Pathology of the Adrenal Glands

Question 1

Briefly describe how congenital problems can cause adrenocortical hyperplasia?

Answer 1

Group of autosomal recessive disorders
Deficiency/ lack of enzyme required for biosynthesis
Altered biosynthesis leads to increased androgen production
Reduced cortisol stimulates ACTH release and cortical hyperplasia

Question 2

What are the 2 causes of endogenous ACTH production in acquired adrenocortical hyperplasia?

Answer 2

Pituitary adenoma (Cushing's disease)
Ectopic ACTH (paraneoplastic syndrome - SCLC)

Question 3

With adrenocortical hyperplasia, is the adrenal gland enlargement diffuse or nodular?

Answer 3

Could be either
Diffuse - ACTH driven
Nodular - usually ACTH independent

Question 4

What is the most common presentation of adrenocortical tumours?

Answer 4

Adults M=F 
Incidental finding
Hormonal effects 
Mass lesion 
Carcinoma with necrosis can cause fever

Question 5

What do adrenocortical adenomas look like?

Answer 5

Well circumscribed and differentiated
encapsulated lesions 
2-3 cm 
Yellow/ yellow brown surface 
Small nuclei, rare mitoses

Question 6

Are most adrenocortical adenomas functional or non-functional?

Answer 6

Most commonly non-functional but can be functional

Question 7

Are most adrenocortical carcinomas more likely to be functional?

Answer 7

Yes

Question 8

Are adrenocortical carcinomas common?

Answer 8

No - rare

Question 9

Where do adrenocortical carcinomas spread?

Answer 9

Local invasion - retroperitoneum, kidney
Mets - usually vascular (liver, lung and bone)
Peritoneum and pleura
regional lymph nodes

Question 10

Adrenocortical carcinomas and adenomas can be hard to tell apart. What features are suggestive of malignancy?

Answer 10

Large size (>50g, often >20cm)
Haemorrhage and necrosis 
Frequent mitoses, atypical mitoses 
lack of clear cells 
capsular or vascular invasion

Question 11

What is the only definite criteria for an adrenocortical carcinoma?

Answer 11

Metastatic spread

Question 12

Define primary aldosteronism.

Answer 12

Autonomous production of aldosterone independent of it’s regulators (ATII and K+)

Question 13

How does primary aldosteronism present?

Answer 13

Significant hyperthyriodism
Hypokalaemia (~30% cases)
Alkalosis

Question 14

What are the 4 subtypes of 1y aldosteronism?

Answer 14

Adrenal adenoma – Conn’s syndrome
Bilateral adrenal hyperplasia
Rare – genetic mutations and unilateral hyperplasia

Question 15

How do you confirm aldosterone excess?

Answer 15

Measure Plasma aldosterone & renin (aldo:renin ratio)
Ratio >750 then Ix with saline suppression test
Failure of plasma aldosterone to suppress by >50% with 2L normal saline confirms 1y aldosteronism

Question 16

How do you decide what the cause of the 1y aldosteronism is?

Answer 16

Confirm sub-type:
Adrenal CT – adenoma
Sometimes adrenal vein sampling to confirm adenoma is true source of aldosterone excess

Question 17

How is bilateral adrenal hyperplasia managed?

Answer 17

Spironolactone or Epelerone (MR anatgonists)

Question 18

How is 1y aldosteronism caused by an adrenal adenoma managed?

Answer 18

Unilateral laproscopic adrenalectomy - cures hypokalaemia and HTN in 30-70% cases

Question 19

What is congenital adrenal hyperplasia?

Answer 19

Rare conditions associated with enzyme defects in the steroid pathway.

Question 20

What is the most common enzyme defect associated with congenital adrenal hyperplasia?

Answer 20

21a-hydroxylase deficiency

Question 21

Why is congenital adrenal hyperplasia a problem?

Answer 21

Altered biosynthesis leads to androgen excess. Decreased cortisol production stimulates ACTH release and cortical hyperplasia

Question 22

What investigations are required for CAH?

