this presentation was uploaded after my own need to find online presentation with the same content and had failed to find. My references were Robbins Pathology textbook, my lecturers notes and some chemistry pathology textbooks that i lack good memory of . I greatly apologize if the content appears copied or if its similar to another's. i also do apologize for improper grammar in some areas. If you find this set helpful please do tell me if you have time.

1. Pituitary gland

2. THERE IS NO LEARNING WITHOUT
REMEMBERING
Socrates

3. normal
 Has anterior(adenohypophysis, 80% of gland) and posterior lobe(neurohypophysis).
 Production of pituitary hormones mostly regulated by hypothalamus ( factors
affecting the anterior carried by portal vascular system)
 Anterior pituitary histology:
colourful array of cells:acidophil(eosinophilic cytoplasm)
basophil with basophilic cytoplasm
chromophobe cells with poorly staining cytoplasm
 Six terminally differentiated cell types in anterior pituitary :
somatotrophs for GH
mammosomatotrophs for GH and prolactin
Lactotrophs for prolactin
Corticotrophs for adenocorticotrophic ,proopiomelanocortin
(POMC) and melanocyte stimulating hormone
Thyrotrophs producing thyroid stimulating hormone
Gonadotrophs for FSH and LH.

5. Try to locate the five cell types

6. Continuation of the normal
 Embryonic origin of pituitary is Rathke’s pouch
 Transcription factors identified for the differentiation of pluripotent
stem cells to the terminally differentiated are;
PIT-1 for sommatotrophs, lactotrophs and
mammosomatotrophs
Steroidogenic factor (SF-1) and GATA-2 for
gonadotrophin differentiation
 Posterior pituitary has modifed glial cells called pituicytes and axonal
processes extending from hypothalamus through pituitary stalk to
posterior lobe. Secretes two hormones; oxytocin and vassopressin (
ADH ). These are synthesised in the hypothalamus and stored within
the axon terminals in the posterior pituitary. In response to
appropriate stimuli, the preformed hormones are released directly
into the systemic circulation through the venous channels of the
pituitary.

7. CLINICAL MANIFESTATIONS OF PITUITARY DISEASE
 These are related to either excess or deficiency of pituitary hormone or mass
effects
 Hyperpituitarism ; from excess secretion of trophic hormones . Its
causes include pituitary adenoma, hyperplasia and carcinomas of the
anterior pituitary , secretion of hormones by nonpituitary tumours, and
certain hypothalamic disorders. They vary with different tumours
 Hypopituitarism ; from deficiency of trophic hormones. Cause :
destructive process including ischemic injury , surgery or radiation ,
inflammatory reactions, and nonfunctional pituitary adenomas.

8.  Local mass effects; Among the earliest changes referable to mass effects
are radiographic abnormalities of the sella turcica including the sella
expansion, bony erosion and disruption of the diaphragma sella. The
close proximity of the optic nerves and chiasm to the sella causes the
expanding lesions of the pituitary to often compress the decussating
fibres in optic chiasm thus giving rise to visual abnormalities' (n both
lateral visual fields that is called bilateral hemianopia) . In addition
there’s elevated intracranial pressure( has headache, nausea and
vomiting). Those extending into the base of brain may produce
seizures or obstructive hydrocephalus. The involvement of nerves likely
to cause cranial nerve palsy.
 Note: occasionally acute haemorrhage into an adenoma is associated
with clinical evidence of rapid enlargement of the lesion , a situation
termed pituitary apoplexy. If acute its a neurosurgical emergency that
may cause death.
 Posterior pituitary disease manifestation are brought to attention by
either an increase or decrease of ADH secretion.

9. PITUITARY ADENOMAS AND HYPERPITUITARISM
 Most common cause of hyperpituitarism ; adenoma arising in anterior lobe
 These benign tumours classification is :
on the basis of hormones produced by neoplastic cells which
are detected by immunohistochemical stains.
on clinical evaluation as either microadenomas (<1cm
diameter , hyperprl = 1000-3000) or macroadenomas (> 1 cm diameter ,
hyperprolactinemia = >6000)
depending on cause most are sporadic and a 5% are from
genetic predisposition
Pituitary adenomas can be also be classified as functional (
associated with hormone excess and resultant clinical manifestations) or non-
functioning ( thus no clinical symptoms of hormone excess but may have mass effects
with large non-functioning pituitary adenomas known to encroach on surrounding
pituitary parenchyma).
 Epidemiology:
mostly in adults with peak incidence of 35-60 yrs of age
 Mostly made up of a single cell type; but there are exceptions of double cell typed
mostly those of growth hormone and prolactin. Rarely is there a plurihormonal
occurrence.

