By: Mohammad Jomaa & Amer Al-Salamat

Lec:Pathology of pituitary gland

**Sheet contain the slide in Bold.

**some book information in Red.

Pathology of pituitary gland

Before we start :( from book)

The endocrine diseases can be generally classified as:

1)diseases of underproduction(hypo) or overproduction(hyper) of hormones with associated

biochemical and clinical consequences.

2)diseases associated with development of mass lesions.

mass lesion may be nonfunctional Or may be associated with overproduction or underproduction of

hormones(functional).

Firstly we will discuss the pituitary gland because it’s the brain and the central to control the remaining

endocrine gland

• Sellaturcica (located in the base of brain within sella turcica).

• Adenohypophysis (80%): the anterior lobe which form the major part of the gland (80%)

- epithelial cells>> the anterior lobe contain epithelial cell so that have the name of “adenohypophysis”

**adeno mean epithelial cell

- acidophil , basophil , chromophobe>> name according to the histological appearance after H&E stain

The type of cell histologically (mean according to color) is determined by type of hormone which the

cell secrete

- Somatotrophs, Mammosomatotrophs, Corticotrophs, Thyrotrophs, Gonadotrophs

Somatotrophs : secrete growth hormone

Mammosomatotrophs : secrete prolactin and growth hormone

Corticotrophs : secrete ACTH Thyrotrophs : secrete TSH

Gonadotrophs : secrete LH and FSH Mammotroph : secrete prolactin

- blood supply from the low-pressure portal venous system.

The importance to know the type of blood supply to anterior pituitary (which is portal veins) is the fact

of susceptibility to ischemia if the patient have shock >> because the low blood pressure render the

gland more susceptible to ischemia

As we see in figure there is a heterogeneous

population of cells (3 types of cells according to the

color of the cytoplasm)

all the hormones that come from the

hypothalamus is stimulatory except

-dopamine: inhibit prolactin

-somatostatin: inhibit growth

hormone

• Neurohypophysis:

Have the name of neurohypophysis because>>- modified glial cells, axonal processes, axon terminals

(from nerve cell bodies in the supraoptic andparaventricular nuclei of the hypothalamus)

- Oxytocin, antidiuretic hormone (ADH) /vasopressin

Oxytocin >> cause the contraction of smooth muscle in pregnant uterus and of muscle surrounding

the lactiferous duct of the mammary glands(apocrine).

antidiuretic hormone>> cause reabsorption of water from kidney

- Receives its blood directly from arterial branches

So more resistance to ischemia than the anterior lobe

• pituitary disease:(sign and symptoms)

1)Hyperpituitarism ---- anterior pituitary adenoma

Adenoma : benign tumor composed of epithelial cell

2)Hypopituitarism ---- ischemic injury(mainly affect anterior lobe), surgery, radiation, inflammatory

reactions, nonfunctional pituitary adenomas

nonfunctional pituitary adenomas

** its large tumor of pituitary that compress the remaining part of gland tissue which finally cause

hypopituitarism

3)Local mass effects:

- radiographic abnormalities of the sellaturcica(earliest change referable to mass effect)

(including sellar expansion,bony erosin,and disruption of the diaphragma sella).

- bitemporal hemianopsia

When the gland in the sella turcica enlarged it will comprise the optic nerve and chiasm >> which will

cause loss of lateral eye vision (lateral side)

- headache, nausea, and vomiting (+ICP)>>increase the intra cranial pressure

- Seizures, obstructive hydrocephalus

Seizures: if the mass compress the brain tissue

obstructive hydrocephalus : if the mass compress ventricular system (system responsible for CSF

circulation)

