Ch44 Pituitary adenoma - Evaluation and Non-surgical Management

Question 1

How do you perform a directed examination of the pituitary gland?

Answer 1

Endocrine hyperfunction (prolactin = amenorrhea / galactorrhea; thyroid = heat intolerance sweating etc; GH = acromegaly features; cortisol = cushing’s disease and hyperpigmentation) Endocrine loss of function (hypothyroid, addisons etc) Visual dysfunction (bitemporal hemianopia) Cavernous sinus defect (cranial nerve defects causing opthalmoplegia, proptosis and chemosis)

Question 2

What investigations would you perform in a patient with a suspected pituitary lesion?

Answer 2

Endocrine (8 am cortisol and 24 h urine free cortisol, prolactin, FSH/LH, testosterone (M) and oestradiol (F), IGF-1 and fasting glucose, T4 and TSH). Visual fields - Humphrey perimetry MRI +/- contrast pituitary

Question 3

Why do you perform both 8am cortisol and 24h urine free cortisol testing?

Answer 3

8 am cortisol if best to detect pituitary insufficiency 24h urine free cortisol if best to detect Cushing’s disease

Question 4

What is the other name for IGF-1?

Answer 4

Somatomedin-C

Question 5

What are the ways the visual fields can be tested?

Answer 5

Humphrey automated perimetry > Visual evoked potentials > OCT (document extent of damage to the optic disc)

Question 6

What does red light detection loss signify?

Answer 6

Desaturation of light is an early sign of chiasmal compression

Question 7

What is more common, a pre- or post-fixed chiasm?

Answer 7

Pre (8%) and post (4%). The rest are directly above the sella!

Question 8

What visual field loss is associated with a pituitary adenoma?

Answer 8

Bitemporal hemianopsia! If post-fixed then can have unilateral visual loss with junctional scotoma (pie in the sky) in the contralateral eye due to compression of Willbrand’s knee. If pre-fixed then may have homonymous hemianopia from compression of the ipsilateral optic tract.

Question 9

Which hormones should be replaced pre-op if found to be deficient?

Answer 9

Hydrocortisone and T4. Replaced hydrocortisone first otherwise the T4 may precipitate an Addisonian crisis.

Question 10

How does autoimmune hypophysitis present?

Answer 10

Single hormone loss and thickening of the pituitary stalk

Question 11

What does an 8AM cortisol <6 mcg/100 ml suggest?

Answer 11

Adrenal insufficiency.

Question 12

How is the diagnosis of Cushing’s disease made?

Answer 12

Urine 24 h free cortisol >3 times the upper limit of normal.

False positives with stress and chronic alcoholism.

Question 13

What further tests would you perform is T4 is low and TSH low?

Answer 13

TRH stimulation test.

Check baseline TSH, give TRH 500 mcg then check TSH after 30 and 60 mins.

If the TSH has not doubled by 30 mins then suggests pituitary thyroid deficiency. If TSH goes very high then suggest primary hypothyroidism

Question 14

How do you assess the gonadal axis?

Answer 14

FSH & LH as well as Testosterone (M) and estradiol (F).

Question 15

What does a Prolactin level >200 ng/ml suggest?

Answer 15

Macroadenoma

Question 16

When should prolactin levels be measured?

Answer 16

Mid-morning and not after stress which may falsely elevate it.

Question 17

What is the only pituitary hormone primarily under inhibitory control?

Answer 17

Prolactin (inhibited by Dopamine)

Question 18

What is the treatment of a raised Prolactin due to a stalk effect?

Answer 18

Remove the compression. Don’t start Bromocriptine!

Question 19

What is the Hook effect?

Answer 19

When the prolactin level saturates the assay resulting in a falsely low result. Requires the lab to run serial dilutions.

Question 20

What is macroprolactinaemia?

Answer 20

When the prolactin is bound to Ig and is biochemically non-functional

Question 21

How do you test for DI?

Answer 21

The concentration of urine with water deprivation test.

Further tests include measurement of ADH in response to infusion of hypertonic saline.

Question 22

Why does chronic primary hypothyroidism cause pituitary hyperplasia?

