ENDOCRINE PATHOLOGY
Robbins and Cotran Patho Basis of Disease 10th Ed.
*use at your own risk
TRANS BY: MA.AC.CE.CC.AD.SM
Disease Description Pathogenesis Morphology Clinical Features Treatment and Prognosis
PITUITARY GLAND
- ANTERIOR PITUITARY (ADENOHYPOPHYSIS)- 80% of the gland
● Somatotrophs - growth hormone (GH)
● Mammosomatotroph - GH & Prolactin
● Lactotrophs - Prolactin
● Corticotrophs - adrenocorticotropic hormone(ACTH), pro-opiomelanocorticotroph (POMC) & melanocyte-stimulating hormone (MSH)
● Thyrotrophs - thyroid-stimulating hormone (TSH)
● Gonadotrophs - follicle-stimulating hormone (FSH) & luteinizing hormone (LH)
- POSTERIOR PITUITARY (NEUROHYPOPHYSIS)- modified glial cells (pituicytes) & axonal process from hypothalamus through the pituitary stalk to posterior lobe (axon terminals)
● Oxytocin - stimulates smooth muscle cell contraction in gravid uterus and mammary lactiferous ducts
● ADH (vasopressin) - water regulation
-Manifestations of pituitary disorders are related to either excess or deficiency of pituitary hormones, or to mass effects
● Hyperpituitarism - excess of trophic hormone which may be caused by hyperplasias, adenomas, carcinomas of the anterior pituitary, secretion of hormones by nonpituitary tumors, and hypothalamic disorders
● Hypopituitarism - deficiency of trophic hormones which may be caused by ischemic injury, surgery, or radiation, inflammatory disorders, and the mass effects of nonfunctional pituitary adenomas.
● Symptoms of related to mass effects
○ Bitemporal hemianopsia - lateral (temporal visual defects due to expanding pituitary lesions that often compress decussating fibers in the optic chiasm.
○ Elevated intracranial pressure due to expanding intracranial mass = headache, nausea & vomiting
○ Pituitary Apoplexy
PITUITARY ADENOMAS - Most common cause of GNAS mutations GROSS -s/sx related to endocrine -immunohistochemical stains
(AND hyperpituitarism is an adenoma -abrogate the GTPase activity with Gsɑ - soft and well-circumscribed abnormalities and mass effects for hormones and lineage-
HYPERPITUITARISM) arising in the anterior lobe. - activation of Gsɑ - 30% are not encapsulated specific transcription factors
- Some pituitary adenomas secrete - persistent generation of cAMP - Aggressive adenomas infiltrate neighboring LOCAL MASS EFFECTS
used to identify specific
two hormones and rarely - unchecked cellular proliferation tissues such as cavernous and sphenoid - radiographic abnormalities of the
- 40% of somatotroph cell adenomas sinuses, dura & brain sella turcica pituitary adenoma subtypes
plurihormonal
- GH and prolactin are the most - described in minority of corticotroph - Small adenomas expansion erode the sella - visual field abnormalities
common combination of secreted adenomas turcica and anterior clinoid processes - s/sx related to elevated
hormones - absent in thyrotroph, lactotroph, and -Larger lesions extend superiorly through intracranial pressure
- 35 to 60 years of age gonadotroph, because their trophic diaphragma sella into suprasellar region, - occasionally hypopituitarism
- pituitary carcinomas &some hypothalamic release hormones act via compressing optic chiasm and cranial nerves. - pituitary apoplexy assoc. w/
hypothalamic disorders - other signaling pathways. acute hemorrhage into an
>hypopituitarism MICROSCOPIC adenoma
- large pituitary adenomas (esp. Activation of ubiquitin-specific protease - these 2 distinguish pituitary adenomas from
Nonfunctioning ones) -> 8 (USP8) normal anterior pituitary parenchymas
hypopituitarism - 30 to 60 % of corticotroph adenomas (1) uniform (monomorphic) polygonal cells
- removes ubiquitin residues from arrayed in sheets of cord
Microadenomas proteins like epidermal growth factor (2) sparse reticulin, or connective tissue w/c
- less than 1cm in diameter receptor (EGFR) causes soft, gelatinous consistency
- enhances activity of EGFR and other
Macroadenomas pro-growth signaling pathways Mitotic activity and expression of Ki-67 (MIB-1,
, -exceed 1 cm in diameter marker of cycling cells)
Loss-of-function in MEN1, CDKN1B, - low in pituitary adenomas
Nonfunctional adenomas PRKAR1A, or AIP - higher-than-normal rates of cell division in
-clinical attention at later stage aggressive tumors.
