Biology of Disease

physiological values. Angiotensin II also stimulates thirst that helps to increase

blood pressure. The adrenal cortex secretes androgens, such as testosterone,

dehydroepiandrosterone sulfate (DHEAS) and androstenedione. Testosterone

is the hormone that stimulates the growth and development of the male

characteristics (Section 7.10).

Addison’s Disease

Adrenal hypofunction or Addison’s disease is a rare condition but is simple

to treat once diagnosed. It can arise from one of a number of causes: an

autoimmune destruction of the adrenal cortex, as a response to tuberculosis

(TB), amyloidosis, hemochromatosis, following adrenalectomy or hypo-

thalamic or pituitary diseases referred to as secondary adrenal insufficiency.

Addison’s disease is characterized by a deficiency of glucocorticoids and

mineralocorticoids. Its clinical features include weakness, lethargy, anorexia,

nausea, vomiting, weight loss, hypotension, skin pigmentation, hypoglycemia

and depression (Figure 7.30). In the first few months, symptoms are usually

vague with only lethargy, weakness and weight loss presenting as a result of

glucocorticoid deficiency. Later, patients start to vomit and have abdominal

pain. The lack of mineralocorticoids leads to an excessive loss of Na+ and

therefore hypotension is common in these patients. Plasma ACTH is increased

because of pituitary response to low levels of cortisol given the lack of a

negative feedback mechanism. Adrenocorticotrophic hormone can stimulate

melanocytes in skin to produce the melanin, hence pigmentation is a common

feature in Addison’s disease.

Diagnosis and treatment of Addison’s disease

A clinical suspicion of Addison’s disease can be confirmed by demonstrating

hyperkalemia with hyponatremia (Chapter 8). The plasma cortisol is usually,

but not always, low in these patients. A high concentration of ACTH coupled

with a low concentration of cortisol is indicative of Addison’s disease

whereas low cortisol and ACTH values are suggestive of secondary adrenal

insufficiency. The situation can be resolved using complex biochemical

tests with the analog of ACTH, synacthen. The short synacthen test involves

an intramuscular injection of 0.25 mg of synacthen. The concentration of

plasma cortisol is measured within 30 min. If it rises by at least 200 or to a

value greater than 550 nmol dm–3, then Addison’s disease is unlikely. If this

is not the case, then it is appropriate to proceed to the long synacthen test

which involves an intramuscular injection of 1 mg of ACTH daily for three

days. On the fourth day, the short synacthen test is performed and the serum

concentration of cortisol is measured. If this is less than 200 nmol dm–3 with

no increase following administration of synacthen there is primary adrenal

failure and the patient is suffering from Addison’s disease. If, however, there

is an incremental increase of at least 200 nmol dm–3 above the baseline, then

the decreased output of cortisol from adrenal gland is secondary and due to

a deficiency of ACTH caused by a hypothalamic or pituitary disorder. Once

Addison’s disease is diagnosed, it is necessary to ascertain its cause. A number

of laboratories test for the presence of antibodies against the adrenal glands to

see if there is an autoimmune cause. A plain abdominal X-ray may be useful in

that it can detect calcification of adrenal glands as a result of TB (Chapter 3).

The conventional therapy for Addison’s disease involves treatment with

steroids, such as hydrocortisone and fludrocortisone, which possess

glucocorticoid and mineralocorticoid activities respectively. If a patient is left

untreated he or she will eventually experience an adrenal crisis precipitated

by stress, bacterial infection, trauma or surgery, which is a medical emergency.

Typical clinical features of a crisis are abdominal pain, vomiting, hypotension

together with hyponatremia, hypoglycemia and hyperkalemia. Its treatment

involves administering saline infusions to correct the hypotension, fluid

X]VeiZg,/ DISORDERS OF THE ENDOCRINE SYSTEM

&-) W^dad\nd[Y^hZVhZ

Figure 7.29 (A) Structure of aldosterone and

(B) the regulation of its secretion.

H

O = C C = O

CH 2 OH

CH 3

HO

O

A)

Kidneys

(enzyme

action)

Angiotensin I

Angiotensin II

Angiotensinogen

Adrenal

cortex

Aldosterone

B)

Increased

Na+ retention

in kidneys

Increased

blood pressure

Renin