- cranial nerve palsy>> if mass compress any cranial nerve

• pituitary apoplexy:

rapid enlargement of the lesion(this is the cause)

which will result in acute hemorrhage into an adenoma (mainly ) …(also it can be ischemic injury to

adenoma)

depression of consciousness, sudden headache, neusea , vomitting, vision loss---hypopituitarism(in

long term)

neurosurgical emergency>> because the patient have shock

we must differentiate between pituitary apoplexy and Sheehan's syndrome

Sheehan's syndrome: the patient don’t have tumor in pituitary, it’s just enlargement of the normal

pituitary gland in pregnant woman (because increase the size of prolactin producing cell) >> the

syndrome caused by the enlargement of the gland that’s not accompanied by increase in blood supply

which finally cause ischemia

**the Sheehan's syndrome don’t affect all pregnant women and mainly occur in postpartum and may

cause shock due to bleeding

HYPERPITUITARISM ANDPITUITARY ADENOMAS

The most common cause of hyperpituitarism is an adenoma arising in the anterior lobe.

Anterior lobe affected mainly by adenoma but may in rare cases affected by carcinoma

Hyperplasia of the anterior pituitary,

Carcinomas of the anterior pituitary (rare)

extrapituitary tumors,

hypothalamic disorders

We classify the pituitary adenoma according to the type of hormone secreted by the cell

**the doctor read the first two columns(pituitary cell type and hormone)

Pituitary adenomas:

Adenoma can be classified according to several criteria

First classification

Functional

There is hyper-secretion of the hormones that appear in the serum and announce the hyper-secretion

(eg: if the hormone is prolactin >> will give the symptom of hyperprolactinemia // if growth hormone >>

symptoms of excess growth hormone)

Nonfunctioning --- +IHC stain

This type of adenoma cause increase secretion of the hormone (which seen by using

immunohistochemical stains in the pituitary adenoma or secreted to the plasma) but don’t reach level

that sufficient to produce symptoms

hormone negative---- -IHC stain / null cell

there is adenoma but there is no evidence for increase secretion of hormone by immunohistochemical

stains

** the main type of adenoma that produce hormone negative adenoma is gonadotroph adenoma (LH

&FSH secreting adenoma)(absence of immunohistochemical reactivity or ultrastructural evidence of

hormone production).

Second classification

Sporadic ---- G protein mutation(non familial)

Inherited (5%)---- MEN1(cause MEN1 syndrome), CDKN1B, PRKAR1A, and AIP(familiar)

Third classification according to the size as following

Microadenomas ----- less than 1 cm

Macroadenomas ----- exceed 1 cm ----- Nonfunctioning ----- hypopituitarism(mass effect on the

remaining pituitary tissue)

**G-protein is one of the most functional proteins that work in the

endocrine system (act as connection between inside effector protein and

outside receptor)

• Gsα:stimulatory G protein which is responsible for the action

**encoded by GNAS gene which located in chromosome 20

**in resting state the Gsαbind to GDP but when the ligand bind to the

receptor the Gsα will bind to GTP

• G-protein mutations

• Mutation in the α-subunit/ GNAS mutations

• Interferes with GTPase activity

**as a summary >>normal physiological response of binding of ligand to its receptor is elected by G-

protein which make a response for specific period of time as result of GTPase enzyme activity (hydrolyze

the GTP which bind to Gsα>> render the G-protein inactive)

**in case of GNAS gene mutation >>this will cause the Gsα to interfere with the GTPase activity and the

G-protein will continue to be active even in the absence of ligand)

• TP53 mutaion

In case of TP53 mutation will cause aggressive adenoma (atypical adenoma) have the characteristic of

high mitosis but it’snot malignant tumor

**the pituitary adenoma is confirmed to the

sellaturcicabut the aggressive adenoma cause invasion

of tissue outside sellaturcica (may cause destruction of

the sellaturcica)

• pituitary adenoma:

well-circumscribed

cellular monomorphism

In normal pituitary gland tissue there is polymorphism

cellular population >> if adenoma occur all cells well

converted to one type of cells

absence of a significant reticulin network(use silver

stain to detect the absence of reticulinnetwork which found normally between the cells)…its important

characteristic which indicate adenoma

Atypical adenomas: brisk mitotic activity, P53

mutation, aggressive behavior (invasion and

recurrence)

** the cells in this figure is momomorphism and its

acidophil

• Prolactinomas: most common pituitary adenoma

- M.c hyperfunctioning pituitary adenoma

- Microadenomas / macroadenomas(they range in size from small microadenomas to

large,expansile tumor(macroadenoma).

