Pathology 1

Endocrine System

highly integrated and widely distributed group of organs that orchestrate a state of metabolic equilibrium

Signaling can be grouped into three categories of transmission:

autocrine

paracrine

endocrine

In endocrine signaling, secreted molecules, hormones, act on target cells ___ from their site of synthesis

distant

How are endocrine hormones frequently carried?

by blood

The target tissue often secretes factors that down-regulate the activity of the gland producing the hormone, a process known as ___

feedback inhibition

prevents XS

Endocrine diseases often feature either ___ or ___ of hormones

underproduction

overproduction

Endocrine diseases are often associated with the development of ___, which can be either nonfunctional or functional

mass lesions

F = produces hormones

UF = does not

List (some of) the endocrine organs:

• Pituitary

• Thyroid gland

• Parathyroid glands

• Endocrine pancreas

• Adrenal glands

• Multiple endocrine

neoplasia

• Pineal gland

Pituitary-Hypothalamus Axis

links the nervous system with the endocrine system

Production of most hormones in the anterior

pituitary is controlled by factors secreted by the

___.... These factors are carried to the AP by a ___ system

hypothalamus

portal vascular

Meanwhile, the posterior pituitary secretes two peptide hormones, which are first synthesized in the ___ and then transported/stored via ___

hypothalamus

axon terminals

Which hormones does the anterior pituitary produce?

FLAT PiG

Which hormones does the posterior pituitary produce?

none!

Which hormones does the posterior pituitary store and secrete?

AO

What structure contains both the portal vessels and the axon terminals that connect the hypothalamus to both parts of the pituitary, respectively?

infundibular stalk

What are the 5 cell types of/in the anterior pituitary?

somatotrophs —> GH

lactotrophs —> PRL

corticotrophs —> ACTH

thyrotrophs —> TSH

gonadotrophs —> FSH, LH

Which of these cells stain PAS negative? Positive?

- : somatotrophs, lactotrophs

+ : corticotrophs, thyrotrophs, gonadotrophs

What colors are associated with PAS staining?

+ purple

- clear

The posterior pituitary contains ___, which are modified glial cells that store and release AO

pituicytes

When are AO released into systemic circulation, on behalf of the posterior pituitary?

labor

postpartum

dehydration and hypovolemia

Clinical manifestations of hyperpituitarism:

- adenomas

- hyperplasia

- carcinomas (very rare)

- secretion of hormones by nonpituitary tumors

- certain hypothalamic disorders

Clinical manifestations of hypopituitarism:

- ischemic injury, surgery or radiation

- inflammatory reactions

- nonfunctional pituitary adenomas

What is the most common cause of hyperpituitarism?

pituitary adenoma

—may be functional or nonfunctional, classified on the basis of hormones produced

Pituitary adenomas may target each cell of the anterior pituitary gland... what condition is associated with adenomas of corticotrophs?

Cushing Syndrome

Of somatotrophs?

gigantism, acromegaly

Of lactotrophs?

galactorrhea, amenorrhea, sexual dysfunction, infertility

Of gonadotrophs?

hypogonadism, mass effects, hypopituitarism

Of thyrotrophs?

hyperthyroidism

95% of pituitary adenomas are caused by sporadic mutations of the ___

G-protein in alpha subunit

What is a familial genetic cause of pituitary adenomas?

MEN1 gene

Pituitary adenomas are normally soft and well-circumscribed... when they infiltrate surrounding tissues, they are dubbed "___"

invasive

may be considered aggressive, as well, if mitotic activity is brisk and nuclear p53 immunoreactivity is extensive

What is the most common adenoma type?

prolactinomas (of lactotrophs)

Second most common?

somatropinomas

Somatotropinomas often have a lot of ___ involvements/progressions that are implicated

diabetic

(not using glucose)

What is the most common treatment option for adenomas?

surgical excision

___ adenomas, as previously mentioned, do not produce hormones... their typical presentation is ___

Non-functioning

mass effects

What is MEN1 syndrome?

autosomal dominant

mutations in MEN1 gene, which is on Chromosome11 (q13 portion of it)

characterized by adenomas of parathyroid, AP, pancreas

Hypopituitarism is most often caused by ...

- ischemic injury, surgery or radiation

- inflammatory reactions

- nonfunctional pituitary adenomas

At least 75% of ___ is lost in hypopituitarism

parenchyma

Pituitary Apoplexy

sudden massive hemorrhage/ischemia and degeneration of the pituitary gland associated with a pituitary tumor

common symptoms include severe headache, visual problems, and loss of consciousness

Hypopituitarism: GH

dwarfism

Hypopituitarism: LH, FSH

amenorrhea, infertility, etc.

Hypopituitarism: TSH

hypothyroidism

Hypopituitarism: ACTH

hypoadrenalism

(Addison's)

Hypopituitarism: PRL

failure of postpartum lactation

Diabetes Insipidus involves the ___'s hormone: ___

posterior pituitary

ADH (deficiency)

Diabetes Insipidus has two types:

Central

Nephrogenic

Central Diabetes Insipidus

ADH deficiency due to hypothalamic or psoterior pituitary pathology

(tumor, trauma, infection, inflammation)

Nephrogenic Diabetes Insipidus

kidneys do not respond to ADH

ADH Deficiency

huge output of dilute urine and intense thirst

hypernatremia — high sodium concentration in blood due to fervent water loss

What if you have too much ADH?

hyponatremia, cerebral edema, hypervolemia

What defects can lesions of the hypothalamus lead to?

hypopituitarism

hyperprolactinemia

neurologic (ex: visual field defects)

Why hyperprolactinemia???

disrupts transmission of PIH (dopamine)

Hypothalamic Suprasellar Tumors

neoplasms in this location may induce hypofunction or hyperfunction of the anterior pituitary, diabetes insipidus, or combinations of these manifestations

2 types of HST:

gliomas

craniopharyngiomas

Craniopharyngiomas

slow-growing

commonly cystic and multiloculated

usually recurrence-free with excellent survival

abnormalities in WNT signaling pathway

mutation of beta-catenin gene

There are two distinct types of craniopharyngiomas:

adamantinomatous = children

papillary = adults

How can you tell the difference between the two, histologically?

A —> keratinized

P —> not

WHO graded gliomas on a scale of I to ___ based on their severity (I is least)

IV (most) = glioblastoma multiforme

Pineal Gland

midline structure that secretes melatonin

Melatonin is derived from ___ and inhibits ___ release

serotonin

GnRH

A girl may experience periods at the age of 8/9 if a lesion of the ___ takes place

pineal gland