Guerin: Pituitary Flashcards
What is the most common cause of hyperpituitarism ?
anterior lobe pituitary adenoma
What is the difference between a macro and micro adenoma?
> or < 1cm in diameter
What are functioning adenomas associated with?
distinct endocrine signs and symptoms
What do nonfunctioning adenomas presnt with?
mass effects, including visual disturbances
What are lactotroph adenomas
- secrete prolactin
- can present with amenorrhea, galactorrhea, loss of libido, and infertility
What is a somatotroph adenoma
- secretes GH
- presents with gigantism in children and acromegaly inadults; also with impaired glucose tolerance and diabete mellitus
What is corticotroph adenoma?
-secretes ACTH and presents with cushing syndrome and hpyperigmentation
What are the distinct morphologic features of most adenomas?
- their cellular monomorphism and…
* *absence of reticulin network**
What is hypopopituitarism typically?
a destructive process of the anterior pituitary
-When combined with diabetes insipidus, think hypothalamic problem
What is pituitary apoplexy?
-a sudden hemorrhage into the pituitary gland (often an adenoma) and is a neurosurgical emergency
What is Sheehan syndrome?
-results from postpartum necrosis of the anterior pituitary
What do the clinically relevant posterior pituitary syndromes involve?
- ADH!
- Diabetes insipidus… too low
- SIADH…. too high
Which part of the pituitary is just an extension of the hypothalamus?
Post pit
What are the things that the hypothalamus secretes?
- TRH
- PIF (dopamine)
- CRH
- GHRH
- GIH (somatostatin)
- GnRH
Which hormones are carried via portal vascular system?
- TRH… TSH
- PIF….PRL
- CRH….ACTH
What are the anterior pituitary cell types and what do they secrete?
- somatotrophs… GH
- mammosomatotrophs…. GH and PRL
- Lactotrophs…. PRL
- Corticotrophs…. ACTH and POMC and MSH
- Thyrotrophs… TSH
- Gonadotrophs…. FSH and LH
What are the 2 hormones that the post pit makes?
- Oxytocin
- ADH
What does Oxytocin do?
- stimulates uterine contractions
- stimulates smooth muscle around lactiferous ducts
What does ADH do?
- vasopressin
- conserve water
Where are the hormones that the post pit secretes made?
Hypothalamus
-stored in axon terminals
What is the visual effect of a pituitary tumor?
-bitemporal hemianopsia
What are the signs of elevated intracranial pressure?
- headache
- nausea
- vomiting
What was bolded and bigger on the slide labeled “hyperpitutitarism”?
- Pituitary adenomas
- if non-functional, can cause hypopituitarism
What is a pituitary adenoma?
- functional
- adults
- micro is <1cm and macro is >1cm
- Atypical adenomas: more likely to behave aggressively (invasive, recur)
what does a typical pituitary adenoma look like?
- soft and well-circumscribed
- when small, confined to the sella turcica
- as they expand, they erode the sella turcica nad anterior clinoid processes
- larger ones extend superiorly and often compress the optic chiasm and adjacent structures (like cranial nerves)
What will tell us that it is an adenoma as opposed to normal? (histology)
-monomorphism and the absence of a significant reticulin
What is the mutation in the G-protein signaling that renders the alpha subunit active all the time?
-GNAS
Lactotroph adenoma
- most frequent type of hyperfunctioning pituitary adenoma- 30% of all clinically recognized cases
- Secrete prolactin
- range from small micradenomas to large tumors with mass effect
Clinical course of prolactinemia
- amenorrhea, galactorrhea, loss of libido, and infertility
- in men and postmenopausal women, it may be subtle
When is it normal to have hyperprolactinemia?
- preggo
- nipple stimulation
- response to many types of stress
What is hyperprolactinemia pathologic?
- loss of dopamine mediated inhibition of prolactin (hypothalamus secretes dopamine)
- damage of pituitary stalk (trauma)
- drugs that block dopamine receptors on lactotroph cells
- any mass in the suprasellar compartment may interfere with inhibitory effect of hypothalamus on prolactin secretion
Lactotroph adenoma treatment?
