1.
1° hypothyroidism: feat: fatigue, weight gain, constipation, slow relaxation of DTR, and dry, coarse skin
TSH rise occurs well before low thyroid hormone level seen=>best marker for Dx
*exception in cases of central hypothyroidism (deficiency in TSH) but cases are rare
2.
24hr urinary cortisol and dexmethasone suppression test screening: tests for Cushing syndrome
feats: central obesity, skin striae, rounded facies, deposition of supraclavicular fat, and proximal weakness
3.
Addison's disease: autoimmune condition=>adrenal glands bc markedly atrophic
*assoc with diffuse atrophy of adrenal cortex
4.
aldose reductase: enzyme that concerts glucose to sorbitol
plays role in development of chronic complications of diabetes
has low affinity for glucose; *in normal indiv very little glucose metabolized by this enzyme but in diabetics glucose metabolism by this enzyme is high due to chronically high blood glucose concentrations
5.
amino acids with three titratable protons: histidine
arginine
lysine
aspartic acid
glutamic acid
cysteine
tyrosine
6.
aromatase: expressed in ovarian tissue and present in subcutaneous fat, normal breast tissue, and cancerous breast tissue
*in postmenopausal state, extraovarian aromatase maintains a low level of estrogen in peripheral circulation
7.
aromatase inhibitors: anastrazole, letrozole, exemestane
aromatase inhibitors that inhibit synthesis of estrogen from its androgenic substrate=>suppressing estrogen to postmenopausal levels
*in Tx of metastatic cancer aromatase inhibitors are equivalent or superior to tamoxifen
**3rd generation are highly selective and potent
8.
autoimmune hypophysitis: inflammation of pituitary sometimes seen during late pregnancy or early postpartum
present: acute with headaches, visual field defects, and cortisol deficiency
9.
clomiphene: antiestrogen=>interferes with neg feedback of estrogens on hypothalamus and pituitary
increases synthesis of GnRH=>increases gonadotropins
used to Tx infertility esp when assoc with anovulation
10.
congenital adrenal hyperplasia: encompasses a group of disorders that stem from various defects in enzymes involved in cortisol biosynthesis=>increased cortisol precursors proximal to enzyme deficiency
21-hydroxylase deficiency the most common cause=>90%; converts 17-hydroxyprogesterone to 11-deoxycortisol in zone fasciculata; converts progesterone to deoxycorticosterone in zona glomerulosa
*accum cortisol precursors diverted towards adrenal androgen biosynthetic pathway=>increased adrenal androgens
**low cortisol levels stim ACTH prod=>further increases adrenal androgens production
***female infants get masculinized and males look normal
11.
Conn's syndrome: increased aldosterone secretion=>hypertrophy of glomerular layer of adrenal cortex
12.
cryptorchidism: seminiferous tubules are damaged
interstitial Leydig cells are preserved
13.
Cushing's sydrome: XS cortisol production
14.
danazol: synthetic androgen
clinical use: endometriosis, hereditary angioedema
side effects: hirsutism, masculinization, fluid retention, and weight gain
15.
Ehler's Danlos syndrome: heritable CT disorder characterized by skin hyperextensibility, joint hypermobility, tissue fragility, poor wound healing, and easy brusing
16.
epinephrine and glucose metabolism: increases glucose by multiple mech:
1. liver-increased glycogenolysis and gluconeogenesis
2. skeletal muscle-decreases glucose uptake; increases alanine released from skeletal m.=>serves as source of gluconeogenesis in liver
3. adipose tissue-increases breakdown of TG=>increasing FA and glycerol in circulation=>utilized as gluconeogenetic substrates
*glucagon has insig effect on adipose tissue and skeletal m.
17.
essential fructosuria: in pts with essential fructosuria=>metabolism of fructose by hexokinase to fructose-6-phosphate is 1° method of metabolizing dietary fructose
*this pathway not sig in normal indiv
18.
glucose-6-phosphatase: converts glucose-6-phosphate to glucose
*only found in liver
19.
glucose-6-phosphate metabolism: can be metabolized 3 ways:
1) conversion to G1P by phosphoglucomutase=>used for glycogen synthesis
2) conversion to glucose by glucose-6-phosphatase
*this enzyme absent in muscle
3) conversion to 6-phosphogluconolactone by glucose-6-phosphate dehydrogenase in first step of PPP
20.
