Learning Outcomes

Intended learning outcomes:

1. Explain By the can
how ACTH end of thetosession,
lead you should be able
increased
Disorders of the adrenal to:
1- Explain how
pigmentation in certain areas of the body.
2. Explain secretion
cortisol is controlled
the effects by ACTH
of over- and under- and CRH.
cortex 2- Explain how ACTH can lead to
secretion of cortisol.increased pigmentation
of the body. 3. Describe tests of adrenal cortical function
in certain areas

3- Describe the
4. main actions
Explain how of cortisol.
cortisol can have weak
4- Explain the effects
mineralocorticoid under-secretion
of over- and of cortisol.
and androgen effects.
Professor & Consultant pathologist 5- Describe tests of adrenal cortical function
Dr. Alaa Hani 6- Explain how cortisol can have weak mineralocorticoid and androgen
effects.

Disorders of adrenocortical function C- Congenital adrenal hyperplasia:

Abnormal function of the adrenal cortex produces a number of clinical
problems: Genetic disorder(s) Enzyme(s) deficiency in the
A- Hypoactivity: Decreased activity of the adrenal cortex (Addison’s
disease) may be due to: pathway of cortisol synthesis Absence of feedback
1: Diseases of the adrenal cortex (auto-immune destruction) - reduce
glucocorticoids and mineralocorticoids. control of the pituitary gland Increased ACTH
2: Disorders in pituitary or hypothalamus that lead to decreased secretion
of ACTH or CRF only affects glucocorticoids. secretion Adrenocortical hyperplasia Increase sex
B-Hyperactivity: Increased secretion of glucocorticoids (Cushing’s
syndrome) may be due to Boys
1: Increased activity of the adrenal cortex due to tumor (adenoma). hormones secretion
2: Disorders in the secretion of ACTH caused by pituitary adenoma (Androgens) Girls
(Cushing s disease) or ectopic secretion of ACTH
3: Iatrogenic
 So Adrenocortical disorders can be summarized as Excess Cortisol (Cushing's syndrome): Causes
Secondary causes in the
Primary causes in the adrenal cortex pituitary gland or
hypothalamus or other causes
1- ACTH dependent Cushing’s syndrome
A: Pituitary adenoma secreting ACTH (70%)
Hypoactivity 1- Addison diseases (Destruction of the adrenal cortex resulting in Hypopituitarism
(Hormone low levels of glucocorticosteroids and mineralocorticosteroids) B: Ectopic ACTH secretion for example from lung carcinoma (10%)
deficiency)
2- Congenital adrenal hyperplasia: Low cortisol and high
androgens
2- ACTH independent Cushing’s syndrome
Non-ACTH-dependent ACTH-dependent either from: A: Adrenal cortical adenoma (15%)
Cushing’s syndrome (Due to adenoma or hyperplasia of the 1- Pituitary adenoma (Cushing
adrenal cortex) resulting in increased cortisol disease) B: Adrenal cortical carcinoma
Hyperactivity 2- Some cancers that secret
(Hormone excess) ACTH (Like lung cancer, this is C: Adrenal cortical hyperplasia
called Ectopic hormone
secretion)

Primary hyperaldosteronism: Due to Adenoma in the adrenal

3- Iatrogenic (Prolong use of steroids)
cortex secreting Aldosterone (Conn’s syndrome)

Excess Cortisol (Cushing's syndrome): Clinical features & their
pathogenesis
1- Increased muscle proteolysis and hepatic gluconeogenesis that may lead to
hyperglycaemia with associated polyuria and polydipsia (“steroid diabetes”).
2- Increased muscle proteolysis leads to wasting of proximal muscles and
producing thin arms and legs and muscle weakness.
3- Increased lipogenesis in adipose tissue leading to deposition of fat in
abdomen, neck and face and producing characteristic body shape, moon-
shaped face and weight gain.
4- Purple striae on lower abdomen, upper arms and thighs reflecting the
catabolic effects on protein structures in the skin and leading to easy bruising
because of thinning of skin and subcutaneous tissue.
Excess Cortisol (Cushing's syndrome): Clinical features & their
pathogenesis
5- Immunosuppressive, anti-inflammatory and anti-allergic reactions of
cortisol leading to increased susceptibility to bacterial infections and producing
acne.
6- May be back pain and collapse of ribs due to osteoporosis caused by
disturbances in calcium metabolism and loss of bone matrix protein.
7- Mineralocorticoid effects of excess cortisol may produce hypertension due to
sodium and fluid retention.
Excess Cortisol (Cushing's syndrome): symptoms Excess Cortisol (Cushing's syndrome): signs
• Central weight gain
• Change of facial appearance • ‘moon face’
• Insomnia • Plethora
• Depression • Thin skin
• Thin skin • Bruising
• Hair growth • Hypertension
• Acne • Pathological fractures
• Poor libido • Striae

