* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Assessing endocrine function
Survey
Document related concepts
Hormonal contraception wikipedia , lookup
Neuroendocrine tumor wikipedia , lookup
Menstrual cycle wikipedia , lookup
Breast development wikipedia , lookup
Xenoestrogen wikipedia , lookup
Triclocarban wikipedia , lookup
Adrenal gland wikipedia , lookup
Bioidentical hormone replacement therapy wikipedia , lookup
Hormone replacement therapy (menopause) wikipedia , lookup
Hormone replacement therapy (male-to-female) wikipedia , lookup
Hyperandrogenism wikipedia , lookup
Hyperthyroidism wikipedia , lookup
Transcript
Endo 1.06 Investigation and assessment of endocrine disease • Measuring hormones - bioassays, radioimmunoassays, IRMAs and ELISAs • Measuring ‘free’ thyroxine and thyroid hormone antibodies • Negative feedback and interpreting results • Dynamic tests of endocrine function • Pituitary function tests • Dexamethasone suppression test • Insulin induced hypoglycaemia for GH stimulation Assessing endocrine function • Bioassays • Radioimmunoassays • IRMA’s Antibodies • ELISA’s • Protein binding assays • Receptor assays Bioassays? Pan-hypopitutarism - presumed autoimmune Cushing’s syndrome Bioassay of LH by measuring its ability to stimulate testosterone secretion in Leydig cells of the testis H + Ab H . Ab H*. Ab H* Concentration of radioactivity [ H*] is inversely proportional to the concentration of the unlabled hormone in the sample or standard Radioimmunoassay - competitive binding unlabelled hormone AB labelled hormone Immuno-radiometric assay (IRMA) double antibody hormone Radioactive label Enzyme linked immunoabsorbant assay (ELISA) hormone ENZYME + substrate colour intensity radioactivity % bound radioactivity Standard curves for different competitive binding assays hormone conc. RIA hormone conc. hormone conc. IRMA ELISA Bound versus free hormones An equilbrium exists between bound and free hormone. H + BG H.BG Keq = [H.BG] (H bound) [H] [BG] (H free) [H] = [H.BG] x 1 Keq [BG] Changes in binding proteins alter concentration of total and free hormone Does ratio change in capillary bed? Measuring ‘free’ T4 Phosphate 1) Add serum sample or standard (T4 ) to latex beads coated with Abs 2) Add T4 labelled with alkaline phosphatase. This will bind to any unoccupied Ab binding sites 3) Add a substrate that will fluoresce when the alkaline phosphatase removes a phosphate group 4) Fluorescent intensity will be inversely proportional to the concentration of T4 Graves’ disease measuring antibodies Patient’s serum (IgG) Thyroid growth TSH receptors (porcine) I125-TSH (bovine) Assay of antibodies to the human TSH receptors Patients serum Add 125I-TSH + TSH receptors (bovine) (porcine) Precipitate Count Feedback control of the H-P axis External stimuli Feed back HYPOTHALAMUS 3o PITUITARY GLAND 2o EFFECTOR ORGAN 1o Endocrine disorders • 1o excess: low trophic hormone • 1o deficiency: high trophic hormone • 2o excess: high trophic hormone and hormones of target gland • 2o deficiency: low trophic hormone and hormones of the target gland • 3o deficiency: also low trophic hormone and hormones of the target gland Pituitary function tests Hypothalamus Feed back Injection of releasing hormone PITUITARY GLAND Measure trophic hormone hypo 1o High basal response Low basal hyper 1o response Pituitary function tests Hypothalamus Feed back Bolus injection of releasing hormone PITUITARY GLAND Measure trophic hormone Low or absent response 2o Pituitary function tests Hypothalamus 3o Feed back Bolus injection of releasing hormone PITUITARY GLAND Measure trophic hormone No response or delayed peak response (60 mins vs 20 mins) Feedback control of thyroid hormone synthesis and release Measuring trophic hormones and hormones of the peripheral endocrine gland High TSH - Low T3/T4 1o Hypothyroidism Low TSH - High T3/T4 1o Hyperthyroidism Low TSH - Low T3/T4 2o Hypothyroidism Other signs and symtoms usually determine whether primary (1o) or secondary (2o) e.g. goitre Dynamic tests of endocrine function • Hyperfunction of an endocrine organ - suppresion tests • Hypofunction of an endocrine organ - stimulation tests Examples of dynamic tests of endocrine function • Pituitary function tests • Dexamethasone suppression test • Insulin stimulation of GH Hypofunction of an endocrine organ - stimulation tests Example of a pituitary function test The ACTH response to a bolus injection of CRH is measured The grey shaded area shows the range of responses measured in control subjects In hypopituitarism there is no response In primary hypoadrenalism there is no feedback and basal ACTH concentrations are high Hyperfunction of an organ suppression test Circadian rhythm of cortisol secretion The dexamethasone suppression test. In a normal person dexamethasone will suppress ACTH secretion (feedback) and cortisol production is consequently reduced. In pituitary- dependent Cushings only high doses may suppress ACTH secretion Hypofunction of an endocrine organ - stimulation tests Insulin induced hypoglycaemia to investigate suspected GH deficiency. Insulin decreases plasma glucose concentrations and in a normal person this stimulates the release of GH (A) A reduced or absent response is seen in a GH deficient patient (B)