Endocrine Flashcards
1
Q
Hormone Synthesis
A
Steroids from Cholesterol
-Peptides are transcribed into the ER with an N terminal signal sequence (PreProhormone), in ER N terminal sequence is cleaved off and hormone becomes Prohormone in Golgi. In secretory vesicles final processes allows for clevage to active hormone
2
Q
Feedback loops
A
- Long is Test to hypothalamus and AP
- Short is AP to hypo
- ultrashort is AP on AP
3
Q
Positive Feedback
A
- Estrogen on AP during ovulation
- During labor, oxytocin is induced by cervical distension and stimulate uterine contraction. More contraction leads to more distension leads to more oxytocin
4
Q
Down R
A
- Beta Arestin and receptor degredation
- Progesterone downregulates estrogen receptors in uterus
- T3 downregualtes TRH receptors in AP
5
Q
Up regulation
A
- Prolactin stimulates own receptors in breast
- GH stimulates own receptors in muscle
- Estrogen stimulates own receptors in uterus
6
Q
GPCR
A
- i inhibits adenylate cyclase and decreases cAMP
- PDE degrade cAMP
- Gq goes through PLC and activates PKC
7
Q
Guanylate Cyclase
A
NO, ANP
8
Q
Ser/Threonine
A
Calcium Calmodulin
-MAPK
9
Q
RTK
A
Insulin and growth factors.
-IP3 and PKB
10
Q
RATK
A
GH and cytokines
-JAK STAT
11
Q
Steroid
A
Intracellular (Nuclear for thyroid), dimerization and zn finger domains act as transcription factors for SREs
12
Q
AP
A
Acidophils: PRL and GH
Basophils: LH, FSH, TSH, ACTH
-LH, FSH, TSH, HCG are glyocproteins with the same alpha subunit and different beta subunit
-ACTH is released by basophils in the POMC form
13
Q
GH
A
- 2 disulfide bonds, highly similar to PRL
- Stimulated at pubeity by steroids
- Also released during stage III and IV sleep
- Released in response to low glucose levels and stress
- Causes and increase in blood glucose and lipid levels, diabetogenic effect, opposes action of insulin in tissues, but insulin is still secreted
- Inhibited by somatostatin (Gi)
- Increased by GHRH (Gs)
- Is trophic to chondrocytes to increase long bone growth
- Excess treated with octreotide (also used in esophageal varicies)
14
Q
PRL
A
- Binds to JAK STAT receptor and increases growth of breast tissue during pregnancy and suclkling (Direct stimulation)
- Actions are opposed during pregnancy at the level of the receptor due to elevated E and P levels
- Inhibited by dopamine (Gi) from AP in portal system
- Increaed by TRH (Gs), Suckling
- Also inhibits GNRH leading to infertility and amenorrhea (Clinical signs of AP adenoma)
- Bromocritine is a dopamine analog that will block release
- Antipsychotics are D2 antagonists that will increase release (Loss of inhibition)
15
Q
Post Pit
A
Neurons directly secrete hormones into the blood stream in response to direct neural stimualtion.
