Pituitary Gland Pathology Flashcards
The major way in which nonfunctioning pituitary pathology comes to attention is via mass effect. What are some manifestations of this mass effect?
Increased intracranial pressure —> headaches, nausea/vomiting, confusion, shallow breathing
Visual disturbances (bitemporal hemianopsia d/t compression of optic chiasm, blurred vision, diplopia, etc.)
Pituitary apoplexy
Underproduction of pituitary hormones
Hyperprolactinemia (not necessarily due to prolactin-producing tumor, just that inhibitors have been destroyed)
What is pituitary apoplexy?
Hemorrhage into pituitary adenoma
Types of cells found in anterior pituitary adenomas and the hormones they produce
Lactotroph — prolactin
Somatotroph — growth hormone
Corticotroph — ACTH
Gonadotroph — LH/FSH
Thyrotroph — TSH
Most common secretory pituitary adenoma
Lactotroph adenoma (aka prolactinoma)
Presentation of lactotroph adenoma (prolactinoma) in females
Menstrual irregularities (adenomas responsible for >20% of amenorrhea)
Galactorrhea
Diminished libido
Infertility
Mass effect
Presentation of lactotroph adenoma (prolactinoma) in males
Decreased libido
Decreased sperm count
Mass effect [more likely to present as mass effect in males because hormone changes are more subtle — they don’t come to attention until very large]
Lactotroph adenomas can be classified as sparsely granulated or densely granulated. Which is more common? Which one is more severe?
Sparsely granulated is more common
Densely granulated is more severe because they are associated with more secretory product
Morphology and progression of lactotroph adenomas
Stromal hyalinization with psammoma bodies (calcifications)
Dense calcification progresses —> pituitary stone
Treatment options for lactotroph adenoma
Dopamine agonist — Bromocriptine (Cabergoline)
Surgery (via trans-sphenoidal approach)
What are some causes of hyperprolactinemia in the absence of an adenoma?
Pregnancy
Lactation/nipple stimulation
Loss of dopamine —> lactotroph hyperplasia (may occur with damage to neurons d/t stroke or head trauma, or d/t drugs like antipsychotics, antidepressants, verapamil, or metoclopramide)
Mass effect
Renal failure (increased production and decreased clearance of PRL)
Hypothyroid (increased TSH can stim PRL production)
Somatotroph adenomas present differently based on what?
Whether the growth plate (epiphysis) has closed
Prior to closure, somatotroph adenomas manifest as gigantism
After closure, somatotroph adenomas manifest as acromegaly
Clinical features of acromegaly
Enlargement of face and hands
Protruding jaw
Enlarged nose
Thickened lips
Joint pain/limited mobility
Enlarged viscera (including cardiomegaly)
Shortened lifespan (typically d/t CV complications)
How is a diagnosis of somatotroph adenoma established?
Serum levels of IGF-1 (secreted by the liver and present in more stable, predictable amounts than GH)
If IGF-1 is elevated, an oral glucose tolerance test is done to check for GH response (in normal physiology, glucose should inhibit GH production, so if it remains high there is an abnormality)
Treatment options for somatotroph adenoma
Somatostatin analogs
GH receptor antagonists
Surgical excision
All adenomas tend to show _____ growth on histology. Somatotroph adenomas can be sparsely or densely granulated, and can be mixed with _____-secreting cells
Diffuse; PRL
[somatotroph adenomas combined with PRL-secreting cells are called mammosomatotroph adenomas]
Cushing syndrome is different from Cushing disease. Which one is specifically derived from a pituitary corticotroph adenoma that produces ACTH?
Cushing disease
Cushing syndrome refers to hypercortisolism and the associated symptoms. What are some of the associated symptoms?
Central obesity, hirsutism, moon facies, striae, thin skin, dorsocervical fat pad, edema, menstrual changes, decreased libido, headache, psychiatric disturbances, renal calculi, osteoporosis/fracture, abnormal glucose tolerance
Major form of underlying cancer in cases of Cushing syndrome
Small-cell carcinoma of lung
[may also be due to pancreatic carcinoma or neural tumors]
What is the most common cause of Cushing Syndrome?
