Approach to pituitary tumours

1. Chairperson – Dr. Raghuvansh Kumar
Speaker – Dr. Vivek Rana

2. Normal Pituitary Anatomy
Lechan RM. Neuroendocrinology of Pituitary Hormone Regulation. Endocrinology and Metabolism Clinics 16:475-501, 1987

3. Normal Pituitary Anatomy
 Pituitary gland is oval in shape, measuring 8 mm antero-
posteriorly and 12 mm transversely.
 It weighs around 600 mg and is located in sella turcica
ventral to diaphragma sella.
 It comprises anatomically and functionally distinct anterior
and posterior lobes.
 The sella is contiguous to vascular and neurologic
structures, including the cavernous sinuses, cranial nerves
and optic chiasm.

4. Normal Pituitary Anatomy
Modified from Lechan RM. Neuroendocrinology of Pituitary Hormone Regulation. Endocrinology and Metabolism Clinics 16:475-501, 1987

5. Normal Pituitary Physiology
 Anterior pituitary is often referred to as “master gland”
because, together with hypothalamus, it orchestrates the
complex regulatory function of multiple endocrine glands.
 The anterior pituitary gland produces 6 major hormones
Prolactin(PRH)
Growth hormone(GH)
Adrenocorticotropin hormone(ACTH)
Luteinizing hormone(LH)
Follicle stimulating hormone(FSH)
Thyroid stimulating hormone(TSH)

6. Epidemiology
 Pituitary adenomas are most common cause of pituitary
hormone hypersecretion and hyposecretion syndromes in
adults.
 They account for 15% of intracranial neoplasm.
 At autopsy up to one quarter of all pituitary glands harbor
an unsuspected microadenoma(<10 mm in diameter).
 Pituitary imaging detects small in apparent pituitary
lesions in at least 10% of the individuals.

7. Pituitary and Other sellar masses
 Non-Functioning Pituitary Adenomas ( Most common)
 Endocrine active pituitary adenomas
 Prolactinoma ( 50% of functioning tumors)
 Somatotropinoma ( 10-15% of all pituitary tumors)
 Corticotropinoma ( 10-15% of all pituitary tumors)
 Thyrotropinoma
 Other mixed endocrine active adenomas

8. Pituitary and Other sellar masses
 Malignant pituitary tumors: Functional and non-functional
pituitary carcinoma
 Metastases in the pituitary (breast, lung, stomach, kidney)
 Pituitary cysts: Rathke's cleft cyst, Mucocoeles, Others
 Empty sella syndrome
 Developmental abnormalities: Craniopharyngioma (occasionally
intrasellar location), Germinoma, Others

9. Pituitary and Other sellar masses
 Primary Tumors of the central nervous system: Perisellar
meningioma, Optic glioma, Others
 Vascular tumors: Hemangioblastoma, Others
 Malignant systemic diseases: Hodgkin's disease, Non-Hodgkin
lymphoma, Leukemic infiltration, Histiocystosis X, Eosinophilic
granuloma, Giant cell granuloma (tumor)
 Granulomatous diseases: Neurosarcoidosis, Wegner's
granulomatosis, Tuberculosis, Syphilis
 Vascular aneurysms (intrasellar location)

10. Natural History
 Pituitary adenomas have long natural history.
 Vary in size and direction of spread.
 Microadenomas < 10 mm – may cause focal bulging.
 Macroadenomas > 10 mm – cause problems due to mass
effect.

11. Clinical Presentations
 Most common are endocrine abnormalities –:
Hyper-/Hyposecretion of anterior pituitary hormones.
 Visual effects – Bitemporal hemianopsia and superior
temporal defects.

12. Endocrine-Active Pituitary Adenomas
CLINICAL PRESENTATIONS
 Prolactin – Amenorrhea, galactorrhea, impotence.
 Growth hormone – Gigantism and acromegaly.
 Corticotropin – Cushing’s disease, Nelson’s syndrome
(post adrenalectomy).
 TSH – Hyperthyroidism.

13. Non-functioning Adenomas
CLINICAL PRESENTATIONS
 25-30 % of patients do not have classical hypersecretory
syndromes.
 May grow to a large size before they are detected.
 Present due to mass effect
 Visual deficits
 Hormone deficiency like hypogonadism,
hypothyroidism, hypoadrenalism and
hyposomatotropism.