- Release is almost immediate to stimulation
- Stored in vesicles with neurophysins (Supraoptic ADH) paraventricular (Oxytocin)
- 9AA peptide with significant homolgy
16
Q
ADH
A
- Secreted via AP in reesponse to increased osmolarity sensed in the anterior hypothalamus
- V1 receptors are Gq and present on vascular smooth muscle
- V2 receptors are on principal cells and increase aquaorin and urea transport
- Can also respond to large drops in BP (AngII) and also direct vagal stimulation from carotid and aortic baroreceptors
- Central DI treated with vasopressin
- Nephrogenic DI treated with Thiazides
- SIADH treated with demeclocycline
17
Q
Oxytocin
A
- Main function is to constrict myoepithelum in response to suckling
- May also have a role in uterine contraction and stopping bleeding after birth
- Can be released by suckling, Conditoining to baby, Diltaion of cervix (Positive feedback during partruition)
18
Q
Thyroid Production
A
- Follicles contain basolateral Na/I active transport of I into cells and is transported to the apical membrane where it is oxidized to yield I2
- Anions like thyocyanate will impair transport of Iodine into cell
- Thyroglobulin is made and secreted by the nucleus into the colloid
- In they colloid, thyroperoxidase organifies iodine to thyroglobulin generatig MIT and DIT
- Wolff Chiakoff effect will impair organification
- Thyroid peroxidase then couples MIT and DIT together to generate T3 and T4 that are still attached to thryoglobulin
- Thyroglublin will remain in coloid until TSH stimulation leads to endocytosis and lysosomal degredation yielding T3 and T4
- There is generally 10x mor T4 than T3
19
Q
Transport
A
T4 the binds to TBG and is transported to target tissues
- Hepatic failure will decrease total T levels but will have normal free T levels
- Pregnancy will increase TBG and total levels will rise, with normal free
- Tissue mediated 5’ deiodinase will change T4 into the active T3, 50% is inactive rT3
- Regulation occurs at this step, starvation etc will lead to a decrease in T3 levels due to 5’ deiodinase
20
Q
Regulation
A
- TRH is stimulatory to Basophilic thyrotrophs in AP (Gs) also stimulatory to PRL secretion
- TSH stimulates thryoid growht and hormone release
- T3 feedbacks to AP by decreasing TRH receptors and thus decreasing TSH release
21
Q
Thyroid Functions
A
- Nuclear receptor targets a number of genes
- Increase BMR, Na/K ATPase
- Increase cardiac contractility and HR (increase B1 expression and increase contractile proteins)
- Has permissive caetacholamine effects throughout body
- Overall catabolic on tissues and can increase blood glucose levels
- Works synergytsially with GH for skeletal maturation
- Necessary for proper synapse formation
22
Q
Hyperthyroidism
A
- Graves: AutoAb, myxedema and proptosis (increase GAG secretion, TSH)
- Adenom: Increase TSH and pretibial myxedema
- Iatogenic: No goiter and low TSH
23
Q
Hypothyroidism
A
- Hashimotos: GOiter and high TSH
- I deficecny; Goiter and high TSH
- Loss TRH or TSH: no goiter and low TSH
24
Q
Fetal Cortex
A
-Fetal Cortex is present at 8 weeks of gestation and degrades by birth
25
Steroid Horomone Synthesis
- Requires NADPH and Cyp-450 enzymes, also oxygen
- Takes place in the mitochondria
- Rate limiting step is desmolase which is stimulated by ACTH and inhibited by Ketocolanazole
26
Glomerulosa
- Can produce corticosterone before aldosterone which can funtion as a glucocorticoid
- 17 Deficency leads to a decrease in aldosterone because 11-DOC and corticosterone are active enough constrictors on vasculature to shut off via increased Renin
- RAAS is major control
- K also is major control through opening channel and increaseing intracellular Ca
- AT2 which regulates aldosterone synthase is a Gi receptor. In vasculature increases Ca and in Glomerulosa increases aldosterone synthesis
27
Reticularis
- All are 17 ketosteroids and can be converted to androgens in the testis
- In femalse they play a role in the development of pubic and axillary hair
28
HPA
- CRH is Gs
- ACTH is Gs
- Major control is cortisol feedback
- Reduced cortisol leads to increase ACTH and hyperplasia in CAH
- Also, longterm steroids lead to atrophy of ACTH and adrenals
29
Glucocorticoid Functions
- Increase blood glucose: GNG, Lipolysis, Proteolysis
- Increase alpha 1 expression
- Bind aldosterone receptors on smooth muscle and constrict
- Decrease collagen type 1 synthesis: Striae and osteoporosis, also decrease intestinal absorption
- Pulsatile releaese leads to increased wakefulness in the limbic system
