Escolar Documentos
Profissional Documentos
Cultura Documentos
Paracrine
Autocrine
Juxtacrine
Exocrine
Neurocrine
Neuroendocrine
Glycoproteins
Polypeptides
Steroids
Amines
Hypothalamus
Pineal gland
Pituitary gland
Anterior Pituitary
(Adenohypophysis)
GH (Somatotropin)
Dwarfism
Acromegaly
GH deficiency tests
Tests for Acromegaly
FSH
LH
TSH (Thyrotropin)
ACTH (Corticotropin)
Prolactin
Endocrinology
Hormone blood circulation specific receptor
Hormone interstitial space adjacent cell
Hormone self-regulation
Hormone direct cell-to-cell contact
Hormone gut
Hormone neurons extracellular space
Hormone neurons nerve endings
FSH, hCG, TSH, LH
ACTH, ADH, GH, angiotensin, calcitonin, CCK, gastrin, glucagons,
insulin, MSH, oxytocin, PTH, PRL, somatostatin
Precursor: cholesterol
Aldosterone, cortisol, estrogen, progesterone, testosterone,
vitamin D
Derived from amino acids
Catecholamines, T3, T4
Connected to the posterior pituitary by the infundibulum stalk
Hypophyseal hormones: TRH, GnRH, GH-IH, GH-RH, PIF
Melatonin: decreases pigmentation of the skin
Master Gland
Located in the sella turcica or Turkish saddle
True endocrine gland
Hormones: PRL, GH, FSH, LH, TSH, MSH, ACTH
Most abundant of all pituitary hormones
Structurally similar to PRL and HPL
Markedly elevated during deep sleep
Decreased GH
Increased GH
1. Insulin tolerance test = Gold standard (Confirmatory test)
2. Arginine stimulation test = 2nd confirmatory test
1. Somatomedin C or insulin-like growth factor I (Screening)
-Increased: Acromegaly
-Decreased: GH deficiency
2. OGTT (Confirmatory)
-75g glucose
Spermatogenesis
Helps Leydig cells to produce testosterone (male)
Ovulation (female)
Synthesis of androgens, estrogens, and progesterone
Stimulates thyroid gland to produce T3 and T4
Increased: 1 hypothyroidism, 2 hyperthyroidism
Decreased: 1 hyperthyroidism, 2 hypothyroidism, 3
hypothyroidism
Highest: 6-8 AM
Lowest: 6-11 PM
Not allowed to have contact with glass because it adheres to glass
surface
Collect blood in plastic tubes
Initiation and maintenance of lactation
Inhibited by Dopamine
Highest: 4AM and 8AM, and 8PM and 10PM
Increased: Menstrual irregularity, infertility, amenorrhea,
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Panhypopituitarism
Pituitary ischemia
(Shechans)
Posterior pituitary
(Neurohypophysis)
Oxytocin
ADH/AVP (Arginine
vasopressin)
Overnight water
deprivation test (Conc.
test)
Neurogenic DI
Nephrogenic DI
SIADH
Thyroid Gland
Follicle
Follicular cells
Parafollicular or C cells
Thyroglobulin
Thyroid hormone
Biosynthesis
Protein-bound
hormones
Free hormones
(FT3/FT4)
Reverse T3 (rT3)
I2 intake <50 g/day
T3
T4
TBG
TBPA (Transthyretin)
galactorrhea
From pituitary tumor (adenoma) or Ischemia
Hemorrhage or shock in a pregnant female at the time of deliver
Release but not produce oxytocin and vasopressin
Uterine contraction and milk ejection
H2O reabsorption (DCT and CD)
Stimulus: Increased plasma osmolality (>295 mOsm/kg),
decreased blood vol.
