External jugular venous sampling for Cushing’s disease in a patient with hypoplastic inferior petrosal sinuses

The authors report the case of a 30-year-old female patient with suspected Cushing’s disease with an anatomical variation of hypoplastic inferior petrosal sinuses and nearly exclusive anterior drainage from the cavernous sinus, who underwent external jugular venous blood sampling with successful disease confirmation and microadenoma localization. The patient presented with signs and symptoms consistent with Cushing’s syndrome, but with discordant preliminary diagnostic testing. She underwent attempted bilateral inferior petrosal sinus sampling; however, she had hypoplastic inferior petrosal sinuses bilaterally and predominantly anterior drainage from the cavernous sinus into the external jugular circulation. Given this finding, the decision was made to proceed with external jugular venous access and sampling in addition to internal jugular venous sampling. A positive adrenocorticotropic hormone (ACTH) response to corticotropin-releasing factor was obtained in the right external jugular vein alone, suggesting a right-sided pituitary microadenoma as the cause of her Cushing’s disease. The patient subsequently underwent a transsphenoidal hypophysectomy that confirmed the presence of a right-sided ACTH-secreting microadenoma, which was successfully resected. She was hypocortisolemic on discharge and has had no signs of recurrence or relapse at 6 months postoperation.

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Clinical, Biological, Radiological Pathological and Immediate Post-Operative Remission of Sparsely and Densely Granulated Corticotroph Pituitary Tumors: A Retrospective Study of a Cohort of 277 Patients With Cushing’s Disease

Frontiers in Endocrinology ◽

10.3389/fendo.2021.672178 ◽

2021 ◽

Vol 12 ◽

Author(s):

Beata Rak ◽

Maria Maksymowicz ◽

Monika Pękul ◽

Grzegorz Zieliński

Keyword(s):

Cushing’S Disease ◽

Pituitary Tumors ◽

Signs And Symptoms ◽

Cortisol Concentration ◽

Cushing's Disease ◽

Ki 67 ◽

Remission Status ◽

Multiple Data ◽

The Mean ◽

Corticotroph Adenomas

PurposeCushing’s disease is the most common cause of endogenous hypercortisolemia due to a corticotroph pituitary tumor. Up-to-date there is no reliable biomarker of invasiveness among corticotroph tumors, while it is well established in the literature that sparsely granulated somatotroph tumors are characterized by poorer prognosis. The aim of the study was to correlate multiple data including clinical, biochemical, radiological, and pathological findings (including granulation pattern) as well as immediate post-operative remission status among patients operated on due to corticotroph tumors.MethodsWe enrolled all patients consecutively operated on for planned transsphenoidal neurosurgery due to corticotroph PitNETs in years 2010–2018. We excluded from analysis silent corticotroph tumors, plurihormonal PitNETs, and the Crooke’s cell adenomas.ResultsWe recorded 348 hormonally active corticotroph PitNETs. The results of the analysis showed the female predominance 79.88% (n = 278), with the mean age of Cushing’s disease occurrence 43.27 years of age. The mean time from the first signs and symptoms to the operation was 2 years. The women were diagnosed earlier (20–40 years of age vs. 50–60 years of age among men). We performed a detailed analysis of 277 cases classified by granularity pattern as DG or SG corticotroph PitNETs. Densely granulated tumors (DG) occurred four times more frequently than sparsely granulated (SG) (n = 225 vs. n = 52), at similar age (mean 42.94; median 40 vs. mean 45.46; median 45.5; p = 0.3896), but were characterized by lower Knosp’s scale grades (p = 0.0147*), smaller preoperative tumors’ volumes measured at MRI, and more commonly exhibited lower Ki-67 labeling index (<3%) (p = 0.0168*). What is more, DG adenomas more frequently achieved an immediate remission status (measured as postoperative cortisol concentration <2 µg/dl; p = 0.0180*), and the mean postoperative cortisol concentration in DG group was lower than in SG group (mean 5.375 µg/dl vs. 10.47 µg/dl; median 2.49 µg/dl vs. 6.52 µg/dl; p = 0.0028**).ConclusionsOur study indicates that DG corticotroph adenomas occurred at younger age, more commonly were microadenomas as compared to SG tumors, less frequently had invasive features in comparison to SG corticotroph adenomas (p = 0.0019**), and more commonly achieved an immediate postsurgical hormonal remission (p = 0.0180*). We highlight the need for an accurate differentiation of DG and SG subtypes in the pathomorphological diagnosis of corticotropic tumors, especially in invasive PitNETs.

