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 Assessment of Vitamin D Metabolism in Patients with Cushing’s Disease in Response to 150,000 IU Cholecalciferol Treatment

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4329
Author(s):  
Alexandra Povaliaeva ◽  
Viktor Bogdanov ◽  
Ekaterina Pigarova ◽  
Artem Zhukov ◽  
Larisa Dzeranova ◽  
...  
Keyword(s):  
Vitamin D ◽  
Cushing’S Disease ◽  
Serum Vitamin ◽  
Urinary Free Cortisol ◽  
Cushing's Disease ◽  
Control Group ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Serum Vitamin D ◽  
Free Cortisol

In this study we aimed to assess vitamin D metabolism in patients with Cushing’s disease (CD) compared to healthy individuals in the setting of bolus cholecalciferol treatment. The study group included 30 adults with active CD and the control group included 30 apparently healthy adults with similar age, sex and BMI. All participants received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3 and 7 after the administration. All data were analyzed with non-parametric statistics. Patients with CD had similar to healthy controls 25(OH)D3 levels (p > 0.05) and higher 25(OH)D3/24,25(OH)2D3 ratios (p < 0.05) throughout the study. They also had lower baseline free 25(OH)D levels (p < 0.05) despite similar DBP levels (p > 0.05) and lower albumin levels (p < 0.05); 24-h urinary free cortisol showed significant correlation with baseline 25(OH)D3/24,25(OH)2D3 ratio (r = 0.36, p < 0.05). The increase in 25(OH)D3 after cholecalciferol intake was similar in obese and non-obese states and lacked correlation with BMI (p > 0.05) among patients with CD, as opposed to the control group. Overall, patients with CD have a consistently lower 25(OH)D3/24,25(OH)2D3 ratio, which is indicative of a decrease in 24-hydroxylase activity. This altered activity of the principal vitamin D catabolism might influence the effectiveness of cholecalciferol treatment. The observed difference in baseline free 25(OH)D levels is not entirely clear and requires further study.

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 Long-Term Control of Urinary Free Cortisol With Osilodrostat in Patients With Cushing’s Disease: Final Results From the LINC 2 Study

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A521-A522
Author(s):  
Maria Fleseriu ◽  
Beverly M K Biller ◽  
Jerome Bertherat ◽  
Jacques Young ◽  
Giorgio Arnaldi ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Cushing’S Disease ◽  
Clinical Signs ◽  
Urinary Free Cortisol ◽  
Cushing's Disease ◽  
Efficacy And Safety ◽  
Entire Treatment Period ◽  
Free Cortisol ◽  
Long Term Treatment

Abstract Introduction: During the 22-week core LINC 2 study, the oral 11β-hydroxylase inhibitor osilodrostat normalized mean urinary free cortisol (mUFC) in 79% (15/19) of patients with Cushing’s disease. This report describes long-term LINC 2 efficacy and safety results following an optional extension. Methods: Patients receiving clinical benefit at week 22 could enter the extension (that ran until Oct 22, 2019), continuing the same osilodrostat dose; dose adjustments were permitted based on efficacy and safety. Response rate (mUFC ≤ULN [controlled] or mUFC &gt;ULN but ≥50% decrease from baseline [BL; partially controlled]) was assessed over time. Efficacy/safety were assessed for all patients from core BL until study end. Results: Of 19 enrolled patients (female:male 14:5; mean [SD] age 36.8 years [8.4]), 16 entered the optional extension and 8 of them remained on treatment until study end. Median (range) osilodrostat exposure was 282 weeks (2-351). Mean mUFC decreased from BL (9.9 x ULN) to ≤ULN by week 4 and remained stable throughout the study. All 19 patients achieved mUFC ≤ULN at least once during the study. At each assessment up to month 70 of the extension phase, 50-88% of ongoing patients were controlled, and up to 18% were partially controlled. Mean percentage change in clinical signs from BL (mean [SD]) to last assessment were: fasting plasma glucose, -10.8% (22.1) (from BL: 105.6 mg/dL [49.2]); HbA1c, -2.1% (9.0) (from BL: 5.7% [0.7]); systolic BP, -3.3% (12.6) (from BL: 132.6 mmHg [11.6]); diastolic BP, -2.0% (10.4) (from BL: 85.0 mmHg [6.5]); BMI, -5.9% (8.8) (from BL: 30.7 kg/m2 [7.0]). Overall, 9 patients discontinued treatment (n=2 core and n=7 extension), mostly because of AEs or no longer requiring treatment (n=3 each). The most common AEs during the entire treatment period were nausea (n=10), adrenal insufficiency, and headache (both n=9). AEs related to hypocortisolism and adrenal hormone precursor accumulation occurred in 11 (mostly adrenal insufficiency, n=9) and 12 patients (mostly hypertension, n=4), respectively; most were grade 1/2 and managed with dose adjustment/interruption and/or concomitant medication. Mean (SD) plasma ACTH increased from 1.8 x ULN (0.9) at BL to 7.1 x ULN (12.3) at week 22 and 6.9 x ULN (12.6) at last assessment. Mean (SD) 11-deoxycortisol increased from 1.2 x ULN (1.3) at BL to 13.6 x ULN (12.2) at week 22 and 3.6 x ULN (4.2) at last assessment. In females, mean (SD) testosterone increased from 0.8 x ULN (0.4) at BL to 2.4 x ULN (2.1) at week 22 and 1.0 x ULN (0.9) at last assessment. Two patients, both female, reported an AE of hirsutism. Conclusions: Rapid reductions in mUFC were sustained for up to 6 years of osilodrostat treatment and were accompanied by improvements in clinical signs of hypercortisolism. Osilodrostat was well tolerated, with no new safety signals during long-term treatment.

