Pituitary Incidentalomas

Report
Pituitary Incidentalomas
ENDOCRINOLOGY ROUNDS
KRISTIN CLEMENS PGY 5
N O V E M B E R 7 TH, 2 0 1 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
Case – E.A.
 70 year old man
 HTN, hypercholesterolemia
 Diovan, Crestor
 No family history
 Non smoker, rare ETOH, lives independently with
wife
 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
Pituitary MRI
 How to assess him at follow-up endocrinology
appointment?
Pituitary incidentaloma
 Previously unsuspected pituitary lesion discovered
on an imaging study performed for an unrelated
reason
 Increasingly common
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%
Etiology
 Rathke cleft cysts
 Craniopharyngiomas
 Meningiomas
 Pituitary hyperplasia
 Metastases
 Pituitary adenoma – 10%
 Macroadenoma >1cm
 Microadenoma <1 cm, most common
 Functioning and non-functioning
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
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
 Size range from 0.1 to 20 mm
 Only 3 were macroadenomas
 Some with multiple adenomas
 Multiple staining techniques
 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
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
Natural History?
 Small observational cohort studies
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
 Outcomes of interest including development of
visual field defects, neurological defects, alteration in
pituitary function, pituitary apoplexy
 MEDLINE, EMBASE, Cochrane from 1966 through
2009
 Abstraction of data in duplicate
 Event rate per 100 person years and associated 95%
confidence interval
 Subgroup analysis specified a priori according to
tumour size at presentation (micro vs.
macroadenoma), tumour characteristics (solid vs.
cystic lesion), patients age and sex
Results
 14 publications from 1069 references
 Small studies
 Majority single centre studies
 Limited quality
 Often >30 % lost to follow up
 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
 Among symptomatic patients most common
complaint was headache at baseline
 Most common pituitary dysfunction at baseline was
hypogonadism
Outcomes
 Outcomes reported in aggregate as unable to
differentiate between incidentalomas and nonfunctioning 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
 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)
Pituitary Incidentaloma: An Endocrine Society
Clinical Practice Guideline
 2011
 Consensus guided by systematic review of evidence
and expert opinion
 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
Initial evaluation of a patient with a pituitary
incidentaloma?
Recommendation 1.1.1 (+++)
 All patients with a pituitary incidentaloma should
undergo complete history and physical and
evaluation for hormone hypersecretion
What hormones to be assessed?
 Prolactin
 Adenoma, stalk compression
 Recommended as hyperprolactinemia treatable
medically
 Growth hormone
 Generally recommended as silent growth hormone
secretion has been reported
 Medical comorbidity
 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
 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
 If hormonal overproduction treat medically or
surgically as per guidelines
Recommendation 1.1.2 (+++)
 We recommend that patients with a pituitary
incidentaloma with or without symptoms also
undergo clinical and laboratory evaluations for
hypopituitarism
 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%
 Favoured testing in macroadenomas but variable
amongst contributors
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
 Growth may lead to sight loss
 5-15% may have unrecognized visual fields at
presentation
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
Follow-up testing of the pituitary incidentaloma?
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
 2.1.2 (++++)
 Visual field testing in those with an incidentaloma
that enlarges to abut the chiasm or optic nerves
 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
Indications for surgical therapy of the pituitary
incidentaloma?
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
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
 Transphenoidal approach favoured
Algorithm
 Although guidelines, variable practice among
clinicians
 Given prevalence of pituitary adenomas, cost
