PITUITARY TUMORS

Dr. Mãdãlina Muşat

Inst. de Endocrinologie C.I.Parhon, Bucuresti
 Pituitary tumors
Incidence: 10%-25% in adult (autopsies); 1% in children
clinically overt pit adenomas: 1-2: 100.000
Mostly benign (adenoma), rarely malignant (only in the presence of
extranevraxial mets)
Mostly sporadic, rarely familial

Pathogenesis
Somatic mutation : most sporadic pituitary adenomas are
monoclonal
 Progenitor cell

1st hit Princeps mutation Differentiated cell

Oncogenic gene activation
Tumor suppressor gene inactivation

Transformed cell
Clonal expansion

Proliferation promotors Adenoma

Growth factors
Hypothalamic RH
Deregulation of normal feedback Carcinoma
Protooncogene overexpression

2nd hit (mutation)

Epidemiology and etiopathogenesis of pituitary adenomas
Elena D. Aflorei • Marta Korbonits J Neurooncol, 2014
 Pituitary Adenoma Classification

• Clinical: functional (clinical secreting T)

non-functional adenomas
• Size: microadenoamas <1cm, macroadenoamas>1cm
•Imunohistochemistry:
 GH secreting tumors(somatotropinomas)
 PRL (prolactinomas)
 ACTH (corticotropinomas)
 TSH (tirotropinomas)
 FSH , LH (gonadotropinomas)
 mixt secretion: e.g. GH+PRL (somatomamotropinoame)
 negative (null adenomas)
• Evolution: Hardy encapsulate, invasive
• Extension : supraselar, infraselar, paraselar
 Clinical Presentation

1. Hormonal excess signs and symptoms

2. Pituitary insufficiency signs and symptoms

3. Mass-related signs and symptoms

 Headache
• Frontal and retro-orbital mostly
• It is not correlated with tumor dimension
• Rarely intracranial hypertension
Optic Chiasm Compression
• Visual field defects
(uni/bilateral
temporal field defects
Cavernous Sinus Compression
Cranial nerve palsies: III, IV, VI, V
GH SECRETING PITUITARY ADENOMAS
(Somatotrophinomas)
GIGANTISM
ACROMEGALY
 History of Acromegaly
David and Goliath
Giant Goliath probably had visual field defectS and muscle weakness
both present in acromegaly
 History of Acromegaly
• 1886: First Medical description of
acromegaly by Pierre Marie
• 1900: Benda & al, sugest pituitary
involvement in acromegaly
• 1909: Harvey Cushing reports alleviation
of acromegaly symptoms after partial
Hypofisectomy

Sheaves R. Pituitary 1999:2:7–28

 Epidemiology Of Acromegaly
• Incidence 3-4 new cases : 1 million people/an1
• Prevalence 40-90 :1 million de locuitori 1
=> in Romania 800-1800 existing cases .
Pathophysiology
Prolonged excessive GH secretion stimulates
bone and tissue growth, increases BP, and
insulin resistance.

In 99% of cases this is due to a GH secreting

pituitary adenoma
1% of cases: excessive, ectopic GHRH
stimulation or ectopic GH secretion
Symptoms of Acromegaly
• Unspecific symptoms
• Headache
• Increased sweating
• Fatigue
• Joint aches
• Change in ring and shoe size
 Acromegaly Clinical Signs
• Facial Appearance: coarse
features, frontal bossing,
enlarged nose, deep nasolabial
furrows , prognatism, increased
interdental separation
• Tongue enlargement
(Macroglosia)

• Soft tissue swelling

• Goitre and other
organomegaly
Enlargement of Hands and Feet
Degenerative changes in joints leading to osteoarthritis
Generalized myopathy
Increased Shoe-size
• Barrel Thorax
Osteoarthritis in Acromegaly
• Usualy appears in 10
yrs of evolution
• Inflamation, cartilage
erosion
• Increased cartilage
space
• Mostly in lumbar
spine, hips, knees,
ankles
Goiter

• Thyroid enlargement
(goiter) is present in
10.5% of cases
 ACROMEGALY COMPLICATIONS

1. HYPERTENSION (40%)

2. DIABETES MELLITUS (20%)

3. OBSTRUCTIVE SLEEP APNEA

4. ISCHAEMIC HEART DISEASE AND CARDIAC FAILURE

5. Colonic Polyps and si COLON CARCINOMAS and OTHER

NEOPLASMS
6. PITUITARY FAILURE

8 . TUMOR MASS EFFECT

OBSTRUCTIVE SLEEP APNEEA
• Macroglosia and soft tissue
swelling in nasopharyngeal
region can cause obstruction of
airflow and breathing pause
(apnea), followed by hypoxemia
of the brain and sleep
interruption that will restore
normal breath
• If severe (frequency, duration) it
results in tiredness, increased
nervosity, sleepiness during the
day
• It is associated with pulmonary
hypertension and stroke
Secondary Diabetes Mellitus
• Gh causes
insulin-
resistance
either as
direct effect
on GHR, or
mediated by
IGF1
 Carpal Tunnel Syndrome
Normal Carpal Tunnel
Carpal tunnel Syndrome
Median
Ligamentul Nerve
transvers compression

Median
Nerve

Tingling of the hand, decreased hand grip

In 60% of acromegalic patients
 Associations
1. Multiple endocrine Neoplasia: MEN1/MEN4:
Acromegaly, Hyperparathyroidism, pancreatic tumors:insulinom, gastrinom, adrenal
tumors
2. Carney Complex: GH secr. Pit adenomas, spotty skin pigmentation, adrenocortical
hyperplasia
3. Isolated Familial Pituitary Tumors
4. McCune Albright syndrome polyostotic fibrous dysplasia, irregular café-au-lait
skin spots, precocious puberty in girls, goiter, adrenal Cushing syndrome
 INVESTIGATIONS
• Oral glucose tolerance test
Failure to suppress GH < 1mcg/L in response to 75 g oral glucose load
N.B.False positive in chronic renal failure, chronic liver failure, malnutrition,
heroin addicts, diabetes mellitus, puberty , anorexia nervosa
• IGF1 elevated in addition to OGTT
• GH day curve medioan GH over 5 samples during 24 h <2.5mcg/L