Promotes factor VII and vWF release
Diagnostic test for ADH
True Diabetes Insipidus
Failure of the pituitary gland to secrete ADH
Failure of the kidneys to respond to normal or elevated ADH
Syndrome of inappropriate ADH
Sustained production of ADH
Decreased urine volume
Low plasma osmolality
Low serum electrolytes
Butterfly-shaped
2 lobes = connected by the isthmus
Fundamental structural unit of the thyroid gland
Secrete T3 and T4
Secrete calcitonin
Preformed matrix containing tyrosyl groups
Stored in the follicular colloid of the thyroid gland
1. Trapping of Iodine
2. Iodination: I2 Tyrosine ring MIT and DIT
3. Condensation: MIT+DIT=T3 / DIT+DIT=T4
4. Release: T3/T4 Blood circulation
5. Transport of T3/T4 by proteins
Metabolically inactive
Biologically inert
Do not enter cells
Storage sites
Physiologically active
Readily enters cells
From removal of one iodine from T4 (product of T4 metabolism)
Metabolically inactive
Deficiency of hormone secretion
3,5,3-Triiodothyronine
Most active thyroid hormonal activity
75-80% is produced from the tissue deiodination of T4
Diagnosis of T3 thyrotoxicosis
3,5,35-Tetraiodothyronine
Principal secretory product
All originated in the thyroid gland
Transports 70-75 of TT4, and majority of T3
Transports 15-20% of TT4
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TBA
Thyroid autoantigens
Thyroid disorders
Primary
hyperthyroidism
Secondary
hyperthyroidism
T3 Thyrotoxicosis
(Plummers disease)
Graves disease
(Diffuse toxic goiter)
Riedels thyroiditis
Subclinical
hyperthyroidism
Subacute
granulomatous/
Subacute
nonsuppurative/ De
Quervains thyroditis
Hypothyroidism
Primary hypothyroidism
Hashimotos disease
(Chronic autoimmune
thyroiditis)
Myxedema coma
Secondary
hypothyroidism
Tertiary hypothyroidism
Congenital
hypothyroidism
(Cretinism)
Subclinical
hypothyroidism
TRH stimulation test
No affinity for T3
Transports T3 and 10% of T4
TPO
Tg
TSHR
Screening is recommended when a person reaches 35 yrs old and
every 5 yrs thereafter
T3 and T4
TSH
T3 and T4
TSH
T3
N-T4
TSH
1 Hyperthyroidism
Most common cause of thyrotoxicosis (autoimmune)
Women > Men
Anti-TSH receptor
Thyroid woody or stony-hard mass
No symptoms
N-T3 and T4
TSH
Hyperthyroidism
Painful thyroiditis
Neck pain, low-grade fever
(-) anti-TPO, ESR and Tg
Treatment: Levothyroxine
T3 and T4
TSH
Most common cause of 1 hypothyroidism
Thyroid is replaced by a nest of lymphoid tissue (T cells)
Goiter
(+) anti-TPO
TSH
Severe form of 1 hypothyroidism
Peculiar nonpitting swelling of the skin
Skin is infiltrated by mucopolysaccharides
Puffy face, thin eyebrows
T3 and T4
TSH
T3 and T4
TSH
TRH
Mental retardation (child)
Screening: T4
Confirmatory: TSH
N-T3 and T4
TSH
Most specific and sensitive test for diagnosing thyroid disease
Confirm borderline cases and euthyroid Graves disease
: 1 hypothyroidism
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Radioactive Iodine
Uptake (RAIU)
Thyroglobulin (Tg)
assay
rT3
Free Thyroxine Index
(FT4I)
T3 Uptake test
TBG test
Fine-needle aspiration
Recombinant Human
TSH
Tanned Erythrocyte
Hemagglutination
method
Serum calcitonin test
FT4 and TSH
FT3 and FT4
Euthyroid sick
syndrome
Parathyroid gland
PTH
1 hyperparathyroidism
: Hyperthyroidism
Measure the ability of the thyroid gland to trap iodine
Postoperative marker of thyroid cancer
: Untreated and metastatic differentiated thyroid cancer,
hyperthyroidism
: Hypothyroidism, thyrotoxicosis factitia
Assess borderline or conflicting laboratory results
Indirectly assesses the level of FT4 in blood
Equilibrium relationship of bound T4 and FT4
Reference method: Equilibrium dialysis
FT4I = TT4 x T3U(%) or TT4 x THBR
100
FT4 test: differentiates drug induced TSH elevation and
hypothyroidism
TT3 or FT3: confirm hyperthyroidism
Reference method (FT4): Equilibrium dialysis
Measures the number of available binding sites of the thyroxine
binding proteins (TBG)
TBG = T3U
TBG = T3U
Confirm results of FT3 or FT4 or abnormalities in the relationship of
TT4 and THBR test
Estrogen: TBG
Androgen: TBG
Most accurate tool in the evaluation of thyroid nodules
Test patients w/ thyroid cancers for the presence of residual or
recurrent dis.
