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1
Basic biochemical examination in endocrinology
Zdislava Vaníčková
2005/06
Diabetes mellitus
Endocrinology of reproduction
Endocrinology
Hormones - definitionHormoness are endogenous substances produced by specializeded cells
Secretion: continuous (thyroid hormones)with diurnal rhythm (cortisol)with monatial rhythm (menstrual cycle)seasonal rhythm
Hormones - typesProteohormones and peptides
Steroid hormones
Low molecular weight hormones derived from modified amino acids
Prostanoids
Autocrine
Paracrine
Endocrine
(Neurocrine)
Action of hormones
hypothalamus
pituitary gland
target organ
HRH
RH
H
-
-
-
Endocrinopathies
States hyperfunctionhypofunctiondysfunction
Diseases primar (periferal)secundar (central)
Diabetes mellitus
2
DM definitionWHO 1985
Status characterized by chronic elevation of blood glucose, that could be connected with clinical syndromes and could lead to death without proper care.
Langerhans islets B (beta) cells
70%Produce insulin
InsulinMen and other mammals1 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 pregnancy)Secretion decreased: fats, sympaticus action, somatostatin, adrenalin
Insulin
C peptid
PREPROINSULIN
PROINSULIN
INSULIN
Insulin
dE
Daily production:40-50 units(15-20% of pancreatic depot)50% basal secretion50% postprandial secretion
Plasmatic halftime:3-5 minutes, no transport protein
First-pass effect:50% used during firs passage through liver
C peptidFunction unknown
Variable lengths
Used as marker of endogenous insulin production (produced in equimolar proportion, can be used in patients on insulin therapy as well)
No first-pass effect
Insulin like growth factors
IGF-I70 AMK
IGF-II67 AMK
62 % homology (IGF-I and IGF-II)50 % homology with insulin
More stimulate growth than insulinHave less metabolic effect than insulin
A (alpha) cells25%Produce glucagon
3
Glucagon29 amino acids
Synthetized as proglukagon
Plasmatic halftime 5 minutes
No transport protein
Inactivation in liver
Glucagon
Enhances
glycogenolysislipolysisgluuconeogenesisketogenesis
Receptors mainly in liver
D (delta) cells5%Produce somatostatin
Somatostatincyclic 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 cellsRare
Produce pancreatic polypeptid
Peptid, 36 amino acids
Unknown function
Other hormonesTRH
Beta-endorfin
CRH-like peptid
Pancreastatin
Blood glucose regulation
- + INSULIN GLUCAGONglucagon like peptid catecholaminsutilization in CNS glucocorticoidesMuscle work growth hormone
Blood glucose regulation
- + INSULIN GLUCAGONglucagon like peptide catecholaminsutilization in CNS glucocorticoidesMuscle work growth hormon
FOOD INTAKE
DM diagnosisFasting glycemia (venous and capillary blood)
<6 mmol/l no DM6,1-7,0 mmol/l impaired fasting glycemia>7 mmol/l DM present
Glycemia in random sample
Several times >10mmol/l DM present
4
OGTT (oral glucose tolerance test)
75 g of glucose in 400 ml water (tea)
Measurement at time 0 and 120 min (60 min and 180 min sometimes added)
6,7
0 60 120
NORMAL
DM diagnosis
6,7
0 60 120
10
repeat OGTTevery 2-3 years
OGTT
Impaired glucose tolerance
DM diagnosis
6,7
0 60 120
10
DM
OGTT
DM diagnosis
DM
6,7
10
Insulinsensitivity
Insulinsecretion glycemia
8-10 years
Hypoglycemia3,5 mmol/l
3,3 mmol/l contra regulation starts
higher katecholamines, corticoids, glukagon, thyroidal hormones, growth hormon
first clinical signs
2,8 mmol/l neuroglycopenia
Hypoglycemic coma
Hyperglycemic coma
Lab: haemoconcentration hyperglycemia ketonemia metabolic acidosis and hypokalemia
Hyperosmolar comaLab: hyperglycaemia
hyperosmolarity
Lab tests in DM
