Lyrics · 完整歌詞
As lipid-soluble hormones, glucocorticoids cross cell membranes and bind intracellular receptors,
linking an extracellular signal to changes in gene expression.
The complex alters gene transcription and induces lipocortin, also called annexin-1,
which inhibits phospholipase A2.
Prostaglandin and leukotriene synthesis fall at their source,
which explains an onset measured in hours rather than seconds.
Long-term use resorbs bone, impairs osteoblasts and reduces intestinal calcium absorption,
so osteoporosis is the commonest chronic complication.
Hyperglycaemia, central obesity, cataract, impaired healing and peptic ulceration follow,
and active ulceration is a contraindication.
The most dangerous consequence is silent.
Exogenous cortisol suppresses ACTH,
and the zona fasciculata atrophies within weeks of a course above physiological doses.
Abrupt cessation, or an intercurrent illness without a dose increase,
leaves no cortisol to meet the stress, and adrenal crisis follows.
Because aldosterone answers to renin and potassium rather than ACTH,
secondary insufficiency spares the mineralocorticoid axis:
potassium remains normal and pigmentation is absent.
Primary Addison's disease, by contrast, shows hyperkalaemia,
salt wasting and pigmentation from the high ACTH.
Treatment cannot wait for confirmation: hydrocortisone 100 mg intravenously,
then 200 mg over twenty-four hours, with rapid saline.
Sick-day rules then prevent recurrence,
doubling the oral dose when unwell and giving intramuscular hydrocortisone if vomiting.
As lipid-soluble hormones, glucocorticoids cross cell membranes and bind intracellular receptors,
linking an extracellular signal to changes in gene expression.
Normal physiology explains each of these rules.
Cortisol peaks in the early morning under the suprachiasmatic clock
and ACTH pulses.
ACTH signals through cAMP and protein kinase A, and StAR protein,
which carries cholesterol into the mitochondrion,
sets the rate of all steroid synthesis.
The cortex is layered salt, sugar, sex from outside inwards,
and high potassium stimulates the glomerulosa directly.
In 21-hydroxylase deficiency, blocked cortisol and aldosterone remove negative feedback,
ACTH rises and precursors divert into androgens, giving virilisation with salt loss.
Endocrine drugs are best remembered by the station at which they act.
Methimazole inhibits thyroid peroxidase and is first-line for hyperthyroidism,
whereas propylthiouracil also blocks peripheral conversion of T4 to T3
and is reserved for thyroid storm and the first trimester.
Bisphosphonates, denosumab, raloxifene and calcitonin all reduce resorption,
whereas intermittent teriparatide is the only anabolic agent; continuous PTH,
as in disease, destroys bone.
Alendronate is taken fasting and upright to protect the oesophagus.
Diabetes drugs follow the same logic.
Sulfonylureas close the beta-cell K-ATP channel regardless of glucose,
so hypoglycaemia and weight gain follow.
Repaglinide shares the mechanism but is excreted in bile
and suits renal impairment.
Metformin suppresses hepatic gluconeogenesis and risks lactic acidosis with alcohol.
GLP-1 agonists must be injected and reduce weight.
SGLT2 inhibitors now treat heart failure and chronic kidney disease,
yet they are withheld before surgery to prevent euglycaemic ketoacidosis.
No oral agent treats type 1 diabetes.
As lipid-soluble hormones, glucocorticoids cross cell membranes and bind intracellular receptors,
linking an extracellular signal to changes in gene expression.