Endocrinology of reproduction

Transcription

1 Basic biochemical examination in endocrinology Zdislava Vaníčková Endocrinology Diabetes mellitus Endocrinology of reproduction 2005/06 Hormones - definition Hormoness are endogenous substances produced by specializeded cells Hormones - types Proteohormones and peptides Steroid hormones Secretion: continuous (thyroid hormones) with diurnal rhythm (cortisol) with monatial rhythm (menstrual cycle) seasonal rhythm Endocrine Prostanoids (Neurocrine) Endocrinopathies - HRH States hyperfunction hypofunction dysfunction Diseases primar (periferal) secundar (central) pituitary gland RH Paracrine Low molecular weight hormones derived from modified amino acids hypothalamus - Action of hormones Autocrine Diabetes mellitus target organ H 1

2 DM definition Langerhans islets B (beta) cells WHO 1985 Status characterized by chronic elevation of blood glucose, that could be connected with clinical syndromes and could lead to death without proper care. 70% Produce insulin Men and other mammals 1 gen on chromosome 11 (rodents, 2 genes) 51 AMK, 2 strands Homology between species high: pig, dog, hare 1 AMK; cow 3 AMK; sheep, horse 4 AMK. Secretion increased: elevation of blood sugar, aminoacids, parasympaticus system action, glukagon, glucocorticoides, growth hormone, placental lactogen,estrogenes, gestagenes (during ) Secretion decreased: fats, sympaticus action, somatostatin, adrenalin PREPROINSULIN PROINSULIN INSULIN C peptid Daily production: d units (15-20% E of pancreatic depot) 50% basal secretion 50% postprandial secretion Plasmatic halftime: 3-5 minutes, no transport protein First-pass effect: 50% used during firs passage through liver Function unknown Variable lengths C peptid IGF-I 70 AMK like growth factors 62 % homology (IGF-I and IGF-II) 50 % homology with insulin 25% Produce glucagon A (alpha) cells Used as marker of endogenous insulin production (produced in equimolar proportion, can be used in patients on insulin therapy as well) IGF-II 67 AMK More stimulate growth than insulin Have less metabolic effect than insulin No first-pass effect 2

3 Glucagon 29 amino acids Synthetized as proglukagon Plasmatic halftime 5 minutes No transport protein Inactivation in liver Enhances glycogenolysis lipolysis gluuconeogenesis ketogenesis Receptors mainly in liver Glucagon 5% Produce somatostatin D (delta) cells Somatostatin cyclic peptide, 14 amino acids in CNS neurotransmitter function synthesized also in other places in GIT Inhibition of insulin and glucagon secretion Slowers gastric emptying, lowers gastrin secretion, pancreatic exocrine secretion, F cells Rare Produce pancreatic polypeptid Peptid, 36 amino acids Unknown function TRH Beta-endorfin CRH-like peptid Pancreastatin Other hormones Blood glucose regulation - + INSULIN GLUCAGON glucagon like peptid catecholamins utilization in CNS glucocorticoides Muscle work growth hormone Blood glucose regulation - + INSULIN glucagon like peptide utilization in CNS Muscle work GLUCAGON catecholamins glucocorticoides growth hormon FOOD INTAKE DM diagnosis Fasting glycemia (venous and capillary blood) <6 mmol/l no DM 6,1-7,0 mmol/l impaired fasting glycemia >7 mmol/l DM present Glycemia in random sample Several times >10mmol/l DM present 3

4 DM diagnosis DM diagnosis DM diagnosis OGTT (oral glucose tolerance test) 75 g of glucose in 400 ml water (tea) OGTT Impaired glucose tolerance OGTT Measurement at time 0 and 120 min (60 min and 180 min sometimes added) ,7 NORMAL 6,7 6,7 DM repeat OGTT every 2-3 years DM 3,5 mmol/l Hypoglycemia Hypoglycemic coma secretion glycemia 10 3,3 mmol/l contra regulation starts 6, years sensitivity higher katecholamines, corticoids, glukagon, thyroidal hormones, growth hormon first clinical signs 2,8 mmol/l neuroglycopenia Lab: Hyperglycemic coma haemoconcentration hyperglycemia ketonemia metabolic acidosis and hypokalemia Lab: Hyperosmolar coma hyperglycaemia hyperosmolarity Lab tests in DM BLOOD GLUCOSE fasting random oral glucose tolerance test (OGTT) glycemic profile GLYCATED HAEMOGLOBIN, PEPTIDES, AGEs INSULIN, C PEPTID, anti-gad antibodies, antibodies against insulin, antibodies against B cells 4

