1. Pituitary Incidentalomas
Fawn M. Wolf, MD
2/2/2018

2. Outline Prevalence Clinical presentation and evaluation
Natural history
Management

7. Over 18,000 pituitaries examined at autopsy:
10.6% contained adenomas (1.5-27%)
Frequency similar for men and women and across all age groups
Vast majority were microadenomas
Only 7 of 18,000 were macroadenomas- significantly differs from what we see in practice, and speaks to the fact that most all macroadenomas come to clinical attention
Note: half stain for prolactin, though this does not mean half of these patients would have detectable hyperprolactinemia
Molitch ME Endcrinol Metab Clin North Am 2008;37:151

8. Prevalence of Incidentalomas on Imaging
Incidentally discovered signal abnormalities
< 10mm (hypodensities):
CT: 4-20%
MRI: 10-38%
Incidental macroadenomas on CT/MRI are quite rare: %
Higher than autopsy series, as not all “signal abnormalities” are true adenomas or other masses

9. Differential Diagnosis of Incidental Pituitary Masses
Adenoma: functional or nonfunctional
Hyperplasia, infarction, hemorrhage
Craniopharyngiomas, Rathke’s cleft cyst
Meningioma
Malignancy: metastases, primary pituitary
Infiltrative: sarcoidosis, TB/fungal
Inflammatory: hypophysitis (autoimmune, etc)
Physiologic hypertrophy: pregnancy, puberty, primary hypothyroidism
Normal variant: large pituitary
Autoimmune hypophysitis: similar to hashimoto’s; case of 52 yo white male with DM1, pernicious anemia, found to have hypogonadism and hyperprolactinemia but no mass, probably has autoimmune hypophysitis

10. Final Clinical Diagnoses of 282 Incidentalomas

11. Final Histopathological Diagnoses of Incidentalomas
Autoimmune hypophysitis: similar to hashimoto’s; case of 52 yo white male with DM1, pernicious anemia, found to have hypogonadism and hyperprolactinemia but no mass, probably has autoimmune hypophysitis

12. Pituitary Adenomas are Common
Is it causing any:
Hormonal hyper secretion?
Hormonal hypo secretion?
Mass effects?

13. Endocrine Evaluation: Functional Adenomas
Prolactin % of adenomas are prolactinomas
ALWAYS test
Acromegaly (growth hormone): IGF % of adenomas are GH secreting.
Cushing’s disease (ACTH): cortisol. 1-15% of adenomas are ACTH secreting.
Consider testing
FSH/LH
TSH
Generally don’t test
Prolactinomas are the most common functional adenoma, and respond well to medical therapy. Autopsy series that look at pituitary stains find a different distribution, with much higher rates of various adenomas (lactotroph, somatotroph, gonadotroph), however a large proportion of these are clinically silent (prolactinomas occur in range of /100,000 patient years).

14. Endocrine Evaluation: Hypopituitarism
Macroadenomas and larger microadenomas (6-9mm):
Common, screening recommended
Smaller microadenomas (<6mm):
Hypopituitarism rarely occurs
Screen only if clinically indicated

15. Evaluation for Hypopituitarism
FSH/LH: common, occurs in 30-70% of patients
Pre-menopausal women: menstrual history
Normal: no labs needed
COCP: labs unhelpful
IUD: labs may be helpful, especially if FSH/LH and estradiol are low
Post-menopausal women:
No HRT: draw FSH, should be elevated
HRT: labs unhelpful
Men
FSH, LH, total +/- free testosterone

16. Evaluation for Hypopituitarism
ACTH: 20-40%
Central adrenal insufficiency
8am cortisol or cosyntropin stimulation test
GH: 10-50%
IGF-1: neither sensitive nor specific. Falsely low: obesity, insulin resistance.
Stimulation test: insulin, glucagon
TSH 20-40%
Overtly low free T4 (or significant drop from known baseline), with inappropriately normal or low TSH
PRL:
Inability to lactate; overtly low PRL typically only seen following apoplexy or with certain medications (aripiprazole)
Central adrenal insufficiency: ACTH directs adrenals to produce cortisol and sex steroids; aldosterone/renin axis still intact. Therefore these patients have less hypotension, and no hyperkalemia.
GH: expensive, cumbersome, modest benefits, last resort once all hormones optimized

17. Additional Work-up
Formal visual field (VF) testing for all patients with a macroadenoma, or a microadenoma abutting the optic nerves or chiasm, even if there are no apparent visual symptoms
Pituitary dedicated MRI (fine cuts though the sella w/w/o gadolinium), if initial study was a CT or brain MRI

18. Natural History of Incidental Nonfunctional Adenomas: Review of 8 Series
2008 review, follow up of up to 8 years: Microadenomas: 85% unchanged, 10% increased in size, 5% decreased. Macroadenomas: 70% unchanged, 20% increased in size, 10% decreased.

19. Natural History: 2016 Canadian referral based registry
328 patients with incidentalomas included
52% female, median age 55 years
73% adenomas, of which 25% were functional and 36% had secondary hormonal deficiency (SHD)
71% presented with macroadenomas

20. Natural History: Risk of growth and worsening hormonal status

21. Indications for Surgery
Visual field deficit, ophthalmoplegia or neurological compromise due to the lesion
Lesion abutting/compressing optic nerves or chiasm
Apoplexy with visual disturbance
Functional tumors, other than prolactinomas
Consideration of surgery: significant growth over time, hypopituitarism (with resolution in 15-50% of patients), lesions close to the optic chiasm with plans for pregnancy

23. Take Home Points
Pituitary adenomas are very common: 10% prevalence on autopsy series
History and physical necessary to assess for visual compromise, hormonal hyper- or hyposecretion
Check prolactin in all pituitary incidentalomas, and consider screening for cushings and acromegaly
Macroadenomas: more likely to grow and cause visual compromise, also more likely to lead to hypopituitarism

24. References
2016 Analysis and Natural History of Pituitary Incidentalomas. Eur J Encrinol 175(1):1-9
2012 Best Pract Res Clin Endocrinol Metab 26(1):9-19
2011 Pituitary Magnetic Resonance Imaging for Sellar and Parasellar Masses: Ten Year Experience in 2598 patients. J Clin Endocrinol Metab 96(6):1633
2011 Natural History of Nonfunctioning Pituitary Adenomas and Incidentalomas: A Systematic Review and Metaanalysis. J Clin Endocrinol Metab 96(4):905
2011 Pituitary Incidentaloma: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 96(4):894
2008 Nonfunctioning Pituitary Tumors and Pituitary Incidentalomas. Endocrinol Metab Clin N Am 37:151.
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