Pathology of the Pituitary Flashcards
most susceptible part of the pitutitary
infundibulum (stalk)
two negative feedbacks in the pituitary
doapine –> - PRL
somatostain –> - GH
Somatotrophs,
producing growth hormone (GH)
Mammosomatotrophs,
producing GH and prolactin (PRL)
Lactotrophs,
producing PRL
Corticotrophs
producing adrenocorticotropic hormone (ACTH) and pro-opiomelanocortin (POMC), melanocyte-stimulating hormone (MSH)
Thyrotrophs,
, producing thyroid-stimulating hormone (TSH),
Gonadotrophs
producing follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
normal pituitary stains
heterogeneously
lost of different stuff
bitemporal hemianopia
from pituitary tumor compressing optic chiasm
how does cerebral edema present?
vomiting
headaches
look in eye- optic cup widened = papilledema
female complaining of leaky nipples, new onset headaches, serum prolactin elevated
pituitary adenoma
The most common cause of hyperpituitarism
is an adenoma arising in the anterior lobe
pituitary adenomas usually found what age?
adults, peak 25-50 years
microadenomas vs macroadenomas
micro less than 1 cm, likely to be functional
; macro is greater than 1 cm, likely to be nonfunctional
pituitary monomorphism
probably a prolactin adenoma
reticulin stain would normally show a network in the pituitary, but in adenoma it’s missing
dense core granules in MRI indicate
neuroendocrine
Clinical course of pituitary adenoma
The signs and symptoms of pituitary adenomas are related to endocrine abnormalities and mass effects. Local mass effects may be produced by any type of pituitary tumor.
these effects include radiographic abnormalities of the sella turcica, visual field abnormalities, signs and symptoms of elevated intracranial pressure, and occasionally hypopituitarism.
Acute hemorrhage into an adenoma is sometimes associated with pituitary apoplexy
Increased serum levels of prolactin cause
amenorrhea, galactorrhea, loss of libido, and infertility.
The diagnosis of an adenoma is made more readily in women than in men, especially between the ages of 20 and 40 years, presumably because of the sensitivity of menses to disruption by hyperprolactinemia.
Lactotroph adenoma
underlies almost a quarter of cases of amenorrhea. In contrast, in men and older women, the hormonal manifestations may be subtle, allowing the tumors to reach considerable size (macroadenomas) before being detected clinically
Somatotroph Adenomas
Growth hormone (GH)-secreting somatotroph adenomas are the second most common type of functioning pituitary adenoma, and cause * gigantism in children and acromegaly in adults (epyphyses are closed). Somatotroph adenomas may be quite large by the time they come to clinical attention because the manifestations of excessive GH may be subtle.
Clinical course of somatotroph adenomas
Persistently elevated levels of GH stimulate the hepatic secretion of insulin-like growth factor 1 (IGF-1), which causes many of the clinical manifestations.
If a somatotroph adenoma appears in children before the epiphyses have closed,
the elevated levels of GH (and IGF-1) result in gigantism. This is characterized by a generalized increase in body size with disproportionately long arms and legs.
If a somatotroph adenoma increased levels of GH are present after closure of the epiphyses,
acromegaly develops. In this condition, growth is most conspicuous in skin and soft tissues, viscera (thyroid, heart, liver, and adrenals), and the bones of the face, hands, and feet.
Growth hormone excess can also cause
Bone density may increase (hyperostosis) in both the spine and the hips.
Enlargement of the jaw results in its protrusion (prognathism), and broadening of the lower face. The feet and hands are enlarged, and the fingers become thickened and sausage-like. In most instances gigantism is also accompanied by evidence of acromegaly. These changes may develop slowly over decades before being recognized, hence the opportunity for the adenomas to reach substantial size.
GH excess can also be associated with a variety of other disturbances, including gonadal dysfunction, diabetes mellitus, generalized muscle weakness, hypertension, arthritis, congestive heart failure, and an increased risk of gastrointestinal cancers.
The diagnosis of pituitary GH excess relies on
documentation of elevated serum GH and IGF-1 levels. In addition, *** failure to suppress GH production in response to an oral load of glucose is one of the most sensitive tests for acromegaly.
Corticotroph Adenomas
Excess production of ACTH by functioning corticotroph adenomas leads to adrenal hypersecretion of cortisol and the development of hypercortisolism (also known as Cushing syndrome).
Cushing disease.
When the hypercortisolism is due to excessive production of ACTH by the pituitary, it is designated Cushing disease.
Nelson syndrome
Large destructive pituitary adenomas can develop in patients after surgical removal of the adrenal glands for treatment of Cushing syndrome. This condition, known as Nelson syndrome, occurs most often because of a loss of the inhibitory effect of adrenal corticosteroids on a preexisting corticotroph microadenoma.
