Guideline sources The following summarized guidelines for the evaluation and management of nonfunctioning pituitary adenoma (NFPA) are prepared by our editorial team based on guidelines from the European Society of Endocrinology (ESE 2021), the American College of Radiology (ACR 2019), the Congress of Neurological Surgeons (CNS 2016), the French Endocrine Society (FES 2015), and the Endocrine Society (ES 2011). 1 2 3 4 5 6 7 8 9 10 11 12 13 14 14 15 Definition A NFPA is a benign neoplasm of neuroendocrine origin that lacks clinical evidence of hormonal hypersecretion. 12 Epidemiology The factors that induce neoplastic transformation of pituitary cells include various abnormalities in cell cycle regulation and genetic mutations (p16, PTTG1, PRKRA1, and AIP. 14 Pathophysiology https://web.pathway.md/diseases/recZltHkLpZagBnpF 1/7 6/30/23, 1:20 AM Nonfunctioning pituitary adenoma Pathway The prevalence and incidence of non-functioning pituitary adenoma are 7.0-41.3 per 100,000 population and 0.65-2.34 per 100,000 person-years, respectively. 13 Disease course The clinical manifestations of NFPAs are related to local mass effect (headache, visual field abnormalities, pituitary apoplexy, hypopituitarism, and hyperprolactinemia). 14 Prognosis and risk of recurrence A complete surgical resection of symptomatic NFPAs is achieved in 40-50% of patients undergoing surgery. 15 Guidelines 1. Diagnostic investigations Pituitary imaging: As per CNS 2016 guidelines, obtain high-resolution MRI for preoperative assessment in patients with NFPA. B Show 2 more As per ES 2011 guidelines, obtain MRI, if possible, to evaluate the pituitary incidentaloma (if initially diagnosed by CT) to better delineate the nature and extent of the incidentaloma. A Endocrine evaluation: As per CNS 2016 guidelines, obtain routine evaluation of all anterior pituitary endocrine axes to assess for hypopituitarism in patients with NFPA. B Show 2 more As per FES 2015 guidelines, obtain routine prolactin testing in patients with pituitary microincidentaloma suggesting microadenoma. E Show 3 more As per ES 2011 guidelines, elicit a complete history and perform a physical examination including assessments for evidence of hypopituitarism and hormone hypersecretion syndrome in all patients with pituitary incidentaloma, including asymptomatic cases. Obtain biochemical evaluation in patients with evidence of either of these conditions. B Opthalmologic evaluation: As per CNS 2016 guidelines, obtain a pretreatment evaluation by an ophthalmologist (including assessments of acuity, visual fields, disc appearance, quantitation of afferent pupillary defect and visual evoked potentials, and optical coherence tomography) to identify asymptomatic visual deficits, as well as to provide prognostic factors for recovery and, when paired with postoperative evaluation, document postoperative change in patients with NFPAs. B Show 3 more As per FES 2015 guidelines: https://web.pathway.md/diseases/recZltHkLpZagBnpF 2/7 6/30/23, 1:20 AM Nonfunctioning pituitary adenoma Pathway Do not obtain visual assessment in patients with suspected microadenoma or when the lesion is remote from the optic chiasm. D Obtain visual assessment in patients with a lesion situated close to the optic chiasm or found to be compressing it on MRI. E As per ES 2011 guidelines, obtain a formal visual field assessment in all patients with pituitary incidentaloma abutting the optic nerves or chiasm on MRI. A 2. Diagnostic procedures Histopathology: calculate the NFPA proliferative index and perform staining for adrenocorticotrophic hormone to identify silent corticotroph adenomas and provide guidance on the risk of adenoma progression as well as the benefit of earlier adjuvant radiation. B 3. Medical management Watchful waiting: As per FES 2015 guidelines, do not obtain imaging or hormonal surveillance in patients with nonfunctioning microadenoma of 5 mm diameter. Provide reassurance to the patient. D Show 5 more As per ES 2011 guidelines, obtain follow-up with clinical, imaging, visual, and laboratory assessments in patients with incidentalomas not meeting the criteria for surgical removal. B Show 4 more 4. Perioperative care Preoperative hormone replacement: initiate HRT preoperatively in all patients with adrenal insufficiency or significant hypothyroidism. B Perioperative corticosteroids: initiate corticosteroid supplementation in the perioperative period in patients with NFPA with preoperative or immediate postoperative (day 2) hypocortisolemia. B Postoperative