Pneumocystis pneumonia as a major complication of medical treatment for severe Cushing's syndrome linked either to ectopic ACTH secretion or to Cushing's disease

Abstract. The 24-h plasma cortisol profile was obtained at 20-min intervals in 18 patients with Cushing's syndrome (10 with Cushing's disease, 5 with adrenal adenoma, 2 with ectopic ACTH secretion and 1 of questionable aetiology). The mean cortisol level was maximum in the case of ectopic ACTH secretion. The coefficient of variation of cortisol levels was subnormal in all except 2 subjects. Periodogram calculations, providing a best-fit curve (B F C) for each profile, showed that the existence of a significant baseline variation is a frequent feature. In certain cases, it is compatible with the persistance of a true circadian rhythm (2 patients with Cushing's disease; 1 patient with adrenal adenoma). The alteration of plasma cortisol pulsatility is much more pronounced in patients with adrenal adenoma than in patients with Cushing's disease. This is consistent with the hypothesis of a predominantly tonic secretion blunting the episodic hormone release. In 9 patients with Cushing's disease, the plasma cortisol pattern was suggestive of a combination of episodic cortisol release under CRF control and of continuous cortisol secretion due to constant stimulation from an autonomous ACTH source. Two cases were possibly of hypothalamic origin, as suggested by the presence of enhanced cortisol pulsatility and of a normal circadian amplitude. The analysis of the 24-h profile of plasma cortisol in Cushing's syndrome contributes to our understanding of the physiopathological mechanisms underlying this disorder and may help the diagnosis of its aetiology.

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The role of inferior petrosal sinus sampling in the diagnostic localization of Cushing's disease

Neurosurgical FOCUS ◽

10.3171/foc.2007.23.3.3 ◽

2007 ◽

Vol 23 (3) ◽

pp. 1-6 ◽

Cited By ~ 17

Author(s):

Shivanand P. Lad ◽

Chirag G. Patil ◽

Edward R. Laws ◽

Laurence Katznelson

Keyword(s):

Pituitary Adenoma ◽

Cushing’S Syndrome ◽

Cushing’S Disease ◽

Treatment Decisions ◽

Cushing's Syndrome ◽

Cushing's Disease ◽

Inferior Petrosal Sinus ◽

Acth Secretion ◽

Ectopic Acth ◽

Inferior Petrosal Sinus Sampling

✓ Cushing's syndrome can present a complex problem of differential diagnosis. Of cases in which hypercortisolemia results from an adrenocorticotropic hormone (ACTH)–dependent process, approximately 80% are due to a pituitary adenoma (Cushing's disease [CD]), 10% are due to adrenal lesions, and the remaining 10% are secondary to ectopic ACTH secretion. For patients with CD, surgical removal of the pituitary adenoma is the treatment of choice. Thus, localization of the source of ACTH secretion is critical in guiding timely treatment decisions. Inferior petrosal sinus sampling (IPSS) is considered to be the gold standard for confirming the origin of ACTH secretion in patients with Cushing's syndrome. The authors present an overview of IPSS—both the technique and its interpretation—as well as a summary of recent studies. A number of other techniques are discussed including sampling from the cavernous sinus, the jugular vein, and multiple sites to aid the diagnosis and lateralization of ACTH-producing pituitary adenomas. Management is best undertaken by a comprehensive multidisciplinary team taking into account the results of all the biochemical and imaging studies available, to provide the best advice in patient treatment decisions.

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MON-178 Cyclical Cushing’s Syndrome in 12 Patients with Ectopic ACTH Secretion

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1277 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Anna Zenno ◽

Raven McGlotten ◽

Atil Kargi ◽

Lynnette Nieman

Keyword(s):

