The document provides a comprehensive overview of pituitary adenomas, including their epidemiology, clinical features, and diagnostic methods. It discusses tumor development, hormonal functions, and complications such as headaches and visual disturbances. The manuscript emphasizes contemporary surgical management approaches, particularly the expanded endoscopic endonasal techniques, highlighting their benefits in treating aggressive cases and the importance of a multidisciplinary approach.

1. Erion Junior de Andrade
PGY 4 NEUROSUGERY RESIDENT
University of Campinas -UNICAMP
Pituitary Adenomas:
Contemporary Management

2. Introduction
• Neuroepithelial tumors of ADENOhypophysis

3. Epidemiology:
• Most common tumor in sella region (except
CRANIOPHARYNGIOMAS in childhood)
• Prevalence is 19-28 cases per 100,000 people.
• Meta-analysis of autopsy data and radiologic
studies in healthy volunteers: pituitary adenomas
are found in 14% of autopsies and 23% of CT/MRI
studies

4. Epidemiology:
• Mean prevalence of 17%
• 4-20 % of all CNS tumors.
• Young adults (peak 3-4th decades);
• men = women (symptomatic prolactinomas and
Cushing disease are found more frequently in
women)

5. Tumor development
• Adenomas grow slowly!
• Initially confined to sella turcica → may grow out
of sella and compress /encase / destroy:
a) optic chiasm
b) cavernous sinus and internal carotids (lateral
extension)
c) hypothalamus
d) surrounding bony structures (e.g. sphenoid sinus)

6. Tumor development
• Locally invasive adenomas nearly always are
histologically benign! CNS metastases and, rarely,
distant metastases can occur!
• Pituitary adenomas never have calcifications!?
(look at CT – if calcium is present, it is
craniopharyngioma)?
. Toshihiro Ogiwara et al. Acta Neurochirurgica 2017 August 19

7. Tumor development
Adenomas lack discrete capsule, but presence of
pseudocapsule facilitates surgical separation.

8. Microscopic Anatomy
• Routine staining:
a) chromophilic cells (acidophilic or basophilic)
b) chromophobic cells.
routine staining is meaningless - tumor can be
difficult to differentiate from normal tissue or
metastatic disease and immunohistochemical
staining and electron microscopy are essential!
.

9. Microscopic Anatomy
Adenoma - packeted arrangement of cells resembles that
of anterior pituitary, together with prominent vascular
network:

10. Macroscopic Anatomy

11. Clinical Features
HORMONAL FUNCTION CONTROL
A) hormonal hypersecretion (most commonly
prolactin!)
B) destruction of normal gland → hypopituitarism
(partial in 37-85% patients with nonsecretory
tumors, pan in 6-29% patients with nonsecretory
tumors)
• All MACROADENOMAS eventually cause
hypopituitarism.

12. Clinical Features
HORMONAL FUNCTION CONTROL
• If hypopituitarism occurs, hormone loss is
sequential: GH → gonadotropins → ACTH → TSH.
• Primary pituitary tumors rarely cause ADH
deficiency (except when induced by
hypophysectomy)
diabetes insipidus is more common in
CRANIOPHARYNGIOMAS.

13. Clinical Features
MASS EFFECT
1) Headache occurs in 20% (can be diffuse and
nonpulsatile and may be mistaken for daily
headaches; more often in females) – due to
stretching of diaphragma sellae and adjacent dural
structures; ICP is normal!!
Rizzoli P. et al “Headache in Patients With Pituitary
Lesions: A Longitudinal Cohort Study” Neurosurgery:
March 2016 - Volume 78 - Issue 3 - p 316–323

14. Clinical Features
2) crossing fibers in optic chiasm (superior
bitemporal quadrantanopia → full bitemporal
hemianopia - chief and earliest finding in most
patients!)

15. Clinical Features
• Relationship of pituitary and optic chiasm:
a) chiasm directly above pituitary (80%).
b) chiasm anteriorly to pituitary (9%) – PRE FIXED
c) chiasm behind pituitary (11%) – POST FIXED

16. Clinical Features
• further expansion compromises noncrossing
fibers - affects lower and finally upper nasal
quadrants.
any pattern of visual loss is possible, e.g.:
– asymmetrical loss results from chiasm ischemia
produced by vessel occlusion.

17. Clinical Features
3) Lateral extension into cavernous sinus → diplopia,
ophthalmoplegias, postganglionic Horner syndrome.
4) Hypothalamic compression (e.g. Stalk effect
leading to hyperprolactinemia, diabetes insipidus,
alterations in consciousness, memory, intake of food
and water).
5) Extension into sphenoid sinus → CSF rhinorrhea (≈
0.5% cases) - cortical bone separating sella from
sphenoid sinus is quite thin in normal individuals!

18. Clinical Features
6) Compression of 3rd ventricle → obstructive
hydrocephalus.
7) Basal forebrain abnormalities (personality
changes, dementia, anosmia).
8) Temporal lobe seizures.

