Adrenal Disorders

Question 1

What is the mass of the adrenal gland

Answer 1

3-5 grams each

Question 2

What are the various regions of the adrenal cortex and what they produce

Answer 2

Zona Glomerulosa : Aldosterone (Mineralocorticoid)
Zona Fasiculata : Cortisol (Glucocorticoid)
Zona Reticularis : Dihydroepiandrosterone (DHEA) (Androgen)

Question 3

What does the inner medulla of the adrenal gland produce

Answer 3

Catecholamines

Question 4

What are the functions of aldosterone

Answer 4

Acts on renal tubules,intestines, sweat gland)
Sodium reabsorption
K+ excretion
H+ excretion
Water reabsorption
Increase ECF volume
Increase blood volume & maintain blood pressure

Question 5

What are some functions of cortisol

Answer 5

Effects on carbohydrates, protein & fat metabolism
During acute trauma, exercise, infection, operations and other stresses
Increased cortisol
Increased glucose & fatty acid releases for energy
Anti-inflammatory actions
Maintain adequate vascular tone during stress

Question 6

What are functions of adrenal androgens

Answer 6

Early development of male sex organs during childhood
Growth of pubic & axillary hairs
Promote protein synthesis

Question 7

What are some disorders of the adrenal cortex

Answer 7

Adrenal hypofunction – Addison’s disease
Adrenal hyperfunction :
Cushing syndrome (Mainly hypercortisolism)
Conn’s syndrome (Hyperaldosteronism)
Congenital Adrenal Hyperplasia (CAH)

Question 8

What are the two main adrenal hyper-function disorders

Answer 8

Cushing’s syndrome
Conn’s syndrome

Question 9

What are some disorders of the adrenal medulla

Answer 9

Pheochromocytoma

Question 10

What causes primary hypoadrenalism

Answer 10

Destruction of the adrenal cortex by any process producing deficiency of aldosterone, cortisol and adrenal androgens

Question 11

What causes secondary hypoadrenalism

Answer 11

Secondary hypoadrenalism is caused by deficiency of ACTH

Question 12

What is the ratio of contraction of Addison’s disease (male:female)

Answer 12

3:1

Question 13

What are some etiologies (risk factors) of Addison’s disease

Answer 13

Autoimmune
Tuberculosis
Glucocorticoid treatment
Surgical bilateral adrenalectomy
Secondary tumour deposits
Fungal disorders – Histoplasmosis
Hemochromatosis, amyloidosis, sarcoidosis,
Adrenal haemorrhage : septicaemia, anticoagulant therapy, waterhouse – Friderichsen syndrome, bleeding disorders.
Radiation therapy

Question 14

What are some clinical features of Addison’s disease

Answer 14

Generalized weakness, fatigue, lethergy.
Anorexia, weight loss, nausea, vomiting.
Dizziness, postural hypotension, dehydration, shock.
Muscle, joint pain, fever.
Loss of body hairs, menstrual abnormalities.
Hyper-pigmentation of the palms of the hand
Depression

Question 15

What are some laboratory investigations for Addison’s disease

Answer 15

Plasma Cortisol – Low to absent.
Plasma ACTH – High ( in primary hypoadrenalism)
ACTH Stimulation Test:
Morning plasma cortisol
ACTH ( Cosyntropin) 250 mg I/M or I/V
Second plasma cortisol level after 30, 60 mins.
Cortisol level fail to rise appropriately after ACTH suggestive of Addison disease
Hyperkalaemia, hyponatraemia.
Increased urea
Hypoglycaemia
Mild anaemia, Neutropenia, Eosinophilia
Anti-adrenal antibodies.

Question 16

What is another name for Cushing’s syndrome

Answer 16

Hypercortisolism

Question 17

What are some radiological investigations to make in Addison’s disease

Answer 17

Chest X-ray – R/O Tuberculosis
Abdomen X-ray – R/O Tuberculosis
Ultrasound abdomen
CT abdomen

Question 18

What is another name of Addison’s disease

Answer 18

Primary Adrenal Insufficiency

Question 19

What is Cushing’s syndrome

Answer 19

Cushing’s syndrome refers to manifestations due to excessive glucocorticoids in the body. Generally affect young ( mean age 33 years). Common in females 5 :1

Question 20

What are some etiology of Cushing’s syndrome

Answer 20

ACTH hypersecretion by pituitary (Cushing disease) (Pituitary adenomas)
ACTH hypersecretion by ACTH producing tumors (small cell carcinoma lungs, carcinoid tumors, thymus, pancreas)
Excessive cortisol secretion by adrenal neoplasm (Adrenal adenoma, carcinoma) & hyperplasia
Prolonged corticosteroid treatment

Question 21

What are some clinical features of Cushing’s syndrome

Answer 21

Effects of Glucocorticoid Excess:
Central obesity, moon face, dorsocervical fat pad, (buffalo hump), supraclaviculer fat pad, protuberant abdomen
Muscle wasting, weakness, fatigue.
Thin skin, easy bruisability, purple striae, poor wound healing, osteoporosis
Hypogonadism, menstrual abnormalities, decrease libido.
Psychosis, depression, impaired memory
Children (Slow growth)