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Selective Venous Sampling for ACTH in Cushing’s Syndrome: Differentiation Between Cushing’s Disease and the Ectopic ACTH Syndrome

The Journal of Urology ◽

10.1016/s0022-5347(17)53960-9 ◽

1982 ◽

Vol 127 (3) ◽

pp. 618-619

Author(s):

J.W. Findling ◽

D.C. Aron ◽

J.B. Tyrrell ◽

J.H. Shinsako ◽

P.A. Fitzgerald ◽

...

Keyword(s):

Cushing’S Syndrome ◽

Cushing’S Disease ◽

Cushing's Syndrome ◽

Cushing's Disease ◽

Ectopic Acth Syndrome ◽

Syndrome Differentiation ◽

Venous Sampling ◽

Ectopic Acth ◽

Selective Venous Sampling

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Lateralization of inferior petrosal sinus sampling in Cushing's disease correlates with cavernous sinus venous drainage patterns, but not tumor lateralization

Heliyon ◽

10.1016/j.heliyon.2020.e05299 ◽

2020 ◽

Vol 6 (10) ◽

pp. e05299

Author(s):

Mohammad Ghorbani ◽

Hamideh Akbari ◽

Christoph J. Griessenauer ◽

Christoph Wipplinger ◽

Alireza Dastmalchi ◽

...

Keyword(s):

Cavernous Sinus ◽

Cushing’S Disease ◽

Venous Drainage ◽

Cushing's Disease ◽

Inferior Petrosal Sinus ◽

Inferior Petrosal Sinus Sampling ◽

Drainage Patterns

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Treatment effectiveness of pasireotide on health-related quality of life in patients with Cushing's disease

Acta Endocrinologica ◽

10.1530/eje-13-1013 ◽

2014 ◽

Vol 171 (1) ◽

pp. 89-98 ◽

Cited By ~ 14

Author(s):

Susan M Webb ◽

John E Ware ◽

Anna Forsythe ◽

Min Yang ◽

Xavier Badia ◽

...

Keyword(s):

Quality Of Life ◽

Cushing’S Disease ◽

Treatment Effectiveness ◽

Clinical Signs ◽

Signs And Symptoms ◽

Cushing's Disease ◽

Health Related Quality ◽

Related Quality ◽

Health Related

ObjectiveCushing's disease (CD) can significantly impair patients' health-related quality of life (HRQOL). This study investigated the treatment effectiveness of pasireotide on HRQOL of CD patients, and assessed the relationships between HRQOL and urinary free cortisol (UFC) and CD-related signs and symptoms.DesignIn this phase III, randomized, double-blind study, patients with UFC ≥1.5×upper limit of normal (ULN) received s.c. pasireotide 600 or 900 μg twice daily. The trial primary endpoint was UFC at or below ULN at month 6 without dose titration. Open-label treatment continued through month 12. HRQOL was measured using the Cushing's Quality of Life Questionnaire (CushingQoL) instrument at baseline and follow-up visits until month 12 during which clinical signs and features of CD, and the Beck Depression Inventory II (BDI-II), were also collected.MethodsPearson's/Spearman's correlations between changes in CushingQoL and changes in clinical signs and symptoms were assessed. Changes in CushingQoL and the proportion of patients achieving a clinically meaningful improvement in CushingQoL were also compared among patients stratified by mean UFC (mUFC) control status (controlled, partially controlled, and uncontrolled) at month 6. Analyses were also conducted at month 12, with multivariable adjustment for baseline characteristics and CushingQoL.ResultsChange in CushingQoL was significantly correlated with changes in mUFC (r=−0.40), BMI (r=−0.39), weight (r=−0.41), and BDI-II (r=−0.54) at month 12 but not at month 6. The percentage of CushingQoL responders at month 12 based on month 6 mUFC control status were as follows: 63, 58.8, and 37.9% in the controlled, partially controlled, and uncontrolled groups respectively. Adjusted CushingQoL scores at month 12 were 58.3 for controlled patients (Δ=11.5 vs uncontrolled,P=0.012) and 54.5 for partially controlled patients (Δ=7.7 vs uncontrolled,P=0.170).ConclusionsPasireotide treatment can result in a meaningful HRQOL improvement among those who complete a 12-month treatment period, most often among patients achieving biochemical control.

