Krzysztof Baut

Diseases of the pituitary gland

Department of Endocrinology and Internal Medicine

Medical University of Gdask

MRI of the
Normal Hypothalamo-Pituitary System

A sagittal section

B frontal section

1 pituitary gland
2 infundibulum (pituitary stalk)
3 third ventricle
7 internal carotid artery

4 optic chiasm
5 sphenoid sinus
6 cavernous sinus

Krzysztof Baut

Pituitary gland tumors

Department of Endocrinology and Internal Medicine

Medical University of Gdask

Incidental pituitary tumors

Clinically "silent" adenomas of the anterior lobe of
pituitary gland (incidentalomas):
quite often
MRI: 4,8 - 27%, most authors 10 - 20%

Incidental pituitary tumors

Microadenoma 1 cm

Macroadenoma > 1 cm

Clinically "silent" nonsecreting

Incidental pituitary tumors

Nonsecreting pituitary adenomas can cause:

diabetes insipidus
insufficiency of the piruitary anterior lobe
visual field defects

Incidental pituitary tumors

Non-functioning pituitary adenoma without visual
field defects - observation
Pituitary hormonal function: 1, 2, 5 year
Microadenoma MRI: 1, 2, 5 year
Macroadenoma MRI + visual field: , 1, 2, 5 year
If stable end of the observation
In any other case radical treatment

Metastases to the pituitary gland

1 - 4% of oncology units patients on atopsy.

Most often in the posterior lobe (blood supply

directly from the systemic circulatory system).

Metastases to the pituitary gland

Usually at autopsy. Clinical features are missed

because of the poor general condition.
but

Clinical features of metastasis to the pituitary

gland can be the first manifestation of malignancy.

Metastases to the pituitary gland

Intrasellar metastases

brest cancer 53,0%

bronchial cancer
19,0%
colorectal cancer 7,3%
prostatic cancer
6,3%
pancreas cancer
4,0%
others
10,4%

Metastases to the pituitary gland

Clinical features:

Diabetes insipidus
Insufficiency of the pituitary anterior lobe
Visual field defects (less often)

Acromegaly - characteristics
acromegaly

is an insidious, debilitating disorder

resulting in high circulating levels of GH and IGF-I,
associated with bony and soft tissue overgrowth.

survival

reduced - approximately 10 years

mortality

increased 2 4 x

Acromegaly - epidemiology
rare disease

prevalence 60 cases / million

incidence 3.3 new cases / million / year
average age 40 - 50 years
female = male
diagnosis delay - about 8 years

Acromegaly - etiology
Pituitary adenoma 98%
Others:
Pituitary carcinoma
Ectopic GH-RH secretion
intracranial hamartoma, hypophyseal gangliocytoma;
extracranial carcinoid: pancreas, lung, gastro - intestinal

Ectopic GH secretion
intracranial
extracranial tumors of: pancreas, brest, lung

Acromegaly - symptomatology
Clinical picture:
In childhood gigantism (before epiphyseal fusion)
In adults:
changes in appearance (face, hands, feet, mandible)
organomegaly, including cardiomegaly with cardiac
insufficiency, goiter
headaches
visual field defects
carpal tunnel syndrome
arterial hypertension
diabetes mellitus
excessive sweating

Acromegaly - exclusion
1. Single GH < 0.4 g/L + IGF-1 within normal ranges

2. GH supression < 1 g/L in OGTT

(Glc 75g p.o.) + IGF-1 within normal ranges
(age- and gender-matched)
3. mean (diurnal) GH < 2.5 g/L
useless are:
stimulation tests: TRH, GH-RH, Gn-RH
IGF-BP 3 level

1 g/L = 2 mU/l

Acromegaly - treatment
The goals of therapy in patients with acromegaly are
the elimination of morbidities associated with the
disease and normalization of the increased mortality.
Biochemical criteria for cure of acromegaly:
IGF-1 within normal ranges (age- and gender-matched)
and
GH supression < 1 g/L in OGTT
(Glc 75g p.o.)