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 Use of late-night salivary cortisol to monitor response to medical treatment in Cushing’s disease

2020 ◽  
Vol 182 (2) ◽  
pp. 207-217 ◽  
Author(s):  
John Newell-Price ◽  
Rosario Pivonello ◽  
Antoine Tabarin ◽  
Maria Fleseriu ◽  
Przemysław Witek ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Salivary Cortisol ◽  
Clinical Signs ◽  
Urinary Free Cortisol ◽  
Phase Iii ◽  
Cushing's Disease ◽  
Late Night ◽  
Late Night Salivary Cortisol ◽  
Free Cortisol ◽  
Two Samples

Objective Monitoring of patients with Cushing’s disease on cortisol-lowering drugs is usually performed with urinary free cortisol (UFC). Late-night salivary cortisol (LNSC) has an established role in screening for hypercortisolism and can help to detect the loss of cortisol circadian rhythm. Less evidence exists regarding the usefulness of LNSC in monitoring pharmacological response in Cushing’s disease. Design Exploratory analysis evaluating LNSC during a Phase III study of long-acting pasireotide in Cushing’s disease (clinicaltrials.gov: NCT01374906). Methods Mean LNSC (mLNSC) was calculated from two samples, collected on the same days as the first two of three 24-h urine samples (used to calculate mean UFC [mUFC]). Clinical signs of hypercortisolism were evaluated over time. Results At baseline, 137 patients had evaluable mLNSC measurements; 91.2% had mLNSC exceeding the upper limit of normal (ULN; 3.2 nmol/L). Of patients with evaluable assessments at month 12 (n = 92), 17.4% had both mLNSC ≤ULN and mUFC ≤ULN; 22.8% had mLNSC ≤ULN, and 45.7% had mUFC ≤ULN. There was high variability in LNSC (intra-patient coefficient of variation (CV): 49.4%) and UFC (intra-patient CV: 39.2%). mLNSC levels decreased over 12 months of treatment and paralleled changes in mUFC. Moderate correlation was seen between mLNSC and mUFC (Spearman’s correlation: ρ = 0.50 [all time points pooled]). Greater improvements in systolic/diastolic blood pressure and weight were seen in patients with both mLNSC ≤ULN and mUFC ≤ULN. Conclusion mUFC and mLNSC are complementary measurements for monitoring treatment response in Cushing’s disease, with better clinical outcomes seen for patients in whom both mUFC and mLNSC are controlled.

scholarly journals Partial restoration of GH responsiveness to ghrelin in Cushing's disease after 6 months of ketoconazole treatment: comparison with GHRP-6 and GHRH

2009 ◽  
Vol 161 (5) ◽  
pp. 681-686 ◽  
Author(s):  
Silvia R Correa-Silva ◽  
Sérgio O Nascif ◽  
Patrícia Molica ◽  
Larissa B P C Sá ◽  
José G Vieira ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Urinary Free Cortisol ◽  
Cushing's Disease ◽  
Partial Restoration ◽  
Gh Secretion ◽  
Treatment Comparison ◽  
Time Period ◽  
Free Cortisol ◽  
Before And After ◽  
Serum Gh

