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PBL 1: Natalie Kovic: 1. Anatomy of The Pituitary Gland, Hypothalamus and Related Structures
PBL 1: Natalie Kovic: 1. Anatomy of The Pituitary Gland, Hypothalamus and Related Structures
The pituitary gland is also known as the hypophysis, an is a component of the endocrine
system with two major parts: an anterior pituitary (adenohypophysis) and a posterior
pituitary (neurohypophysis). Each part secretes particular hormones, the anterior pituitary is
an outpouching from Rathke’s pouch and forms a cluster of secretory cells, non-neural in
origin. The posterior pituitary is a direct extension of neural cell bodies in hypothalamus,
and are involved in the secretion of AVP and Oxytocin.
Vasculature:
The adenohypophysis receives arterial supply via the superior hypophyseal artery (a
branch of the ICA)
This vessel first forms a capillary network around the hypothalamus, which then
drains into a secondary capillary plexus around the anterior pituitary
This is known as the hypothalamo-hypophysial portal system
Posterior pituitary and the infundibulum receive rich blood supply from many
arteries
The superior hypophyseal artery
Infundibular artery
Inferior hypophyseal artery
2. Physiology of the pituitary gland and the role of the hypothalamus in pituitary
control
Anterior Pituitary
Hypothalamic Target Cell Hormone Released Target of Anterior Pituitary
Releasing factor Hormone
GHRH and Ghrelin Somatotroph GH Multiple somatic tissues
(stimulatory)
Somatostatin
(inhibitory)
TRH (negative Thyrotroph TSH Thyroid follicular cells,
feedback loop) stimulated to make thyroid
hormone
CRH (inhibited by Corticotroph ACTH Fasciculata and reticularis cells
glucocorticoids like of the adrenal cortex to make
cortisol) corticosteroids
GnRH (negative Gonadotroph FSH Ovarian follicular cells, to make
feedback loop) oestrogens and progestins and
Leydig cells to make
testosterone
GnRH Gonadotroph LH Ovarian follicular cells to makes
oestrogens and progestins, and
Leydig cells to make
testosterone
Dopamine (tonically Lactotroph PRL Mammary glands – initiates
inhibits lactotrophs) and maintains production of
TSH, GnRH and VIP milk
(stimulatory)
Posterior Pituitary
Hormone Synthesized in Hormone Released into Target of Posterior Pituitary
Hypothalamus Posterior Pituitary
AVP AVP Collecting duct of nephron
to increase water
permeability, increase urea
cycling (also has
vasoconstrictive effects)
Oxytocin Oxytocin Uterus and breast
The breasts are paired structures on the anterior thoracic wall in the pectoral region in both
males and females. However, they are more prominent in females following puberty. In
females the breasts contain the mammary glands – an accessory gland of the female
reproductive system, which are involved in lactation.
Surface Anatomy:
The breast is found on the anterior thoracic wall, extending horizontally from the
lateral border of the sternum to about the mid axillary line
Vertically it spans between the second and sixth intercostal cartilages and lies
superficial to the pectoralis major and serratus anterior muscles
The breast can be considered as two regions:
Circular body: the largest and most prominent part of the breast
Axillary tail: smaller part which runs along the inferior lateral edge of the
pectoralis major toward the axillary fossa
At the centre of the breast is the nipple (smooth muscle fibres), and surrounding this
is skin termed the areolae
The areolae contain numerous sebaceous glands which enlarge during pregnancy
Anatomical Structure:
The breast is composed of mammary glands surrounded by a connective tissue
stroma
The mammary glands are modified sweat glands
Series of ducts and secretory lobules (15-20)
Each lobule consists of many alveoli drained by a single lactiferous duct which
converge at the nipple
The connective tissue stroma is a supporting structure, surrounding the mammary
glands with a fibrous and fatty component
The fibrous stroma condenses to form suspensory ligaments (of Cooper) which
function to attach and secure the breast to the dermis and underlying pectoral
fascia, and separate the secretory lobules of the breast
Pectoral fascia which forms the base of the breast is a connective tissue sheet
associated with the pectoralis major muscles and provides an attachment site for the
suspensory ligaments of Cooper
There is a potential space between the pectoral fascia and the breast known as the
retromammary space
This is used in reconstructive plastic surgery
Lactation:
Process by which milk is synthesised from the mammary glands of a post-partum female.
Milk is produced in response to a suckling infant. The breast milk provides nutrition and
passive immunity for the infant. It also encourages mild uterine contractions to return the
uterus to its pre-pregnancy size (involution) and induces substantial metabolic increase in
the mother, consuming fat reserves stored during pregnancy.