-likely to be macroadenomas
LACTOTROPH - prolactin-secreting Sparsely granulated lactotroph adenomas Prolactinemia/ inc. serum levels of - surgery
ADENOMAS - most common type of - chromophobe cells prolactin cause: - Bromocriptine - a dopamine
hyperfunctioning pituitary adenoma - juxtanuclear localization of the transcription ● Amenorrhea receptor agonist that causes
- 30% clinically recognized cases factor PIT-1 ● Galactorrhea
the lesions to diminish in size.
- small microadenomas to large, ● Loss of libido
expansile tumors Densely granulated lactotroph adenomas ● Infertility
- symptomatic mass effects - rarer eosinophilic - diagnosis more readily in women
- women between 20 to 40 years of - diffuse cytoplasmic PIT-1 localization bec. hyperprolactinemia disrupts
age the menstrual cycle
- hormonal manifestations are
Immunohistochemical chains
subtle in men and older women
- prolactin within cytoplasmic secretory granules
- estrogen receptor alpha (ERɑ ) co-expressed
Other causes of
with PIT-1, lactotroph differentiation
hyperprolactinemia
-Physiological hyperprolactinemia
-dystrophic calcification, ranging from isolated ● pregnancy
psammoma bodies to extensive calcification ● suckling in lactating
(“pituitary stone”) women (nipple
-prolactin secretion is efficient and proportional stimulation) & stress
to size of the adenoma ● any suprasellar mass
- Pathologic hyperprolactinemia
● lactotroph hyperplasia
● loss of dopamine-
mediated inhibition of
prolactin secretion
● damage of the
dopaminergic neurons of
the hypothalamus or the
pituitary stalk, or exposure
to drugs that block
dopamine receptors on
lactotroph cells
SOMATOTROPH - growth hormone (GH)-secreting MICROSCOPIC - silent somatotroph are rare TREATMENT
ADENOMA - 2nd most common type of (1) Densely granulated somatotroph adenoma - persistently elevated GH - Failure to suppress GH
functioning pituitary adenoma - monomorphic, eosinophilic cells w/ granular stimulate insulin-like growth production in response to oral
- Gigantism in children cytoplasm factor (IGF-1) load of glucose - most
- Acromegaly in adults - large central nucleus w/ prominent nucleoli
- diffuse, strong immunoreactivity for GH sensitive test for acromegaly
GIGANTISM
- surgery
- somatotroph adenoma (inc
(2) Sparsely granulated somatotroph adenoma levels of GH and IGF-1) - GH receptor antagonists -
- chromophobes with patchy, weak staining appears in children before the prevent hormone binding to
for GH epiphyses closed target organs such as the liver
- fibrous body - paranuclear glossy inclusion, - generalized increase in body
composed of intermediate filaments that stain size with disproportionately *Sparsely granulated
for cytokeratin
, long arms and legs somatotroph adenoma tend
Mammosomatotroph adenoma to have more aggressive
- synthesize GH and prolactin in the same cell ACROMEGALY course than densely
- resemble densely granulated somatotroph - somatotroph adenoma (inc granulated somatotroph
adenoma levels of GH)) appears in
-immunohistochemical reactivity with GH and adenoma
children after the epiphyses
prolactin closed
- growth most conspicuous in PROGNOSIS
Somatotroph-lactotroph adenomas skin and soft tissues, viscera - depends on accurate
- GH and prolactin expression in different cells. (thyroid, heart, liver, & subtyping of somatotroph
adrenals) adenomas
- Hyperostosis in both spine
and the hips (inc in bone
density)
- Prognathism - protrusion of
jaw d/t enlargement
- broadening of the lower face
- feets and hands are enlarged
- Fingers become thickened
and sausage-like
-accompanied by evidence of
acromegaly