5 Glucose haemoglobin glycation HC=O Reference values < 3,8 mmol/l hypoglycemia > 7,8 mmol/l hyperglycemia ß-NH2 + HC=N-ß C=O HOCH HOCH HOCH rychle pomalu CH2OH CH2OH CH2OH Aldimin (labile HbA1c) Haemoglobin A1c excellent Haemoglobin and derivates Subunits present sugar content HbA0 α 2 ß2 - > 90% HbA2 α2δ2 α2γ2-2% 0.5% <1% HbF Ketoamin (stabile HbA1c) HbA1a1 α2(ß-f-d-p)2 HbA1a2 α2(ß-g-6-p)2 HbA1b Fructose-1,6diphosphate Glucoss-6phosphate HbA1c HbA1d α2(ß-g)2 Glucose <4% traces HbA1e traces <1% <1% AGEs Nonenzymatic bond of glucose to proteins in tissues (collagen ) and DNA Reference values 2,8 4,0 % (95 % interval) DM compensation Haemoglobin - types CH2-NH-ß AGE = advanced glycation end products Endocrinology of reproduction Values given by IFCC applicable from < 4,5 % good 4,5 6,0 % bad > 6,0 % Gonadotropic hormones Gonadotropic hormones Gonadotropic hormones FSH FSH LH LH function: follicles growth, stimulation of estrogens secretion function: peak precedes ovulation, afterwards stimulation of both estrogen and gestagen secretion structure: proteohormon, 207 amino acids, subunits alpha a beta structure: proteohormon, 205 amino acids, alpha and beta subunits lab: immunochemistry prolactin Lab assessment: RIA, EIA 5

6 Gonadotropic hormones Native estrogens Native estrogens prolaktin function: structure: lab: mainly milk production, acts also on ovaries proteohormon, 198 amino acids, 1band immunochemistry structure: 18C steroids aromatic A circle lab: immunochemistry Native gestagens structure: 21C steroids Lab: immunochemistry Native gestagens Androgens female: ovary and suprarenals (male: testes and suprarenals) Structure: 19C steroids testosteron androstendion dehydroepiandrostendion Menstrual cycle Pregnancy - EPF early factor Produced by the ovary gland First marker, 48 hours Immunosuppressive No routine method 6

7 - hcg Glycoprotein, 2 subunits: alpha (92) and beta (145) detectable 8-11 day - - HPL human placental lactogen Polypeptid, 191 amino acids Concentration doubles every two days Weeks of Weeks of - PAPP A-D SP1 associated plasma proteins specific protein Infertility 15-20% couples Causes female 50% male 40% unclear 10% Start testing after 12 (18) months examination male: Spermiogram, (androgens) female: Sonography several times in one menstrual cycle Lab: FSH LH any time (hypo- resp. hypergonadotropic status) 3-5 day of cycle basal secretion examination Hyperandrogenic syndrome Hyperandrogenic syndrome Lab (cont.): Estradiol Progesteron Prolactin older marker, useful without sono middle of the luteal phase 3-5 day hyperprolactinemia leads to anovulation = HAS, syndrome of polycystic ovaries Most common endocrinopathy in fertile age women % women Basic criterion: increased androgens level Ethiology not known Examination: Androgens Gonadotropins (LH and FSH, LH/FSH ratio) SHBG Familial 7

8 Literature Bureš: Základy vnitřního lékařství, Galén, 2003 Harperova biochemie, HaH, 2002 Cibula: Základy gynekologické endokrinologie, Grada, 2002 Stárka: Endokrinologie, Maxdorf, 1997 Rabe: Memorix Gynekologie, Scientia Medica,