Prolactin is released from the anterior pituitary and is instrumental in establishing
and maintain break milk supply. It is also needed to mobilise micronutrients for
breast milk
Oestrogen, progesterone and other hormones inhibit prolactin-mediated milk
synthesis during pregnancy
After expulsion of the placenta this inhibition is lifted, and milk production
commences
Upon suckling by an infant, there are sensory nerve fibres in the areolae which
trigger a neuroendocrine reflex resulting in milk production
The posterior pituitary releases oxytocin which stimulates myoepithelial cells to
squeeze milk from alveoli to drain into lactiferous ducts
Growth hormone, cortisol, parathyroid hormone and insulin all contribute to
lactation by the transport of maternal amino acids, fatty acids, glucose and calcium
into breast milk
The neuroendocrine reflex due to suckling down-regulates dopamine release from
the hypothalamus (which normally inhibits prolactin release) and upregulates
vasoactive intestinal peptide (VIP) release which normally promotes prolactin release
Mammary Gland:
Modified sweat glands, composed primarily of adipose and collagenous tissue. Expand and
branch extensively during pregnancy, composed of milk-transporting lactiferous ducts. They
expand in response to oestrogen, growth hormone, cortisol and prolactin. In response to
progesterone, clusters of breast alveoli bud from the ducts and expand outward toward the
chest wall – these buds are lined with milk-secreting cuboidal cells (lactocytes)
Clusters of alveoli draining into a common duct are called a lobule
Lactating females have 12-20 lobules radially organised around the nipple
The milk drains from lactiferous ducts into lactiferous sinuses which then meet at
perforations in the nipple called pores
The small bumps of the areolae are called Montgomery glands which secrete oil to
cleanse the nipple opening and prevent chapping and cracking of the nipple during
breastfeeding
Galactorrhea is lactation in men or women who are not breast feeding. There are two
primary mechanisms which can cause this:
Increase in prolactin levels
Reduction in dopamine inhibition of prolactin
Description:
Galactorrhea is a milky nipple discharge not associated with gestation or present
more than 1 year after weaning. Galactorrhea does not include serous, purulent or
bloody nipple discharge
Epidemiology:
Predominantly effects females between 15-50
Can occur in MEN1 and prolactinomas
Disorder Cause
Affected afferent Chest wall trauma
neural stimulation Chiari-Frommel, del Castillo and Forbes-Albright
syndromes
Herpes zoster
Nipple stimulation
Spinal cord injury
Organic Craniopharyngiomas
hyperprolactinemia Irradiation
Meningiomas or other tumours
Multiple sclerosis
Pituitary stalk compression or injury
Post-breast augmentation surgery
Prolactinoma
Sarcoidosis
Traumatic injury
Vascular malformations (aneurysms)
Functional Adrenal insufficiency (Addison’s disease)
hyperprolactinemia CKD
Cirrhosis
Hypothyroidism (reduced release of thyroxine, leading
to increased release of TSH which stimulates prolactin)
Lung cancer
Renal cell cancer
Medications Cardiology
Reserpine, verapamil
GI
H2 blockers, PPIs
Herbal
Anise, barley, thistle
Illicit
Cocaine, marijuana, opioids
Other
Anti-psychotic s, SSRI’s (not always), neuroleptics,
tricyclic antidepressants
5. The effects of antidepressants and antipsychotics on the hypothalamus and
pituitary gland, and how they may cause galactorrhoea
Anti-depressants:
SSRI’s and SNRI’s are the major class of anti-depressants used in the clinical studying
nowadays and so will be the focus of this dot point.
Tricyclic antidepressants have more obvious effects on dopamine inhibition
SSRI’s mode of action involves selectively blocking the reuptake transporters of
serotonin at the presynaptic terminal, thereby increasing serotonin levels in the
synaptic cleft and potentiating it’s effects
Anti-Psychotics:
Antipsychotics also known as neuroleptics are used particularly in the treatment of
schizophrenia and other disorders involving psychosis and delusions.
