[031]+[035]+[040] Electrolytes, Adrenal& Calcium cases

Question 1

1. What do the levels of cortisol tell you and what further tests would you perform?

Answer 1

Blood and urine tests for cortisol are used to help diagnose Cushing’s syndrome and Addison’s disease, two serious adrenal disorders. Once an abnormal cortisol concentration has been detected, additional testing to help confirm the excess or deficiency and to help determine its cause should be carried out.

In normal people, cortisol levels are very low at bedtime and at their highest just after waking. This pattern will change if a person works irregular shifts (such as the night shift) and sleeps at different times of the day. In this case, this pattern is obviuously lost (as evident by the given values of plasma cortisol concentrations). Increased or normal cortisol concentrations in the morning along with levels that do not drop in the afternoon and evening suggest an overproduction of cortisol.

In this scenario, ACTH levels are found to be elevated, as well. This would steer the diagnosis towards a pituitary cause or an ectopic secretion of ACTH.

The next helpful test is Dexamethasone Suppression: it will help to determine whether the cause of the cortisol is related to excess ACTH production by the pituitary. This test involves giving the patient oral dexamethasone (a synthetic glucocorticoid) and then measuring their blood and urine cortisol levels. Dexamethasone suppresses ACTH production and should decrease cortisol production if the source of the excess is pituitary related. There are a variety of dosing schedules, but the medication is usually given every 6 hours for either 2 or 4 days prior to blood or urine collection. Separate 24 hour urine samples are collected prior to and throughout the testing period and then the blood and urine samples are measured for cortisol and evaluated.

If the excess cortisol is not suppressed, then the increased cortisol could be due to an ACTH producing tumor outside of the pituitary, due to a problem with the adrenal gland, or due to a medication that the patient is taking.

Question 2

2. What is your diagnosis?

Answer 2

Cushing’s disease. (ACTH dependent Cushing’s syndrome)

Question 3

3. What are the relevant symptoms in this scenario?

Answer 3

• hair growth/acne

• weight gain around the central regions (centripetal obesity)

• change of facial appearance (fuller face “moon face” with facial flushing)

• amenorrhoea/oligomenorrhoea

• Linea rubra (red stretch marks)

• depression

• muscular weakness (proximal myopathy)

Question 4

4. How would you treat the pituitary abnormality with medication ?

Answer 4

Question 5

4. How would you treat the pituitary abnormality with surgery ?

Answer 5

Question 6

1. What is the possible underlying endocrine cause of secondary hypertension in this case?

Answer 6

To diagnose this case you have to be aware of the possible endocrine causes of secondary hypertension:

Hyperaldosteronism:
-Primary hyperaldosteronism (also known as Conn’s syndrome), is due to an aldosterone secreting adrenal tumor (adenoma) or adrenal hyperplasia.

Pseudohyperaldosteronism:
-Genetic causes include Liddle’s syndrome, an ENaC mutation, and Apparent Mineralocorticoid Excess (AME). AME is a rare form of pseudohyperaldosteronism characterized by very early onset and severe hypertension, associated with low renin levels and hypoaldosteronism.

-Among the causes of causes of pseudohyperaldosteroneism is the chronic excessive ingestion of liquorice. Liquorice inhibits the 11-beta hydroxysteroid dehydrogenase type II (HSD11B2, an enzyme that converts cortisol to cortisone) enzyme resulting in inappropriate stimulation of the mineralocorticoid receptor by cortisol due to the structural similarties between cortisol and aldosterone.

-Other endocrine causes of secondary hypertension: hyperthyroidism, acromegaly, pheochromocytoma, etc…

Question 7

2. How would you differentiate between Conn’s syndrome and pseudohyperaldosteronism?

Answer 7

Aldosterone levels are high in primary hyperaldosteronism (Conn’s syndrome), whereas they are low to normal in pseudohyperaldosteronism.

Question 8

3. The doctor prescribes spironolactone for the hypertension and it has no effect, therefore what would the diagnosis be?

Answer 8

The administration of spironolactone did not treat hypertension in this case, thus, the diagnosis is most likely Liddle’s syndrome.

Spironolactone is an aldosterone antagonist, which acts by displacing aldosterone from the mineralocorticoid receptors. Although it is a potassium sparing diuretic drug, it is not effective in Liddle’s syndrome because it acts by regulating aldosterone receptor, thus Liddle syndrome does not respond to this regulation. (as it needs a potassium sparing diuretic that acts directly on ENaC)

Question 9

1. What is your diagnosis?

Answer 9

Vitamin D deficiency is common, particularly in children, pregnant women, breastfed babies, and anyone who stays indoors or covers their skin. It is important to treat and prevent deficiency to ensure good health, growth and strong bones. See your doctor if you think you are at risk of vitamin D deficiency, or if you have symptoms such as muscle or bone pains.

Question 10

2. What treatments are available?

Answer 10

Vitamin D is made in the skin with the help of sunlight – this is the main source of vitamin D. It needs bare skin and direct sunlight (not through a window). People with darker skins will need more sun to get the same amount of vitamin D. Vitamin D is also found in certain foods: liver, some types of fish, and egg yolk. Some cereals or margarines contain added vitamin D. Growing children, pregnant women, and breastfeeding women need extra vitamin D because it is required for growth. So, vitamin D deficiency is more likely to develop in the following groups of people: Pregnant or breastfeeding women.

Breastfed babies whose mothers are lacking in vitamin D, or with prolonged breastfeeding. (These babies do not need to stop breastfeeding, they can have breast milk plus vitamin drops – “breast is still best”). People who get very little sunlight on their skin such as those who are stay indoors a lot, or cover up when outside, for example, if wearing a veil. People with conditions that affect the way the body handles vitamin D such as those with coeliac disease, Crohn’s disease, and some types of liver and kidney disease. People taking certain medicines: carbamezepine, phenytoin, primidone or barbiturates.

People with dark skins or of South Asian origin, elderly people, and those with a family history of vitamin D deficiency.

Question 11

3. How common is this condition?

Answer 11

It is very common. Research suggests that in the UK around 2 in 10 adults, and 9 in 10 adults of South Asian origin, may be vitamin D deficient. Most people don’t have symptoms and are unaware of the problem.