scholarly journals SAT-277 A Fierce Presentation of Cushing Disease

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Farah Laith Al Sabie ◽  
Meenu Jain ◽  
Ammara Aziz
Keyword(s):  
Pituitary Adenoma ◽  
Hypertensive Crisis ◽  
Serum Cortisol ◽  
Serum Cortisol Level ◽  
Cushing Disease ◽  
Ectopic Acth ◽  
Free Cortisol ◽  
Ectopic Acth Production ◽  
Cortisol Levels ◽  
Work Up

Abstract Introduction: Cushing disease refers to the endogenous overproduction of glucocorticoid due to an ACTH-producing pituitary adenoma. It is important to recognize and treat due to the adverse health outcomes associated with it. We describe an unusual case of Cushing disease which presented very rapidly and progressively with extremely high cortisol levels mimicking those seen in ectopic production of ACTH.Case Presentation: A 43 year old Caucasian man, with no past medical history, presented with hypertensive crisis. He was discharged home with anti-hypertensive medications. Over the next 4 months, he gained 20 pounds, mainly around his abdomen, developed fatigue, and blood pressure continued to be high despite six anti-hypertensive medications, developed diabetes and hypokalemia, requiring 120 meq/day of potassium chloride. On exam, he had plethora, central obesity and wide, purple striae over his abdomen. Work-up for secondary causes of hypertension showed normal renal Doppler US, normal aldosterone and renin activity, normal plasma metanephrines, however, his 24 hour urinary free cortisol was dramatically elevated at 4022ug/day with a urine volume of 4 L, 1 mg dexamethasone suppression test showed unsuppressed serum cortisol of 55ug/dl. Morning ACTH of 125 pg/ml with concurrent serum cortisol level of 53.8 mcg/dl, indicated ACTH-dependent hypercortisolism. Inferior petrosal sinus sampling indicated a pituitary source of ACTH. Sellar MRI initially did not show a pituitary adenoma, however, repeat MRI with a 3-Tesla magnet showed a 4 mm pituitary adenoma. He was treated with ketoconazole and was started on atovaquone for PCP prophylaxis while awaiting trans-sphenoidal resection, which he had a month later. Pathology showed a 4 mm adenoma which stained strongly for ACTH. On postoperative day 1, serum cortisol dropped to 2.1 from 52.3 mcg/dl, and patient was discharged on hydrocortisone replacement. Three weeks later, he had lost 12 pounds, hyperglycemia improved with discontinuation of insulin, hypokalemia resolved and hypertension was well controlled on two anti-hypertensives. Discussion: ACTH-dependent Cushing syndrome is either caused by Cushing disease, or from ectopic ACTH production from a tumor. Cushing disease is characterized by a gradual onset and subtle manifestations of hypercortisolism. Acute, severe presentation favors an ectopic ACTH producing tumor, and is associated with much higher cortisol levels. In our patient, clinical data suggested ectopic ACTH production, yet he was found to have Cushing disease, and was treated successfully with trans-sphenoidal resection of the pituitary adenoma. It is imperative to consider all possibilities, and do the full work up so as not to miss an atypical presentation of Cushing disease, and direct treatment accordingly.

A Case of Cushing Syndrome Secondary to Ectopic Adrenocorticotropic Hormone Producing Carcinoid of the Duodenum

2005 ◽  
Vol 71 (5) ◽  
pp. 445-446 ◽  
Author(s):  
John M. Uecker ◽  
Matthew T. Janzow
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Cushing Syndrome ◽  
English Literature ◽  
Hypertensive Crisis ◽  
Serum Cortisol ◽  
Large Mass ◽  
Serum Cortisol Level ◽  
Ectopic Acth ◽  
Ectopic Acth Production ◽  
Head Of The Pancreas

