Week 4

Question 1

What do adrenal glands consist of and where are they located

Answer 1

The adrenal glands, located on the cephalad portion of
each kidney and consist of a
 Cortex
 Medulla

The adrenal cortex and adrenal medulla each have
separate endocrine functions.

Question 2

Structure of Adrenal Gland

Answer 2

Cortex
>Zona glomerulosa
>Zona fasciculata
>Zona reticularis

Medulla
>Modified post-ganglionic neurons intimately connected to sympathetic neurons.

Question 3

Adrenal Regulation

Answer 3

Adrenal glands interact with the hypothalamus and pituitary
gland in the brain.
 The hypothalamus makes corticotropin-releasing hormone (CRH).
 This stimulates the pituitary gland to make adrenocorticotropic hormone (ACTH).
 The ACTH stimulates the adrenal glands to make and release hormones into the blood.
 Both the hypothalamus and the pituitary gland can sense
whether the blood has the right amount of a hormone in it.
 If there is too much or too little cortisol, these glands change the amount of CRH and ACTH they release.

Question 4

Hormones of Adrenal Cortex

Answer 4

The adrenal cortex produces
• Glucocorticoids (primarily cortisol)
• Mineralocorticoids (primarily aldosterone)
• Androgens

Question 5

Glucocorticoids

Answer 5

• Promote and inhibit gene transcription in many cells and
organ systems.
• Prominent effects include anti-inflammatory actions and
increased hepatic gluconeogenesis.

Question 6

Mineralocorticoids

Answer 6

• Regulate electrolyte transport across epithelial surfaces,
particularly renal conservation of sodium in exchange
for potassium.

Question 7

Adrenal androgens’

Answer 7

• Chief physiologic activity occurs after conversion

to testosterone and dihydrotestosterone.

Question 8

Glucocorticoid-Cortisol

Answer 8

Affects glucose, protein, fat metabolism.
 Inhibits synthesis of protein in 
tissues.
 Promotes the use of fatty acids 
as energy source and decreases the 
use of glucose.
 Stimulates liver cells to synthesize 
glucose from non-carbohydrates 
(gluconeogenesis) and increases 
blood glucose concentrations

Question 9

Effects of Glucocorticoid-Cortisol on Inflammation and Immune Function

Answer 9

Regulate adaptive immunity by inhibiting
lymphocyte activation and promoting lymphocyte
apoptosis.

At high concentrations, glucocorticoids also inhibit
the production of B cells and T cells.

Glucocorticoids have potent anti-inflammatory and
immunosuppressive properties.

Question 10

Mineralocorticoid-Aldosterone

Answer 10

 Affects the body's ability to regulate 
blood pressure. 
 It sends the signal to organs, like the 
kidney and colon, that can increase 
the amount of sodium the body 
sends into the bloodstream or the 
amount of potassium released in the 
urine. 
 The hormone also causes the 
bloodstream to re-absorb water with 
the sodium to increase blood volume

Question 11

Androgen

Answer 11

The major sex hormone in men is
testosterone, which is produced
mainly in the testes

Question 12

Hormones of Adrenal Medulla

Answer 12

 Composed of chromaffin cells, which 
synthesize and secrete 
catecholamines 
(mainly epinephrine and lesser 
amounts of norepinephrine). 
 Chromaffin cells also produce 
bioactive amines and peptides (eg, 
histamine, serotonin, chromogranins, 
neuropeptide hormones). 
 Epinephrine and norepinephrine, the 
major effector amines of the 
sympathetic nervous system, are 
responsible for the “flight or fight” 
response

Question 13

Adrenal Insufficiency

Answer 13

Most adrenal deficiency syndromes affect

output of all adrenocortical hormones

Question 14

ADDISON’S DISEASE (Primary Adrenal Insufficiency)

Answer 14

In Addison’s disease,
 There is increased excretion of Na and decreased excretion of K, chiefly in the urine
 Low blood concentrations of Na and Cl and a high concentration of serum K result.

Inability to concentrate the urine, combined with
 changes in electrolyte balance,
 produces severe dehydration,
 plasma hypertonicity, acidosis, decreased circulatory volume, hypotension, and circulatory collapse.