Test for anti-Tg disorders
Marker for familial medullary thyroid carcinoma
Best indicators of thyroid status
More specific indicators of thyroid function than meas. of total
hormone
Not affected by TBG
Acutely ill but without thyroid disease
T3 and T4
N/ TSH
rT3
4 parathyroid glands
Smalles endocrine gland
Hypercalcemic hormone
Ca2+ (bone resorption and renal reabsorption) and Mg 2+
iPO4
Defective: Parathyroid gland
Most common cause of hypercalcemia
Parathyroid adenoma
PTH and iCa2+
Hypercalciuria
Phosphaturia Hypophosphatemia
If goes undetected severe demineralization (osteitis fibrosa
cystica)
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2 hyperparathyroidism
3 hyperparathyroidism
Hypoparathyroidism
Hyperparathyroidism
Hypoparathyroidism
Adrenal glands
Adrenal cortex
CPPP ring
3 layers (Adrenal
cortex)
Cortisol
Porter-Silber method
Zimmerman reaction
Pisano method
Kober reaction
Cushings syndrome
(Hypercortisolism)
Screening tests
(Cushings)
In response to Ca2+
Hyperplasia of all 4 glands
Causes: Vit. D deficiency and chronic renal failure
PTH
Ca2+
Occurs w/ 2 hyperparathyroidism ( Ca2+)
Autonomous function of hyperplastic PT glands or PT adenoma
PO4
Calcium phosphates precipitate in soft tissues
Accidental injury of the PT glands (neck) during surgery
Autoimmune parathyroid destruction
PTH = Ca2+
Acidosis
Alkalosis
Pyramid-shaped
Above the kidneys
Adrenal cortex = outer (yellow)
Adrenal medulla = inner (dark mahogany)
Has prime effects on blood pressure
Major site of steroid hormone production
G cells: convert cholesterol pregnenolone
17-carbon skeleton derived from cholesterol
1. Zona Glomerulosa = Mineralocorticoids (Aldosterone)
2. Zona Fasciculata = Glucocorticoids (Cortisol)
3. Zona Reticularis = Weak androgens (androstenedione, DHEA)
Gluconeogenesis hyperglycemia
The only adrenal hormone that inhibit the secretion of ACTH
Anti-inflammatory and immunosuppressive
Diurnal: 6-8AM / 10PM-12AM
Urinary metabolites: 17-OHCS and 17-KGS
Meas. 17-OHCS
Rgt: DNPH in H2SO4 + Alcohol
(+) Yellow
Meas. 17-KGS
Rgt: m-dinitrobenzene
(+) Reddish purple
Oxidation procedure: Norymberski (Na+ bismuthate)
For quantitating metanephrines and normetanephrines
For estrogen
Rgt: H2SO4 + hydroquinone
(+) Reddish brown color
Excessive production of cortisol and ACTH
Overuse of corticosteroids
Buffalo hump
Hyperglycemia
Hypertension
Hypercholesterolemia
Lymphocytes
1. 24-hour urine free cortisol test
2. Overnight dexamethasone suppression tests = Most widely used
(1mg)
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2 Hyperaldosteronism
Liddles syndrome
Bartters syndrome
Gitelmans syndrome
Hypoaldosteronism
Postural stimulation
test
Florinef
Weak androgens
DHEA
(Dehydroepiandrostero
ne)
Adrenal medulla
9:1
Norepinephrine
Epinephrine
Dopamine
Pheochromocytoma
Clonidine test
Neuroblastoma
Methods
(Catecholamines)
Estrogens
Pancreas (Exocrine)
Pancreas (Endocrine)
hCG
Human placental
lactogen (HPL)
Gastrin
Serotonin
(5-hydroxytryptamine)
5-HIAA
Norepinephrine (Children)
urinary HVA, VMA or both and dopamine
Specimen: 24-hr urine and plasma
1. Chromatography: HPLC or GC-MS
2. RIA: sensitive screening test
->2000pg/mL = diagnostic for pheochromocytoma
Estrone = Postmenopausal women
Estradiol = Premenopausal women (most potent, secreted by the
ovary)
Estriol = Pregnancy (placenta)
AFP
Unconjugated Estriol
hCG
Inhibin A
Test for Down syndrome (amniotic fluid)
Produced mainly by the corpus luteum
Det. whether ovulation has occurred
Luteal phase
Estrogen
Progesterone
FSH
LH
hCG
PRL
FT4
TSH
FSH
