Pathology Exam 4 Flashcards
2 Main categories of hormones
- Hormones that bind to cell surface receptors
2. Hormones that bind to intracellular receptors
Hormones to cell surface receptors
peptide hormone and small molecules, which when bound to surface receptors leads to an increase in intracellular second messengers (cAMP)
Hormones that bind to intracellular receptors
lipid soluble hormones that pass through plasma membrane and interact with receptors in the cytosol. These complexes then bind to regulatory elements in DNA (steroids, retinoids, thyroxine)
3 main causes of endocrine diseases
- Underproduction or overproduction of hormones with associated biochemical and clinical consequences
- End-organ resistance to hormone effect
- Neoplasms (nonfunctional, hormone overproduction, hormone underproduction)
Pituitary Gland
is a small bean shaped structure that lies at the base of the brain within the sella turcica. It is connected to the hypothalamus via a stalk composed of axons and portal circulation.
Anterior pituitary gland
Hormones released by anterior pituitary gland are produced in response to the release of hypothalamic factors carried to the anterior pituitary gland via portal circulation.
Posterior pituitary gland
Posterior pituitary (neurohypophysis) is made of modified glial cells and axons that extend from the hypothalamus. Hormones synthesized by hypothalamus are stored in these axon terminals and will be released by posterior pituitary gland.
Anterior pituitary gland hormones
- Thyroid stimulating hormone (TSH)
- Adrenocorticotropic hormone (ACTH)
- Prolactin (PRL)
- Growth hormone (GH)
- Follicle stimulating hormone (FSH)
- Luteinizing hormone (LH)
Posterior pituitary gland hormones
Oxytocin
Vasopressin (ADH)
Hypothalamus Hormones
- Thyroid releasing hormone (TRH)
- Corticotropin-releasing hormone (CRH)
- Growth hormone releasing hormone (GHRH)
- Gonadotropin releasing hormone (GnRH)
- Somatostatin (GIH)
- Dopamine (PIF)
The most common cause of hyperpituitarism
is an adenoma arising in the anterior lobe
Pituitary adenomas are classified on the basis of…
hormone(s) produced by the neoplastic cells.
Silent Pituitary Adenoma
produces hormones only at the tissue level → no clinical manifestations
Functional Pituitary Adenoma
pituitary adenoma that produces hormones
Usually: composed of a single cell-type, produce a single predominant hormone
Non-functional Pituitary Adenoma
- Does not produce hormones and is often found late
- Destroys adjacent pituitary parenchyma → hypopituitarism
- Can also compress the optic chiasm → visual changes, loss of vision
Microadenoma Size
< 1 cm
Macroadenoma Size
> 1 cm
3 most common types of functioning pituitary adenomas
- Lactotroph (most common)
- Somatotroph (2nd most common)
- Corticotroph
Lactotroph
Most common, accounts for 30%. Prolactin-secreting adenomas = hyperprolactinemia which causes amenorrhea, galactorrhea, loss of libido, and infertility.
Clinical Presentation: Tumors size ranges from microadenomas to large. They are diagnosed earlier in premenopausal women because of amenorrhea and small in size. The effects of the tumor are much more subtle in older women and men and the tumor may reach a large size before detection.
Somatotroph
Tumor that secretes growth hormone (GH).
Clinical Presentation: Causes gigantism in children and acromegaly in adults. GH stimulates hepatic insulin-like growth factor 1 (IGF1) which works with GH to start overgrowth of muscles and bones.
Persistent GH excess can lead to metabolic abnormalities, most importantly diabetes mellitus
Corticotroph
Excess production of ACTH which leads to adrenal hypersecretion of cortisol and eventually the development of hypercortisolism (a.k.a Cushing Syndrome)
Clinical Presentation: Usually small sized tumors. Nelson Syndrome: May develop after surgical removal of adrenal glands for treatment of Cushing Syndrome.
Definition of hypothyroidism
loss or absence of +75% of anterior pituitary
Sheehan Syndrome
(postpartum necrosis) ischemic necrosis of anterior pituitary
hyperplasia of anterior pituitary w/o blood supply
Antidiuretic Hormone (ADH)
Acts on collecting tubules of kidney to promote resorption of water.
Oxytocin
Stimulates contraction of smooth muscle in the pregnant uterus and the lactiferous ducts of mammary glands.
