The Lab / Core medicine / Lesson 15
Two small glands on your kidneys make cortisol, and your brain keeps them in check with a brake. Build the loop one piece at a time, see what happens with too much or too little, then watch why steroid drugs switch the loop off.
Educational, not for clinical use
Build the idea
Your two adrenal glands sit like caps on top of the kidneys. A gland is an organ that makes and releases chemicals. Each adrenal gland has an outer layer, the cortex, wrapped around an inner core, the medulla.
Build the idea
The cortex releases cortisol into the blood. Cortisol is a hormone, a chemical messenger carried in the blood, and a steroid, one of a family of hormones built from fats. It helps the body cope with long-lasting stress.
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Cortisol tells the body to break down its stores, so more glucose, the sugar cells burn for energy, enters the blood. That is why cortisol and its relatives are called glucocorticoids: steroids from the cortex that act on glucose.
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Cortisol also turns down the immune system, the body’s defence against germs. That calms inflammation: the redness, heat and swelling of an immune response. More cortisol means calmer inflammation; less cortisol, fiercer.
Build the idea
The cortex also makes aldosterone, the main mineralocorticoid: a steroid that manages minerals. It tells the kidneys to keep sodium, the main salt in blood, and pass potassium, another mineral, out in urine (Lesson 5).
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The pituitary, a pea-sized gland at the base of the brain, sends ACTH (adrenocorticotropic hormone) through the blood to the adrenal cortex. ACTH tells the cortex to make cortisol. More ACTH, more cortisol.
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Just above sits the hypothalamus, a small brain region linking nerves to hormones. It sends CRH (corticotropin-releasing hormone) to the pituitary, which answers with ACTH. The three together are the HPA axis: hypothalamus, pituitary, adrenal.
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Long-lasting stress, such as illness, injury or hunger, makes the hypothalamus send more CRH. ACTH rises, the cortex makes more cortisol, and glucose climbs to fuel the body. Even without stress, the chain rises and falls in a daily rhythm.
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Cortisol in the blood reports back to the brain. When it runs high, the hypothalamus and pituitary send less CRH and ACTH, so the cortex slows down. The result switches off its own cause: negative feedback.
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When cortisol runs low, the brake eases. The hypothalamus and pituitary send more CRH and ACTH and push the cortex harder until cortisol climbs back. So when only cortisol changes, ACTH answers in the opposite direction.
Build the idea
Hypothalamus, pituitary and adrenal cortex form one loop, held steady by the brake. Its effects show on routine blood tests, measurements made on a blood sample: glucose, sodium and potassium. Here cortisol and ACTH are drawn only as low, usual or high.
What changes it
Cushing’s syndrome is the body under too much cortisol, from any cause. Shown here is Cushing’s disease, most often a pituitary tumor, an abnormal growth, pouring out ACTH that ignores the brake. Cortisol and glucose climb; CRH falls.
What changes it
In adrenal insufficiency, such as Addison’s disease, the cortex makes too little of its steroids. Glucose and sodium fall. With the brake weak, CRH and ACTH climb and push hard on a cortex that cannot answer.
What changes it
Glucocorticoid drugs, such as prednisone, are lab-made cortisol relatives that calm inflammation. The brain reads them as cortisol, so CRH and ACTH fall and the body’s own cortisol switches off. After long use they are stopped slowly, or tapered.
What changes it
Mineralocorticoid drugs, such as fludrocortisone, act like aldosterone on the kidneys and replace it in Addison’s disease. In excess, the kidneys keep more sodium and lose more potassium: blood sodium rises, potassium falls. CRH, ACTH and cortisol stay put.
What changes it
Steroid synthesis inhibitors block steps the cortex uses to build its steroids. Less cortisol is made, so the brake eases: CRH and ACTH rise and push on the cortex, which still makes less than usual.
Start with Next, or use the arrow keys. Pictures are illustrative, not measurements.
Loading reference values…
Normal teaching baseline.
The blue line on each bar, and the large number beside it, show where an illustrative teaching model sits: not a patient measurement and not a sourced value. The shaded bands are the reference ranges quoted under each row. Selecting a disease or drug shows the expected direction of each value from the cited passage, compared with a normal body, and applies that state to the model. The saved sources give no reference ranges for cortisol, ACTH or CRH, so those appear only in the picture, as low, usual or high.
An illustrative teaching model of the settled loop. Pick a starting body, switch drugs on and off (they combine), and move the sliders. Dashed marks are the normal body; solid marks are your settings.
While the drug holds the brake on, the body’s own cortex makes little and, in this model, slowly loses its working capacity. Compare stopping all at once with tapering.
Every level is worked out relative to the normal body and settles to a steady state. The hypothalamus’s CRH rises with long-term stress and falls in proportion to the glucocorticoid signal in the blood (the body’s own cortisol plus any glucocorticoid drug): that is the negative-feedback brake. The pituitary’s ACTH follows CRH and is braked directly too; a pituitary tumor adds ACTH that the brake cannot touch. The cortex’s cortisol output is its working capacity × the share of its steroid-building a synthesis inhibitor leaves (half) × the drive from ACTH, which saturates at three times normal. The loop settles where these agree, found by halving the search range seventy times. The saved sources give no direction for glucose or inflammation with a synthesis inhibitor, so the model never lets the inhibitor move them: they are worked out as if the block were absent. In the same way, the cited Addison’s passage gives no potassium direction, so a change in the working cortex is never allowed to move potassium.
Glucose follows the total glucocorticoid signal, and inflammation is calmed by it. Aldosterone output follows the working cortex, and a mineralocorticoid drug adds to it; more of this signal moves sodium up and potassium down. In the stopping chart, the cortex’s working capacity drifts toward what ACTH asks of it, so it shrinks while the drug holds ACTH low and recovers slowly afterwards. The sizes of all these effects, and the time axis, are illustrative choices; only their directions are meant to teach.
Here in Explore freely the model never turns its levels into lab numbers: the sources give only the direction of each change, so the readout says where each level sits against its healthy band. The real reference numbers are in the Clinical values tab, which also prints the model’s level in each row’s unit as a clearly labelled illustrative value. Left out: the daily rhythm, binding proteins, the adrenal medulla, the renin–angiotensin system, other medicines and every real-world difference between people. Nothing here is a prediction for a real person, and nothing here is a treatment plan.