LH
Estradiol
Progesterone
Digestive enzymes (AMS, LPS)
Acinus: functional secretory unit
Hormones:
Alpha cells (20-30%) = glucagon
Beta cells (60-70%) = insulin
Delta cells (2-8%) = somatostatin
Produced by the syncytiotrophoblasts (placenta)
Maintain progesterone production by the corpus luteum
Stimulates development of mammary gland
Increases maternal plasma glucose levels
Diagnosis of intrauterine growth retardation
Secreted by G cells (stomach)
Stimulates parietal cells to secrete HCl
Stimulus: Amino acid
Zollinger-Ellison syndrome
Pernicious anemia
Synthesized by argentaffin cells (GIT)
Metabolite: 5-HIAA
Diagnostic marker for carcinoid syndrome
Test: Ehrlichs aldehyde test = (+) purple color
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Somatostatin
1 amenorrhea
2 amenorrhea
Cushings disease
Cushings syndrome
Gynecomastia
Hirsutism
Mullerian agenesis
Nonthyroidal illness
Sipples syndrome (MEN
II)
Stein-Leventhal
syndrome
Thyroid stones
Normal Values
(Endocrinology)
A.k.a. GH-IH
Inhibitor of GH, glucagon and insulin
Menstruation having never occurred
Absence of menses for 6 months
Abnormal increased secretion of ACTH
Chronic excessive production of cortisol by the adrenal cortex
-Large doses of glucocorticoids
-Pituitary tumor (ACTH) = most common cause
Development of breast tissue in males
Excessive hair growth w/ a male distribution pattern in a female
Most common endocrine disorder in women
Congenital malformation or absence of the fallopian tubes, uterus
or vagina
N-FSH, LH and testosterone
Illness that do not directly involve the thyroid gland
Medullary carcinoma of the thyroid
Pheochromocytoma
Parathyroid adenoma
Mild hirsutism w/ normal menses to excessive hirsutism w/
amenorrhea
A.k.a. thyroid crisis
Life-threatening
Uncontrolled thyrotoxicosis
T3:
Adult = 80-200 ng/dL
Children 1-14 y.o. = 105-215 ng/dL
T4:
Adult = 5.5-12.5 g/dL
Neonate = 11.8-22.6 g/dL
T3U = 25-35%
Therapeutic Drug Monitoring
Biochemical pathway responsible for the greatest portion of drug
metabolism
100% bioavailability
Drug Release
Drug Blood (most: by passive diffusion)
Drug Tissues
Drug Chemical modification
Drug metabolites excreted
Fraction of the dose that reaches the blood
Dilution of the drug after it has been distributed in the body
Drugs Liver Decreased bioavailability
Linear relationship bet. the amt. of drug eliminated per hour and
the blood level of drug
Relationship bet. drug concentration at the target site and
response of the tissues
Relationship bet. drug dose and drug blood level
Study of genes that affect the performance of a drug in an
individual
Ratio bet. the minimum toxic and maximum therapeutic serum
conc.
lec.mt 04 |Page | 9
Trough concentration
Peak concentration
Cardioactive Drugs
Class I
Class II
Class III
Class IV
Digoxin
Lidocaine (Xylocaine)
Quinidine
Procainamide
(Pronestyl)
Disopyramide
Propanolol
Amiodarone
(Cordarone)
Verapamil
Antibiotics
Aminoglycosides
Vancomycin
Antiepileptic Drugs
Phenobarbital
Phenytoin (Dilantin)
Valproic acid
(Depakene)
Carbamazepine
(Tegretol)
Ethosuximide
(Zarontin)
Gabapentin (Neurontin)
Others (Antiepileptic)
Psychoactive Drugs
Lithium
Tricyclic
antidepressantas (TCA)
Fluoxetine (Prozac)
Bronchodilator
Theophylline
Tx: Asthma and other COPD
Anti-inflammatory and Analgesic Drugs
Salicylates/Aspirin
Antiplatelet (inhibits cyclooxygenase)
(Acetylsalicylic acid)
Method: Trinder assay
Acetaminophen
Hepatotoxic
(Tylenol)
Ibuprofen
Lower risk of toxicity than salicylates and acetaminophen
Neuroleptics (Antipsychotic major tranquilizers)