Iatrogenic [d/t excess glucocorticoid administration]
Workup for hypercortisolism NOT due to iatrogenic glucocorticoid administration
Check ACTH levels —
If high, it is ACTH-dependent hypercortisolism. Do inferior petrosal sinus sampling and MRI of the brain to determine whether d/t pituitary tumor or ectopic ACTH-producing tumor
If it is low, it is ACTH-independent hypercortisolism. Do CT/MRI of abdomen to determine whether adrenal adenoma/adrenal cancer or bilateral adrenal hyperplasia
[if ACTH levels are borderline, do a CRH stimulation test to clarify]
T/F: Pituitary tumors retain some ability to be suppressed by corticosteroids, thus a high-dose dexamethasone suppression test can be used to help diagnose a pituitary microadenoma (Cushing disease)
True
[in contrast, a low-dose dexamethasone suppression test would fail to suppress ACTH]
Treatment options for corticotroph adenoma
Somatostatin analogs
Bromocriptine
Surgical excision
[corticotroph adenomas can express dopamine receptors and somatostatin receptors]
Condition characterized by large destructive pituitary adenoma that develops after surgical removal of the adrenal glands for treatment of Cushing syndrome
Nelson syndrome
[occurs most often d/t loss of inhibitory effect of adrenal corticosteroids on a preexisting corticotroph microadenoma. Because the adrenals are absent, hypercortisolism does not develop, and pts present with mass effects due to the pituitary tumor. There can be hyperpigmentation because of the stimulatory effect of other products of the ACTH precursor molecule on melanocytes]
Somatic gene mutation that can be seen in 40% of somatotroph adenomas (and rarely in corticotroph adenomas)
Mutation of GNAS gene — makes the alpha subunit of Gs lose its GTPase activity (so GDP isn’t there to keep it shut off; GTP will initiate cascade with cAMP-driven cell proliferation)
Somatic genetic mutation associated with 36-62% of corticotroph adenomas, resulting in EGFR upregulation
USP8 mutation
Familial gene mutation associated most commonly with somatotroph adenomas
AIP (FIPA)
—leads to what is known as Pituitary Adenoma Predisposition (PAP)
Name some examples of causes of hypopituitarism
Tumors/mass lesions/cysts
TBI/hemorrhage
Apoplexy
Ischemic necrosis/Sheehan syndrome
Inflammatory disorders
Genetic defects
Consequences of anterior hypopituitarism
No growth hormone —> increased body fat, decreased muscle mass, reduced strength
No gonadotropins —> poor libido/impotence, infertility, reduced facial and body hair (men); amenorrhea, dyspareunia, infertility, breast atrophy (women)
No TSH —> decreased energy, constipation, weight gain
No adrenocorticotropic hormone —> weakness, tiredness, hypoglycemia
No prolactin —> lactation failure
What is Sheehan syndrome? Differentiate acute vs. chronic presentation
Postpartum ischemia/infarct/necrosis of the anterior pituitary
Acute — hypotension and lactation failure
Chronic — may result in any of the symptoms characterizing hypopituitarism
A cystic mass derived from ____ ____ is a major cause of hypopituitarism when it expands and compresses the normal pituitary; it can also rupture and result in inflammation of the pituitary or meningitis
Rathke’s cleft cyst
Primary vs. secondary empty sella syndrome
Primary: CSF leaks into the sella and compresses the pituitary
Secondary: the pituitary expands and infarcts within the sella, leaving an empty space
Presentation of craniopharyngioma in kids age 5-15
Most often adamantinomatous craniopharyngiomas
Present with growth retardation from hypopituitarism
Presentation of craniopharyngioma in adults >65
Usually papillary craniopharyngiomas
Present with signs of increased intracranial pressure or hypopituitarism
Histology of craniopharyngiomas
Derived from Rathke’s pouch remnants — so it has squamous epithelium, “wet” keratin, and can present with calcified cyst
Disease resulting from increased reclaimed free water from renal collecting system, leading to hyponatremia, hypernatriuria, mental status changes, muscle weakness, and seizures
SIADH
Major causes of SIADH
Small cell carcinoma of the lung (other malignancies as well)
Traumatic brain injury/subarachnoid hemorrhage
Drugs (SSRIs)
Disease resulting from decreased reclaimed free water from renal collecting system leading to hypernatremia, dilute urine, and polyuria
Diabetes insipidus
What symptom is present in both SIADH and diabetes insipidus?
THIRST
In DI, it is due to a legitimate need to replace fluids
In SIADH, it is a direct effect of ADH on the brain resulting in inappropriate thirst
