PITUITARY PATHOPHYSIOLOGY PRESENTATION.ppt

Pituitary gland.
pathophysiology
DR. H.M Kenneth
Year 1 resident General Surgery

Learning objectives
-Describe the anatomy of the pituitary gland
-List of all pituitary hormone
-Describe pathophysiology of pituitary
dysfunction
-Apply pituitary physiology in its surgical
management

 A 27-year-old woman had persistent headache and
amenorrhea.In addition, the size of her foot was increased by
0.5 cm for 6months and lower jaw protrusion was observed.
O/E
BP- 110/60, PR- 68, Temp 37,
Swelling of superciliary arch, hypertrophy of nose and lip,
macroglossia, lower jaw protrusion, thickening of the plantar,
enlargement of the palm and bitemporal hemianopsia
The data on admission were as follows: GH, 51.12 ng/ml(1-
14ng/ml); IGF-1, 1,538.9 ng/ml (88-246ng/ml); (FT3), 5.56
pg/ml (reference range: 2.3–4.3 pg/ml); (FT4), 2.52 ng/dl
(0.9–1.7 ng/ml); TSH, 2.26
mU/ml. Cea/ca19-9 normal
A CASE
University of Nairobi ISO 9001:2008 3 Certified
http://www.uonbi.ac.ke

 MRI BRAIN- a giant tumor (51 × 34 × 22 mm)
around pituitary fossa, pressuring on optic chiasm
from the middle Bilateral internal carotid arteries
were surrounded by the tumor, and infiltration
into the cavernous sinus was observed.
 Diagnosis?
 Management?
 Follow up

Introduction
 The pituitary gland, also called the hypophysis (master
gland ) is a small, pea-sized gland that sits at the base of
the brain (sphenoid bone ) and is connected to the
hypothalamus by the pituitary (or hypophysial) stalk.
 Physiologically : the gland is divided into two distinct parts
1. anterior pituitary , also know as the adenohypophysis,
2. the posterior pituitary, also known as the
neurohypophysis.
Between these portions lies a small, relatively avascular zone
called the pars intermedia

 Embryologically, the two portions of the
pituitary originate from different sources—
I. The anterior pituitary from Rathke’s pouch,
which is an embryonic invagination of the
pharyngeal epithelium,
II.The posterior pituitary from a neural tissue
outgrowth from the hypothalamus.

Hormones of the
pituitary gland
 Anterior lobe cells types and their hormones :
 Somatotropes - Growth hormone.
 Corticotropes - Adrenocorticotropin (corticotropin).
 Thyrotropes - Thyroid-stimulating hormone (thyrotropin) .
 Lactotropes - Prolactin
 Gonadotropes - Two separate gonadotropic hormones, follicle stimulating hormone and
luteinizing hormone.
Posterior lobe hormones :
1)Antidiuretic hormone (also called vasopressin) .
2) Oxytocin .

The neuro-endocrine
relationship
 The hypothalamus is a collecting center for information and much of
this information is used to control secretions of the many globally
important pituitary hormones. Hypothalamus is connected to the
pituitary gland in two ways :
 Neural connection : Secretion from the posterior pituitary is controlled by
nerve signals that originate in the hypothalamus and terminate in the
posterior pituitary.
 Vascular connection : secretion by the anterior pituitary is controlled by
hormones called hypothalamic releasing and hypothalamic inhibitory
hormones (or factors) secreted within the hypothalamus and then conducted
to the anterior pituitary through minute blood vessels called hypothalamic-
hypophysial portal vessels.

DISORDER OF
PITUITARY

Pituitary tumors
 Pituitary tumors represent from 10% to 25% of all intracranial
neoplasms. Depending on the study cited, pituitary tumors can be
classified into one of the following three groups according to their
biological behavior:
 Benign adenoma.
 Invasive adenoma.
 Carcinoma.
 Adenomas comprise the largest portion of pituitary neoplasms with
an overall estimated prevalence of 17%. Few adenomas are
symptomatic. Invasive adenomas, which account for approximately
35% of all pituitary neoplasms, may invade the dura mater, cranial
bone, or sphenoid sinus. Carcinomas account for 0.1% to 0.2% of all
pituitary tumors.

