Week 26-27: HPO Axis & Adrenals

Question 1

At pt demonstrates elevated prolactin. What is the order of investigation?

Answer 1

1. Rule out pregnancy
2. Repeat prolactin level to rule out misreading due to stress/satiation/exercise
3. Obtain detailed drug history to rule out medication effect
4. Ensure no renal insufficiency
5. If prolactin is persistently elevated, image with MRI or CT if MRI is not available.

Question 2

Why isn’t GH a good test?

Answer 2

Released in a pulsatile fashion. Use IGF-1 instead.

Question 3

24 hour urine cortisol.

Answer 3

Screen for Cushing’s.

• integrated measurement of free cortisol
• The higher the value (2-3 times more than normal), the more certain of Cushing’s
• results can be normal in early/mild disease

Question 4

How should we screen for Cushings?

Answer 4

1. 24 hour urine cortisol.

2. Overnight dexamethasone suppression test

Question 5

Overnight dexamethasone test

Answer 5

Screen for Cushing’s.

• Bolus of dexamethasone at midnight and measure serum cortisol at 8am
• The lower the measured cortisol, the more certain we can be at ruling out cushing’s

Question 6

When might overnight dexamethasone test give you a false positive?

Answer 6

Pseudo-Cushings; 
Increased CBG (OCP, estrogen, pregnancy); 
Lower dexamethasone levels (poor absorption, drugs that induce metabolism);

Question 7

Pituitary incidentaloma

Answer 7

10% of normal people have hypointensities that are consistent with pituitary adenoma.

Question 8

What to do if you discover a pituitary incidentaloma

Answer 8

Scan to see if it is functioning.
If it is a macroadenoma, scan for hypopituitarism and check visual fields if it is close to the optic chiasm.
Follow up imaging in the next year.

Question 9

Why is it important to establish a biochemical and clinical diagnosis before imaging?

Answer 9

10% of the population has an incidentaloma. If you jump to imaging you might find one of those and be misled!

Question 10

First line therapy for prolactin-producing tumors?

Answer 10

dopamine agonists

Question 11

First line treatment for functioning pituitary tumours (other than a prolactin-secreting tumor) and symptomatic non-functioning tumor

Answer 11

pituitary surgery

Question 12

common causes of goitre in order

Answer 12

1. iodine deficiency
2. Hashimotos
3. Graves
4. multinodular disease

Question 13

Thyroid adenoma

Answer 13

a benign neoplasm derived from follicular cells. More common in women
older than 30.
Do not require further workup unless they are growing or compressive.

Question 14

How does prolactin cause testosterone insufficiency?

Answer 14

Prolactin inhibits GnRH, thus interfering with release of LH and FSH. LH is responsible for stimulating Leydig cells to synthesize testosterone from cholesterol (a series of steps)

Question 15

What are the risks of the oral glucose tolerance test? When is it contraindicated?

Answer 15

Risk of hypoglycemia. Absolutely contraindicated in patients with chronic heart disease, cerebrovascular disease, and epilepsy.

Question 16

If a patient is hypothyroid due to primary defect of the Thyroid (i.e., Hashimoto’s thyroiditis), what would you expect TSH levels to be in the patient (low, normal, or high)?

Answer 16

We expect high TSH,

Hashimotos is low thyroid due to destruction of the thyroid gland. The feedback will be lost and the brain is thinking “I need to produce thyroid hormone.

Question 17

In addition to the HPA (ACTH) axis, what other HPO axis can be tested with insulin administration?

Answer 17

Growth hormone. This is because GH and cortisol are two of the four coutnerregulatory hormones for insulin (in addition to glucagon and epinephrine). Their role is to increase blood glucose when it is low.

Question 18

what would you expect LH and FSH levels to be if there is a case of primary hypogonadism?

Answer 18

Both would be high in an attempt to stimulate testosterone

Question 19

What would you expect circulating LH and FSH levels to be in a case of secondary hypogonadism

Answer 19

Both would be low because they aren’t being stimulated/secreted from the hypothalamus/pituitary

Question 20

What is a circadian rhythm and an example

Answer 20

aka diurnal; 24 hour
Ex: cortisol - ACTH and cortisol levels are highest in the early morning and lowest at midnight. The circadian rhythm of the HPA is dependent on day:night and sleep:wake patterns.

Question 21

What is an ultradian rhythm and an example

Answer 21

Less than 24 hours; pulsatile;

Examples include GH, LH, and FSH secretion.

Question 22

what is an infraradian rhythm and an example

Answer 22

more than 24 hours;

Ex: menstrual cycle

Question 23

How do pulsatile secretions of sex hormones change throughout life?

Answer 23

In adolescence: rapid, high amplitude bursts of LH secretion at night
Sexual maturity: amplitude of bursts is lower and occurs throughout 24 h.

Bursts of LH occur in response to pulsatile secretion of GnRH (90 mins apart)

Question 24

why aren’t random measures of ACTH or coritsol helpful for determining conditions of glucocorticoid excess or adrenal deficiency

Answer 24

You don’t want a random sample. Take it in the morning when they should be high or at night when they should be low.

