How can HCPs provide optimal care for Cushing’s syndrome patients?

Priorities in treating Cushing’s syndrome

The top priority in the treatment of Cushing’s syndrome is to achieve and sustain normal levels of cortisol. Untreated Cushing’s syndrome is associated with significant morbidity and mortality.20 Early treatment is essential to manage the comorbidities associated with hypercortisolism, and lifelong symptom monitoring is essential to improve patient quality of life (QoL).9

Therapeutic options


Surgery is the first-line treatment for most patients with Cushing’s syndrome.9

For patients with Cushing’s disease (the most common form of Cushing’s syndrome), surgical removal of the causative tumour is most commonly performed via the transsphenoidal route.9

However, not all patients with Cushing’s are candidates for surgery because of medical reasons, lack of access to a specialised centre for the treatment of pituitary tumours, or refusal of surgery.21

While surgery can be successful and achieves a mean remission rate of 78%, a review of 74 studies performed between 1976 and 2014 in patients with Cushing’s disease indicated that pituitary surgery was associated with long-term failure, including immediate relapses and late recurrences, in an average of 32% of patients.22

That is why it is important to monitor the patient’s symptoms before, during, and after surgery to detect and manage persisting and recurrent symptoms, which over 88% of patients report experiencing.1

Recurrence following pituitary surgery is a persistent risk for patients for at least 10 years after surgery and is characterised as the reappearance of clinical and biochemical features of hypercortisolism after initial remission. It is also important to bear in mind that:10,22

  • Low or undetectable cortisol concentrations in the immediate postoperative period is a defining criterion of remission, but does not necessarily predict lack of recurrence22
  • Some patients who show early remission with very low (<2–5 μg/dL) postoperative cortisol concentrations might experience recurrence later23

In fact, up to 50% of patients can experience disease reoccurrence following surgery.24

Therefore, it is critical that patients understand the importance of monitoring for the reappearance symptoms after treatment. This is essential to catch reoccurrence early and initiate medication to help control rising cortisol levels.11

Encouraging open communication with patients helps to identify recurrences and treat them early.14

Prof. Annamaria Colao MD, PhD
Endocrinology and Pituitary expert

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Medical therapies

Due to the prevalence of recurrence and/or persistence of hypercortisolism after surgery, long-term treatment with medical therapies is often required.22

Several drugs can be used to control cortisol production and most commonly target these systems:10

  • Adrenal steroidogenesis
  • Somatostatin and dopamine receptors
  • Glucocorticoid receptors

After initiation of medication, assessing levels of cortisol can be achieved through measurement of the levels of late-night salivary cortisol (LNSC), 24-hour urinary free cortisol (UFC), and serum cortisol after dexamethasone-suppression test (DST).22

If there is clear resistance to treatment, guidelines suggest switching to a different therapy. This change in treatment should be considered if cortisol concentrations are persistently elevated after 2–3 months on the maximum tolerated doses of the current treatment.10 However, it is important to ensure that insufficient disease control due to underdosing is not misinterpreted as treatment resistance.6,22

Up to 30% of patients treated with medical therapy do not achieve cortisol control.24

Other options can include:

Pituitary irradiation: 
This is an option for patients who are not surgical candidates, have persistent or recurrent hypercortisolism following pituitary surgery, and/or remain uncontrolled on medical therapy. However, the response to pituitary irradiation is slow and is related to the type of radiation administered.25

Bilateral adrenalectomy:
It provides immediate control of hypercortisolism but is associated with several limitations and risks for the patient, including permanent hypoadrenalism and risk of corticotroph tumour progression (Nelson’s syndrome) in patients with Cushing’s disease.26,27

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‘Clinical complications are persistent, and then probably patients have to face with that for the rest of their life.’

Prof. Rosario Pivonello MD, PhD

Endocrinology and Pituitary expert

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