Hardy’s classification of
pituitary tumors

Pathophysiology -
anterior lobe
Hyperpituitarism
Group of disorders characterized by excessive production or
secretion of one or more of the pituitary hormones secondary to
pituitary gland dysfunction.
The most frequent cause is tumors of the pituitary gland
(adenomas)
Hormones involved:
• Lactotrophs- Prolactin
• Somatotrophes- Growth hormone
• Corticotrophs- Adrenocorticotropic hormone
• Thyrotrophs- Thyroid-stimulating hormone
• Gonadotrophes- FSH and LH

 GH- 191 amino acids, secreted by somatotrophs
 Pulsatile secretion 4-11 pulses ( hence its measurement
not useful)
 GHRH stimulates release of GH
 Somatostatin- inhibits GH release
 Somatostatin and GHRH regulates each other in a
paracrine manner
 GH stimulates IGF-1 from liver (igf-1 is similar to insulin)
 IGF-1 (70 amino acid) has negative feedback to
somatostatin and GHRH
GROWTH HORMONE

GH-producing pituitary
adenoma
 Gigantism
Also called pediatric acromegaly , is defined by hypersecretion
of growth hormones production by acidophilic growth
hormones producing- cells of the anterior pituitary gland.
 Features: very rare
A.If the condition occurs before adolescence, before fusion of
long bone epiphyses, characterized by tall stature.
B. Hyperglycemia ,DM(degeneration of B cell of islet of
Langerhans) (growth hormone increases the expression of the
insulin-like growth factor 1 (IGF-1) gene to a greater extent in
the liver compared to other tissues. IGF-1 mediates the effects
of GH on growth)

Physical characteristic of
Gigantism(complications )
Aside of being very tall/large for their age , physical
characteristic include:
1. Very prominent forehead and prominent jaw.
2. Gaps between their teeth.
3. Thickening of their facial feature
4. Large hands and feet with thick fingers and toes
Others symptoms of gigantism include:
I. Enlargement of internal organ (heart ) , excessive
sweating (hyperhidrosis) , delayed puberty , sleep
apnea and muscle weakness
II. Metabolic complications such as type 2 diabetes

Causes and effect of
Gigantism
95% caused by GH- secreting adenoma in pituitary
gland.
1. Tumors : most common cause ;
Benign (noncancerous )pituitary adenoma , in children
almost macroadenomas
2. Pituitary hyperplasia
3. Some genetic mutations associated gigantism e.g,
AIP( aryl hydrocarbon protein-interacting) gene
mutation or deletion which account approximately
29%of the population of people with gigantism

Genetic disorders associated with GH hypersecretion;
1.Carney complex : is genetic condition that affects
skin color (pigmentation )and causes benign tumors of
skin .GH-secreting pituitary adenomas occur in about
10% to 13%of carney complex cases and usually have
slow progression
2.McCune-Albright syndrome : is genetic condition that
affects bones , skin and endocrine system . Excess GH
is present in 20%to 30% cases .
3.Multiple endocrine neoplasias (MEN ) type 1or type 4

4. Neurofibromatosis : this is a condition that’s a
part of a group of genetic conditions know as
neurocutaneous disorders that affect skin and
nervous system.
5. Familia idiopathic pituitary adenomas (FIPA):
this is an inherited condition characterized by the
development of pituitary adenomas , which can
include a GH-secreting adenoma.

Diagnosis?
In general : suspicion can be made when a child’s height is
three standard deviation above the normal average height
of their sex and age or two standards above the adjusted
average based on the height of their biological parents.
Following are tests help diagnose the condition:
Labs
 GH and IGF-1(insulin-like growth factor )blood test , OGTT,
GHRH
Imaging
 (MRI ,CT) Eco , sleep study tests , x-rays or DEXA
(DXA )scan

Management ,
complications and
prognosis
 Management :
1. Surgery is the most common treatment option for gigantism.
 Transsphenoidal approach is perform surgery through
sphenoid sinus ( Diabetes insipidus, Ant pituitary hormone
deficiency)
2. Radiation therapy
Complication of R/:
 Hypopituitarism (60% of people of gigantism )
 Bleeding ,CSF leaks , meningitis
 Impaired fertility (radiation )
 Vision loss and brain injury

3 Medical management
 Dopamine agonist- Carbegoline, act on
somatotrophes and reduce GH secretion
 Somatostatin receptors ligand- octreotide
 GH receptor antagonist- Pegvisomant, prevent
dimerization and post receptor signalling.

