Diagnosis and selective cure of Cushing's disease during pregnancy by transsphenoidal surgery

1995 ◽  
Vol 132 (6) ◽  
pp. 722-726 ◽  
Author(s):  
RJM Ross ◽  
SL Chew ◽  
L Perry ◽  
K Erskine ◽  
S Medbak ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Transsphenoidal Surgery ◽  
Serum Cortisol ◽  
Cushing's Disease ◽  
Successful Outcome ◽  
Small Female ◽  
Free Cortisol ◽  
Cortisol Levels ◽  
Biochemical Features ◽  
Mr Scanning

Ross RJM, Chew SL, Perry L, Erskine K, Medbak S, Afshar F. Diagnosis and selective cure of Cushing's disease during pregnancy by transsphenoidal surgery. Eur J Endocrinol 1995;132:722–6. ISSN 0804–4643 The diagnosis of Cushing's Disease during pregnancy is complex because the biochemical features are obscured by changes in the normal hypothalamo-pituitary-adrenal axis that occur during gestation. To date, treatment has not been successful and there is a high incidence of maternal and fetal complications. We report the case of a 24-year-old woman with Cushing's disease who presented during her 16th week of pregnancy. Diagnosis was confirmed by the finding of elevated serum and urinary free cortisol levels with loss of the normal circadian rhythm of serum cortisol. Cortisol levels failed to suppress after a low-dose dexamethasone test but suppressed after a high-dose test. There was an exaggerated serum cortisol and plasma adrenocorticotrophin (ACTH) response to corticotrophinreleasing hormone (CRH). Magnetic resonance (MR) scanning demonstrated a pituitary tumour and cure was effected by transsphenoidal surgery where tumour immunostaining for ACTH was removed. Postoperatively the patient made an uncomplicated recovery; serum cortisol and plasma ACTH levels were undetectable at 9 days following surgery and recovery of the hypothalamo-pituitary axis occurred at 99 days after surgery. Caesarean section was performed at 38 weeks of pregnancy and a healthy but small female infant was delivered. This case illustrates the biochemical features of Cushing's disease during pregnancy and is the first report of the use of CRH testing and MR scanning in this clinical situation. The cure by surgery and successful outcome for mother and infant, with preservation of normal anterior pituitary function, suggest that transsphenoidal surgery may be the treatment of choice. RJM Ross, Dept of Endocrinology, St Bartholomew's Hospital, London ECIA 7BE, UK

scholarly journals Dynamics of Serum Cortisol Levels after Transsphenoidal Surgery in a Cohort of Patients with Cushing’s Disease

2004 ◽  
Vol 89 (3) ◽  
pp. 1131-1139 ◽  
Author(s):  
G. A. F. S. Rollin ◽  
N. P. Ferreira ◽  
M. Junges ◽  
J. L. Gross ◽  
M. A. Czepielewski
Keyword(s):  
Cushing’S Disease ◽  
Transsphenoidal Surgery ◽  
Serum Cortisol ◽  
Cushing's Disease ◽  
Cortisol Levels

scholarly journals Utility of the Immediate Postoperative Cortisol Concentrations in Patients With Cushing's Disease

Neurosurgery ◽  
2010 ◽  
Vol 67 (3) ◽  
pp. 688-695 ◽  
Author(s):  
Michael E. Sughrue ◽  
Jugal K. Shah ◽  
Jessica K. Devin ◽  
Sandeep Kunwar ◽  
Lewis S. Blevins
Keyword(s):  
Confidence Interval ◽  
Cortisol Level ◽  
Cushing’S Disease ◽  
Transsphenoidal Surgery ◽  
Fixed Effects ◽  
Serum Cortisol ◽  
Cushing's Disease ◽  
Recurrence Rates ◽  
Cumulative Rate ◽  
Cortisol Levels