Cushing syndrome caused by adrenocorticotropic hormone (ACTH) production from solid tumors can result in life-threatening hypercortisolemia. Ectopic ACTH production is most commonly associated with bronchial carcinoids and squamous cell carcinoma of the lung. We report a case of Cushing syndrome caused by ectopic ACTH production from a carcinoid of the duodenum. The patient presented to an outside hospital in hypertensive crisis and diabetic ketoacidosis. After stabilization, diagnostic studies including a serum cortisol level, and computed tomography (CT) scans of the head, chest, abdomen, and pelvis revealed hypercortisolemia and a large mass in the head of the pancreas. Pancreaticoduodenectomy was performed. Pathologic investigation revealed a 1-cm carcinoid of the duodenum with two large metastatic lymph nodes near the head of the pancreas. This is the first reported case in the English literature of Cushing syndrome caused by ectopic ACTH production from a carcinoid of the duodenum.

scholarly journals Fluconazole treatment in severe ectopic Cushing syndrome

2019 ◽  
Vol 2019 ◽  
Author(s):  
Teresa M Canteros ◽  
Valeria De Miguel ◽  
Patricia Fainstein-Day
Keyword(s):  
Liver Metastases ◽  
Alternative Treatment ◽  
Cushing Syndrome ◽  
Serum Cortisol ◽  
Bilateral Adrenalectomy ◽  
Ectopic Acth Syndrome ◽  
List Type ◽  
Ectopic Acth ◽  
Free Cortisol ◽  
Cortisol Levels

Summary Severe Cushing syndrome (SCS) is considered an emergency that requires immediate treatment to lower serum cortisol levels. Fluconazole may be considered an alternative treatment in Cushing syndrome when ketoconazole is not tolerated or unavailable. We report a 39-year-old woman with a history of partial pancreaticoduodenectomy due to a periampullary neuroendocrine tumor with locoregional extension. Three years after surgery, she developed liver metastases and was started on 120 mg of lanreotide/month, despite which, liver metastases progressed in the following 6 months. The patient showed extreme fatigue, muscle weakness, delirium, moon face, hirsutism and severe proximal weakness. Laboratory tests showed anemia, hyperglycemia and severe hypokalemia. 24-h urinary free cortisol: 2152 nmol/day (reference range (RR): <276), morning serum cortisol 4883.4 nmol/L (RR: 138–690), ACTH 127.3 pmol/L (RR: 2.2–10). She was diagnosed with ectopic ACTH syndrome (EAS). On admission, she presented with acute upper gastrointestinal tract bleeding and hemodynamic instability. Intravenous fluconazole 400 mg/day was started. After 48 h, her mental state improved and morning cortisol decreased by 25%. The dose was titrated to 600 mg/day which resulted in a 55% decrease in cortisol levels in 1 week, but then had to be decreased to 400 mg/day because transaminase levels increased over 3 times the upper normal level. After 18 days of treatment, hemodynamic stability, lower cortisol levels and better overall clinical status enabled successful bilateral adrenalectomy. This case report shows that intravenous fluconazole effectively decreased cortisol levels in SCS due to EAS. Learning points: Severe Cushing syndrome can be effectively treated with fluconazole to achieve a significant improvement of hypercortisolism prior to bilateral adrenalectomy. Intravenous fluconazole is an alternative treatment when ketoconazole is not tolerated and etomidate is not available. Fluconazole is well tolerated with mild side effects. Hepatotoxicity is usually mild and resolves after drug discontinuation.

Postoperative Day 1 Morning Cortisol Value as a Biomarker to Predict Long-term Remission of Cushing Disease

2020 ◽  
Vol 106 (1) ◽  
pp. e94-e102
Author(s):  
Fang Wang ◽  
Michael P Catalino ◽  
Wenya Linda Bi ◽  
Ian F Dunn ◽  
Timothy R Smith ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Logistic Regression Analysis ◽  
Serum Cortisol ◽  
Serum Cortisol Level ◽  
Cushing Disease ◽  
Kaplan Meier ◽  
Free Cortisol ◽  
Morning Serum Cortisol