laboratory assessment: Obtain monitoring of serum sodium levels on the first 2 days after surgery and on postoperative days 7-8 to prevent symptomatic postoperative hyponatremia. B Insufficient evidence to recommend testing and treatment of postoperative diabetes insipidus. I 5. Surgical interventions Surgical resection, indications: https://web.pathway.md/diseases/recZltHkLpZagBnpF 3/7 6/30/23, 1:20 AM Nonfunctioning pituitary adenoma Pathway As per CNS 2016 guidelines, perform surgical resection as first-line treatment in patients with symptomatic NFPA. B As per ES 2011 guidelines: Perform surgery in patients with pituitary incidentaloma in the presence of the following: visual field deficit due to the lesion 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 pituitary apoplexy with visual disturbance hypersecreting tumors other than prolactinomas. A Consider performing surgery in patients with pituitary incidentaloma in the presence of the following: clinically significant growth of the pituitary incidentaloma loss of endocrinological function lesion close to the optic chiasm while planning to become pregnant unremitting headache. C Surgical resection (technical considerations): perform transsphenoidal microsurgery or endoscopic resection for symptomatic relief in patients with NFPA. B Show 4 more 6. Specific circumstances Pregnant patients (evaluation): obtain neuro-ophthalmologic evaluation in pregnant patients with adenomas impinging visual pathways or in case of suspected tumor progression or pituitary apoplexy. B Show 3 more Pregnant patients (management): consider performing surgery to reduce the risk of chiasmal compression and enhance fertility in patients with nonfunctioning adenoma near the optic chiasm planning pregnancy. C Show 2 more Pregnant patients (monitoring): Monitor pregnant patients with a known pituitary adenoma, particularly in large sizes (> 1 cm) and with pituitary deficiencies, by an endocrinologist and an advanced nurse practitioner where relevant. Decide on the frequency based on the underlying condition and individualized needs. B Avoid obtaining routine endocrinological follow-up during pregnancy in patients with intrasellar nonfunctioning microadenoma and an uneventful pregnancy. D Pregnant patients (delivery and breastfeeding): https://web.pathway.md/diseases/recZltHkLpZagBnpF 4/7 6/30/23, 1:20 AM Nonfunctioning pituitary adenoma Pathway Consider providing standard obstetrical care with close maternal and fetal surveillance in pregnant patients with pituitary adenomas. C Recognize that breastfeeding is generally feasible and not contraindicated. B 7. Patient education Preoperative counseling: counsel older patients and patients with longer duration (> 4 months) of vision loss regarding the reduced chance of postoperative vision improvement. B Preconception counseling: manage female patients of reproductive age contemplating pregnancy with a diagnosis of pituitary adenoma, functioning or nonfunctioning, by an endocrinologist. B Show 3 more 8. Follow-up and surveillance Postoperative imaging surveillance: As per ACR 2019 guidelines, obtain sellar MRI for surveillance after pituitary or sellar mass resection in adult patients. B As per CNS 2016 guidelines, obtain serial neuroimaging when no residual tumor is present or only a small intrasellar tumor remains postoperatively. B As per FES 2016 guidelines, obtain MRI with the addition of T2- and T1-weighted images with fat suppression sequences for imaging follow-up of NFPA after surgical treatment or radiotherapy. B Show 4 more Postoperative endocrine surveillance: obtain endocrine evaluation for pituitary dysfunction after surgery or radiotherapy in patients with NFPA. B Show 5 more Postoperative ophthalmic surveillance: obtain postoperative ophthalmologic surveillance to evaluate the postoperative change in the visual field and visual acuity after surgical treatment or radiotherapy of NFPA. Insufficient evidence regarding the frequency and length of this surveillance. B Management of residual or recurrent adenoma (repeat surgery): perform repeat resection for the treatment of symptomatic recurrent or residual NFPAs. B Management of residual or recurrent adenoma (radiosurgery and radiotherapy): perform radiosurgery and radiation therapy for the treatment of residual or recurrent NFPA, to lower the risk of subsequent tumor progression. B Show 2 more Clinical findings https://web.pathway.md/diseases/recZltHkLpZagBnpF 5/7 6/30/23, 1:20 AM Nonfunctioning pituitary adenoma Pathway Symptoms