ObjectiveIn Cushing's disease (CD), GH responsiveness to several stimuli, including ghrelin, GHRP-6, and GHRH, is blunted. Recovery of GH secretion after remission of hypercortisolism after transsphenoidal surgery, radiotherapy, or adrenalectomy is controversial. There are no studies evaluating the effect of primary clinical treatment with ketoconazole on GH secretion in CD. The aim of this study is to compare ghrelin-, GHRP-6-, and GHRH-induced GH release before and after ketoconazole in CD.DesignGH responses to ghrelin, GHRP-6, and GHRH of eight untreated patients with CD (mean age: 33.8±3.1 years; body mass index: 28.5±0.8 kg/m2) were evaluated before and after 3 and 6 months of ketoconazole treatment, and compared with 11 controls (32.1±2.5; 25.0±0.8).MethodsSerum GH was measured by an immunofluorometric assay and urinary free cortisol (UFC) by liquid chromatography and tandem mass spectrometry.ResultsAfter ketoconazole use, mean UFC decreased significantly (before: 222.4±35.0 μg/24 h; third month: 61.6±10.1; sixth month: 39.1±10.9). Ghrelin-induced GH secretion increased significantly after 6 months (peak before: 6.8±2.3 μg/l; sixth month: 16.0±3.6), but remained lower than that of controls (54.1±11.2). GH release after GHRP-6 increased, although not significantly, while GH responsiveness to GHRH was unchanged.ConclusionsGhrelin-induced GH release increases significantly after 6 months of ketoconazole treatment in CD. This could suggest that a decrease in cortisol levels during this time period can partially restore glucocorticoid-induced GH suppression in CD. GH-releasing mechanisms stimulated by ghrelin/GHS could be more sensitive, as no changes in GHRH-induced GH release were observed.

Increased urinary excretion of free 20 alpha- and 20 beta-dihydrocortisol in a hypercortisolemic but hypocortisoluric patient with Cushing's disease.

1983 ◽  
Vol 29 (2) ◽  
pp. 385-389 ◽  
Author(s):  
M Schöneshöfer ◽  
B Weber ◽  
S Nigam
Keyword(s):  
Mass Spectrometry ◽  
Urinary Excretion ◽  
Cushing’S Disease ◽  
Urinary Free Cortisol ◽  
Cushing's Disease ◽  
Gas Chromatography Mass Spectrometry ◽  
Highly Sensitive ◽  
Free Cortisol ◽  
Excretion Rates ◽  
Liquid Chromatographic

Abstract We identified non-metabolized, non-conjugated 20 alpha- and 20 beta-dihydrocortisol (20 alpha- and 20 beta-DHF) in urine from a patient with Cushing's disease, by use of three different liquid-chromatographic systems and by gas chromatography-mass spectrometry. We document that these 20-isomers of dihydrocortisol may strongly contribute to unspecific interferences with the immunological assessment of urinary free cortisol (F). The urinary excretion rates of 20 alpha- and 20 beta-DHF were quantified radioimmunologically with use of a cross-reacting cortisol antiserum after effective purification by liquid chromatography. The patient with Cushing's disease had mean peripheral cortisol concentrations of 1018 nmol/L. The urinary excretion rates (nmol/24 h) were 1455 for 20 alpha-DHF, 330 for 20 beta-DHF, and 18 for F. The corresponding reference values (median in nmol/24 h) were 174 for 20 alpha-DHF, 111 for 20 beta-DHF, and 68 for F (n = 22). We conclude that (a) specific estimation of urinary free F is not as highly sensitive for diagnosis of chronic hypercortisolemic states as is generally assumed; and (b) measurement of urinary free 20 alpha- and 20 beta-DHF or of the corresponding 20-DHF:F ratios may be more sensitive.

A critical evaluation of transsphenoidal pituitary surgery in the treatment of Cushing's disease: Prediction of outcome

1990 ◽  
Vol 123 (4) ◽  
pp. 423-430 ◽  
Author(s):  
Richard D Arnott ◽  
Richard G Pestell ◽  
Penelope A McKelvie ◽  
J Keith Henderson ◽  
Peter M McNeill ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Cushing’S Disease ◽  
Critical Evaluation ◽  
Pituitary Surgery ◽  
Urinary Free Cortisol ◽  
Cushing's Disease ◽  
Late Relapse ◽  
Free Cortisol ◽  
Transsphenoidal Pituitary Surgery ◽  
Cortisol Excretion

Abstract. Twenty-eight patients underwent transsphenoidal pituitary surgery for Cushing's disease. Selective surgical procedures were performed in 26. In 19 patients pituitary adenoma was confirmed histologically and 5 had clumps or clusters of ACTH-staining cells. At follow-up after 22.3 (range 5-56) months 21 (75%) patients remained in clinical and biochemical remission. The 24-h urinary free cortisol performed between 1 and 4 weeks postoperatively while patients took replacement doses of dexamethasone (0.5 to 0.75 mg per day) was found to predict outcome. All patients with suppressed urinary free cortisol excretion have remained in remission, 3 with levels in the normal range have suffered late relapse after initial remission, and 4 with elevated urinary free cortisol excretion were regarded as having failed to remit. Furthermore, all patients with unsuccessful outcomes had no pituitary adenoma and 3 had features consistent with corticotrope nodular hyperplasia at histological examination compared to only 2 and 1, respectively, of patients still in remission. We conclude that 24-h urinary free cortisol performed at 1 to 4 weeks postoperatively whilst on low-dose dexamethasone and the histological findings may predict outcome following transsphenoidal pituitary surgery in Cushing's disease.

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