10. pathogenesis
 Sources:
G – protein mutations  GNAS1 gene( most common)
in the genetic predisposed: Responsible genes : MEN1, CDKN 1B, PRKARIA,
AIP
Tp53 mutations
G-protein mutations
 G-proteins normally have role in signal transduction from the surface receptors.
the most important is the Gs- stimulatory G protein with pivotal role in endocrine
organs including pituitary. The Gs exists as an inactive protein with GDP bound to the
guanine nucleotide binding site of the alpha subunit of Gs encoded by GNAS1 gene.
technically in the normal the order of route is hormone attach to the receptor
causing GDP dissociation and thus causing GTP binds to Gs alpha and the GTP bound to
the Gs alpha directly interacts and activates effectors such as adenylyl cyclase thus an
increase in cAMP and this is where the real action starts !!!!
in the presence of a mutation in the alpha subunit this interferes with intrinsic
GTPase activity which causes a constitutive activation of Gs alpha resulting in persistent
generation of cAMP and resulting in undirected cell proliferation.
40% of growth hormone secreting sommatotroph cell adenoma and in a few of
ACTH secreting corticotroph cell adenomas.

11. • AIP-Aryl hydrocarbon receptor interacting protein . Patients with this germline
mutation develop GH secreting adenomas at a younger age (<35yrs) than the
typical for sporadic GH adenoma patients.
• CDKN1B  the product of this gene is the cell cycle check point regulator P27
or KP1 therefore mutations are responsible for patients with MEN1 like
syndrome who lack MEN1 abnormalities.
 Tp53 mutations in pituitary adenomas associated with a propensity for
aggressive behaviour (recurrence and invasion)

12. Morphology
 Well circumscribed soft lesion
 Small tumours are confined to sella
 Large lesions compress optic chiasm and adjacent structures, erode the sella
turcica and anterior clino9id processes, extend locally into the cavernous
sinuses and sphenoidal sinuses
 30% of the lesions: nonencapsulated and infiltrate adjacent bone , dura and
uncommonly brain
 Larger adenomas commonly have haemorrhagic and or necrosis foci

13.  Microscopic
 Polygonal cells arrayed in sheets, cords or papillae
 Supporting connective tissue or reticulin is sparse thus the soft
gelatinous consistency of tumour . This characteristic helps
differentiate it from the normal portion of the pituitary
parenchyma
 Nuclei may be uniform or pleomorphic
 Mitotic activity usually scanty with exception of Tp53 mutations
which demonstrate brisk mitotic activity and higher
proliferaton rates thus causing it to be called atypical adenoma
. The rapid proliferation reinforces their aggressiveness.
 Cytoplasm : dependent on amount and type of secretions and
type of cell involved. Thus may be chromophobic, basophilic or
eosinophilic.

14. INDIVIDUAL TYPES OF TUMORS
Anterior pituitary in hyperpituitarism
 Lactotroph adenoma
 Somatotroph adenoma
 Corticotroph Adenoma
 Other Anterior Pituitary Adenomas: Gonadotroph
adenomas, Thyrotroph adenomas, Non-functioning
Pituitary Adenoma, pituitary carcinoma

15. Lactotroph Adenoma
 Prolactin secreting
 30% of clinically recognized are hyper functioning cases
 Range from small microadenomas to large, expansile tumours
associated with substantial mass effect.
 MORPHOLOGY;;;;;; Chromophobic cells with juxtanuclear localization
of the transcription factor PIT-1(called sparsely granulated lactotroph
adenomas),
;;;;;;;; rarely, acidophilic densely granulated lactotroph
adenomas which are characterised by diffuse cytoplasmic PIT-1
expression localization.
;;;;;;;; undergo dystrophic calcification which ranges from
isolated psammoma bodies to extensive calcification of virtually the
entire tumour mass (pituitary stone).
;;;;;;;; prolactin secretion by functioning adenomas is
usually efficient even microadenomas secrete sufficient prolactin to
cause hyperprolactemia and proportional in that serum concentrations
tend to correlate with size of adenoma.

