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Open access

Matthieu St-Jean, Jessica MacKenzie-Feder, Isabelle Bourdeau and André Lacroix

Summary

A 29-year-old G4A3 woman presented at 25 weeks of pregnancy with progressive signs of Cushing’s syndrome (CS), gestational diabetes requiring insulin and hypertension. A 3.4 × 3.3 cm right adrenal adenoma was identified during abdominal ultrasound imaging for nephrolithiasis. Investigation revealed elevated levels of plasma cortisol, 24 h urinary free cortisol (UFC) and late-night salivary cortisol (LNSC). Serum ACTH levels were not fully suppressed (4 and 5 pmol/L (N: 2–11)). One month post-partum, CS regressed, 24-h UFC had normalised while ACTH levels were now less than 2 pmol/L; however, dexamethasone failed to suppress cortisol levels. Tests performed in vivo 6 weeks post-partum to identify aberrant hormone receptors showed no cortisol stimulation by various tests (including 300 IU hLH i.v.) except after administration of 250 µg i.v. Cosyntropin 1–24. Right adrenalectomy demonstrated an adrenocortical adenoma and atrophy of adjacent cortex. Quantitative RT-PCR analysis of the adenoma revealed the presence of ACTH (MC2) receptor mRNA, while LHCG receptor mRNA was almost undetectable. This case reveals that CS exacerbation in the context of pregnancy can result from the placental-derived ACTH stimulation of MC2 receptors on the adrenocortical adenoma. Possible contribution of other placental-derived factors such as oestrogens, CRH or CRH-like peptides cannot be ruled out.

Learning points:

  • Diagnosis of Cushing’s syndrome during pregnancy is complicated by several physiological alterations in hypothalamic–pituitary–adrenal axis regulation occurring in normal pregnancy.

  • Cushing’s syndrome (CS) exacerbation during pregnancy can be associated with aberrant expression of LHCG receptor on primary adrenocortical tumour or hyperplasia in some cases, but not in this patient.

  • Placental-derived ACTH, which is not subject to glucocorticoid negative feedback, stimulated cortisol secretion from this adrenal adenoma causing transient CS exacerbation during pregnancy.

  • Following delivery and tumour removal, suppression of HPA axis can require several months to recover and requires glucocorticoid replacement therapy.

Open access

Carine Ghassan Richa, Khadija Jamal Saad, Georges Habib Halabi, Elie Mekhael Gharios, Fadi Louis Nasr and Marie Tanios Merheb

Summary

The objective of this study is to report three cases of paraneoplastic or ectopic Cushing syndrome, which is a rare phenomenon of the adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome. Three cases are reported in respect of clinical presentation, diagnosis and treatment in addition to relevant literature review. The results showed that ectopic ACTH secretion can be associated with different types of neoplasm most common of which are bronchial carcinoid tumors, which are slow-growing, well-differentiated neoplasms with a favorable prognosis and small-cell lung cancer, which are poorly differentiated tumors with a poor outcome. The latter is present in two out of three cases and in the remaining one, primary tumor could not be localized, representing a small fraction of patients with paraneoplastic Cushing. Diagnosis is established in the setting of high clinical suspicion by documenting an elevated cortisol level, ACTH and doing dexamethasone suppression test. Treatment options include management of the primary tumor by surgery and chemotherapy and treating Cushing syndrome. Prognosis is poor in SCLC. We concluded that in front of a high clinical suspicion, ectopic Cushing syndrome diagnosis should be considered, and identification of the primary tumor is essential.

Learning points:

  • Learning how to suspect ectopic Cushing syndrome and confirm it among all the causes of excess cortisol.

  • Distinguish between occult and severe ectopic Cushing syndrome and etiology.

  • Providing the adequate treatment of the primary tumor as well as for the cortisol excess.

  • Prognosis depends on the differentiation and type of the primary malignancy.

Open access

Runa Acharya and Udaya M Kabadi

Summary

Diabetic ketoacidosis (DKA) is commonly encountered in clinical practice. The current case is a unique and rare presentation of DKA as the initial manifestation of Cushing’s disease secondary to ACTH-secreting pituitary adenoma. Appropriate management as elaborated in the article led to total remission of diabetes as well as the Cushing’s disease.

Learning points:

  • DKA is a serious and potentially life-threatening metabolic complication of diabetes mellitus.

  • Some well-known precipitants of DKA include new-onset T1DM, insulin withdrawal and acute illness.

  • In a patient presenting with DKA, the presence of a mixed acid–base disorder warrants further evaluation for precipitants of DKA.

  • We present a rare case of DKA as an initial manifestation of Cushing’s disease secondary to ACTH-producing pituitary adenoma.

