This case involves a 22-year-old woman presenting with galactorrhea and amenorrhea. Her prolactin level was elevated at 144 ng/mL. MRI showed a 5mm microadenoma in her right pituitary gland. She was prescribed cabergoline to lower her prolactin levels, with plans to follow up in 2-3 months. The document then provides background information on pituitary adenomas including causes, classifications, clinical presentations, investigations and management options such as surgery, medication and radiotherapy. The main treatment discussed is dopamine agonists as first-line therapy for prolactinomas.

1. Case Presentation
Dr.Usman Haqqani
TMO NSBW
LRH PESHAWAR

2. History and Examination
• A 22 year woman wants to become
pregnant has no menses since she
discontinued the use of OCPs one year
ago,recently she developed
galactorrhea,she takes no medication and
has no headaches,visual loss,dyspareunia
or decreased libido

3. History based diagnosis??

4. • O/E she has no abnormality except
bilateral breast discharge

5. Labs
• B hcg is negative
• prolactin level was also elevated, at 144
ng/mL
» Males: less than 20 ng/dL
» Nonpregnant females: 5 to 40 ng/dL
» Pregnant women: 80 to 400 ng/dL

6. Imaging
• MRI with contrast showed a “subtle area
of delayed enhancement in the right
pituitary, consistent with a 5-mm
microadenoma.

7. Managment
• The patient was prescribed the dopamine
agonist cabergoline (0.25 mg, to be taken
twice a week), with a plan to follow up in
two to three months

8. Introduction
o The pituitary gland, or hypophysis, is
an endocrine gland
o Produce number of hormones which control
the secretions of many other endocrine glands
o Its anatomical position is important

9. Development
The anterior pituitary
(adenohypophysis) arises
from Rathke's pouch, an
upward growth from the
ectodermal roof of the
stomodeum
The posterior pituitary
(neurohypophysis) arises from a
downward growth from the floor of the
diencephalon

10. Anatomy
• Occupies a cavity of the
sphenoid bone called sella
turcica at the middle
cranial fossa
• Roof is formed by
diaphragma sellae
• The stalk of pituitary is
attached above to the
floor of third ventricle
• Size of a pea (< 8 mm)
• It weighs about 0.5 gm.

12. Secretions
• Anterior Lobe:
– FSH
– LH
– ACTH
– TSH
– Prolactin
– GH
• Posterior Lobe:
– ADH
– Oxytocin

13. Hypothalamic prolactin axis

15. Pituitary Adenoma
Benign tumors of pituitary gland

16. Epidemiology
• Etiology is unknown
• 10-15% of all primary brain tumors
• 75% of adenomas are endocrinogically
secreting
• 25% of those with MEN-I develop pituitary
adenomas

17. Classification
Hormones Clinical features
Secreting (75%) Chromophobes
(50%)
Prolactin Female: Infertility,
amenorrhea,
galactorrhea
Male :
Hypogonadism,
impotency, sterility,
↓libido,
gynecomastia,
galactorrhea
Acidophils (20%) GH Acromegaly(adult)
Gigantism(child)
Basophils(5%) ACTH, FSH & TSH Cushing disease,
FSH & TSH tumors
Nonsecreting
(25%)

18. Classification
Microadenoma < 10 mm diameter Secreting adenoma
Macroadenoma > 10 mm diameter Mass effects
Non secreting

19. Clinical presentation
• 1. Endocrine effects –
Mainly due to the effect of the excess of
the hormone in question.
• 2. Space-occupying effects –
• Superior expansion
• Lateral extension
• Inferior extension

20. Clinical presentation
• Localized mass effects
– Chiasmal syndromes
– Compression of other adjacent structures
~ Cavernous sinus (paresis of 3rd, 4th or 6th CN causing
disorders of extraocular motility)
~ Hypopituitarism (direct pressure, vascular damage)
~ Papilloedema (raised ICP, very rare)
• Endocrine effects
– Hypersecretion

21. Hyperscretion
Prolactin
• Female
– Infertility, amenorrhea, galactorrhea
• Male
– Hypogonadism, impotence, sterility, ↓ libido,
gynecomastia, galactorrhea

22. Chiasmal Syndromes
• compression of the
optic chiasm
• bitemporal
hemianopsia
• post fixed chiasm
• optic nerve
compression>loss
of vision in the
ipsilateral eye
• pre-fixed chiasm
• compression of the
optic tract>
homonymous
hemianopsia

23. Prolactin levels

24. • Prolactin level correlates with size of
prolactinomas
– if PRL is<200ng/ml, ≈80% of tumors are
microadenomas
– if PRL>200, only ≈20% are microadenomas
– PRL>500 usually indicates that surgery alone will not
be able to normalize the PRL

