Pituitary Tumors

What is pituitary apoplexy?

1. Acute hemorrhage into adenoma with clinical evidence of rapid enlargement. 2. Result in acute-onset hypopituitarism and local compression symptoms.

State 3 clinical features of hypothalamic damage in craniopharyngioma.

1. Hyperphagia. 2. Obesity. 3. Loss of sensation of thirst. 4. Disturbance of temperature regulation.

Growth hormone-secreting somatotroph adenomas are the second most common type of functioning pituitary adenoma, and cause gigantism in children or acromegaly in adults. State 2 microscopic findings of this functional adenoma.

1. CAM5.2 immunostaining (IHC): presence of ball-like (dot-like) cytoplasmic fibrous bodies in >70% of cells. 2. Anti-GH antibody staining: demonstrates growth hormone within the cytoplasm of the cells

State two distinct morphologic features of most pituitary adenomas.

1. Cellular monomorphism (uniform, polygonal cells arrayed in sheets, cords, or papillae). 2. Absence of reticulin network. 3. Cytoplasm of the cells may be acidophilic, basophilic, or chromophobe.

Approximately 5% of pituitary adenomas arise as a consequence of an inherited predisposition. Four genes have been identified as a cause of familial pituitary adenomas. Name two causative genes.

1. MEN1 gene mutation: cause multiple endocrine neoplasia syndrome 1 (MEN1). 2. AIP (Aryl hydrocarbon receptor-interacting protein) gene mutation: growth hormone (GH) secreting adenomas at a younger age (before 35 years).

State 3 systemic features of acromegaly.

1. Mental disturbances. 2. Prominent lower jaw. 3. Cardiomegaly. 4. Hypertension. 5. Hyperglycemia. 6. Large feet.

Explain briefly the G protein mutations in the pathogenesis of pituitary adenomas.

1. Mutation in GNAS1 gene which encodes G protein α subunit interferes with its intrinsic GTPase activity. 2. Results in constitutive activation of G protein and persistent generation of cAMP. 3. Leads to unchecked cellular proliferation.

State the pathogenesis causing the invasive pituitary adenomas.

1. Mutations of TP53 gene is associated with a propensity for an adenoma with an aggressive behavior, such as invasion and recurrence. 2. Activating mutations of the RAS oncogene are observed in rare pituitary carcinomas

State the clinical manifestation results from compression of the optic chiasm by pituitary tumor.

Bitemporal hemianopia.

What happen when the pituitary tumor compress the 3rd, 4th or 6th cranial nerves?

Diplopia and strabismus. 1. Diplopia is the perception of 2 images of a single object. 2. Strabismus is a condition in which the eyes do not properly align with each other when looking at an object.

State the cause of Cushing's syndrome.

Excess production of ACTH by functioning corticotroph adenomas leads to adrenal hypersecretion of cortisol and development of hypercortisolism.

Most pituitary adenomas occur as a result of an inherited predisposition. True or False.

False. 1. Most pituitary adenomas occur as sporadic (i.e., non familial) lesions. 2. In about 5% of cases, adenomas can occur as a result of an inherited predisposition

Tumors of the posterior pituitary are more common. True or False.

False. 1. Tumours of the anterior pituitary are more common than those of the posterior pituitary and hypothalamus. 2. Most common of the anterior pituitary tumours are adenomas. 3. Primary and metastatic carcinomas are rarely seen

State the response on administration of high doses of dexamethasone in patient with Cushing's syndrome.

Patients show therapeutic response on administration of high doses of dexamethasone which suppresses ACTH secretion and causes fall in plasma cortisol level.

Differentiate the two types of microscopic finding in the craniopharyngioma.

1. Adamantinomatous type: ghost cells, peripherally palisaded nuclei, stellate reticulum, focal calcification, surrounding piloid gliosis with Rosenthal fiber formation. 2. Papillary craniopharyngioma: composed of nonkeratinizing stratified epithelium that is devoid of ghost cells and peripheral palisaded nuclei

Pituitary gland is a small, bean-shaped structure that lies at the base of the brain within the confines of the sella turcica. State 3 relations of pituitary gland.