15. Evaluation of a Pituitary Mass
Clinical Evaluation
Radiologic Evaluation
Hormonal Evaluation

16. Clinical Evaluation
 Patients should be asked and examined for any clinical
signs suspicious for pituitary hyperfunction or
hypofunction.
 Hormonal and radiological evaluations.
 All patients with macroadenomas should have formal
visual field testing.

17. Radiologic Evaluation: MRI
 Preferred imaging study for the pituitary.
 Better visualization of soft tissues and vascular structures
than CT.
 No exposure to ionizing radiation.
 T1-weighted images produce high–signal intensity images
of fat. Structures such as fatty marrow and orbital fat show
up as bright images.
 T2-weighted images produce high-intensity signals of
structures with high water content, such as cerebrospinal
fluid and cystic lesions.

18. Radiologic Evaluation: CT
 Better at visualization of bony structures and calcifications
within soft tissues.
 Better at determining diagnosis of tumors with calcification,
such as germinomas, craniopharyngiomas, and
meningiomas.
 May be useful when MRI is contraindicated, such as in
patients with pacemakers or metallic implants.
Mulinda, J. Pituitary Macroadenomas, 9/19/05. http://www.emedicine.com/med/topic1379.htm

19. Pituitary Incidentaloma
< 10 mm > 10 mm
Evaluate for
Hormonal
Hypersecretion
Evaluate for:
• Hormonal Hypersecretion
• Hormonal Hyposecretion
• Visual Changes/defects
Hormonal or Visual
AbnormalitiesNormal No Abnormalities
Observe ObserveTreatment

20. Hormonal Evaluation
 May include of both basal hormone measurement and
dynamic stimulation testing.
 All pituitary masses should have screening basal
hormone measurements, including:
 Prolactin
 TSH, FT4
 ACTH, AM cortisol, midnight salivary cortisol
 LH, FSH, estradiol or testosterone
 Insulin-like growth factor-1 (IGF-1)
Mulinda, J. Pituitary Macroadenomas, 9/19/05. http://www.emedicine.com/med/topic1379.htm

21. Treatment of Pituitary
Neoplasia
Observation
Pharmacotherapy
Surgery
Radiation Therapy

22. Observation and Follow-up
 If less than 20 mm and no neurologic or hormonal
abnormalities:
 Monitor for adenoma size, visual changes, and hormonal
hypersecretion in 6 and 12 months, then annually for a
few years.
 Lesions less than 10 mm and proven to have no hormonal
hypersecretion:
 Lesions 2 to 4 mm: no further testing required.
 Lesions 5 to 9 mm: MRI can be done once or twice over
the subsequent two years, if the lesion is stable in this
period, the frequency can be decreased.
Peter J Snyder MD, “Pituitary incidentaloma” UpToDate November 25, 2003

23. Pharmacotherapy
 Most useful in prolactinomas, alone or with other
intervention.
 May be used in certain other functioning tumors as
adjunctive therapy along with surgical and/or
radiotherapy.

24. Indications for Surgery
 Surgery is the first-line treatment of symptomatic
pituitary adenomas.
 Useful when medical or radiotherapy fails.
 Surgery provides prompt relief from excess hormone
secretion and mass effect.
 Indicated in pituitary apoplexy with compressive
symptoms.

25. Pituitary Surgery
 Transsphenoidal approach:
used for 95% of pituitary
tumors
 Endonasal submucosal
transseptal approach
 Septal Pushover/Direct
Sphenoidotomy
 Endoscopic approach

26. Complications of Transsphenoidal
Surgery
Outcome Measure Incidence (%)
Mortality <0.5
Major complication (CSF
leak, meningitis, ischemic
stroke, intracranial
hemorrhage, vascular
injury, visual loss)
1.5
Minor complication
(sinus disease, septal
perforations, epistaxis,
wound infections and
hematomas)
6.5
.
h
t
m

27. Radiation Therapy
 Reserved for patients with larger tumors and/or persistent
hormonal hyperfunction despite surgical intervention.
 Conventional radiotherapy
 Gamma knife radiosurgery

28. Conventional Radiotherapy
 Response is slow, may take 5 to 10 years for full effect.
 Successful in up to 80% of acromegalics and 55-60% of
Cushing’s disease.
 High rate of hypopituitarism: up to 60%.
 Other complications: optic nerve damage, seizures,
radionecrosis of brain tissue.
Pituitary, 100-162.