Abstract BACKGROUND Several investigators have recommended serial measurements of serum cortisol in the days following pituitary surgery to identify patients at risk of recurrence. OBJECTIVE We systematically reviewed the literature on this topic and analyzed the usefulness of this test in our own patient population. METHODS We identified studies publishing data regarding recurrence rates after transsphenoidal surgery for Cushing's disease, focusing on studies with data regarding patients with early postoperative cortisol levels. We determined a cumulative relative risk of having a subnormal vs normal cortisol level postoperatively using a fixed-effects meta-analysis model. Additionally, we analyzed our own patients with Cushing's disease undergoing transsphenoidal surgery and performed Kaplan-Meier analysis of recurrence-free survival for patients with undetectable, subnormal but detectable, and normal immediate 8 AM serum cortisol levels. RESULTS Fourteen studies met inclusion criteria. The length of follow-up varied between 32 and 115 months. The cumulative rate of recurrence in the group of patients with subnormal cortisol levels was 9% (95% confidence interval: 6%–12%). The cumulative rate of recurrence in the group with normal cortisol levels was 24% (95% confidence interval: 17%–31%). We analyzed 73 of our own patients and found similar recurrence rates in patients with subnormal vs normal early postoperative cortisol levels (4% vs 22%, χ2 test, P < .05). CONCLUSION Although a subnormal early postoperative cortisol level is predictive of improved outcome after transsphenoidal surgery for Cushing's disease, it is not analogous with cure, nor is a normal level completely predictive of future failure.

scholarly journals Dynamics of postoperative serum cortisol after transsphenoidal surgery for Cushing’s disease: implications for immediate reoperation and remission

2018 ◽  
Vol 129 (5) ◽  
pp. 1268-1277 ◽  
Author(s):  
Marc Mayberg ◽  
Stephen Reintjes ◽  
Anika Patel ◽  
Kelley Moloney ◽  
Jennifer Mercado ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Transsphenoidal Surgery ◽  
Serum Cortisol ◽  
Late Recurrence ◽  
Cushing's Disease ◽  
Entire Cohort ◽  
Temporal Course ◽  
Postoperative Serum ◽  
Cortisol Levels ◽  
Immediate Reoperation

OBJECTIVESuccessful transsphenoidal surgery for adrenocorticotropin hormone (ACTH)–producing pituitary tumors is associated with subnormal postoperative serum cortisol levels, which may guide decisions regarding immediate reoperation. However, little is known about the detailed temporal course of changes in serum cortisol in the immediate postoperative period, and the relationship of postoperative cortisol dynamics to remission and late recurrence.METHODSA single-center retrospective cohort analysis was performed for all patients undergoing pituitary surgery from 2007 through 2015. Standardized diagnostic and treatment algorithms were applied to all patients with potential Cushing’s disease (CD), including microsurgical transsphenoidal adenomectomy (TSA) by a single surgeon. All patients had serum cortisol levels drawn at 6-hour intervals for 72 hours after surgery, and were offered reoperation within 3 days for normal or supranormal postoperative cortisol levels. Primary outcomes were 6-month remission and late recurrence; secondary outcomes were persistent postoperative hypocortisolism and surgical morbidity. Discriminatory levels of postoperative serum cortisol for predicting remission were calculated at various intervals after surgery using receiver operating characteristic (ROC) curves.RESULTSAmong 89 patients diagnosed with CD, 81 underwent initial TSA for a potentially curable lesion; 23 patients (25.8%) underwent an immediate second TSA. For the entire cohort, 6-month remission was achieved in 77.8% and late recurrences occurred in 9.5%, at a mean of 43.5 months. Compared with patients with a single surgery, those with an immediate second TSA had similar rates of remission (78.3% vs 77.6%) and late recurrence (5.6% vs 11.1%). The rate of hypocortisolism for patients with 2 surgeries (12/23, 52.2%) was significantly greater than that for patients with single surgeries (13/58, 22.4%; p < 0.001). There was no difference in the incidence of CSF leaks between the first and second operations. Remission was achieved in 58 (92.1%) of 64 patients who completed the 2-surgery protocol. The temporal course of postoperative serum cortisol levels among patients varied considerably, with subnormal nadir levels < 2 μg/dl occurring between 12 hours and 66 hours. Patients achieving remission had significantly lower mean serum cortisol levels at every time point after surgery (p < 0.01). By ROC curve analysis, nadir cortisol levels < 2.1 μg/dl were predictive of 6-month remission for the entire cohort over 3 days (positive predictive value [PPV] = 94%); discriminating cortisol levels for predicting remission on postoperative day (POD) 2 were < 5.4 μg/dl (PPV = 97%), although patients with remission after postoperative cortisol levels of 2–5 μg/dl had a significantly higher rate of late recurrence.CONCLUSIONSThere is substantial variation in the temporal course of serum cortisol levels over the first 72 hours after TSA for CD, with nadir levels predictive for remission occurring as late as POD 3. Although a cortisol level of 2.1 μg/dl at any point was an accurate predictor of 6-month remission, levels less than 5.4 μg/dl on POD 2 were reasonably accurate. These data may enable decisions regarding the efficacy of an immediate second surgical procedure performed during the same hospitalization; immediate reoperation is associated with excellent remission rates and low recurrence rates in patients otherwise unlikely to achieve remission, but carries a higher risk of permanent hypocortisolism.