Effects of androgen excess: ( if present)
Hirsuitism, acne, virilization in females
Pseudoprecocious puberty in children

Effects of ACTH excess: (if present)
Hyperpigmentation
Effects of mineralocorticoid excess: (if present)
Hypertension
Hypokalaemia

Effects of pituitary tumour: (if present)
Headache
Visual field defects
Hypopituitarism

Question 22

How do you diagnose hypercortisolism

Answer 22

Establish diagnosis of hypercortisolism
Find out the cause of hypercortisolism. Is it?:
Adrenal source
Pituitary pathology (Cushing disease)
Ectopic ACTH producing tumors

Plasma cortisol concentrations are at their highest shortly after waking and then decline throughout the day to reach a nadir in the late evening.
Because of this variation, it is important that blood samples are taken at times that coincide with either the peak or the trough

Investigations
To establish the diagnosis of hypercortisolism:
Plasma cortisol:
In normal individuals:
Morning samples at 0800 Hrs: 10 – 28 ug/dl
Evening samples at 2000 Hrs: 5 – 10 ug/dl
In Cushing syndrome:
Plasma cortisol high
Loss of diurnal variation
High level also found in stress, obesity, depression, pregnancy, alcoholism
To differentiate we perform DMX Suppression test

Overnight Dexamethasone Suppression Test:
Best Screening Test
2mg oral dexamethasone given at 2300 Hrs.
Blood specimen for plasma cortisol-next morning at 0800Hrs
Normal individuals: Plasma Cortisol Suppressed to < 50% of basal level.
Cushing Syndrome: Failure to suppression of plasma cortisol levels

Prolonged Dexamethasone Suppression Tests.
Low dose: 0.5 mg six hourly for first two days.
If suppressed : Normal
No suppression : Go with high dose
High dose: 2.0 mg six hourly for next two days
If suppressed : Cushing’s disease
No Suppression : Adrenal tumor - ACTH secreting tumour

To find out the cause of hypercortisolism:
Plasma ACTH:
High plasma ACTH
Pituitary Adenoma (Cushing’s disease)
Ectopic ACTH secretion by tumors
Low plasma ACTH
Adrenal tumors

Other laboratory tests:
Urinary free Cortisol: High
Plasma glucose : High due to anti Insulin effect of Cortisol
Serum K : ± low due to mineralocorticoid effects of cortisol in more severe ACTH dependent disease
Leukocytosis with lymphopenia

Question 23

Talk about Conn’s syndrome

Answer 23

Excessive production of aldosterone
Hypertension (usually mild), polyuria, fatique and weakness.
Hypokalemia, metabolic alkalosis.
Elevated plasma & urine aldosterone
Suppressed plasma renin.
Adrenal adenoma (75%), bilateral adrenocortical hyperplasia (25%).
CT/MRI of adrenal.

Question 24

What are some radiological investigations for Cushing’s syndrome

Answer 24

For localization of tumors
MRI – pituitary
CT Scan – chest, abdomen
CT Scan – Adrenals

Radioisotopic studies:
Distinguish adrenal adenoma from hyperplasia

Question 25

What is congenital adrenal hyperplasia (CAH)

Answer 25

It is an inborn error of steroid synthesis due to enzyme deficiency. It is autosomal recessive. It is a 21 hydroxylase deficiency & 11 Beta – hydroxylase deficiency

Question 26

What are the three main presentations of CAH

Answer 26

Simple virulism at birth/neonatal period (mild deficiency of enzyme & salt wasting not a feature)
Salt wasting & virulism at birth (severe enzyme deficiency)
Late onset with hirsutism and infertility

Question 27

Elevated ACTH, 17-0H progesterone, progesterone, testosterone, DHEA (dehydroepiandrosterone)
This happens in what condition

Answer 27

CAH

Question 28

What are the effects of CAH

Answer 28

Decreased cortisol, increased ACTH, increased adrenal activity & hyperplasia
Deficiency of cortisol & other steroids e.g. aldosterone
Clinical effects of increased precursors – virulization

Question 29

Talk about pheochromocytoma

Answer 29

Catacholamine secreting tumors of adrenal medulla.
Rough “rule of ten”:
10% cases – Extra adrenal (along sympathetic nervous chain)
10% cases – Children
10% cases – Familial
10% cases – Bilateral adrenal involvement
10% cases – Metastatic
10% cases – Extra abdominal (Thorax, Bladder, brain)
10% cases – No hypertension

Paroxysmal or sustained hypertension
Sometimes postural hypotension
Episodes of perspiration, palpitation.
Headache, Anxiety, nausea, chest or abdominal pain, dyspnea, visual disturbances.
Hyper-metabolism with normal thyroid tests.
Hyperglycemia due to anti-insulin effect of catecholamines
Elevated urinary catecholamines & their metabolites e.g. metanephrines & VMA
CT/MRI can confirm & localize the tumor