Answer 22

Basal (or stimulated) 17-hydroxylase progesterone (key enzyme that helps us make cortisol and aldosterone)

Question 23

What is the classical presentation of CAH?

Answer 23

males: poor weight gain
Adrenal insufficiency
Decreased Na+ but high potassium
Females: genital ambiguity

Question 24

What S&S are seen in non-classical presentation of CAH?

Answer 24

hirsutes, acne, oligomenorrhoea, precocious puberty, infertility

Question 25

What are the prinicples of treatment of CAH in a child?

Answer 25

``` Timely recognition required Glucocorticoid replacement Mineralocorticoid replacement (in some) Surgical correction of ambiguous genitalia Achieve maximal growth ```

Question 26

If CAH is realised in an adult, what treatment principles are required?

Answer 26

Control androgen excess Restore fertility Avoid steroid over-replacement

Question 27

What are acquired forms of adrenocortical hyperplasia?

Answer 27

Endogenous ACTH production (ituitary adenoma or ectopic ACTH from other tumour: paraneoplastic syndrome) Bilateral adrena enlargement

Question 28

The 2 forms of adrenocrotical hyperplasia are diffuse and nodular. What differentiates them?

Answer 28

Diffuse: ACTH driven Nodular: ACTH independent

Question 29

What can cause secondary adrenalcortical hypofunction?

Answer 29

Failure to stimulate adrenal cortex (hypothamalic disorder) | Suppression of adrenal cortex

Question 30

What can cause acute primary adrenalcortical hypofunction?

Answer 30

Rapid withdrawl of steroid treatment Adrenal crisis in pts with chronic adrenocortical insufficiecy Massive adrenal haemorrhage

Question 31

How is adrenalcortical insufficiency treated?

Answer 31

Hydrocortisone Fludrocortisone Education

Question 32

What test is used to diagnose adrenalcortical insufficiency?

Answer 32

Short Synacthen test

Question 33

What colour are phaeochromocytomas typically described as?

Answer 33

Tan

Question 34

Which cells are phaeochormocytomas derived from?

Answer 34

Chromaffin cells of adrenal medulla

Question 35

What do phaeochromocytomas secrete?

Answer 35

Cathecholamines

Question 36

What scan can detect phaeochromocytomas and neuroblastomas?

Answer 36

MIBG scan

Question 37

How are phaeochromocytomas treated?

Answer 37

Surgical excision HTN treatment Full alpha and beta-blockade - Phenoxybenzamine and Atenolol Fluid and/or blood replacement

Question 38

Describe both normal and results showing adrenal insufficiency from a short synacthen test.

Answer 38

Measure plasma cortisol before and 30 mins after IV ACTH injection Normal: baseline >250nol/L Post-ACTH >480nmol/L Addisons – baseline is very low Post-ACTH rise is very high

Question 39

What are the biochemical abnormalities associated with phaeochormocytoma?

Answer 39

``` Hyperglycaemia Decreased K+ (maybe) High haemotocrit Mild hypercalcaemia lactic acidosis - in absence of shock ```

Question 40

In the case of phaeochromocytoma, who should be investigated?

Answer 40

``` Family members with syndromes resistant HTN <50yo with HTN Classical symptoms Consider Ix if HTN and hyperglycaemia ```

Question 41

What are the classical symtpoms of phaeochromocytoma?

Answer 41

``` “dreadful” “feeling of impending doom” Pallor Anxiety constipation Weight loss abdominal pain Pyrexia and sweating Hypertension postural hypotension Headache palpitations ```

Question 42

Why are phaeochromocytomas known as the 10% tumour?

Answer 42

``` 10% exra-adrenal 10% bilateral 10% malignant 10% not associated with HTN 10-25% familial ```

Question 43

How is MEN inherited?

Answer 43

Autosomal doinant genetic condition

Question 44

Briefly , what is Von-Hippel-Lindau syndrome?

Answer 44

Mutation in HIF 1-alpha Autosomal dominant Range of ascular tumours Family screening vital