scholarly journals Increased Risk of Ocular Hypertension in Patients with Cushing’s Disease: An Underestimated Comorbidity

2020 ◽  
Author(s):  
Zhengyuan Chen ◽  
Yichen Ma ◽  
Zengyi Ma ◽  
Zhao Ye ◽  
Wenqiang He ◽  
...  
Keyword(s):  
Ocular Hypertension ◽  
Cushing’S Disease ◽  
Odds Ratio ◽  
Cushing's Disease ◽  
Control Groups ◽  
Fiber Layer ◽  
Nerve Fiber Layer Thickness ◽  
Increased Risk ◽  
Free Cortisol

Abstract BackgroundThe association between ocular hypertension and endogenous hypercortisolemia, as well as the ophthalmological outcomes after endocrine remission due to a surgical resection were still unknown. MethodsIntraocular pressure (IOP), visual field and peripapillary retinal nerve fiber layer thickness were documented in all patients with Cushing’s disease (CD) admitted to a tertiary pituitary center for surgery from Jan to Jul 2019. Patients with acromegaly and patients with nonfunctioning pituitary adenoma (NFPA) during the same study period were served as controls. We calculated the odds ratio and identified risk factors of developing ocular hypertension, and presented postoperative trends of IOP.Results52 patients (38.4±12.4 years old) with CD were included. IOP was higher in patients with CD (left 19.4 ± 5.4 mmHg and right 20.0 ± 7.1 mmHg) than patients with acromegaly (left 17.5 ± 2.3 mmHg and right 18.6 ± 7.0 mmHg, p = 0.033) and patients with NFPA (left 17.8 ± 2.6 mmHg and right 17.4 ± 2.4 mmHg, p = 0.005). 21 eyes (20.2%) in patients with CD were diagnosed with ocular hypertension comparing to 4 eyes (4.7%) in the acromegaly group and 4 eyes (4.5%) in the NFPA group. The odds ratio of developing ocular hypertension in patients with CD was 5.1 (95% CI, 1.3 – 25.1, p = 0.029) and 6.6 (95% CI, 1.8 – 30.3, p = 0.007), comparing with the two control groups, respectively. Among patients with CD, those with higher urine free cortisol were more likely to develop ocular hypertension (OR 19.4, 95% CI 1.7 – 72.6). IOP decreased at one-month follow-up in patients with CD and the change sustained at three-month follow-up. ConclusionsIn conclusion, patients with CD had increased risk of developing ocular hypertension comparing to other types of pituitary adenomas, which warrant the discretion of both ophthalmologists and neuroendocrinologists.

Gamma Knife surgery for Cushing's disease

2007 ◽  
Vol 106 (6) ◽  
pp. 980-987 ◽  
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.

scholarly journals SUN-305 Hair Cortisol Measurement: An Innovative Method for Diagnosis and Follow-Up in Patients with Cushing’s Disease

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Natalia Gabriela Deligiannis ◽  
Soledad Sosa ◽  
Diego Gonzalez ◽  
Carolina Ibar ◽  
Dario Gustavo Jacobsen ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Reference Interval ◽  
Urinary Free Cortisol ◽  
Cushing's Disease ◽  
Control Group ◽  
Hair Cortisol ◽  
Kappa Index ◽  
Free Cortisol ◽  
Pituitary Lesion

