Pituitary Gland

byprof/ GOUDA ELLABBAN

prof of surgery , hepatobiliary and laparoscopy scu hospital/ Egypt

Pituitary Gland• Small, bean-shaped structure at the base

of the brain within the sella turcica• Intimately related to the hypothalamus

with stalk (=composed of axons extending from the hypothalamus, & rich venous plexus)

• 0.5 gm in adult, 10-15 mm in greatest diameter

• Composed of two morphologically and functionally distinct components:

– Anterior lobe (adenohypophysis) : secretary gland

– Posterior lobe (neurohypophysis) : neuronal tissue

• Blood supply by: – Portal system– Branches of internal carotid artery

Adenohypophysis• Derived embryologically from the

mouth via Rathke's pouch.• constitutes about 80% of the gland.• Basophilic, eosinophilic, poorly-

staining (chromophobe) cells• EM, IHC : staining properties

related to the presence of various trophic hormones within their cytoplasm.

• Produces ACTH, TSH, FSH, LH, GH, and Prolactin.

• Released into the circulation in response to various releasing factors secreted by the hypothalamus

If the input from the hypothalamus is interrupted, the adenohypophysis makes more prolactin and less of everything else.

Pituitary GlandDiseases

• Caused by:– Increased production of tropic hormone– Decreased production of tropic hormone– Local space-occupying effects

Hyperpituitarism

• Too much of one (or maybe two) of the hormones from the adenohypophysis.

• This may be due to: – autonomous over-production i.e.,

• a primary adenoma (in most cases) • Hyperplasia and cancer of the adenohypophysis (very rare)

– certain hypothalamic disorders – underproduction of inhibiting factors or loss of inhibition

following destruction of other endocrine glands.– secretion of hormones by nonpituitary tumors

Overproduction of Prolactin• Most common hormone produced by a pituitary adenoma• Causes impotence, loss of libido in men; amenorrhea,

galactorrhea, infertility in women and obesity in both• But remember that there are many other causes of

hyperprolactinemia including: – hypothalamic tumors ( i.e., craniopharyngiomas, gliomas,

hypothalamic germinomas) – anti-dopamine drugs (phenothiazines, reserpine, alpha-methyldopa

-- common).– pregnancy, high-dose estrogen therapy, renal failure, hypothyroidism

• Stalk effect : any mass in the suprasellar compartment may disturb the normal inhibitory influence (dopaminergic) of the hypothalamus on prolactin secretion

• Sx. : more obvious in premenopausal females - early diagnosis

Overproduction of GH• The second most common hormone produced by a pituitary functional

adenoma• Persistent hypersecretion of GH stimulates the hepatic secretion of insulin-

like growth factor I (IGF-I or somatomedin C), which causes many of the clinical manifestations.

– Gigantism : prepubertal children• generalized increase in body size, with excessive bone with disproportionately long

arms and legs• A giant is defined to be a human over seven feet tall (200 cm). • In the past, these people typically were crippled by nerve, muscle, and joint

problems, acquired acromegalic features as they got older, and died young of complications of their diabetes.

– Acromegaly : GH excess persist, or present, after closure of the epiphyses• The typical acromegalic has a huge jaw ("prognathism"), huge brows, huge tongue,

and huge hands (with "spade fingers"), develops a deep guttural voice, gets an oily skin (extra sebaceous glands), gets joint deformities (if not frank arthritis), and suffers from secondary diabetes.

– Others :• including gonadal dysfunction, diabetes mellitus, generalized muscle weakness,

hypertension, arthritis, congestive heart failure, and an increased risk of gastrointestinal cancers.

• The lab workup of acromegaly is straightforward. Screening test is a spot blood (IGF-I). If this is normal, you have ruled out acromegaly.

• failure to suppress GH production in response to an oral load of glucose is one of the most sensitive tests for acromegaly

• Most pituitary giants and acromegalic patients have a pituitary macro-adenoma (i.e., >10 mm)

Overproduction of ACTH

• Cushing’s disease• Nelson’s syndrome : large clinically

aggressive adenoma develop from microadenoma, after surgical removal of adrenal glands for treatment of Cushing’s syndrome

• Hyperpigmentation : stimulatory effect of the ACTH precursor molecule on melanocytes

Hypopituitarism

• May occur with loss or absence of 75% or more of the anterior lobe

• May be primary or secondary, and less frequently hypothalamic origin– Nonsecretory pituitary adenomas– Ischemic necrosis– Ablation by surgery or radiation– Empty sella syndrome, inflammatory lesions, trauma,

and metastatic neoplasms

• C/F varies according to the age of the pt.