16.  Clinical course: Prolactinemia which causes amenorrhea, galactorrhea , loss of
libido and infertility. The diagnosis of these adenomas is thus readily identifiable
in women than men especially between the ages of 20-40 yrs, presumably
because of sensitivity to menses disruption. This adenoma underlies a ¼ of the
cases of amenorrhea. In the case of men though the adenomas may continually
grow to macroadenomas before clinical detection is done
 spoiler alert!!! There are various other causes of hyperprolactemia such as
pregnancy, nipple stimulation in lactating mothers when breastfeeding, as a
response to stress, renal failure , anorexia , cirrhosis and hypothyroidism. Thus
an increase in serum prolactin in a person with a pituitary adenoma does not
necessarily indicate a prolactin secreting tumour.
Some other causes of prolactinemia ; antipsychotics, antidepressants , drugs used
for cardiovascular reactions, histamine receptor agonists and PPI, monoamine
oxidase inhibitors , Opiates and Oestrogen ( in combined pill).

17.  MAJOR CLINICAL PROBLEMS SUMMARY;
decreased libido, osteoporosis, galactorrhoea,
hypogonadism, amenorrhea, breast tenderness,
erectile dysfunction, gynaecomastia, infertility,
headache and visual disturbances.

18. Flashback on prolactin physiology and some minor facts
 10% in men and 30% in women of lactotrophs cell population
 Main location of prolactin receptors is the mammary gland where
their activation stimulates lactation and alveolar growth. Also has a
role in complex processes controlling gonadal function.
 Macroprolactin ; state where normal prolactin produced brings on
an activation of production of antibodies which results in prolactin
IgG complex with 170kDa thought to be biologically inactive.
However due to its long half life sometimes may cause high levels
of prolactin in the test results.
 Thus total prolactin levels= monomeric prolactin + macroprolactin
 pulsatile release and diurnal rhythm of prolactin secretion with
highest levels occurring at night during sleep and lowest between
9a.m and noon.

19.  Pathologic hyperprolactemia: result from lactotroph hyperplasia caused
by loss of dopamine mediated inhibition of prolactin secretion. It may
occur with damage of the dopaminergic neurons of the hypothalamus ,
damage of the pituitary stalk (e.g. due to head trauma), or exposure to
drugs that block dopamine receptors on lactotroph cells. Any mass in
the suprasellar compartment such as pituitary adenoma may actually
disturb the normal inhibitory influence of the hypothalamus on
prolactin secretion resulting in hyperprolactinemia.

20. DIAGNOSIS
NORMAL PROLACTIN RANGE < 500mU/L
 Careful and accurate history
 Drug withdrawal possible if its an anti-emetic or tranquiliser. Anti-
psychotics may be difficult to withdrawal however a change can be
taken to one with lesser prolactin effects before taking serum tests for
prolactin. E.g. change of olanzapine( commonly administered in
schizophrenia) or clozapine with aripiprozole which has no effect on
prolactin.
 Measurements repeated over and over to confirm the consistent raise
to eliminate the possibilities of one time stresses that lead to a short
time raise. Macroprolactemia should also be eliminated.
 a third of prolactinomas cause a raise in levels between 700-
1000mU/L however with all other causes eliminated and a persistent
level of 1000mU/L is maintained a tumour is definitely present
 Additional confirmation are radiological abnormalities visible in
pituitary fossa.

21. HYPERPROLACTINAEMIA IN PSYCHIATRIC PATIENTS
 Common finding in psychiatric patients especially those taking anti-psychotic
medication. Therefore it’s a common clinical problem to decide if it’s the
medicine only or there’s a masking of hyperprolactinemia due to a pituitary
tumor. This is addressed by taking a test just before dose administration of
drug .
 It should be appreciated that patients with severe depression and those
taking antipsychotic medication have an increase in pituitary size. A
consideration to be taken into account when radiological investigations are
taken upon.
 Also some protocols should be followed before antipsychotics are
administered :
screen for symptoms and measure prolactin prior to medication
+choice of drug should be determined by prolactinemia history
screen for symptoms on each visit until stable then at this point it
could be yearly if drug is known to raise PRL
Check PRL if symptoms persist beyond > 3000mU/L even with
change of medication
care should be taken where there’s known osteoporosis, lactation or
breast cancer.