CORTICOTROPH - excess production of ACTH by - usually microadenomas - clinical manifestations of cushing
ADENOMA functioning corticotroph adenomas - Densely granulated - most often basophilic syndrome
leads to adrenal hypersecretion of - Sparsely granulated - occasionally
cortisol and the development of chromophobic CUSHING DISEASE
hypercortisolism (a.k.a CUSHING - hypercortisolism is due to
SYNDROME) STAIN excessive production of ACTH by
- both variants stain positively with periodic the pituitary
acid-Schiff (PAS)
- because of the presence of CHO in NELSON DISEASE
proopiomelanocortin (POMC), the precursor of - large destructive pituitary
ACTH adenomas can develop in pxns
after surgical removal of the
adrenal glands
CROOKE CELL ADENOMA
- loss of the inhibitory effect of
- 3rd common variant
adrenal corticosteroids on a
- ringlike deposition called Crooke change
corticotroph adenoma
- has an aggressive natural history
- hypercortisolism does not
develop
- mass effects
- hyperpigmentation from
melanotropin
OTHER ANTERIOR PITUITARY TUMORS
, GONADOTROPH - LH-producing and FSH-producing - steroidogenic factor (SF-1), GATA-2, - do not cause a recognizable
ADENOMA - middle-aged men and women and ERa syndrome
- most are nonfunctioning
- neurologic symptoms such as
impared vision, headaches,
diplopia,or pituitary apoplexy
Impaired secretion of LH
- decreased energy and libido in
men
- amenorrhea in premenopausal
women
THYROTROPH - uncommon, rare cause of - PIT-1
ADENOMA hyperthyroidism
- 1% of pituitary adenomas
NULL CELL ADENOMAS - do not express any markers of - symptoms stemming from mass
hormonal or lineage differentiation effects
- Hypopituitarism may appear
slowly d/t gradual enlargement of
the adenoma or abruptly bec. of
acute intratumor hemorrhage
(pituitary apoplexy)
PITUITARY CARCINOMA - rare - presence of craniospinal or - metastasis appear late in the
- less than 1% systemic metastases is a sine qua course, ff multiple local
non of a pituitary adenoma recurrences
- functional, with prolactin and
ACTH as most commonly secreted
PITUITARY BLASTOMA - children - DICER1 mutations - immature “blastema-like”cells (so-called - signs and symptoms of Cushing
- younger than 2 year of age “small round blue cells”) disease
- rosette-like formations resembling primitive - children develop “blastema-
Rathke epithelium like”neoplasms in other organs,
most commonly pleuropulmonary
blastoma
HYPOPITUITARISM - decreased secretion of pituitary Destructive processes involving ant. pituitary: CLINICAL MANIFESTATIONS
hormones, which can result from - tumors and other mass lesions - GH deficiency- pituitary dwarfism
diseases of the hypothalamus or of - traumatic brain injury and subarachnoid hemorrhage - LH & FSH (gonadotropin) deficiency
pituitary - pituitary surgery or radiation ● Women - amenorrhea and infertility
- 75% of the parenchyma is lost or ● Surgical excision and radiation may inadvertently include nonadenomatous ● Men - dec. libido, impotence, & loss of pubic & axillary
absent pituitary hair
- when accompanied by posterior - Pituitary apoplexy - TSH and ACTH def - hypothyroidism & hypoadrenalism,
pituitary dysfunction (in the form of ● Caused by sudden hemorrhage into the pituitary gland respectively
DM), almost always hypothalamic - Sheehan syndrome - Prolactin deficiency- failure of postpartum lactation
origin ● Ischemic necrosis of the pituitary - Melanotropins - same precursor of ACTH; pallor
● A.k.a postpartum necrosis
● Physiologic expansion of the gland during pregnancy
● The ischemic area is resorbed and replaced by a nubbin of fibrous tissue attached
Robbins and Cotran Patho Basis of Disease 10th Ed.
