Pituitary tumors

ED yr V
Internal diseases, endocrinology
Diseases of pituitary and
hypothalamus
Prof. Marek Bolanowski, M.D., Ph.D.
Department of Endocrinology,
Diabetes and Isotope Therapy
Wrocław Medical University
Pituitary tumors
Hypopituitarism
Diabetes insipidus
Pituitary tumors
adenomas
Monoclonal, slowly growing, benign neoplasms
• clinical 0.02-0.025% but autopsy 10-20%
Hormonally active
• prolactin - prolactinoma - 50%
• GH - acromegaly - 20%
• ACTH - Cushing’s disease - 10%
• TSH, LH, FSH, α-subunit
Hormonally inactive - 20%
Other pituitary tumors
• Craniopharyngioma
• Glioma, chordoma
• Germinoma, dysgerminoma
• Metastatic
Metastatic tumors to the pituitary
•
•
•
•
•
•
breast
lung
gastrointestinal tract
prostate
melanoma
other
50%
20%
6-10%
6-10%
2%
8-16%
Pituitary tumors
• presence of endo- or exogenous stimulatory
factors/lack of inhibitory factors
• receptor defects, mutations, protooncogenes
activation, second messenger disturbances
• differentiation of stem cells
• clone expansion
• tumor formation
11q13 chromosome deletion in MEN-1, only
Pituitary tumors
Mass effects
• headache and visual disturbances: visual loss, visual field
deficit, optic pallor, ocular dysmotility, pupillary abnormalities
Radiological
• sella enlargement, erosion of dorsum
• calcifications in the tumor
Hormonal
• hormonal excess/deficit
• diabetes insipidus
Pituitary adenomas
• microadenomas
< 10 mm
• macroadenomas ≥ 10 mm
Clinical presentation of
hyperprolactinemia in women
•
•
•
•
•
amenorrhea and galactorrhea
amenorrhea
oligomenorrhea and galactorrhea
regular menses and galactorrhea
visual field defect
81.0%
12.0%
1.4%
1.4%
1.4%
Clinical presentation of
hyperprolactinemia in men
•
•
•
•
•
loss of libido/potency
headache
visual failure
gynecomastia
galactorrhea
47%
13%
13%
6%
2%
Diagnosis of hyperprolactinemia
• Sustained hyperprolactinemia
> 20 ng/ml in women
> 10 ng/ml in men
< 200 ng/ml - microprolactinoma
> 200 ng/ml - macroprolactinoma
100-200 ng/ml – pseudoprolactinoma
• Macroprolactinemia
Macroadenoma of the pituitary
(acromegaly)
Symptoms and signs of acromegaly
•
•
•
•
•
•
•
•
acral/facial changes
oligo/amenorrhea
excessive perspiration
headache
paresthesias/carpal tunnel syndrome
erectile dysfunction
hypertension
goiter
98%
72%
64%
55%
40%
36%
28%
19%
Gigantism
Diagnostic criteria of acromegaly
• lack of GH suppression during OGTT < 1 µg/l (ng/ml)
• elevated IGF-1 level
Clinical features of Cushing’s
disease/Cushing’s syndrome
•
•
•
•
•
•
central obesity
facial plethora
hirsutism
menstrual disorders
striae
weakness
85%
80%
75%
75%
50%
50%
Localization tests in Cushing’s
syndrome
•
•
•
•
•
•
ACTH
high dose dexamethasone suppression test
CRH stimulation test
pituitary MRI
adrenal CT/MRI
inferior petrosal sinus sampling
• Cortisol profile
• Urinary free cortisol excretion
Clinical presentation of TSHoma
•
•
•
•
•
goiter
visual field defects
ophthalmopathy
acromegaly
amenorrhea/galactorrhea
94%
42%
6%
16%
12%
Baseline laboratory changes in
TSHomas
• T4, T3 elevated
• TSH detectable
• α-subunit/TSH ratio > 1.0
• GH, Prl, LH, FSH elevated
Gonadotroph adenomas
•
•
•
•
•
•
•
decreased visual acuity
hypopituitarism
asymptomatic
headache
combination of symptoms
testes enlargement
ovarian hyperstimulation
43%
22%
17%
8%
10%
rare
rare
Gonadotroph adenomas
•
•
•
•
normal LH, FSH for age in women
sometimes LH, FSH increased in men
testosterone decreased in men
exaggerated LH, FSH response in TRH test
Differential diagnostics
•
•
•
•
pseudotumors / pituitary cells hyperplasia
incidentaloma
empty sella
lymphocytic hypophysitis
Pituitary enlargement
• Pregnancy
• Hypothyroidism
• CRH or GHRH secretion in excess