Neurosurgical Treatment

Transsphenoidal Approach

Neurosurgical Treatment
Effects of surgical treatment

Without SSA pre-teatment recovery 40 - 60%

After SSA pre-teatment recovery
78 - 91%
microadenoma normalisation of IGF-1: 82%
macroadenoma normalisation of IGF-1: <50%

Neurosurgical Treatment
complications

20%

postoperative pituitary insufficiency

8%

recurrence after 10 years

10%

diabetes insipidus, rhinorrhea

(cerebrospinal fluid leakage),
meningitis

Somatostatin analogues
Biochemical crteria for cure 60-70%
1/3 patients reduction of the tumor
size (20-80%)
>70% patients subjective
improvement
Presurgical treatment
Microadenomas 3-6 months preparation
with SSA; macro 6-12 months

Before Somatostain Analogue Treatment

After Somatostain Analogue Treatment

Classical radiotherapy

Delayed effect
IGF-1 normalisation >70%
(but after 7 years <5%)
after 10 years pituitary
insufficiency in about 50%
Cumulated risk of CNS
neoplasm:
1.9% after 20 years

Steroeotactic radiotherapy

Acromegaly
preoperative SSA

Selected cases

neurosurgery

SSA
+
-

SSA +/- dopamine agonists

radiotherapy

reoperation
-

SSA
-

prolonged SSA

GH-receptor antagonist

Secondary hyperthyroidism (TSH-oma)

1 - 3% of all pituitary adenomas

women : men

1:1

clinical features of hyperthyroidism

FT4, FT3, N / TSH
macroadenoma 90%, invasive (CT, MRI)
mixed adenoma 28% (GH, PRL, FSH)
prolonged medical therapies, 131I-therapy contraindicated!
treatment neurosurgery after euthyreosis achieved

Beck-Peccoz P., et. al. 1996

Prolactinoma
Most common hormone-secreting pituitary
adenoma (40-50%)
Microprolactinoma PRL < 200 ng/ml
Macroprolactinoma PRL > 200 ng/ml

Pituitary Apoplexy
Apoplexy hemorrhagic infarction of the adenoma or anterior
lobe of the pituitary gland.
Most often macroadenomas.
Due to pituitary crucial role in maintaining hormonal
homeostasis and close anatomical relation to important
brain structures - it is a medical emergency and requires
prompt diagnosis and appropriate management.
clinically "overt" - about 1% of all pituitary adenomas
clinically "silent"
10-20% operated adenomas
1-3% adenomas on autopsy

Pituitary Apoplexy
Clinical features - depends on the extent and direction of tumor
spread and on the extent of necrotic and hemorrhagic mass:
> sudden headache;
> meningismus (accompanied sometimes by fever) blood and
necrotic debris penetration to the subarachnoid space;
> vision field defects suprasellar expansion;
> oftalmoplegia oculomotor palsy compression of nerves
running in cavernous sinus;
> consciousness impairment;
> acute multihormonal pituitary failure (seldom reversible) anterior lobe destruction:
- GH deficiency - 88% of cases,
- gonadotropin deficiency - 85%,
- secondary adrenal insufficiency - 66%,
- secondary hypotyreosis - 44%,
- diabetes insipidus - rarely (independent pituitary posterior
lobe blood supply);

Pituitary Apoplexy
Patophysiology - has not been clarified.
Vascular theory - tumor compresses arteries and it
leads to impairment of pituitary nutritive
microcirculation.
In microadenomas main role of vasoconstriction
and/or other, liberins administration cause
metabolic hyperstimulation triggering sudden
tumor mass increase, vasculature compression
and finally oxygen lack .

Treatment

Pituitary Apoplexy

Early apoplexy
corticostroids

(dexamethasone)

Substitutive treatment
(pituitary insufficiency)
reduction of intracranial hypertension

First week
neurosurgery

(emergency)

progressive visual field deficit or progressive

mental state deterioration, no improvement
after glucocorticosteroid treatment

Krzysztof Baut

Pituitary Insufficiency

Department of Endocrinology and Internal Medicine

Medical University of Gdask

Selective (defficiency of a single function),

dwarfism, Kallmanns syndrome, etc.
Multiple
Posterior lobe deficiency diabetes
insipidus.
Anterior lobe deficiency secondary
deficiency of target glands.

