Desmopressin test in the diagnosis and follow-up of cyclical Cushing's disease

Abstract Introduction The clinical practice and research in the diagnosis and management of Cushing’s disease remains heterogeneous and challenging to this day. We sought to establish the characteristics of Cushing’s disease, and the trends in diagnosis, management and reporting in this field. Methods Searches of PubMed and Embase were conducted. Study protocol was registered a-priori. Random-effects analyses were conducted to establish numerical estimates. Results Our screening returned 159 papers. The average age of adult patients with Cushing’s disease was 39.3, and 13.6 for children. The male:female ratio was 1:3. 8% of patients had undergone previous transsphenoidal resection. The ratio of macroadenomas: microadenomas:imaging-undetectable adenomas was 18:53:29. The most commonly reported preoperative biochemical investigations were serum cortisol (average 26.4µg/dL) and ACTH (77.5pg/dL). Postoperative cortisol was most frequently used to define remission (74.8%), most commonly with threshold of 5µg/dL (44.8%). Average remission rates were 77.8% with recurrence rate of 13.9%. Median follow-up was 38 months. Majority of papers reported age (81.9%) and sex (79.4%). Only 56.6% reported whether their patients had previous pituitary surgery. 45.3% reported whether their adenomas were macroadenoma, microadenoma or undetectable. Only 24.1% reported preoperative cortisol, and this did not improve over time. 60.4% reported numerical thresholds for cortisol in defining remission, and this improved significantly over time (p = 0.004). Visual inspection of bubbleplots showed increasing preference for threshold of 5µg/dL. 70.4% reported the length of follow up. Conclusion We quantified the characteristics of Cushing’s disease, and analysed the trends in investigation and reporting. This review may help to inform future efforts in forming guidelines for research and clinical practice.

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Outcomes of endoscopic transsphenoidal surgery for Cushing's disease

BMC Endocrine Disorders ◽

10.1186/s12902-021-00679-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zarina Brady ◽

Aoife Garrahy ◽

Claire Carthy ◽

Michael W. O’Reilly ◽

Christopher J. Thompson ◽

...

Keyword(s):

Diabetes Insipidus ◽

Cushing’S Disease ◽

Transsphenoidal Surgery ◽

Remission Rate ◽

Cushing's Disease ◽

Endoscopic Transsphenoidal Surgery ◽

Endocrine Society ◽

Csf Leakage ◽

Remission Rates

Abstract Background Transsphenoidal surgery (TSS) to resect an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma is the first-line treatment for Cushing’s disease (CD), with increasing usage of endoscopic transsphenoidal (ETSS) technique. The aim of this study was to assess remission rates and postoperative complications following ETSS for CD. Methods A retrospective analysis of a prospective single-surgeon database of consecutive patients with CD who underwent ETSS between January 2012–February 2020. Post-operative remission was defined, according to Endocrine Society Guidelines, as a morning serum cortisol < 138 nmol/L within 7 days of surgery, with improvement in clinical features of hypercortisolism. A strict cut-off of < 50 nmol/L at day 3 post-op was also applied, to allow early identification of remission. Results A single surgeon (MJ) performed 43 ETSS in 39 patients. Pre-operative MRI localised an adenoma in 22 (56%) patients; 18 microadenoma and 4 macroadenoma (2 with cavernous sinus invasion). IPSS was carried out in 33 (85%) patients. The remission rates for initial surgery were 87% using standard criteria, 58% using the strict criteria (day 3 cortisol < 50 nmol/L). Three patients had an early repeat ETSS for persistent disease (day 3 cortisol 306-555 nmol/L). When the outcome of repeat early ETSS was included, the remission rate was 92% (36/39) overall. Remission rate was 94% (33/35) when patients with macroadenomas were excluded. There were no cases of CSF leakage, meningitis, vascular injury or visual deterioration. Transient and permanent diabetes insipidus occurred in 33 and 23% following first ETSS, respectively. There was one case of recurrence of CD during the follow-up period of 24 (4–79) months. Conclusion Endoscopic transsphenoidal surgery produces satisfactory remission rates for the primary treatment of CD, with higher remission rates for microadenomas. A longer follow-up period is required to assess recurrence rates. Patients should be counselled regarding risk of postoperative diabetes insipidus.