HER2/neu: many pts with breast cancer overexpress this protein
involved in cell prolif=>assoc with worse prognosis
inhibition of epidermal growth factor and HER2/neu pathways can lead to apoptosis of breast cancer cells
*monoclonal Ab against HER2/neu receptors (e.g., trastuzumab) have been successful in Tx of breast cancer
21.
high waist to hip ratio associations: insulin resistance
metabolic syndrome
DM II
*meas visceral obesity
22.
hirsutism: male-like pattern terminal hair (coarse, curly, and pigmented) growth in females
idiopathic: increased conversion of testosterone into DHT by 5-alpha-reducatase or due to higher sensitivity of hair follicles to DHT
*occurs due to increased testosterone secretion or increased conversion of testosterone to DHT
causes: idiopathic (most likely cause if reg menses and no Sx of virulization), PCOS, Cushing syndrome, ovarian and adrenal tumors
Tx: spironolactone (blocks androgen receptors), flutamide (testosterone receptor antagonist), finasteride (5-alpha-reductase inhibitor)
*should be distinguished from virilization
23.
histidinemia: rare autosomal disorder that causes increased histidinemia=>pts deficient in histidase=>required for catabolism of histidine
clinical manifest: speech defects, pschomotor and gen retardation, emotional disturbance
*most frequent inborn metabolic disorder in Japan
24.
hypoglycemia: initially manifests with pallor and sweaty skin=>worsens with bizarre behavior, convulsions, and unconsciousness can develop
caught early can be self-Tx with consumption of 15-30 g of fast-acting carbs (e.g., glucose tablets, sweetened fruit juices, milk, soft drinks, or hard candy)
when severe enough to induce unconsciousness parenteral Tx is required=>intramuscular glucagon injection in non-medical setting =>correct hypoglycemia by increasing hepatic glycogenolysis and gluconeogenesis=>return to consciousness within 10-15min
*in medical-setting Tx with IV dextrose
25.
indications for Tx with cortisol: used as immunosuppressive drug in Tx of allergic rxns
can be injected or applied topically
26.
indications for Tx with desmopression: used to Tx central diabetes insipidus and nocturnal enuresis
also increases circulating levels of von Willebrand factor (factor VIII:R) and promotes coagulant activity of factor VIII:C
27.
indications for Tx with subcutaneous epinephrine: indicated primarily for Tx of anaphylaxis
28.
insulin: acts via tyrosine kinase that also has cytosolic tyrosine kinase activity=>*activates protein phosphatase=>dephosphorylates (activates) glycogen synthase=>glycogen synthesis
*protein phosphatase dephosphorylates and inactivates F16BP=>inhibits gluconeogenesis
anabolic hormone that promotes synthesis of glycogen (in liver and skeletal m.), TG, nucleic acids, and proteins
inhibits glycogenolysis and gluconeogenesis
29.
insulin vs. glucagon: insulin opposes glucagon action
glucagon stim insulin secretion from pancreas, glycogenolysis, gluconeogenesis, lipolysis, and ketone body prod
insulin increases glucose, AA and K+ uptake by cells, inhibits ketoacid formation and inhibits lipolysis
30.
janus protein kinase (JAK): 2nd messenger system for peptide hormones in JAK-STAT pathway
*signal transducers and activators of transxn
JAK has tyrosine kinase activity
31.
Kallman's syndrome: congenital absence of GnRH-secreting neurons
32.
ketoconazole and estrogen production: antifungal agent that decreases androgen synthesis by inhibiting multiple enzyme pathways involved in synthesis of androgens
33.