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.

scholarly journals Surgical management of pediatric Cushing's disease: an analysis of 15 consecutive cases at a specialized neurosurgical center

2010 ◽  
Vol 54 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Ricardo Santos de Oliveira ◽  
Margaret de Castro ◽  
Sonir Roberto Rauber Antonini ◽  
Carlos Eduardo Martinelli Júnior ◽  
Ayrton Custódio Moreira ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Transsphenoidal Surgery ◽  
Pediatric Patients ◽  
Serum Cortisol ◽  
Plasma Cortisol Level ◽  
Hormone Deficiency ◽  
Cushing's Disease ◽  
Specialized Center ◽  
Biochemical Cure

OBJECTIVE: The aim of this study was to review the results of surgery for pediatric patients with Cushing's disease who were less than 18 years old and underwent transsphenoidal surgery in a specialized center during a 25-year period. SUBJECTS AND METHODS: Retrospective study, in which the medical records, histology and pituitary imaging of 15 consecutive pediatric patients with Cushing's disease (mean age: 13 years) were evaluated by the same team of endocrinologists and a neurosurgeon from 1982 to 2006. Patients were considered cured when there was clinical adrenal insufficiency and serum cortisol levels were below 1. 8 µg/dL or 50 nmol/L after one, two, three, or seven days following surgery; they therefore required cortisone replacement therapy. Follow-up was for a median time of 11.5 years (range: 2 to 25 years). RESULTS: Clinical and biochemical cure was achieved in 9/15 patients (60%) exclusively after transsphenoidal surgery. Hypopituitarism was observed in four patients; growth hormone deficiency, in two; permanent diabetes insipidus, in one case. CONCLUSIONS: Cushing's disease is rare in children and adolescents. Transsphenoidal surgery is an effective and safe treatment in most of these patients. Plasma cortisol level < 1. 8 µg/dL following surgery is the treatment goal and is a good predictive factor for long-term cure of Cushing's disease.

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 SAT-266 Accelerated Osteoporosis - a Rare Presentation of Cushing’s Disease

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Vijaykumar Sekar ◽  
Joseph Hughes ◽  
Sugam Gouli
Keyword(s):  
Cushing’S Disease ◽  
Low Dose ◽  
Incidental Finding ◽  
Serum Cortisol ◽  
Cushing's Disease ◽  
Adrenal Hyperplasia ◽  
Bilateral Adrenal Hyperplasia ◽  
Cortisol Levels ◽  
Post Menopausal ◽  
Dexamethasone Suppression

