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Basic biochemical examinationin endocrinologyZdislava Vaníčková2012

Diabetes mellitusEndocrinology of reproduction

Endocrinology

Hormones - definitionHormones are endogenous substances produced byspecializeded cellsSecretion:continuous (thyroid hormones)with diurnal rhythm (cortisol)with monatial rhythm (menstrual cycle hormones)seasonal rhythm (parathormon)

Hormones - typesProteohormones and peptidesSteroid hormonesLow molecular weight hormones derived from modified aminoacidsProstanoids

Action of hormonesAutocrineParacrineEndocrine

Diabetes mellitus

DM definitionWHO 1985Status characterized by chronic elevation of blood glucose,that could be connected with clinical syndromes and couldlead to death without proper care.

Langerhans islets

B (beta) cells70%Produce insulin

InsulinMen and other mammals1 gen on chromosome 11(rodents, 2 genes)51 AA, 2 strandsHomology between species high:pig, dog, hare 1 AA; cow 3 AA; sheep, horse 4 AA.Secretion increased: elevation of blood sugar, aminoacids,parasympaticus system action, glukagon, glucocorticoides,growth hormone, placental lactogen,estrogenes, gestagenes(during pregnancy)Secretion decreased: fats, sympaticus action, somatostatin,adrenalin

InsulinPREPROINSULINC peptidPROINSULININSULIN

InsulinDaily production:40-50 units(15-20% of pancreatic depot)50% basal secretion50% postprandial secretionPlasmatic halftime:3-5 minutes, no transport proteinFirst-pass effect:50% used during first passage through liver

C peptidFunction unknownVariable lengthUsed as marker of endogenous insulin production(produced in equimolar proportion, can be used in patientson insulin therapy as well)No first-pass effect

Insulin like growth factorsIGF-I70 AMKIGF-II67 AMK62 % homology (IGF-I and IGF-II)50 % homology with insulinMore stimulate growth than insulinHave less metabolic effect than insulin

A (alpha) cells25%Produce glucagon

Glucagon29 amino acidsSynthetized as proglukagonPlasmatic halftime 5 minutesNo transport proteinInactivation in liver

esisketogenesisReceptors mainly in liver

D (delta) cells5%Produce somatostatin

Somatostatincyclic peptide, 14 amino acidsin CNS – neurotransmitter functionsynthesized also in other places in GITInhibition of insulin and glucagon secretionSlowers gastric emptying, lowers gastrin secretion,pancreatic exocrine secretion,

Blood glucose regulationFOOD INTAKEINSULINglucagon like peptidutilization in CNSmuscle work GLUCAGONcatecholaminsglucocorticoidesgrowth hormone

Blood glucose regulationINSULINglucagon like peptidutilization in CNSMuscle work GLUCAGONcatecholaminsglucocorticoidesgrowth hormone

DM diagnosisFasting glycemia (venous and capillary blood) 5,6 mmol/l5,7-7,0 mmol/l 7 mmol/lno DMimpaired fasting glycemiaDM presentGlycemia in random sampleSeveral times 10mmol/lDM present

DM diagnosisOGTT (oral glucose tolerance test)75 g of glucose in 400 ml water (tea)Measurement at time 0 and 120 min (60 min and 180 minsometimes added)7.8NORMAL060120

DM diagnosisOGTTImpaired glucose tolerance11.17.8repeat OGTTevery 2-3 years060120

DM diagnosisOGTT11.17.7DM060120

DMInsulinsecretionglycemia11.17.78-10 yearsInsulinsensitivity

Lab tests in DMBLOOD GLUCOSEfastingrandomoral glucose tolerance test (OGTT)glycemic profileGLYCATED HAEMOGLOBIN, PEPTIDES, AGEsINSULIN, C PEPTID, anti-GAD antibodies, antibodies againstinsulin, antibodies against B cells (ICA, IA2)

haemoglobin glycationHC Oß-NH2 HCOH HOCH HCOHfast HCOH CH2OHHC N-ßCH2-NH-ß HCOHC O HOCHHOCH HCOH slow HCOH HCOHHCOH CH2OHCH2OHAldimin(labile HbA1c)Ketoamin(stabile HbA1c)

Haemoglobin - typesHaemoglobinand derivatesSubunitspresentsugarcontentHbA0α2ß2- hateGlucose-6phosphate? 1%Glucose 4%HbA1dα2(ß-G)2?tracesHbA1e?traces 1% 1%

Haemoglobin A1cReference values 28 – 40 (95 % interval)DM compensationexcellentValues given by IFCCapplicable from 1. 1. 2004 45good45 – 60bad 60

Endocrinology of reproduction

hypothalamusHRHpituitary glandRHtarget organH

Female hormonal systemGonadotropic hormonesFSHLHprolactin

Female hormonal systemGonadotropic hormonesFSHfunction:follicles growth, stimulation of estrogens secretionstructure:proteohormon, 207 amino acids,subunits alpha and betaLab assessment:immunoanalysis

Female hormonal systemGonadotropic hormonesLHfunction:peak preceedes ovulation, afterwardsstimulation of both estrogen and gestagensecretionstructure:proteohormon, 205 amino acids,alpha and beta subunitslab:immunoanalysis

Female hormonal systemGonadotropic hormonesprolaktinfunction:mainly milk production, acts also on ovariesstructure:proteohormon, 198 amino acids, 1bandlab:immunoanalysis

Female hormonal systemNative estrogensstructure:lab:18C steroidsaromatic A circleimmunochemistry

Female hormonal systemNative estrogens

Female hormonal systemNative gestagensstructure:21C steroidsLab: immunochemistry

Native gestagens

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Endocrinology of reproduction. hypothalamus pituitary gland HRH--target organ RH H-Female hormonal system Gonadotropic hormones FSH LH prolactin. Gonadotropic hormones FSH Female hormonal system function: follicles growth, stimulation of estr