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Pituitary Incidentalomas

Pituitary Incidentalomas. Endocrinology Rounds Kristin Clemens PGY 5 November 7 th , 2012. Objectives. Epidemiology of pituitary incidentalomas Underlying causes Outline understanding of natural history Review recent practice guidelines on pituitary incidentalomas

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Pituitary Incidentalomas

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  1. Pituitary Incidentalomas Endocrinology Rounds Kristin Clemens PGY 5 November 7th, 2012

  2. Objectives Epidemiology of pituitary incidentalomas Underlying causes Outline understanding of natural history Review recent practice guidelines on pituitary incidentalomas Illustrative cases for work up and management

  3. Case – E.A. 70 year old man HTN, hypercholesterolemia Diovan, Crestor No family history Non smoker, rare ETOH, lives independently with wife

  4. Acute onset memory impairment – ER Diagnosis of transient global amnesia CT to rule out stroke demonstrated 2 x 1.9 x 1.6 cm pituitary macroadenoma MRI encroachment of left cavernous sinus, touching L optic nerve

  5. Pituitary MRI

  6. How to assess him at follow-up endocrinology appointment?

  7. Pituitary incidentaloma Previously unsuspected pituitary lesion discovered on an imaging study performed for an unrelated reason Increasingly common

  8. Prevalence Estimated from pituitary adenomas found at autopsy and from imaging inpatients who underwent CT or MRI Combined autopsy data suggests frequency of 10.6%, distributed equally amongst genders, age range MRI and CT incidence of 4-38%

  9. Etiology • Rathke cleft cysts • Craniopharyngiomas • Meningiomas • Pituitary hyperplasia • Metastases • Pituitary adenoma – 10% • Macroadenoma >1cm • Microadenoma <1 cm, most common • Functioning and non-functioning

  10. Pituitary Adenomas • Variety of subtypes • Data from small observational studies • Buurman, 2006 • Series of 3048 autopsy cases examined to detect incidence of subclinical adenomas in postmortem pituitaries • 1991-2004

  11. Buurman et al Found a total of 334 adenomas out of 3048 cases (10.4%) examined 157 males and 159 females Mean age of 73

  12. Size range from 0.1 to 20 mm Only 3 were macroadenomas Some with multiple adenomas Multiple staining techniques

  13. 39.5% stained positive for prolactin 31.7% null cell adenoma/oncocytomas 13.8% stained positive for ACTH 7.2% for gonadotropins 1.8% stained positive for GH 0.6% for TSH 3% for multiple hormones Small percentage unclassified

  14. Clinical history Clinical significance? 99 patients with HTN, 65 with diabetes No symptoms of adenohypophyseal hormone hypersecretion were reported Rare cases of clinical hypo and hyperthyroidism No clear correlation between clinical data and adenoma type in this sample

  15. Natural History?

  16. Small observational cohort studies

  17. Fernandez-Balsells, 2011 • Systematic review of longitudinal observational cohort studies that enrolled patients with: • Incidentalomas (asymptomatic lesions) • Non-functioning pituitary adenomas (mass effect/hypopituitarism) • Followed without any treatment from the time of detection

  18. Outcomes of interest including development of visual field defects, neurological defects, alteration in pituitary function, pituitary apoplexy

  19. MEDLINE, EMBASE, Cochrane from 1966 through 2009 Abstraction of data in duplicate Event rate per 100 person years and associated 95% confidence interval

  20. Subgroup analysis specified a priori according to tumour size at presentation (micro vs. macroadenoma), tumour characteristics (solid vs. cystic lesion), patients age and sex

  21. Results 14 publications from 1069 references Small studies Majority single centre studies Limited quality Often >30 % lost to follow up

  22. Median follow up of 3.9 years (range 1-15 years) Frequency of PI/NFPA’s higher in females Wide age range 5 months to 89 years

  23. Among symptomatic patients most common complaint was headache at baseline Most common pituitary dysfunction at baseline was hypogonadism

