Pathology of The Adrenal Gland

Describe the Hypothalamo-pituitary-adrenal axis

3 causes of Adrenocortical Hyperfunction (Hyperadrenalism)

▪ Cushing’s syndrome

▪ Hyperaldosteronism

▪ Adrenogenital (Virilising) syndromes

Clinical features of Cushing’s Syndrome

Most common cause of Cushing’s Syndrome

Iatrogenic

What is Cushing’s disease

Excessive ACTH production due to a benign pituitary adenoma

2 other causes of ACTH dependent Cushing’s

ectopic ACTH secretion (paraneoplastic)

ectopic CRH secretion

3 causes of ACTH-independent Cushing’s

adrenal adenoma

adrenal carcinoma

primary cortical hyperplasia

Prevalence of each type of endogenous Cushing’s Syndrome

Cushing’s Disease incidence rate per year

2/10⁶/yr

Cushing’s Disease gender & age risk factors

Commoner in females: (4:1, F:M)

Age: 20-40 years

Main cause of Cushing’s Disease

Small pituitary adenoma

Other cause of Cushing’s Disease

Corticotroph cell hyperplasia in the anterior pituitary

3 causes of Adrenal Cushing’s Syndrome

▪ Adrenal adenoma

▪ Adrenal carcinoma

▪ Cortical hyperplasia

Effect of Adrenal Cushing’s Syndrome on adrenals function

Adrenal Cushing’s Syndrome → The adrenals function autonomously

Adrenal Cushing’s Syndrome main 2 causes

Adenomas and carcinomas are equally common in adults

Adrenal Cushing’s Syndrome main cause in children

In children, carcinomas predominate

Age & Gender risk factors for Adrenal Cushing’s Syndrome

More common in women

Age: 30-50

How common is Autonomous hyperplasia in Adrenal Cushing’s Syndrome

Autonomous hyperplasia is uncommon

What is wrong in Primary Hyperaldosteronism

Autonomous overproduction of aldosterone

How is the RAAs affected by Primary Hyperaldosteronism

Suppression of the renin-angiotensin system

How does Primary Hyperaldosteronism affect electrolytes & what is the effect of this

Excessive Na+ retention & K+ excretion → hypertension

What’s wrong in Secondary Hyperaldosteronism

↑ Activation of RAAS → ↑ Renin → ↑ Aldosterone release

3 causes of Primary Hyperaldosteronism

▪ Primary idiopathic hyperaldosteronism 60%

▪ Adrenal adenoma (Conn syndrome) 35%

▪ Aldosterone-producing carcinoma (rare)

5 causes of Secondary Hyperaldosteronism

▪ Activation of renin-angiotensin system

▪ Heart failure

▪ ↓ renal perfusion

▪ Hypoalbuminaemia

▪ Cirrhosis

True/False Primary Hyperaldosteronism can → severe HTN

True - it can → Moderate to severe HTN

Sx of Hypokalaemia associated with Hyperaldosteronism

Usually asymptomatic

May present with cramps, myopathy, polyuria & nocturia (diabetes insipidus)

Name 2 Adrenogenital Syndromes

Adrenocortical neoplasms

Congenital adrenal hyperplasia

Are Adrenocortical neoplasms more likely to be a carcinoma / adenoma

more likely to be a carcinoma

What causes Congenital adrenal hyperplasia

An inborn enzyme deficiency, which causes a partial block in the synthesis of adrenocortical steroids and an increase in the production of androgens

21-hydroxylase deficiency accounts for approximately 90% of cases

What is the effect of increased testosterone associated with Adrenogenital Syndromes

It can cause Precocious (early) puberty

Primary adrenocortical insufficiency can be acute/chronic - give an example of both

Acute (adrenal crisis)

Chronic (Addison’s disease)

