8.5 Pituitary

Question 1

How does a patient with pituitary tumour present?

Answer 1

• Hormonal dysfunction—
  could be over/under secretion of pituitary hormones.
• Mass effect—
  compression of surrounding tissues due to the rapidly growing tumour,
  increased intracranial pressure.
• Incidentalomas—
  with no hormonal or pressure effect.
  Diagnosed during imaging for other conditions.
• Pituitary apoplexy—
  emergency situation with signs of acute hormonal imbalance, meningism, visual impairment and other signs of intracranial pathology.
  This is due to infarction or sudden haemorrhage in an already existing pituitary adenoma.

Question 2

Describe the anatomy of the pituitary gland.

Answer 2

Pituitary is the ‘master gland’,

secreting hormones that control most of the body functions.

It is a pea-sized organ present beneath the hypothalamus
in the sella turcica—

a depression at the base of skull.

It is made up of two types of tissues forming the anterior and posterior pituitary gland.

Question 3

Anterior pituitary gland

Answer 3

Anterior pituitary gland (adenohypophysis)

is an evagination of the ectodermal Rathke’s pouch

(nasopharynx) containing epithelial tissue.

• Traditionally, three cell types were distinguished
  when stained with hematoxylin and eosin.

° Acidophils
stain orange/red and secrete polypeptide hormones—
growth hormone (GH) and prolactin (PRL)

° Basophils
stain blue and secrete glycopeptide hormones—
thyroid-stimulating hormone (TSH), gonadotrophic hormones
(LH/FSH), and adrenocorticotrophic hormone (ACTH).

° Chromophobes
are non staining, due to the nonsecretory nature of
the cells.

Question 4

How are cells classified

Answer 4

• Currently these cells are classified according to the hormones they
  produce.

1. ° Somatotropes
   make up the majority of the anterior pituitary cells.
   They produce GH and are responsible
   for 20% of all pituitary microadenomas.
2. ° Lactotropes
   secrete PRL, and prolactinomas are the commonest
   cause of pituitary adenomas.
3. ° Thyrotropes—TSH.
4. ° Gonadotropes—LH/FSH
5. ° Corticotropes—ACTH

Question 5

How are these hormones stimulated

Answer 5

The signal for the secretion by these cells comes from the hypothalamus via
individual regulatory hormones.

The hypothalamic and the corresponding pituitary hormones,
their site of action, and their functions are depicted in
Table 8.1.

Question 6

Posterior pituitary gland

Answer 6

Posterior pituitary gland (neurohypophysis) is an

extension of the brain at the level of the diencephalon
and hence contains neural tissue.

• Made of pituicytes, which are similar to glial cells.
• It does not produce any hormones
  but rather stores and releases the hypothalamic hormones

oxytocin ( paraventricular)
and
antidiuretic hormone (supraoptic)

Although each nucleus secretes a small proportion of the other hormone

which then pass through the neural axons into the posterior pituitary.

The terminal portions of the axons,
which store these hormone granules called
Herring bodies,

are closely associated with fenestrated capillaries.

Question 7

Hypothalamic and pituitary hormones and their functions

Answer 7

1. GHRH
   Somatotropes—GH
   All body cells –
   Protein synthesis,
   Gluconeogenesis, lipolysis,
   sodium and water absorption
2. PIH
   Lactotropes—inhibits PRL secretion

Breast –
Prolactin causes milk production

3. GnRH
   Gonadotropes—LH/ FSH
   Testes, ovaries –
   Spermatogenesis, ovarian follicular growth
4. TRH Thyrotropes—TSH
   Thyroid gland
   T3 and T4
   General growth and metabolism
5. CRH Corticotropes—ACTH
   Adrenal gland
   Glucocorticoids Mineralocorticoids

Gluconeogenesis, lipolysis,
sodium and water reabsorption,
anti-inflammatory

6. Oxytocin – Breast, kidney – Milk secretion and contraction
   of uterus, water retention
7. ADH – Blood vessel, kidney – Arterial vasoconstriction, water
   reabsorption

Question 8

What is the blood supply of the pituitary gland?

Answer 8

Arterial supply
Superior and inferior hypophyseal arteries,
which are branches of the internal carotid artery.

The superior hypophyseal artery ramifies into the hypthalamo hypophyseal portal circulatory system.
The primary capillary network lies at the pituitary stalk,
where the hypothalamic hormones are released.

This capillary bed is drained by a set of long portal veins that give rise to the
second capillary bed in the anterior pituitary.

The veins originating in the neurohypophyseal capillary plexus give rise to
the short portal veins that will also contribute to the adenohypophyseal
capillary plexus and connect the two circulatory systems.

This hypothalamo-hypophyseal portal system creates a communication
between the endocrine and neural cells providing an easy short-loop
feedback between the two sets of cells.

Question 9

Venous drainage

Answer 9

Cavernous sinus -> Petrosal sinus -> Jugular vein

Question 10

What is portal circulation, and what are the other examples in the body?

Answer 10

The portal circulation begins and ends in capillaries.

Arterial capillaries normally end up forming a vein that
enters the right side of the heart.

