Pituitary Incidentalomas: Evaluation and Treatment Guidelines

1. Practice guidelines for the evaluation and treatment of pituitary incidentalomasA case-based imaging review Narayana S Mamillapalli MD; Marco Pinho MD; William A. Moore MD; Thomas O’Neill MD; Abreu, Marconi MD UT Southwestern Medical Center, Dallas.

2. PURPOSE • To increase awareness within the Neuroradiology community of the evidence based current clinical guidelines for evaluation and treatment of pituitary incidentalomas provided by The Endocrine Society.

3. PART I – PRE TEST Let’s try out a few cases first to evaluate your baseline knowledge (or intuition) before reviewing the formal guidelines… Pick the best option mentally and you’ll have a chance to review these cases later with the correct answers…

4. Case 1 61 yr old female found to have a pituitary lesion during imaging work-up for headaches

5. FINDINGS ? What are the most likely diagnostic possibilities ? Round, subcentimetric lesion within the left aspect of the pituitary gland, mildly deviating the pituitary stalk to the right, demonstrating homogeneous marked hyperintensity on T2-weighted images and no enhancement on T1-weighted post contrast images. The suprasellar cistern is clear without contact on the optic chiasm.

6. What are the most likely diagnostic possibilities ? These findings are most consistent with an intrasellar Rathke’s cleft cyst or cystic microadenoma

7. What should be done next ? A. Follow-up pituitary MRI in 6 months. B. Clinical evaluation with H&P, physical exam and lab evaluation. C. Clinical evaluation with H&P, physical exam, lab evaluation and visual field testing. D. No follow up

8. Case 2 51 yr old female with headache and nausea found to have a pituitary incidentaloma.

9. FINDINGS ? What are the most likely diagnostic possibilities ? Marked, mass-like diffuse enlargement of the pituitary gland extending cranially into the suprasellar cistern and compressing the optic chiasm. Homogeneous enhancement and signal intensity on T2-weighted images.

10. What are the most likely diagnostic possibilities ? Main diagnostic possibilities include macroadenoma, hypophysitis and pseudotumoral pituitary hyperplasia.

11. What should be done next ? Follow-up pituitary MRI in 6 months. Follow-up pituitary MRI in 1 year. C. Clinical evaluation with H&P, physical exam and lab evaluation(for hypersecretion and hypopitutarism). D. Clinical evaluation with H&P, physical exam, lab evaluation and visual field testing. D. Transphenoidal biopsy

12. Case 3 45 yr old female with dull headache and visual changes which became significantly worse in the past week.

13. FINDINGS ? What are the most likely diagnostic possibilities ? Large sellar mass with cystic, septated areas of T1 shortening which are not suppressed on fat saturated images (methemoglobin) extending into the suprasellar cistern with marked compression of the optic chiasm. Focal areas of solid enhancement along the peripheral non-hemorrhagic mass components. There is smooth remodeling of the sella indicating a pre-existing slow growing mass lesion.

14. What are the most likely diagnostic possibilities ? Findings are very suggestive of hemorrhagic infarction of an underlying macroadenoma (pituitary apoplexy). Apoplexy can also rarely occur in healthy glands. Hemorrhagic Rathke’s cleft cyst and craniopharyngeoma are less likely diagnoses.

15. On further evaluation, patient was found to have no lab evidence of hypersecretion, mild hypopituitarism and bilateral visual field defects. What will be the most likely initial treatment approach? Supportive care Dopamine agonists C. Surgical decompression

16. PART IIENDOCRINE SOCIETY RECOMMENDATIONS

17. In 2011, The Endocrine Society published clinical practice guidelines* to help clinician manage pituitary incidentalomas, a modern clinical issue which became reality due to the sensitivity of cross sectional imaging studies such as CT and MRI. Introduction The Endocrine Society defines a pituitary incidentaloma as an "unsuspected pituitary lesion that is discovered on an imaging study for an unrelated lesion". By definition, the imaging study is not done for a symptom such as visual loss, clinical manifestation of hypopituitarism or hormone excess. The prevalence of incidentalomas varies among studies from 4-20% on CT and 10-38% on MRI. **, *** The guidelines were formulated by a task force based on systematic review of evidence and expert consensus. Evidence was developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system to describe the strength of recommendations and quality of evidence. *Journal of Clinical Endocrinology & Metabolism, 96(4):894–904, 2011. ** Ann Intern Med, 15;120(10):817-20, 1994. *** Ann Intern Med, 15;120(10):817-20, 1994.