22. Endocrine changes in Anorexia Nervosa
 Eating disorder
 Results in abnormal endocrine findings ( are from alteration in
hypothalamic responses) :
- secretion of GnRH is impaired, where BMI is < 20kg/ m2 thus
low LH,FSH and oestradiol
- GH levels raised due to starvation
-TSH levels and prolactin usually normal but may be raised in
some
-serum cortisol is always raised because of its long half life and
increased production and the diurnal variation is lost.

23.  Somatotroph adenomas
- cause gigantism in children and acromegaly in adults
- quite large by time of clinical attention
 MORPHOLOGY:
- Histology; also classified as densely granulated and sparsely
granulated subtypes.
Densely granulated- monomorphic, acidophilic cells with a strong
cytoplasmic GH on immunohistochemistry
Sparsely granulated- chromophobe cells with considerable nuclear and
cytologic pleomorphism and focal weak staining for GH.
Bihormonal mammosomatotroph adenoma- prolactin and GH
synthesised together. Appear like densely granulated distinguished
by the GH production

24.  CLINICAL COURSE;
this are usually majorly due to elevated
levels of GH which stimulate the hepatic secretion of
insulin growth factor -1 which result in the following
manifestations:
1. if a somatotroph adenoma appears in children
before the epiphyses have closed, the elevated levels of
GH (and IGF-1) result in gigantism. This is characterised
by a generalised increase in body size with
disproportionately long arms and legs.
2. if its after closure of the epiphyses, acromegaly
develops. In this condition , growth is most conspicous in
skin and soft tissues , viscera

25. (thyroid, heart, liver, and adrenals), and the bones of face, hand and feet. Bone
density may increase (hyperosity) in both spine and hips. Jaw enlargement
results in protrusion and broadening of the lower face. Feet and hands are
enlarged with fingers being sausage-like and thickened.
3. GH excess can also be associated with a variety of other
disturbances, including gonadal dysfunction , diabetes mellitus, generalized
muscle weakness, hypertension, arthritis, congestive heart failure, and an
increased of GIT cancers.
DIAGNOSIS:
1. elevated serum GH and IGH-1 levels.
2. most sensitive test : the failure to suppress GH production in response to
an oral load of glucose
TREATMENT:#
- surgical removal
- somatostatin analogs
- GH receptor antagonists

26.  Corticotroph Adenomas
• Excess production of ACTH by functioning corticotrophin adenomas leads to
adrenal hyper secretion of cortisol and the development of hypercortisolism (
also known as Cushing syndrome).
Features of Cushing syndrome: Mnemonic
 C - Central obesity, Clavicle fat pads, Collagen fiber weakness, Comedones
(acne)
U - Urinary free cortisol and glucose increase
S - Striae, Suppressed immunity
H - Hypercortisolism, Hypertension, Hyperglycemia,
Hypercholesterolemia, Hirsutism, Hypernatremia, Hypokalemia
I - Iatrogenic (Increased administration of corticosteroids)
N - Noniatrogenic (Neoplasm)
G - Glucose intolerance, Growth retardation

27. MORPHOLOGY:
• Are usually micro adenomas at the time of
diagnosis.
• Most often basophilic(densely granulated) and
occasionally chromophobic (sparsely granulated).
• Both variants stain positively with PAS because of
the presence of carbohydrate in
proopiomelanocortin (POMC), the ACTH
precursor molecule; in addition they demonstrate
variable immunoreactivity for POMC and its
derivatives including ACTH and beta-endorphin

28.  large destructive pituitary adenomas can develop in
patients after surgical removal of the adrenal glands for
treatment of Cushing syndrome. This condition is known
as Nelson Syndrome occurs most often because of a loss
of the inhibitory effect of adrenal corticosteroids on a
pre-existing corticotrophin micro adenoma. The adrenals
are absent in person with this disorder thus
hypercorticolism does not happen but rather mass effects
due to pituitary tumour and there can be hyper
pigmentation because of the stimulatory effect of other
products of the ACTH precursor molecule on
melanocytes.