Question 15

Pathophysiology Addison’s disease

Answer 15

Mineralocorticoid deficiency
Mineralocorticoids stimulate sodium reabsorption and
potassium excretion:
 Deficiency results in increased excretion of sodium and
decreased excretion of potassium, chiefly in urine but also in sweat, saliva, and the gastrointestinal tract.
 A low serum concentration of sodium (hyponatremia) and a high concentration of potassium (hyperkalemia) result.

Glucocorticoid deficiency
 Contributes to hypotension and causes severe insulin sensitivity
and disturbances in carbohydrate, fat, and protein metabolism.
 In the absence of cortisol, insufficient carbohydrate is formed from
protein; hypoglycaemia and decreased liver glycogen result.
 Weakness follows, due in part to deficient neuromuscular function.

Glucocorticoid deficiency
Decreased cortisol blood levels result in increased pituitary
ACTH production and
 increased blood levels of lipotropin, which has
melanocyte-stimulating activity and produces the
hyperpigmentation of skin and mucous membranes
characteristic of Addison’s disease.

Question 16

Laboratory Findings for Addison’s disease

Answer 16

Abnormal serum electrolyte levels 
 including low Na (< 130 mmol/L), 
 high K (> 5 mmol/L), 
 low HCO3 (15 to 20 mmol/L) 
 and high BUN
 Diagnosed by demonstrating failure 
to increase plasma cortisol levels, or 
urinary free-cortisol excretion, upon 
administration of ACTH

Question 17

SECONDARY ADRENAL INSUFFICIENCY

Answer 17

Patients with secondary adrenal 
insufficiency are not hyperpigmented, as 
are those with Addison's disease.
 They have relatively normal 
electrolyte levels.
 Hyperkalaemia and elevated BUN 
generally are not present because 
of the near-normal secretion of 
aldosterone in these patients.

Question 18

SECONDARY ADRENAL INSUFFICIENCY Diagnosis

Answer 18

 ACTH Stimulation Test

 CRH Stimulation Test

Question 19

Adrenal Hyperfunction

Answer 19

Distinct clinical syndromes depending on the hormone
involved:
 Hypersecretion of aldosterone results
in hyperaldosteronism.
 Hypersecretion of glucocorticoids results in Cushing
syndrome.
 Hypersecretion of androgens results in adrenal virilism.
 Hypersecretion
of epinephrine and norepinephrine results in symptoms
of pheochromocytoma.

Question 20

Primary Aldosteronism

Answer 20

 is a disease in which the adrenal gland(s)
make too much aldosterone which leads to
hypertension (high blood pressure) and low
blood potassium levels.
 Increases the renal distal tubular exchange of
sodium for potassium and hydrogen
 Progressive depletion of potassium and
hydrogen leads to hypokalemia and acidosis
 Excess sodium reabsorption leads to
hypertension

Classification 
 Primary – excess secretion by the 
adrenal glands 
 Secondary – renin-mediated 
secretion 
 Seen in congestive heart failure, 
nephritic syndrome, cirrhosis, 
renal artery hypertension, severe 
arteriolar nephrosclerosis, rare 
renin-secreting tumors

Question 21

Pathophysiology of Primary Aldosteronism

Answer 21

Mechanisms by which this can occur 
are many: 
 1) an adrenal tumour that 
autonomously secretes 
aldosterone; 
 2) unilateral or bilateral 
hyperplasia of the zona 
glomerulosa that oversecretes 
aldosterone; 
 3) or germline or somatic 
mutations that induce aldosterone 
hypersecretion

Question 22

Primary Aldosteronism Diagnosis

Answer 22

Patients with primary aldosteronism typically hav:
 High plasma aldosterone > 15 ng/dL (> 0.42 nmol/L)
 Low levels of PRA, with a ratio of plasma aldosterone (in
ng/dL) to plasma renin activity (in ng/mL/h) > 20.
Electrolytes
 Low K+ and high Na+

Question 23

Secondary Aldosteronism

Answer 23

Caused by something outside the 
adrenal glands.
 Occurs in states of low effective 
arterial blood volume, which 
activates the renin-angiostensin 
concentration and stimulates the 
distal reabsorption of sodium by 
the kidney to restore blood 
volume.

Question 24

Adrenal Virilism

Answer 24

Is a syndrome in which excessive
adrenal androgens cause virilisation

Causes:
Androgen-secreting adrenal tumours
• secrete excess androgens, cortisol, or
mineralocorticoids (or all three).