18. GRADE SYSTEM The GRADE working group published in 2008* a standardization method to rate the quality of evidence available and strengths of recommendation in clinical guidelines. • For the quality of evidence, GRADE uses a system of four cross-filled circles: • “+000 “ denotes very low quality evidence • “++00 “ low quality • “+++0” moderate quality • “++++” high quality • For the strength of recommendation, GRADE uses two categories: • Strong recommendation = “we recommend” and the number 1 • Weak recommendation = “we suggest” and the number 2 • Recommendations listed on this presentation will be annotated according to the GRADE system. *BMJ. 2008 Apr 26; 336(7650): 924–926

19. INITIAL EVALUATION OF A PATIENT WITH A PITUITARY INCIDENTALOMA • Which is the initial clinical evaluation recommended for all patients presenting with a pituitary incidentaloma ? The Endocrine Society recommends: - History and physical examination - Initial lab evaluations for hormone hypersecretion (1, +++0) and hypopituitarism (1,+++0) - Those with lesions abutting the optic nerves or chiasm on MRI should also undergo formal visual field examination (1,++++).

20. IMAGING EVALUATION OF INCIDENTALOMAS • Which is the acceptable imaging modality to initially characterize and follow-up pituitary incidentalomas? The Endocrine Society recommends: - MRI with contrast is recommended to all patients (if the lesion was initially diagnosed by CT) to better delineate the nature and extent of incidentalomas (1,++++). - CT with contrast is the second option in case of contraindications for MR.

21. SURGICAL CONSIDERATIONS FOR PITUITARY INCIDENTALOMAS • When should patients be referred to surgery for a clinically non-functioning incidentaloma? The Endocrine Society recommends surgical consideration for (1,++++): - Lesions causing visual field defects. - Other visual abnormalities, such as ophthalmoplegia or neurological compromise due to compression by the lesion. - Lesion abutting or compressing the optic nerves or chiasm on MRI – an imaging diagnosis. In this case the age of the patient and other factors needs to be taken in consideration. - Pituitary apoplexy with visual disturbance.

22. SURGICAL CONSIDERATIONS FOR PITUITARY INCIDENTALOMAS • When should surgery be considered for clinically hyperfunctioning incidentalomas ? The Endocrine Society recommends surgical consideration for (1,++++): - Hypersecreting tumors other than prolactinomas as recommended by other guidelines of The Endocrine Society and The Pituitary Society. - Macroprolactinomas that failed medical therapy (continues to grow, demonstrate significant mass effect, visual defect, loss of endocrine function)

23. SURGICAL CONSIDERATIONS FOR PITUITARY INCIDENTALOMAS • In which situations should surgery be considered ? The Endocrine Society suggests that surgical may be considered if (2,++00): • Clinically significant growth of the pituitary incidentaloma. • Loss of endocrinological function. - A lesion close to the optic chiasm and a plan to become pregnant. • Unremitting headache.

24. IMAGING FOLLOW-UP OF NONSURGICAL PATIENTS • In patients not meeting criteria for surgical treatment, how should follow-up be performed? The Endocrine Society recommends: - Periodic clinical assessments. - MRI every six months for macroincidentalomas (> 1 cm). (1, ++00) • - MRI every year for microincidentalomas (< 1 cm). (1, ++00) • - If unchanged, repeat MRI every year for macroincidentalomas and every 1–2 yr in microincidentalomas, for the following 3 yr and gradually less frequently thereafter (2, ++00) - Visual field testing in patients with a pituitary incidentaloma that enlarges to abut or compress the optic nerves or chiasm on a follow-up imaging study (1, ++++).

25. BIOCHEMICAL FOLLOW UP OF NON-SURGICAL PITUITARY INCIDENTALOMAS The Endocrine Society recommends: • Patients with hypopituitarism should be performed 6 months after the initial testing and yearly thereafter in patients with a pituitary macroincidentaloma (1, ++00). • Do not need to test for hypopituitarism in patients with pituitary microincidentalomas whose clinical picture, history, and MRI do not change over time (2,++00). • Patients who develop any signs or symptoms potentially related to the incidentaloma or who show an increase in size of the incidentaloma on MRI should undergo more frequent or detailed evaluations as indicated clinically (1,++00).

26. FLOW DIAGRAM FOR THE EVALUATION AND TREATMENT OF PITUITARY INCIDENTALOMAS

27. PART III – POST TEST Now let’s review the initial 3 cases and review a few more to check how much of the recommendations you were able to incorporate into your working knowledge. We’ll also try out some of your neuroradiology skills…

28. Case 1 61 yr old female found to have a pituitary lesion during imaging work-up for headaches

29. What should be done next ? A. Follow-up pituitary MRI in 6 months. B. Clinical evaluation with H&P, physical exam and lab evaluation. C. Clinical evaluation with H&P, physical exam, lab evaluation and visual field testing. D. No follow up

30. What should be done next ? Best option is B, which is the recommended initial follow-up for incidentalomas not compressing the optic chiasm. This patient had normal clinical evaluation and labs. A. Follow-up pituitary MRI in 6 months. B. Clinical evaluation with H&P, physical exam and lab evaluation. C. Clinical evaluation with H&P, physical exam, lab evaluation and visual field testing. D. No follow up

31. What follow up is recommended A. MRI in 3 months B. MRI in 6 months C. MRI in 1 year D. No follow-up necessary.

32. What follow up is recommended Best option is C, which is the recommended initial follow-up for microincidentalomas. Review of follow up recommendations for nonsurgical lesions: - Periodic clinical assessments. - MRI every six months for macroincidentalomas (> 1 cm). • - MRI every year for microincidentalomas (< 1 cm). • - If unchanged, repeat MRI every year for macroincidentalomas and every 1–2 yr in microincidentalomas, for the following 3 yr and gradually less frequently thereafter. A. MRI in 3 months B. MRI in 6 months C. MRI in 1 year D. No follow-up necessary.