Mainly micro because it is a functional adenoma that giving rise to symptoms of hyperprolactinemia

- Hyperprolactinemia (amenorrhea, galactorrhea, loss of libido, and infertility). subtle in men

and older women(postmenopausal female)

**the symptoms of hyperprolactinemia is more clear seen in young female(premenopausal)

Hyperprolactinemia:(other causes that result in Hyperprolactinemia)

• prolactin-secreting pituitary adenomas

• pregnancy,

• high-dose estrogen therapy

• renal failure

Prolactin is excreted in the kidney so that in case of renal failure the prolactin accumulated in the blood

• hypothyroidism,

• hypothalamic lesions

• dopamine-inhibiting drugs (e.g., reserpine)

• any mass in the suprasellar compartment may disturb the normal inhibitory influence of

hypothalamus on prolactin secretion(stalk effect).

• Growth Hormone–Producing (Somatotroph Cell) Adenomas:(second most common

type of adenoma)

- 2ndm.c

- insulin-like growth factor I (somatomedin C)------- liver

**the factor that responsible for somatotroph adenoma symptoms it’s not growth hormone itself >> the

responsible factor is insulin-like growth factor I (somatomedin C) which secreted by the liver in

response to persistent hypersecretion of growth hormone that coming to it

The increase in the growth hormone cause one of these two disease

- Gigantism---- increase in body size,long arms and legs---- before the epiphyses close

- Acromegaly ---- soft tissues, skin, and viscera bones----- after closure of the epiphyses

**As seen from figure the patient

haveanterior protruded lower jaw

(Prognathism)

**also the patient with acromegaly may

experience protruded forehead ,increases

the tongue and heart size and other tissue

**as physician we can detect the increase in

hand and feet size by the patient complain

of:

-ring being small for his finger

-or shoes/boot being small to wear in his feet

• abnormal glucose tolerance and diabetes

mellitus,

• generalized muscle weakness,

• hypertension,

• arthritis,

• osteoporosis,

• and congestive heart failure.

• Adrenocorticotropic Hormone–Producing (Corticotroph Cell) Adenomas:

Hypercortisolism: - Cushing disease :in case of pituitary adenoma

-Cushing syndrome :hypercortisolismin general(not from adenoma)>> may be from

exogenous administration of cortisol or maybe from endogenous source(adrenal adenoma/adrenal

carcinoma/adrenal hyperplasia)

Hyperpigmentation /MSH

Nelson syndrome ---- hypercortisolism does not develop ---- No adrenals

In case of patient that have removed its adrenal gland this will result in loss of feedback inhibition on

pituitary gland and continue to stimulate the release of ACTH (the patient don’t have hypercortisolism)

**symptoms>>

-Moon face

-Hypertension

-Hyperglycemia

-Buffalo hump: fatin the upper back position

-Purple striae تشقق المعدة

-hirsutism (in female) :hair appear in female but

as in male distribution >> may found in female

who use make-up contain cortisol

• Gonadotroph (luteinizing hormone [LH]–producing and follicle-stimulating hormone [FSH]–

producing) adenomas:

Mass effect(nonfunctional adenoma)

Thyrotroph (thyroid-stimulating hormone [TSH]–producing) adenomas:

1% of all pituitary adenomas

rare cause of hyperthyroidism

HYPOPITUITARISM

• Loss or absence of 75% or more of the anterior pituitary parenchyma.

