endocrine yr3 Flashcards
what are the 4 types of hormones
1.peptide: insulin, acth, growth hormone, LH,FSH
-protein synthesis
-exocytosis (require stimuli)
-transport: hydrophilic (circulate freely)
2. steroidal: cortisol, aldosterone, sex hormones
-enzymatic conversion of cholesterol
-stimuli increase enzyme activation
-transport: binds with plasma protein
3. tyrosine: thyroid and catecholamines
-pre-cursor: tyrosine
-diffusion across membrane (stimulus)
-binds to plasma protein
4. eicosanoids: prostaglandin, leukotrienes
-peroxidation of arachidonic acid by COX, phospholipase and lipoxygenases
-poorly diffuse
-transport: require a transporter (anionic)
what are the targets of peptide and steroid hormones
-peptide: GPCR and catalytic receptors (surface)
-steroid: cytosolic and nuclear receptor (inside)
what are the causes of hypersecretion and hyposecretion
-hypersecretion: tumor (primary or secondary or ectopic), immunological
-hyposecretion: genetic, immunological, destruction by disease (autoimmune disease)
what hormones are secreted by anterior and posterior pituitary
Anterior: Growth hormone (by somatotropin)
-prolactin (by lactotropon)
-ACTH (by corticotroph)
-TSH (by thyrotrophin)
-LH, FSH (by gonadotropin)
Posterior: oxytocin and ADH
what is growth hormone
-secreted by acidophilic cells in pituitary
-peptide hormone( 21.4K DA single-chain polypeptide, 190AA with 2 disulphide bridges)
-stored in cells as granules
-increase glucogenesis, increase protein synthesis, increase lipolysis
-increase cell size, cell division and skeletal growth
what factors affect levels of GH
-blood glucose
-free fatty acid
-sleep
-exercise
what are growth hormone disorders
Dwarfism: low GH
-can be acquired or congenital
symptoms: low blood sugar, anxiety, osteoporosis, poor muscular tone
treatment: hormone replacement (somatotrpin)
Acromegaly: High GH (hypertension, diabetes, arthritis)
Treatment: surgery, radiation, drugs
Octreotide: slows down GH release (monthly injection)
Pevgisomant: GH receptor antagonist (symptoms)
Bromocriptine: D receptor agonis (stop GH production)
what is cortisol (corticosteroid)
- ACTH stimulates adrenal gland to release cortisol
- steroid hormone
-increase glucogenesis, protein breakdown and lipolysis
-anti-inflammatory effect: increase lipocortin which inhibits COX and phospholipase A2 so decrease prostaglandin and thromboxane (also downregulates anti-inflammatory genes)
-immunosuppressive effect: inhibits humoral factor, suppress immune cell’s maturation, differentiation, proliferation
-sleep wake cycle: high in the morning, low at night
-stress response
what is Crushing syndrome
-high cortisol levels
-obesity, high glucose, high androgen levels, diabetes, depression, sleep disturbances, osteoporosis, susceptibility to infections, CNS irritability
-causes: 80% secondary tumor (pituitary), 10%primary
treatment: secondary-surgery, radiation
primary: metyrapone: CYP11B1 inhibitor
(reduction of conversion 11-deoxycortisol to cortisol)
ketoconazole: CYP17A1 inhibitor
(blocks biosynthesis of cortisol, aldosterone and adrogens)
what is Addison disease
-not producing adrenal hormones
-autoimmune disease
symptoms: hair loss, blurred vision, abdominal pain, decreased appetite, darkening of skin, hypoglycemia)
what are aldosterone disorders
-hypoaldosteronism: enzyme deficiency
(hyponatremia, hypovolemia, hyperkalemia)
-conn’s syndrome: hyperaldosteronism
(hypernatremia, hypertension, hypokalemia
what does thyroid do?