Medical Treatment ◽

Cushing’S Syndrome ◽

Cushing's Syndrome ◽

Inferior Petrosal Sinus ◽

Acth Secretion ◽

Diagnostic Challenge ◽

Ectopic Acth ◽

Ectopic Acth Secretion ◽

Inferior Petrosal Sinus Sampling ◽

Acth Secreting

Abstract Background: Cyclical Cushing’s syndrome (CCS) is characterized by alternating periods of endogenous hypercortisolism and eucortisolism. A literature survey of 60 adult patients with CCS found 15 to have ectopic ACTH secretion (EAS) (1). The duration and frequency of hypercortisolemia are unpredictable, creating a diagnostic challenge. Objective: Describe biochemical and clinical characteristics of patients with CCS due to occult or histologically proven ectopic ACTH-secreting neuroendocrine tumor (NET). Methods: We conducted a retrospective medical record review of 12 adults with EAS admitted to our institution. Inclusion required 1) evidence of ectopic ACTH tumor from biochemical testing (CRH stimulation, 8 mg dexamethasone suppression [DST], and/or inferior petrosal sinus sampling [IPSS]) or pathology results and 2) cycles of hypercortisolism (Hi-F) to eucortisolism (Eu-F) off medical treatment. Results: Average age on admission was 61 (46-79) years; 58% were women. All 12 had biochemical evidence of ACTH-dependent Hi-F. IPSS results suggested EAS in 9 patients, 8 of whom had Hi-F for more than two months, and 1 whose cycles occurred every 5 - 7 days. IPSS was consistent with Cushing’s disease (CD) in 2 patients after Hi-F of only 6 -7 weeks and one with Eu-F on admission, estimated duration < 4 weeks. DST suggested EAS in 9 patients, and CD in the one with recent Eu-F. CRH was consistent with EAS in 10 patients, but suggested CD in 2 with marginal increases in ACTH (34.5%, 38%) but not cortisol. 7 patients had ACTH-secreting tumor on pathology (5 pulmonary, 1 pancreas, 1 appendix NET), and 5 had occult presumed EAS. Time from one Hi-F episode to the next ranged from 1 week to 6 years with Hi-F duration of 3 days to 5 years. 24-hour urine free cortisol (UFC) levels were 17 - 301 times the upper reference range (RR) during Hi-F periods. During Eu-F, lowest UFCs were within RR in 9 patients and subnormal in 3. Hypokalemia occurred in 11 patients with Hi-F; increasing values paralleled movement to Eu-F. Conclusion: Patients with possible ectopic ACTH-secretion and CCS may pose a diagnostic challenge: clinical and biochemical evidence of hypercortisolemia may not be present, depending on the timing and/or duration of hypercortisolism. Furthermore, test results may inappropriately suggest Cushing’s disease if performed after less than 8 weeks of hypercortisolism, or with recent eucortisolism. Thus, weekly UFC measurement may facilitate diagnosis of cyclical Cushing’s syndrome and determine appropriate timing of dynamic testing such as inferior petrosal sinus sampling. Potassium may be a useful marker to determine when medical treatment can be tapered or stopped. 1. Meinardi JR, et al. Eur J Endocrinol. 157:245, 2007.

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The value of [68Ga]Ga-DOTA-TATE PET/CT in diagnosis and management of suspected pituitary tumors

European Journal of Hybrid Imaging ◽

10.1186/s41824-021-00104-3 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Fuad Novruzov ◽

Aziz Aliyev ◽

Ming Young S. Wan ◽

Rizwan Syed ◽

Elnur Mehdi ◽

...

Keyword(s):

Cushing’S Syndrome ◽

Cushing’S Disease ◽

Somatostatin Receptor ◽

Cushing's Syndrome ◽

Cushing's Disease ◽

Receptor Subtype ◽

Somatostatin Analogue ◽

Ectopic Acth ◽

Ectopic Acth Secretion ◽

Pet Ct

Abstract Background Gallium 68-tetraazacyclododecane-tetraacetic acid-octreotate ([68Ga]Ga-DOTA-TATE) is a selective somatostatin analogue ligand, which shows increased affinity for somatostatin receptor subtype (SSTR) 2 and has been used routinely for imaging neuroendocrine tumors with PET/CT. We investigated the utility of [68Ga]Ga-DOTA-TATE positron emission tomography/computed tomography (PET/CT) in patients with suspected pituitary pathology. We reviewed imaging for twenty consecutive patients (8 men, 12 women, mean age of 48.2, range 14–78) with suspected pituitary pathology who were referred for [68Ga]Ga-DOTA-TATE PET/CT. Results Nine patients presented with recurrent Cushing’s syndrome following surgical resection of pituitary adenomas due to recurrent Cushing’s disease (seven patients) and ectopic ACTH secreting tumor (2 patients). All seven patients with recurrent Cushing’s disease showed positive pituitary [68Ga]Ga-DOTA-TATE uptake while both cases of ectopic hormonal secretion had absented pituitary uptake. In 1 of these 2 patients, [68Ga]Ga-DOTA-TATE was able to localize the source of ectopic ACTH tumor. Six patients presented de novo with Cushing’s due to ectopic ACTH secretion; [68Ga]Ga-DOTA-TATE PET/CT was able to localize ectopic tumors in six of eight patients (3 lungs, 2 pancreases, 1 mid-gut) There was high uptake [68Ga]Ga-DOTA-TATE in 3 cases of recurrent central hyperthyroidism (SUVmax 6.6–14.3) and 2 cases of prolactinoma (SUVmax 5.5 and 11.3). Conclusion Absent [68Ga]Ga-DOTA-TATE activity in the pituitary fossa is useful in excluding pituitary disease in recurrent Cushing’s. Recurrent pituitary thyrotropinomas and prolactinomas showed moderate to high pituitary activity. In addition, in Cushing’s syndrome, [68Ga]Ga-DOTA-TATE is useful for detection of ectopic sources of ACTH production, especially where anatomic imaging is negative.

