Ectopic Cushing’s syndrome with periodic hormonogenesis--a case suggesting a pathogenetic mechanism

Estopiñán, V; Varela, C; Riobó, P; Domínguez, José Ramón Fernández; Sancho, J.

doi:10.1136/pgmj.63.744.887

Cited by 19 publications

(8 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The molecular basis for this significant variability in hormonal release has been little studied in molecular terms (36). Several hypotheses have been suggested to explain the phenomenon, including episodic haemorrhage, the synchronous growth and death of tumour cells (9,10) or fluctuations in adrenal-pituitary axis feedback (14). It seems unlikely that there is abnormal hypothalamic control as such regulation should be absent in the presence of an autonomous tumour (9,28,(37)(38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

“…Cyclicity has also been reported in patients with adrenal tumours (13) and ectopic ACTH syndrome (14), but it is most described in patients with Cushing's disease. Owing to the lack of any comprehensive data on the prevalence of the phenomenon, the aim of the present study was to investigate the presence of 'cyclicity' (defined as the presence of clinical and biochemical peaks and troughs) and of 'variability' (biochemical fluctuations of cortisol secretion) in a large cohort of patients with Cushing's disease.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The prevalence and characteristic features of cyclicity and variability in Cushing's disease

Alexandraki¹,

Kaltsas²,

Isidori

et al. 2009

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective: Cyclical Cushing's syndrome may render the diagnosis and management of Cushing's disease difficult. The aim of the present study was to investigate the prevalence of cyclicity and variability in patients with Cushing's disease, and to identify putative distinctive features. Design: Retrospective case-note study. Methods: We analysed the case records of 201 patients with Cushing's disease in a retrospective casenote study. Cyclicity was considered as the presence of at least one cycle, defined as a clinical and/or biochemical hypercortisolaemic peak followed by clinical and biochemical remission, followed by a new clinical and/or biochemical hypercortisolaemic peak. The fluctuations of mean serum cortisol levels, as assessed by a 5-point cortisol day curve, defined the variability. Results: Thirty (14.9%; 26 females) patients had evidence of cyclicity/variability. 'Cycling' patients were older but no difference in sex or paediatric distribution was revealed between 'cycling' and 'noncycling' patients. The median number of cycles was two for each patient, and 4 years was the median intercyclic period. A trend to lower cure rate post-neurosurgery and lower adenoma identification was observed in 'cycling' compared with 'non-cycling' patients. In multivariate analysis, older patients, longer follow-up, female sex and no histological identification of the adenoma were associated with an increased risk of cyclic disease. Conclusions: This large population study reveals that cyclicity/variability is not an infrequent phenomenon in patients with Cushing's disease, with a minimum prevalence of 15%. Physicians should be alert since it can lead to frequent problems in diagnosis and management, and no specific features can be used as markers.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The prevalence and characteristic features of cyclicity and variability in Cushing's disease

Alexandraki¹,

Kaltsas²,

Isidori

et al. 2009

European Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Nevertheless, the strict regularity of cyclic cortisol secretion, observed in several patients with cyclic CS, is difficult to explain by fluctuating cell growth and death only. Another mechanism might be persistence of negative feedback control of tumoural ACTH secretion by cortisol in cyclic CS (54). A third theory regards only cyclic Cushing's disease and supposes a hypothalamic origin, with periodic changes in substances contributing to pituitary ACTH secretion being involved.…”