*use at your own risk
TRANS BY: MA.AC.CE.CC.AD.SM
Disease Description Pathogenesis Morphology Clinical Features Treatment and Prognosis
PITUITARY GLAND
- ANTERIOR PITUITARY (ADENOHYPOPHYSIS)- 80% of the gland
● Somatotrophs - growth hormone (GH)
● Mammosomatotroph - GH & Prolactin
● Lactotrophs - Prolactin
● Corticotrophs - adrenocorticotropic hormone(ACTH), pro-opiomelanocorticotroph (POMC) & melanocyte-stimulating hormone (MSH)
● Thyrotrophs - thyroid-stimulating hormone (TSH)
● Gonadotrophs - follicle-stimulating hormone (FSH) & luteinizing hormone (LH)
- POSTERIOR PITUITARY (NEUROHYPOPHYSIS)- modified glial cells (pituicytes) & axonal process from hypothalamus through the pituitary stalk to posterior lobe (axon terminals)
● Oxytocin - stimulates smooth muscle cell contraction in gravid uterus and mammary lactiferous ducts
● ADH (vasopressin) - water regulation
-Manifestations of pituitary disorders are related to either excess or deficiency of pituitary hormones, or to mass effects
● Hyperpituitarism - excess of trophic hormone which may be caused by hyperplasias, adenomas, carcinomas of the anterior pituitary, secretion of hormones by nonpituitary tumors, and hypothalamic disorders
● Hypopituitarism - deficiency of trophic hormones which may be caused by ischemic injury, surgery, or radiation, inflammatory disorders, and the mass effects of nonfunctional pituitary adenomas.
● Symptoms of related to mass effects
○ Bitemporal hemianopsia - lateral (temporal visual defects due to expanding pituitary lesions that often compress decussating fibers in the optic chiasm.
○ Elevated intracranial pressure due to expanding intracranial mass = headache, nausea & vomiting
○ Pituitary Apoplexy
PITUITARY ADENOMAS - Most common cause of GNAS mutations GROSS -s/sx related to endocrine -immunohistochemical stains
(AND hyperpituitarism is an adenoma -abrogate the GTPase activity with Gsɑ - soft and well-circumscribed abnormalities and mass effects for hormones and lineage-
HYPERPITUITARISM) arising in the anterior lobe. - activation of Gsɑ - 30% are not encapsulated specific transcription factors
- Some pituitary adenomas secrete - persistent generation of cAMP - Aggressive adenomas infiltrate neighboring LOCAL MASS EFFECTS
used to identify specific
two hormones and rarely - unchecked cellular proliferation tissues such as cavernous and sphenoid - radiographic abnormalities of the
- 40% of somatotroph cell adenomas sinuses, dura & brain sella turcica pituitary adenoma subtypes
plurihormonal
- GH and prolactin are the most - described in minority of corticotroph - Small adenomas expansion erode the sella - visual field abnormalities
common combination of secreted adenomas turcica and anterior clinoid processes - s/sx related to elevated
hormones - absent in thyrotroph, lactotroph, and -Larger lesions extend superiorly through intracranial pressure
- 35 to 60 years of age gonadotroph, because their trophic diaphragma sella into suprasellar region, - occasionally hypopituitarism
- pituitary carcinomas &some hypothalamic release hormones act via compressing optic chiasm and cranial nerves. - pituitary apoplexy assoc. w/
hypothalamic disorders - other signaling pathways. acute hemorrhage into an
>hypopituitarism MICROSCOPIC adenoma
- large pituitary adenomas (esp. Activation of ubiquitin-specific protease - these 2 distinguish pituitary adenomas from
Nonfunctioning ones) -> 8 (USP8) normal anterior pituitary parenchymas
hypopituitarism - 30 to 60 % of corticotroph adenomas (1) uniform (monomorphic) polygonal cells
- removes ubiquitin residues from arrayed in sheets of cord
Microadenomas proteins like epidermal growth factor (2) sparse reticulin, or connective tissue w/c
- less than 1cm in diameter receptor (EGFR) causes soft, gelatinous consistency
- enhances activity of EGFR and other
Macroadenomas pro-growth signaling pathways Mitotic activity and expression of Ki-67 (MIB-1,
, -exceed 1 cm in diameter marker of cycling cells)
Loss-of-function in MEN1, CDKN1B, - low in pituitary adenomas
Nonfunctional adenomas PRKAR1A, or AIP - higher-than-normal rates of cell division in
-clinical attention at later stage aggressive tumors.