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Endoscopic transsphenoidal pituitary surgery: a good and safe primary treatment option for Cushing's disease, even in case of macroadenomas or invasive adenomas

Acta Endocrinologica ◽

10.1530/eje-13-0325 ◽

2013 ◽

Vol 169 (3) ◽

pp. 329-337 ◽

Cited By ~ 48

Author(s):

M A E M Wagenmakers ◽

H D Boogaarts ◽

S H P P Roerink ◽

H J L M Timmers ◽

N M M L Stikkelbroeck ◽

...

Keyword(s):

Treatment Option ◽

Cushing’S Disease ◽

Remission Rate ◽

Pituitary Surgery ◽

Primary Treatment ◽

Endoscopic Technique ◽

Cushing's Disease ◽

Recurrence Rates ◽

Transsphenoidal Pituitary Surgery

ContextAlthough the endoscopic technique of transsphenoidal pituitary surgery (TS) has been widely adopted, reports on its results in Cushing's disease (CD) are still scarce and no studies have investigated long-term recurrence rates. This is the largest endoscopic series published till now.ObjectiveTo gain insight into the role of endoscopic TS as a primary treatment option for CD, especially in patients with magnetic resonance imaging (MRI)-negative CD and (invasive) macroadenomas.DesignRetrospective cohort study.Patients and methodsThe medical records of 86 patients with CD who underwent endoscopic TS were examined. Data on preoperative and postoperative evaluation, perioperative complications, and follow-up were collected. Remission was defined as disappearance of clinical symptoms with a fasting plasma cortisol level ≤50 nmol/l either basal or after 1 mg dexamethasone.ResultsThe remission rate in different adenoma subclasses varied significantly: 60% in MRI-negative CD (n=20), 83% in microadenomas (n=35), 94% in noninvasive macroadenomas (n=16), and 40% in macroadenomas that invaded the cavernous sinus (n=15). The recurrence rate was 16% after 71±39 months of follow-up (mean±s.d., range 10–165 months).ConclusionsEndoscopic TS is a safe and effective treatment for all patients with CD. Recurrence rates after endoscopic TS are comparable with those reported for microscopic TS. Our data suggest that in patients with noninvasive and invasive macroadenomas, the endoscopic technique of TS should be the treatment of choice as remission rates seem to be higher than those reported for microscopic TS, although no comparative study has been performed.

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T1 mapping in Cushing's disease: a follow-up study

Journal of Cardiovascular Magnetic Resonance ◽

10.1186/1532-429x-17-s1-p310 ◽

2015 ◽

Vol 17 (S1) ◽

Author(s):

Roux Charles ◽

Nadjia Kachenoura ◽

Peter Kamenicky ◽

Elie Mousseaux ◽

Philippe Chanson ◽

...

Keyword(s):

Cushing’S Disease ◽

T1 Mapping ◽

Cushing's Disease ◽

Follow Up Study

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Long term follow-up of transsphenoidal surgery for the treatment of Cushing's disease in childhood.

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.80.8.7629245 ◽

1995 ◽

Vol 80 (8) ◽

pp. 2475-2479 ◽

Cited By ~ 1

Author(s):

M C Leinung ◽

L A Kane ◽

B W Scheithauer ◽

P C Carpenter ◽

E R Laws ◽

...

Keyword(s):

Cushing’S Disease ◽

Transsphenoidal Surgery ◽

Cushing's Disease ◽

Long Term Follow Up

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Outcome of endoscopic vs microsurgical transsphenoidal resection for Cushing’s disease

Endocrine Connections ◽

10.1530/ec-17-0312 ◽

2018 ◽

Vol 7 (1) ◽

pp. R26-R37 ◽

Cited By ~ 4

Author(s):

Nidan Qiao

Keyword(s):