• Causes:

• Nonfunctioning pituitary adenomas

• Ischemic necrosis(important cause of pituitary insufficiency)(Sheehan syndrome, DIC, sickle

cell anemia, elevated intracranial pressure, traumatic injury, and shock of any origin)

• surgery or irradiation

• sarcoidosis

• Tuberculosis

• Trauma

• metastatic neoplasms

**the patient with hypopituitarism come with manifestation of anterior lobe hypopituitarism but the

posterior lobe it’s not affected because the posterior lobe is more resistant to ischemic lesion due to

the nature of it’s blood supply

• Hypopituitarism accompanied by evidence of posterior pituitary dysfunction in the form of

diabetes insipidus is almost always of hypothalamic origin(mean If the hypopituitarism in both

anterior and posterior lobe we must consider a dysfunction in something that control these two

lobe and its mainly the hypothalamus)

Manifestations:

• Children--- growth failure (pituitary dwarfism) ---- growth hormone deficiency

• Gonadotropin deficiency (amenorrhea and infertility in women (because the LH is responsible

for ovulation) and to decreased libido, impotence, and loss of pubic and axillary hair in men>>

LH & FSH responsible for regulation of testosterone and androgens in males)

• TSH---- Hypothyroidism

• ACTH----- hypoadrenalism

• Prolactin deficiency---- failure of postpartum lactation.

• MSH deficiency -------------- pallor>> loss of stimulation of melanocyte

(MSH and ACTH synthesized from the same precursor molecule)

POSTERIOR PITUITARY SYNDROMES

• Oxytocin:

stimulates the contraction of smooth muscle in the pregnant uterus and of muscle surrounding the

lactiferous ducts of the mammary glands.

Impairment of oxytocin synthesis and release has not been associated with significant clinical

abnormalities.

• ADH:(peptide hormone,from supraoptic nuclei)

Released in response to:

- increased plasma oncotic pressure,

- left atrial distention

- Exercise

-certain emotional states,

----- collecting tubules of the kidney to promote the

resorption of free water

• ADH deficiency causes diabetes insipidus, a condition characterized by excessive urination

(polyuria)(caused by an inability of the kidney to properly resorb water from urine)

**one of the most important manifestation of the ADH deficiency is polyuria(excessive urination)

followed by polydipsia (excessive thirsty)

Causes of diabetes inspidus:

- head trauma,

- neoplasms,

- inflammatory disorders of the hypothalamus and pituitary,

- surgical procedures involving the hypothalamus or pituitary

- spontaneously (idiopathic)

• Central diabetes insipidus (ADH deficiency)>> from the pituitary itself

• Nephrogenic diabetes insipidus>> problem in the renal receptor (renal tubular

unresponsiveness to circulating ADH).

Clinical manifestations:

• Large volumes of dilute urine with an inappropriately low specific gravity.

• Serum sodium and osmolality are increased as a result of excessive renal loss of free water,

• Resulting in thirst and polydipsia.

Dehydration

**if the patient take sufficient amount of water >> will be protected but if he don’t take sufficient

amount of water will result in dehydration

• syndrome of inappropriate ADH (SIADH) secretion:

**this syndrome is one of the Para neoplastic syndrome caused by lung lesion (benign or malignant

>>like small cell carcinoma of the lung)

ADH excess

resorption of excessive amounts of free water, hyponatremia

• The most common causes of SIADH

- secretion of ectopic ADH by malignant neoplasms (particularly small cell carcinomas of the lung)

- non-neoplastic diseases of the lung

- local injury to the hypothalamus or neurohypophysis.

- hyponatremia,

- cerebral edema(brain edema) , and resultant neurologic dysfunction.

- Although total body water is increased, blood volume remains normal, and peripheral edema

does not develop.

The doctor ask student question for next lecture …why in cases of excessADH the patient have increase

body water but the blood volume remain normal ?

Good luck *-*

“Something

deep“