- Increase RPF by constricting afferent arteriole
30
Calcium in Blood
Half of Ca is bound to albumin or to other plasma proteins and only half is in the free ionized form
- When alkalemic OOH residues lose their H and are OO- which can bind Ca. Alkalosis leads to decreased Ca levels
- Hypercalcemia will cause constipation, stones, etc
- Hypocalcemia makes membranes less depolarized and hyperexcitable leading to chovteks sign etc
31
PTH
Secreted by the chief cells of the parathyroid gland
- Works via a Gs protein to increase Ca
- Osteoblasts have receptors for PTH and actually build bone in response. Only over long term exposure will bone start to be broken down through the release of cytokines
- Vitamin D also stimulates bone resorption so that new bone can be formed. In the absence of Ca this can't happen. Reason for increased ALK phos in bone problems
32
Familial Hypercalcemia
-Defect in Ca sensors leads to abarent PTH secretion and aberrant Ca absoprtion in the GI
33
1 alpha hydroylase
-Functions in the renal tubular mitochondria. All steroids work or are synthesized in the mitochondria
34
Thyroid Embryology
Invagination off pharynx, endodermal origin
- Descends behind foramen cecum along thyroglossal duct
- Duct cyst is midline and moves with swallowing
- Branchial cyst is lateral
- Pyramidal lobe is sometimes in thyroglossal duct or at base of tongue
35
Fetal Adrenal Gland
Sits interior to the cortex that is developing
- Secretes some androgens in gestation to augment mothers supply
- Late in gestation secretes cortisol under influence of mother and self pit to mature lungs
36
Pheo and Nueroblastom
Adrenal Medullary tumors
- RET associated for pheo when part of MEN
- N-Myc for kids neuroblastoma
- Treat with surgey and phenoxybenzamine
37
Fetal Adrenal Gland
Placenta can't make own steroids but can aromatize DHEA from maternal and fetal adrenals into estrone which is major placenta estrogen
38
Cushings Syndrome
- Elevated Cortisol Levels, check with 24 hour urine cortisol
- Immunodeficency (Lipocortin supresses AA, IL-2 decrease, Stabalize lysosomes, decrease histamine and seretonin release from Mast Cells)
- Hyperglycemia
- Muscle wasting and truncal obesity
- Striae and osteoporosis (Colalgen type 1 decreased)
- Hypertension: Cortisol has mineralocorticoid action, but at normal levels is deactivated at kidney. Also induces alpha 1 expression on vasculature
- Mania: roles in sleep wake cycles and circadian rythms
- Disease is from an ectopic ACTH secreting adenoma (will be supressed with high dose dex)
- Ectopic tumor (RCC, Small Cell Lung, bronchial carcinoid) will not supress with high dose dex
- Primary adrenal tumor will show decreased ACTH levels
- Iatrogenic is most common cause and will show decreased ACTH
- 11-deoxy and corticosterone are weak glucocorticoids
39
Hyperaldosteronism
- Increased secretion from adrenal
- HTN, Sodium retention, decreased H and K leading to alkalosis
- Primary from an adrenal tumor and will have low renin
- Secondary from a renin tumor or poor renal perfusion: renal artery stenosis, or decreased effective blood volume, edema (Nephrotic, CHF, Renal Failure)
- Diuretics can also cause a lower effective blood volume
- Tx is spironolactone
40
Addisons
- Adrenal insuffency leading to decreased Cortisol and Aldosterone
- Hypoglycemia, fatigue, hypotension, hyperkalemia and acidosis
- Primary will show an elevated ACTH level and there will be skin hyperpigmentation. (Metastasis (lungs), CMV, TB infection, most common is autoimmune, ketocolanazole also possible
- Also can be waterhouse freidrichson which is hemorrhagic infarction from sepsis or meningococemic septicemia
- Can be secondary to abrupt withdrawl of steroids (usually will have ACTH atrophy and low ACTH levels)
- Secondary is to low ACTH levels
- Adrenal Crisis can develop post rapid withdrawl of cotrisol. Massive physiology and psychosis
41
Pheochromocytoma
- Tumor of the adrenal medulla. Most common inadults (NC derived)
- Associated with VHL, MEN 2 (Also med C), and NF-1
- Hypersection of epi, norepi, and DA leads to episodic HTN, headaches, flushing, etc
- Urine will have high metanephrines and vanilic acid (DA)
- Treat with surgical removal and phenoxybenzamine
- MIBG scan used to localize lesion
42
Caetacholamine Synthesis
- Phenylalanine and phenylalanine hydroxulase (tetrahydrobiopterin and NADPH)
- Tyronse to Dopa (tyrisine hydroxylase) requires NADPH and Tetrahydrobiopterin
- Dopa to dopamine Dopa decarboxylase (B6)
- Dopamine to Norepi Dopamine hydroxylase (Vitamin C)
- Norepi to Epi PNMT (SAM)
- DA - HVA