Prognosis and life
expectancy
 The prognosis of children and adolescents diagnosed with
gigantism depends on several factors :
1) How early or late they’re diagnose
2) How effective treatment is at managing growth hormone
levels.
3) If they develop complications related to gigantism
In general , people who are older at diagnosis tend to have
complications than people who are diagnosed at a younger
age .
Untreated gigantism associated with significant complications
and an increased death rate of around twice the normal
average

Acromegaly :
an acidophilic tumor occurs after adolescence—
that is, after the epiphyses of the long bones have
fused with the shafts—the person cannot grow
taller, but the bones can become thicker and the
soft tissues can continue to grow. Enlargement is
especially marked in the bones of the hands and
feet and in the membranous bones.

 Hands and feet
enlargement
 Hyperhydrosis & skin
tags
 Deep voices
 Obstructive sleep apnea
 Elongation of the jaw
and malocclusion

 Acromegalic gigantism is a rare disorder with
symptoms of both gigantism and acromegaly
 Over production of GH in children, before the
fusion of epiphysis with shaft of the bones causes
gigantism and if hypersecretion of GH is continued
even after the fusion of epiphysis, the symptoms of
acromegaly also appear.
Acromegalic
gigantism

Precocious
puberty( excess
gonadotropin )
 Precocious puberty is when a child's body begins
changing into that of an adult (puberty) too soon. When
puberty begins before age 8 in girls and before age 9 in
boys.
 Causes :
 Production of GnRH from hypothalamus lead to
stimulate pituitary gland to the production of more
hormones in the ovaries for females (estrogen) and the
testicles for males (testosterone).
Types
1.central precocious puberty
2.Peripheral precocious puberty

Central precocious puberty :
causes
A tumor in the brain or spinal cord (central nervous system)
A defect in the brain present at birth, such as excess fluid
buildup (hydrocephalus) or a noncancerous tumor
(hamartoma)
Radiation to the brain or spinal cord
Injury to the brain or spinal cord
McCune-Albright syndrome — a rare genetic disease that
affects bones and skin color and causes hormonal problems
Congenital adrenal hyperplasia — a group of genetic
disorders involving abnormal hormone production by the
adrenal glands

Peripheral precocious puberty ;
causes
A tumor in the adrenal glands or in the pituitary gland that
releases estrogen or testosterone
McCune-Albright syndrome, a rare genetic disorder that affects
the skin color and bones and causes hormonal problems
Exposure to external sources of estrogen or testosterone, such as
creams or ointments
In girls , ovarian cyst and ovarian tumors
Boys , A tumor in the cells that make sperm (germ cells) or in the
cells that make testosterone (Leydig cells).
A rare disorder called gonadotropin-independent familial sexual
precocity, which is caused by a defect in a gene, can result in the
early production of testosterone in boys, usually between ages 1
and 4.

Risk factor and complication
• Being a girl.
• Being African-American.
• Being obese.
• Being exposed to sex hormones.
• Complications
• Short height.
• Social and emotional problems.
Treatment:
• This treatment, called GnRH analogue therapy-
Lupron Depot

Thyrotropes ( TSH)
 TSH excess:
Pituitary tumors that secret TSH ( high T3 , T4 =
secondary hyperthyroidism )
Thyroid disease that decrease T3 , T4 secretion
( primary hypothyroidism )
 TSH deficiency
Pituitary tumors that decrease T3 , T4 secretion
(secondary hypothyroidism )
Thyroid disease that increase T3 , T4 secretion
(primary hyperthyroidism )

The hypersecretion of glucocorticoids, particularly
cortisol. It is due to pituitary origin.
ACTH
-secreted by the basophilic chromophilic cells of
anterior pituitary
ACTH is a single chained polypeptide with 39 amino
acids. The daily output of this hormone is 10 ng and
the
concentration in plasma is 3 ng/dL. Half-life of ACTH is
10 minutes.
Cushing disease

ACTH is synthesized from a protein called
preproopiomelanocortin (POMC). Along with ACTH,
the POMC gives rise to some more byproducts called
β-lipotropin, γ-lipotropin and β-endorphin. Two more
byproducts, namely α-melanocyte-stimulating
hormone (α-MSH) and β-melanocyte-stimulating
hormone (β-MSH) are
also secreted in animals.
However, MSH activity is shown by ACTH and other
byproducts from POMC in human beings
Synthesis

 Tumor in pituitary cells, particularly in basophilic
cells which secrete ACTH
 Malignant tumor of non-endocrine origin like
cancer of lungs or abdominal viscera
 Hypothalamic disorder causing hypersecretion of
corticotropin-releasing hormone.
Increased ACTH OF PITUITARY ORIGIN

Metyrapone
stimulation tests
 The metyrapone stimulation test is based upon the
principle that it inhibits conversion of 11-deoxycortisol to
cortisol
 the metyrapone stimulation test is based upon the
principle that decreasing serum cortisol concentrations
normally cause an increase in corticotropin-releasing
hormone (CRH) secretion from the hypothalamus and
corticotropin (ACTH) secretion from the anterior pituitary
due to a decrease in glucocorticoid negative feedback.
 The test is performed primarily to detect partial defects
in pituitary ACTH secretion.

