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

Outline Prevalence Clinical presentation and evaluation Natural history Management

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

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: 0.1-0.2% Higher than autopsy series, as not all “signal abnormalities” are true adenomas or other masses

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

Final Clinical Diagnoses of 282 Incidentalomas

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

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

Endocrine Evaluation: Functional Adenomas Prolactin. 10-40% of adenomas are prolactinomas ALWAYS test Acromegaly (growth hormone): IGF-1. 2-10% 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 20-100/100,000 patient years).

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

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

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

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

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.

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

Natural History: Risk of growth and worsening hormonal status

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

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

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. 1994 Am J Neuroradiol. 15(4):675 1994 Ann Intern Med. 120(10):817 1997 Radiology 314:287 1937 Am J Pathology Vol 12:205