1. Bridged over by a fold of dura mater called the diaphragma sellae. 2. Located with the sphenoidal air sinuses below. 3. Located with the optic chiasm above. 4. Located with the cavernous sinuses at the lateral - cavernous sinus contain 3rd, 4th and 6th cranial nerves and internal carotid arteries.

State 3 characteristic features in patient with Cushing's syndrome.

1. Central and truncal obesity contrasted with relatively thin arms and legs, buffalo hump due to prominence of fat over the shoulders, and rounded oedematous moonface. 2. Increased protein breakdown resulting in wasting and thinning of skeletal muscles, atrophy of subcutaneous tissue with the formation of purple striae on abdomen. 3. Systemic hypertension. 4. Impaired glucose tolerance and diabetes mellitus are found in about 20% of cases. 5. Amenorrhoea, hirsutism and infertility in many women.

Name the clinical manifestations when the pituitary tumor compress the optic nerve & optic tract respectively.

1. Compress the optic nerve - unilateral loss of acuity. 2. Compress the optic tract - homonymous hemianopia.

State 3 gross morphology of craniopharyngioma.

1. Encapsulated. 2. Adherent to surrounding structures. 3. Typically cystic, reddish-grey mass. 4. The fluid in the cystic cavity has color and consistency of machinery oil.

Overproduction of GH in adults following cessation of bone growth and increase IGF1 results in acromegaly. State 3 physical features of acromegaly.

1. Enlargement of hands and feet. 2. Prominent lower jaw and prognathism. 3. Prominent supraorbital ridges. 4. Coarseness of facial features with increase in soft tissues. 5. Enlargement of tongue (macroglossia) and lips. 6. Thickening of the skin and kyphosis. 7. Dilated cardiomyopathy.

Expansion of the lesion in pituitary adenoma resulting in destruction of the surrounding glandular tissue by pressure atrophy. State two results of pressure atrophy.

1. Erosion and enlargement of sella turcica. 2. Extension of the tumour damaging the optic chiasm, optic nerves, neurohypophysis and adjacent cranial nerves.

Pituitary adenomas can be functional or nonfunctioning or silent. Differentiate them briefly.

1. Functional pituitary adenomas: associated with hormone excess and clinical manifestations. 2. Nonfunctioning pituitary adenomas: there is no production of hormone. 3. Silent adenomas: demonstration of hormone production at the tissue level only, without clinical manifestations of hormone excess. + In most cases, both functional and nonfunctioning pituitary adenomas usually are composed of a single cell type and produce a single predominant hormone.

State three common syndromes of adenohypophyseal hypersecretion (hyperpituitarism).

1. Gigantism and acromegaly. 2. Hyperprolactinaemia. 3. Cushing's syndrome.

State 3 features of panhypopituitarism.

1. Gonadotropin deficiency: (women - amenorrhea, infertility)( men - decreased libido, impotence, loss of pubic and axillary hair). 2. TSH deficiency - symptoms of hypothyroidism. 3. ACTH deficiency - symptoms of hypoadrenalism. 4. Prolactin deficiency - failure of postpartum lactation. 5. GH deficiency - growth retardation, decreased muscle mass and strength

Nonsecretory (chromophobe) pituitary adenoma can cause two important syndromes. Name the two syndromes.

1. Panhypopituitarism. 2. Pituitary dwarfism.

Name 2 staining available for corticotroph adenomas.

1. Periodic acid-Schiff (PAS) stains. 2. Immunohistochemical stain.

Name 3 types of pituitary tumours.