- Norepi - VMA
- Epi - Metanephrine
- COMT breaks down all ternimal caethacholamines with SAM
43
Neuroblastoma
- Most common tumor of the adrenal medulla in kids
- NF-1 associated
- Rarely produces Nor/Epi and is more likele to have HVA
- May be located somethwer else in the abdomen MIBG scan
- N-MYC oncogene
44
Hypothyroidism
- Slowed reflexes and other symptoms
- Facial and periorbital myxedema. TSH activie on fibs
- Skin yellowing, TSH necessary to convert beta carotene
- Hypercholesterolemia
- Myxedema crisis is precipitated by stress, patients get respiratory and cardiac depression
- Give thyroid, cortisol and respiratory support
45
Hashimotos
- DR5 associated
- immune infiltration and germinal center formation leads to hypothyroidism
- Elevated TSH leads to diffuse goiter with low T3 and T4 levels
- Also see anti-TPO antibodies (Microsomal)
- Hurthle cells (Large eosinophillic giant cells)
- Treat with levo
- Can increase risk of marginal zone lymphoma (NHL Bcell) at germinal centers
- May present early as hyperthyroid
46
Cretinism
- Thyroid necessary for bone and brain development (Synapses)
- Perinatal hyopthyroidism leads to short stature and retardation
- Could be mutation in TPO or iodine deficency
- Myxeda, leads to produbert stomach and puffy face and protuding umbilicus
47
Subacute Thyroiditis
- Post viral granulomatous inflammation of thryoid
- Diffuse painful goiter
- May be hyper or hypothyroid
- resolves after a month
- Elevated ESR and Jaw Pain
48
Drugs
Lithium - interferes with GPCR signalling
| Amiodarone (Can be up or down)
49
Riedel's
Thyroid replaced by fibrous tissue leads to hypofunction
- Differentiate from Anaplastic carcioma based on patients age
- Firm thyroid
- Related to systemic sclerosing disorders IgG4 related
50
Hyperthryroidism
Hyperthyroid signs with pretibial myxedema
51
Toxic Multinodular Goiter
- Specific portions of thyroid develop autonomous secretion due to mutation in TSH receptor leading to automaticity
- Nodular goiter
- Can occur after a persion with iodine deficent goiter is made iodine replete
52
Graves
TSI antibodies lead to stimuation of thyroid
- Pretibial myxedema, exopthalmous
- Often rpsents with childbrith
53
Thyroid Storm
- Thyroid induces increased BMR and icnreased B1 expression, especially on the heart
- Stressful situation in the context of hyperthyroid can lead to massive caetacholamine release and arryhtmia
- Death is by arrythmia
- Give beta blockers and anti-thyroid meds
- May also be elevated alk phos from bone turnover
54
Struma Ovarii
-Ovarian teratoma that secretes thyroid hormone
55
Female Ligaments
- Suspensory of ovary carries ovarian vessels
- Ovarian ligament connects ovary to uterus (derivative of gubernaculum)
- Round ligamen connects uterus to labia majora (gubernaculum)
- Cardinal Ligament connects cervix to lateral wall
- Uterosacral ligament connects cervix to sacrum
- Broad ligament is double fold of peritoneum that holds all of it
56
Epithelial layers
Vagina and ectocervix are stratified non keratinized squamous epithelium
- Endocervix and uterus are simple columnar epithelium
- Uterin glands are pseudostratified columnar epithelium
- Fallopian tubes are ciliated simple columnar
- OVary is cuboidal
57
Male anatomy
- Testis: Seminiferous tubiules dump into rete testis then into head of epididymis and then tail of epidydims then to vas deferens
- Vas deferens ascend and wrap around prostate to enter prostatic urethra
- Seminal vesicles are posterior to prostat and dump in
- ejaculatory duct is within the prostate
- Cowpers glands dump in as well
58
Male sexual respnse
- PANS from pelvic splanchnics increase NO and lead to cGMP
- SANS release NE (hypogastric nerve) and cause emssion and stop erection
- Pudendal controls ishciocavernosum and ejaculation
59
Klienfelters
-XXY due to maternal nondisjuntion
-Seminferous tubule dysgenesis with decreased funtion leading to decreased inhibin and increased FSH
-Decreased T and Increased E with normal or increased estrogen
Bar body will be present
-Small hard testis with fibrous displacement of tissue
-Extra X chromosomes can elad to retardation
60
Turners
- XO paternal nondisjuntion or silencing/mocasism
- May be the cause of a x linked recessive trait expressed in females
- Preductal coarc and bucuspid aorta
- Horsehoe kidney
- Diabetes
- Eye problems
- Dysgenesis and streak ovaries leading to increased FSH and LH with little to no estrogen
- Lymphedema
- Hypothyroidism
61
Female Pseudohermaphrodite
Elevated levels of androgens from CAH (21 or 11) or exogenous steroids.