concern
Randall et al, 2010
 Single institution review of patients with pituitary
tumour, adenoma, Cushing disease, acromegaly,
prolactinoma
 2002-2009
 Pituitary tumours that were discovered incidentally
were about 15% of sample
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 treatment
Panel 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
 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
 Results most sensitive to patient anxiety and shifts to
endocrine panel
 Concluded that single PRL may be most cost
effective screen for microadenoma
Thus….
 Some groups suggest only prolactin for
hyperfunction and other hormonal work up
depending on clinical suspicion
 No routine visual field testing
 No routine screening for hormone hypofunction
Back to E.A
 History
 No headaches, visual impairment, facial weakness or
parasthesias
 No overt symptoms of hormone hyperfunction
 No symptoms of hypofunction
 Physical exam
 No orthostatic change in vitals
 Normal visual fields to confrontation, normal
extraocular movements
 Clinical euthyroid, no features of acromegaly,
Cushing’s, well-androgenized
 Clinical suspicion for hormone dysfunction low
Investigations
 Cortisol 498 nmol/L
 LH 4.8 IU/L, FSH 12.9 IU/L, total testosterone 14
nmol/L
 Prolactin 5 ug/L
 TSH 1.57 mIU/L, free T4 15 pmol/L, free T3 4.4
pmol/L
 IGF 1 normal
 Visual fields unreliable with multiple false positives
and negatives
 Repeat examination normal
Follow-up
 Repeat MRI at 6 months stable
 Repeat MRI at 1 year stable
 Plan to repeat visual fields and assess for hormone
hypofunction
Case 2 – Z.K.
 78 year old man
 CVA, HTN
 “Blood pressure pill”
 No family history
 Non smoker, no alcohol, lives independently with
wife
 Presented to ER with history of headache
 CT 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
Pituitary MRI
Endocrine follow-up
 Son translator
 Headaches improved
 Denied vision impairment, facial weakness or
parasthesia
 No symptoms of pituitary hyperfunction
 ?Cold intolerance – multiple layers of clothing
around the house
 Physical exam
 No orthostatic change in vitals, no lightheadedness
 Visual fields difficult to assess
 No features of Cushing’s or acromegaly, well
androgenized
 Wearing double layers and hat in summer
Investigations
 AM cortisol 144 nmol/L
 LH 1 IU/L, FSH 3.1 IU/L, total testosterone <0.1
nmol/L
 TSH 1.14 mIU/L, free T4 9 pmol/L, free T3 3.5
pmol/L
 Prolactin 21 ug/L
 IGF 1 <15 ug/L
 What next?
 Started hydrocortisone 20 mg q am and 10 mg q pm
 Levothyroxine 75 micrograms po daily
 BMD and consideration of testosterone replacement
 Growth hormone replacement?
Case
 Visual field examination unreliable as language
barrier
 Suggested ongoing MRI’s for follow up
 Repeat MRI at 6 months stable
 Plan for 1 year repeat exam
 Low threshold for surgical management
Case #3 – R. J.
 50 year old lady
 Colonic polyps, hypercholesterolemia, thyroid
nodule
 Previous hysterectomy
 Family history of DMII
 Previous smoker
 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
MRI
 History
 Increased shoe size and hand size over last several






year
20 lb weight gain
Flushing
Snoring
Voice deepening
No galactorrhea
No symptoms suggestive of hormone insufficiency
Physical Exam
 No orthostatic change in blood pressure
 Normal visual fields to confrontation
 Several clinical manifestations of acromegaly
Investigations
 ACTH, cortisol normal
 LH 2.2 IU/L, FSH 4.7 IU/L, estradiol 164 pmol/L
 TSH 0.93 mIU/L, fT4 14 pmol/L, fT3 5.9 pmol/L
 Prolactin 40 ug/L
 GH 35 ug/L, IGF 1 711 ug/L
Management
 75 g OGTT confirmed acromegaly
 Visual field testing normal
 Referral for surgical management
Take home messages
 With increased imaging, more pituitary
incidentalomas
 Relatively common endocrinology referral
 Pituitary adenomas among other etiologies
 Clinical guidelines helpful but need to consider






individual patient
Detailed history and physical
Screen for hormone hyperfunction – prolactin, IGF
1, others if clinically suspicious
Screen for hormone hypofunction – macroadenomas
Refer for visual field assessment if close to the optic
chiasm
Consider medical or surgical management
Long term monitoring for clinical changes
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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