoid metabolism and
increases the dose requirement.
 DOSE ADJUSTMENTS
During illness, injury, or the perioperative period, the dose
of prednisone must be increased.
1.For minor illnesses, the patient should double the
dose for 3 days. If the illness resolves, the
maintenance dose is resumed.
2.For severe illness or injury, hydrocortisone, 50 mg
IV q8h, should be given, with the dose tapered as
severity of illness wanes.
3.The same regimen is used in patients undergoing
surgery, with the first dose of hydrocortisone
given preoperatively. The dose can be tapered to
maintenance therapy by 2-3 days after
uncomplicated surgery.
 TREATMENT CONTD.
– In primary adrenal failure, fludrocortisone, 0.1 mg
PO daily, should be given, along with liberal salt
intake. The dose is adjusted to maintain blood pressure
(BP; supine and standing) and serum potassium within the
normal range; the usual dosage is 0.05-0.2 mg PO daily.
– Patients should be educated in management of their
disease, including adjustment of prednisone dose
during illness. They should wear a medical identification
tag or bracelet.
 CUSHING’S SYNDROME
AETIOLOGY
1. IATROGENIC
2. ACTH-SECRETING PITUITARY
MICROADENOMA(CUSHING’S
DISEASE)
3. ADRENAL TUMOURS
4. ECTOPIC ACTH SECRETING
TUMOURS
 CLINICAL FEATURES
Clinical findings include
1.Truncal obesity, rounded face, fat deposits in the
supraclavicular fossae and over the posterior neck,
hypertension, hirsutism, amenorrhea, and
depression.
2.More specific findings include thin skin, easy bruising,
reddish striae, proximal muscle weakness, and
osteoporosis.
3.Diabetes mellitus develops in some patients.
4.Hyperpigmentation or hypokalemic alkalosis suggests
Cushing's syndrome due to ectopic ACTH secretion.
 COMPLICATIONS
• DIABETES MELLITUS
• HYPERTENSION
• OSTEOPOROSIS
• MYOPATHY
• DELAYED WOUND HEALING
• HPA AXIS SUPPRESSION
• HIRSUTISM,MENSTRUAL
,DEPRESSION,etc
 DIAGNOSIS
• Diagnosis is based on increased cortisol
excretion and lack of normal feedback inhibition
of ACTH and cortisol secretion.22
– The best initial test is the 24-hour urine cortisol
measurement test.
– Alternatively, an overnight dexamethasone
suppression test (1 mg dexamethasone given
PO at 11:00 p.m.; plasma cortisol measured at
8:00 a.m. the next day; normal range: plasma
cortisol <2mcg/dL) may be performed.
– Both tests are very sensitive, and a normal
value virtually excludes the diagnosis
 DIAGNOSIS CONTD

– If the 24-hour urine cortisol excretion is more than

four times the upper limit of the reference range in a
patient with compatible clinical findings, the
diagnosis of Cushing's syndrome is established.
– In patients with milder elevations of urine cortisol, a
low-dose dexamethasone (0.5 mg Q6h for 48 hrs)
suppression test should be performed.
– DO NOT TEST-RANDOM CORTISOL(wide
fluctuation),DURING DEPRESSION/PHENYTOIN
THERAPY(false positive).
 OTHER TESTS
• CT/MRI
• SELECTIVE PETROSAL SINUS
SAMPLING
 OTHER ADRENAL
DISORDERS
PHEOCHROMOCYTOMA-
• TUMORS SECRETE CATECHOLAMINES
• 80% UNILATERAL & SOLITARY
• 10%-BILATERAL,EXTRAADRENAL &
MALIGNANT.
• FAMILIAL TYPES ASSOCIATED WITH-
MEN2A/2B/VHL/VON RECKLINGHAUSEN’S
• PRESENT IN YOUNG-MID ADULT LIFE WITH
PAROXYSMS OR CRISES,HYPERTENSION,etc
The diagnosis is established by the demonstration of increased
production of catecholamines or catecholamine metabolites.
The diagnosis can usually be made by the analysis of a single 24-h
urine sample, provided the patient is hypertensive or symptomatic at
the time of collection

The VMA assay is both less sensitive and less specific than
assays of metanephrines or catecholamines. Accuracy of
diagnosis is improved when two of three determinations are employed

A modified version of the adrenolytic test may be of some use,

however, as a therapeutic trial in a patient in hypertensive
crisis with features suggestive of pheochromocytoma. A positive
response to phentolamine (5-mg bolus following a test dose of
0.5 mg) is a reduction in blood pressure of at least 35/25 mmHg
after 2 min that persists for 10 to 15 min. The pharmacologic
response is never diagnostic, and biochemical confirmation is essential

Other tests-CT/MRI/PET SCAN/MIBG .

TREATMENT-SURGICAL,after pharmacological stabilisation.

 OTHER ADRENAL
DISORDERS
• HYPERALDOSTERONISM
• INCIDENTALOMA
• ADRENAL TUMORS
• CONGENITAL ADRENAL HYPERPLASIA
• ADRENAL ANDROGEN EXCESS.