19. Diagnosis – MRI :
• Gold standard, more sensitive method for tumor
identification (esp. 1-mm cuts and magnified views through
sella – pituitary protocol)
Normal NEUROHYPOPHYSIS
• on T1-MRI shows increased signal (representing
neurosecretory granules in ADH-containing axons).
Normal ADENOHYPOPHYSIS:
• isointense with grey matter on all MR sequences.
• circumventricular organ without an intact BBB - enhances
homogeneously

20. Diagnosis – MRI :
• MICROADENOMAS enhance later and/or lesser than
normal pituitary tissue!
• other indirect MRI signs:
1) gland height ↑ (normally < 10 mm)
2) gland upper margin contour alteration from concave or
straight to convex
3) erosion of sella turcica floor adjacent to hypointensity area
4) displacement of pituitary stalk (normally midline) away from
hypointensity area.

21. Diagnosis – MRI :

22. Diagnosis – MRI :

23. Diagnosis – SPECT:
• 99mTc(V)-DMSA is actively taken up by adenomas relative to
other sellar/suprasellar lesions.
• Radiolabeled somatostatin or dopamine can potentially
differentiate hormone producing from nonfunctioning
pituitary adenomas and identify patients who would benefit
from pharmacotherapy, although the clinical feasibility of this
is unclear.

24. Diagnosis– Laboratory:

25. Diagnosis – Laboratory:
• IPSS: Inferior petrosal sinus sampling is used to localize
tumors not seen radiographically (e.g. many ACTH-secreting
microadenomas are < 5 mm).
• Central hypothyroidism is typically confirmed by the
thyrotropin releasing hormone (TRH) stimulation test, in
which serum TSH is measured serially post-TRH at 20 and 60
minutes, with a normal response defined as the 20- minute
TSH value being higher than the 60-minute TSH value. A flat
response is seen in pituitary disease, and delayed response,
with the 60-minute value higher than the 20-minute value, is
seen in hypothalamic disease.

26. Diagnosis – Laboratory:
• PROLACTIN
• Nonsecreting tumors are commonly associated with slight
elevations of serum prolactin (< 150*).
• STALK SYNDROME (compression of pituitary stalk,
interrupting dopaminergic fibers that inhibit prolactin
release).
- Hook effect (s. prozone effect) - resulting in false negatives or
inaccurately low results – too much antigen (prolactin)
interferes with results (H: diluting blood sample; modern labs
do it automatically):

27. Diagnosis – Laboratory:
• Prolactin

28. Aggressive Pituitary Tumors
• 25-55% of pituitary tumors are invasive
• WHO Classification
– Typical adenomas
– Atypical adenomas
– Pituitary carcinomas
Di Ieva, A. et al. (2014) Aggressive pituitary adenomas—diagnosis and emerging treatments
Nat. Rev. Endocrinol. doi:10.1038/nrendo.2014.64

29. Atypical Adenomas
• Atypical morphological features
• Elevated mitotic index
• Ki-67 ≥ 3%
• Positive p53 staining
• 2.7% - 15% of all pituitary tumors
Di Ieva, A. et al. (2014) Aggressive pituitary adenomas—diagnosis and emerging treatments
Nat. Rev. Endocrinol. doi:10.1038/nrendo.2014.64

30. Pituitary Carcinomas
• Must have craniospinal dissemination or
systemic metastases
• 0.2% of all pituitary tumors
• Can share morphological features with
pituitary adenomasDi Ieva, A. et al. (2014) Aggressive pituitary adenomas—diagnosis and emerging treatments
Nat. Rev. Endocrinol. doi:10.1038/nrendo.2014.64

31. Aggressive vs Invasive
Aggressive
- Clinical behavior
Invasive
- Radiological, surgical, and histopathological

32. Recognizing Aggressive Tumors

33. Hardy Classification System
Di Ieva, A. et al. (2014) Aggressive pituitary adenomas—diagnosis and emerging treatments
Nat. Rev. Endocrinol. doi:10.1038/nrendo.2014.64

34. Knosp Classification System
Di Ieva, A. et al. (2014) Aggressive pituitary adenomas—diagnosis and emerging treatments
Nat. Rev. Endocrinol. doi:10.1038/nrendo.2014.64

35. Outline
• Evolution of Surgical Approaches to
Pituitary Tumors

36. “If I have seen further it is by standing
on the shoulders of Giants”
- Sir Isaac Newton
Presentation Title l October 20,
2019 l 36

37. Historical Approaches
Perneczky A, Müller-Forell W, van Lindert E, Fries G. Keyhole concept in neurosurgery.
New York: Thieme. 1999

38. Historical Approaches

39. Historical Approaches
Courtesy of Robert Wilkins, M.D.

40. Microscopic TSH

41. Microscopic TSH

42. Endoscopic TSH

43. The Right Plan: What does not change
• Goal of Surgery
– Same indications, end points, criteria of
success
• Basic techniques of tumor resection
– Suction, curettes
• Angle of approach and relevant
anatomy

44. The Right Plan: What does not change
• Major complications to avoid:
– Carotid injury
– Optic nerve damage, CSF leak, endocrine
complications, post-op hemorrhage
Picture from Johns Hopkins i-star lab website

45. The Right Plan: What does change
• Speculum use
• Nasal trauma
• Visual perspective
– 3-D at a distance = microscope
– 2-D plus proprioception up close =
endoscope
– Narrow vs wide visual working space
One surgeon vs Two surgeons

46. Visualization Difference
Simmen DB, Briner HR, Jones N. Endoscopically assisted bimanual operating technique. In Stamm AC(ed):
Transnasal endoscopic skull base and brain surgery. New York: Thieme. 2011. p 92-8.