25. Stalk effect
• PRL is the only pituitary hormone primarily under inhibitory
regulation .Injury to or compression of the hypothalamus or pituitary
stalk from surgery or compression by any type of tumor can cause
modest elevation of PRL due to decrease in prolactin inhibitory
factor (PRIF).
• Persistent post-op PRL elevation may occur even with total tumor
removal as a result of injury to stalk (usually≤90ng/ ml; stalk effect
doubtful if PRL>150).
• For stalk effect, patients are followed,bromocriptine is not used

26. Hook effect
• extremely high PRL levels may overwhelm the assay
(the large numbers of PRL molecules prevent the
formation of the necessary PRL-antibody-signal
complexes for radioimmunoassay) and producefalsely
low results.
• Therefore, for large adenomas with a normal PRL level,
have the lab perform several dilutions of the serum
sample and re-run the PRL, especially in patients with
clinical hyperprolactinemia

27. Macroprolactinemia
• Prolactin molecules polymerize and bind to
immunoglobulins. Prolactin in this form has reduced
biologically activity but produces a laboratory finding of
hyperprolactinemia.
• Asymptomatic patients usually do not require treatment

28. Remember
• Not all hyperprolactinemia is
due to a prolactinoma

29. Other causes of hyperprolactinoma

30. Hardy classification based on radiology
0 Pituitary gland appears normal.
I Microadenoma enclosed within the sella turcica.
II Macroadenoma enclosed within the sella turcica.
III Tumour invades into the sella turcica locally (in one place).
IV Tumour invades into the sella turcica diffusely (in more than one place)
Classification for pituitary adenomas based on imaging (Invasion)
A 0–10 mm suprasellar extension occupying the suprasellar cistern
B 10–20 mm extension and elevation of the third ventricle
C 20–30 mm extension occupying the anterior (front) of the third ventricle
D
Larger than 30 mm extension, beyond the foramen of Monro, or grade C with lateral
extensions
Grading for suprasellar extension

32. investigations
 Hormonal workup
 Rule out pregnancy
 Visual Perimetry
 MRI pituitary protocol
 CT brain for surgical planning

33. MRI
• MRI Brain with and without contrast (pituitary protocol
includes thin coronal cuts through sella showing
cavernous sinus and optic chiasm)
• For microadenoma, dynamic MRI increases the
chances of catching the tumor at a time when it
enhances differentially from the gland
• 75% are low signal on T1WI, and high signal on T2WI (but 25% can behave
in any way, including completely opposite to above).
• Enhancement is very time-dependent.
• Initially, gadolinium enhances the normal pituitary (no blood brain barrier)
but not the pituitary tumor.
• After ≈ 30minutes, the tumor enhances about the same.

36. • Findings: Information about
– invasion of cavernous sinus
– location
– involvement of para-sellar carotids.
• Neurohypophysis: normally is high signal on T1WI
• Deviation of the pituitary stalk may also indicate the
presence of a microadenoma.
• Normal thickness of the pituitary stalk is approximately
equal to basilar artery diameter.

37. • Thickening of stalk is usually NOT adenoma, differential
diagnosis for a thickened stalk:
– lymphoma,
– autoimmune hypophysitis
– granulomatous disease
– hypothalamic glioma.

38. For cavernous sinus invasion, there are three signs to look out
for:
-Is there more than 50% encirclement of the carotid artery?
Note: meningiomas tend to constrict the carotid artery,
macroadenomas do not.
–Is there lateral displacement of the lateral wall of the
cavernous sinus compared to the opposite side?
-Is there an increased amount of tissue interposed between the
carotid artery and the lateral wall of the cavernous sinus?

39. Therapeutic Modalities Summary
Surgery Radiotherapy Medical
Non-functioning
adenoma
1st line 2nd line -
Prolactinoma 2nd line 2nd line 1st line
Acromegaly 1st line 2nd line 2nd line
Cushing’s
disease
1st line 2nd line -

40. Prolactinoma Managment
• prolactin level (PRL)<500ng/ml
– PRL may be normalized with surgery
• PRL>500ng/ml
– the chances of normalizing PRL surgically are very low
• a) if no acute progression (worsening vision), an initial attempt at purely
medical control should be made (these tumors may shrink dramatically with
bromocriptine)
• b) response should be evident by 4–6 weeks (significant decrease in PRL, improvement
of visual deficits, or shrinkage on MRI)
• c) if tumor is not controlled medically (≈18% will not respond to
bromocriptine): surgery followed by reinstitution of medical therapy may
normalize PRL

41. Dopamine agonists
• Side effects (may vary with different preparations) nausea, H/A, fatigue, orthostatic
hypotension with dizziness, cold induced peripheral vasodilatation, depression,
nightmares and nasal congestion.

42. Dopamine Agonists
• Treatment response to DA is assessed with serial prolactin
• Discontinuation:
– Microadenomas or macroadenomas that are no longer visible on MRI are
candidates for DA agonist withdrawal
– Recurrence rate is highest during 1st year,check prolactin levels and clinical
symptoms every 3 months during the 1st year. Long-term follow up is required,
especially for macroadenomas.