29. Where Cushing Syndrome happens
Lab diagnosis
 24-Hour Urinary Free Cortisol Level
 This is the most specific diagnostic test. The patient's
urine is collected over a 24-hour period and tested for the
amount of cortisol. Higher levels more than 50-100
 Saliva test. Cortisol levels normally rise and fall
throughout the day. In people without Cushing
syndrome, levels of cortisol drop significantly in the
evening. if cortisol levels are too high late at night it ,
suggests a diagnosis of Cushing syndrome.
 Imaging tests. Computerized tomography scans or
magnetic resonance imaging scans for pituitary tumors.

30. Dexamethasone Suppression Test
 This test helps to distinguish patients with excess production of
ACTH due to pituitary adenomas from those with ectopic ACTH-
producing tumors.
 Patients are given dexamethasone, a synthetic glucocorticoid, by
mouth every 6 hours for 4 days. For the first 2 days, low doses of
dexamethasone are given, and for the last 2 days, higher doses are
given. Twenty-four hour urine collections are made before
dexamethasone is administered and on each day of the test. Since
cortisol and other glucocorticoids signal the pituitary to lower
secretion of ACTH, the normal response after taking
dexamethasone is a drop in blood and urine cortisol levels. Different
responses of cortisol to dexamethasone are obtained depending on
whether the cause of Cushing's syndrome is a pituitary adenoma or
an ectopic ACTH-producing tumor.

31. OTHER ANTERIOR PITUITARY ADENOMAS
 Gonadotroph ( LH-Producing and FSH-producing)adenomas. Difficult to
recognize because they secrete hormones insufficiently and variably and the
secretory products do not cause a recognizable clinical syndrome (non-functioning
adenomas) . Gonadotroph adenomas are most frequently found in middle-aged
men and women when they become large enough to cause neurologic problems(
vision problems, headaches, diplopia or pituitary apoplexy) due to mass effects.
Most commonly impaired secretion of LH which causes decrease in energy and
libido in men ( due to reduced testosterone) and amenorrhea in premenopausal
women.
 Thyrotrophs adenoma, very rare and rarely cause hyperthyroidism.
 Non-functioning pituitary adenomas. A heterogeneous group that consists
approximately 25% of all pituitary tumours. In the past called silent tumours or
null-cell adenomas. Present with mass effects. This lesions may compromise the
residual anterior pituitary sufficiently to cause hypopituitarism which may appear
slowly due to gradual adenoma or abruptly because of acute intratumoral
haemorrhage (pituitary apoplexy).

32.  Pituitary carcinomas are rare with them being less than 1% of pituitary
tumours. Most pituitary carcinomas are functional with prolactin, and ACTH
being the most commonly produced products. Metastases show up late after
multiple local recurrences.

33. HYPOPITUITARISM
Tumours: pituitary adenoma,craniopharyngioma,cerebral tumours
Trauma: head injury
Vascular disease: Severe hypotension, cranial arteritis, infarction especially of
pre-existing tumour, post partum necrosis(Sheehan syndrome)
Infection; meningitis especially tuberculous
Iatrogenic; surgery, radiotherapy
Hypothalamic disorders; tumours, Cushing’s syndrome
Granulomatous disease; Sarcoidosis
 Most pituitary adenomas produce a single hormone in excess however,
pressure effects may decrease secretion of other pituitary hormones so that in
all patients where that in all patients with a decrease in pituitary function
should be thoroughly assessed.

34. PRESENTING FEATURES IN HYPOPITUITARISM
 Features of hormone deficiency
 infertility
 Menstrual disturbances
 Decreased libido
 Erectile dysfunction
 Reduction n muscle bulk
 Decreased body hair
 Fatigue and cold intolerance
 Weight gain
 Polyuria and polydypsia
 Pituitary dwarfism due to growth hormone
deficiency
 Failure of postpartum lactation due to
prolactin deficiency
 Pallor due to loss of stimulatory effects of
MSH on melanocytes. . The rich source of
MSH is the same precursor molecule as
that producing ACTH which may be
deficient with anterior pituitary lesions.
 Features of a tumor
 Headache
 Neuro-opthamological defects
 Facial pan
 Functional adenoma – features
depend on hormone secreted e.g.
prolactinoma may present with
loss of libido , amenorrhea and
galactorrhea due to loss of LH
and FSH . In men this is
accompanied by loss of pubic
and axillary hair.