29. Gamma Knife Radiosurgery
 Stereotactic CT guided cobalt 60 gamma radiation to narrowly
focused area.
 Long term data not yet available but suggest up to a 70%
response rate for acromegaly and up to 70% for Cushing’s in
some centers.
 Complication rate likely lower, but still high rate of
hypopituitarism (~55%).
Basic and Clinical Endocrinology, 6th ed. Chapter 5 Hypothalamus and Pituitary, 100-162.

30. Prolactinoma
 It arises from lactotrope cells account for about half of all the
functioning pituitary tumors.
 Mixed tumors secreting combinations of GH & PRL, ACTH &
PRL and rarely TSH & PRL, are also seen.
 The female: male is 20: 1 for microadenomas while its same for
macroadenomas.
 PRL concentration > 100μg/L are usually associated with
macroadenomas.(normal : 10-25 μg/L).
 About 5% of microadenomas progress in long term to
macroadenomas.

31. Prolactinoma
 Hyperprolactinemia resolves spontaneously in about 30%
of microadenomas.
 Women usually present with amenorrhea, infertility and
galactorrhea.
 Men often present with impotence, loss of libido and
infertility.
 If tumor extends outside of sella, visual field defects or
other mass effects may be seen.

32. Management
 As microadenomas rarely progress to become
macroadenomas, no treatment may be needed if fertility is
not desired.
 Estrogen replacement is indicated to prevent bone loss and
other consequences of hypoestrogenemia.
 For symptomatic microadenomas, therapeutic goals
include :
• Control of hyperprolactinemia.
• Reduction of tumor size.
• Restoration of menses and fertilty.
• Resolution of galactorrhea.

33. Management
 Medical management with oral dopamine agonist are the
main stay of therapy for patients with micro or macro
prolactinomas.
 Dopamine agonist suppress PRL secretion and synthesis as
well as lactotrope cell proliferation.
 Various drugs available are:
 Cabergoline : 0.5 to 1 mg twice weekly.
 Bromocriptine : 2.5 mg thrice a day
 Pergolide mesylate
 Lisuride

34. Management
 Side effects of Dopamine agonists include :
 Nasal stuffiness, dry mouth, nightmares, insomnia and
vertigo.
 Nausea, vomiting and postural hypotension with faintness
can also occur after the initial dose.
 Rare reports of leukopenia, thrombocytopenia, pleural
fibrosis, cardiac arrythmias and hepatitis have been
described.
 Surgery may be needed in dopamine resistance or
intolerance, or in presence of invasive macroadenoma with
compromised vision.

35. Acromegaly
 It usually results from somatotrope adenoma but rarely
may arise from extrapituitary lesions.
 Patients with empty sellae may
present with GH- hypersecretion
due to small GH secreting adenoma
within the compressed rim of
pituitary tissue.
 GH secreting tumors rarely arise from
ectopic pituitary tissue remanents
in nasopharynx or midline structures.

36. Clinical Findings of Acromegaly
Symptoms and signs at
presentation
Overall prevalence (%)
Facial change, acral enlargement, and soft-tissue
swelling
100
Excessive sweating 83
Acroparesthesiae/ carpal tunnel syndrome 68
Tiredness and lethargy 53
Headaches 53
Oligo- or amenorrhea, infertility 55*
Erectile dysfunction and/or decreased libido 42#
Arthropathy 37
Impaired glucose tolerance/ diabetes 37
Goiter 35
Ear, nose throat and dental problems 32
Congestive cardiac failure/ arrythmia 25
Hypertension 23
Visual field defects 17
http://www.endotext.com/neuroendo/neuroendo5e/neuroendoframe5e.htm