-Ovaries and uterus will be present due to lack of MIF, but secondary sex will appear male
62
Androgen insensitivity
- Defect in androgen receptor that is contained in the X chromosome leads to increase in all hormone levels but absence of testosteron
- Testis will be in labia and should be removed to prevent malignancy
- CAG repeat number correlates with strength of androgen receptor
63
5 Alpha reductase deficency
- Leads to inabiltiy to convert T to DHT
- Leads to normal internal genetailia but ambiggous external genetalia
- AR
- At puberty there will be rapid increase in T that leads to development of secondary sex
64
Kallman syndrome
Improper migration of GnRH secreting neurons to arcuate nucleus of hypothalamus
- Leads to decreased of all hormones
- Anosmia is also present
65
Mullerian Agenesis
-Normal female internal but there is a problem and no female external
66
Complete Mole
- Egg without any genetic material is fertilized by 2 sperm or one sperm that divides
- Leads to 46 XX/Y chromosomes
- Massive increase in hCG and large uterus with abnormal bleeding
- Proliferatino of synctititrophoblasts and edematous villi with out any fetal tissue
- May risk of uterine rupture
- Can progress to choriocarcinoma or other malignancy
- D and C and treat with MTX, monitor hCG for recuurence
67
Partial Mole
- 2 sperm fertalize a single egg leading to 69 chromosomes
- less severe, presence of some fetal tissue, decreased hCG in comparison, lower risk of choriocarcinoma and will not rupture
68
Pre Eclampsis
- HTN and proteinuria during pregnancy that leads to edema (Cerebral and pulmonary are potentially dangerous)
- Caused by dysfucntional fetal maternal interface leading to ischemia and vasoactive substances being released
- Increased risk with autoimmune disorders, pre-existing HTN, DM
- May progress to eclampsia if there are siezures. Treat with MgSO4
- May also progress to HELPP with hemolysis, DIC, low platelets and elevated liver enzymes
- If occurs before 20 weeks think of a molar pregnancy as normal presentation is after 20 weeks
- Death due to ARDS and cerebral edema
69
Abruptio Placenta
- Early rupture of membranes leading to massive hemorrhage
- Delivery must occur immediately or risk baby abd mother
- Associated with trauma, cocaine, smoking, HTN
- Painful bleeding in third trimester
70
Placenta Acreta
- Placenta attached to myometruim
- Difficult delivery of afterbirth and massive hemorrhage may require C-section of hysterectomy
- Risk factors are inflammation, prior C-Section and DandC
71
Placenta Previa
- Placenta forms over the cervical os
- Usually presents with painless late term bleeding
- Must deliver by C-section or risk fetal ischemia
- Increased risk with multiparitry and prior C-section
72
Retained placenta tissue
- Can cause hemorrhage
| - Can also lead to infection. Staph Ureus and anaerobes are classic
73
Ectopic
- Generally occurs in tubal
- Occurs due to impaired ciliary action of tubes
- Related to previous tubal scarring: Endometriosis, PID, prior surgery/inflammation, appendix rupture
- Endometrium will be decidulaized but there will be no vili because ther eis no implantation
- hCG will be lower than expected
74
Polyhydramnios
- TOo much fluid from swallowing defect
- Duodenal or TEF
- Also anencephaly
75
Oligohydramnios
- Too little fluid from problem with renal system
- Bilateral renal agenesis
- Posterior urethral valves
- Placental insufficecny (Can't deliver enough fluids to make proper fluid)