2 subtypes of Diabetes Insipidus
- Central
2. Nephrogenic
Central DI
Central = ADH deficiency
Etiology: head trauma, neoplasms, inflammation disorders of hypothalamus/pituitary, surgical procedures of hypothalamus/pituitary
Nephrogenic DI
Nephrogenic = Renal tubular unresponsiveness to circulating ADH
Etiology: Due to underlying kidney pathology
Syndrome of inappropriate ADH (SIADH)
secretion is associated with:
excess ADH → resorption of excessive amounts of free water → hyponatremia
Causes of SIADH
1) malignant neoplasms (especially small-cell carcinoma of lung) that secretes ectopic ADH, 2) non-neoplastic disease of the lung, & 3) local injury to the hypothalamus or neurohypophysis (posterior pituitary)
Breast Objective #2:
Most common symptoms of women with breast complaints
- Pain (5% cancer)
- Inflammation (<1% cancer)
- Nipple discharge (7& cancer)
- Lumpiness (1% cancers)
- Palpable masses (5% cancer)
Breast Objective #3:
2 principal mammographic signs of breast carcinomas
- Densities: Normal breast tissue is replaced with radio-plaque breast lesions
- Calcification: Formed on secretions, necrotic debris, and hyalinized stroma
Breast Objective #4:
3 groups of benign epithelial lesions of the breast each associated with different degree of cancer risk
- Non-proliferative disease: Not associated with increased CA risk
- Proliferative disease w/out atypia: encompasses polyclonal hyperplasias that are associated with a slight increase for breast CA risk
- Proliferative disease w/ atypia: Includes monoclonal “precancers” that are associated with a modest increase in breast CA (13-17% develop breast CA)
Breast Objective #5:
Define gynecomastia, underlying hormone imbalance, examples of predisposing factors, and risk of CA.
Definition: Increased breast tissue in males. Only common symptom in males. An increase in both stroma and epithelia cells.
Hormones: Imbalance between estrogens, which stimulate breast tissue, and androgens, which counteract these effects
Predisposing factors:
Risk of CA:
Breast Objective #6:
List risk factors that convey highest relative risk for invasive breast carcinomas & indicate life time risk in US
Most important:
- Age and gender
- Family Hx of breast CA
- Geographic factors
- Race/Ethnicity
- Reproductive Hx
- Ionizing radiation
- Other risk factors
Lifetime risk: 1 in 8 women living to age 90
Breast Objective #7:
3 groups of hormone receptor breast cancers
- Estrogen receptor
- Progesterone receptor
- HER2
Breast Objective #7:
Incidence by expression of hormone receptor
- ER + (HER2-): 50-65%
- HER2 + (ER +/-): 10-20%
- Triple Neg (ER, PR, HER2 -): 10-20%
Breast Objective #7:
Mutations responsible for most single gene familial breast cancer
- BRCA 1
- BRCA 2
These account for half of the cases associated with single gene mutations
Breast Objective #8:
The 2 most common locations of tumors
- Upper outer quadrant 50%
2. Central portion 20%
Breast Objective #9:
ER positive / HER2 Negative frequency, typical patient groups, common metastatic patterns, and relapse pattern
Frequency: 50-65%
Patient Groups: older women, men. cancers detected by screening; germline BRCA2 mutation carriers
Metastatic: Bone (70%), viscera (25%), brain (<10%)
Relapse: May be late (>10 years after diagnosis)
Breast Objective #9:
HER2 + / ER + or - : frequency, typical patient groups, common metastatic patterns, and relapse pattern
Frequency: 20%
Patient group: Young women, germline TP53 mutation carriers
Metastatic: Bone (70%), viscera (45%), brain (30%)
Relapse: short (10 years; survival with mets is rate)
Breast Objective #9:
Triple Negative: frequency, typical patient groups, common metastatic patterns, and relapse pattern
Frequency: 15%
Patient group: young women; germline BRCA1 mutation carriers
Metastatic: Bone (40%), viscera (35%), brain (25%)
Relapse: Short (<5 years; survival with mets rare
Breast Objective #10:
Distingush between LCIS and DCIS on basis of calcification and risk for invasive carcinoma
DCIS: Ductal carcinoma in situ
Calcification: frequently associated
Invasive Risk: 1/3rd if not treated , but 97% long-term survival
LCIS: Lobular carcinoma in situ
Calcification: Rarely associated
Invasive Risk: Approx 1/3rd of women will develop invasive
Breast Objective #11:
List prognostic factors for invasive breast cancer, and know which is the most important
Need lecture first***
Breast Objective #12:
Describe the epidemiology of, the typical clinical presentation of, and any associated risk of malignancy with fibroadenoma.
Fibroadenoma: benign tumor contains a mixture of proliferating ductal elements (adenoma) embedded in loose fibrous tissue (fibroma)
Epidemiology: Most common benign tumor of the female breast; most occur in women in their 20s and 30s, and they are frequently multiple and bilateral. 10% of women will develop a fibroadenoma during their lifetime
Clinical presentation: Vary in size from <1 cm to large tumors that replace most of the breast; well-circumscribed, rubbery, grayish white nodules that bulge above the surrounding tissue and often contain slitlike spaces (feels like a moveable marble in the breast)
Associated risk of malignancy: Benign, but a mildly increased risk of subsequent cancer
