endocrinology rounds kristin clemens pgy 5 november 7 th, 2012 pituitary incidentalomas
TRANSCRIPT
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ENDOCRINOLOGY ROUNDSKRISTIN CLEMENS PGY 5
NOVEMBER 7 T H , 2012
Pituitary Incidentalomas
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Objectives
Epidemiology of pituitary incidentalomasUnderlying causesOutline understanding of natural historyReview recent practice guidelines on
pituitary incidentalomasIllustrative cases for work up and
management
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Case – E.A.
70 year old manHTN, hypercholesterolemiaDiovan, CrestorNo family historyNon smoker, rare ETOH, lives independently
with wife
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Acute onset memory impairment – ERDiagnosis of transient global amnesiaCT to rule out stroke demonstrated 2 x 1.9 x
1.6 cm pituitary macroadenomaMRI encroachment of left cavernous sinus,
touching L optic nerve
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Pituitary MRI
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How to assess him at follow-up endocrinology appointment?
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Pituitary incidentaloma
Previously unsuspected pituitary lesion discovered on an imaging study performed for an unrelated reason
Increasingly common
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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%
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Etiology
Rathke cleft cystsCraniopharyngiomasMeningiomasPituitary hyperplasiaMetastases Pituitary adenoma – 10%
Macroadenoma >1cm Microadenoma <1 cm, most common Functioning and non-functioning
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Pituitary Adenomas
Variety of subtypesData from small observational studiesBuurman, 2006
Series of 3048 autopsy cases examined to detect incidence of subclinical adenomas in postmortem pituitaries
1991-2004
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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
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Size range from 0.1 to 20 mmOnly 3 were macroadenomasSome with multiple adenomasMultiple staining techniques
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39.5% stained positive for prolactin31.7% null cell adenoma/oncocytomas13.8% stained positive for ACTH7.2% for gonadotropins1.8% stained positive for GH0.6% for TSH 3% for multiple hormonesSmall percentage unclassified
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Clinical history
Clinical significance?99 patients with HTN, 65 with diabetesNo symptoms of adenohypophyseal hormone
hypersecretion were reportedRare cases of clinical hypo and
hyperthyroidismNo clear correlation between clinical data
and adenoma type in this sample
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Natural History?
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Small observational cohort studies
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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
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Outcomes of interest including development of visual field defects, neurological defects, alteration in pituitary function, pituitary apoplexy
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MEDLINE, EMBASE, Cochrane from 1966 through 2009
Abstraction of data in duplicateEvent rate per 100 person years and
associated 95% confidence interval
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Subgroup analysis specified a priori according to tumour size at presentation (micro vs. macroadenoma), tumour characteristics (solid vs. cystic lesion), patients age and sex
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Results
14 publications from 1069 referencesSmall studiesMajority single centre studiesLimited qualityOften >30 % lost to follow up
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Median follow up of 3.9 years (range 1-15 years)
Frequency of PI/NFPA’s higher in femalesWide age range 5 months to 89 years
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Among symptomatic patients most common complaint was headache at baseline
Most common pituitary dysfunction at baseline was hypogonadism
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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
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A priori subgroup analysisGreater event rate of growth in size in
macroadenomas (12.5) compared with microadenomas (3.3) and cystic lesions (0.1)
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Pituitary Incidentaloma: An Endocrine Society Clinical Practice Guideline
2011Consensus guided by systematic review of
evidence and expert opinion
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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
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Initial evaluation of a patient with a pituitary incidentaloma?
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Recommendation 1.1.1 (+++)
All patients with a pituitary incidentaloma should undergo complete history and physical and evaluation for hormone hypersecretion
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What hormones to be assessed?
ProlactinAdenoma, stalk compressionRecommended as hyperprolactinemia
treatable medically
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Growth hormoneGenerally recommended as silent growth
hormone secretion has been reportedMedical comorbidity
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ACTHVariable recommendations Cushing's with significant morbidity and risk
of progression to overt Cushing’sOne small study noted progression to overt
Cushing disease in 4/22 or 18% of cases
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Focused assessment of gonadotropins High gonadotropins rarely cause clinical symptoms so
screening would not necessarily influence therapyFocused assessment of TSH
Rare for TSH secreting adenomas
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If hormonal overproduction treat medically or surgically as per guidelines
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Recommendation 1.1.2 (+++)
We recommend that patients with a pituitary incidentaloma with or without symptoms also undergo clinical and laboratory evaluations for hypopituitarism
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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%
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Favoured testing in macroadenomas but variable amongst contributors
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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
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Growth may lead to sight loss5-15% may have unrecognized visual fields at
presentation
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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
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Follow-up testing of the pituitary incidentaloma?
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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
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2.1.2 (++++)Visual field testing in those with an
incidentaloma that enlarges to abut the chiasm or optic nerves
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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
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Indications for surgical therapy of the pituitary incidentaloma?