76
Erythroblastosis fetalis
-Rh incompatibility
77
Hydrops
Hemoglobin bartz and 4 alpha thal
| parvovirus
78
Cervical Dysplasia
-Associated with HPV 16 and 18 which contain proteins E6 which inhibits p53 and E7 which inhibits Rb
-Generally occurs at the ecto/endo transition from squamous to columnar epithelium
-CIN is progressing layers of inclusion with CIS all the layers but not through the basement membrane
-Majority of invasive are SCC and invade locally to cause renal obstruction
-Adenocarcinoma is possible but less common
-
79
Vaginal Cancer
- Associated with HPV 16,18
- Clear cell with DES
- Embryonal rhabdomyosarcoma is desmin positive and presents in young girls
- Vaginal drainage: Exterior 1/3 is to the superficial nodes and superior 2/3 is to the hypogastric nodes
80
Endometriosis
- Endometrial tissue that gets pushed into somewhere else
- Hormonally responsive and pain around with cycles and pain on intercourse.
- A common location is posterior to the uterus in the rectouterine pouch of douglas which is the most dependent part of the peroneum
- Can be risk for ectopic pregnancies and infertility
- Treat with OCP, Flutamide, Danazol (inhibits gonadotropes at AP)
81
Adenomyosis
-Endometrial tissue that is present in myometrium and causes pain with menses
-Not located elsewhere
Enlarged uterus
82
Endometrial Hyperplasia
- Associated with anything that increases estrogen
- Nuliparity, obesity, HRT, early menarche and late menopause
- Presents as abnormal uterine bleeding (Post menopausal) and can be risk factor for endometrial cancer
- PCOS, Anovulatory Cycles, Granulosa Cell tumor
83
Endometrial Carcinoma
-Most common type is endometroid and arises from hyperplasia
-Spread is usually local and may cause renal obstrucion.
Most common gyn malignany in females
-Also can be a serrous form that is not related to estrogen exposure (Papillary structures and serrous)
84
Leiomyoma
- Extremely common and presents with pain that is cycle respondent
- May cause bleeding and lead to many abortions
- May cause anemia
85
Leiomyosarcom
- Not related to leiomyoma
- Malignant with splindle cells and many mitoses (other is well demarcated and whorled)
- Bulky, areas of necrosis and hemorrhage. Increase incidence in AA
- Tendency to recur
86
Epidemiology
Endometrial > Ovarian > cervical
| Severity: Ovarian > Cervical > Endometrial
87
Pagets Disease
Can also occur in the vagina with adenocarcionoma cells invading squamous epithelium.
-Be sure to distinguish between melanoma which will be keratin negative
88
PCOS
- Characterized by elevated LH, Elevated androgens and insulin resistance
- Decreased FSH because of elevated androgens
- Obesity and hirsuitism
- Treat with metformin for DM
- Clomiphine (SERM at hypothalamus) for fertility
- OCP for LH/FSH imbalance
- Antiandrogens (Spironolactone) for hirsuitism
- Increased risk of endometrial cancer (Elevated estrogens from adipose aromatization of androgens) There will be no progesterone to oppose
- Tx: Low dose progesterone decreases LH and decreases androgens
89
Cysts
Follicular: Anovulatory cycle. May lead to hyperestrineism, common
- CL cyst: common and inconsequental
- Theca Leutin: may hemorrhage and bleed, associated with molar pregnancies and twinning (elevated hCG stimulation)
- Hemorrhagic: Resolves
90
Mature Teratoma/ dermoid cyst
-various types of tissue, common
91
Strumaa Ovarii
-Monodermal teratoma
92
Endometroid
-Endometriosis in ovary leads to choclate cyst
