Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2023) 97 019 | DOI: 10.1530/endoabs.97.019

BES2023 BES 2023 Section (29 abstracts)

In search of the source; a challenging diagnostic work-up of ACTH dependent Cyclic Cushing syndrome

Buyse Stephanie 1 & Lapauw Bruno 2

1,2 Department of Endocrinology, Ghent University Hospital, Belgium

Introduction: Cyclic Cushing Syndrome (CCS) is a rare entity of Cushing’s syndrome (CS), characterized by a cyclic excretion of cortisol, resulting in periods of hypercortisolism intertwining with periods of hypo- or normocortisolism. Diagnosis of CS as such can be challenging, moreover the cyclicity of CCS may necessitate repeated testing. (1)

Case: A 68 year old woman consulted because of periodically appearing edema of the lower extremities. A blood test showed a hypokalemia of 2,04 mmol/l (reference 3,5-5,1mmol/l). At that time she was completely asymptomatic. Clinical examination was, except for obesity, unremarkable. CS was diagnosed based on an elevated 24-hour urinary free cortisol excretion (1117,2µg/24h - reference <90µg/24h), a high bedtime salivary cortisol (6,063 µg/dl - reference <0,107µg/dl) and lack of suppression of cortisol after an overnight 1 mg dexamethasone suppression test (1355nmol/l - reference 50nmol/l). A high ACTH (131 pg/mL - reference <46pg/mL), suggested Cushing disease (CD) or ectopic ACTH production. Pituitary MRI was unremarkable. During hospitalization, hypokalemia disappeared together with a normalizing morning cortisol and ACTH. Within a couple of days, a relapse occurred with immeasurably high serum cortisol levels, hyperglycemia and recurrent hypokalemia. FDG-PET-CT showed a hypermetabolic adenopathy at the right lung hilum, where a biopsy showed no abnormalities. Given the suspicion of CD, a sinus petrosus sampling with CRH stimulation was performed with the results being suggestive of a pituitary source of ACTH production. Despite a right hemiphysectomy, hypercortisolism persisted. A 68Ga-DOTATOC PET/CT was performed in search of an ectopic source of ACTH, showing increased uptake at the right lung hilum. A repeat biopsy showed atypical carcinoïd, which was resected. Unfortunately, hypercortisolism persisted. Lanreotide was commenced, but had to be stopped because of intolerance. Repeated episodes of hypercortisolism, intertwined with periods of hypocortisolism with the need for hydrocortisone therapy occurred. Ultimately, a bilateral adrenalectomy was performed. After surgery, hydrocortisone and fludrocortisone therapy was started, after which the patient no longer experienced episodes of leg oedema or electrolyte disorders.

Discussion: CCS is a rare entity of CS, characterized by fluctuating cortisol levels. Like CS, CCS can be associated with ACTH-dependent or ACTH-independent hypercortisolism. CD is the most frequent underlying disorder, followed by ectopic ACTH syndrome. (1) Symptoms do not differ from classical CS, but can fluctuate over time, coinciding with the cortisol levels. (2) In this case, the patient suffered from fluctuating leg oedema, hyperglycemia, hypokalemia in periods of hypercortisolism and hyponatremia in periods of hypocortisolism. In order to establish the diagnosis of CCS, late-night salivary cortisol, 24h urine free cortisol and low dose dexamethasone suppression test can be used. (2) Testing can be normal when tested in periods of normo- or hypocortisolism, advocating for repeat testing, ideally in a symptomatic period. (1) Diagnostic work-up of CCS is the same as in classical CS. ACTH dependent CS requires differentiation of a pituitary vs ectopic source. Pituitary MRI showing an adenoma or a positive sinus petrosus sampling is suggestive of a pituitary source. The latter test should be performed in an episode of hypercortisolism. (2) Imaging modalities for ectopic ACTH-producing tumors encompass CT-scanning, FDG-PET-CT or functional scanning (like 68-Ga DOTATATE PET-CT). (1) Treatment primarily involves resection of the primary tumor. In cases where no (residual) tumor can be found, pharmacotherapy is possible with somatostatin analogues, steroid synthesis inhibitors, dopamine agonists, and glucocorticoid receptor antagonists as possible treatment options. In case of inadequate control, bilateral adrenalectomy, combined with gluco- and mineralocorticoid replacement therapy, offers definitive treatment. (2)

Conclusion: This case highlights the complexity of diagnostic work-up in a patient with endogenous hypercortisolism, moreover complicated by a cyclic course of hypercortisolism. In patients with fluctuating symptoms, CCS should be kept in mind, with testing being performed during episodes of hypercortisolism.

References: 1. Cai Y, Ren L, Tan S, et al. Mechanism, diagnosis, and treatment of cyclic Cushing’s syndrome: A review. Biomed Pharmacother. 2022; 153(May):113301. Doi:10.1016/j.biopha.2022.1133012. Świątkowska-Stodulska R, Berlińska A, Stefańska K, Klosowski P, Sworczak K. Cyclic Cushing’s Syndrome – A Diagnostic Challenge. Front Endocrinol (Lausanne). 2021;12(April):1-7.doi:10.3389/fendo.2021.658429

Article tools

My recent searches

No recent searches.