Neuroleptics
Block the action of dopamine and serotonin
Tx: Schizophrenia
2 classes:
-Phenothiazines (chlorpromazine)
-Butyrophenones (haloperidol)
Examples:
-Risperdal
-Olonzapine (Zyprexa)
-Quetiapine (Seroquel)
-Aripiprazole (Abilify)
Immunosuppressant Cyclosporine
s
Tacrolimus (FK-506)
Rapamycin (Sirolimus)
Mycophenolate mofetil
Lefluamide
Chemotherapeutic
Busulfan
agents
Methotrexate
Toxicology
Toxic Agents
Alcohols (%w/v)
Common CNS depressants
0.01-0.05
No obvious impairment, some changes observable on performance
testing
0.03-0.12
Mild euphoria, decr. inhibitions, some impairment of motor skills
0.09-0.25
Decr. inhibitions, loss of critical judgment, memory impairment,
decr. rxn time
0.18-0.30
Mental confusion, dizziness, strongly impaired motor skills (slurred
speech)
0.27-0.40
Unable to stand/walk, vomiting, impaired consciousness
0.35-0.50
Coma and possible death
0.10
Presumptive evidence of driving under influence of alcohol
Ethanol (Grain alcohol)
Most common abused drug
Ethanol Acetic acid
Major metabolic pathway:
Ethanol ------(Alcohol Dehydrogenase)------> Acetaldehyde
Testing: Use benzalkonium chloride as antiseptic
Methanol (Wood
Cause blindness
alcohol)
Methanol Formaldehyde Formic acid (liver)
Isopropanol
Liver metabolism:
(Rubbing alcohol)
Isopropanol Acetone
Ethylene glycol
Antifreezing agent
(1,2-ethanediol)
Ethylene glycol Oxalic acid and glycolic acid
lec.mt 04 |Page | 11
Carbon Monoxide
Cyanide
Arsenic
Cadmium
Lead
Mercury
Drugs of Abuse
Opiates
Tranquilizers
Barbiturates:
Sedative Hypnotics
Dopaminergic pathway
stimulants
Hallucinogens
Amphetamines
Annabolic steroids
Cannabinoids
Tetrahydrocannabinol
(THC)
Cocaine (Crack)
Opiates
Phencyclidine
(Angel dust or angel
hair)
Sedative hypnotics
Lysergic acid
diethylamide (LSD,
Lysergide)
Methaqualone
(Quaalude)
Vitamins
Vitamin A
Vitamin E
Vitamin D2
Vitamin D3
Vitamin K
Vitamin B1
Vitamin B2
Vitamin B3
Vitamin B5
Vitamin B6
Vitamin B9
Vitamin B12
Vitamin C
Biotin
Carnitine
Cardiac toxicity
Prozac: inhibit the action of cocaine
Urine metabolite: benzoylecgonine
From opium poppy
Heroin
Morphine
Codeine
Methadone
Major metabolites: N-acetylmorphine (heroin) and morphine
Antagonist: Nalaxone (Narcan)
Hallucinogen
Admin: Ingestion or inhalation
Major metabolite: Phencyclidine HCl
Barbiturates (Secobarbital, pentobarbital, Phenobarbital)
Benzodiazopines: Diazepam (Valium), Lorazepam (Ativan),
Chlordiazepoxide (Librium)
Major metabolite (barbiturates): Secobarbial
Undulating vision
Bad trip panic reactions
Pyramidal signs (Hypertonicity, hyperreflexia, myoclonus)
Vitamins
Water soluble: B1, B2, B3, B5, B6, B9, B12, Biotin, C, Carnitine
Fat soluble: A, D, E, K
CN: Retinol
Def: Night blindness
CN: Tocopherol
Def: Mild hemolytic anemia, RBC fragility
CN: Ergocalciferol, Cholecalciferol (D2), 1,25dihydroxycholecalciferol (D3)
Def: Rickets (young), Osteomalacia (adult)
CN: Phylloquinones, Menaquinones
Def: Hemorrhage
CN: Thiamine
Def: Beriberi, Wernicke-Korsakoff syndrome
CN: Riboflavin
Def: Angular stomatitis, dermatitis, photophobia
CN: Niacin/Niacinamide/Nicotinic acid/Nicotinamide
Def: Pellagra (dermatitis, disorientation, weight loss)
CN: Panthotenic acid
Def: Depressed immune system, muscle weakness
CN: Pyridoxine, Pyridoxal
Def: Facial seborrhea
CN: Folic acid, Pteroylglutamic acid
Def: Megaloblastic anemia
CN: Cyanocobalamin
Def: Megaloblastic anemia, neurologic abnormalities
CN: Ascorbic acid
Def: Scurvy
Def: Dermatitis
Def: Muscle weakness, fatigue
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