43. • Bromocriptine:
– inhibit synthesis and secretion of PRL to<10% of pretreatment
values in most patients.
– With a microadenoma, one year of bromocriptine may reduce
the surgical cure rate by as much as 50%, possibly due to
induced fibrosis.
– Thus, it is suggested that if surgery is to be done that it be done
in the first 6 months of bromocriptine therapy.
– Shrinkage of large tumors due to bromocriptine may cause CSF
rhinorrhea

44. – Dose:
• Start 1.25mg (half of a 2.5mg tablet) PO q hs
– Microadenoma
» Dose change/increase 2-4 week (serial prolactine level)
– Macroadenoma
» every 3–4 days

45. Cabergoline
• Side effects :
– H/A and GI symptoms are reportedly less problematic than with
bromocriptine.than with bromocriptine.
• Contraindications:
– eclampsia or pre-eclampsia, uncontrolled HTN. Dosage should be reduced with
severe hepatic dysfunction
• Dose
– Supplied: 0.5mg tablets.
– Start with 0.25mg PO twice weekly, and increase each dose by 0.25mg every 4
weeks as needed to control PRL (up to a maximum of 3mg per week

46. Radiotherapy
• Reserved for patients with larger tumors and/or persistent hormonal
hyperfunction despite surgical intervention
• Conventional radiotherapy
• When used, doses of 40 or 45Gy in 20 or 25 fractions, respectively, is
recommended.
• Gamma knife radiosurgery
• Close proximity to the optic nerve
• Cavernous sinus invasion

47. SURGICAL
APPROACHES

48. Surgical Treatment

49. APPROACHES TO THE
SPHENOID SINUS
 Various routes for transsphenoidal
surgeries are:
1. Transseptal route.
2. Sublabial
3. Transethmoidal route.
4. Transnasal route.

51. • Transethmoidal route
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52. Endoscopic
Transsphenoidal
Hypophysectomy

53. Preparation for surgery
• NASAL PREPARATION :
1. The application of topical vasoconstriction (e.g.
xylomatazoline 0.1 percent spray) to the nasal mucosa
of both nostrils
2. Injection of local anaesthetic agent and adrenaline
(lignocaine 2 percent with 1:80,000 adrenaline) into the
nasal mucosa.

54. • Patients are catheterized prior to surgery.
• Standard preparation of the nose is performed with
topical vasoconstriction and infiltration.
• lumbar drain: may be used with some macroadenomas
(to inject fluid in order to help bring the tumor down, also may be
used for post-op CSF drainage following transsphenoidal repair of
CSF fistula)
• intraoperatively 100mg hydrocortisone IV q 8 hrs

55. • POSITIONING :
• Body is placed supine
• elevate thorax 10–15°(reduces venous pressure)
• Head turned slighty towards the right to face the
surgeon
• ET tube positioned down and to patient’s left

58. • The endoscope and microdebrider are passed medial to
the middle turbinate and the superior turbinate and often
the sphenoid ostium are identified

59. • The next step is to remove bilaterally the lower two-thirds of
the superior turbinate and expose the natural ostium of the
sphenoid sinus
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60. • The sphenoidotomies are enlarged up to the lateral wall
of the sphenoid.
• The next step is to remove the sphenoid mucosa
starting on the sphenoid septum in the larger of the two
sinuses.
• The sphenoid sinus septum is removed.

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62. • The thin bone of
the anterior face
of the pituitary is
fractured and
removed with a
Kerrison punch
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63. • Coagulate and incise the dura centrally in an
“X”pattern (NOT“+”pattern).
• Malleable suction ring curettes and standard
pituitary ring curettes are used to first clear
the tumor along the floor of the pituitary fossa
until the posterior wall of the pituitary fossa is
seen

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65. • Once the tumor has been completely removed, Gelfoam
paste (Gelfoam powder mixed with saline to form a paste)
is placed within the pituitary fossa.
• The preserved dural flap and sphenoid mucosa are
positioned over the anterior face of the sella and fibrin glue
applied to the surface

67. • The middle turbinates are repositioned in their correct
orientation and the operation is complete.
• If the patient has a CSF leak from the diaphragm, then
the hole in the diaphragm is identified and a conically
shaped fat graft is placed into the defect and gently
pushed through the hole with the malleable probe until the
leak is completely sealed.

68. COMPLICATIONS OF
SURGERY
• Intraoperative complications :
1.haemorrhage
2. CSF leak
Early postoperative complications :
1. Diabetes insipidus
2. CSF leak
3. Meningitis

69. • Late postoperative complications :
-Persistent diabetes insipidus.
-Nasal and sinus complications.
-Recurrence of the tumour.

70. INDICATIONS FOR TRANSCRANIAL APPROACH TO THE
PITUITARY GLAND
• Large intracranial element of the tumour that is
unlikely to be accessible during transsphenoidal
surgery, then this approach should be considered.

71. Transfrontal
Trans-
sphenoidal
Surgery
Radiotherapy
Observation
Medical therapy