Answer 22

As the pituitary grows in response to a high TRH and TSH due to a lack of T4 negative feedback. A low/normal T4 with high TSH suggest primary hypothyroidism (i.e. problem with the thyroid gland).

Question 23

Why do non-functioning pituitary adenomas cause secondary hypothyroidism?

Answer 23

Mass effect. T4 and TSH are low. There is a reduced response to TRH stimulation.

Question 24

What causes:

1. High TSH and High T4
2. Low TSH and High T4

Answer 24

1. Secondary hyperthyroidism
2. Primary hyperthyroidism

Question 25

What are the causes of a high prolactin?

Answer 25

Pregnancy / lactation Adenoma Stalk effect Drugs (metaclopramide / OCP / TCA / SSRIs / Verapamil etc) Primary hypothyroidism Empty sella syndrome Ectopic secretion Macroprolactinaemia Renal / liver failure

Question 26

Which disease causes the ACTH response to CRH to be exaggerated?

Answer 26

Cushing's syndrome

Question 27

What tests would you perform if the 24h urine free cortisol was unequivocal?

Answer 27

1. Low dose Dexamethasone suppression test (give 1 mg Dex at 11 pm and measure cortisol at 8am). If the cortisol suppresses to \<1.8 mcg/dl then Cushing's syndrome is ruled out. 2. 11 pm salivary cortisol (should be at its lowest point)

Question 28

How do you differentiate Cushing's disease from ectopic ACTH secretion?

Answer 28

High dose Dexamethasone suppression test (give 8 mg at 11 pm and measure plasma cortisol at 8 AM). In 95% of Cushing's disease the ACTH level reduced by 50%. In ectopic causes, it does not suppress. CT CAP Metyrapone test - causes a rise in 11-deoxycortisol with Cushing's disease CRH stimulation test - causes a rise in ACTH and cortisol with Cushing's disease but not with exogenous source IPSS (baseline to peripheral ACTH \>1.4:1 is consistent with Cushing's disease)

Question 29

How is an IPSS performed?

Answer 29

Catheter placed in the IPSS and ACTH levels are measured at baseline and following CRH at 2, 5 and 10 minutes. Comparison between both sides may help lateralisation. Can lead to false lateralisation due to communication throught the intercavernous sinus.

Question 30

What is the compication rate of IPSS?

Answer 30

2% including puncture of the sinus wall

Question 31

How do you assess for Addison's disease?

Answer 31

ACTH stimulation test (synacthin test) if 8am cortisol is low. Measure baseline cortisol, given 250 mcg synacthin and then measure cortisol at 60 mins. If cortisol \>20 mcg/dl then rules out Addisons. If \<20 need steroid replacement. If unequivocal then need to do insulin tolerance test. Insulin given to reduce the BM\<4 and then measure cortisol. If \<20 then need steroid replacement.

Question 32

How can Acromegaly be diagnosed?

Answer 32

IGF-1 level Oral glucose tolerant test - 75 mg glucose given an GH levels measured every 30 mins for 2 hours. The GH level should fall to \<1 ng/ml in normal cases. Octreotide SPECT scan for diagnosis of ectopic GH secretion

Question 33

What is the normal size of the pituitary gland?

Answer 33

\<9 mm (or \<11 mm in females of childbearing age / puberity)

Question 34

What MRI should be requested for suspected pituitary adenomas?

Answer 34

Dedicated 3T MRI of the pituitary +/- contrast If microadenoma then a dynamic MRI allows enhancement to be differentiated from the rest of the gland. Normally the gland enhances before the adenoma.

Question 35

Why does the posterior pituitary have high T1 signal (bright spot) without contrast?

Answer 35

High phospholipid content

Question 36

What does absence of the pituitary bright spot on T1 MRI suggest?

Answer 36

Corresponds with DI due to autoimmune hypophysitis

Question 37

What is the cause of a thickened pituitary stalk?

Answer 37

Lymphoma Autoimmune hypophysitis Granulomatous disease Hypothalamic glioma \*\*note pituitary stalk is approx the same diameter as the basilar artery

Question 38

Why is a CT performed prior to transphenoidal surgery?

