What is Cushing’s syndrome?
Cushing’s syndrome is a symptom complex. It reflects chronic, excessive exposure of the tissues to glucocorticoids. Glucocorticoids are steroid hormones made by the adrenal cortex, and cortisol is the main one. The state of cortisol excess itself is called hypercortisolism.
What sets the adrenal’s output?
Cortisol, the main glucocorticoid, comes from the adrenal cortex, so the next question is what sets how much the adrenal makes. The pituitary normally releases ACTH, and ACTH stimulates the adrenal cortex. When cortisol is in excess, the question is therefore whether the adrenal cortex is driven from outside or acts on its own. Endogenous Cushing’s syndrome is divided by whether the excess is ACTH-dependent or ACTH-independent.
In one case a tumour makes ACTH, either in the pituitary or in another place, and the adrenal glands are stimulated, so cortisol rises with them. A tumour that makes ACTH drives the adrenal in the same way, as the causes note showed. In the other case the adrenal cortex overproduces cortisol by itself, and ACTH is suppressed. ACTH from the pituitary drives the adrenal cortex, and cortisol switches ACTH off through negative feedback, as the causes note showed.
Why does the family matter?
Once the family is known, every later note follows from it. ACTH dependence splits the causes into two families: ACTH-dependent and ACTH-independent. It also directs the investigation of each family, and it directs the treatment of each family. So each later note depends on knowing which family a patient falls into.
How was the split found?
The first descriptions and later findings are set out here. Harvey Cushing was the first to codify the complex of symptoms of obesity, diabetes, hirsutism and adrenal hyperplasia. He also discovered that most patients with this symptom complex had basophilic adenomas. Later researchers found adrenalectomy useful in improving symptoms in most patients. More recently, ectopic production of ACTH and CRH was found. CRH, which is used here without a gloss, has its role set out in the causes note.
How is the subject taught?
The four notes are ordered for learning, not for the clinic, which suspects, confirms, traces, then treats. In practice, the syndrome is suspected from the clinical features, confirmed with the screening tests, and only then traced to its cause before treatment.
- Causes and Forms of Cushing’s Syndrome: where the excess cortisol comes from in each family, and how often each form occurs.
- Clinical Manifestations of Cushing’s Syndrome: the clues that raise the question, from the non-specific to the changes in skin, muscle, bone, fat and mood.
- Diagnosis of Cushing’s Syndrome: how the excess is confirmed, and how ACTH separates the two families.
- Treatment of Cushing’s Syndrome: how each family is treated, and the complications that need follow-up after treatment.
Where to start?
If the subject is new, start with the causes. Where does the excess cortisol come from in each family?