- bromocriptine
- surgery
What is bromocriptine?
a dopamine receptor agonist that cuases the lesions to diminish in size
What is the second most common type of functioning pituitary adenoma?
Somatotroph adenomas
what do somatotroph adenomas secrete?
GH
- stimulates hepatic secretion of IGF1
- Gigantism in children
- Acromegaly in adults
What is a somatotroph adenoma so big when it comes to clinical attention?
because we need a LOT of GH to cause clinical signs
-can take decades
When does gigantism occur?
- if it starts before the epihpyses have closed
- disproportionaltely long arms and legs
When does acromegaly occur?
- after closure of the epihpyses
- large jaw and feet and hands
- sausage fingers
- increased bone density in both the spine and the hips
How to diagnose somatotroph adenoma?
- look for elevated serum GH and IGF-1 levels
- failure to suppress GH production in response to an oral load of glucose***
Which test was very sensitive for acromegaly?
-look for failure to suppress GH production in response to an oral load of glucose
tx of somatotroph adenoma
- surgery
- pharmacotherapy: somatostatin analogs, GH receptor antagonists
Mammosomatotroph adenomas
- make both GH and prolactin
- more frequently recognized
- immunohistochemical reactivity for prolactin and GH
- signs and symptoms of both
- treatment same
Corticotroph adenomas
- Secrete ACTH… adrenal hypersecretion of cortisol… hypercortisolism (cushing syndrome)
- usually microadenomas
- Adenomas are PAS positive
Clinical course of cushing syndrome
- more later under adrenal gland… can be caused by a wide variety of conditions
- Hirsutism, round face, buffalo hump, easy bruising, abdominal weight gain, stretch marks
What is it called when there is hypercortisolism due to excessive production of ACTH by the pituitary?
Cushing Disease
Nelson syndrome
- pt with preexisting corticotroph microadenoma
- occurs after surgical removal of the adrenal glands for treatment of Cushing syndrome
- loss of inhibitory effect of adrenal corticosteroids…. large destructing pituitary adenoma with mass effect
- hypercortisolism does not develop (no adrenal glands)
- can get hyperpigmentation because of the stimulatory effect of other products of the ACTH precursor molecule on melanocytes
Gonadotroph Adenomas
- produce FSH and LH or nonfunctioning
- can be difficult to recognize: secretes hormones ineffeiciently and variably
- most frequently found in middle-aged men and women when they bocome large enough to cause mass effect
What is the result of decreased LH?
- decreased energy and libido in men (bc reduced testosterone
- amenorrhea in premenopausal women
Thyrotroph adenomas (TSH-producing)
- uncommon, about 1% of all pituitary adenomas
- rare cause of hyperthyroidism
Plurihormonal adenomas
- elaborate more than one hormone
- example: mammosomatotroph adenomas
- others secrete multiple hormones
- usually aggressive
Nonfunctioning Pituitary Adenomas
- 25-30% of all pituitary tumors
- typically present with sypmtoms of mass effect
- may also compress the residual ant pit… hypopituitarism
What is pituitary apoplexy?
What we have abrupt hypopituitarism from acute intratumoral hemorrhage
Pituitary Carcinoma
- rare
- <1% of pituitary tumors
- defined by metastases
- most are functional: most commonly PRL and ACTH
Hypopituitarism
- decreased secretion of pituitary hormons
- can happen d/t diseases of the hypothalamus or of the pituitary
- need to lose 75% of ant pit
What should we think of if we see hypopituitarism+posterior pituitary dysfunction?
Hypothalamic origin
Causes of hypopituitarism?
- tumors
- traumatic brain injury and SA hemorrhage
- pituitary surgery or radiation
- pituitary apoplexy
- ischemic necrosis of the pituitary and Sheehan syndrome
Sheehan syndrome
- postpartum necrosis of the ant pit
- most common form of clinically significant ischemic necrosis of the an pit
- during preggo, the ant pit enlarges to almost twice its normal size… without increase in blood supply
- any further reductin in blood supply from obstetric hemorrhage or shock may result in infarction of the anterior lobe
Why does Sheehan syndrome affect the anterior lobe and not so much the posterior?
the post pit receives its blood directly from arterial branches, so it is much less susceptible to ischemic injury and therefore usually not affected
if there is diminished secretion of ADH, what does that result in?
diabetes insipidus
Primary Empty Sella
-defect in the diaphragma sella
-arachnoid mater and CSF herniate into the sella… expands sella and compresse pituitary
-obese women w/ multiple preggos
-pts present with visual field defects and occasionally with endocrine anomalies
-
Clinical manifestations of hypopituitarisms?