Abstract Diagnosis of endogenous Cushing’s syndrome entails corticotropic autonomy, lack of circadian rhythm and/or hypercortisolism, evaluated through 24h urinary free cortisol (UFC). Hair cortisol measurement (HCM) has been described as an alternative marker of cortisol exposure over the preceding three months. OBJECTIVES To evaluate HCM in Cushing’s disease (CD). To analyze the correlation between HCM and UFC. To compare HCM values in CD vs controls. PATIENTS AND METHODS 3 cm hair from posterior vertex in CD and in controls age- and gender-matched between May 2017 and May 2019. Controls were low level stressed individuals (Holmes-Rahe’s scale) without adrenal disease. Normal reference interval of HCM was defined (40-128 pg/mg hair). Measurement: Siemens Immulite 2000 (Gwynedd, UK) automated chemoluminiscent immunoassay (CLIA) UFC values within the 3 months previous to hair collection were considered. Controlled CD defined as UFC ≤1 upper normal limit (UNL) with or without treatment, remission as UFC ≤1 without pituitary lesion. Results are presented as median (m) and range. Kruskal-Wallis ANOVA used for median difference evaluation and Kappa index for concordance determination. Chi2 test for comparison of recategorized UFC and HCM. Statistical analysis performed with SPSS 23.0 RESULTS 23 CD patients recruited, median age 42 ± 11 years; 91% (n=21) female; 10 samples collected at diagnosis and 13 during follow-up. Control group composed of 50 individuals 45% (n=10) had controlled CD (mUFC 0.42 UNL, range 0.1-0.9) and a mHCM of 134.5 pg/mg (62-334) and 55% (n=12) did not have control (mUFC 2.2, 1.1-6) and a mHCM of 150.5 (75-459). After recategorization of UFC (> o ≤ 1 UNL) and HCM (> o ≤ 128 pg/mg), determinations were associated (Chi2, p= 0.18), however, the concordance was acceptable (Kappa index = 0.276). After dividing CD patients according to HCM, 35% (n=8) had normal HCM: mHCM 113.5 (62-126) and mUFC 0.45 (0.1- 4.4). Among them, 63% (n=5) had controlled CD (mHCM 110, 62-121; mUFC 0.39, 0.1-0.85); 25% (n=2) had active CD (mUFC 2.7, 1.1-4.4; mHCM 121, 75-126). 65% had high HCM (n=15): mHCM 167 (132-459) and mUFC 1.36 (0.1-6). Most of them had active CD (n=11, 73%): mHCM 160 (132-459) and mUFC 2.2 (1.1-6). Four patients with elevated HCM (m 248, 148-334) had normal UFC (m 0.61, 0.12-0.92): 2 were in remission, 1 had normal postsurgical UFC with active disease in the follow-up and 1 had normal UFC under medical treatment. Controls (n=50) had mHCM 62.5 (40-126), significantly different from CD. CONCLUSIONS We evaluated HCM in CD, proposing this method as an additional diagnostic test for hypercortisolism. The acceptable concordance between UFC and HCM is possibly due to the different duration of the evaluated periods. The difference in the HCM values observed between controlled or active CD patients and controls permits the consideration of the method as an alternative in the diagnosis and/or follow-up of CD.

scholarly journals Outcomes of Therapy for Cushing’s Disease due to Adrenocorticotropin-Secreting Pituitary Macroadenomas1

1998 ◽  
Vol 83 (1) ◽  
pp. 63-67 ◽  
Author(s):  
Lewis S. Blevins ◽  
James H. Christy ◽  
Masheed Khajavi ◽  
George T. Tindall
Keyword(s):  
Confidence Interval ◽  
Cavernous Sinus ◽  
Cushing’S Disease ◽  
Odds Ratio ◽  
Remission Rate ◽  
Cushing's Disease ◽  
Tumor Diameter ◽  
Cavernous Sinus Invasion ◽  
Free Cortisol ◽  
Acth Secreting

We reviewed our experience with 21 patients who had Cushing’s disease due to ACTH-secreting macroadenomas to clarify the natural history of this disease. All patients had typical clinical and biochemical features of ACTH-dependent hypercortisolism. Their mean maximal tumor diameter was 1.6 ± 0.1 cm, and the range was 1.0–2.7 cm. Six patients had cavernous sinus invasion, three had invasion of the floor of their sella, and nine had suprasellar extension. The observed remission rate was significantly lower in macroadenoma patients than in microadenoma patients (67% vs. 91%; χ2 = 5.7; P < 0.02). Cavernous sinus invasion (odds ratio, 35; 95% confidence interval, 2.6–475; P < 0.008) and presence of a maximum tumor diameter 2.0 cm or more (odds ratio, 12.9; 95% confidence interval, 1.4–124; P< 0.02) emerged as the only predictors of residual disease after surgery. The observed recurrence rate was significantly higher in macroadenoma patients than in microadenoma patients (36% vs. 12%; χ2 = 4.2; P< 0.05). Macroadenoma patients tended to suffer from recurrences earlier than did microadenoma patients (16 vs. 49 months). Stepwise multiple logistic regression did not identify any predictors of disease recurrence in macroadenoma patients. Eight macroadenoma patients underwent a total of nine repeat surgical procedures, but none of these resulted in clinical remissions. Only four of seven (57%) patients followed for a sufficient period of time achieved normal urinary free cortisol levels after conventional radiotherapy. Three (75%) of these four patients had re-recurrent hypercortisolism after brief periods of eucortisolism. Pharmacological agents and adrenalectomy were effective in the management of hypercortisolism in patients with residual and recurrent disease. Our results indicate that ACTH-secreting macroadenomas are more refractory to conventional treatments than are ACTH-secreting microadenomas.