35.  Lets take a brief discussion and review on some of the causes of
hypopituitarism . We will basically dwell on those that cause destructive
processes to the anterior pituitary.
 Tumours and other mass lesions; this ones cause destruction by exerting
pressure on adjacent pituitary cells.
 Traumatic bran injury and subarachnoid haemorrhage; are among the most
common causes of pituitary hypo function.
 Pituitary surgery or radiation;
 Pituitary apoplexy: caused by a sudden haemorrhage into the pituitary gland
often occurring into a pituitary adenoma. When it decides to take on drama,
apoplexy presents with excruciating headache , diplopia due to pressure on the
occulomotor nerves and hypopituitarism. In severe cases, can cause CVS
collapse, loss of consciousness and even sudden death . Thus mass effects from
the haemorrhage+ acute hypopitutarism = perfect recipe for neurosurgical
emergency.

36.  Ischemic necrosis of pituitary and Sheehan syndrome: Sheehan
syndrome is also known as postpartum necrosis of the anterior
pituitary , it is the most common form of clinically significant ischemic
necrosis of anterior pituitary. During pregnancy the anterior pituitary
doubles to twice its normal size. This physiologic expansion of the
gland is not accompanied by an increase in blood supply from the low-
pressure venous system thus relative hypoxia.
If this is followed up by obstetric haemorrhage or shock it may precipitate
infarction of anterior pituitary lobe .
WHY NOT AFFECT POSTERIOR PITUTARY? This is because the
posterior is supplied by direct arterial branches thus less susceptible to
ischemic injury and is therefore not usually affected.
the ischemic area is resorbed and replaced by a nubbin of fibrous tissue
attached to wall of empty sella.

37. Other causes of ischemic necrosis are: DIC , Sickle cell anaemia, elevated ICP, ,
traumatic injury and shock of any source.
 Rathke cleft cyst: these cysts are lined by ciliated cuboidal epithelium with
occasional goblet cells and anterior pituitary cells can accumulate
proteinaceous fluid and expand compromising the normal gland.
 Empty sella syndrome: any condition or treatment that destroys part or all of
the pituitary gland such as ablation of the pituitary or surgery or radiation can
result in empty sella syndrome. There are basically two types of this
syndrome :
primary : its when there is defect of the diaphragm sellae that
allows herniation of the cerebrum and cerebrospinal fluid into the sella thus
compressing pituitary and expanding the sella. Commonly happens in obese
women who have heard multiple pregnancies. This multiple pregnancies mess
up with the hypothalamic regulatory system thus may also present with hyper
prolactinemia. And with sufficient loos of parenchyma hypopitutarism may
result.
secondary: this is from any mass such as pituitary adenoma that
undergoes surgical excision or infarction and then we lose pituitary function
thereafter.

38.  Hypothalamic lesions; these interfere with the delivery of pituitary hormones
thus with lesser factors stimulating the hormone to release then hypopituitarism
results. They can be tumours, which may be benign ( e.g. craniopharyngioma) or
malignant where the malignant are mostly metastases from breast and lung
carcinoma. Hypothalamic insufficiency may be precipitated by irradiation of
brain or nasopharyngeal tumours.
 Inflammatory disorders and infections such as sarcoidosis or tuberculous
meningitis can involve the hypothalamus and cause deficiency of anterior
pituitary hormone and diabetes insipidus.
 Genetic defects ; Congenital deficiency of transcription factors required for
normal pituitary function would be a cause of hypopituitarism. E.g. Mutation opf
PIT-1 gene results in combined pituitary hormone deficiency of GH, prolactin and
TSH.

