Adrenal gland

Question 1

What is the embryonic link between gonads and adrenal gland?

Answer 1

Originate within close proximity before travelling to final location

Question 2

In which part of the adrenal gland does the production of androgens occur?

Answer 2

Within the zona reticularis of the cortex

Question 3

What is Congenital Adrenal Hyperplasisa (CAH)?

Answer 3

An autosomal recessive condition causing a partial or complete block in steroidgenesis of the adrenal cortex affecting cortisol production.

Question 4

What is the most common cause of CAH?

Answer 4

21-hydroxylase deficiency due to a defect in CYP21. Results in cortisol deficiency and androgen excess, with or without aldosterone deficiency.

Question 5

How does 21-hydroxylase deficiency result in the characteristics of CAH?

Answer 5

As cortisol (and aldosterone) pathways are blocked, ACTH stimulates excess production of DHEA and results in ambiguous genitalia = 46 xx, DSD

Question 6

How is CAH diagnosed?

Answer 6

Measuring serum 17OHP (hydroxyprogesterone) levels.

HIGH = 21 OH deficiency as levels build up from the lack of progression into glucocorticoids.

Question 7

Why do boys present later with CAH?

Answer 7

Present with normal genitalia, unless the have an aldosterone deficiency in which case they will present with adrenal crisis

Question 8

What staging system is used to characterise the severity of CAH in females?

Answer 8

Prader staging

Question 9

What will result from a lack of aldosterone?

Answer 9

Adrenal crisis due to a loss of salt

Question 10

Why does adrenal crisis not present straight away?

Answer 10

Infant is protected for 10-14 day by the mother’s steroids.

Question 11

What are the three types of severities that can result from 21 OH deficiency?

Answer 11

Severe salt wasting CAH - Low cortisol and aldosterone = dehydration and low BP. Presents within first 2 weeks of life

Moderate simple virilizing CAH - Low cortisol = mascularisation

Mild non-classical CAH = No change in cortisol or aldosterone

Question 12

What are the two other deficiencies that can result in CAH?

Answer 12

17 OH

11 beta OH

Question 13

Who are raised as female pseudohermaphrodite?

Answer 13

CAH females who are raised as males due to their high levels of androgens that were not treated in time. = 46 xx males

Question 14

If CAH is not detected at birth what else may lead to diagnosis at a late stage?

Answer 14

Inhibition of growth as excess androgens causes epiphyseal plates to fuse early.

Question 15

What treatment is used in CAH?

Answer 15

Glucocorticoids are given to downregulate ACTH to increase cortisol levels and decrease androgen levels.

Question 16

What happens if too much glucocorticoids are given?

Answer 16

Obesity, osteoporosis, LH and FSH suppression = amenorrhea

Question 17

What happens if too little glucocorticoids are given?

Answer 17

Adrenal crisis and androgen excess = anovulation and oligomenorrhea

Question 18

What is an adrenal incidentaloma?

Answer 18

An adrenal benign or malignant tumour detected on a CT scan that is being carried out for other reasons. Detects 3-5% of cases.

Question 19

What does a tumour of the adrenal gland result in?

Answer 19

Excess production of hormones from the medulla or cortex. Usually detected at late stage

Question 20

How can you determine between hormone excess and a malignancy?

Answer 20

Imaging has poor sensitivity and specificity.
Exclude Cushing’s - Dexamethasone 1mg suppression test or 24hr urinary free cortisol.
Exclude phaeochromocytoma - measure plasma metanephrines (catecholamine metabolites)
Exclude primary hyperaldosteronism in pts presenting with high BP and low K - measure renin and aldosterone (diagnostic pair)
Measure DHEA as excess = malignancy
Exclude CAH with 17 OHP levels

Question 21

Why would the removal of the adrenal gland in a Cushing’s patient be fatal?

Answer 21

The excess cortisol production will have inhibited the HPA and wouldn’t restart to return levels to normal, resulting in death.

Question 22

Why are metanephrines measured instead of catecholamines?

Answer 22

Catecholamines have a shorter half life

Question 23

How can imaging be used to determine between benign and malignant tumours?

Answer 23

Carcinomas are irregular and present with bleeding. More likely to be malignant in younger pts.
Cannot determine if ACC or Phaeo
A non-uniform,irregular, >4cm mass with a high density = risk of malignancy and requires surgery

Question 24

Why are benign tumours less dense?

Answer 24

Contain more fat and water

Question 25

What is a phaeochromocytoma?

Answer 25

Tumours of chromaffin cells in the adrenal medulla, causing excess secretion of Ad and NAd.

Question 26

What is a paraganglioma?

Answer 26

A tumour in the sympathetic ganglia outside of the adrenal gland.

Question 27

Is there a genetic link to phaeochromomcytomas?

Answer 27

40% have a genetic cause.

Question 28

What is the most common mutation in Phaeo?

Answer 28

Most common is RET oncogene mutation resulting in multiple endocrine neoplasia (Adrenal, thyroid, parathyroid)
Requires whole family testing

Question 29

Name 4 other mutations that result in phaeo.

Answer 29

VHL
NF-1
SDHC/D
SDHB

Question 30

How do pts with Phaeo present?

Answer 30

Hypertension, headaches, sweating, palpitations, pallor, nausea, postural hypotension, supraventricular tachycardia, fever, weight loss, HF, MI

Question 31

How can Phaeo be diagnosed?

Answer 31

24hr urinary metanephrines and plasma metanephrines

Question 32

What must be done before surgery to remove Phaeo and why?

Answer 32

Must administer:
alpha blockade - e.g. doxazosin. Prevent vasoconstriction and therefor stroke or MI
beta blockade - e.g. propanolol. Treat tachycardia
If the Ad producing tumour is manipulated it will cause a hypertensive crisis due to the Ad release from the tumour and the Ad given in surgery.

Question 33

Why must a FNA not be carried out for ACC or Phaeo?

Answer 33

ACC causes metastasis from seeding

Phaeo causes adrenal hypertensive crisis from Ad excess.

Question 34

How should an ACC be treated?

Answer 34

Complete tumour removal through open surgery. Use adjuvant therapy e.g. mitotane. Survival increased if capsule remains intact.
Use cytotoxic chemo and mitotane if advanced