Past medical history Amenorrhea Diabetes inspidus Blurry vision Hypogonadism Cold intolerance Hypopituitarism Fatigue Hypothyroidism Headache Infertility Low sex drive Pituitary apoplexy Menstrual irregularity Neurological exam Oligomenorrhea Thirst Bitemporal hemianopia Urinary frequency Ophthalmoplegia Vertigo Visual field defect Vision loss Gynecologic exam Weakness Weight gain Anovulation Weight loss Imaging findings Anthropomorphic exam Pituitary mass Delayed puberty Ocular exam Central vision loss Optic atrophy Peripheral vision loss Lab findings ACTH serum GH serum TSH serum cortisol References 1. Fran oise Galland, Marie-Christine Vantyghem, Laure Cazabat et al. Management of nonfunctioning pituitary incidentaloma. Ann Endocrinol Paris). 2015 Jul;76 3 191 200. Open 2. Expert Panel on Neurologic Imaging:, Judah Burns, Bruno Policeni et al. ACR Appropriateness Criteria Neuroendocrine Imaging. J Am Coll Radiol. 2019 May;16 5S S161 S173. Open 3. A Luger, L H A Broersen, N R Biermasz et al. ESE Clinical Practice Guideline on functioning and nonfunctioning pituitary adenomas in pregnancy. Eur J Endocrinol. 2021 Aug 23;185 3 G1 G33. Open 4. Ziu M, Dunn IF, Hess C et al. Congress of Neurological Surgeons Systematic Review and Evidence- Based Guideline on Posttreatment Follow-up Evaluation of Patients With Nonfunctioning Pituitary https://web.pathway.md/diseases/recZltHkLpZagBnpF 6/7 6/30/23, 1:20 AM Nonfunctioning pituitary adenoma Pathway Adenomas. Neurosurgery. 2016 Oct;79 4 E541 3. Open 5. Sheehan J, Lee CC, Bodach ME et al. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline for the Management of Patients With Residual or Recurrent Nonfunctioning Pituitary Adenomas. Neurosurgery. 2016 Oct;79 4 E539 40. Open 6. Newman SA, Turbin RE, Bodach ME et al. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Pretreatment Ophthalmology Evaluation in Patients With Suspected Nonfunctioning Pituitary Adenomas. Neurosurgery. 2016 Oct;79 4 E530 2. Open 7. Fleseriu M, Bodach ME, Tumialan LM et al. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline for Pretreatment Endocrine Evaluation of Patients With Nonfunctioning Pituitary Adenomas. Neurosurgery. 2016 Oct;79 4 E527 9. Open 8. Pamela U Freda, Albert M Beckers, Laurence Katznelson et al. Pituitary incidentaloma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011 Apr;96 4 894 904. Open 9. Lucas JW, Bodach ME, Tumialan LM et al. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Primary Management of Patients With Nonfunctioning Pituitary Adenomas. Neurosurgery. 2016 Oct;79 4 E533 5. Open 10. Chen CC, Carter BS, Wang R et al. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Preoperative Imaging Assessment of Patients With Suspected Nonfunctioning Pituitary Adenomas. Neurosurgery. 2016 Oct;79 4 E524 6. Open 11. Kuo JS, Barkhoudarian G, Farrell CJ et al. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Surgical Techniques and Technologies for the Management of Patients With Nonfunctioning Pituitary Adenomas. Neurosurgery. 2016 Oct;79 4 E536 8. Open 12. Tampourlou M, Fountas A, Ntali G et al. Mortality in patients with non-functioning pituitary adenoma. Pituitary. 2018 Apr;21 2 203 207. Open 13. Ntali G, Wass JA. Epidemiology, clinical presentation and diagnosis of non-functioning pituitary adenomas. Pituitary. 2018 Apr;21 2 111 118. Open 14. Mercado M, Melgar V, Salame L et al. Clinically non-functioning pituitary adenomas: Pathogenic, diagnostic and therapeutic aspects. Endocrinol Diabetes Nutr. 2017 Aug Sep;64 7 384 395. Open 15. Delgado-Lopez PD, Pi-Barrio J, Duenas-Polo MT et al. Recurrent non-functioning pituitary adenomas: a review on the new pathological classification, management guidelines and treatment options. Clin Transl Oncol. 2018 Oct;20 10 1233 1245. Open 16. A Luger, L H A Broersen, N R Biermasz et al. ESE Clinical Practice Guideline on functioning and nonfunctioning pituitary adenomas in pregnancy. Eur J Endocrinol. 2021 Aug 23;185 3 G1 G33. Open 17. John S Kuo, Garni Barkhoudarian, Christopher J Farrell et al. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Surgical Techniques and Technologies for the Management of Patients With Nonfunctioning Pituitary Adenomas. Neurosurgery. 2016 Oct;79 4 E536 8. Open 18. Mateo Ziu, Ian F Dunn, Christopher Hess et al. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Posttreatment Follow-up Evaluation of Patients With Nonfunctioning Pituitary Adenomas. Neurosurgery. 2016 Oct;79 4 E541 3. Open https://web.pathway.md/diseases/recZltHkLpZagBnpF 7/7