What’s wrong in secondary adrenocortical insufficiency

↓ stimulation of adrenals due to ↓ ACTH

6 Causes of Primary Adrenal Insufficiency

Autoimmune conditions

Infections

Adrenal hemorrhage

Infiltrations

Neoplasms

Drugs

Name 2 Autoimmune conditions that can → Primary Adrenal Insufficiency

adrenalitis (60-70%)

polyglandular autoimmune syndromes

Name 4 Infections that can → Primary Adrenal Insufficiency

Tuberculosis

Histoplasmosis

CMV infection

HIV-associated infection

Name 3 causes of Adrenal hemorrhage that can → Primary Adrenal Insufficiency

Waterhouse-Friderichsen syndrome

Coagulopathy

Traumatic birth

What is Waterhouse-Friderichsen Syndrome

Rapid development of adrenal insufficiency associated with massive bilateral adrenal haemorrhage

Pathogenesis of Waterhouse-Friderichsen Syndrome & complication

Neisseria meningitidis septicaemia → DIC with widespread purpura → Waterhouse-Friderichsen Syndrome → Profound hypotension

Name 3 infiltrations that can → Primary Adrenal Insufficiency

amyloidosis, sarcoidosis, haemochromatosis

Name 3 neoplasms that can → Primary Adrenal Insufficiency

primary and secondary carcinomas (esp. lung and breast), lymphomas

Name 4 drugs that can → Primary Adrenal Insufficiency

ketoconazole, fluconazole, phenytoin, rifampicin

Addison’s Disease sx & signs (including biochemical abnormalities)

▪ Nausea, vomiting, abdominal pain

▪ Weight loss

▪ Muscle weakness, myalgia

▪ Fatigue

▪ Postural hypotension

▪ Darkening of the skin in both exposed and non-exposed parts of the body

▪ Hyponatraemia, hyperkalaemia, hypoglycaemia, hypercalcaemia

3 causes of Secondary Adrenal Insufficiency

▪ Hypothalamic disease

▪ Hypopituitarism

▪ Rapid withdrawal of exogenous corticosteroids or failure to increase steroid dose in periods of stress

4 causes of hypopituitarism

tumour, infiltration, surgery, radiation

Is hyperpigmentation seen more in primary/secondary Adrenal Insufficiency - why?

Seen more in primary

The hyperpigmentation of primary Addison’s disease is lacking in secondary insufficiency because pro-opiomelanocortin levels (derived from ACTH) are low

What are Phaeochromocytomas

Adrenomedullary catecholamine-secreting tumours

Sx of Phaeochromocytomas

Cause 0.1-0.6% of cases of hypertension

What % of Phaeochromocytomas are malignant

10%

What % of Phaeochromocytomas are extra-adrenal

10%

Where would extra-adrenal Phaeochromocytomas be

paraganglionomas in Organ of Zuckerkandl (@ aortic bifurcation) or carotid body

What % of Phaeochromocytomas are not associated with hypertension

10%

What % of sporadic cases of Phaeochromocytomas are bilateral

10%

What % of Phaeochromocytomas are familial

25%

Name 2 Syndromes Associated with Phaeochromocytomas

MEN type IIA

MEN type IIB

Von Hippel-Lindau

Von Recklinghausen

Sturge-Weber (→ port wine stains)

Name 2 conditions other than Phaeochromocytomas that are associated with MEN type IIA

Medullary thyroid CA

Hyperparathyroidism

Name 3 conditions other than Phaeochromocytomas that are associated with MEN type IIB

Medullary thyroid CA

Mucosal neuromas

Marfanoid features

How are Phaeochromocytomas diagnosed

Tumour turns black when treated with potassium dichromate fixative

Why do pheochromocytomas turn black when treated with potassium dichromate fixative

Oxidation of stored catecholamines

Name the 4 classic features of pheochromocytomas & give some others as well

Classic 4:

▪ Sweating

▪ Headaches

▪ Tremor

▪ Palpitations

Others

▪ Sustained or episodic ↑BP

▪ Pallor or flushing

▪ Anxiety

▪ Paraesthesiae

▪ Seizures

▪ Chest pain

▪ Dyspnoea

▪ Abdominal pain

▪ Nausea