DISEASES OF

ADRENAL GLAND
Dr Samir Chakraborty
 Physiology of adrenal gland

■ Adrenal gland is one of the main sites of endogenous steroid hormone biosynthesis
■ Mainly 3 types of steroid hormones are secreted by this gland- glucocorticoids,
minerelocorticoids and androgens
■ Most superficial layer of adrenal cortex or zona glomerulosa produces mineralocorticoids,
middle layer or zona fasciculata produces glucocorticoids and inner most cortical layer or zona
reticular produces androgens
■ Glucocorticoids and androgen production is chiefly regulated by ACTH, secreted by pituitary
gland whereas mineralocorticoid production is chiefly regulated by Angiotensin II (RAAS) and
only partly by ACTH
■ So in case of deregulated ACTH secretion glucocorticoids and androgen axes are deranged,
whereas dysregulated RAAS secretion affects mineralocorticoids axis
 HPA Axis

■ Hypothalamo-pituitary-adrenal axis- As we discussed in last slide that glucocorticoids

secretion from adrenal gland is regulated by pituitary through ACTH, similarly ACTH
secretion from pituitary is regulated by hypothalamus through CRH (Corticotropin
releasing hormone)
■ Glucocorticoids, on the other hand, exerts negative feedback action on pituitary and
hypothalamus to down regulate ACTH and CRH secretion thus forming a feedback
loop, the so called HPA axis.
 Cushing’s syndrome

■ Cushing’s syndrome is constellation of clinical features resulting from chronic exposure

to excess glucocorticoids of any etiology. The fault may lie at pituitary to secrete ACTH
in excess quantity (as in pituitary adenoma) resulting in increased cortisol secretion
from adrenal or adrenal gland may itself produce excess cortisol or cortisol may come
from outside of body in the form of steroid drugs
■ Cushing’s disease- when there is excess ACTH production in pituitary resulting in
clinical manifestations it is called Cushing’s disease. All other etiologies are called
Cushing’s syndrome but not Cushing’s disease.
 Epidemiology

■ Rare disease; 1-2/ lakh population/ year

■ Female are more affected
■ ACTH producing pituitary tumor (Cushing’s disease) is the predominant etiology for
endogenous Cushing’s syndrome with only 10% being primary adrenal cause
■ Overall iatrogenic cause is the leading cause of Cushing’s syndrome
Etiology
 Clinical manifestations

■ Habitus- patients are obese. Central obesity, Moon facies, Buffalo hump are
characteristically described (glucocorticoids increase fat deposition in central body parts)
■ Skin- Facial plethora( glucocorticoids augment erythropoiesis), thin and brittle skin
(metabolism of dermal proteins), easy brising, broad and purple stria, acne, hirsutism
(due to excess androgens); increased pigmentation at knuckles, creases, scrotum and
generalized skin is feature of increased ACTH activity and is found only in ACTH
dependent Cushing’s syndrome.
■ Bone- Osteopenia, osteoporosis (due to catabolism of bone proteins) leading to vertebral
fractures
■ Muscles- weakness, proximal myopathy (due to metabolism of muscle protein)
 Contd

■ Cardiovascular- Diastolic hypertension, hypokalemia, edema (due to mineraloco- rticoid

activity)
■ Metabolism- glucose intolerance, diabetes, dyslipidemia (glucocorticoids antagonize
insulin action)
■ Reproduction- decreased libido, amenorrhea (due to feed back inhibition of gonadotropin
release by very high level of circulating steroids including androgens)
■ CNS- Irritability, emotional liability, depression, psychosis
■ Blood- increased WBC count in peripheral blood, eosinopenia, hypercoagulable state with
increased risk of thrombosis
■ Immune system- increased susceptibility to infections
 DIAGNOSIS

■ Step 1: Establishing diagnosis of corticosteroids excess

Any of the following 3 tests are performed-
1. Midnight plasma cortisol level assay- plasma cortisol level has considerable diurnal variation with
peak being at around 8am and trough around 12 midnight. So to establish diagnosis of cortisol
excess we need to show elevated cortisol level at midnight when it is supposed to be lowest and to
establish diagnosis of cortisol insufficiency (addison’s disease) we need to show low cortisol level
at 8am when it is supposed to be highest. Midnight plasma cortisol level > 130 nmol/L establishes
diagnosis of Cushing’s syndrome.
2. 24 hrs overnight urinary free cortisol excretion- Free cortisol is excreted in urine. 24 hrs urine is to
be collected and amount of free cortisol excreted in 24 hrs is to be estimated. The test needs to be
repeated 3 times (3× 24 hrs samples). If free cortisol excretion is consistently elevated diagnosis of
Cushing’s syndrome is established
 Contd

3. 1 mg overnight Dexamethasone suppression test- As both the above tests are

cumbersome this is the most commonly employed test for diagnosis of Cushing’s
syndrome. Dexamethasone is an exogenous potent steroid and is known to suppress HPA
axis and thus ACTH release. 1mg Dexamethasone is administered orally at 11pm and
plasma cortisol level is assayed at 8-9 am next morning. A value > 50 nmol/L is diagnostic.
IN CASE OF ANY DOUBT OR BORDERLINE RESULT FURTHER CONFIRMATORY
TEST PERFORMED-
Low dose Dexamethasone suppression test- 0.5 mg Dexamethasone is administered orally
every 6 hourly for 2 days and then plasma cortisol level assayed. Value >50 nmol/L is
confirmatory.
 Contd

■ Step 2- Establishing site of pathology (pituitary/ ectopic ACTH secretion/ adrenal)

Plasma ACTH level assay- if ACTH level is normal or high it is ACTH dependent Cushing’s syndrome and if
ACTH level is low it is ACTH independent Cushing’s syndrome. The rationale being feedback inhibition of
ACTH by excess cortisol.
1. IF ACTH DEPENDENT- excess ACTH secretion is main pathology here and it is secreted either from
pituitary or from ectopic source (e.g. bronchogenic Ca). Now we need to distinguish between the two
conditions by the following test
High dose Dexamethasone suppression test-
2 mg Dexamethasone is administered orally every 6 hourly6for 2 days and plasma cortisol level assayed after
2 days. If plasma cortisol level is suppressed >50% the source is pituitary. The rationale is pituitary secretion
of ACTH even if pathological is under inhibitory control of high dose of steroid. However ectopic ACTH
secretion in under no such control; hence ectopic ACTH secretion will not be suppressed.
 Contd

■ IF SOURCE OF ACTH IS PITUITARY- MRI of pituitary gland to locate the pathology

(i.e. adenoma)
■ IF SOURCE ECTOPIC- Necessary investigations to search for ectopic source (e.g.
CECT Thorax to look for bronchogenic Ca)
2. IF ACTH INDEPENDENT- Pathology lies in adrenal gland.
Unenhanced CT adrenal- to delineate nature of pathology (e.g adenoma/ hyperplasia)
 Treatment

■ Surgical removal of adrenal/ pituitary/ ectopic source is the mainstay of treatment

■ Short term or long term steroid supplementation is often required after surgery
■ Pharmacological treatment- rarely employed. Metyrapone/ Ketoconazole are found to
effectively inhibit cortisol synthesis