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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 apoplexyHypersecreting tumours other than
prolactinomas
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Recommendation 3.2 (++)
Surgery if:Clinically significant growth of the
incidentalomaLoss of endocrine functionA lesion close to the chiasm with a plan to
become pregnantUnremitting headache
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Transphenoidal approach favoured
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Algorithm
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Although guidelines, variable practice among clinicians
Given prevalence of pituitary adenomas, cost concern
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Randall et al, 2010
Single institution review of patients with pituitary tumour, adenoma, Cushing disease, acromegaly, prolactinoma
2002-2009Pituitary tumours that were discovered
incidentally were about 15% of sample
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King et al, 1997
Cost effective analysis using Markov modeling to compare strategies for management of asymptomatic patient with incidental pituitary microadenoma
Expectant- no management unless symptoms PRL screening with treatmentPanel of hormone secreting tests – PRL, IGF 1,
cortisol after dexamethasone administration with treatment
Follow up MRI screening – 6 and 12 months with hormone testing if size change
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Incorporated natural history, pharmacological and surgical treatment outcomes
Direct medical costs - costs of hormone testing, MRI’s, hospitalization for surgery and physician services into analysis
Mortality, morbidity from endocrine and neurological dysfunction, anxiety about knowing about the tumour
Quality of life (QALY)- measure of quality of life that assigns to each year, a weight of quality of life
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Results most sensitive to patient anxiety and shifts to endocrine panel
Concluded that single PRL may be most cost effective screen for microadenoma
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Thus….
Some groups suggest only prolactin for hyperfunction and other hormonal work up depending on clinical suspicion
No routine visual field testingNo routine screening for hormone
hypofunction
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Back to E.A
HistoryNo headaches, visual impairment, facial
weakness or parasthesiasNo overt symptoms of hormone hyperfunctionNo symptoms of hypofunction
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Physical examNo orthostatic change in vitalsNormal visual fields to confrontation, normal
extraocular movementsClinical euthyroid, no features of acromegaly,
Cushing’s, well-androgenizedClinical suspicion for hormone dysfunction
low
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Investigations
Cortisol 498 nmol/LLH 4.8 IU/L, FSH 12.9 IU/L, total
testosterone 14 nmol/LProlactin 5 ug/LTSH 1.57 mIU/L, free T4 15 pmol/L, free T3
4.4 pmol/LIGF 1 normal
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Visual fields unreliable with multiple false positives and negatives
Repeat examination normal
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Follow-up
Repeat MRI at 6 months stableRepeat MRI at 1 year stablePlan to repeat visual fields and assess for
hormone hypofunction
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Case 2 – Z.K.
78 year old man CVA, HTN“Blood pressure pill”No family historyNon smoker, no alcohol, lives independently
with wife
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Presented to ER with history of headacheCT showed 3.1 x 2.8 x 3.8 cm macroadenoma MRI demonstrated suprasellar extension and
extension into the sphenoid sinus and R cavernous sinus
Mild compression of the optic chiasm
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Pituitary MRI
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Endocrine follow-up
Son translatorHeadaches improvedDenied vision impairment, facial weakness or
parasthesiaNo symptoms of pituitary hyperfunction?Cold intolerance – multiple layers of clothing
around the house
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Physical examNo orthostatic change in vitals, no
lightheadednessVisual fields difficult to assessNo features of Cushing’s or acromegaly, well
androgenizedWearing double layers and hat in summer
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Investigations
AM cortisol 144 nmol/LLH 1 IU/L, FSH 3.1 IU/L, total testosterone
<0.1 nmol/LTSH 1.14 mIU/L, free T4 9 pmol/L, free T3
3.5 pmol/LProlactin 21 ug/LIGF 1 <15 ug/L
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What next?
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Started hydrocortisone 20 mg q am and 10 mg q pm
Levothyroxine 75 micrograms po dailyBMD and consideration of testosterone
replacementGrowth hormone replacement?
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Case
Visual field examination unreliable as language barrier
Suggested ongoing MRI’s for follow up
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Repeat MRI at 6 months stablePlan for 1 year repeat examLow threshold for surgical management
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Case #3 – R. J.
50 year old ladyColonic polyps, hypercholesterolemia, thyroid
nodulePrevious hysterectomyFamily history of DMIIPrevious smoker
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ENT for feelings of oropharyngeal swelling and shortness of breath
Referred for “incidental” 14 x 21 x 21 mm macroadenoma on sinus CT
MRI mild stalk deviation, suprasellar extension
Encroachment of right optic nerve without compression
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MRI
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HistoryIncreased shoe size and hand size over last
several year20 lb weight gainFlushingSnoringVoice deepeningNo galactorrheaNo symptoms suggestive of hormone
insufficiency
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Physical Exam
No orthostatic change in blood pressureNormal visual fields to confrontationSeveral clinical manifestations of acromegaly
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Investigations
ACTH, cortisol normalLH 2.2 IU/L, FSH 4.7 IU/L, estradiol 164
pmol/LTSH 0.93 mIU/L, fT4 14 pmol/L, fT3 5.9
pmol/LProlactin 40 ug/LGH 35 ug/L, IGF 1 711 ug/L
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Management
75 g OGTT confirmed acromegalyVisual field testing normalReferral for surgical management
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Take home messages
With increased imaging, more pituitary incidentalomas
Relatively common endocrinology referralPituitary adenomas among other etiologies
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Clinical guidelines helpful but need to consider individual patient
Detailed history and physicalScreen for hormone hyperfunction – prolactin,
IGF 1, others if clinically suspiciousScreen for hormone hypofunction –
macroadenomasRefer for visual field assessment if close to the
optic chiasmConsider medical or surgical managementLong term monitoring for clinical changes
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References
Buurman H, Saeger W. Subclinical adenomas in postmortem pituitaries: classification and correlations to clinical data. European Journal of Endocrinology 2006; 154: 753-758.
King JT et al. Management of incidental pituitary microadenomas: a cost effectiveness analysis. JCEM 1997; 82: 3625-3632.
Pituitary Incidentaloma: An Endocrine Society Clinical Practice Guideline 2011
Randall BR et al. Cost of evaluation of patients with pituitary incidentaloma. Pituitary 2010; 13: 383-384.
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Thanks!