Because the adrenals are absent in persons with this disorder, hypercortisolism does not develop, and patients present with mass effects due to the pituitary tumor, and there can be hyperpigmentation because of the stimulatory effect of other products of the ACTH precursor molecule on melanocytes
Gonadotroph adenomas
(LH-producing and FSH-producing) adenomas can be difficult to recognize because they secrete hormones inefficiently and variably, and the secretory products usually do not cause a recognizable clinical syndrome (nonfunctioning adenomas). Gonadotroph adenomas are most frequently found in middle-aged men and women when they become large enough to cause neurologic symptoms, such as impaired vision, headaches, diplopia, or pituitary apoplexy.
Pituitary hormone deficiencies
most commonly impaired secretion of LH. This causes decreased energy and libido in men (due to reduced testosterone) and amenorrhea in premenopausal women. The neoplastic cells usually demonstrate immunoreactivity for the common gonadotropin α-subunit and the specific β-FSH and β-LH subunits; FSH is usually the predominant secreted hormone.
Thyrotroph (TSH-producing) adenomas
are uncommon, accounting for approximately 1% of all pituitary adenomas. Thyrotroph adenomas are a rare cause of hyperthyroidism.
Nonfunctioning pituitary adenomas
are a heterogeneous group that constitutes approximately 25% to 30% of all pituitary tumors. Their lineage can be established by immunohistochemical staining for hormones or by biochemical demonstration of cell type-specific transcription factors.
In the past, many such tumors have been called silent variants or null-cell adenomas. Not surprisingly, 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).
Robbins Key Concepts: hyperpituitarism
most common cause- anterior lobe pituitary adenoma
can be macro or micro (less than 1 cm)
functioning- associated with endo signs and symptoms. Nonfunctioning- mass effects, including visual disturbances
lactotroph adenomas- amenorrhea, galactorrhea, loss of libido, infertility
somatotroph adenomas- gigantism in kids, acromegaly in adults, impaired glucose tolerance, diabetes mellitus
corticotroph adenomas- cushing syndrome and hyperpigmentation
distinctive morphologic features of most adenomas: cellular monomorphis and absence of reticulin network
25-year-old male sustains a IED explosion and survives with multiple medical problems
He complains of being tired
He notices a loss of libido, impotence, and loss of pubic and axillary hair
hypopituitarism
TSH, FSH, LH, and MSH decreased
brain shaking can beat up the stalk
Hypopituitarism
refers to decreased secretion of pituitary hormones, which can result from diseases of the hypothalamus or of the pituitary
Most cases of hypopituitarism arise from destructive processes directly involving the anterior pituitary.
Differential diagnosis of hypopituitarism
Tumors and other mass lesions
*** Traumatic brain injury and subarachnoid hemorrhage are among the most common causes of pituitary hypofunction
Pituitary surgery or radiation
Pituitary apoplexy
Ischemic necrosis of the pituitary and Sheehan syndrome
Rathke cleft cyst
Empty sella syndrome
Hypothalamic lesions
Inflammatory disorders and infections
Genetic defects
Clinical manifestations of hypopituitarism
Children can develop growth failure (pituitary dwarfism) due to growth hormone deficiency.
Gonadotropin (LH and FSH) deficiency leads to amenorrhea and infertility in women and decreased libido, impotence, and loss of pubic and axillary hair in men.
TSH and ACTH deficiencies result in symptoms of hypothyroidism and hypoadrenalism, respectively.
Prolactin deficiency results in failure of postpartum lactation.
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.
Posterior Pituitary Syndromes
diabetes insipidus and SIADH
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
Syndrome of inappropriate ADH (SIADH) secretion
ADH excess causes resorption of excessive amounts of free water, resulting in hyponatremia
52-year-old male presents with confusion and headache
20+ years smoker, chest x-ray performed
hyponatremia
SIADH
23-year-old male suffered head trauma secondary to motor vehicle accident
On exam is mildly confused but oriented times three
hypernatremia
BUN and creatinine elevated
diabetes insipidus
Diagnosis of diabetes insipidus
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.
central vs nephrogenic diabetes insipidus
Diabetes insipidus from ADH deficiency is designated as central to differentiate it from nephrogenic diabetes insipidus, which is a result of renal tubular unresponsiveness to circulating ADH.
The clinical manifestations of these two disorders are similar and 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.
normal shape of lateral ventricles
V shape
Hypothalamic Suprasellar Tumors
Neoplasms in this location may induce hypofunction or hyperfunction of the anterior pituitary, diabetes insipidus, or combinations of these manifestations.
The most commonly implicated tumors are gliomas and craniopharyngiomas.
A bimodal age distribution is observed, with one peak in childhood (5 to 15 years) and a second peak in adults 65 years or older. Patients usually come to attention because of headaches and visual disturbances, while children sometimes present with growth retardation due to pituitary hypofunction and GH deficiency
The craniopharyngioma is thought to arise from
vestigial remnants of Rathke pouch. These slow-growing tumors account for 1% to 5% of intracranial tumors.
morphology of craniopharyngiomas
average 3-4 cm,
2 types: adamantinomatous (kids)- frequently have calcifications
papillary (more in adults)- less frequent calcifications
prognosis with craniopharyngiomas and frequent findings
excellent recurrence-free and overall survival.
crankcase oil and calcifications
