Endocrine system overview
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1 Endocrine system overview Nature of the hormonal system -Major integrator of body function Classification of hormones Endocrine vs paracrine Nature of hormone-receptor systems Role of the hypothalamuspituitary system and feedback
2 Endocrine system overview Nature of the hormonal system Co-ordinated with nervous system - eg.adrenergic systems, brain/gut hormones Notion of secretory vs target organ Feedback critical Central regulator
3 Endocrine system overview Nature of the hormonal system Co-ordinated with nervous system - eg.adrenergic systems, brain/gut hormones Notion of secretory vs target organ Feedback critical Central regulator
4 Endocrine system overview Nature of the hormonal system Co-ordinated with nervous system - eg.adrenergic systems, brain/gut hormones Notion of secretory vs target organ Feedback critical Central regulator
5 Endocrine system overview Nature of the hormonal system Co-ordinated with nervous system - eg.adrenergic systems, brain/gut hormones Notion of secretory vs target organ Feedback critical Central regulator
6 Classification of hormones Peptide Steroid Amine Eicosanoid
7 Classification of hormones (2) Steroid hormones Cholesterol-derived: eg. cortisol, sex steroids aldosterone Thyroid hormones
8 Steroid Hormones Cholesterolderived: eg. cortisol, sex steroids aldosterone
9 Peptide Hormones Somatostatin, GnRH, GRF, GHRP, CRF, TRH GH, ACTH, TSH, FSH, LH, Prolactin, ADH Insulin, glucagon, IGF PTH, calcitonin
10 Endocrine system overview Endocrine vs paracrine Circulating versus local Role of pulsatility Role of binding proteins
11 Endocrine system overview Endocrine vs paracrine Circulating versus local Role of pulsatility Role of binding proteins
12 Endocrine system overview Endocrine vs paracrine Circulating versus local Role of pulsatility IGFBP-3:mechanisms of action Role of binding proteins? MULTIFUNCTIONAL
13 Hormone-receptor systems - Steroid vs Peptide ie. Lipid-soluble vs lipid-insoluble
14 Steroid Receptor System:
15 Peptide receptor systems Cell membrane receptors Seven transmembrane/g-protein/camp Cytokine receptors - jak-stat Insulin/IGF - tyrosine kinase
16 Hypothalamic-pituitary system Conductor of endocrine symphony
17 Hypothalamic-pituitary system The Role of feedback
18 Hypothalamic-pituitary system Role of releasing factors Review of hormones GH TSH/T4 FSH/LH ACTH ADH
19 Hypothalamic-pituitary hormones
20 GH-IGF system
21 GnRH-LH/FSH-Sex steroids Inhibin
22 TRH/TSH-Thyroid system
23 Hypothalamic-pituitary system CRF---> ACTH---> Cortisol (adrenal gland) Negative feedback
24 Hypopituitarism Pituitary insufficiency Congenital Acquired Maldevelopment Homeobox genes - Pit1 (GH,TSH. PRL), Prop1(+LH/FSH) Tumour (craniopharyngioma), trauma, infection, DXRT (via hypothalmus)
25 Hypopituitarism Pituitary Hormone loss order (Teleologic) (usually hypothalamic damage) Growth hormone Gonadotrophins Thyroxine ACTH Note: Prolactin negatively regulated elevated if hypothalamic damage
26 CRANIOPHARYNGIOMA
27 Craniopharyngioma - Presenting features Growth failure - 93% Visual disturbance - 71% Headache - 50% Hypothyroid - 42% Cortisol deficient - 24% Diabetes Insipidus 23%
28 Craniopharyngioma - Hormone deficits PRE-OP GH: 75% Thyroxine: 25% FSH/LH: 40-80% ACTH/Cortisol:25% ADH: 10-25% POST-OP GH: % Thyroxine: 65% FSH/LH: 80% ACTH: 65% ADH: 80% Sklar: Ped Neurosurg 21 Suppl Lyen and Grant: Arch dis Child 11:
29 Craniopharyngioma - Fluid Disturbances Diabetes insipidus versus adipsia: Note triple reponse Damage to OVLT in floor of 3rd ventricle leads to loss of thirst Usually combined with Diabetes Insipidus Needs strict fluid intake plus DDAVP
30 Craniopharyngioma - Growth +/- GH Linear growth often continues normally despite absence of GH secretion IGF-I levels may be normal Usually associated with obesity - ie. nutritional overregulation of IGF-I
31 Diagnosing Hypopituitarism Clinical suspicion growth, puberty, thyroid, energy, fluids Investigation: Non-provocative TFT (note TSH unhelpful) Prolactin (hypothalamic damage) FSH/LH if low may be normal Provocative (pulsatile hormones) (ensure euthyroid) GH, ACTH (via cortisol) exercise/glucagon etc ADH water deprivation Serum osmo >300 or urine >700
32 Managing Hypopituitarism Hypothyroidism T4 full replacement ACTH deficiency Hydrocortisone 50% of maintenance (half of 10-15mg/m2) why? GH deficiency - if growing slowly daily GH Delayed puberty Testosterone or Oestrogen Diabetes Insipidus DDAVP 0.05ml bd
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