1. Pituitary adenomas. 2. Craniopharyngioma. 3. Granular cell tumour of neurohypophysis. 4. Mixed pituitary adenoma-gangliocytoma. 5. Pituitary carcinoma. 6. Metastatic tumours

Pituitary-specific transcription factors play a role in the determination of pituitary cell lineages. Name 2 transcription factors.

1. Pituitary transcription factor-1 (PIT1) for prolactin (PRL). 2. Steroidogenic factor-1 (SF1) for gonadotroph adenomas.

Severe deficiency of GH in children before growth is completed results in retarded growth and pituitary dwarfism. State 3 clinical features of pituitary dwarfism.

1. Proportionate retardation in growth of bones. 2. Normal mental state for age. 3. Poorly-developed genitalia. 4. Delayed puberty. 5. Episodes of hypoglycaemia.

State 2 histological features of normal anterior pituitary gland.

1. The gland is populated by several distinct cell types that express different peptide hormones. These hormones are basophilic (blue), eosinophilic (red), or non-staining in routine sections stained with H & E. 2. Presence of a fine reticulin network between the cells.

State 3 gross features of pituitary adenomas.

1. Well-circumscribed, soft and most of them are encapsulated. 2. Microadenoma: < 10 mm in size & Macroadenoma: > 1 cm in size. 3. Small lesions are confined to the by the sella turcica. 4. Larger lesions can erode the sella turcica and compress the adjacent structures. 5. Foci of hemorrhage and/or necrosis are common in larger adenomas.

Define craniopharyngioma

A benign tumour arising from remnants of Rathke's pouch (Rathke's pouch tumour). + Childhood tumour (more common than adenomas), can also occur in elderly (> 60 year old)

Both these clinical syndromes result from sustained excess of growth hormone (GH) - most commonly due to somatotroph (GH-secreting) adenoma. Name the clinical syndromes.

Acromegaly & Gigantism.

State the cause & results of prolactinaemia in females & males respectively.

Cause: excessive production of prolactin usually due to lactotroph (PRL-secreting) pituitary adenoma, also called prolactinoma. In females: amenorrhoea-galactorrhoea syndrome (type III) - infertility and discharge of milk from breast. In males: : Impotence or reduced libido.

What is Nelson syndrome?

Clinically aggressive corticotroph cell adenomas may develop after surgical removal of the adrenal glands for the treatment of Cushing syndrome. + As the adrenals are absent in individuals with Nelson syndrome, hypercortisolism does not develop - Instead, patients present with the mass effects of the pituitary tumour.

Some pituitary adenomas can secrete two different hormones. State the most common combination.

Growth hormone (GH) + Prolactin.

State the common non-specific presentation in patient with pituitary adenoma.

Headache.

Name the method to classify the functional pituitary adenomas.

Immunohistochemical staining - pituitary adenomas are classified according to the hormones produced by the neoplastic cells.

Pituitary adenomas can be classified according to their functional features. State the most common functional pituitary adenoma.

Lactotroph (prolactin-secreting) adenoma.

Define the pituitary carcinoma.

Pituitary carcinoma is defined by the presence of cerebrospinal and systemic metastases. + Exceedingly rare cases (less than 0.5% of all pituitary region masses)

Prolactin-secreting lactotroph adenomas are the most frequent type of hyperfunctioning pituitary adenoma. True or False.

True.

GH excess occurs prior to epiphyseal closure in which excessive level of GH together with the insulin-like growth factor 1 (IGF1) result in gigantism. True or False.

True. 1. Gigantism occurs in prepubertal boys and girls. 2. Gigantism is much less common than acromegaly. 3. Main clinical feature: excessive growth of the child (generalized increase in body size)

Nonfunctioning pituitary adenomas constitute about 30% of all pituitary tumors. State the typical presentation in patient with this tumor.

Typical presentation is characterized by mass effects. 1. Gradual enlargement of adenoma which Impinge on the residual anterior pituitary and produce hypopituitarism. 2. Can also cause intratumoral haemorrhage (pituitary apoplexy).