Nelson syndrome is a disorder that develops after surgical
removal of both adrenal glands. It is because of the growth
of pituitary tumor that secretes excess ACTH.
The features include headache and visual problems.
Nelson syndrome can be treated with radiation or surgical
removal of the pituitary gland.
Nelson syndrome

Hypopituitarism
Panhypopituitarism :
-Means decreased secretion of all the anterior pituitary hormones.
-May be congenital (present from birth), or it may occur suddenly or slowly
at any time during life, most often resulting from a pituitary tumor that
destroys the pituitary gland
-Its occurs in adulthood frequently results of one of the three
abnormalities ;
1. Craniopharyngiomas or chromophobe tumors, may compress the
pituitary gland until the functioning anterior pituitary cells are totally
or almost totally destroyed.
2. Thrombosis of the pituitary blood vessels.
3. Sheehan’s syndrome (pituitary infraction )
4. Infection (TB , meningitis )

Anterior pituitary
Dwarfism (short stature )
Most instances of dwarfism result from generalized deficiency
of anterior pituitary secretion (panhypopituitarism) during
childhood.
It can be due to GHRH deficiency , GH deficiency or deficient
secretion of IGF-1
 A person with panhypopituitary dwarfism does not pass
through puberty and never secretes sufficient quantities of
gonadotropic hormones to develop adult sexual functions.

Types of dwarfs
a.Laron dwarfism (growth hormone
insensitivity – abnormal GH receptors)
b.Psychosocial dwarfism (kaspar Hauser
syndrome ) extreme emotion deprivation
c.Achodroplasia . The most common type
form of dwarfism in human
d.Dwarfism in dystrophia adiposogenitalis
Dystrophia adiposogenitalis or Fröhlich
syndrome is a pituitary disorder Dwarfism
occurs if it develops in children.

Acromicria
Deficiency of GH in adults,
commonly associated with
 reduced GHRH from
hypothalamus.
 Atrophy of anterior
pituitary
 panhypopituitarism
Simmond disease(pituitary
cachexia)
Panhypopituitarism, degeneration of
ant. Pituitary
Symptoms
- Rapidly developing senile decay. A 30
year old looks like a 60 year old, loss of
hair over the body, loss of teeth, skin
wrinkled

Pathophysiology –
posterior lobe
SIADH
Disease characterized by Loss of sodium due to
unopposed hypersecretion of ADH
Characterized by;
Reduced osmotic pressure
Increased water retention
Hyponatremia
Hypo-osmolality
hyponatremia (ie, serum Na+ < 135 mmol/L) with concomitant hypo-osmolality
(serum osmolality < 280 mOsm/kg) and high urine osmolality that are the
hallmark of SIADH.The hyponatremia results from an excess of water rather than
a deficiency of sodium

causes :
CNS disturbances (enhance release of ADH )
Pneumonia
Lung tumors (Small cell lung cancer (SCLC) is the
most common tumor leading to ectopic ADH
production
Drugs like cyclophosphamide ,chlorpropamide ,
carbamazepine , oxcarbamazepine
Cerebral Tumors

A confirmed diagnosis
has seven elements:
 A decreased effective serum osmolality - <275 mOsm/kg of water
 urinary sodium concentration high - over 40 mEq/L with adequate
dietary salt intake;
 no recent diuretic usage
 no signs of ECF volume depletion or excess
 No signs of decreased arterial blood volume - cirrhosis, nephrosis, or
congestive heart failure;
 Normal adrenal and thyroid function; and
 No evidence of hyperglycemia (diabetes mellitus)
hypertriglyceridemia, or hyperproteinia (myeloma).
Treatment :
 It can be treated by drugs that decrease the sensitivity of renal
receptors to ADH (demeclocycline )

Arginine vasopressin
deficiency (Central DI)
Clinical syndrome characterized by
 Abnormal passage of large volumes of urine(diabetes) that
is dilute( hypotonic) and devoid of dissolved solute(insipid)
 Associated with insufficient Arginine vasopressin, ADH
secretion or renal response to AVP
 Resulting to Hypotonic polyuria and compensatory
polydipsia
Hall marks
Polyuria 50mls/kg
≥
Dilute urine 300mOsm/L
≤
Increased thirst 20l/day