Empty sella
Pituitary carcinoma
•
•
•
•
rare, less than 1%
about 100 cases in the literature
carcinoma similar to invasive adenoma
clinical course with frequent recurrences, treatment
resistance and manifestation of metastases
Surgical treatment
• selective, transsphenoidal adenomectomy
• repeated approaches
• transcranial surgery
The goals of neurosurgery
• complete cure
• vision preservation
• hormonal balance
Medical treatment of prolactinomas
Dopamine agonists:
• ergot derivatives
bromocriptine: Parlodel, Bromergon, Bromocorn, Ergolaktyna
1-3 times daily, 1.25-15 mg/day
pergolide, lisuride, once daily
Cabergoline: Dostinex 0.25-2 mg twice weekly
• non-ergot derivatives
quinagolide: Norprolac 37.5-150 mg/day
• The effect of
bromocriptine
treatment on
prolactinoma
Medical treatment of acromegaly GH secreting tumors
• somatostatin analogs
octreotide: Sandostatin, Sandostatin LAR
lanreotide: Somatuline Autogel
vapreotide
• dopamine agonists
bromocriptine: Parlodel, Bromergon
cabergoline: Dostinex
• GH receptor antagonist
pegvisomant blocks peripheral GH action
Radiotherapy of pituitary tumors
• conventional radiotherapy 40-50 Gy, fractioned in
doses 2.0-2.5 Gy at 4-5 sessions a week
• gamma unit stereotactic radiosurgery „gamma knife”
Incidentaloma
Problem of modern technology
• head trauma
• accidents
• CNS events
with a need for head CT/MRI scans
Pituitary incidentaloma
• on CT scans
up to 20%
• on MR scans
10%
• autopsy
10% - 20% (micro)
Incidentaloma – management
algorithm
•
•
•
•
•
hormonal function
size, growth
visual abnormalities presence
other local disturbances
generalized systemic disturbances
Pituitary incidentaloma
hormonal function assessment
functioning
Prl
GH, ACTH,
TSH, Gn
non-functioning
macro
visual field
function
micro
MR
½, 1, 2, 5 years
DA
surgery
SMSA
MR
1, 2, 5 years
Hypopituitarism
• Idiopathic
• Due to pituitary tumor
• Iatrogenic
– Neurosurgery
– Radiotherapy
Hypopituitarism
• secondary hypocortisolism
• secondary hypothyroidism
• secondary hypogonadism
• GH deficiency
Secondary hypocortisolism
(ACTH deficiency)
• nausea, vomiting, abdominal pain, hypothermia
• hypovolemia, low blood pressure, postural hypotension
• asthenia, hypoglycemia
• hyponatremia, hyperkalemia
• no skin hyperpigmentation
• low ACTH, low cortisol
Secondary hypothyroidism
(TSH deficiency)
• cold intolerance, easy fatigability, weakness
• constipation, pale and dry skin, intellectual impairment
• bradycardia, slowed speech, hypothermia, oedema
• delayed relaxation of deep tendon reflexes
• low TSH and fT4
Secondary hypogonadism
(gonadotropin deficiency)
• eunuchoid proportions and sexual infantilism
(prior to puberty)
• absence of axillary and pubic hair, no breast
development
• secondary or primary amenorrhea
• impotence, loss of libido, infertility
• decrease in muscle and bone mass
• low LH/FSH, E2, T
GH deficiency
• growth retardation (prior to puberty)
• body composition changes:
adipose tissue increase,
muscles and bone mass decrease
• no GH increment following stimulation, low IGF-1
Sequence of the pituitary
hormonal deficiencies
•
•
•
•
GH, IGF-1
LH, FSH, E2, P, T
TSH, fT4
ACTH, cortisol
Necessity for hormonal replacement
Hormonal replacement
• Cortison, Hydrocortison
• L-Thyroxine
• Estrogen/Progesterone
• Testosteron
• Growth hormone
10-30 mg/d
50-150 mcg/d
Diabetes insipidus
•
•
•
•
•
•
deficiency/lack of ADH
kidneys insensitivity for ADH
polyuria, polydipsia, thirst
serum hyperosmolality > 295 mOsm/kg H20
urine hypoosmolality
urine specific gravity 1000-1008 g/l
Diabetes insipidus
• Desmopressin
Minirin tabl. 2 x 0.1 – 3 x 0.2 mg daily
Adiuretin nasal spay 1-2 x 10-40 µg
• Lysine-Vasopressin