Cyclic Cushing syndrome due to an ectopic pituitary adenoma

Zerikly, R. Kurdi; Eray, Esin; Faiman, Charles; Prayson, Richard A.; Lorenz, Robert R.; Weil, Robert J.; Hamrahian, Amir H.

doi:10.1038/ncpendmet1039

Cited by 16 publications

(7 citation statements)

References 12 publications

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“…Cyclical secretion of ACTH in EAS has been described in association with typical bronchial and malignant carcinoid tumour of the lung, gastric carcinoid, oncocytic carcinoid of the kidney, bronchial adenoma, phaeochromocytoma, ectopic pituitary adenoma and in occult tumours [48,69,[82][83][84]. A recent review reported a prevalence of 26% of EAS in patients with cyclic Cushing's syndrome from published series and case reports [83].…”

Section: Specific Considerations In Easmentioning

confidence: 95%

The ectopic ACTH syndrome

Alexandraki

Grossman

2010

Rev Endocr Metab Disord

184

131

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Ectopic Cushing's syndrome usually relates to the ectopic ACTH syndrome (EAS) and represents ∼20% of ACTH-dependent and ∼10% of all types of Cushing's syndrome (CS). Nearly any neuroendocrine or non-endocrine tumours may be associated with EAS, but the more prevalent tumours are bronchial carcinoids, small cell lung carcinomas, pancreatic carcinoids, thymic carcinoids, medullary carcinomas of the thyroid, and phaeochromocytomas. Occult tumours are highly represented in all the series (12-38%) and constitute the more challenging cases of EAS, requiring long term follow-up. The lack of any completely reliable diagnostic test procedure and imaging to clearly reveal the source of EAS suggests that we should adopt a step-by-step multidisciplinary approach for their diagnosis and therapeutic management. Clinical features are often similar in ACTH-dependent CS, but the rapid onset and progress may suggest an ectopic source. A combination of biochemical tests and imaging studies seems the most appropriate approach for the prompt identification of EAS, even if there are several pitfalls to be avoided along the way. The most appropriate management for cure of EAS, when its source is identified, is surgical excision after controlling the hypercortisolaemia by inhibitors of cortisol secretion and other newer modalities alone or in combination; bilateral adrenalectomy remains an alternative option. Tumour histology, the presence of metastases and the effective control of hypercortisolaemia affect mortality and morbidity. If a source repeatedly fails to be found, the prognosis is often favourable but the identification of a malignant tumour should still be sought during life-long follow-up to avoid the calamity of misdiagnosis.

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Section: Specific Considerations In Easmentioning

confidence: 95%

The ectopic ACTH syndrome

Alexandraki

Grossman

2010

Rev Endocr Metab Disord

184

131

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“…Neuroendocrine tumors of the thymus are the most frequently represented, followed by neuroendocrine bronchial tumors [4, 19–26]. Other tumors reported as responsible of cyclic ectopic CS are pancreatic, renal and gastric NET [27–29], epithelial thymoma [30], phaeochromocytoma [31], carotid glomus tumor [32] and ectopic pituitary adenoma [33]. Surprisingly, although small cell lung carcinoma is frequent in patients with ectopic CS, biochemical episodes of cycling seem to be rare.…”

Section: Discussionmentioning

confidence: 99%

A pitfall of bilateral inferior petrosal sinus sampling in cyclic Cushing’s syndrome

