TCD Second Medical Year

Biochemistry and Molecular Medicine

www.medicine.tcd.ie/clinical_biochemistry

http://mymodule.tcd.ie

Pituitary Function
Dr Gerard Boran
Consultant Chemical Pathologist
Tallaght Hospital, Dublin 24
 Topics
HYPOTHALAMIC AND
PITUITARY FUNCTION

Pituitary tumours
Hypopituitarism
Hyperprolactinaemia
Acromegaly
Introduction Hypothalamic and Pituitary Function

Normal MRI Brain showing

hypothalamus and pituitary fossa
Anterior Pituitary: derived from Rathkes pouch
Posterior Pituitary: derived from 3rd ventricle floor
 Pituitary
Tumours
Commonest cause of
pituitary disease
Mostly benign pituitary
adenomas, but can cause
serious pressure effects:-
Expansion / suprasellar
extension
Optic chiasm compression
bitemporal hemianopia
Raised Intracranial pressure
 PITUITARY TUMOURS

Effects of pituitary tumours:-

Excess hormone secretion
Local effects of tumour
Inadequate production of
hormone by the remaining
normal pituitary
(hypopituitarism)
 PITUITARY TUMOURS

Investigation:-
1. Is there a tumour?
2. Is there hormonal excess?
3. Is there deficiency of any hormone?
 PITUITARY TUMOURS
Do: Skull XRay
Investigation:- MRI Pituitary
1. Is there a tumour? Visual Fields
Visual field defects / visual loss
Cranial nerve lesions
Headache meningism
Hydrocephalus, raised ICP
CSF Rhinorrhoea
 PITUITARY TUMOURS
Do: Basal serum/plasma
Investigation:- hormone levels
2. Is there hormonal excess?
Prolactin may be (prolactinoma)
Prolactin sometimes without prolactinoma
GH may be Is there Acromegaly?
ACTH may be Cushings disease?
Multiple hormones often (e.g. GH and PRL)
Hormone elevations may be clinically silent
Tumour may be non-functioning
 PITUITARY TUMOURS

Investigation:-
3. Is there deficiency of any hormone?
Gonadal problems? FSH/LH deficiency?
Is there short stature? GH deficiency?
Slow lethargic adult? TSH/GH deficiency?

Do: Basal serum/plasma hormone

levels; combined pituitary function test
 HYPOTHALAMUS

Regulates appetite / thirst / heat /

sleep-wake cycle / stress / mood /
circadian rhythms / menstrual
cyclicity

Hypothalamic tumours may affect the

above, and cause pituitary hypofunction
 Causes of hypopituitarism

Pituitary-specific
transcription factor 1
(rare)

Craniopharyngioma is
a hypothalamic
tumour arising from
Rathkes pouch
(children)
Nelsons syndrome: pigmentation due to ACTH associated
with an enlarging pituitary tumour, occurs in about 20% of cases
after bilateral adrenalectomy for Cushings disease (now rare)
 Hypopituitarism
Hypopituitarism may be
GENERALISED (commonest)
LH/FSH lost first
Then GH, PRL,
TSH, ACTH preserved until last
Prolactin often early on (unless PRL cells affected)

ISOLATED HORMONE DEFICIENCY

e.g. isolated LH/FSH deficiency (with anosmia Kallmans
syndrome)
Isolated ACTH deficiency
 Hypopituitarism
Panhypopituitarism

Loss of all hormone secretion

Due to tumour, surgery, radiation

Vasopressin, Oxytocin secretion

Usually intact in pituitary disease.
Can be secreted from the hypothalamus even when the pituitary
stalk is damaged
May become deficient in hypothalamus disease (e.g. hypothalamic
tumour or suprasellar extension of a pituitary tumour)
 Hypopituitarism
CLINICAL FEATURES
LH/FSH
libido, loss of secondary sexual characteristics,
amenorrhoea, impotence, hairlessness
GH
may be silent, wellbeing in adults
PRL
Galactorrhoea, hypogonadism
TSH
Malaise, pallor, tiredness, weight gain, dry skin, cold
intolerance
ACTH
Low BP, hyponatraemia, CVS collapse, weight loss, pallor
 A patient with hypopituitarism.
Pallor, skin wrinkling, and absence
of facial hair can be clearly seen.

Coronal MRI of pituitary.

(a) arrowed- left sided lucent intrasellar microadenoma. Pituitary stalk deviated slightly to the right;
(b) arrowed macroadenoma with moderate suprasellar extension and lateral extension compressing the left cavernous sinus;
(c) arrowed - sagittal MRI of head showing pituitary macroadenoma with massive suprasellar extension.
 HYPOPITUITARISM
Investigations
Basal Serum TSH and Free T4
Basal LH and FSH, Oestradiol, Testosterone
Basal Prolactin, Growth Hormone
Basal Serum/Plasma Cortisol (< 100 nmol/L needs
further evaluation may be deficient; > 500 nmol/L
probably OK)

Combined pituitary function test (insulin, TRH, GnRH

I.V.)

