--- module: 023-01 language: en chapter: 23 title: "Hypothalamic-Pituitary Control and Endocrine Feedback" module_title: "Foundations" source_sha256: 515b35431b6db8672ab382f7eedf09986c7fdb497d1b1749bc9d38b85db02130 --- # Hypothalamic-pituitary control and endocrine feedback ## Hormones, classes, and binding ### Level reflects secretion, binding, metabolism, clearance #### Not gland activity alone ### Peptides: precursors, vesicles, exocytosis #### Membrane receptors and second messengers ### Steroids: from cholesterol, made on demand #### Protein-bound, intracellular receptors, transcription ### Thyroid hormones act through nuclear receptors ### Catecholamines act through surface receptors ### Only unbound hormone reaches tissues #### Binding changes alter total, not free activity #### Pregnancy, oestrogen, liver disease, protein loss ## Feedback, rhythms, and dynamic testing ### Releasing hormone, trophic hormone, peripheral gland ### Primary failure: low target, high trophic ### Central failure: low target, low or normal trophic ### Autonomous secretion suppresses upstream signals ### Pulsatile and circadian secretion #### Gonadotropin-releasing hormone must be intermittent #### Continuous exposure suppresses the axis #### Cortisol peaks near waking, falls at midnight ### A single value can mislead ### Suppression tests: can autonomy be restrained ### Stimulation tests: can reserve respond ## Hypothalamus and anterior pituitary ### Regulatory peptides enter portal circulation ### Releasing hormones drive trophic hormones ### Somatostatin inhibits growth and thyroid-stimulating hormones ### Dopamine tonically inhibits prolactin ### Masses secrete, compress, or both #### Upward: optic chiasm, temporal fields #### Lateral: ocular motor nerves, sympathetic fibres ### Tumour haemorrhage or infarction #### Headache, visual loss, ophthalmoplegia #### Acute adrenal insufficiency ## Posterior pituitary and water balance ### Vasopressin made in hypothalamic nuclei ### Stimuli: rising osmolality, volume depletion ### V2 receptors insert aquaporins ### Diabetes insipidus: large dilute urine volumes #### Hypernatraemic dehydration without water access #### Central responds to desmopressin #### Nephrogenic: correct cause, reduce solute load #### Primary polydipsia can mimic ### Inappropriate antidiuresis #### Low sodium, concentrated urine #### Rapid correction risks osmotic demyelination ## Growth hormone ### Linear growth via insulin-like growth factor one ### Direct lipolysis and insulin resistance ### Insulin-like growth factor one integrates secretion ### Excess: gigantism before closure, acromegaly after #### Glucose fails to suppress growth hormone ### Deficiency: poor growth, reduced lean mass #### Random value unhelpful, stimulation testing ## Prolactin ### Suckling reduces dopamine, raises prolactin ### Falling sex steroids permit lactation ### High prolactin suppresses gonadotropin-releasing hormone #### Infertility, sexual dysfunction, bone loss #### Galactorrhoea neither required nor specific ### Causes: tumour, stalk, drugs, hypothyroidism ### Repeat mild rise, check macroprolactin ### Dopamine agonists shrink prolactinomas ### Distinguish tumour from drug or stalk effect ## Hypopituitarism ### Tumours, surgery, radiation, postpartum haemorrhage ### Deficits emerge gradually, variable order ### Adrenocorticotropic deficiency immediately dangerous #### Aldosterone kept by renin-angiotensin system ### Replace cortisol before thyroid hormone #### Thyroid first can precipitate crisis ## Functional pituitary tumours ### Adrenocorticotropic tumours: pituitary cortisol excess ### Thyroid-stimulating tumours: central hyperthyroidism ### Gonadotroph tumours often non-functioning ### Surgery, drugs, radiotherapy, replacement ### Long-term surveillance for late change ## Investigation in practice ### Start from phenotype and medicines ### Measure target with controlling hormone ### Repeat surprising results ### Imaging follows biochemistry #### Incidental lesions do not prove secretion ### Urgent: vision, apoplexy, sodium, adrenal crisis