Open access

Elise Flynn, Sara Baqar, Dorothy Liu, Elif I Ekinci, Stephen Farrell, Jeffrey D Zajac, Mario De Luise and Ego Seeman

Summary

ACTH-secreting phaeochromocytoma (ASP) is a rare cause of ACTH-dependent Cushing’s syndrome (CS). We report the case of a 63-year-old female presenting with CS secondary to an ASP complicated by bowel perforation. This case report highlights ASP as an uncommon but important cause of ectopic ACTH secretion (EAS). There have been 29 cases of ASP, all of which were unilateral and benign, but associated with significant complications. Patients presenting with ASP have the potential for cure with unilateral adrenalectomy. Given this promising prognosis if recognised, ASP should be considered in the diagnostic workup of ACTH-dependent CS. As this case demonstrates, gastrointestinal complications can arise from severe hypercortisolaemia associated with CS. Early medical and surgical intervention is imperative as mortality approaches 50% once bowel perforation occurs.

Learning points

  • Consider phaeochromocytoma in the diagnostic workup of ACTH-dependent CS; screen with plasma metanephrines or urinary catecholamines.

  • Serial screening may be required if ACTH-secreting phaeochromocytoma is suspected, as absolute levels can be misleading.

  • Early catecholamine receptor blockade and adrenal synthesis blockade may avoid the need for rescue bilateral adrenalectomy in ACTH-secreting phaeochromocytoma.

  • Consider early medical or surgical management when gastrointestinal features are present in patients with CS, as bowel perforation due to severe hypercortisolaemia can occur and is associated with significant mortality.

Open access

M J Trott, G Farah, V J Stokes, L M Wang and A B Grossman

Summary

We 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 points

  • Ectopic corticotrophin (ACTH) secretion should always be considered in the diagnostic workup of young patients with Cushing’s syndrome

  • There 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 cohort

  • An 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 populations

  • The relapsing and remitting course of our patient’s symptoms is noteworthy, given the paucity of this finding among other published cases

Open access

Ya-Wun Guo, Chii-Min Hwu, Justin Ging-Shing Won, Chia-Huei Chu and Liang-Yu Lin

Summary

A functional lesion in corticotrophin (ACTH)-independent Cushing’s syndrome is difficult to distinguish from lesions of bilateral adrenal masses. Methods for distinguishing these lesions include adrenal venous sampling and 131I-6β-iodomethyl-19-norcholesterol (131I-NP-59) scintigraphy. We present a case of a 29-year-old Han Chinese female patient with a history of hypercholesterolaemia and polycystic ovary syndrome. She presented with a 6month history of an 8kg body weight gain and gradual rounding of the face. Serial examinations revealed loss of circadian rhythm of cortisol, elevated urinary free-cortisol level and undetectable ACTH level (<5pg/mL). No suppression was observed in both the low- and high-dose dexamethasone suppression tests. Adrenal computed tomography revealed bilateral adrenal masses. Adrenal venous sampling was performed, and the right-to-left lateralisation ratio was 14.29. The finding from adrenal scintigraphy with NP-59 was consistent with right adrenal adenoma. The patient underwent laparoscopic right adrenalectomy, and the pathology report showed adrenocortical adenoma. Her postoperative cortisol level was 3.2μg/dL, and her Cushingoid appearance improved. In sum, both adrenal venous sampling and 131I-NP-59 scintigraphy are good diagnostic methods for Cushing’s syndrome presenting with bilateral adrenal masses.

Learning points

  • The clinical presentation of Cushing’ syndrome includes symptoms and signs of fat redistribution and protein-wasting features.

  • The diagnosis of patients with ACTH-independent Cushing’s syndrome with bilateral adrenal masses is challenging for localisation of the lesion.

  • Both adrenal venous sampling and 131I-NP-59 scintigraphy are good methods to use in these patients with Cushing’s syndrome presenting with bilateral adrenal masses.

Open access

Satoru Sakihara, Kazunori Kageyama, Satoshi Yamagata, Ken Terui, Makoto Daimon and Toshihiro Suda

Summary

ACTH-dependent Cushing's syndrome includes Cushing's disease and ectopic ACTH syndrome (EAS). The differential diagnosis of Cushing's disease from EAS in cases of ACTH-dependent Cushing's syndrome is a challenging problem. We report here a case of EAS with an unknown source of ACTH secretion. Extensive imaging procedures, involving computed tomography (neck to pelvis), pituitary magnetic resonance imaging, and whole-body 18F-fluorodeoxyglucose-positron emission tomography, failed to reveal the source of ACTH secretion. Intermittent administration of bromocriptine, a short-acting and nonselective dopamine agonist, has afforded adequate suppression of plasma ACTH and cortisol levels over the long term.

Learning points

  • Tumor excision is the primary treatment for EAS. However, when surgery is impossible, medical therapy is needed to treat hypercortisolism.

  • In cases where the source of ACTH secretion is unknown, inhibitors of steroidogenesis, such as metyrapone, mitotane, ketoconazole, and etomidate, are mostly used to suppress cortisol secretion.

  • Medications that suppress ACTH secretion are less effective, therefore less popular, as standard treatments.

  • In the present case, short-term treatment with dopamine agonists was effective for the long-term suppression of both ACTH and cortisol levels.