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

Neurosurgical FOCUS ◽

10.3171/2014.12.focus14780 ◽

2015 ◽

Vol 38 (2) ◽

pp. E7 ◽

Cited By ~ 9

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.

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Factors associated with recurrence after endoscopic transphenoidal surgery for Cushing’s disease

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2015.186 ◽

2015 ◽

Vol 42 (S1) ◽

pp. S41-S41

Author(s):

Y Meng ◽

S Suppiah ◽

L Gonen ◽

G Klironomos ◽

F Gentili ◽

...

Keyword(s):

Cavernous Sinus ◽

Cushing’S Disease ◽

Univariate Analysis ◽

Cushing's Disease ◽

Serum Cortisol Level ◽

Surgical Removal ◽

Significant Variable ◽

Safe Procedure ◽

Sinus Wall

Introduction: Surgical removal is the standard treatment for Cushing’s disease. Although endoscopic transsphenoidal surgical (ETS) approach has grown in popularity, its efficacy has not yet been established. Furthermore, achieving long-term remission remains challenging. Methods: We conducted a retrospective chart review of 39 consecutive patients who underwent ETS for Cushing’s disease at our institution between 2005 and 2014. Univariate analysis using Pearson’s χ2 test was carried out on variables of patient demographics, radiology, pathology, biochemical markers versus recurrence. Results: The mean age was 40, with 82% females. Average length of follow-up was 44.8 months. Based on serum cortisol level, 28 patients (71%) achieved mid to long-term remission after ETS. Of them, 25 experienced an immediate remission, and 3 achieved a delayed remission as long as 4 months postoperatively. MRI findings of (1) microadenomas or no detectable abnormality, (2) adjacency to the cavernous sinus wall were associated with significantly higher recurrence rate (p<0.05). Histologically, MIB-1 >5% was not a significant variable (p=0.55). Conclusion: We found ETS resection to be an effective and safe procedure for majority of the ACTH-secreting adenomas, with remission rates >70%. Additionally, patients with microadenomas, negative preoperative MR, and cavernous sinus adjacency were less likely to achieve remission.

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PC3 - 142 Gamma Knife Radiosurgery in Patients with Persistent Acromegaly or Cushing’s Disease: Long-Term Risk of Hypopituitarism

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2016.393 ◽

2016 ◽

Vol 43 (S4) ◽

pp. S22-S22

Author(s):

O. Cohen-Inbar

Keyword(s):