-likely to be macroadenomas
LACTOTROPH - prolactin-secreting Sparsely granulated lactotroph adenomas Prolactinemia/ inc. serum levels of - surgery
ADENOMAS - most common type of - chromophobe cells prolactin cause: - Bromocriptine - a dopamine
hyperfunctioning pituitary adenoma - juxtanuclear localization of the transcription ● Amenorrhea receptor agonist that causes
- 30% clinically recognized cases factor PIT-1 ● Galactorrhea
the lesions to diminish in size.
- small microadenomas to large, ● Loss of libido
expansile tumors Densely granulated lactotroph adenomas ● Infertility
- symptomatic mass effects - rarer eosinophilic - diagnosis more readily in women
- women between 20 to 40 years of - diffuse cytoplasmic PIT-1 localization bec. hyperprolactinemia disrupts
age the menstrual cycle
- hormonal manifestations are
Immunohistochemical chains
subtle in men and older women
- prolactin within cytoplasmic secretory granules
- estrogen receptor alpha (ERɑ ) co-expressed
Other causes of
with PIT-1, lactotroph differentiation
hyperprolactinemia
-Physiological hyperprolactinemia
-dystrophic calcification, ranging from isolated ● pregnancy
psammoma bodies to extensive calcification ● suckling in lactating
(“pituitary stone”) women (nipple
-prolactin secretion is efficient and proportional stimulation) & stress
to size of the adenoma ● any suprasellar mass
- Pathologic hyperprolactinemia
● lactotroph hyperplasia
● loss of dopamine-
mediated inhibition of
prolactin secretion
● damage of the
dopaminergic neurons of
the hypothalamus or the
pituitary stalk, or exposure
to drugs that block
dopamine receptors on
lactotroph cells
SOMATOTROPH - growth hormone (GH)-secreting MICROSCOPIC - silent somatotroph are rare TREATMENT
ADENOMA - 2nd most common type of (1) Densely granulated somatotroph adenoma - persistently elevated GH - Failure to suppress GH
functioning pituitary adenoma - monomorphic, eosinophilic cells w/ granular stimulate insulin-like growth production in response to oral
- Gigantism in children cytoplasm factor (IGF-1) load of glucose - most
- Acromegaly in adults - large central nucleus w/ prominent nucleoli
- diffuse, strong immunoreactivity for GH sensitive test for acromegaly
GIGANTISM
- surgery
- somatotroph adenoma (inc
(2) Sparsely granulated somatotroph adenoma levels of GH and IGF-1) - GH receptor antagonists -
- chromophobes with patchy, weak staining appears in children before the prevent hormone binding to
for GH epiphyses closed target organs such as the liver
- fibrous body - paranuclear glossy inclusion, - generalized increase in body
composed of intermediate filaments that stain size with disproportionately *Sparsely granulated
for cytokeratin
, long arms and legs somatotroph adenoma tend
Mammosomatotroph adenoma to have more aggressive
- synthesize GH and prolactin in the same cell ACROMEGALY course than densely
- resemble densely granulated somatotroph - somatotroph adenoma (inc granulated somatotroph
adenoma levels of GH)) appears in
-immunohistochemical reactivity with GH and adenoma
children after the epiphyses
prolactin closed
- growth most conspicuous in PROGNOSIS
Somatotroph-lactotroph adenomas skin and soft tissues, viscera - depends on accurate
- GH and prolactin expression in different cells. (thyroid, heart, liver, & subtyping of somatotroph
adrenals) adenomas
- Hyperostosis in both spine
and the hips (inc in bone
density)
- Prognathism - protrusion of
jaw d/t enlargement
- broadening of the lower face
- feets and hands are enlarged
- Fingers become thickened
and sausage-like
-accompanied by evidence of
acromegaly