37. Complications of Acromegaly
Cardiovascular
 Ischemic heart disease
 Cardiomyopathy
 Congestive heart failure
 Arrhythmias
 Hypertension
Respiratory
 Kyphosis
 Obstructive sleep apnea
Metabolic
 Diabetes mellitus/IGT
 Hyperlipidemia
Neurologic
•Carpal Tunnel syndrome
•Stroke
Neoplastic
•Colorectal
•(Breast and prostate - uncertain)
Musculoskeletal
•Degenerative arthropathy
•Calcific discopathy,
pyrophosphate arthropathy
http://www.endotext.com/neuroendo/neuroendo5e/neuroendoframe5e.htm

38. Diagnosis of Acromegaly
 Random GH – not useful.
 Insulin like growth factor 1 (IGF-1) – best for screening.
 Oral glucose GH suppression testing – gold standard to
confirm diagnosis. Failure of GH suppression to <1μg/L
within 1-2 hr of an oral glucose load of 75 gms.

39. Management
 Surgical resection is the initial treatment for most patients.
 Somatostatin analogues are used as adjuvant treatment for
preoperative shrinkage of large macroadenomas.
 Irradiation or repeat surgery may be required for patients
who cannot tolerate or do not respond to adjuntive medical
therapy.
 Drugs used are :
 Somatostatin
 Octerotide and lanreotide
 GH receptor antagonist : Pegvisomant

40. Cushing’s Disease
William’s Textbook of Endocrinology. 8th Ed. Foster, DW, Wilson, JD (Eds), WB Saunders, Philadelphia, 1996

41. Cushing’s Disease
• Moon facies
• Facial plethora
• Supraclavicular fat
pads
• Buffalo hump
• Truncal obesity
• Weight gain
• Purple striae
•Proximal muscle weakness
•Easy bruising
•Hirsutism
•Hypertension
•Osteopenia
•Diabetes mellitus/IGT
• Impaired immune
function/poor wound healing

42. Buffalo hump Purple striae

43. Progressive Obesity of Cushing’s Disease
William’s Textbook of Endocrinology. 8th Ed. Foster, DW, Wilson, JD (Eds), WB Saunders, Philadelphia, 1996
Age 6 Age 7 Age 8 Age 9 Age 11

44. Diagnosis of Cushing’s Syndrome
 Measurement of 24-hr urine free cortisol(UFC) is precise
and cost effective screening test.
 Failure to suppress plasma cortisol after overnight 1 mg
dexamethasone suppression test.
 Elevated midnight samples of cortisol are suggestive of
Cushing’s syndrome.
 Basal plasma ACTH levels.

45. Management
 Selective transsphenoidal resection is the treatment of
choice.
 Repeat surgery or pituitary irradiation may be needed
when initial surgery is unsucessful.
 Various drugs inhibiting steroidogenesis:
 Ketoconazole
 Metyrapone
 Mitotane
 Aminoglutethimide
 Trilostane
 Cyproheptadine

46. Non functioning and Gonadotropin
producing pituitary adenomas
 These secrete little or no pituitary hormones.
 These are the most common type of pituitary adenomas and are
usually macroadenoma at time of presentation.
 Based on immunohistochemistry, most clinically non-
functioning adenomas can be shown to originate from
gonadotrope cells.
 They may be incidentally discovered but often presents with
mass effects.
 Menstrual disturbances and ovarian hyperstimulation rarely
occur in women. More commonly, adenoma compression of
pituitary stalk or surrounding pituitary tissue leads to attenuated
LH and features of hypogonadism.

47. TSH secreting adenomas
 These are rare but often large and locally invasive when
they occur.
 Patient usually presents with goiter and hyperthyroidism.
 Diagnosis is based on demonstrating elevated FT4 and
TSH and MRI evidence of pituitary adenomas.
 Surgery is the treatment of choice.
 Thyroid ablation and anti-thyroid drugs can also be used.

48. Conclusion
 Pituitary microadenomas are common, not all are of clinical
concern.
 All pituitary tumors require evaluation of hormonal status.
 Follow up and monitoring will depend on size and other
features of tumor.
 Dopamine agonists are the treatment of choice for most
prolactinomas.
 Surgical intervention is initial TOC for large tumors and
other hyperfunctional tumors (GH, ACTH secreting)