Recurrence Rate ◽

Cushing’S Disease ◽

Meta Analysis ◽

Cushing's Disease ◽

Recurrence Rates ◽

Microscopic Surgery ◽

Significant Difference ◽

Comprehensive Search ◽

Definition Of

Introduction It is unclear whether the proportions of remission and the recurrence rates differ between endoscopic transsphenoidal surgery (TS) and microscopic TS in Cushing’s disease (CD); thus, we conducted a systematic review and meta-analysis to evaluate studies of endoscopic TS and microscopic TS. Methods We conducted a comprehensive search of PubMed to identify relevant studies. Remission and recurrence were used as outcome measures following surgical treatment of CD. Results A total of 24 cohort studies involving 1670 adult patients were included in the comparison. Among these studies, 702 patients across 9 studies underwent endoscopic TS, and 968 patients across 15 studies underwent microscopic TS. Similar baseline characteristics were observed in both groups. There was no significant difference in remission between the two groups: 79.7% (95% CI: 73.1–85.0%) in the endoscopic group and 76.9% (95% CI: 71.3–81.6%) in the microscopic group (P = 0.485). It appears that patients who underwent endoscopic surgery experience recurrence less often than patients who underwent microscopic surgery, with recurrence proportions of 11.0% and 15.9%, respectively (P = 0.134). However, if follow-up time is taken into account, both groups had a recurrence rate of approximately 4% per person per year (95% CI: 3.1–5.4% and 3.6–5.1%, P = 0.651). Conclusions We found that remission proportion and recurrence rate were the same in patients who underwent endoscopic TS as in patients who underwent microscopic TS. The definition of diagnosis, remission and recurrence should always be considered in the studies assessing therapeutic efficacy in CD.

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Gamma Knife surgery for Cushing's disease

Journal of Neurosurgery ◽

10.3171/jns.2007.106.6.980 ◽

2007 ◽

Vol 106 (6) ◽

pp. 980-987 ◽

Cited By ~ 192

Author(s):

Jay Jagannathan ◽

Jason P. Sheehan ◽

Nader Pouratian ◽

Edward R. Laws ◽

Ladislau Steiner ◽

...

Keyword(s):

Gamma Knife ◽

Cushing’S Disease ◽

Pituitary Adenomas ◽

Cranial Nerve ◽

Gamma Knife Surgery ◽

Cushing's Disease ◽

Free Cortisol ◽

Radiation Induced ◽

The Mean

Object In this study the authors address the efficacy and safety of Gamma Knife surgery (GKS) in patients with adrenocorticotropic hormone–secreting pituitary adenomas. Methods A review of data collected from a prospective GKS database between January 1990 and March 2005 was performed in patients with Cushing's disease. All but one patient underwent resection for a pituitary tumor, without achieving remission. Successful endocrine outcome after GKS was defined as a normal 24-hour urinary free cortisol (UFC) concentration posttreatment after a minimum of 1 year of follow up. Patient records were also evaluated for changes in tumor volume, development of new hormone deficiencies, visual acuity, cranial nerve neuropathies, and radiation-induced imaging changes. Ninety evaluable patients had undergone GKS, with a mean endocrine follow-up duration of 45 months (range 12–132 months). The mean dose to the tumor margin was 23 Gy (median 25 Gy). Normal 24-hour UFC levels were achieved in 49 patients (54%), with an average time of 13 months after treatment (range 2–67 months). In the 49 patients in whom a tumor was visible on the planning magnetic resonance (MR) image, a decrease in tumor size occurred in 39 (80%), in seven patients there was no change in size, and tumor growth occurred in three patients. Ten patients (20%) experienced a relapse of Cushing's disease after initial remission; the mean time to recurrence was 27 months (range 6–60 months). Seven of these patients underwent repeated GKS, with three patients achieving a second remission. New hormone deficiencies developed in 20 patients (22%), with hypothyroidism being the most common endocrinopathy after GKS. Five patients experienced new visual deficits or third, fourth, or sixth cranial nerve deficits; two of these patients had undergone prior conventional fractionated radiation therapy, and four of them had received previous GKS. Radiation-induced changes were observed on MR images in three patients; one had symptoms attributable to these changes. Conclusions Gamma Knife surgery is an effective treatment for persistent Cushing's disease. Adenomas with cavernous sinus invasion that are not amenable to resection are treatable with the Gamma Knife. A second GKS treatment appears to increase the risk of cranial nerve damage. These results demonstrate the value of combining two neurosurgical treatment modalities—microsurgical resection and GKS—in the management of pituitary adenomas.

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