33. What follow up is recommended This lesion was stable for 4 years on MRI follow up and most likely represents a Rathke’s cleft cyst. A. MRI in 3 months B. MRI in 6 months C. MRI in 1 year D. No follow-up necessary.

34. Case 2 51 yr old female with headache and nausea found to have a pituitary incidentaloma.

35. What should be done next ? Follow-up pituitary MRI in 6 months. Follow-up pituitary MRI in 1 year. C. Clinical evaluation with H&P, and lab evaluation. D. Clinical evaluation with H&P, lab evaluation and visual field testing. D. Transphenoidal biopsy

36. What should be done next ? Best option is D, which is the recommended initial follow-up for incidentalomas abutting or compressing the optic chiasm. Follow-up pituitary MRI in 6 months. Follow-up pituitary MRI in 1 year. C. Clinical evaluation with H&P, and lab evaluation. D. Clinical evaluation with H&P, lab evaluation and visual field testing. D. Transphenoidal biopsy

37. FOLLOW-UP • Visual field testing: Normal • Labs: TSH 256 (Normal: 0.40 - 4.50 mcIU/mL) FT4: 0.1 (Normal: 0.8 - 1.8 ng/dL) • Diagnosed with severe hypothyroidism and started on levothyroxine.

38. POST TREATMENT FOLLOW-UP 12/2012 03/2013 09/2014

39. Given the presentation and serial imaging + lab findings, what is the correct diagnosis ? 12/2012 03/2013 09/2014 Thyrotropin secreting macradenoma Null cell macroadenoma C. Hypophysitis D. Pseudotumoral Pituitary Hyperplasia

40. Given the presentation and serial imaging + lab findings, what is the correct diagnosis ? 12/2012 03/2013 09/2014 Thyrotropin secreting macradenoma Null cell macroadenoma C. Hypophysitis D. Pseudotumoral Pituitary Hyperplasia

41. Given the presentation and serial imaging + lab findings, what is the correct diagnosis ? 12/2012 03/2013 09/2014 Longstanding hypothyroidism can induce massive pituitary hyperplasia, which can simulate a primary mass. Gland enlargement usually resolves after exogenous administration of thyroid hormones, like in this case.

42. Case 3 45 yr old female with dull headache and visual changes which became significantly worse in the past week.

43. On further evaluation, patient was found to have no lab evidence of hypersecretion, mild hypopituitarism and acute bilateral visual field defects. What will be the most likely initial treatment approach? Supportive care Dopamine agonists C. Surgical decompression

44. On further evaluation, patient was found to have no lab evidence of hypersecretion, mild hypopituitarism and acute bilateral visual field defects. What will be the most likely initial treatment approach? Supportive care Dopamine agonists C. Surgical decompression

45. On further evaluation, patient was found to have no lab evidence of hypersecretion, mild hypopituitarism and acute bilateral visual field defects. What will be the most likely initial treatment approach? Supportive care Dopamine agonists C. Surgical decompression Best option is C. Visual field compromise is usually a formal indication for surgical decompression, specially in the acute/subacute setting to prevent permanent damage to the optic apparatus.

46. Case 4 56 year old female, sellar mass found on head CT after motor vehicle accident

47. What is the most likely diagnosis ? A. Microadenoma. B. Macroadenoma. C. Craniopharyngeoma. D. Rathke’s Cleft Cyst

48. What is the most likely diagnosis ? A. Microadenoma. B. Macroadenoma. C. Craniopharyngeoma. D. Rathke’s Cleft Cyst

49. What is the most likely diagnosis ? Optic chiasm Rathke’s cleft cyst Intracystic nodule A well defined intracystic nodule within a cystic, nonenhancing sellar or suprasellar mass is very suggestive of a Rathke’s cleft cyst with intracystic nodule*,**. *AJNR Am J Neuroradiol 21:485–488, March 2000 **Journal Neurosurgery, 103:837–840, 2005.

50. What should be done next? Follow-up pituitary MRI in 6 months. Follow-up pituitary MRI in 1 year. C. Clinical evaluation with H&P, physical exam and lab evaluation. D. Clinical evaluation with H&P, physical exam, lab evaluation and visual field testing. D. Transphenoidal biopsy