Page 444 - Medicine and Surgery

P1: FAW
BLUK007-11 BLUK007-Kendall May 25, 2005 8:5 Char Count= 0

440 Chapter 11: Endocrine system

Age ACTH-secreting tumour of the pituitary which enlarges
Anyage, peak 20–40 years. post-bilateral adrenalectomy).

Sex Addison’s disease
8F : 1M
Definition
Aetiology First described by Thomas Addison in 1857, Addison’s
In virtually all patients, an ACTH-secreting pituitary disease is primary adrenal insufficiency.
adenoma is found, occasionally the cause is hypothala-
mic oversecretion of corticotrophin releasing hormone
Aetiology
(CRH).
In Western countries autoimmune disease is the com-
monest cause (80%). It is familial, and associated with
Pathophysiology/clinical features other organ specific autoimmune diseases, especially
As for Cushing’s syndrome. Unlike patients with ec- thyroid failure (Schmidt syndrome), autoimmune gas-
topic ACTH syndrome, patients with pituitary adeno- tritis, pernicious anaemia and vitiligo. Presence of HLA-
mas rarely have hypokalaemia, weight loss, anaemia or B8 association carries a x12 risk of developing disease.
hyperpigmentation. Worldwide, tuberculosis is still a very important cause
(see Table 11.11).
Macroscopy
Bilateral adrenocortical hyperplasia twice the size of
Pathophysiology
normal, with thickening of zona reticularis and the
The mineralocorticoids (90% activity by aldosterone,
zona fasciculata. The zona glomerulosa appears normal,
some by cortisol) act on the kidneys to conserve
because mineralocorticoid production is controlled pri-
+
sodium by increasing Na /K exchange in the dis-
+
marily by the renin–angiotensin system.
tal tubules and collecting ducts. In Addison’s dis-
ease, gradual loss of these hormones causes increased
Microscopy sodium and water loss with a consequent decrease in
The pituitary tumour is normally a microadenoma. The
cellscontain ACTH and its related peptides.
Table 11.11 Causes of adrenal insufficiency
Investigations
Primary
As for Cushing’s syndrome (see page 438).
Congenital/familial
Adrenal enzyme defects
Management Congenital adrenal hypoplasia
The treatment of choice is transsphenoidal hypophysec- Acquired
tomy.Irradiationisusedpost-surgery,forpatientswhere Infectious – TB, histoplasmosis, HIV associated
cytomegalovirus
complete resection was not possible. Drugs which in-
Autoimmune
hibit adrenal cortisol synthesis are often used as adjunc- Vascular – haemorrhage (associated with meningococcal
tivetherapy,e.g.ketoconazole,metyraponeandaminog- septicaemia – Waterhouse-Friderichsen syndrome),
lutethimide. Their disadvantage is that they increase thrombosis
ACTH secretion so this enzyme inhibition is overcome Neoplastic – secondary carcinoma (e.g. lung)
Degenerative – amyloid
and the clinical effect is short-lived. Secondary
Bilateraladrenalectomyisstillusediftheadrenalshave Hypopituitarism
become semi-autonomous, however it must be followed Isolated ACTH deficiency
by pituitary treatment (e.g. irradiation) as otherwise the Following glucocorticoid therapy
Drug-induced glucocorticoid metabolism
pituitary adenoma can progress to cause hyperpigmen-
Rifampicin, carbamazepine
tation, local pressure effects and Nelson’s syndrome (an