  24. Outcomes • Outcomes reported in aggregate as unable to differentiate between incidentalomas and non-functioning pituitary macroadenomas • Event rate per 100 PY’s • Tumour growth 5.8 (5-6.5) • Pituitary apoplexy 0.2 (0.0-0.2) • Worsening of visual field defects 0.7 (0.5-0.8) • Overall incidence of new endocrine dysfunction 2.4 (0-6.4) • Significant heterogeneity

  25. A priori subgroup analysis Greater event rate of growth in size in macroadenomas (12.5) compared with microadenomas (3.3) and cystic lesions (0.1)

  26. Pituitary Incidentaloma: An Endocrine Society Clinical Practice Guideline 2011 Consensus guided by systematic review of evidence and expert opinion

  27. Evidence developed using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system to describe strength of recommendations and quality of evidence +Very low quality ++++ High quality

  28. Initial evaluation of a patient with a pituitary incidentaloma?

  29. Recommendation 1.1.1 (+++) All patients with a pituitary incidentaloma should undergo complete history and physical and evaluation for hormone hypersecretion

  30. What hormones to be assessed? Prolactin Adenoma, stalk compression Recommended as hyperprolactinemia treatable medically

  31. Growth hormone Generally recommended as silent growth hormone secretion has been reported Medical comorbidity

  32. ACTH Variable recommendations Cushing's with significant morbidity and risk of progression to overt Cushing’s One small study noted progression to overt Cushing disease in 4/22 or 18% of cases

  33. Focused assessment of gonadotropins • High gonadotropins rarely cause clinical symptoms so screening would not necessarily influence therapy • Focused assessment of TSH • Rare for TSH secreting adenomas

  34. If hormonal overproduction treat medically or surgically as per guidelines

  35. Recommendation 1.1.2 (+++) We recommend that patients with a pituitary incidentaloma with or without symptoms also undergo clinical and laboratory evaluations for hypopituitarism

  36. Systematic review Hypopituitarism in 7/66 (10%) and 19/46 (40%) patients in smaller observational studies Hypogonadism in 30% Hypothyroidism 28% Adrenal insufficiency in 18% Growth hormone insufficiency in 8%

  37. Favoured testing in macroadenomas but variable amongst contributors

  38. Recommendation 1.1.3 (++++) We recommend that all patients presenting with a pituitary incidentaloma abutting or compressing the optic nerves or chiasm on MRI undergo formal visual field testing

  39. Growth may lead to sight loss 5-15% may have unrecognized visual fields at presentation

  40. Recommendation 1.1.4 (++++) We recommend that all patients have a MRI scan to better delineate the nature and extent of the incidentaloma Specific pituitary protocol with fine cuts through the sella

  41. Follow-up testing of the pituitary incidentaloma?

  42. Recommendation 2.1 (++) • Patients with incidentalomas who do not meet criteria for surgical removal, should receive non surgical follow-up with: • 2.1.1 MRI scan 6 months after initial scan for macroadenoma or 1 year if microadenoma (++) • Repeat MRI every year for macroadenoma • MRI every 1-2 years for microadenoma for 3 years and then less frequently • Systematic review on natural history

  43. 2.1.2 (++++) Visual field testing in those with an incidentaloma that enlarges to abut the chiasm or optic nerves

  44. 2.1.3 (++) Clinical and biochemical evaluation for hypopituitarism 6 months after the initial testing and 1 year thereafter in macroadenoma Follow up to continue for several years

  45. Indications for surgical therapy of the pituitary incidentaloma?

  46. Recommendation 3.1 (++++) • Refer for surgery if: • Evidence of VF defect or other visual field abnormalities • Relatively higher value put on prevention of VF abnormalities than on avoiding the morbidity (hypopituitarism) and cost of the surgery • Lesion abutting or compressing the optic nerves or chiasm on MRI • Pituitary apoplexy • Hypersecreting tumours other than prolactinomas

  47. Recommendation 3.2 (++) Surgery if: Clinically significant growth of the incidentaloma Loss of endocrine function A lesion close to the chiasm with a plan to become pregnant Unremitting headache

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