Idiopathic AVP-D- 30-50%
Familial and congenital
Neurosurgery and trauma
Cancer
Adipsic DI
Hypoxic encephalopathy
Infiltrative disorder
Aetiology

 2. Arginine Vasopressin Resistance (AVP-R,
formerly known as Nephrogenic Diabetes
Insipidus or NDI)
 Pregnancy-Induced/Gestational form of
Arginine Vasopressin disorder (gAVP-d)
 Primary Polydipsia
Other types of Diabetes
insipidus

 Arginine vasopressin disorder (AVP-D), based on the site of pathology, can
be caused by two different defects, ie, central and peripheral (nephrogenic)
types.
 AVP-D is secondary to inadequate or impaired secretion of AVP from the
posterior pituitary gland in response to osmotic stimulation and a decrease
in blood pressure
 VP is synthesized as a precursor complex in the supraoptic and
periventricular nuclei of the hypothalamus and encoded by the AVP-
neurophysin II gene. It is released by calcium-dependent exocytosis
 Neurohypophysis is destroyed by various acquired or congenital anatomic
lesion secondary to pressure or infiltration.
 Resultant hypotonic diuresis depends upon the degree of destruction of
neurohypophysis, leading to complete or partial deficiency of AVP secretion
 https://www.ncbi.nlm.nih.gov/books/NBK470458/
Pathophysiology

Algorithms
1.Confirmation of hypotonic polyuria
2.Diagnosis of the type of polyuria-polydipsia
syndrome
3.Identification of the underlying etiology
Diagnosis

Evaluation

 (DDAVP) is a synthetic analogue (1‐deamino‐8‐
D‐arginine vasopressin)
 Oral, Sub Q, IV
 10mcg for adults nasal, 4mcg SubQ,
 Monitor
 Hyponatremia
 Thiazides, Carbamazepine, nsaids,
Chlopropamide
Treatment

Hypoactivity of both anterior and
posterior pituitary
Dystrophia Adiposogenitalis;
Fröhlich syndrome or
hypothalamic eunuchism.
- Affects mostly boys
- is a rare endocrine disorder
characterized by obesity,
hypogonadism, and delayed puberty,
typically caused by hypothalamic-
pituitary dysfunction.
Pathophysiology
Damage to the hypothalamus (especially the
ventromedial nucleus) disrupts:
Appetite regulation hyperphagia obesity.
→ →
Gonadotropin-releasing hormone (GnRH)
secretion hypogonadotropic hypogonadism
→
(low LH/FSH).
Symptoms
Obesity Sexual
infantilism
Dwarfsim in younger age
Behavioral changes
Treatment
Surgery
Hormonal replacement
therapy
Life style support

The stress response to
trauma and surgery
The endocrine response to surgery
The stress response to surgery is characterized by increased
secretion of pituitary hormones and activation of the sympathetic
nervous system.
 The changes in pituitary secretion have secondary effects on
hormone secretion from target organs For example, release of
corticotrophin from the pituitary stimulates cortisol secretion from
the adrenal cortex. Arginine vasopressin is secreted from the
posterior pituitary and has effects on the kidney. In the pancreas,
glucagon is released and insulin secretion may be diminished.
The overall metabolic effect of the hormonal changes is increased
catabolism which mobilizes substrates to provide energy sources,
and a mechanism to retain salt and water and maintain fluid
volume and cardiovascular homeostasis.

Principle hormonal
response to surgery
Endocrine gland Hormone Change in secretion
Anterior pituitary ACTH
GH
TSH
FSH &LH
Increase
Increase
May increase or decrease
May increase or decrease
Posterior pituitary AVP Increase
Adrenal gland Cortisol
Aldosterone
Increase
Increase
Pancreases Insulin
Glucagon
Often decrease
Usually small increase
Thyroid gland Thyroxine , T3 Decrease

 https://pmc.ncbi.nlm.nih.gov/articles/PMC2742723/
#:~:text=Pathology%20of%20GH%2Dproducing%20P
ituitary,%E2%80%9Csilent%E2%80%9D%20GH%20ce
ll%20adenomas
.
 KSembulingam _EssentialsofMedical_Physiology, 6th
Edition
 Ganong
 Guyton’s

PITUITARY PATHOPHYSIOLOGY PRESENTATION.ppt

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