Transsphenoidal Surgery for Cushing's Disease: Endocrinological Follow-up Monitoring of 82 Patients

Neurosurgery ◽  
2002 ◽  
Vol 51 (1) ◽  
pp. 57-62 ◽  
Author(s):  
Ilan Shimon ◽  
Zvi Ram ◽  
Zvi R. Cohen ◽  
Moshe Hadani
Keyword(s):  
Cushing’S Disease ◽  
Transsphenoidal Surgery ◽  
Adrenocorticotropic Hormone ◽  
Remission Rate ◽  
The United States ◽  
Cushing's Disease ◽  
Free Cortisol ◽  
Remission Rates ◽  
Surgical Failure

Abstract OBJECTIVE Transsphenoidal surgery is the preferred treatment modality for adrenocorticotropic hormone-secreting pituitary adenomas. In the past 2 decades, several institutions in the United States and Europe have reported remission rates of 70 to 85% after transsphenoidal surgery for treatment of Cushing's disease. We analyzed our postoperative results for a large cohort of patients with Cushing's disease. METHODS Eighty-two patients with adrenocorticotropic hormone-secreting adenomas (79 microadenomas and 3 macroadenomas) underwent transsphenoidal surgery between 1990 and 2000. Seventy-seven patients were surgically treated for the first time, and 13 patients underwent reoperations (5 had undergone the first operation elsewhere) because of previous surgical failure (10 patients) or recurrence (3 patients). The mean postoperative follow-up period was 4.2 ± 2.8 years. Biochemical remission was defined as postoperative normalization of elevated 24-hour urinary free cortisol secretion and suppression of morning cortisol levels with 1 mg of dexamethasone. RESULTS Remission was achieved for 78% of all patients after one operation and for 62% of patients who underwent a second operation. The recurrence rate was 5%. Ten patients did not exhibit a visible tumor on magnetic resonance imaging scans, and the other patients were divided according to adenoma size (2–5 or 6–10 mm). Remission rates were similar for the three groups of patients (78–80%). Pituitary tumor stained for adrenocorticotropic hormone was detected in 78% of resected pituitary tissue specimens obtained from patients who achieved remission, compared with 53% from patients who experienced surgical failure (P = 0.06). CONCLUSION Our series demonstrates the efficacy of transsphenoidal surgery for Cushing's disease resulting from pituitary microadenomas. Microadenoma size had no effect on the remission rate. Reoperations are indicated after initial surgical failures.

scholarly journals Ketoconazole revisited: a preoperative or postoperative treatment in Cushing's disease

2008 ◽  
Vol 158 (1) ◽  
pp. 91-99 ◽  
Author(s):  
F Castinetti ◽  
I Morange ◽  
P Jaquet ◽  
B Conte-Devolx ◽  
T Brue
Keyword(s):  
Cushing’S Disease ◽  
Transsphenoidal Surgery ◽  
Urinary Free Cortisol ◽  
Postoperative Treatment ◽  
Cushing's Disease ◽  
Intention To Treat ◽  
Free Cortisol ◽  
In Series