Klinefelter syndrome: typical genotype: 47 XXY; most clinical manifestations result of extra X c'some; can occur whe there is "non-disjunction" of sex c'somes during meiotic division in either parent
presentation: hypogonadism, small firm testes, elongated limbs, gynecomastia
seminiferous tubules progressively destroyed and hyalinized=>testes small and firm; serum inhibin decreased, decreased Leydig cells=>low testosterone, ED, increased LH and FSH
*hypogonadism causes delayed epiphyseal fusion=>elongated limbs
**most are infertile
34.
lipoxygenase: enzyme involved in arachidonic acid metabolism
responsible for pathway that synthesizes leukotrienes
35.
Marfanoid habitus: tall
slender
disproportionately long arms, legs, fingers
36.
McArdle's disease: type 5 glycogen storage disease=>myophosphorylase deficiency=>failure of glycogenolysis
*glycogenolysis provides immed NRG for strenuous muscle contraction
clinical manifest: decreased exercise tolerance, myoglobinuria, muscle pain with physical activity
37.
medroxyprogesterone (Depo Provera): progesterone-only OC administered as intramuscular injection once every 12wks
38.
MEN 1: autosomal dominant condition characterized by:
parathyroid gland
tumors of pituitary gland
tumors of pancreas
39.
MEN 2B: characteristics: Marfanoid habitus, mucosal neuromas, medullary thyroid carcinoma, pheochromocytoma
40.
metabolic syndrome: group of risk factors:
HTN
abdominal obesity
atherogenic dyslipidemia
insulin resistance
41.
mifepristone (RU-486): synthetic steroid with anti-progestin and anti-glucocorticoid effects
used primary as abortifacient
42.
mitotane: andrenocorticolytic drug
clinical use: adrenocortical carcinoma
43.
neurofibromatosis type 2: more "central" form
characterized by:
bilateral acoustic neuromas
brain meningiomas
shwannomas of the dorsal roots in spinal cord
44.
neurofribromatosis type 1: characterized by:
café-au-lait spots
cutaneous neurofibromas,
axillary or inguinal freckling
optic glioma
iris hamartomas
osseous lesions
45.
phospholipase C: active in G-protein/IP3/Ca2+ 2nd messenger system
hormone binds receptor and activates G-protein=>activates PLC=>degrade phospholipids to IP3 and DAG
*both DAG and increased intracellular Ca2+ caused by IP3 will activate PKC
46.
pituitary cancer: 1° cancer is extremely rare=>more prone to metastases due to rich vascular supply
present: tumor mass effects
*infiltrative lesions involving suprasellar space typically compress the pituitary stalk=>decreased hypothalamic dopamine and loss of inhibition of pituitary lactotrophs=>increased prolactin
47.
pituitary hypoplexy: hemorrhage into preexisting pituitary adenoma=>medical emergency
present: acute, severe headache, ophthalmoplegia, and altered sensorium
Tx: urgen neurosurgical consultation and stress doses of glucocorticoids
48.
prolactin inhibition: inhibited by dopamine=>acts on D2 dopamine receptor of lactotrophs
*dopamine secreted by hypothalamus
49.
protein kinase A: primary intracellular affector enzyme in G-protein/adenylate cyclase 2nd messenger system
increased levels of cAMP stim PKA
50.
Sheehan syndrome: high estrogen levels of pregnancy stim growth of pituitary=>enlarge and bc more vascular
*sig hypotension (most common cause is postpartum hemorrhage) while still large=>ischemic necrosis=>panhpopituitarism
commonly see prolactin deficiency (unable to lactate), hypothyroidism, and hypocortisolism
51.
spironolactone: K+-sparing diuretic
anti-andronergic properties: blocks androgen receptors at hair follicles, decreases testosterone prod
side effects: gynecomastia and testicular atrophy in men
52.
tamoxifen: acts as antagonist or partial agonist of estrogen receptor=>depending on tissue type
breast tissue: antagonizes estrogen receptor=>used as adjuvant therapy for estrogen receptor+ breast cancer
bone: partial agonist
endometrium: partial agonist
CV tissue: partial agonist
*assoc with side effects such as DVT, thromboembolism, and endometrial cancer
53.
virilization: hirsutism
clitoromegaly
increased muscle mass
acne
increased libido
voice deepening