Answer 38

To demonstrate the nasal / sphenoid septal anatomy

Question 39

Should you treat hypothyroidism in a patient with pituitary adenoma?

Answer 39

Check for adrenal insufficiency first with synacthen test. Treat adrenal insufficiency first before giving thyroxine.

Question 40

How should you treat GH secreting tumours before surgery?

Answer 40

Somatostatin analogue before surgery to reduce the surgical risks (general and cardiac). Then transphenoidal surgery.

Question 41

What is the recommended treatment for symptomatic non-functioning adenomas?

Answer 41

Surgery Bromocriptine + octreotide may reduce size in 60% of cases Radiotherapy is an effective adjunct for recurrent or residual disease \*\*Observation is only recommended for asymptomatic non-functioning adenomas

Question 42

What are the indications for surgery on a pituitary adenoma?

Answer 42

Mass effect Endocrinopathy Apoplexy Diagnosis Nelson's syndrome (30% of cases of bilateral adrenalectomy develop high ACTH levels which causes pigmentation and enlargement of the pituitary adenoma)

Question 43

What are the side effects of Bromocriptine / Cabergoline?

Answer 43

Postural hypotension, dizziness, depression, nightmares and nasal congestion. Improved by bedtime dosing. Starting bromocriptine can restore fertility but is teratogenic and can lead to spontaneous abortions.

Question 44

What is the difference between Cabergoline and Bromocriptine?

Answer 44

Bromocriptine is D1 and D2-agonist, whilst cabergoline is D2 only. The half life is longer with cabergoline so once weekly dosing.

Question 45

What side effect is associated with Cabergoline?

Answer 45

Cardiac valvular disease due to effect on fibromyoblasts which causes regurgitation due to valvular fibroplasia.

Question 46

How do you manage elderly patients with asymptomatic GH releasing adenomas?

Answer 46

Conservative

Question 47

How long do IGF-1 levels take to normalise after GH adenoma surgery?

Answer 47

Months. There is no defintion of a biochemical cure. Repeat surgery is usually not successful so medical therapy and radiotherapy may be needed as second-line.

Question 48

What are the medical management options for GH-adenomas?

Answer 48

Somatostatin analogues e.g. octreotide GH antagonists - pegvisomant

Question 49

What are the side effects of octreotide?

Answer 49

Gallstones Bradycardia Diarrhoea / abdominal discomfort

Question 50

What is pegvisomant?

Answer 50

Genetically engineered GH-R antagonist

Question 51

What is the management of Cushing's disease?

Answer 51

SURGERY if microadenoma is visible. If not, then IPSS. Surgery on the side suggested by IPSS. If IPSS is negative then look for ectopic source.

Question 52

What is the management if surgery for cushing's disease is unsuccessful?

Answer 52

1. Re-exploration / Completion hypophysectomy 2. SRS if residual cannot be resected e.g. in cavernous sinus 3. Medical therapy 4. Bilateral adrenalectomy

Question 53

What is the difference between a low and high dose Dexamethasone test?

Answer 53

Low dose will only suppress cortisol from a normal gland not an adenoma. Suppression with low dose Dexamethasone rules out a CD. High dose will suppress an adenoma but not an ectopic source.

Question 54

What are the medical treatment options for Cushing's disease?

Answer 54

Ketaconazole - blocks adrenal steriod synthesis Aminoglutethimide - prevents cholesterol to pregnenolone Metyrapone - inhibits 11-beta hydroxylase preventing 11-deoxycortisol to cortisol Mitotane - inhibits multiple steps in steroid synthesis Ciproheptadine - seratonin-R antagonist

Question 55

What is the management for pituitary adenomas secreting TSH?

Answer 55

Surgery Radiotherapy to residual Medical therapy = octreotide. Causes tumour shrinkage in 1/3,

Question 56

What is the side-effect of radiotherapy to pituitary adenomas?

Answer 56

50% are panhypopituitary at 10 years. May cause blindness due to optic nerve / chiasm injury Mental / cognitive disturbance Cranial nerve palsies Apoplexy

Question 57

How long does radiotherapy take to work for acromegaly and Cushings?

Answer 57

10-20 years for Acromegaly and 1-2 years for Cushing's