ContextAlthough transsphenoidal surgery remains the first-line treatment in Cushing's disease (CD), recurrence is observed in about 20% of cases. Adjunctive treatments each have specific drawbacks. Despite its inhibitory effects on steroidogenesis, the antifungal drug ketoconazole was only evaluated in series with few patients and/or short-term follow-up.ObjectiveAnalysis of long-term hormonal effects and tolerance of ketoconazole in CD.DesignA total of 38 patients were retrospectively studied with a mean follow-up of 23 months (6–72).SettingAll patients were treated at the same Department of Endocrinology in Marseille, France.PatientsThe 38 patients with CD, of whom 17 had previous transsphenoidal surgery.InterventionKetoconazole was begun at 200–400 mg/day and titrated up to 1200 mg/day until biochemical remission.Main outcome measuresPatients were considered controlled if 24-h urinary free cortisol was normalized.ResultsFive patients stopped ketoconazole during the first week because of clinical or biological intolerance. On an intention to treat basis, 45% of the patients were controlled as were 51% of those treated long term. Initial hormonal levels were not statistically different between patients controlled or uncontrolled. Ketoconazole was similarly efficacious as a primary or postoperative treatment. Among 15 patients without visible adenoma at initial evaluation, subsequent follow-up allowed identification of the lesion in five cases. No adrenal insufficiency was observed. Adverse effects were rare in patients treated long term.ConclusionsKetoconazole is a safe and efficacious treatment in CD, particularly in patients for whom surgery is contraindicated, or delayed because of the absence of image of adenoma on magnetic resonance imaging.

scholarly journals Five years follow up of patients with Сushing’s disease with and without visualized pituitary adenoma on MRI, who underwent transsphenoidal adenomectomy

2017 ◽  
Vol 63 (5) ◽  
pp. 276-281
Author(s):  
Patimat M. Khandaeva ◽  
Zhanna E. Belaya ◽  
Lyudmila Ya. Rozhinskaya ◽  
Aleksandr V. Vorontsov ◽  
Andrey Yu. Grigoriev ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Cushing’S Disease ◽  
Remission Rate ◽  
Serum Cortisol ◽  
Urinary Free Cortisol ◽  
Cushing's Disease ◽  
Surgery Complications ◽  
Free Cortisol ◽  
Transsphenoidal Adenomectomy

The remission rate of Cushing’s disease in patients after neurosurgery varies from 59 to 94%, while the recurrence rate is 3 to 46%. Aim — to evaluate the five-year outcome in neurosurgery patients with Cushing’s disease (CD), depending on preoperative MRI-based identification of pituitary adenoma. Material and methods. The study included 105 neurosurgery patients with histologically confirmed CD. CD remission was confirmed by the development of adrenal insufficiency and/or normalization of serum cortisol and 24-hour urinary free cortisol (24h UFC) levels, as well as by clinical remission. Results. Pituitary adenoma was not visualized by gadolinium MRI in 35 cases. The size of visualized pituitary adenoma varied from 0.3 to 29 mm. After first neurosurgery, remission was achieved in 87 (82.8%) patients. After second neurosurgery, remission occurred in 12 patients. Radiation therapy was conducted in 24 patients. Six patients had bilateral adrenalectomy. Two patients died during remission: one patient died from stroke two years after neurosurgery, and the other patient died due to surgery complications. During five-year follow-up after neurosurgery, remission continued in 76 (72.8%) patients, including 27 (77%) of 35 patients without MRI-detected adenoma and 49 (70%) of 70 patients with MRI-detected pituitary adenoma, p=0.15. Sixty-six patients developed recurrence, and 14 patients had active hypercortisolism. Conclusion. There was no correlation between the rate of preoperative MRI-based detection of pituitary adenoma and the rate of remission in neurosurgery patients with Cushing’s disease during the five year follow-up. The size of pituitary adenoma was a risk factor for adenoma recurrence.

scholarly journals Ocular hypertension secondary to high endogenous steroid load in Cushing’s disease

2019 ◽  
Vol 12 (1) ◽  
pp. bcr-2018-226738 ◽  
Author(s):  
Sofia Noor Habib ◽  
Zhiheng Lin ◽  
Narman Puvanachandra
Keyword(s):  
Ocular Hypertension ◽  
Cushing’S Disease ◽  
Adrenocorticotropic Hormone ◽  
Disease Duration ◽  
Management Plan ◽  
Cushing's Disease ◽  
Endogenous Cortisol ◽  
Endogenous Steroid ◽  
Transsphenoidal Resection

