Zona Glomerulosa •
Zona Fasiculata •
Zona Reticularis
•
Steroid Hormones
•
Glucocorticoids
•
Mineralcorticoids
•
Sex Steroids
–
–
–
–
–
–
–
–
–
CHO, lipid & fat metabolism
Increases blood glucose levels & gluconeogenesis
Increases protein breakdown
Inhibits protein synthesis
Elecrolyte & fluid balance
Increases sodium & water retention
Regulated by renin & andiotensin
Low synthesis in adrenals compared to gonads
Virilising hormones may be secreted
4
Conditions Affecting Adrenal Cortex
Adrenocortical Hyperfunction
•
Cushing’s syndrome
•
Hyperaldosterone
•
–
Increased glucocorticoid levels
–
Excessive water retention  Ht
–
Excess androgens (testosterone) in peripheral tissue
Adrenogenital syndromes
•
•
Dehydroepiandrosterone
Androstentendione
Adrenocortical Insufficiency
•
•
Acute Adrenocortical Insufficiency
Chronic Adrenocortical Insuffeciency (Addison’s)
5
Acute Adrenocortical Insufficiency
Aetiology & pathogenesis
•
Sepsis  Waterhouse-Friderichsen syndrome
•
Sudden withdrawal of long term corticosteroid
treatment
–
–
–
–
•
Neisseria meningitidis (classic)
Pseudonomas; pneumococci; H. influenzae (others)
Unclear pathogenesis  endotoxin induced vascular injury
(massive haemorrhage) with associated DIC
Inability of atrophic adrenals to produce glucocorticoids
Stress with underlying chronic adrenal insufficiency
–
Acute adrenal crises on limited physiological reserves
6
Massive adrenal
haemorrhage, resulting in
primary acute adrenal
insufficiency
Metastatic breast
carcinoma affecting the
adrenal gland and causing
primary chronic adrenal
insufficiency
Chronic Adrenocortical Insufficiency
“Addison’s Disease”
Aetiology & pathogenesis
•
•
Primary  Addison’s disease
Secondary causes
–
–
Tuberculosis  caseous necrosis of adrenal cortex
Autoimmune adrenalitis
–
–
–
–
–
–
AIDS
Metastatic disease
Systemic amyloidosis
Fungal infections
Haemochromatosis
Sarcoidosis
•
Ass with e.g. pernicious anaemia; thyroiditis; IDDM
8
9
Morphology
• Primary autoimmune adrenitis
– Irregularly shrunken glands
• TB; fungi; sarcoidosis
– Granulomas in adrenals
• Metastatic Ca
– Adrenals enlarged
– achitecture obscured
• Secondary hypoadrenalism
– Adrenals small & flattened
– Atrophy of corticol cells
10
Clinical Features
•
Insidious onset
•
Primary adrenal disease
•
•
•
•
•
•
–
–
Progressive weakness & fragiability
Non-specific complaints (anorexia; N/V; WL)
–
Hyperpigmentation (increased ACTH)
–
Infections; trauma; sugery  intractable vomiting; abdominl
pain; hypotension; vascular collaspe  death
Hyperkalaemia & hyponatraemia
Hypotension (volume depletion) & dehydration
Hypoglycaemia
Sexual dysfunction
Adrenal crises
Diagnosis
–
Low plasma cortisol
11
Laboratory findings.
1.
A low serum Na level and a high serum P level together
2.
with a characteristic clinical picture suggest the possibility of Addison’s
disease.
Adrenal insufficiency can be specifically diagnosed by:
•
•
3.
low levels of plasma glucocorticoids and
mineralocorticoids, or urinary 17 – hydroxycorticosteroid
(17 – OHCS) or 17 – ketogenic steroid (17 – KGS);
demonstrating failure to increase plasma cortisol levels,
or urinary 17 – OHCS or 17 – KGS excretion, upon
administration of ACTH (in patients with primary adrenal
insufficiency, those with secondary adrenocortical insufficiency will have
a significant increase in plasma cortisol or 24 - h urinary corticosteroid
levels.)
To distinguish between primary and secondary adrenal insufficiency, me
have to find the level of plasma ACTH: primary shows increased, and
secondary shows decreased level.
Features of Addison’s d.
This is a caseating granuloma of tuberculosis in the adrenal gland.
Tuberculosis used to be the most common cause of chronic adrenal
insufficiency.
Now, idiopathic (presumably autoimmune) Addison's disease is much more
14
often the cause for chronic adrenal insufficiency.
The pair of adrenals in the center are normal.
Those at the top come from a patient with adrenal atrophy (with either Addison's
disease or long-term corticosteroid therapy).
The adrenals at the bottom represent bilateral cortical hyperplasia.
This could be due to a pituitary adenoma secreting ACTH (Cushing's disease), or
16
Cushing's syndrome from ectopic ACTH production, or idiopathic adrenal
hyperplasia.
Case Discussion
A 26-year old man is admitted to the
Intensive Care Unit
3 days vomiting – hourly
Drowsy
BP 60/30
Deeply pigmented
Na+
125 mmol/l (N 135-145)
K+
5.4 mmol/l (N 3.5-5.0)
Questions
Diagnosis
Pathogenesis
What hormone is deficient
Diagnostic test
Treatment
Complications
Addison’s disease
Pathogenesis

Destruction of adrenal glands
 Autoimmune
 Tuberculosis
 Tumour/infiltration
 Infective (meningococcus)
Hormone deficiency


Cortisol
Aldosterone
Diagnostic test

Synacthen test
Treatment

Cortisol replacement
 Hydrocortisone/Cortisone

Aldosterone replacement
 Fludrocortisone
Complications

Adrenal crisis – intercurrent illness
Synacthen test
Pituitary
•Baseline cortisol may be
normal in Addison’s disease
•Synacthen test: uses
synthetic ACTH analogue
•Normal response: rise in
cortisol
Synacthen
(=synACTHen)
Adrenal
gland
Cortisol