Adrenal hyperplasia
• usually congenital; delayed virilising adrenal
hyperplasia is a variant of congenital adrenal
hyperplasia.
• Both are caused by a defect in production of
androgens.
• The defect is only partial in delayed virilising
adrenal hyperplasia, so clinical disease may not
develop until adulthood.

Question 25

What is Congenital Adrenal Hyperplasia

Answer 25

 Congenital Adrenal Hyperplasia (CAH) is
a family of inherited disorders affecting
the adrenal glands.
 Autosomal recessive (mutation of
chromosome 6 21-hydroxylase enzyme
impairment)
 Commoner in consanguineous marriage

Question 26

Congenital Adrenal Hyperplasia Pathophysiology

Answer 26

Results in a decrease in cortisol 
secretion leads to increased ACTH 
production, which in turn stimulates 
 (1) excessive synthesis of 
adrenal products in those 
pathways unimpaired by the 
enzyme deficiency and 
 (2) a build-up of precursor 
molecules in pathways blocked 
by the enzyme deficiency.

Question 27

Congenital Adrenal Hyperplasia Clinical Manifestation

Answer 27

Androgen excess – ambiguous 
genitalia, virilization of external 
genitalia , hirsutism, early 
appearance of pubic hair,  penile 
enlargement , excessive height gain 
and skeletal advance.

Question 28

Congenital Adrenal Hyperplasia Diagnosis

Answer 28

Elevated 17-hydroxyprogesterone.
 The most characteristic biochemical abnormality in 21-
hydroxylase deficiency is elevation of 17-
hydroxyprogesterone (17-OHP), the main substrate for the
enzyme.

Question 29

Hypercortisolism (CUSHING’S SYNDROME)

Answer 29

Hyperfunction of the adrenal cortex may be:
 ACTH- independent of ACTH regulation, 
eg, production of cortisol by an 
adrenocortical adenoma or carcinoma. 
 ACTH-dependent hyperfunction of the 
adrenal cortex may be due to 
1. hypersecretion of ACTH by the 
pituitary gland 
2. secretion of ACTH by a nonpituitary 
tumor, such as small cell carcinoma 
of the lung (the ectopic ACTH 
syndrome); or 
3. administration of exogenous ACTH.

Question 30

Hypercortisolism Pathophysiology

Answer 30

Caused by a benign monoclonal pituitary corticotroph
adenoma that secretes excessive ACTH which causes
supraphysiological secretion of glucocorticoids from
the adrenal glands.
The excess circulating cortisol disrupts the normal
physiological diurnal variation in cortisol levels and
exerts negative feedback inhibition on CRH secretion
from the hypothalamus.

Question 31

Hypercortisolism Diagnosis

Answer 31

3 most common tests
 Measurement of midnight 
plasma cortisol or late-night 
salivary cortisol
 24-hour urinary free 
cortisol test 
 and the dexamethasone 
suppression screening test.

24-hour urinary free cortisol test 
Measurement of midnight plasma 
cortisol or late-night salivary cortisol
Dexamethasone suppression 
screening test.

Question 32

Hypercortisolism Diagnosis-Suppression test

Answer 32

Dexamethasone is a synthetic steroid that should suppress the cortisol
production in normal subjects to a very low level.
 Measures whether adrenocorticotrophic hormone (ACTH)
secretion by the pituitary can be suppressed.
 Dexamethasone is given and levels of cortisol are measured.
 Cortisol levels should decrease in response to the administration
of dexamethasone.

Question 33

Hypercortisolism Differential Diagnostic Testing

Answer 33

Once the diagnosis of Cushing’s syndrome has been established, its cause must be identified

ACTH-dependent disease:
 Pituitary Adenoma (also known as Cushing’s Disease)
In this condition, a small tumour causes increased ACTH production.
 Pituitary adenomas are the most common cause of Cushing’s syndrome and makes up
about 70% of cases.
 Ectopic ACTH-producing Tumour
 In this rare condition, a tumour outside of the pituitary is making too much ACTH.
 These tumours are most found in the lung and thymus gland, but have also been found in the thyroid,
ovary, adrenal gland, and liver.

ACTH-independent Disease
 In this condition, either both adrenal glands are hyperactive or there is an adrenal tumour
that is making too much cortisol.

Question 34

Pheochromocytoma

Answer 34

 Is a catecholamine-secreting tumour 
of chromaffin cells typically located in 
the adrenals. 
 It causes persistent or paroxysmal 
hypertension.