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

2007 ◽  
Vol 23 (3) ◽  
pp. 1-6 ◽  
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.

scholarly journals Cyclic Cushing's disease with misleading inferior petrosal sinus sampling results during a trough phase

2015 ◽  
Vol 38 (2) ◽  
pp. E7 ◽  
Author(s):  
Vivien Bonert ◽  
Namrata Bose ◽  
John D. Carmichael
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Adrenocorticotropic Hormone ◽  
Diagnostic Testing ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Inferior Petrosal Sinus ◽  
Inferior Petrosal Sinus Sampling ◽  
Acth Secreting ◽  
Transsphenoidal Resection

Diagnosing Cushing's syndrome is challenging and is further hampered when investigations are performed in a patient with cyclic Cushing's syndrome. A subset of patients with Cushing's syndrome exhibit periods of abnormal cortisol secretion with interspersed normal secretion. Patients can have periods of clinical improvement during these quiescent phases or remain symptomatic. Initial diagnostic testing can be challenging because of the unpredictable durations of the peak and trough phases, and it is especially challenging when the diagnosis of cyclic Cushing's syndrome has not yet been determined. Here, the authors present the case of a patient with Cushing's disease with a pathology-proven adrenocorticotropic hormone (ACTH)–secreting pituitary adenoma and whose initial inferior petrosal sinus sampling (IPSS) results were deemed indeterminate; further studies elucidated the diagnosis of cyclic Cushing's syndrome. Repeat IPSS was diagnostic of a central source for ACTH secretion, and the patient was treated successfully with transsphenoidal resection. Literature concerning the diagnosis and management of cyclic Cushing's syndrome is also reviewed.

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

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.

The 24-h cortisol secretory pattern in Cushing's syndrome

1986 ◽  
Vol 112 (2) ◽  
pp. 230-237 ◽  
Author(s):  
J. Tourniaire ◽  
D. Chalendar ◽  
B. Rebattu ◽  
M. Fevre-Montange ◽  
L. Bajard ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Plasma Cortisol ◽  
Adrenal Adenoma ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Acth Secretion ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Cortisol Release

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.

scholarly journals Rapidly progressive ACTH-dependent Cushing’s disease masquerading as ectopic ACTH-producing Cushing’s syndrome: illustrative case

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Siyuan Yu ◽  
Michael Karsy ◽  
Jeffrey Miller ◽  
Stephanie R. Beldick ◽  
Mark T. Curtis ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Cavernous Sinus ◽  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Rapid Evolution ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Illustrative Case ◽  
Ectopic Acth ◽  
Free Cortisol

BACKGROUND Cushing’s disease (CD) remains a challenging condition to diagnose and treat. This case study highlights the challenges of diagnosing CD when faced with discrepant clinical, biochemical, and radiological findings. OBSERVATIONS A 62-year-old man presented with rapid evolution of symptoms, including depression, fatigue, and extreme muscle atrophy, which resulted in the patient being a wheelchair user over the course of a few months. His rapid clinical course in conjunction with hypercortisolemia in the setting of a pituitary macroadenoma involving the cavernous sinus, two large pulmonary nodules, and urine-free cortisol levels in the thousands suggested an aggressive ectopic adrenocorticotropic hormone (ACTH) source. After extensive testing ruled out CD from an ectopic source and because of the patient’s abrupt clinical deterioration, the authors concluded that the source was likely an aggressive pituitary adenoma. Therefore, the authors performed an endonasal transsphenoidal approach for resection of the pituitary adenoma involving the cavernous sinus, and the patient was scheduled for radiosurgery to control tumor progression. LESSONS Although extremely high levels of cortisol and ACTH are associated with ectopic Cushing’s syndrome, they may also indicate an aggressive form of CD. Suspicion should be maintained for hypercortisolemia from a pituitary source even when faced with discrepant information that may suggest an ectopic source.

scholarly journals The role of bilateral inferior petrosal sinus sampling in the diagnosis of Cushing's syndrome

2007 ◽  
Vol 51 (8) ◽  
pp. 1329-1338 ◽  
Author(s):  
Andrea Utz ◽  
Beverly M.K. Biller
Keyword(s):  
Cushing’S Syndrome ◽  
Venous Drainage ◽  
Cushing's Syndrome ◽  
Blood Levels ◽  
Inferior Petrosal Sinus ◽  
Ectopic Acth ◽  
Inferior Petrosal Sinus Sampling ◽  
Neoplastic Lesion ◽  
Before And After ◽  
Acth Secreting