CORTICOTROPH - excess production of ACTH by - usually microadenomas - clinical manifestations of cushing
ADENOMA functioning corticotroph adenomas - Densely granulated - most often basophilic syndrome
leads to adrenal hypersecretion of - Sparsely granulated - occasionally
cortisol and the development of chromophobic CUSHING DISEASE
hypercortisolism (a.k.a CUSHING - hypercortisolism is due to
SYNDROME) STAIN excessive production of ACTH by
- both variants stain positively with periodic the pituitary
acid-Schiff (PAS)
- because of the presence of CHO in NELSON DISEASE
proopiomelanocortin (POMC), the precursor of - large destructive pituitary
ACTH adenomas can develop in pxns
after surgical removal of the
adrenal glands
CROOKE CELL ADENOMA
- loss of the inhibitory effect of
- 3rd common variant
adrenal corticosteroids on a
- ringlike deposition called Crooke change
corticotroph adenoma
- has an aggressive natural history
- hypercortisolism does not
develop
- mass effects
- hyperpigmentation from
melanotropin
OTHER ANTERIOR PITUITARY TUMORS
, GONADOTROPH - LH-producing and FSH-producing - steroidogenic factor (SF-1), GATA-2, - do not cause a recognizable
ADENOMA - middle-aged men and women and ERa syndrome
- most are nonfunctioning
- neurologic symptoms such as
impared vision, headaches,
diplopia,or pituitary apoplexy
Impaired secretion of LH
- decreased energy and libido in
men
- amenorrhea in premenopausal
women
THYROTROPH - uncommon, rare cause of - PIT-1
ADENOMA hyperthyroidism
- 1% of pituitary adenomas
NULL CELL ADENOMAS - do not express any markers of - symptoms stemming from mass
hormonal or lineage differentiation effects
- Hypopituitarism may appear
slowly d/t gradual enlargement of
the adenoma or abruptly bec. of
acute intratumor hemorrhage
(pituitary apoplexy)
PITUITARY CARCINOMA - rare - presence of craniospinal or - metastasis appear late in the
- less than 1% systemic metastases is a sine qua course, ff multiple local
non of a pituitary adenoma recurrences
- functional, with prolactin and
ACTH as most commonly secreted
PITUITARY BLASTOMA - children - DICER1 mutations - immature “blastema-like”cells (so-called - signs and symptoms of Cushing
- younger than 2 year of age “small round blue cells”) disease
- rosette-like formations resembling primitive - children develop “blastema-
Rathke epithelium like”neoplasms in other organs,
most commonly pleuropulmonary
blastoma
HYPOPITUITARISM - decreased secretion of pituitary Destructive processes involving ant. pituitary: CLINICAL MANIFESTATIONS
hormones, which can result from - tumors and other mass lesions - GH deficiency- pituitary dwarfism
diseases of the hypothalamus or of - traumatic brain injury and subarachnoid hemorrhage - LH & FSH (gonadotropin) deficiency
pituitary - pituitary surgery or radiation ● Women - amenorrhea and infertility
- 75% of the parenchyma is lost or ● Surgical excision and radiation may inadvertently include nonadenomatous ● Men - dec. libido, impotence, & loss of pubic & axillary
absent pituitary hair
- when accompanied by posterior - Pituitary apoplexy - TSH and ACTH def - hypothyroidism & hypoadrenalism,
pituitary dysfunction (in the form of ● Caused by sudden hemorrhage into the pituitary gland respectively
DM), almost always hypothalamic - Sheehan syndrome - Prolactin deficiency- failure of postpartum lactation
origin ● Ischemic necrosis of the pituitary - Melanotropins - same precursor of ACTH; pallor
● A.k.a postpartum necrosis
● Physiologic expansion of the gland during pregnancy
● The ischemic area is resorbed and replaced by a nubbin of fibrous tissue attached