Hypopituitarism Nonsecretory pituitary adenomas

• compress and compromise the anterior lobe

• gradual enlargement of adenoma or abrupt enlargement due to acute hemorrhage (pituitary apoplexy)

HypopituitarismIschemic necrosis

• Important cause of pituitary insufficiency• Anterior lobe tolerates ischemic insults fairly well

– loss of up to half without clinical consequences– 75% or more : hypopituitarism

• Causes:– Sheehan's syndrome (postpartum necrosis)– DIC– sickle cell anemia– elevated ICP– traumatic injury– shock of any origin– vascular problems (i.e., cavernous sinus thrombosis)– etc

HypopituitarismSheehan's syndrome (postpartum necrosis)

• During pregnancy, increase in size and number of prolactin-secreting cells, without increased blood supply from low pressure portal venous system

• → vulnerable to ischemic injury in patient who develop hemorrhage and hypotension during peripartum period

• Posterior lobe : not affected (blood directly from arterial branches)

Hypopituitarism Empty sella syndrome

• Refers to the presence of an enlarged, empty sella turcica that is not filled with pituitary tissue.

• There are two types: – Primary empty sella

• due to a defect in the diaphragma sella that allows the arachnoid mater and cerebrospinal fluid to herniate into the sella, resulting in expansion of the sella and compression of the pituitary.

• Classically, affected patients are obese women with a history of multiple pregnancies.

• The empty sella syndrome may be associated with visual field defects and occasionally with endocrine anomalies, such as hyperprolactinemia, owing to interruption of inhibitory hypothalamic effects. Loss of functioning parenchyma can be severe enough to result in hypopituitarism.

– Secondary empty sella,• Any condition that destroys part or all of the pituitary gland, such as ablation

of the pituitary by surgery or radiation.

PANHYPOPITUITARISM• The symptoms of panhypopituitarism are highly variable.

– Growth hormone doesn't have spectacular effects on adults. It slows the body wasting that occurs in old age. Adults lacking growth hormone have more fat and less muscle per pound of body weight, the heart may be weaker and growth hormone also helps maintain the skeletal muscles.

– Loss of gonadotropins produce loss of libido and body hair. – Loss of prolactin prevents lactation, which would only be noticed after childbirth. – Loss of thyrotropin produces secondary hypothyroidism (i.e., cretinism in

children, problems culminating in myxedema in adults). – Loss of ACTH produces secondary adrenal insufficiency, which is just as deadly

as primary adrenal insufficiency. (Fortunately, this happens only very late in the progression of the disease)

– The anterior pituitary is also a rich source of MSH, synthesized from the same precursor molecule that produces ACTH; therefore, one of the manifestations of hypopituitarism includes pallor due to a loss of stimulatory effects of MSH on melanocytes.

– If the posterior pituitary gland is involved, loss of ADH produces pituitary diabetes insipidus. Nowadays more people are referring to ADH as AVP, arginine vasopressin.

Hypopituitarism• Failure to produce normal amounts of growth hormone in childhood

results in miniature, well-proportioned people. • Causes range from "idiopathic" to various genetic syndromes to other

causes of hypopituitarism. – "idiopathic dwarves"– Laron dwarves (short, frontal bossing; the defect is in the growth hormone

receptors. – Pygmies also have tissues that do not respond well to growth hormone;

some people call this "pituitary dwarfism type II– "Get Shorty!" Now it turns out that a lot of just-plain-short people have

minor defects in their growth hormone receptors• If thyrotropin is normal or thyroid hormone is replaced, the children will

be of normal intelligence. • If gonadotropin production is normal or sex steroids are administered,

puberty should occur normally. • And please don't miss adrenal insufficiency in these kids; they continue

to die of sudden adrenal crisis in disturbingly large numbers

Posterior Pituitary Syndromes Diabetes insipidus

• ADH deficiency - excessive urination (polyuria)

• increased serum sodium and osmolarity → thirst and polydipsia

Diabetes insipidus• Because the posterior pituitary gland is really processes of

hypothalamic neurons, a variety of processes can damage it. Remember:

• Causes within the sella • compression by pituitary adenoma • pituitary infarction from any cause • pituitary ablation (surgical, radiation) • sarcoidosis • mutant ADH (autosomal dominant or acquired in chronic lithium administration

or other serious renal medullary disease) • Causes above the sella

• old bacterial meningitis • damage from encephalitis • meningeal tuberculosis • hypophyseal glioma or germinoma • craniopharyngioma • metastatic cancer • skull trauma

• Also remember nephrogenic diabetes insipidus, the inability of the kidney to respond to ADH (mutant ADH receptor).