39.  CLINICAL MANIFESTATIONS DRIVEN BY VARYING LACK OF SPECIFIC
HORMONES:
• Growth hormone deficiency pituitary dwarfism mostly in children
• Gonadotrophin(LH and FSH) deficiency amenorrhea and infertility in
women, in men decreased libido ,impotence, and loss of pubic and axillary hair
in men.
• TSH and ACTH deficiencies  hypothyroidism and hypoadrenalism
symptoms.
• Prolactin deficiency failure in postpartum lactation
• MSH deficiency  MSH is the stuff that has a common precursor molecule
with ACTH . MSH stimulates melanocytes and thus giving colour. Thus one of
the common manifestations of hypopituitarism is pallor.

40. WORK OUT THE FOLLOWING CASE
 A 26 year old woman admitted to hospital 4 times in a 4 month period with a
background of subclinical hypothyroidism on thyroxine (T4) replacement, short
stature and gravida 3 para 2+1. Clinical presentations included hypoglycaemic
collapse, persistent hypotension , sepsis with acute kidney injury and psychosis.
The patient had no previous mental health issues . However, during this period
they noticed a dramatic change in personality and behaviour. Emotional liability ,
poor short–term memory , unprovoked aggression and delusions were observed.
She felt people could read thoughts , claimed to se dead people and described
tactile hallucinations, the sensation of insects crawling on her skin . Though
cognition apparently remained intact , the patient had very limited insight to her
altered behaviour.
 Why indication of gynaecological history?
 Why the various symptoms such as hypoglycaemic collapse, persistent hypotension , sepsis
with acute kidney injury
 What is your likely suspicion on the causes of psychosis
 Assuming you were the doctor on this case what investigations would you have done
 More time in the hospital is not a cool thing what management would you have undertaken to
help the patient
 Why would the patient likely complain of added wait ( hint; not from the bed rest but from the
treatment and management you give)
 What do you think the first clinician missed that would have prevented the escalation.
 I have no answers for you , just a few hints . Answers are from the lecture and source site.

41. FURTHER HINTS
 After all the investigations were done the conclusions were this was a case of
hypopituitarism presenting with acute adrenal failure with frank psychosis and
empty sella turcica.
 Symptoms originally developed post partum on a background of thyroid
deficiency where subclinical autoimmune lymphocytic hypophysitis (ALH) was
considered as the unifying diagnosis.
 Autoimmune pituitary disease is associated with other autoimmune conditions
notably thyroid thus ACTH was the first hormone deficit
 Lymphocytic infiltration leads to inflammation and expansion of the pituitary
gland . This may occur silently many years before acutely presenting with
adrenal crisis as presumed in this case.
 Psychotic episodes were triggered by the steroid deficiency therefore raising the
levels of stress.
 If this interests you, you can further see about this case in the following :
https://googleweblight.com/i?u=https%3A%2F%2Fedm.bioscientifica.com%2
Fview%2Fjournals%2Fedm%2F2013%2F1%2FEDM13-007.xml&geid=NSTNR

42. POSTERIOR PITUITARY SYNDROMES
 The most clinically relevant involved ADH and include diabetes insipidus and
secretion of inappropriately high levels of ADH.
 Diabetes insipidus . ADH deficiency causes diabetes insipidus , a condition
characterized by excessive urination (polyuria) due to inability of kidney to resorb
water properly from the urine.
 Central diabetes insipidus: It can occur in : head trauma, tumours, inflammatory
disorders of hypothalamus and pituitary and surgery complications. Sometimes this
can arise spontaneously.
 Nephrogenic diabetes insipidus: Diabetes insipidus from ADH deficiency is
designated central to differentiate it from nephrogenic which actually is a result of
renal tubular unresponsiveness to circulating ADH. Causes:
 Certain drugs (such as lithium, amphotericin B, and demeclocycline)
 High levels of calcium in the body (hypercalcemia)
 Kidney disease (such as polycystic kidney disease)
 The clinical manifestations of the two are similar though and include excretion of
large urine volumes which is dilute and with a lower than normal specific gravity.
Serum sodium and osmolality are increased by the excessive renal loss of free water
resulting in thirst and polydipsia. Patients who can drink water are safe unlike
bedridden and obtunded patients who rely on help thus may suffer from life
threatening dehydration.