This case report describes a 35-year-old Caucasian man who was referred to the glaucoma clinic with high intraocular pressure (IOP) after routine optometrist assessment. He was diagnosed with ocular hypertension (OHT) and the management plan was for monitoring without treatment. Three months later, he presented to the endocrine clinic with symptoms of Cushing’s disease and was diagnosed with an adrenocorticotropic hormone secreting pituitary microadenoma. His symptoms preceded his presentation at both departments by 5 years. He underwent definitive surgical treatment of his adenoma via transsphenoidal resection. At 1-year follow-up in glaucoma clinic, it was noted that his IOP had normalised. Due to his high endogenous cortisol level at diagnosis, long disease duration, the pattern of IOP rise and subsequent normalisation after treatment, it is suggestive that his OHT is secondary to his Cushing’s disease. There are infrequent reports of this association in published literature.

Development of Machine Learning Models for Predicting Postoperative Delayed Remission in Patients With Cushing’s Disease

2020 ◽  
Vol 106 (1) ◽  
pp. e217-e231
Author(s):  
Yanghua Fan ◽  
Yichao Li ◽  
Xinjie Bao ◽  
Huijuan Zhu ◽  
Lin Lu ◽  
...  
Keyword(s):  
Machine Learning ◽  
Cushing’S Disease ◽  
Prediction Models ◽  
Spontaneous Remission ◽  
Cushing's Disease ◽  
Recursive Feature Elimination ◽  
Pathological Examination ◽  
Individual Treatment ◽  
Free Cortisol

Abstract Context Postoperative hypercortisolemia mandates further therapy in patients with Cushing’s disease (CD). Delayed remission (DR) is defined as not achieving postoperative immediate remission (IR), but having spontaneous remission during long-term follow-up. Objective We aimed to develop and validate machine learning (ML) models for predicting DR in non-IR patients with CD. Methods We enrolled 201 CD patients, and randomly divided them into training and test datasets. We then used the recursive feature elimination (RFE) algorithm to select features and applied 5 ML algorithms to construct DR prediction models. We used permutation importance and local interpretable model–agnostic explanation (LIME) algorithms to determine the importance of the selected features and interpret the ML models. Results Eighty-eight (43.8%) of the 201 CD patients met the criteria for DR. Overall, patients who were younger, had a low body mass index, a Knosp grade of III–IV, and a tumor not found by pathological examination tended to achieve a lower rate of DR. After RFE feature selection, the Adaboost model, which comprised 18 features, had the greatest discriminatory ability, and its predictive ability was significantly better than using Knosp grading and postoperative immediate morning serum cortisol (PoC). The results obtained from permutation importance and LIME algorithms showed that preoperative 24-hour urine free cortisol, PoC, and age were the most important features, and showed the reliability and clinical practicability of the Adaboost model in DC prediction. Conclusions Machine learning–based models could serve as an effective noninvasive approach to predicting DR, and could aid in determining individual treatment and follow-up strategies for CD patients.

scholarly journals Effects and Side Effects of Pasireotide Treatment in Cushing’s Disease: Experience of a Single Tertiary Center

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A642-A643
Author(s):  
Hande Mefkure Ozkaya ◽  
Serdar Sahin ◽  
Güler Kerimova ◽  
Emre Durcan ◽  
Cem Sulu ◽  
...  
Keyword(s):  
Side Effects ◽  
Cushing’S Disease ◽  
The Body ◽  
Cushing's Disease ◽  
Antidiabetic Medication ◽  
Free Cortisol ◽  
Tertiary Center ◽  
Significant Difference ◽  
Pre Treatment

