scholarly journals Diagnosis of Cushing's disease in a patient with consistently normal urinary free cortisol levels: a case report

2016 ◽  
Vol 4 (12) ◽  
pp. 1181-1183
Author(s):  
Kelley J. Moloney ◽  
Jennifer U. Mercado ◽  
William H. Ludlam ◽  
Frances E. Broyles
Keyword(s):  
Case Report ◽  
Cushing’S Disease ◽  
Urinary Free Cortisol ◽  
Cushing's Disease ◽  
Free Cortisol ◽  
Cortisol Levels

scholarly journals SAT-271 Block and Replace Therapy Successfully Improved Symptoms in Recurrent Cyclic Cushing’s Disease

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Risa Kamigaki ◽  
Hiraku Kameda ◽  
Hiroshi Iesaka ◽  
Rimi Izumihara ◽  
Yuki Ohe ◽  
...  
Keyword(s):  
Weight Gain ◽  
Pituitary Adenoma ◽  
Cushing’S Disease ◽  
Brain Mri ◽  
Urinary Free Cortisol ◽  
Cushing's Disease ◽  
Subjective Symptoms ◽  
Free Cortisol ◽  
Level Elevation ◽  
Cortisol Levels

Abstract BACKGROUND: Cyclic Cushing’s disease is rare and treatments have not been established for post-surgical recurrent cases. Here, we report a patient with recurrent cyclic Cushing’s disease, whose subjective symptoms improved by administration of metyrapone and hydrocortisone. Clinical Case: A 45-year-old woman had exhibited face and peripheral edema, hyperphagia, weight gain, hair loss and limb numbness since September X-10. In May X-9, her ACTH and cortisol levels were high (87.8 pg/mL and 28.8 µg/dL, respectively), and she was referred to our department. A brain MRI revealed a pituitary adenoma of 7mm in diameter. Because blood ACTH and cortisol levels turned normal and typical Cushingoid features were absent at the admission to our department, cyclic Cushing’s disease was suspected. Later in September, because subjective symptoms recurred accompanied with blood cortisol level elevation, she was diagnosed as cyclic Cushing’s disease with the examinations including inferior petrosal sinus sampling. Transsphenoidal surgery was performed in November, and immunohistology confirmed ACTH-producing pituitary adenoma based on ACTH positivity. After the surgery, endocrine test results were normalized and subjective symptoms were ameliorated. In March X-3, the blood ACTH level increased again; however, no subjective symptoms were observed. From May X, she had experienced limb numbness, hyperphagia and weight gain again. MRI showed no apparent recurrence, but endocrine tests showed the activity of Cushing’s disease. Urinary free cortisol (UFC) increased to 300–400 µg/day in a 1-week cycle, indicating the recurrence of cyclic Cushing’s disease. Metyrapone treatment was initiated, and the patient was finally discharged after block and replace therapy with metyrapone 2,000 mg/day and hydrocortisone 15 mg/day. After metyrapone treatment, subjective symptoms improved and UFC was normalized. Conclusion: Block and replace therapy with metyrapone and hydrocortisone may be effective for recurrent cyclic Cushing’s disease, especially in cases with a very short cycle.

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 >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.

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.

How early can one diagnose Cushing’s disease? An early diagnosis in a case of prepubertal Cushing’s disease

2014 ◽  
Vol 27 (11-12) ◽  
pp. 1043-1047 ◽  
Author(s):  
Julia Hoppmann ◽  
Isabel V. Wagner ◽  
Gudrun Junghans ◽  
Stefan A. Wudy ◽  
Michael Buchfelder ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Cushing’S Disease ◽  
Dexamethasone Suppression Test ◽  
Cushing's Disease ◽  
High Dose ◽  
Thyroid Function Tests ◽  
Free Cortisol ◽  
Suppression Test ◽  
Cortisol Levels ◽  
Dexamethasone Suppression

Abstract Background: Cushing’s disease is very rare in children, and the diagnosis is frequently delayed by several years. Objective: We report a case of prepubertal Cushing’s disease with a medical history of only 9 months. This case illustrates the difficulties involved in diagnosing children at the early stage of the disease. Case presentation: An 8-year-old prepubertal boy presented with rapid weight gain accompanied by a decreasing growth velocity and hirsutism. Thyroid function tests and growth factor levels were normal, thus excluding hypothyroidism and growth hormone deficiency. Cushing’s syndrome was confirmed by elevated 24-h urinary free cortisol levels, increased diurnal cortisol levels, and a lack of cortisol suppression in the low-dose dexamethasone suppression test. Further tests to investigate the source of the hypercortisolism showed the following results: Basal morning adrenocorticotropic hormone (ACTH) was normal. The high-dose dexamethasone suppression test led to a 51% decrease in cortisol level. In the corticotropin-releasing hormone (CRH) test, ACTH and cortisol increased only by 28%. Repeated magnetic resonance imaging (MRI) finally revealed a microadenoma in the anterior pituitary, thus establishng the diagnosis of Cushing’s disease. Upon diagnosis, the patient underwent transsphenoidal surgery. Histological analysis confirmed an ACTH-secreting pituitary adenoma. Conclusion: This case illustrates the difficulties associated with the clinical, biochemical, and radiological diagnoses of Cushing’s disease in children. Early diagnosis remains a challenge because test results often do not match standard diagnostic criteria.

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 (&gt; o ≤ 1 UNL) and HCM (&gt; 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 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.

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