NB: Presence of normal libido, erections, ovulation,

menstruation makes generalised hypopituitarism unlikely
Combined Pituitary Function Test

Used to detect hypopituitarism

Warning risk of severe hypoglycaemia

administer insulin, TRH, GnRH IV

Hypoglycaemia is induced (at about 20 minutes),
causing an increase in GH and Cortisol
TRH causes an increase in TSH
GnRH causes an increase in FSH and LH
Combined Pituitary Function Test
 Hypopituitarism
Treatments

Replace deficient hormones (T4, cortisol, androgens,

oestrogens/progestagens
Role of GH replacement in adults controversial
Hyperprolactinaemia
 Causes of hyperprolactinaemia

Range of Prolactin levels

in common causes of
hyperprolactinaemia
 HYPERPROLACTINAEMIA
Causes of Hyperprolactinaemia

Macroprolactinoma = tumour > 10 mm diameter

Macroadenoma + PRL > 5000 u/l = macroprolactinoma
Microadenoma + PRL >2000 u/l = microprolactinoma

PRL > 5000 usually due to a tumour

 HYPERPROLACTINAEMIA
Measurement of prolactin

Macroprolactinaemia complexed non-bioactive

prolactin in circulation

(dont confuse with macroprolactinoma = a large PRL-

secreting tumour >10 mm diameter)
 HYPERPROLACTINAEMIA
Presentation of
Hyperprolactinaemia
60% have galactorrhoea
(spontaneous or expressible),
but normoprolactinaemic
galactorrhoea is also common
Oligomenorrhoea or
amenorrhoea
Decreased libido
Impotency
Subfertility
Delayed puberty
Symptoms/signs of
androgen/oestrogen
deficiency
Headache, visual field
defects (prolactinoma)
Computerized tomography (CT) and magnetic resonance imaging
(MRI) scans of a microadenoma

(a) This postcontrast coronal CT scan demonstrates a 1cm mass

of low density; note the elevation of the diaphragma sellae on
the right side.

(b) Coronal and (c) sagittal MRI scans.

 Treatment of Hyperprolactinaemia

MEDICAL
Dopamine agonists
bromocryptine
Cabergoline,
quinagolide specific
D2 agonist

SURGERY
Risks of hypopituitarism
etc. Medical therapy is
effective in many cases
 Acromegaly and Gigantism
Acromegaly
A pituitary giant

Height 2.3m (7 6 )

Enlargement of the supraorbital Gigantism is the rare clinical counterpart of

ridges and nose, thickening of the acromegaly that occurs in the young before
lips and generalized coarsening of epiphyseal fusion has taken place.
the features over a 13 year period.
Acromegaly and Gigantism

A patient with concomitant

acromegaly and hypopituitarism. The
presence of a GH-secreting pituitary
tumor was the cause of symptoms in
this patient.
 Acromegaly and Gigantism
The secretion of growth hormone (GH) is
stimulated by growth-hormone-releasing hormone
(GHRH) and inhibited by somatostatin both
secreted from the hypothalamus.

Ghrelin is produced by the stomach and is then

transported to the hypothalamus (where it
probably acts as a releasing factor by stimulating
GHRH) and to the pituitary (where it acts as a
paracrine GH stimulator).

At the level of the pituitary, the stimulating effect of

GHRH is modulated by insulin-like growth factor-I
(IGF-I), a peptide formed in the liver and in many
other tissues that are under the influence of GH;
thus, IGF-I becomes part of the negative-feedback
loop control of GH secretion.

The release of somatostatin by the hypothalamus

is stimulated by both GH and IGF-I, thus
comprising the hypothalamic component of the
negative feedback loop for GH regulation.
 Growth Hormone
GH stimulates hepatic production of IGF-1 which
stimulates growth
Metabolic Actions
Increased collagen and protein synthesis
Increased calcium, phosphorus, nitrogen retention
Opposes the action of insulin (diabetogenic)
Mainly nocturnal release (in bursts)
GH secretion increased by stress, exercise
GH secretion suppressed by glucose (basis of
glucose suppression test for acromegaly)
Effect of glucose loading in acromegaly. The figure shows the effects of a 75g glucose load on blood glucose and growth hormone (GH) levels in a normal
subject and a patient with acromegaly. GH levels are acutely suppressed in normal subjects following a glucose load, whereas in acromegaly there is either no
suppression or occasionally even a paradoxical rise. Carbohydrate tolerance is normal in both subjects.
 Glucose Suppression Test
Stress, hypoglycaemia and
ingestion of protein (high
levels of circulating amino
acids) stimulates GH
secretion (counter-
regulatory response against
hypoglycaemia), while high
levels of glucose and FFA
inhibits secretion

In acromegaly, GH secretion is
autonomous and does not
suppress and may paradoxically
rise with hyperglycaemia.