Syndrome of inappropriate ADH (SIADH)

• Patients have continual ADH production no matter what the current plasma osmolality. Water leaks back freely from the collecting ducts, the blood becomes hypotonic.

• Low blood tonicity leads to seizures and then to death.

• The syndrome, when really present, is almost always due to ectopic ADH production by a tumor (typically, oat cell carcinoma; occasionally a carcinoid etc).

• Pituitary problems almost never produce inappropriate ADH.

Pituitary Adenomas

• clinically 10% of diagnosed primary intracranial neoplasms

• incidentally up to 25% of routine autopsies• They can occur at any age, with no great

sex predominance.• 3% of cases : associated with MEN• microadenomas ≤ 1cm < macroadenomas• nonfunctional - present at a later stage

Pituitary Adenomas

• Clinical features– signs & symptoms

• hormonal abnormalities and mass effects– local mass effects

• radiographic abnormalities of the sella turcica : sella expansion, bony erosion, and disruption of the diaphragm

• visual field abnormalities : defects in the lateral (temporal) visual fields - bitemporal hemianopsia

• elevated intracranial pressure : headache, nausea, and vomiting• hypopituitarism : compress the adjacent non- neoplastic anterior

pituitary• Large pituitary adenomas eventually erode the sella,

clinoid processes, diaphragma sellae, optic nerves and chiasm, and even the cavernous sinuses, nasal sinuses, or brain.

Pituitary Adenomas

• Gross – well circumscribed, soft lesion– larger tumors :

• extend superiorly through the sellar diaphragm into the suprasellar region

• compress the optic chiasm and adjacent structures• frequently erode the sella turcica and anterior clinoid

processes• extend locally into the cavernous and sphenoid sinuses

– invasive adenomas• up to 30%, grossly nonencapsulated and infiltrate adjacent

bone, dura, and (uncommonly) brain

Classification of Pituitary Adenomas

• Micro – uniform, polygonal cells– cellular monomorphism and absence of a significant

reticulin network : distinguish from nonneoplasia• Acidophilic adenomas (eosinophilic adenomas) typically make

growth hormone and/or prolactin. • Basophilic adenomas typically make ACTH; less often, they

make TSH or the gonadotropins. • Chromophobe adenomas typically make prolactin or nothing

("null cell adenoma", * stains as a apudoma).

Classification of Pituitary Adenomas• Prolactin cell (lactotroph) adenoma• Growth hormone cell (somatotroph) adenoma• Thyroid-stimulating hormone cell (thyrotroph)

adenomas• ACTH cell (corticotroph) adenomas• Gonadotroph cell adenomas• Mixed growth hormone-prolactin cell

(mammosomatotroph) adenomas• Other plurihormonal adenomas• Hormone-negative adenomas• ACTH, adrenocorticotropic hormone.

Prolactinomas• most common type of hyperfunctioning

adenoma (30%)• from small microadenomas to large,

expansile tumors• Prolactin secretion is characterized by its:

– Efficiency - even microadenomas secrete sufficient prolactin to cause hyperprolactinemia

– proportionality, in that serum prolactin concentrations tend to correlate with the size of the adenoma

• Growth Hormone Adenomas– Second most common type of functional adenoma– large tumor -densely granulated and sparsely granulated

• Corticotroph Cell Adenomas– Small (microadenomas)– Clinically silent or hypercortisolism

Craniopharyngioma ("adamantinoma" "ameloblastoma”)

• A benign tumor of Rathke's pouch remnants• Generally occurs just above the pituitary and sella turcica. • Locally aggressive but does not metastasize. The optic

nerves and chiasm, and then the hypothalamus, are damaged.

• Most patients are under twenty. • Grossly, the tumor is usually filled with little cysts which

contain cholesterol-rich fluid • Microscopically, the tumor generally recalls developing

tooth enamel, with areas of columnar cells, stellate mesenchyme, usually calcification, sometimes stratified squamous stuff and/or bone.