Endocrine system overview - PDF Free Download

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

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

Classification of hormones Peptide Steroid Amine Eicosanoid

Classification of hormones (2) Steroid hormones Cholesterol-derived: eg. cortisol, sex steroids aldosterone Thyroid hormones

Steroid Hormones Cholesterolderived: eg. cortisol, sex steroids aldosterone

Peptide Hormones Somatostatin, GnRH, GRF, GHRP, CRF, TRH GH, ACTH, TSH, FSH, LH, Prolactin, ADH Insulin, glucagon, IGF PTH, calcitonin

Endocrine system overview Endocrine vs paracrine Circulating versus local Role of pulsatility Role of binding proteins

Endocrine system overview Endocrine vs paracrine Circulating versus local Role of pulsatility IGFBP-3:mechanisms of action Role of binding proteins? MULTIFUNCTIONAL

Hormone-receptor systems - Steroid vs Peptide ie. Lipid-soluble vs lipid-insoluble

Steroid Receptor System:

Peptide receptor systems Cell membrane receptors Seven transmembrane/g-protein/camp Cytokine receptors - jak-stat Insulin/IGF - tyrosine kinase

Hypothalamic-pituitary system Conductor of endocrine symphony

Hypothalamic-pituitary system The Role of feedback

Hypothalamic-pituitary system Role of releasing factors Review of hormones GH TSH/T4 FSH/LH ACTH ADH

Hypothalamic-pituitary hormones

GH-IGF system

GnRH-LH/FSH-Sex steroids Inhibin

TRH/TSH-Thyroid system

Hypothalamic-pituitary system CRF---> ACTH---> Cortisol (adrenal gland) Negative feedback

Hypopituitarism Pituitary insufficiency Congenital Acquired Maldevelopment Homeobox genes - Pit1 (GH,TSH. PRL), Prop1(+LH/FSH) Tumour (craniopharyngioma), trauma, infection, DXRT (via hypothalmus)

Hypopituitarism Pituitary Hormone loss order (Teleologic) (usually hypothalamic damage) Growth hormone Gonadotrophins Thyroxine ACTH Note: Prolactin negatively regulated elevated if hypothalamic damage

CRANIOPHARYNGIOMA

Craniopharyngioma - Presenting features Growth failure - 93% Visual disturbance - 71% Headache - 50% Hypothyroid - 42% Cortisol deficient - 24% Diabetes Insipidus 23%

Craniopharyngioma - Hormone deficits PRE-OP GH: 75% Thyroxine: 25% FSH/LH: 40-80% ACTH/Cortisol:25% ADH: 10-25% POST-OP GH: 80-100% Thyroxine: 65% FSH/LH: 80% ACTH: 65% ADH: 80% Sklar: Ped Neurosurg 21 Suppl 18-20.1994 Lyen and Grant: Arch dis Child 11:837.1982

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

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

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

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