• TRH test , if first 2 test are 2 equivocal

200mcg TRH i.v. suppresses GH in normals
In ACRO there is a paradoxal increase of GH ( minim 50%)

• Pituitary MRI

• Imunohistochemistry
 ACROMEGALY TREATMENT

1. SURGERY: transsphenoidal adenomectomy

2. MEDICAL:
• Somatostatin Analogues: Octreotide, Lanreotide, Pasireotide
• GHR Blockers Pegvisomant
• Dopamine agonists: Bromocriptin; Cabergoline
1. Radioterapy
• conventional
• Gammaknife/ cyberknife
PROLACTINOMA
(lactoctroph adenoma)
 INVESTIGATIONS

Serum Prolactin > 100 ng/mL, suggestive of PRL secreting tumors, if >200 ng/mL, suggestive
of macroprolactinomas.
If PRL 2-3 ULN, can be due to stress or other factors

Big PRL (PRL after PEG precipitation of serum) in macroprolactinemia

Thyroid function tests : TSH, fT4, T3

MRI pituitary:
• Microadenomas: hypointense lesions within the pituitary on T-weighted images, stalk
deviation/gland asymmetry
• Macroadenomas often associated wit SEE/bone erosions/cavernous sinus invasion
 Diferential Diagnosis in Hyperprolactinemia
1. Drugs that stimulate prolactin PRL: neuroleptics, antidepressants,
metoclopramid, domperidom, metildopa, rezerpine, verapamil, protease inhibitors
labetalol, estrogens, fenitone, apomorfin, heroin, metadone, morfine, cimetidine
2. ChronicKidney Disease
3. Chronic Liver Disease
4. Hypothyroidism (hyper PRL due to TRH excess)
5. Other pituitary tumors with stalk compression
(PRL<200ng/ml in the presence of a macroadenoma)
6. Hypothalamic lesions (tumors, etc) (dopamine deficit)
7. Infilltrative disease in the stalk: sarcoidosis, histiocytosis
8. Empty sella syndrome
9. Macroprolactinemia
10 Polycyctic ovary syndrome
11. Chest wall lesions: zoster, burns, trauma
12. Stalk section: head injury, surgery
 Prolactinoma Treatment
Aims: - restoration of gonadal function
- reducing tumor size / expansion in macroPRL

1st Choice medical treatment: Dopamine agonists

• Bromocriptine 7,5 mg – 15 mg/day
• Cabergoline 0,5 – 3 mg /week
• Quinagolid 0.15-0.75 mg/zi

Surgical treatment:
•Resistance/intolerance to dopamine agonists
•Macroprolactinoma with optic chiasm compression
Radiotherapy: only in macroPRL
CUSHING’s DISEASE
(ACTH - secreting adenoma)
Cushing’s syndrome is an illness resulting from excess cortisol secretion with a high mortality
if left untreated.

Causes:
ACTH dependent: - pituitary adenoma (Cushing’s disease)
- ectopic ACTH
- ectopic CRH
ACTH independent: - adrenal adenoma
- adrenal carcinoma
- nodula hyperplasia
- iatrogenic
 TYROTROPHINOMAS
Very rare tumors 1% of pituitary adenomas;
Producing TSH or TSH+GH or TSH+PRL
90% are macroadenomas
Clinical features :
- hyperthyroidism
- mass effects (visul field defects, hypopituitarism)
Investigations: elevated FT4 and TSH
- alfa subunitati :TSH >1
- TRH test: blunted response of TSH
Pituitary MRI: macroadenoma

Treatment: surgery cures 1/3 of cases, debullking in 2/3;

adjuvant radiotherapy
somatostatin-analogues (octreotide)
Antithyroid drugs should be avoided
 GONADOTROPHINOMAS

Pituitary tumors secreting FSH/ LH/ alpha-subunits

Clinically mute or
Tumor mass effects and Pituitary Insufficiecy
Diagnostic.
• Elevated FSH is occasionally detected in blood, rarely elevated LH
• Elevated FSH associated with low ACTH/cortisol and
low TSH/tiroxina indicates a gonadotrophinoma.
• Dg imunohistochimic

Management surgery and radiotherapy if relapses

NON-FUNCTIONING PITUITARY ADENOMAS
Clinical features
- headache, visual field defects
- when macro: hypopituitarism: mostly hypogonadism
- asymptomatic, incidentally discovered (incidentalomas)
Investigations
- MRI of the pituitary
- PRL to exclude prolactinomas
- IGF1 to exclude somatotropinomas
FSH. LH, testosterone/estradiol,
Cortisol ACTH, fT4, TSH to detect pituitary failure
- imunohistochemistry:
negative (adenoame nule) or ACTH (silent corticotroph)
gonadotrophs or alpha subunits
Treatment Of Non-Functioning Pituitary Adenomas

1. Transphenoidal surgery if macroadenomas

Observation if microadenomas

2. Medical: hormonal replacement for

hypopituitarism

3. Radiotherapy when recurrent

4. Cabergoline sometimes effective in slowing

progression

Follow-up : at 3 months, then yearly for 5 years after surgery, then bianually
 CONCLUSION

Pituitary tumors, also rare and benign in the majority of cases can affect the entire
endocrine system when hypopituitarism is present or can develop
hormone specific disease which
can trigger metabolic and multiple organ infliction