47. Visualization Difference
Nomikos P, Fahlbusch R, Buchfelder M. Recent developments in transsphenoidal surgery
of pituitary surgery. Hormones (Athens). 3(2):85-91, 2004.

48. Looking Around Corners
Perneczky A, Müller-Forell W, van Lindert E, Fries G. Keyhole concept in
neurosurgery. New York: Thieme. 1999

49. Tools and Working Space
Simmen DB, Briner HR, Jones N. Endoscopically assisted bimanual operating technique. In
Stamm AC(ed): Transnasal endoscopic skull base and brain surgery. New York: Thieme.
2011. p 92-8.

50. Neuronavigation

51. Neuronavigation

52. TEAM APPROACH
§ Two surgeons
§ Simultaneous surgery
§ 2 monitors
§ Increased functional
room in sinus
§ Minimizes insertion
trauma

53. Learning to dance

55. Reconstruction

56. Hadad G, Bassagaisteguy L, Timperley D, Stamm AC. Management of skull base defects after extended
endoscopic skull base surgery: from free grafts to vascularized flaps. In Stamm AC(ed): Transnasal
endoscopic skull base and brain surgery. New York: Thieme. 2011. p 379-85.

57. Reconstruction
Hadad G, Bassagaisteguy L, Timperley D, Stamm AC. Management of skull base defects after extended
endoscopic skull base surgery: from free grafts to vascularized flaps. In Stamm AC(ed): Transnasal
endoscopic skull base and brain surgery. New York: Thieme. 2011. p 379-85.

58. - 39.1% pituitary adenomas, 11.8% meningiomas
- CSF leak most common complication (15.9%)
- <6% CSF leak after adoption of nasal-septal flap

59. Papers on rec outcomes
- Zanation
- Kassam

61. Outline
• Case Examples of
Persistent/Aggressive Tumors

62. Choosing the right approach

63. Choosing the right approach

64. Firm Macroadenoma

65. Firm Macroadenoma

66. Firm Macroadenoma

67. Multiple prior surgeries + XRT

68. Multiple prior surgeries + XRT

69. Multiple prior surgeries + XRT

70. Multiple prior surgeries + XRT

71. Aggressive Recurrent
Macroadenoma

72. Transcranial Options – Extended
Bifrontal
Recinos PF, Goodwin CR, Quiñones-Hinojosa A, Brem H. Transcranial surgery for pituitary macroadenomas. In Quiñones-
Hinojosa A (ed): Schmidek and Sweet Operative Neurosurgical Techniques, 6th edition. Philadelphia: Elsevier: 2012. p. 280-291

73. Transcranial Options – Extended
Bifrontal
Recinos PF, Goodwin CR, Quiñones-Hinojosa A, Brem H. Transcranial surgery for pituitary macroadenomas. In Quiñones-
Hinojosa A (ed): Schmidek and Sweet Operative Neurosurgical Techniques, 6th edition. Philadelphia: Elsevier: 2012. p. 280-291

74. Transcranial Options - COZ
Recinos PF, Goodwin CR, Quiñones-Hinojosa A, Brem H. Transcranial surgery for pituitary macroadenomas. In Quiñones-
Hinojosa A (ed): Schmidek and Sweet Operative Neurosurgical Techniques, 6th edition. Philadelphia: Elsevier: 2012. p. 280-291

75. Transcranial Options - COZ
Recinos PF, Goodwin CR, Quiñones-Hinojosa A, Brem H. Transcranial surgery for pituitary macroadenomas. In Quiñones-
Hinojosa A (ed): Schmidek and Sweet Operative Neurosurgical Techniques, 6th edition. Philadelphia: Elsevier: 2012. p. 280-291

76. Pituitary Carcinoma

77. Pituitary Carcinoma

78. Pituitary Carcinoma

79. Pituitary Carcinoma

80. Pituitary Carcinoma

81. Pituitary Carcinoma

82. Take Home Points
• The expanded endscopic endonasal
approach has greatly increased possible
exposure of the anterior skull base
• Large transnasal exposures can be done
safely provided that vascularized tissue is
used to close the defect
• Expanded endonasal approaches are good
options in cases of previous failed surgery
and radiation
• Management of aggressive pituitary tumors
requires a multidisciplinary approach