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The corticotropin-releasing factor test in the differential diagnosis of Cushing's syndrome: A comparison with the lysine-vasopressin test

Acta Endocrinologica ◽

10.1530/acta.0.1230331 ◽

1990 ◽

Vol 123 (3) ◽

pp. 331-338 ◽

Cited By ~ 32

Author(s):

A. Tabarin ◽

F. San Galli ◽

S. Dezou ◽

F. Leprat ◽

J.-B. Corcuff ◽

...

Keyword(s):

Differential Diagnosis ◽

Cushing’S Syndrome ◽

Cushing’S Disease ◽

Cushing's Syndrome ◽

Cushing's Disease ◽

High Dose ◽

Ectopic Acth ◽

Ectopic Acth Secretion ◽

Etiological Diagnosis ◽

High Dose Dexamethasone

Abstract. The diagnostic accuracy of the CRH test was compared with that of the LVP test in 28 consecutive patients with ACTH-dependent Cushing's syndrome. A false negative response to CRH was found in 3 of 21 patients with pituitary-dependent Cushing's disease and to LVP in 4. The 7 patients with ectopic ACTH secretion were unresponsive to CRH, whereas 2 did respond to LVP. CRH and high-dose dexamethasone tests combination led to concordant results in 79% of patients. In all cases the etiological diagnosis suggested was correct. LVP and high-dose dexamethasone tests combination led to concordant results in only 71% of patients and the etiological diagnosis suggested was erroneous in one. Individual tolerance to the CRH test was also clearly better than that to the LVP test. It is concluded that the CRH test, alone or in combination with the high-dose dexamethasone test must be preferentially used to the LVP test in the differential diagnosis of ACTH-dependent Cushing's disease.

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The Value of Ga68-DOTATATE PET/CT in Diagnosis and Management of Suspected Pituitary Tumors

10.21203/rs.3.rs-172533/v1 ◽

2021 ◽

Author(s):

Fuad Novruzov ◽

Aziz Aliyev ◽

Ming Young S Wan ◽

Rizwan Syed ◽

Elnur Mehdi ◽

...

Keyword(s):

Cushing’S Syndrome ◽

Cushing’S Disease ◽

Somatostatin Receptor ◽

Cushing's Syndrome ◽

Cushing's Disease ◽

Receptor Subtype ◽

Somatostatin Analogue ◽

Ectopic Acth ◽

Ectopic Acth Secretion ◽

Pet Ct

Abstract Backroud Gallium 68-tetraazacyclododecane-tetraacetic acid-octreotate (Ga-68‑DOTATATE) is a selective somatostatin analogue ligand, which shows increased affinity for somatostatin receptor subtype (SSTR) 2 and has been used routinely for imaging neuroendocrine tumors with PET/CT. We investigated the utility of Ga-68‑DOTATATE positron emission tomography/computed tomography (PET/CT) in patients with suspected pituitary pathology. We reviewed imaging for twenty consecutive patients (8 men, 12 women, mean age of 48.2, range: 14-78) with suspected pituitary pathology who were referred for Ga-68-DOTATATE PET-CT. Results Nine patients presented with recurrent Cushing's syndrome following surgical resection of pituitary adenomas due to recurrent Cushing's disease (seven patients) and ectopic ACTH secreting tumor (2 patients). All seven patients with recurrent Cushing's disease showed positive pituitary Ga-68-DOTATATE uptake while both cases of ectopic hormonal secretion had absent pituitary uptake. In 1 of these 2 patients Ga-68-DOTATATE was able to localize the source of ectopic ACTH tumor. Six patients presented de novo with Cushing's due to ectopic ACTH secretion; Ga-68‑DOTATATE PET/CT was able to localize ectopic tumors in six of eight patients (3 lungs, 2 pancreases, 1 mid-gut) There was high uptake Ga-68-DOTATATE in 3 cases of recurrent central hyperthyroidism (SUVmax 6.6-14.3) and 2 cases of prolactinoma (SUVmax 5.5 and 11.3).Conclusion Absent Ga-68-DOTATATE activity in the pituitary fossa is useful in excluding pituitary disease in recurrent Cushing’s. Recurrent pituitary thyrotropinomas and prolactinomas showed moderate to high pituitary activity. In addition, in Cushing’s syndrome Ga-68-DOTATATE is useful for detection of ectopic sources of ACTH production, especially where anatomic imaging is negative.

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