Causes:
dysfunction and/or lesion of
hypothalamus
lesion of the pituitary stalk
dysfunction and/or lesion of pituitary

lesion of pituitary hypoprolactinemia

lesion of pituitary stalk and/or
hypothalamus - hyperprolactinemia

Cranial diabetes insipidus

Deficiency of ADH (vasopressin) leading to failure of urinary
concentration with fluid deprivation.
idiopathic: autoimmune, congenital / familial, others
symptomatic: inflamation / infiltration, e.g. autoimmune, TBC,
sarcoidosis, histiocytosis, leukemia / lymphoma; head injury;
stalk disruption (traffic accident), stalk compression
(infundibuloma, empty sella syndrome); neurosurgery,
radiotherapy of CNS

Cranial diabetes insipidus

Clinical features:
polyuria (>4 l/day, specific weight <1005);
always nocturia
compensatory polydipsia
astenuria

Fluid deprivation hypertonic dehydratation

Cranial diabetes insipidus

Differential diagnosis:

Diabetes mellitus
Nephrogenic diabetes insipidus
Psychogenic polidipsia

Cranial diabetes insipidus

Water deprivation test (8 hours or weight loss 3%)

Urine osmolality < 400 mOsm/l

Serum osmolality > 295 mOsm/l
DESMOPRESIN 2 g i.m.
No reaction after desmopresin nephrogenic
diabetes insipidus
Urine osmolality rises cranial diabetes insipidus

Cranial diabetes insipidus

Treatment:

Causal
Syptomatic: desmopresin (Minirin)
2-3 x 0,1-0,2 mg p.o.
1-3 x 1 dose (nasal aerosol)

Secondary hypothyroidism
Clinical features like in primary hypothyroidism

low fT4
fT3 low or normal
low TSH
no TSH increase after TRH stimulation (in primary
hypothyroidism excessive answer to TRH)

Corticotropic Insufficiency
white Addison
Clinical features like in primary adrenal insufficiency;
without hyperpigmentation or even pallor
(lack of MSH derived from POMC).
Clinical featutes expressed less.
Usually mineralocorticoid suplementation is not necessary
(partial autonomy of the renin-angiotense-aldosterone axis).
Adrenal crisis is less probable and less common.

Somatotropic Insufficiency
Multihormonal pituitary insufficiency
(substitution without GH):
2 3 x increased cardiovascular mortality
increased tendency to atheromatous plaques
formation in carotid arteries

Somatotropic Insufficiency
Similarities of the metabolic disturbances to
the metabolic X-syndrome":
hyperlipidemia,
arterial hypertension,
obesity (abdominal),
resistance to insulin,
increased fibrinogen level

hGH treatment
indication:

GHD, especially childhood onset

contraindications: intracranial hypertension

diabetic retinopathy
active neoplasia (mammography, PSA)

doses:

start: 0.15 0.3 mg/d, e.g. 0.45 0.9 IU/d, adjustment

depends on IGF-1 level (to achieve 140 ng/ml)

administration:

s.c. at sleep time every day

follow-up:

clinical examination, IGF-1, Glc, BMD (DEXA)

time:

probably whole life

Sheehans syndrome
DA

Hemorrhage

Pituitary ischaemia
necrosis

PRL
TSH
ACTH
LH/FSH

(-)

OPI

(+)

(+)
mRNA-PRL
(+)
FGF

E2

normal MRI

MRI: empty sella

Postpartum pituitary necrosis

Sheehans syndrome
Hypopituitarism resulting from an infarct of the pituitary
following postpartum shock or haemorrhage. Damage to the
anterior pituitary gland causes partial or complete loss of
thyroid, adrenocortical, and gonadal function.
clinical features:
rapidly progressing insufficiency of:
thyroid, adrenal cortex, ovaries
no lactation (lack of PRL)
diabetes insipidus - rarely
CT / MRI:
empty sella
Treatment:
suplementarion of thryoid, adrenal cortex, gonadal hormones