-increases basal metabolic rate
-control metabolism of carbs, fat, proteins
-maintenance of water and electrolyte balance
-regulation of plasma calcium
-work with GH to stimulate bone growth
-maturation of brain during prenatal period
-affects memory, mood, sleepiness, speech
-affects fertility, ovulation and menstruation
how is thyroid produced
- TRH is released from hypothalamus
-TSH is released from pituitary
-thyroid follicular cells synthesize thyroglobulin (enters follicular lumen through exocytosis)
-iodine uptake
-thyrocytes uptake iodinated thyroglobulin
-lysosome fuse with endosome containing iodinated thyroglobulin
-proteolytic enzymes cleave thyroglobulin into MIT, T3, T4
-T3 and T4 are released into capillaries by MCT8 transporter
-deionised enzymes remove iodine from MIT and DIT
what is thyroid receptor
-nuclear TH receptor
-ligand-inducible transcription factor
-two classes (α and β)
-T4 is converted to T3 by D1/D2
-T3 binding to the ligand-binding domain results in movement of carboxyterminal helix 12
-promotes coactivator binding
-recruitment of polymerase III and onset of gene trascription
what are the symptoms of hypothyroidism and hyperthyroidism
Hypothyroidism: cold intolerance, weight gain, slow heart rate, depression, constipation, muscle pain
Hyperthyroidism: weight loss or gain, increased sweating, anxiety, racing heart, diarrhea, muscle weakness, heat intolerance, increased appetite
both: insomnia and hair loss
What is thyrotoxicosis and what are the causes
-excess thyroid hormone
-increased metabolic rate and appetite
-nervousness, sweaty, tachycardia, tremor, wide stare
Causes:
Hyperthyroidism: grave’s disease (autoimmune)
goiter, iodine-induced hyperthyroidism, pituitary tumor
Thyrotoxicosis: autoimmune thyroiditis or drug-induced thyroiditis (amiodarone, lithium, interferon, tyrosine kinase inhibitors)
-exogenous thyroid hormone
what is the treatment of hyperthyroidism
-oral carbimazole, methimazole, propylthiouracil
(inhibition of iodide oxidation, inhibition of iodination of tyrosine, inhibition of coupling of iodotyrosines)
-iodides
-b-blockers: propanolol or atenolol (symptom relief)
what is a thyroid storm and how is it managed?
-large amounts of thyroid suddenly (infection or surgery)
-palpitations, tachycardia, tremor, vomiting, seizures, confusion
-treatment: potassium iodide, carbimazole, rehydration, B-blockers steroids
what causes hypothyroidism and how is it managed?
causes: autoimmune thyroiditis (Hashimoto’s disease)
congenital dysfunction, iodine deficiency, thyrotoxycosis
Treatment: replacement (levothyroxine sodium)
what is osteoporosis and what is the pathophysiology
-low bone mass
-abnormal bone architecture
-reduced bone streght
T-score< -2.5 (bone mineral density)
-imbalance in bone remodeling and formation by osteoclasts and osteoblasts
what are the risk factors of osteoporosis
-endocrine disease
-GI conditions
-chronic diseases
-menopause
-immobility
-age
drugs( oral corticosteroids, PPIs, SSRIs, carbamazepine, heparin, methotrexate, antiretrovirals)
-alcohol
-rheumatoid arthritis
how to assess osteoporosis
-Qfracture risk:
High risk (>10%): offer drugs treatment and DEXA
Intermidiate: DEXA for BMD measurment
Low risk: lifestyle advice (healthy diet, calcium intake, VitD, exercise, smocking, less alcohol, low BMI)
what is the drug treatment of osteoporosis
-Bisphosphonates: inhibit bone resorption (increase BMD)
-denosumab: inhibit osteoclasts (6 month injection)
*calcium levels corrected first
-Teriparatide: menopausal women, high risk men or corticosteroid-induced osteoporosis
-romosozumab: inhibit sclerosin, decreases resorption
*CVD effects, stroke, hypocalcaemia (caution)
- Raloxifene: selective oestrogen receptor modulator
when should steroids be withdrawn gradually
-receive more than 40mg prednisolone daily for more than 1 week
-been given repeat doses in the evening
-received more than 3 week treatment
-recently taken repeated doses (more than 3 weeks)
-taken a short course within a year after stopping long term course
-other possible causes of adrenal suppression