Adrenocorticotropin hormone (ACTH)-dependent Cushing's syndrome is most often due to a pituitary corticotroph adenoma, with ectopic ACTH-secreting tumors representing approximately 15% of cases. Biochemical and radiological techniques have been established to help distinguish between these two entities, and thus aid in the localization of the neoplastic lesion for surgical resection. The test that offers the highest sensitivity and specificity is bilateral inferior petrosal sinus sampling (BIPSS). BIPSS is an interventional radiology procedure in which ACTH levels obtained from venous drainage very near the pituitary gland are compared to peripheral blood levels before and after corticotropin hormone (CRH) stimulation. A gradient between these two locations indicates pituitary Cushing's, whereas the absence of a gradient suggests ectopic Cushing's. Accurate BIPSS results require hypercortisolemia to suppress normal corticotroph ACTH production and hypercortisolemia at the time of the BIPSS to assure excessive ACTH secretion. In some cases, intrapituitary gradients from side-to-side can be helpful to localize small corticotroph adenomas within the sella. BIPSS has rare complications and is considered safe when performed at centers with experience in this specialized technique.

scholarly journals Cushing’s Syndrome: Important Issues in Diagnosis and Management

2006 ◽  
Vol 91 (10) ◽  
pp. 3746-3753 ◽  
Author(s):  
James W. Findling ◽  
Hershel Raff
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Evidence Synthesis ◽  
Somatostatin Receptor ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Ectopic Acth Syndrome ◽  
Ectopic Acth ◽  
Late Night ◽  
Recent Monograph

Abstract Context: The diagnosis, differential diagnosis, and treatment of Cushing’s syndrome are challenging problems in clinical endocrinology. We focus on critical questions addressing screening for Cushing’s syndrome, differentiation of Cushing’s subtypes, and treatment options. Evidence Acquisition: Ovid’s MEDLINE (1996 through April 2006) was used to search the general literature. We also relied on previously published reviews and a recent monograph and cite a mix of primary articles and recent reviews. Evidence Synthesis: Although this article represents our opinion, it draws heavily on a recent consensus statement from experts in the field and a recent monograph on Cushing’s syndrome. Conclusions: We concluded that: 1) measurement of late-night or bedtime salivary cortisol is a useful approach to screen for Cushing’s syndrome; 2) measurement of suppressed plasma ACTH by immunometric assay is useful to differentiate ACTH-dependent and -independent Cushing’s syndrome; 3) inferior petrosal sinus sampling for ACTH should be performed in patients with ACTH-dependent hypercortisolism in whom a pituitary magnetic resonance imaging is normal or equivocal (in the absence of a pituitary ACTH gradient, prolactin levels should be measured to confirm the integrity of venous sampling); 4) computed tomography of the chest and abdomen and somatostatin receptor scintigraphy should be performed in patients with the occult ectopic ACTH syndrome; and 5) patients with Cushing’s disease should be referred to a neurosurgeon with extensive experience operating on corticotroph microadenomas. Bilateral laparoscopic adrenalectomy should be considered in patients with Cushing’s disease who fail therapies directed at the pituitary.

scholarly journals Pleurihormonal Pituitary Adenomas Presenting as Acromegaly

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A602-A602
Author(s):  
Megan Schwehr ◽  
Mayumi Endo
Keyword(s):  
Pituitary Adenoma ◽  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Pituitary Adenomas ◽  
Brain Mri ◽  
Fatty Infiltration ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Peripheral Muscle ◽  
Suppression Test