Albani¹,

Berr²,

Beuschlein

et al. 2019

BMC Endocr Disord

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BackgroundClinical care of patients with cyclic Cushing’s syndrome (CS) is challenging. Classical pitfalls include incorrect subtyping, unnecessary surgical procedures and delayed definite treatment.Case presentationA 43-year-old female suffered from a rapidly cycling ectopic CS. She experienced six cycles of severe hypercortisolism within a 2 year period (maximum plasma cortisol 5316 nmol/L, normal range 124.2–662.4 nmol/L; maximum urinary free cortisol 79,469 nmol/24 h, normal range < 414 nmol/24 h) lasting 2–9 weeks. The episodes were associated with pronounced hypokalemia (lowest K+ value recorded 2.4 mmol/l) and progressive signs and symptoms of CS. A bilateral inferior petrosal sinus sampling (BIPSS) performed during a trough phase was false positive for pituitary ACTH overproduction resulting in unnecessary transsphenoidal surgery while a second BIPSS performed during an active phase was indicative for ectopic CS. The 18F-DOPA PET/CT showed a pancreatic lesion, which was subsequently partially removed. Surprisingly, the histopathology was conclusive for ACTH-positive lymph node metastasis located in the retro-duodenal tissue of an occult neuroendocrine tumor WHO grade II. The primary tumor has not been identified so far and, because of the persistent hypercortisolism, the patient underwent bilateral adrenalectomy. Two years later, ACTH levels started to increase progressively. Percutaneous biopsy of a newly identified suspected lesion in the fifth thoracic vertebra revealed a metastasis with positive staining for ACTH, synaptophysin and chromogranin A. Therapy with carboplatin and etoposide was started and, since then, the patient underwent 12 cycles of chemotherapy.ConclusionsWe report the challenging case of a rapidly cycling CS secondary to ACTH-secreting neuroendocrine intestinal tumor of unknown primary. We highlight the importance of performing diagnostic tests only during the phases of active cortisol secretion and as soon as first symptoms appear to avoid pitfalls.

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“…Differential diagnosis includes cyclic Cushing's, characterized by periodic fluctuations of cortisol secretion. Cycles of hypercortisolism alternate with phases of normal or low cortisol production, which can last days or years (17). It can be present in ACTH dependent or independent Cushing's syndrome.…”

Section: Discussionmentioning

confidence: 99%

“…It can be present in ACTH dependent or independent Cushing's syndrome. Approximately in 10% of cases an adrenal tumor is the underlying cause (17). In this case, although there was a paradoxical increase of cortisol with a 100% rise in 24 h UFC during the Liddle's test suggestive of PPNAD, basal urine free cortisol levels were within normal values.…”

Section: Discussionmentioning

confidence: 99%

Factitious Cushing's Syndrome: A Diagnosis to Consider When Evaluating Hypercortisolism

et al. 2019

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Factitious Cushing's syndrome is exceptionally rare. The diagnosis is challenging due to the interference of exogenous corticosteroids with cortisol immunoassays. We present a case of a 26 year old female that presented with clinical and biochemical features of Cushing's syndrome. She denied any exogenous corticosteroid use. She had a suppressed ACTH level with normal adrenal glands on CT scans. There was a paradoxical increase of cortisol with a 100% rise in 24 h urinary free cortisol (UFC) during the Liddle's test suggestive of primary pigmented nodular adrenocortical disease (PPNAD). However, basal UFC levels were within normal values, interpreted as an intermittent variation of cortisol secretion maybe due to cyclic Cushing's. At this point a synthetic glucocorticoid serum screening was ordered, which was denied by the administrators because the test was not available in our hospital. A positron emission tomography (PET)-CT using 18 F-Flurodeoxyglucose did not show any uptake in the adrenal glands. With the diagnosis of probable primary pigmented nodular adrenocortical disease a unilateral right adrenelectomy was performed. Histopathological examination revealed normal adrenal gland. A synthetic glucocorticoid serum screen by liquid chromatography-tandem mass spectrometry (LC-MS/MS) sent to Mayo Clinic lab revealed high levels of serum prednisone and prednisolone. In conclusion, factitious Cushing's syndrome is an important diagnosis to consider in patients being evaluated for hypercortisolism. Discordant hormonal test results as well as normal findings on adrenal glands on CT scan should raise suspicion of this entity, and prompt measurement of synthetic corticosteroids using LC-MS/MS.

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Cyclic Cushing syndrome due to an ectopic pituitary adenoma

Cited by 16 publications

References 12 publications

The ectopic ACTH syndrome

The ectopic ACTH syndrome

A pitfall of bilateral inferior petrosal sinus sampling in cyclic Cushing’s syndrome

Factitious Cushing's Syndrome: A Diagnosis to Consider When Evaluating Hypercortisolism

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