Abstract Background: Osteoporosis in post-menopausal women is usually due to bone loss from estrogen deficiency and/or age. Secondary osteoporosis (SO) is less common. Up to 30% of postmenopausal women and 50% of men with osteoporosis may have an underlying cause. Cushing’s disease (CD) is one cause of SO but rarely the presenting symptoms. The prevalence of osteoporosis (69.6% vs 37.8%) is significantly higher in patients with adrenal rather than pituitary CD. Diagnosing CD remains a challenge to physicians in spite of advances in diagnostic techniques. We report a case of CD in a post-menopausal woman presenting as accelerated osteoporosis. Clinical Case A 63-year-old Caucasian female with a history of hypertension and hysterectomy in her 50s on transdermal estrogen was referred to our Endocrine clinic for evaluation of osteoporosis and incidental finding of bilateral adrenal hyperplasia on CT spine. The patient rapidly developed kyphoscoliosis within the past 2 years. She was debilitated by pain and decreased mobility from compression fractures and spinal stenosis, and underwent thoracic and lumbar fusion surgery. On physical examination, her heart rate was 64 beats per minute, blood pressure 130/92 mmHg, weight 188 lbs. and Height 5.1 ft; a year ago it was 5.5 ft. Her face appeared round but not red. Buffalo hump and supraclavicular pad were noted. No striae or bruises noted. Healing surgical scars over the thoracic and lumbar spine were violaceous. The patient’s urine free cortisol levels, tested a month apart, were 190 mcg and 132 mcg (n 3.5-45 mcg/24h). Midnight salivary cortisol levels taken consecutive nights were 160 ng/dL and 513 ng/dL (n &lt; 100 ng/dL). Morning Serum Cortisol and ACTH were 20.2 ug/dL and 14 pg/mL (n Cortisol 6.0-27.0 ug/dL and ACTH 7.2-63 pg/mL). Following low dose (1mg) dexamethasone suppression testing, her serum cortisol were 12.6 ug/dL, ACTH levels were 32 pg/mL and dexamethasone were 187 ng/dL (n &lt; 30 ng/dL). 25-Hydroxy D total, TSH, Free T4, PTH intact, calcium, renin, aldosterone and SPEP levels were normal. Renal and liver functions were normal except alkaline phosphatase was 142 U/L (n 34-104 U/L). Pituitary MRI with contrast showed pituitary microadenoma. The patient was referred to a neurosurgeon and is planned for an inferior petrosal sinus sampling prior to transsphenoidal resection. Conclusion Cushing’s disease as a cause of osteoporosis is rare. Diagnosis of Cushing’s can be challenging in patients without obvious signs, as in our patient who was referred to an endocrinologist due to incidental finding of bilateral adrenal hyperplasia. A high degree of clinical suspicion is needed when investigating CD, as initial test results can be indecisive. As in our patient, initial ACTH and cortisol levels were normal, the low dose dexamethasone suppression test helped us direct our diagnosis towards CD.

Evaluation of Cushing's disease remission after transsphenoidal surgery based on early serum cortisol dynamics

2013 ◽  
Vol 80 (3) ◽  
pp. 411-418 ◽  
Author(s):  
Fabíola Costenaro ◽  
Ticiana C. Rodrigues ◽  
Guilherme A. F. Rollin ◽  
Nelson P. Ferreira ◽  
Mauro A. Czepielewski
Keyword(s):  
Cushing’S Disease ◽  
Transsphenoidal Surgery ◽  
Serum Cortisol ◽  
Cushing's Disease ◽  
Disease Remission

scholarly journals Etomidate in the management of severe Cushing’s disease and MRSA bacteraemia in a district general hospital in the United Kingdom

2019 ◽  
Vol 2019 ◽  
Author(s):  
Stephanie Wei Ping Wong ◽  
Yew Wen Yap ◽  
Ram Prakash Narayanan ◽  
Mohammad Al-Jubouri ◽  
Ashley Grossman ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
General Hospital ◽  
Cushing’S Disease ◽  
District General Hospital ◽  
Serum Cortisol ◽  
Cushing's Disease ◽  
High Morbidity ◽  
List Type ◽  
Cortisol Levels

Summary We report our experience on managing a case of florid Cushing’s disease with Methicillin-resistant Staphylococcus aureus (MRSA) sepsis using intravenous etomidate in the intensive care unit of a UK district general hospital. Learning points: Severe Cushing’s syndrome is associated with high morbidity and mortality. Etomidate is a safe and effective medical therapy to rapidly lower cortisol levels even in the context of severe sepsis and immunosuppression. Etomidate should ideally be administered in an intensive care unit but is still feasible in a district general hospital. During treatment with etomidate, accumulation of serum 11β-deoxycortisol (11DOC) levels can cross-react with laboratory cortisol measurement leading to falsely elevated serum cortisol levels. For this reason, serum cortisol measurement using a mass spectrometry assay should ideally be used to guide etomidate prescription.

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