43. Dipsogenic diabetes insipidus
 due to a defect or damage to the thirst mechanism, in the
hypothalamus resulting in an abnormal increase in thirst
and fluid intake that suppresses vasopressin secretion
and increases urine output.
Gestational
 Gestational DI only occurs during pregnancy.
 Vasopressinase, produced in the placenta, breaks down
ADH in the mother.
 Most cases of gestational DI can be treated with
desmopressin

44. Diagnosis
 Medical history and examination
 Laboratory diagnosis
 Radiology; imaging
Laboratory diagnosis
 Water deprivation test –
 the patient stops drinking liquids for two to three hours
 alterations in body weight, and urine output and composition are measured.
 If the patient has diabetes insipidus they will continue passing large amounts
of diluted urine, compared to other people who would pass only a small
amount of concentrated urine.
 Urine test - a urinalysis examines the physical chemical content of
urine. If urine osmololarity is low it may mean the patient has diabetes
insipidus. If a large amount of sugar is found in the patient's urine, they
may have diabetes mellitus rather than diabetes insipidus.

45.  MRI (magnetic resonance imaging) scan – of
the pituitary gland or hypothalamus areas for any
abnormalities.
 ADH (antidiuretic hormone) test –
 After the water deprivation test a small dose of ADH in form of
desmopressin is given.
 If the desmopressin (ADH) dosage stops the patient from
producing urine, the condition is caused by a shortage of ADH,
and this is central diabetes insipidus.
 If the patient continues to produce excess urine despite the
ADH dose, the patient has nephrogenic diabetes insipidus (the
kidneys are not responding to ADH).

46. Treatment
 Cranial DI: treat underlying conddition desmopressin has a
role
 Nephrogenic: treat underlyng condition. desmopressin has no
role
 Gestational: desmopressin has a role
 Dipsogenic: desmopressin has no role

47.  SIADH : ADH excess causes resorption of excessive
amounts of free water , resulting in hyponatremia.
The most infrequent causes of SIADH are the
secretion of ectopic ADH by malignant neoplasm (
particularly small cell carcinoma of the lung ), drugs
that increase ADH secretion and variety of CNS
disorders , including infections and trauma. The
clinical manifestations of SIADH are dominated by
hyponatremia cerebral oedema and resultant
neurologic dysfunction . Although total body water is
increased , blood volume remains normal and
peripheral oedema does not develop.

48. HYPOTHALAMC SUPRASELLAR TUMORS
 Neoplasms in this location may induce hypo- or hyper function of the anterior
pituitary, diabetes insipidus, or combinations of these manifestation.
 Most implicated  gliomas and craniopharyngiomas. All these are slow
growing
 Clinical manifestations bringing attention: headaches, visual disturbances with
children sometimes presenting with growth retardation due to pituitary hypo
function and GH deficiency.
 In craniopharyngiomas, from the remnants of Rathke’s pouch , abnormalities
of the WNT signalling pathway and activation of the mutations of gene
encoding B-catenin have been reported.

49. Craniopharyngiomas
 Bimodal age distribution: 1st peak 5-15 yrs and a 2nd peak 6th decade.
 two histologic variants; adamantinomatous and papillary, the former
in children and the latter in adults
 Adamantinomatous known to presents with calcification which is
rare in the papillary
 Adamantinomatous consists of nests or cords of stratified squamous
epithelium embedded in a spongy reticulum that becomes more
prominent in the internal layers. Diagnostic feature: compact
lamellar keratin, wet keratin. Cyst formation, fibrosis sand chronic
inflammation are common characteristics.

50.  A craniopharyngioma is seen here at medium and high power. It is derived
from remnants of Rathke's pouch and forms an expanding mass arising in the
sella turcica that erodes bone and infiltrates into surrounding structures. They
are difficult to eradicate, even though they are composed of histologically
appearing squamoid and columnar epithelium lining cystic spaces filled with
oily fluid.

51.  ANY QUESTIONS ON PITUITARY?

52. YAWN
 It is a result of the reduced oxygen supply to the
paraventricular nucleus of the hypothalamus.
 In pathological yawning: it could be due to vasovagal
stimulation due to problems with deep sleep and
sometimes may be sign of an impending heart attack.
 Why have you just yawned in this class? Do you need
a medical intervention?