Section: Pathophysiology Of Cyclic Csmentioning

confidence: 99%

Cyclic Cushing’s syndrome: a clinical challenge

Meinardi¹,

Wolffenbuttel²,

Dullaart³

2007

eur j endocrinol

125

134

View full text Add to dashboard Cite

Cyclic Cushing's syndrome (CS) is a rare disorder, characterized by repeated episodes of cortisol excess interspersed by periods of normal cortisol secretion. The so-called cycles of hypercortisolism can occur regularly or irregularly with intercyclic phases ranging from days to years. To formally diagnose cyclic CS, three peaks and two troughs of cortisol production should be demonstrated. Our review of 65 reported cases demonstrates that cyclic CS originates in 54% of cases from a pituitary corticotroph adenoma, in 26% from an ectopic ACTH-producing tumour and in about 11% from an adrenal tumour, the remainder being unclassified. The pathophysiology of cyclic CS is largely unknown. The majority of patients with cyclic CS have clinical signs of CS, which can be either fluctuating or permanent. In a minority of patients, clinical signs of CS are absent. The fluctuating clinical picture and discrepant biochemical findings make cyclic CS extremely hard to diagnose. Clinicians should therefore be aware of this clinical entity and actively search for it in all patients with suspected CS but normal biochemistry or vice versa. Frequent measurements of urinary cortisol or salivary cortisol levels are a reliable and convenient screening tool for suspected cyclic CS. Cortisol stimulation or suppression tests may give spurious results owing to spontaneous falls or rises in serum cortisol at the time of testing. When cyclic CS is biochemically confirmed, further imaging and laboratory studies are guided by the presence or absence of ACTH dependency. In cases of suspected ectopic ACTH production, specific biochemical testing for carcinoids or neuroendocrine tumours is required, including measurements of serotonin in platelets and/or urine, chromogranin A and calcitonin.European Journal of Endocrinology 157 245-254

show abstract

“…The periodic nature of the clinical symptoms and highly variable degree of hypercortisolaemia in this case is also noteworthy, as to our knowledge there are only four published cases of relapsing and remitting Cushing’s syndrome due to thymic NETs ( 2 , 3 , 5 , 6 ). These features may be considered more suggestive of a pituitary source; however, this was excluded in this case by the normal BIPSS and normalisation of clinical and biochemical features following resection of the thymic tumour.…”

Section: Discussionmentioning

confidence: 54%

“…Features of this rare group include a young age at diagnosis (median age 35years), male preponderance, and the absence of cyclical features. Although cyclical Cushing’s syndrome due to a pituitary adenoma is a well-recognised phenomenon, within the published literature to date, there exist very few cases of relapsing and remitting Cushing’s syndrome due to ectopic ACTH secretion from any source, and only four identified cases due to thymic NETs ( 2 , 3 , 5 , 6 ). Although the relapsing and remitting symptoms experienced by our patient are akin to those seen in cyclical Cushing’s syndrome of pituitary origin, the timing of the periods of her symptomatic hypercortisolaemia remained highly variable, a feature not yet widely described in this context.…”

Section: Introductionmentioning

confidence: 99%

A thymic neuroendocrine tumour in a young female: a rare cause of relapsing and remitting Cushing’s syndrome

Trott

Farah

Stokes

et al. 2016

Endocrinology, Diabetes &Amp; Metabolism Case Reports

View full text Add to dashboard Cite

SummaryWe present a case of a young female patient with a rare cause of relapsing and remitting Cushing’s syndrome due to ectopic ACTH secretion from a thymic neuroendocrine tumour. A 34-year-old female presented with a constellation of symptoms of Cushing’s syndrome, including facial swelling, muscle weakness and cognitive impairment. We use the terms ‘relapsing and remitting’ in this case report, given the unpredictable time course of symptoms, which led to a delay of 2 years before the correct diagnosis of hypercortisolaemia. Diagnostic workup confirmed ectopic ACTH secretion, and a thymic mass was seen on mediastinal imaging. The patient subsequently underwent thymectomy with complete resolution of her symptoms. Several case series have documented the association of Cushing’s syndrome with thymic neuroendocrine tumours (NETs), although to our knowledge there are a few published cases of patients with relapsing and remitting symptoms. This case is also notable for the absence of features of the MEN-1 syndrome, along with the female gender of our patient and her history of non-smoking.Learning pointsEctopic corticotrophin (ACTH) secretion should always be considered in the diagnostic workup of young patients with Cushing’s syndromeThere is a small but growing body of literature describing the correlation between ectopic ACTH secretion and thymic neuroendocrine tumours (NETs)The possibility of a MEN-1 syndrome should be considered in all patients with thymic NETs, and we note the observational association with male gender and cigarette smoking in this cohortAn exception to these associations is the finding of relatively high incidence of thymic NETs among female non-smoking MEN-1 patients in the Japanese compared with Western populationsThe relapsing and remitting course of our patient’s symptoms is noteworthy, given the paucity of this finding among other published cases

show abstract

Ectopic Cushing’s syndrome with periodic hormonogenesis--a case suggesting a pathogenetic mechanism

Cited by 19 publications

References 10 publications

The prevalence and characteristic features of cyclicity and variability in Cushing's disease

The prevalence and characteristic features of cyclicity and variability in Cushing's disease

Cyclic Cushing’s syndrome: a clinical challenge

A thymic neuroendocrine tumour in a young female: a rare cause of relapsing and remitting Cushing’s syndrome

Contact Info

Product

Resources

About