Abstract Context: Cushing’s disease (CD), when uncontrolled despite surgery, requires medical treatment. In this vein, treatments with long-term effectiveness and safety profiles are needed. We aimed to evaluate the effects and side effects of pasireotide treatment in Cushing’s disease in the real world. Methods: Patients who were followed up for Cushing’s disease and treated with pasireotide between 2001-2019 at Cerrahpaşa Medical Faculty Endocrinology, Metabolism and Diabetes Department were evaluated. Pasireotide efficacy and side effects were evaluated. Results: Thirty-four patients were included in the study. The mean duration of treatment was 24.59 (SD ± 15.21) months. Urinary free cortisol (UFC) decreased in 40.59 % of the patients and normalized in 33.3 %. A total of %71.4 of the patients who were in remission at the 3rd month of the treatment preserved their remission status at last follow-up. A significant difference was found between pre-treatment and final UFC (p = 0.001), but the absence of remission at 3 months did not predict final remission (p = 0.274). ACTH decreased by 9.16 % (SD ± 46.67). A significant difference was found between ACTH levels at 3rd, 6 months, and last control (p = 0.014, 0.017, and 0.017, respectively). Serum cortisol decreased by 13.89 %. A significant difference was found between pre-treatment and 3rd month, pre-treatment and final cortisol (p = 0.034 and 0.013, respectively). The body weight decreased by an average of 5.5 [IQR (0.0-11.5)] kg. Cholecystectomy was performed in 3 patients (9%). The percentage of patients requiring antidiabetic medication increased from 33.3% at diagnosis to 81.8% at the last follow-up visit. A significant difference was found between pre-treatment and 3rd month fasting plasma glucose levels ​​(p = 0.008). HbA1c increased by 17 %. There was a positive correlation between UFC and 3rd month HbA1c. All patients with hyperglycemia were controlled with effective antidiabetic therapy. Conclusion: Pasireotide treatment in CD is effective and safe, remission occurs in the first months of treatment and continues for a long time. Although hyperglycemia is the most common side effect, it is successfully controlled with antidiabetic medication.

scholarly journals Late Recurrences of Cushing’s Disease after Initial Successful Transsphenoidal Surgery

2008 ◽  
Vol 93 (2) ◽  
pp. 358-362 ◽  
Author(s):  
Chirag G. Patil ◽  
Daniel M. Prevedello ◽  
Shivanand P. Lad ◽  
Mary Lee Vance ◽  
Michael O. Thorner ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Transsphenoidal Surgery ◽  
Clinical Symptoms ◽  
Medical Center ◽  
Serum Cortisol ◽  
Cushing's Disease ◽  
Recurrence Rates ◽  
Free Cortisol

Abstract Context: Few studies have systematically analyzed the long-term recurrence rates of Cushing’s disease after initial successful transsphenoidal surgery. Setting: This was a retrospective review of patients treated at the University of Virginia Medical Center. Patients: A total of 215 subjects with Cushing’s disease who underwent initial transsphenoidal surgery for resection of a presumed pituitary microadenoma from 1992–2006 were included. Main Outcome Measures: Remission and recurrence rates of Cushing’s disease were examined. Recurrence was defined as an elevated 24-h urine free cortisol with clinical symptoms consistent with Cushing’s disease. Results: Of the 215 patients who underwent transsphenoidal surgery for Cushing’s disease, surgical remission was achieved in 184 (85.6%). The mean length of follow-up was 45 months. Actuarial recurrence rates of Cushing’s disease after initially successful transsphenoidal surgery at 1, 2, 3, and 5 yr were 0.5, 6.7, 10.8, and 25.5%, respectively. Among the 184 patients who achieved remission, 32 (17.4%) patients followed for more than 6 months ultimately had a recurrence of Cushing’s disease. The median time to recurrence was 39 months. Immediate postoperative hypocortisolemia (serum cortisol ≤ 2 μg/dl within 72-h surgery) was achieved in 97 (45.1%) patients. Patients who had postoperative serum cortisol of more than 2 μg/dl were 2.5 times more likely to have a recurrence than patients who had serum cortisol less than or equal to 2 μg/dl (odds ratio = 2.5; 95% confidence interval 1.12–5.52; P = 0.022). Conclusions: A quarter of the patients with Cushing’s disease who achieve surgical remission after transsphenoidal surgery, recur with long-term follow-up. This finding emphasizes the need for continued biochemical and clinical follow-up to ensure remission after surgery.

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