In portal circulation, the primary capillary network drains into a vein known
as portal vein,

which then branches to form the second set of capillaries before draining into a venous system.

other examples of portal circulation in the body are the
hepatic portal, placental, renal, ovarian, and testicular circulations.

Question 11

What are the types of pituitary tumours?

Answer 11

Pituitary tumours are responsible for at least three-fourths of all intracranial
neoplasms. Considering the size of tumour, they could be divided as:

Microadenomas

Macroadenoma

Question 12

Microadenomas

Answer 12

• < 10 mm diameter
• Commonly occurring pituitary adenomas
• Clinical effects are mainly due to hormonal hyper-secretion

Question 13

Macroadenomas

Answer 13

• > 10 mm in size
• Nonsecretory tumours
• Effects are usually due to mass and pressure effects leading to visual
  disturbances, increased intracranial pressure, and hypopituitarism due
  to destruction of pituitary tissue.

Question 14

What are their clinical manifestations?

Answer 14

The pituitary gland is surrounded by structures as shown in Figure 8.6.

so the pressure effects relate to the tissues closely related to the tumour.

Floor—sphenoidal air sinus
Roof—diaphragma sella,
an invagination of dura, which is traversed by the
pituitary stalk, optic chiasm

Lateral walls—cavernous sinus, internal carotid artery, CN III, IV, V1, V2, and VI

Question 15

explain the control of GH release.

Answer 15

IGF-1 (Somatomedin C) is a hormone that is secreted mainly from the liver
upon stimulation by GH.

The functions of this hormone are similar to the GH and
cause bone and muscle growth along with lipolysis.

As the half life of IGF-1 is longer than the GH and does not have a diurnal variation,
IGF-1 assay is used to diagnose GH excess or deficiency.

Question 16

What is acromegaly and what are
its features?

Answer 16

Acromegaly is a condition where there is an increased secretion of the GH
in adults.

The term gigantism is used when this occurs before epiphyseal
fusion.

It is a rare condition affecting 6–8 per million.

Question 17

Airway

Answer 17

Increased size of the skull with prominent lower jaw
and malocclusion, macroglossia,

thickening of the laryngeal and pharyngeal soft tissues,
laryngeal stenosis,
hoarse voice due to recurrent laryngeal nerve palsy.

In a minority of the patients,
there is associated thyroid enlargement leading to tracheal compression.

All these features make acromegaly a recognised
cause of difficult ventilation and intubation.

Careful preassessment, including indirect laryngoscopy,
helps with the choice of intubation technique.

The mallampati grades can be falsely reassuring and every step is taken to
overcome a difficult airway. Awake fibreoptic intubation might be necessary
as is awake tracheostomy.

Question 18

CVS

Answer 18

cardiovascular
About 30% of acromegalic patients have hypertension.

Myocardial hypertrophy,
interstitial fibrosis,
cardiomegaly leads to ischaemic heart disease
left ventricular dysfunction.

ECG and ECHO are mandatory to assess the cardiac function.

Question 19

Respiratory

Answer 19

Coarsening of features leading to upper airway obstruction,
spirometry shows an obstructive picture.

The associated obstructive sleep apnoea
requires investigation and appropriate
treatment to reduce postoperative respiratory morbidity.

Question 20

Neurological

Answer 20

Compression of surrounding structures leading to
visual disturbances,
increased ICP,
cavernous sinus thrombosis.
CN II involvement leads to impaired visual acuity
and bitemporal hemianopia.

CN III, IV, and VI involvement cause ophthalmoplegia and other visual disturbances.

Question 21

Endocrine

+

Others

Answer 21

Impaired glucose tolerance and diabetes mellitus complicates more than
25% of acromegalic patients.

This necessitates careful glucose monitoring
and treatment with variable rate insulin infusion perioperatively.

There is a high likelihood of high PRL secretion
contributing to menstrual problems in
women and sexual dysfunction in men.

others
Increased size of hands and feet, arthropathy, myopathy, osteoporosis.

Question 22

How is acromegaly diagnosed

Answer 22

Due to the insidious onset of the condition, the diagnosis can be delayed for
even a decade.

• Clinical appearance
• Signs and symptoms
• Random GH or IGF-1 concentration
• Failure of suppression of GH after 75 mg glucose administration (GTT)
• MRI to look at the size and extent of tumour

Question 23

what are the different modalities of treatment?

Answer 23

Treatment is aimed at controlling the size and reducing the effects of the
tumour. Untreated acromegaly is associated with a 2 to 2.5 times increased
mortality compared to healthy adults.

• Surgery
  Is the mainstay of treatment and is currently done by minimally invasive
  endoscopic procedure through the transsphenoidal route.
• Drug therapy

° Dopamine agonist —usually Cabergoline.

° Somatostatin analogues—usually octreotide.
This helps to reduce the size of tumour before surgery.

° Growth hormone receptor antagonist—
expensive but has been shown
to normalise the levels of IGF-1.

• Radiotherapy
  Takes longer time to work. But with the invention of the ‘gamma-knife’
  radiosurgery, remission can be achieved in less time.

Question 24

What are the anaesthetic concerns in a patient undergoing surgery for acromegaly?

