ACTH-Dependent Cyclic Cushing's Syndrome Can Be Associated with Pituitary Adenomas
Yes, ACTH-dependent cyclic Cushing's syndrome can be caused by a pituitary adenoma, which is the most common etiology of cyclic Cushing's syndrome. 1, 2
Definition and Characteristics of Cyclic Cushing's Syndrome
- Cyclic Cushing's syndrome is characterized by repeated episodes of cortisol excess interspersed with periods of normal cortisol secretion 1
- The cycles of hypercortisolism can occur regularly or irregularly with intervals between cycles ranging from days to years 1
- To formally diagnose cyclic Cushing's syndrome, three peaks and two troughs of cortisol production should be demonstrated 1
Etiology of Cyclic Cushing's Syndrome
- Pituitary adenomas (Cushing's disease) are the most common cause, accounting for approximately 54% of cyclic Cushing's syndrome cases 1
- Ectopic ACTH-producing tumors account for about 26% of cases 1
- Adrenal tumors represent approximately 11% of cases 1
- The pathophysiology of the cyclic pattern is largely unknown 1
Diagnostic Considerations for Cyclic Cushing's Syndrome
- Hypercortisolemia must be confirmed immediately prior to diagnostic procedures like bilateral inferior petrosal sinus sampling (BIPSS) to ensure the patient is in an active disease phase, which is especially important for cyclical Cushing's disease 3
- Frequent measurements of urinary cortisol or salivary cortisol levels are reliable and convenient screening tools for suspected cyclic Cushing's syndrome 1
- Dynamic tests (such as dexamethasone suppression tests) may give spurious results due to spontaneous fluctuations in cortisol levels 1
- ACTH levels >5 pg/mL suggest ACTH-dependent Cushing's syndrome, which includes pituitary sources 4
Diagnostic Approach for ACTH-Dependent Cyclic Cushing's Syndrome
- Initial diagnosis should be performed using 24-hour urinary free cortisol, low-dose dexamethasone tests, salivary cortisol, or night-time plasma cortisol values 5
- If ACTH is elevated, combinations of high-dose dexamethasone tests, CRH/desmopressin tests, and pituitary MRI can indicate a pituitary source 5
- BIPSS is the gold standard for confirming a pituitary source of ACTH when MRI findings are equivocal 3
- A pituitary source is confirmed by a central-to-peripheral ACTH ratio ≥2:1 before CRH stimulation and ≥3:1 after CRH stimulation 4
- Lateralization of the pituitary adenoma may be suggested by an inter-petrosal sinus ACTH gradient ≥1.4 between the two sides after CRH or desmopressin stimulation 6, 3
Treatment Considerations
- Selective transsphenoidal adenomectomy is the first-line treatment of choice for patients with Cushing's disease, including those with cyclic patterns 6
- Medical therapy with steroidogenesis inhibitors (ketoconazole, metyrapone) may be needed to control hypercortisolism before surgery or after unsuccessful tumor removal 5
- Repeat surgery can be considered for persistent or recurrent disease 6
Clinical Challenges and Pitfalls
- The fluctuating clinical picture and discrepant biochemical findings make cyclic Cushing's syndrome extremely difficult to diagnose 1
- Clinicians should actively search for cyclic Cushing's syndrome in all patients with suspected Cushing's syndrome but normal biochemistry or vice versa 1
- Medical therapy for Cushing's disease must be discontinued before diagnostic procedures like BIPSS to enable accurate interpretation of results 3
- Responses to treatment must be closely monitored due to potential variations in steroidogenesis 2
Practical Recommendations
- When cyclic Cushing's syndrome is suspected, perform frequent cortisol measurements (urinary or salivary) to capture the cyclical pattern 1
- Schedule diagnostic tests during periods of hypercortisolism for optimal accuracy 1
- For confirmed ACTH-dependent cyclic Cushing's syndrome, pituitary MRI should be performed to identify adenomas 4, 7
- If MRI is negative or equivocal, BIPSS should be performed during an active phase of the disease 3