Question 25

Which time of day would it be best to do a cortisol for investigation of suspected cushing’s disease?

Answer 25

Take the test at midnight because this is when levels should be lowest.

Question 26

What time of day should a cortisol test be done to investigate a suspected diagnosis of adrenal insufficiency?

Answer 26

At morning because this is when cortisol levels should be highest.

Question 27

At what stage of life are GH secretions most prominent?

Answer 27

During pubertal growth period

Question 28

What regulates the amplitude and frequency of GH pulsations?

Answer 28

the hypothalamus

Question 29

Describe a long feedback loop, generally

Answer 29

The target hormone (i.e., IGF-1) feeds back on the pituitary, hypothalamus, and/or the CNS to regulate axis

Question 30

Describe a short feedback loop, generally

Answer 30

Anterior pituitary hormone (i.e., GH) feeds back onto the hypothalamus to regulate the axis

Question 31

Describe a very short feedback loop, generally

Answer 31

Anterior pituitary hormone (i.e., GH) feeds back on the pituitary to regulate the axis.

Question 32

Two sources of cholesterol for biosynthesis of steroid hormones

Answer 32

1. Circulating cholesterol: Receptor-mediated endocytosis of cholesterol-containing LDL (the major source);
2. De novo synthesis of cholesterol from acetate

Question 33

Best time of day to screen for adrenal insufficiency?

Answer 33

Morning because levels of cortisol should be at their highest in the morning.

Question 34

best time of day to screen for adrenal excess?

Answer 34

Night because levels of cortisol should be at their lowest at night. I.e., screen for cushing’s syndrome with midnight cortisol.

Question 35

how would a biochemical screen differ from a biochemical confirmation test, in terms of sensitivity and specificity

Answer 35

Screen has high sensitivity and confirmation tests have high specificity. They may both be the same test.

Question 36

Definition of Cushing’s Disease

Answer 36

Hypercortisolism as a result of ACTH overproduction from a pituitary tumor.

Question 37

A 78 year old male has refractory and low K. Aldosterone-renin ratio is 850 (normal <650) and saline suppression test confirmed the diagnosis. What is the diagnosis?

Answer 37

Primary hyperaldosteronism.

Question 38

Why is there increased blood pressure in hypercortisolism?

Answer 38

Cortisol has equal binding affinity for the glucocorticoid receptor and the mineralocorticoid receptor. Cortisol is able to act like aldosterone in peripheral tissues and cause Na/H20 retention, and this high BP.

Question 39

How does the dexamethasone suppression test work? What is it good for?

Answer 39

Dex mimics cortisol so it should suppress CRH and ACTH as cortisol would through negative feedback.
A high does dex suppression test will differentiate between cushings disease (pituitary tumor; ACTH suppressed) vs ectopic source of ACTH (ACTH will not be suppressed).

Question 40

What is a normal/low dose dexamethasone suppression test good for?

Answer 40

Can rule out a pseudo-cushings state - this is a state of elevated cortisol that is less significant than the syndrome. Usually attributed to depression, obesity, EtOH.

Question 41

How do diurnal cortisol pulsations change in cushing’s syndrome?

Answer 41

An endogenous source of cortisol causing cushing’s syndrome will result in loss of diurnal cortisol pulsations. The changed pattern of cortisol release happens because the cortisol source is acting autonomously and not responding to pulsatile ACTH stimulation.

Question 42

Why is salivary/urine cortisol preferred to plasma cortisol?

Answer 42

Cortisol is protein bound in the plasma so it will give misleading information about the actual levels of cortisol in the body

Question 43

What will happen to the adrenal glands in cushings disease?

Answer 43

They may hypertrophy because of excessive ACTH stimulation.

Question 44

If we suspected a pituitary source of cushing’s disease, what imaging would we want to do?

Answer 44

MRI pituitary and inferior petrosal singus sampling.

Question 45

Qualities suggesting a benign mass on radiography of the adrenal gland

Answer 45

• good borders
• homogenous texture
• greater washout (means that it’s less vascularized)
• <10 HU (means it’s more fatty)
• not found to be ‘hot’ in nuclear medicine testing

Question 46

Is biopsy helpful to distinguish benign and malignant adrenal masses?

Answer 46

No. Biopsy can’t actually distinguish benign and malignant adrenal masses. Can detect metastases though. You also don’t want to do a biopsy because if it’s a pheochromocytoma, you may disturb it and cause a cortisol rush that could put the pt into hypertensive crisis.

Question 47

You surgically remove an adrenal mass that had been secreting cortisol and causing cushing’s syndrome. What will happen to the pt after surgery?

Answer 47

They will be hypoadrenal at least immediately after surgery, while the other adrenal gland learns to compensate (may still be hypoadrenal to an extent after that).
The blood glucose will drop immediately after surgery (lifted cortisol stimulation that increased blood glucose) and hypertension will ease immediately post-surgery (lifted RAS stimulation).