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Flashcards in Pituitary Histology and Pathology Deck (46):

Pituitary Anatomy

Small bean shaped structure within the sella turcica that is connected to the hypothalamus via the infundibulum


What is this?

 The ANTERIOR pituitary- derived from the developing oral cavity



Describe what you see here in the anterior pituitary

The pink acidophils secrete growth hormone (GH) and prolactin (PRL)

The dark purple basophils secrete corticotrophin (ACTH), thyroid stimulating hormone (TSH), and gonadotrophins follicle stimulating hormone-luteinizing hormone (FSH and LH)

The pale staining chromophobes have few cytoplasmic granules, but may have secretory activity.


What is this?

 The POSTERIOR pituitary –

The hormones vasopressin (antidiuretic hormone, or ADH) and oxytocin made in the hypothalamus (supraoptic and paraventricular nuclei) are transported into the intra-axonal neurosecretory granules where they are released.



Hyperpituitarism is msot commonly caused by what?

An anterior pituitary adenoma


Pituitary adenomas

Adenomas are classified based on the hormone produces by the neoplastic cells. AND based on if they are functional (hormone-producing WITH clinical manifestations), nonfunctional (hormone-producing but not excessive), or truly hormone negative.

NOTE: nonfunctional adenomas present with mass effect, including bitemporal hemianopsia due to compression of the optic chiasm, nausea and headache (Signs of raising intracranial pressure), and more often hypopituitarism than hyper when they impinge other tissue


Are pituitary adenomas genetic?

Most are sporadic, except 5% are inherited (MEN1 mutations)       


How are adenomas classified based on size and why?

 Given an arbitrary designation based on size (less than 1cm = microadenoma; >1cm macroadenoma)

   This is important because functioning adenomas are more likely to be microadenomas and cause symptoms of hyperpituitarism while nonfunctioning are more likely to be macroadenomas and may go un-noticed until they provide an effect like hypothyroidism or blindness by its mass effect


How do anterior adenomas occur?

About 40% of functioning adenomas (especially GH secreting tumors) have mutations in guanine nucleotide-binding proteins (G-proteins) encoded by GNAS1 that results in cellular proliferaiton


What genes have been assoicated with the 5% of pituitary adenomas that are classified as familial adenomas?

MEN1- associated with MEN syndrome type 1

CDKN1B inactivation (cell cycle checkpoint)- associated with a subset of "MEN-like" abnromalities


AIP- association with GH adenoma pateints that are younger at presentation than sporadic 


Mutations of p53 in pituitary adenomas are associated with what?

more aggressive behavior (invasion/recurrence) and as termed atypical adenomas


How can adenomas be ID'd?

 cellular monomorphisms (cells look similar) and

a lack of reticulin network seen with a reticulin stain (lack of reticulin accounts for the gelatin consistency of pituitary adenomas)


What are prolactinomas?

The most common (35%) type of hyperfunctioning pituitary adenoma that produces hyperprolactinemia leading to amenorrhea and galactorrhea (milk overproduction) in females (more likely to be spotted in young women), and loss of libido or infertility in men

NOTE: Any mass in the area can disturb prolactin secretion, so called the 'stalk effect". Thus, mild elevations in serum prolactin do not necessarily indicate a prolactin secreting neoplasm  (other causes of hyperprolactinemia: pregnancy, estogren, renal failure)


_____ are good for helping demonstrate/reveal prolactin in the cytoplasm of neoplastic cells

IHC stain


What are somatotroph cell adenomas?

The SECOND (10-15%) most common functional pituitary adenoma. Effects can be subtle and presistent secretion of GH stimulates hepatic secretion of IGF-1 (somatostatin C) which stimulates bone, cartilage, and soft tissue growth leading to growths and potentially secondary diabetes mellitus (GH induces liver gluconeogenesis)

NOTE: GH secreting adenomas are much less obvious and are likely to grow larger and produce mass effect


What else follows GH producing adenomas?

Prolactin can also be produced in sufficient quantities to produce signs and symptoms.

GH excess can also be associated with a variety of other disturbances, including gonadal dysfunction, diabetes mellitus, generalized muscle weakness, HTN, arthritis, CHF/dilated cardiomyopathy (most common cause of death), and an increased risk of gastrointestinal cancers.


Describe how Adrenocortictropic Hormone-Producing (Corticotroph Cell) Adenomas present?

Most are small at the time of diagnosis (think why) and can be clinically silent or cause hypercortisolism, that manifests as CUSHING DISEASE 

 In addition, because ACTH is part of the larger prohormone that includes melanocyte-stimulating hormone (MSH), patients may have hyperpigmentation.  


What is this?

Adrenocortictropic Hormone-Producing (Corticotroph Cell) Adenomas 

Typically small at diagnosis and stain with PAS as a result of accumulation of glycosylated ACTH. 


What is Nelson Syndrome? Symptoms? When does it occur?

This condition develops after surgical removal of the adrenal glands (for treatment of Cushing syndrome) and is due to a pre-existing pituitary ATCH adenoma. Because the adrenals are absent in persons with this disorder, hypercortisolism does not develop but there can be hyperpigmentation because of the stimulatory effect of other products of the ACTH precursor molecule on melanocytes.

Other symptoms typically include Moon facies, obesity


What are plurihormonal adenomas?