Gamma Knife ◽

Cavernous Sinus ◽

Cushing’S Disease ◽

Hormone Replacement ◽

Gamma Knife Radiosurgery ◽

Common Adverse Effect ◽

Cushing's Disease ◽

Pituitary Hormone

For patient with a recurrent or residual acromegaly or Cushing’s disease (CD) after resection, Gamma knife radiosurgery (GKRS) is often used. Hypopituitarism is the most common adverse effect after GKRS treatment. The paucity of studies with long-term follow up has hampered understanding of the latent risks of hypopituitarism in patients with a Acromegaly or CD. We report the long-term risks of hypopituitarism for patients treated with GKRS for Acromegaly or CD. Methods: From a prospectively created, IRB approved database, we identified all patients with a Acromegaly or CD treated with GKRS at the University of Virginia from 1989 to 2008. Only patients with a minimum endocrine follow up of 60 months were included. The median follow-up is 159.5 months (60.1-278). Thorough radiological and endocrine assessments were performed immediately before GKRS and at regular follow-up intervals. New onset of hypopituitarism was defined as pituitary hormone deficits after GKRS requiring corresponding hormone replacement. Results: 60 patients with either Acromegaly or CD were included. Median tumor volume at time of GKRS was 1.3 cm3 (0.3-13.4), median margin dose was 25 Gy (6-30). GKRS induced new pituitary deficiency occurred in 58.3% (n=35) of patients. Growth Hormone deficiency was most common (28.3%, n=17). The actuarial overall rates of hypopituitarism at 3, 5, and 10 years were 10%, 21.7%, and 53.3%, respectively. The median time to hypopituitarism was 61 months after GKRS (range, 12-160). Cavernous sinus invasion of the tumor was found to correlate with the occurrence of a new or progressive hypopituitarism after GKRS (p=0.018). Conclusions: Delayed hypopituitarism increases as a function of time after radiosurgery. Hormone axes appear to vary in terms of radiosensitivity. Patients with adenoma in the cavernous sinus are more prone to develop loss of pituitary function after GKRS.

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Cavernous Sinus Sampling Is Highly Accurate in Distinguishing Cushing’s Disease from the Ectopic Adrenocorticotropin Syndrome and in Predicting Intrapituitary Tumor Location1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.84.5.5654 ◽

1999 ◽

Vol 84 (5) ◽

pp. 1602-1610 ◽

Cited By ~ 1

Author(s):

Kathryn E. Graham ◽

Mary H. Samuels ◽

Gary M. Nesbit ◽

David M. Cook ◽

Oisin R. O’Neill ◽

...

Keyword(s):

Cavernous Sinus ◽

Cushing’S Disease ◽

Tumor Location ◽

Cushing's Disease ◽

Ectopic Acth Syndrome ◽

Plasma Acth ◽

Catheter Position ◽

Venous Flow ◽

Ectopic Acth ◽

Before And After

Inferior petrosal sinus sampling (IPSS) is used to distinguish pituitary Cushing’s disease from occult cases of the ectopic ACTH syndrome, but is limited in that it requires the use of ovine CRH (oCRH) and is not highly accurate at predicting the intrapituitary location of tumors. This study was designed to determine whether cavernous sinus sampling (CSS) is as safe and accurate as IPSS, whether CSS can eliminate the need for oCRH stimulation, and whether CSS can accurately predict the intrapituitary location of tumors. Ninety-three consecutive patients with ACTH-dependent Cushing’s syndrome were prospectively studied with bilateral, simultaneous CSS before and after oCRH stimulation. Prediction of a pituitary or ectopic ACTH source was based on cavernous/peripheral plasma ACTH ratios. Intrapituitary tumor location was predicted based on lateralization (side to side) ACTH ratios. These predictions were compared to surgical outcome in the 70 patients who had surgically proven pituitary (n= 65) or ectopic (n = 5) disease. CSS distinguished pituitary Cushing’s disease from the ectopic ACTH syndrome in 93% of patients with proven tumors before oCRH administration and in 100% of patients with proven tumors after oCRH. It was as safe and efficacious as published IPSS results. CSS accurately predicted the intrapituitary lateralization of the tumor in 83% of all patients and 89% of those patients with good catheter position and symmetric venous flow. CSS is as safe and accurate as IPSS for distinguishing patients with pituitary Cushing’s disease from those with the ectopic ACTH syndrome. In addition, CSS appears to be superior to IPSS for predicting intrapituitary tumor lateralization.

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