- varies depending on the specific hormones that are lacking
- GH deficiency
- Gonadotropin (LH and FSH) deficiency
- TSH and ACTH deficiencies… hypothyroidism and hypoadrenalism
- Prolactin deficiency…. failure of postpartum lactation
MSH
- melanocyte stimulating hormone
- MSH is synthesized from the same precursor molecule that produces ACTH
- Hypopituitarism can cause pallor due to a loss of stimulatory effects on melanocytes
What do the clinically relevant post pit syndromes involve?
ADH
- Dabetes insipidus
- SIADH
What does ADH increase the expression of in the collecting duct?
aquaporins
-so H2O can diffuse back into our blood stream
Diabetes Insipidus
- ADH deficiency
- excessive urination
- Central DI (brain) vs. Nephrogenic DI
How to tell central DI from nephrogenic DI?
-see if the renal tubules are responsive to ADH
Clinical manifestations of Diabetes Insipidus
- pee a lot
- increased serum sodium and osmolality
- thirst and polydipsia
- pts who can’t compensate and drink water may develop life-threatening dehydration
SIADH
- too much ADH
- we resorb too much water
- hyponatremia
clinical manifestations of SIADH
- hyponatremia
- cerebral edema
- resultant neurologic dysfunction
Supresellar (hypothalamic) tumors
-may cause hypofunction or hyperfunction of the ant pit, DI, or a combo
Most common tumors of the supresellar variety?
- gliomas
- craniopharyngiomas
Craniopharyngioma
- remnants of Rathke puch
- slow-growing
- bimodal age distribution
- patients usually present with headaches and visual disturbances
- Children can present with growth retardation due to pituitary dypofunction and GH deficiency
- 3-4 cm
- optic chiasm or CN’s
Adamantinomatous Craniopharyngioma
- children
- calcified
- Nests or cords of stratified squamous epithelium with peripheral palisading and compact, lamellar keratin
- Cyst formation: contains that “machine oil”
- fibrosis and chronic inflammation
- Extend little fingers of epithelium into adjacent brain…. a brisk glial reactionq
Papillary Craniopharyngioma
- adults
- rarely calcified
- both solid sheets and papillae lined by well-differentiated squamous epithelium…. lacks peripheral palisading
- Usually lack keratin, calcification, and cysts
Prognosis of Papillary Craniopharyngioma
- excellent
- larger lesions are more invasive but this does not impact on the prognosis
- malignant transformation into squamous carcinomas: very rare, usually occurs after radiation
What is the most common cause of hyperpituitarism
anterior lobe pituitary adenoma
Macro vs microadenoma
1 cm
How do functioning adenomas present?
distinct endocrine signs and symptoms
How do nonfunctioning adenomas present?
mass effects, including visual disturbances
Lactotroph adenomas
-secrete prolactin and can present with amenorrhea, galactorrhea, loss of libido, and infertility
What is galactorrhea?
inappropriate production of milk
Somatotroph adenomas
-secrete GH and present with gigantism in children and acromegaly in adults; also with impaired glucose tolerance and diabetes mellitus
Corticotroph adenomas
-secrete ACTH and present with Cushing syndrome and hyperpigmentation
What are the distinctive morphologic features of mos adenomas?
- their cellular monomorphism
- absence of a reticulin network
What causes hypopituitarism?
-destructive processes of the ant pit
What do we think of when we see ant pit problems combined with diabetes insipidus?
-hypothalamic problem
What is pituitary apoplexy?
- sudden hemorrhage into the pituitary gland
- neurosurgical emergency
What is Sheehan syndrome the result of?
-results from postpartum necrosis of the ant pit
What do the clinically releavant Post pit syndromes involve?
ADH
- DI (too low)
- SIADH (too high)
