--- module: 024-02 language: en chapter: 24 title: "Thyroid, Adrenal, Calcium, and Bone Physiology and Disease" module_title: "Endocrine synthesis pathways, crisis physiology, and skeletal treatment sequencing" source_sha256: f8b90b7ae886e295c8eaa5a468be71e76d32cec610a9036b39930a4c69f11f75 --- # Endocrine synthesis, crisis, and skeletal sequencing ## Thyroid synthesis and iodine effects ### Uptake, organification, coupling, storage, release ### Iodine effect is biphasic #### Deficiency raises stimulating hormone, goitre #### Acute load suppresses organification and release #### Autonomous tissue overproduces #### Autoimmune gland may become hypothyroid ### Most triiodothyronine made outside the gland #### Illness, fasting, drugs alter conversion ## Thyroid tests in context ### Stimulating hormone: sensitive primary screen #### Unreliable: central disease, recent change, illness ### Weeks to a new steady state #### Early testing causes dose oscillation ### Absorption: acidity, coeliac, iron, calcium #### Review administration before escalation ## Thyrotoxic mechanisms and emergencies ### Thyrotoxicosis: excess action from any source ### Hyperthyroidism: increased gland synthesis #### Thionamides cannot stop thyroiditis release ### More beta-adrenergic response and cardiac work ### Storm: clinical decompensation, not a threshold #### Triggers: infection, surgery, interruption, iodine #### Block adrenergic, synthesis, release, conversion ### Myxoedema coma often lacks coma #### Empirical glucocorticoid for hidden adrenal failure ## Adrenal steroid pathways ### All from cholesterol; zonal enzymes differ #### Glomerulosa lacks cortisol capacity #### Fasciculata cortisol, reticularis androgens ### Enzyme defects redirect precursors #### Low cortisol raises drive, causing hyperplasia #### Salt loss, hypertension, virilisation as clues ### Cortisol bound to binding globulin and albumin #### Oestrogen raises total cortisol ## Adrenal insufficiency and stress dosing ### Primary loses cortisol and often aldosterone ### Central keeps aldosterone via renin-angiotensin ### Exogenous glucocorticoids suppress drive #### Abrupt cessation can be dangerous ### Illness needs planned stress dosing #### Vomiting requires parenteral rescue ### Crisis: vasodilation, volume loss, hypoglycaemia ## Cortisol and aldosterone excess ### Glucocorticoid excess redistributes substrate #### Protein catabolism: weakness, thin skin #### Bone formation falls, resorption rises ### Establish autonomy, then localise dependence ### Aldosteronism: harm beyond pressure #### Potassium normal through intake and adaptation #### Posture, sodium, drugs affect the ratio ### Catecholamine tumours: receptor stimulation #### Biochemistry first; nodules are common #### Alpha before beta avoids unopposed constriction #### Restore volume before surgery ## Calcium sensing and phosphate balance ### Sensing receptor detects ionised calcium #### Falling calcium raises parathyroid hormone ### Kidney failure retains phosphate #### Less vitamin D activation #### Secondary hyperparathyroidism, may become autonomous #### Growth factor 23 rises early ### Magnesium: mild reduction stimulates #### Severe deficiency suppresses release #### Calcium fails until magnesium corrected ## Hypercalcaemia and hypocalcaemia logic ### First branch point: parathyroid hormone #### High or normal: primary, tertiary, lithium, familial #### Suppressed: malignancy, vitamin D, granulomas ### Volume depletion reduces calcium excretion #### Isotonic fluid limited by heart, kidney reserve ### Calcitonin fast but transient ### Confirm hypocalcaemia with ionised calcium ## Bone strength and treatment sequence ### Density is not strength #### Geometry, porosity, architecture, falls #### Fragility fracture establishes high risk ### Denosumab: reversible antibody pathway #### Stopping causes rebound vertebral fractures #### Plan a subsequent antiresorptive ### Anabolic therapy for very high risk #### Sequence affects gains and preservation ## Endocrine crisis support ### Organ support before hormones normalise ### Clinical recovery lags biochemistry ### Poor response: reconsider diagnosis, absorption #### Interactions, infection, heart failure, adrenal