Answer 24

Anaesthetic concerns could be divided according to the factors
pertaining to:

• Neurosurgical anaesthesia and its implications

° Haemodynamic stability

° Maintenance of cerebral oxygenation

° Prevention of perioperative complications

° Rapid emergence to facilitate early neurological assessment

° Adequate postoperative analgesia and antiemesis

° Anaesthesia for transsphenoidal pituitary surgery is not covered in this
question.

• Acromegaly and its implications

Question 25

• Acromegaly and its implications

Answer 25

° Effects of acromegaly on various organ functions—airway and other
systems as above

° Intra- and postoperative complications—airway and respiratory
compromise, haemorrhage, air embolism, etc.

° Diabetes insipidus

Question 26

Explain the physiology of diabetes insipidus after pituitary surgery.

Answer 26

Diabetes insipidus (DI) is due to decreased

secretion of (central) or response to (nephrogenic) ADH.

Inappropriate water loss leads to hypernatremia and
increased serum osmolality in the context of large volumes of dilute urine.

Central DI can occur after traumatic brain injury, subarachnoid haemorrhage,
infections, brain tumours, and post pituitary surgery.

There is decreased ADH release characterised by polyuria, polydipsia, and thirst. The treatment aims at replacement of water and ADH.

Intranasal (or intravenous) Deamino D arginine Vasopressin (DDAVP)
has been the mainstay of treatment.

The criteria for the diagnosis of DI include:

• Increased urine volume > 3 L/day
• Increased serum sodium > 145 mmol/L
• Increased serum osmolality > 300 mosm/kg
• Decreased urine osmolality < 300 mosm/kg
• Decreased urine specific gravity < 1.005

Question 27

Nephrogenic DI occurs due

Answer 27

to X-linked recessive mutation or
more commonly because of renal dysplasia and drugs such as lithium.

The ADH secretion is normal but the kidneys fail to respond to ADH,
resulting in polyuria.

Exogenous ADH has no effect but the treatment is aimed
at replacement of water and the use of thiazide diuretics as they allow
increased excretion of sodium along with water and hence breaking the
polydipsia-polyuria cycle.

Question 28

What do you mean by the syndrome of inappropriate ADH secretion SIADH)?

Answer 28

SIADH is a self-limiting condition where there is increased ADH leading
to increased reabsorption of water at the collecting ducts.

There is hyponatremia and decreased serum osmolality in the context of small
volumes of concentrated urine.

Causes could be manifold but are mainly head injury, meningitis, lung
cancer, and infections such as lung and brain abscesses and drugs such as
carbamazepine and amitriptyline
.
The diagnostic features include:
* Decreased serum sodium < 135 mmol/L
* Decreased serum osmolality < 280 mosm/kg
* Increased urine sodium
* Increased urine osmolality
* Normal renal and adrenal function

Treatment is needed only in symptomatic patients and is by electrolyte free
fluid restriction, hypertonic saline and drugs—diuretics (frusemide),
demeclocycline (suppresses renal response to ADH), and ADH receptor
antagonists.

Question 29

How does ADH stimulate water reabsorption?

Answer 29

Vasopressin-2 receptors (V2 or aquaporin-2) are present in the cytoplasm of
the principal cells at the collecting duct of the nephron.

Stimulation by ADH causes transcription of the aquaporin-2,
thereby moving the cytoplasmic aquaporin to the apical membrane.

This results in the formation of water conduits through which water reabsorption occurs.

Question 30

Endocrine Functions of the Pituitary Gland

Answer 30

Adrenocorticotrophic hormone (ACTH): acts on the adrenal glands to produce
glucocorticoids (cortisol, cortisone) and mineralocorticoids (aldosterone).

Beta-melanocyte stimulating hormone: influences skin pigmentation.

Endorphins/enkephalins: endogenous opioid ligands which inhibit nociception.

Follicle stimulating hormone (FSH): ovarian stimulation to produce oocytes and in
the male, stimulation of sperm production.

Growth hormone (GH, also known as somatotropin): has marked anabolic effects on
bone and muscle. This is mediated via hepatic insulin-like growth factor (IGF-1).

Luteinising hormone (LH): similar action to FSH

Prolactin: this stimulates milk production and inhibits ovarian function by antagonizing
the actions of gonadotrophins.

Thyroid stimulating hormone (TSH): stimulates production of thyroid hormones.

Question 31

Posterior Pituitary Hormones and Their Primary Function

Answer 31

Antidiuretic hormone (ADH, arginine vasopressin): this increases the permeability
to water of the renal collecting ducts thereby preventing water loss; it also increases
peripheral vascular resistance.
Oxytocin: this peptide stimulates contraction of uterus during puerperium and the
contraction of milk ducts in lactation.

Question 32

Gamma knife radiosurgery.

Answer 32

This is a technique of delivering highly focused radiation
to intracerebral tumours, including pituitary adenomas. MR scanning allows the exact
‘surgical’ field to be plotted, and a stereotactic frame ensures precise delivery. If the
targeting is not highly accurate, then structures such as the optic chiasm and the
hypothalamus are at risk. This procedure does not require anaesthesia.