BLOOD GLUCOSEfastingrandomoral glucose tolerance test (OGTT)glycemic profile
GLYCATED HAEMOGLOBIN, PEPTIDES, AGEs
INSULIN, C PEPTID, anti-GAD antibodies, antibodies againstinsulin, antibodies against B cells
5
Reference values < 3,8 mmol/l hypoglycemia> 7,8 mmol/l hyperglycemia
Glucose haemoglobin glycationHC=O HC=N-ß CH2-NH-ß| | |
HCOH HCOH C=O| | |
HOCH HOCH HOCHß-NH2 + | | |
HCOH rychle HCOH pomalu HCOH| | |
HCOH HCOH HCOH| | |CH2OH CH2OH CH2OH
Aldimin Ketoamin(labile HbA1c) (stabile HbA1c)
Haemoglobin and derivates
Subunits present sugar content
HbA0 α2ß2 - > 90% HbA2 α2δ2 - 2%
HbF α2γ2 - 0.5%
HbA1a1 α2(ß-F-D-P)2 Fructose-1,6-diphosphate <1%
HbA1a2 α2(ß-G-6-P)2 Glucoss-6-phosphate
<1%
HbA1b ? ? <1% HbA1c α2(ß-G)2 Glucose <4% HbA1d ? ? traces HbA1e ? ? traces
Haemoglobin - types
> 6,0 % bad
4,5 – 6,0 % good
< 4,5 % excellent
Values given by IFCC applicable from 1. 1. 2004 DM compensation
Reference values 2,8 – 4,0 % (95 % interval)
Haemoglobin A1c Nonenzymatic bond of glucose to proteins in tissues (collagen…) and DNA
AGE = advanced glycation end products
AGEs
Endocrinology of reproduction
Female hormonal system
Gonadotropic hormones
FSH
LH
prolactin
Gonadotropic hormones
FSH
function: follicles growth, stimulation of estrogens secretion
structure: proteohormon, 207 amino acids, subunits alpha a beta
Lab assessment: RIA, EIA
Female hormonal system
Gonadotropic hormones
LH
function: peak precedes ovulation, afterwards stimulation of both estrogen and gestagen secretion
structure: proteohormon, 205 amino acids, alpha and beta subunits
lab: immunochemistry
Female hormonal system
6
Gonadotropic hormones
prolaktin
function: mainly milk production, acts also on ovaries
structure: proteohormon, 198 amino acids, 1band
lab: immunochemistry
Female hormonal system
Native estrogens
structure: 18C steroidsaromatic A circle
lab: immunochemistry
Female hormonal system
Native estrogens
Female hormonal system
Native gestagens
structure: 21C steroids
Lab: immunochemistry
Female hormonal system
Native gestagens
Female hormonal system
Androgens
female: ovary and suprarenals(male: testes and suprarenals)
Structure: 19C steroids
testosteronandrostendiondehydroepiandrostendion
Female hormonal system
Menstrual cyclePregnancy
EPF – early pregnancy factor
Produced by the ovary gland
First pregnancy marker, 48 hours
Immunosuppressive
No routine method
Female hormonal system -pregnancy
7
hCG
Glycoprotein, 2 subunits: alpha (92) and beta (145)
detectable 8-11 day
Concentration doubles every two days
Female hormonal system -pregnancy
Female hormonal system -pregnancy
Weeks of pregnancy
HPL – human placental lactogen
Polypeptid, 191 amino acids
Female hormonal system -pregnancy
Weeks of pregnancy
PAPP A-D pregnancy associated plasma proteins
SP1 pregnancy specific protein
Female hormonal system -pregnancy Infertility
15-20% couples
Causes female 50%male 40%unclear 10%
Start testing after 12 (18) months
examinationmale: Spermiogram, (androgens)
female:Sonography several times in one menstrual cycle
Lab: FSH any time
(hypo- resp. hypergonadotropic status)
LH 3-5 day of cyclebasal secretion
Lab (cont.):
Estradiol older marker, useful without sono
Progesteron middle of the luteal phase
Prolactin 3-5 dayhyperprolactinemia leads to anovulation
examination Hyperandrogenic syndrome= HAS, syndrome of polycystic ovaries
Most common endocrinopathy in fertile age women
17-33 % women
Basic criterion: increased androgens level
Ethiology not known
Familial
Examination:
Androgens
Gonadotropins (LH and FSH, LH/FSH ratio)
SHBG
Hyperandrogenic syndrome