Abdominal striae
 Low cortisol level (Addison’s disease) Causes
Addison diseases (Destruction of the adrenal cortex resulting in low levels of
glucocorticosteroids and mineralocorticosteroids)

Destruction of adrenal cortex could occur due to main two reasons:

1-Most commonly auto-immune adrenalitis
2- Infection mostly due to Tuberculosis (TB)

Facial plethora and Buffalo hump

Low cortisol level (Addison’s disease): Clinical features Low cortisol level (Addison’s disease): Clinical features
A- Chronic debilitating disorder (Addison’s disease):
1- Insidious onset with initial non-specific symptoms of tiredness, extreme
muscular weakness, anorexia, vague abdominal pain, weight loss and B- Addisonian crises:
dizziness. All the previously mentioned effects may be exacerbated by stress such as
2- Extreme muscular weakness and dehydration. trauma or severe infection and lead to nausea, vomiting, extreme dehydration,
hypotension, confusion, fever and even coma.
3- A more specific sign is the increased pigmentation, particularly on the
exposed areas of the body, points of friction, buccal mucosa, scars and palmar This constitutes a clinical emergency that must be treated with intra-venous
creases due to ACTH-mediated melanocyte stimulation (ACTH acts like cortisol and fluid replacement (dextrose in normal saline) to avoid death.
MSH).
4- Decreased blood pressure due to sodium and fluid depletion.
5- Postural hypotension due to fluid depletion.
6- Hypoglycaemic episodes especially on fasting.
 Basis of symptoms & signs of Addison’s

• Lack of aldosterone
• Electrolyte disturbances (Na+, K +, water)
• Reduced circulating volume
• Low blood pressure (Hypotension)
• Lack of cortisol
• Reduced blood glucose – weakness
• Reduced inhibition of ACTH (loss of –ve feedback)
• Enhanced ACTH mimics MSH – pigmentation
• (cortisol but not aldosterone regulate HPA axis)
Hyperpigmentation in Addison’s Disease.

Adrenal Insufficiency: Addison’s disease

Hyperpigmentation at site of
Identical twins: The hyperpigmentation and thin body
previous scar habitus that is often seen in primary adrenal insufficiency (the
woman with adrenal insufficiency is on the right).
Who is this man?
1- Which diseases he had?
2- How he died?
3- What did his wife do after his death?

Congenital adrenal hyperplasia:

Genetic disorder(s) Enzyme(s) deficiency in the

pathway of cortisol synthesis Absence of feedback

control of the pituitary gland Increased ACTH

secretion Adrenocortical hyperplasia Increase sex

Boys
hormones secretion
(Androgens) Girls
 Effects of Congenital Adrenal
The most common enzyme defect is 21-hydroxylase deficiency. Deficiency of Hyperplasia
this enzyme or other enzymes in cortisol pathway of synthesis is inherited as
autosomal recessive

• Increased testosterone
•This results in impaired synthesis of cortisol and aldosterone and • Prenatal – masculinisation of external
accumulation of 17OH-progesterone, which is then diverted to form adrenal genitalia in female
androgens. • Post natal
•In about one-third of cases, this defect is severe and presents in infancy with • Early puberty in males
features of glucocorticoid and mineralocorticoid deficiency and androgen • Virilisation in females
excess, such as ambiguous genitalia in girls.

The adrenal glands

The Adrenal Medulla

 Pheochromacytomas

•2- In (10%) of cases there are multiple,

• Tumors of adrenal medulla produce catecholamines bilateral and extra-adrenal that can arise
that cause hypertension which can be fatal. from the paraganglionic cells.
• It occurs in two different patterns:
•These tumors usually produce nor-
• 1- Sporadic cases (90%): usually single, unilateral, in
the adrenal medulla, produce epinephrine and occur epinephrine.
in the (3rd) or (4th) decades of life.

• Clinical features:
• Most patients presents with hypertension that
can be sustained or paroxysmal.
• Also there is palpitation, anxiety, tremor, pallor,
sweating, chest pain, panic reaction & syncope.
• Diagnosis:
• There is elevation of catecholamines in the blood
and their metabolite in the urine.