There are typical and atypical anti-psychotics
Their mode of action involves blocking dopaminergic neurotransmission
Atypical anti-psychotics also have an effect on serotonin receptors
Block dopamine D2 receptors, these are particularly important in the inhibition
of prolactin release from the anterior pituitary
Anti-psychotics can therefore cause disinhibition of prolactin, causing increased
levels of prolactin (hyperprolactinemia)
6. APDTM of pituitary tumours, including the hormonal and mass effects of a
pituitary tumour
Overview:
Most pituitary tumours are adenomas
Symptoms include headache and endocrinopathies (when the tumour either
produces or inhibits hormone production)
Diagnosis is mostly by MRI
Treatment is usually surgery and some medical treatment. Radiation and
dopaminergic agonists may also be used
Most pituitary and suprasellar region masses are pituitary adenomas, which can
either be secretory or non-secretory
Meningiomas, craniopharyngiomas, metastases and dermoid cysts are less
common masses formed in the sella turcica
Secretory adenomas produce pituitary hormones
Microadenoma’s are < 10mm
Macroadenoma’s are > 10mm
Secretory adenomas are classified according to their histologic staining
characteristics
Acidophilic
Basophilic
Correlates with hormone produce
Any pituitary tumour can compress the optic chiasm and/or the optic tract
These tumours may also compress or destroy pituitary and/or hypothalamic tissue
Diagnosis:
Gold standard is using MRI to visualise a mass
Clinical signs and symptoms such as unexplained headaches, visual abnormalities
(particularly bitemporal hemianopia)
CT scan can be useful for macroadenomas but less useful for microadenomas
compared to MRI
Serum testing for pituitary hormones can also be done
Non-Functional Adenomas:
Account for up to half of all pituitary adenomas
Do not cause increased levels of pituitary hormones in the body
Can cause mass effects if they increase in size beyond 10mm
Functional Adenomas:
Produce a particular type of pituitary hormone
Cause effects associated with that hormone, and if large enough can cause mass
effects
Pituitary Carcinoma:
Rare malignant growth which can be functional or non-functional
Can destroy pituitary tissue causing a drop in hormone levels, and if left untreated it
can spread
Sella Mass
Overview Pituitary adenoma (functioning or non-functioning), rarely a
carcinoma
Metastasis to pituitary
Other tumours include craniopharyngioma, germ cell
tumours, meningioma, glioma, pituicytoma, chordoma
Cystic lesions – Rathke’s cleft cyst, dermoid/epidermoid
cysts
Aneurysms, vascular lesions, apoplexy
Hypophysitis – lymphocytic, granulomatous, xanthomatous,
ipilimumab-induced, IgG4
Sign and Headache, mass effect
Symptoms Bitemporal hemianopia
Diplopia (CN III, CN IV, CN VI) (due to involvement of the
cavernous sinus)
Facial pain/ numbness due to involvement of the ophthalmic
branch of CN V
Seizures (temporal lobe)
Hydrocephalus due to impingement of the 3rd ventricle
Treatment Prompt surgical debulking to restore impaired vision
May be difficult to operate if extensive cavernous sinus
involvement, encases of carotid arteries
Radiotherapy used for residual disease
Management of hormonal deficiencies if present
Treat primary cause if due to infection, inflammation and/or
infiltration
Mass Effects:
Microadenomas rarely cause mass effects
Macroadenomas can cause mass effects
Mass effects involves the compression of surrounding structures and their
subsequent impairment due to a mass in the sella turcica
Common mass effects include:
Headaches and pain, if compression of the diaphragma sella (a sheet of dura
mater high in pain afferent density), and/or if there is a rise in ICP
Compression of the cavernous sinus can have a number of effects, depending on
the degree of compression:
o ICA involvement: syncope and dizziness, potential cerebral stroke
o CN III, CN IV, CN VI: innervators of extra-ocular muscles, compression can
lead to diplopia
o CN V1: can lead to upper facial numbness or paraesthesia
If involvement of third ventricle hydrocephalus
Compression of temporal lobe seizures
Compression of optic chiasm bitemporal hemianopsia (recall that only the
nasal retinal fibres from both eyes cross over at the optic chiasm, and these
respectively provide information of the temporal field of view)
Compression of other parts of the pituitary gland hypopituitarism
o Hypopituitarism can in turn have secondary effects such as adrenal
insufficiency or hypothyroidism due to a lack of pituitary hormones being
released
Primary headaches:
Migraine (You did this in depth in the neuro block)
Trigeminal autonomic cephalgia’s
Includes cluster headache, chronic paroxysmal hemicrania continua and short-
lasting unilateral neuralgiform headache with conjunctival injection and tearing
Tension-type headache
Secondary Headaches
Cause Example
Extracranial Disorders Carotid or vertebral artery dissection (also causes
neck pain)
Dental disorders (such as infection, TMJ
dysfunction)
Glaucoma
Sinusitis
Intracranial Disorders Brain tumours or anything causing a positive mass
effect (oedema due to stroke etc.)
Chiari type I malformation
CSF leak with low-pressure headache
Haemorrhage (intracerebral, subdural,
subarachnoid which presents as thunderclap
headache)
Idiopathic intracranial hypertension
Infections (abscess, encephalitis, meningitis,
subdural empyema)
Meningitis and non-infectious
Obstructive hydrocephalus
Vascular disorders (stroke, malformation, vasculitis,
venous sinus thrombosis)
Systemic Disorders Acute severe hypertension
Bacteraemia
Fever
Giant cell arteritis
Hypercapnia
Hypoxia (includes altitude sickness)
Viral infection
Viremia
Drugs and Toxins Analgesic overuse
Caffeine withdrawal
Carbon monoxide
Hormones such as oestrogen
Nitrates
PPI’s