Pituitary adenomas may elaborate more than one hormone (e.g., mammosomatotroph adenomas). Other unusual “plurihormonal” adenomas secrete multiple hormones; these tumors are usually aggressive.


Describe gonadotroph adenomas

 Gonadotroph (LH-producing and FSH-producing) adenomas can be difficult to recognize because they are typically nonfunctioning and have variable presentations. When deficient it is most often impaired secretion of LH. FSH is usually the predominant secreted hormone.



Thyrotroph adenomas

Thyrotroph (TSH-producing) adenomas are uncommon, accounting for approximately 1% of all pituitary adenomas. Thyrotroph adenomas are a rare cause of hyperthyroidism .


What is this?

Pituitary carcinoma


Describe Pituitary carcinomas. Are they common? Typically functional?

very rare, accounting for less than 1% of pituitary tumors. 

Usually can be ID'd because it extends from the sella turcica malignant and metastasizes. Metastases usually appear late in the course, following multiple local recurrences.

Most pituitary carcinomas are functional, with prolactin and ACTH being the most common secreted products.




What is Hypopituitarism?

Hypopituitarism refers to decreased secretion of pituitary hormones, which can result from diseases of the hypothalamus (more common in posterior deficiency) or of the pituitary (anterior) when 75% of the parenchyma is lost


What are the most common causes of anterior hypopituitarism?

 Nonfunctioning adenoma, craniopharyngiomas

 Sheehan's syndrome

 Empty sella syndrome


Describe Nonfunctioning pituitary adenomas

These represent approximately 25% to 30% of all pituitary tumors and are described as nonfunctioning adenomas typically present with symptoms stemming from mass effects.

These lesions may also compromise the residual anterior pituitary sufficiently to cause hypopituitarism, which may appear slowly due to gradual enlargement of the adenoma or abruptly because of acute intratumoral hemorrhage (pituitary apoplexy).


What is Sheehan Syndrome?

Results when the physiologic expansion of the pituitary gland during pregnancy is not accompanied by an increase in blood supply from the low-pressure venous system; hence, there is relative hypoxia causing the anterior pituitary to infarct which commonly presents initially as a lack of being able to lactate, loss of pubic hair, and fatigue.

Because the posterior pituitary receives its blood directly from arterial branches, it is much less susceptible to ischemic injury and is therefore usually not affected. 


What is this?

Pituitary infarct: High power view showing coagulative necrosis of all the pituitary parenchymal cells; the only viable cells are erythrocytes, leukocytes and a few endothelial cells.


What is Empty Sella Syndrome? Who is it common in?

  Any condition or treatment that destroys part or all of the pituitary gland causing the subarachnoid space extends into sella; then, anything that ↑CSF pressure compresses gland and cause it to undergo atrophy (primary type). This is common in overweight, HTN patients, or those with multiple preg Hx or anatomic defects


NOTE: Secondary type- A mass, such as a pituitary adenoma, enlarges the sella and is then either surgically removed or undergoes infarction, leading to loss of pituitary function.




Pallor would be suggestive of deficient ____ hormone

ATCH due to its MSH activity


What is diabetes Insipidus?

 ADH deficiency causes diabetes insipidus, a condition characterized by excessive urination (polyuria) due to an inability of the kidney to resorb water properly from the urine (downregulated AQP2).



How does DI present?

The clinical manifestations include the excretion of large volumes of dilute urine 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. 


Describe SIADH

 ADH excess causes resorption of excessive amounts of free water, resulting in hyponatremia.



What is the most common cause of SIADH?

The most frequent causes of SIADH are the secretion of ectopic ADH by malignant neoplasms (particularly small-cell carcinoma of the lung).

Other causes: cyclophosphamide, pulmonary infection, CNS trauma



How does SIADH present?

The clinical manifestations of SIADH are dominated by hyponatremia causing cerebral edema, and resultant neurologic dysfunction/seizures due to brain shrinkage. Although total body water is increased, blood volume remains normal, and peripheral edema does not develop.

Tx: demecleocycline and water restriction


 Neoplasms in the pituitary may induce hypofunction or hyperfunction of the anterior pituitary, diabetes insipidus, or combinations of these manifestations.  The most commonly implicated tumors are _______ and _______.

gliomas and craniopharyngiomas (anterior pituitary). 


What is this?



Describe Craniopharyngiomas

 Thought to arise from vestigial remnants of Rathke pouch (anterior), these are slow-growing BENIGN (with rare malignant transformation) tumors account for 1% to 5% of intracranial tumors. 


Patient population for craniopharyngioma?

 A bimodal age distribution is observed (mostly younger people)


How do Craniopharyngiomas present?

 Patients usually come to attention because of headaches and visual disturbances (bitemporal hemaniopsia), while children sometimes present with growth retardation due to pituitary hypofunction and GH deficiency.



What causes Craniopharyngiomas?

 Abnormalities of the WNT signaling pathway, including activating mutations of the gene encoding β-catenin, have been reported in craniopharyngiomas 

Papillary craniopharyngiomas are characterized by BRAFv600E mutations


Describe what is seen in this Adamantinomatous craniopharyngioma  

•squamous epithelium (compact, lamellar “wet keratin”=*)

•dystrophic calcification (develops from the odontogenic (tooth-forming) epithelium)



What is happening here?

cholesterol-rich, thick brownish-yellow fluid (“machine oil”) in cysts in a craniopharyngioma