Abstract Background: Pleurihormonal pituitary adenomas represent 10-15% of all functioning pituitary adenomas1. One of the rarest combinations is ACTH-GH co-secretion with concomitant acromegaly and Cushing’s disease. Clinical Case: 30-year-old female with type 2 diabetes (A1c 11.4%) developed rapidly progressive peripheral neuropathy. Labs revealed a transaminitis. Hepatic ultrasound revealed fatty infiltration of the liver consistent with steatosis. Patient endorsed life-long “chicken legs”, buffalo hump, and easy bruising. She continued to have worsening paresthesias and stated her teeth were “more translucent”. At an endocrinology visit peripheral muscle wasting, atraumatic bruising at the ankles and toes,and striae on the abdomen, shoulders, breasts, and armpits were noted. She had also noted teeth separation and thinning over time and worsening diffuse joint aches. Lab results showed elevated cortisol value of 8.4 mcg/dl after 1 mg dexamethasone suppression test. 24-hour urine cortisol was elevated (87 ug/24 hrs, nl < 45 ug/24 hrs), confirming the diagnosis of Cushing’s syndrome. ACTH was inappropriately normal (56 pg/mL, nl 7.2 – 63 pg/mL), suggesting ACTH dependency. IGF-1 was elevated twice (328 ng/dL and 391 ng/dL, nl <303 ng/dL), and a GH suppression test was abnormal (GH 1.14 ng/mL at 90 minutes) confirming the diagnosis of acromegaly. Brain MRI revealed a cystic pituitary microadenoma (0.5 x 0.5 x 0.6 cm), and the patient underwent surgical resection via transnasal transsphenoidal pituitary surgery with total tumor removal. Immunostaining was positive for only synaptophysin and ACTH. Postoperative diagnosis of Cushing’s disease was made, with formal diagnosis of acromegaly pending improvement in follow-up IGF-1 levels. Literature reviews have revealed very few cases of pleurihormonal pituitary adenomas presenting with concomitant Cushing’s Syndrome and acromegaly. Roca et. al examined 17 studies which described 20 patients with this condition; only 4 presented with symptoms of both acromegaly and Cushing’s disease. In many cases previously reported, the clinical presentation of Cushing’s syndrome was subtle, often with subclinical Cushing’s syndrome, while patients had florid symptoms of acromegaly.1. Conclusion: This Cushing’s predominant case of a GH-ACTH co-secreting tumor is an incredibly rare presentation for this pleurihormonal pituitary adenoma, which is already a rare diagnosis. References: 1.Roca E, Mattogno PP, Porcelli T, Poliani L, Belotti F, Schreiber A, Maffezzoni F, Fontanella MM, Doglietto F. Plurihormonal ACTH-GH Pituitary Adenoma: Case Report and Systematic Literature Review. World Neurosurg. 2018 Jun;114:e158-e164. PMID: 29501516.

scholarly journals ACTH Dependent Cushing’s Syndrome: A 72-Hour Trial of Octreotide will Identify Patients with Pituitary Dependent and Ectopic ACTH Overproduction

2020 ◽  
pp. 65-70
Author(s):  
Omayma Elshafie ◽  
Nicholas Woodhouse
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Somatostatin Receptors ◽  
Serum Cortisol ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Pituitary Tumours ◽  
Ectopic Acth ◽  
Suppression Test ◽  
Cortisol Levels

Aims: To determine whether the use of an octreotide suppression test will reliably distinguish pituitary from ectopic ACTH overproduction.  Somatostatin receptors are expressed in NETs, but are downgraded in the pituitary as the result of hypercortisolaemia. Octreotide should therefore lower ACTH and cortisol levels in patients with NETs but not in patients with Cushing’s disease and pituitary tumors. Methodology: A cross sectional study was performed in 13 patents with ACTH dependent Cushing’s (8 women, 5 men) with ages ranging between 21 to 40 years were studied. Serum cortisol concentrations were measured at 0800 hrs before and during the administration of. Octreotide at a dosage of 100 mcg subcutaneously every 8 hours for 72 hours. Results: The serum cortisol concentrations returned to normal in 4 patients who were later documented to have ectopic disease, two with typical bronchial carcinoids and two with pancreatic NETs and metastatic disease. The other 9 patients had no suppression in serum cortisol concentrations and were documented later to have pituitary tumours. Conclusion: These results indicate that a short trial of octreotide will identify patients with ectopic disease as evidenced by a fall in serum cortisol levels whereas in those with Cushing’s disease and pituitary tumours serum cortisol levels remains unchanged.  Recommendation: We recommend all patients with ACTH dependent Cushing’s syndrome have an octreotide suppression test, even if the MRI shows an adenoma, so as to exclude the possibility of a pituitary incidentaloma in a patient with ectopic disease, or false localization from IPSS to the pituitary gland due to ectopic CRH secretion.

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