Abstract Context Recurrence of Cushing disease (CD) can occur even decades after surgery. Biomarkers to predict recurrence of CD after surgery have been studied but are inconclusive. Objective The aim of our study was to identify specific biomarkers that can predict long-term remission after neurosurgery. Design Identification of specific biomarkers to predict long-term remission of CD was performed by logistic regression analysis followed by Kaplan–Meier survival analysis, using recurrence as the dependent variable. Setting A total of 260 patients with CD identified from our institutional research patient data registry search tool and from patients who presented to our longitudinal multidisciplinary clinic between May 2008 and May 2018 underwent statistical analysis. Interventions Data on clinical features, neuro-imaging study, pathology, biochemistry, and treatments were collected by reviewing digital chart records. Main Outcome Measure Postoperative cortisol as a biomarker to predict long-term remission after surgical treatment for CD. Results By logistic regression analysis, postoperative day 1 (POD1) morning (5-10 am) serum cortisol, female sex, and proliferative index had significant association with CD recurrence (odds ratio [OR] = 1.025, 95% CI: 1.002-1.048, P = .032). In contrast, the postoperative nadir cortisol (OR = 1.081, 95% CI: 0.989-1.181, P = .086), urinary free cortisol (OR = 1.032, 95% CI: 0.994-1.07, P = .098), and late night salivary cortisol (OR = 1.383, 95% CI: 0.841-2.274, P = .201) had no significant correlation with recurrence. A significant association between POD1 morning serum cortisol and long-term CD remission was verified by Kaplan–Meier analysis when using POD1 morning serum cortisol &lt;5 μg/dL as the cut-off. Conclusions The POD1 morning serum cortisol level has a significant association with CD recurrence.

scholarly journals Cyclic Cushing's syndrome

2010 ◽  
Vol 56 (4) ◽  
pp. 44-51
Author(s):  
E I Marova ◽  
I A Voronkova
Keyword(s):  
Cushing’S Syndrome ◽  
Clinical Signs ◽  
Serum Cortisol ◽  
Cushing's Syndrome ◽  
Plasma Cortisol Level ◽  
Average Life Expectancy ◽  
Ectopic Acth ◽  
Number Of Patients ◽  
Free Cortisol ◽  
Cortisol Levels

The cyclic Cushing's syndrome is a rare disease characterized by multiple episodes of elevated cortisol levels alternating with periods of its normal secretion. The so-called hypercorticism cycles may be either regular or episodic with intercycle intervals as long as a few days to several years. Most researchers agree that the reliable diagnosis of cyclic Cushing's syndrome should be based on laboratory detection of 3 peaks and 2 falls of plasma cortisol level. Cyclic Cushing's syndrome may be either ACTH dependent or independent. A review of 65 verified cases indicates that this condition may be caused by pituitary corticotropinoma (54%), ectopic ACTH-producing tumour (26%), and adrenal tumour (roughly 11%). The cause of the disease remains uncertain in 9% of the patients. Pathophysiological mechanisms of cyclic Cushing's syndrome are poorly known. In certain cases of bilateral macronodular adrenal hyperplasia or adrenal corticosteroma, it may be associated with the presence of ectopic receptors or anomalous expression of normally located receptors. The majority of the patients presenting with cyclic Cushing's syndrome exhibit symptoms of classical hypercorticism that manifest themselves either on a permanent or cyclic basis. In a small number of patients, clinical signs of cyclic Cushing's syndrome are virtually absent. Variations of the clinical picture and conflicting results of hormonal assays taken together make cyclic Cushing's syndrome difficult to diagnose. Therefore, physicians must be aware of this condition and actively search for it in all patients believed to have an enhanced cortisol production despite normal results of laboratory analysis. Frequent changes of urinary or salivary free cortisol levels are reliable and convenient criteria for cyclic Cushing's syndrome in patients suspected to have this condition. Results of cortisol stimulation or suppression tests are likely to lead to a false conclusion due to spontaneous falls and rises in serum cortisol levels at the time of analysis. Given laboratory confirmation of cyclic Cushing's syndrome, subsequent studies should be focused on the elucidation of its cause. The average life expectancy of patients with cyclic Cushing's syndrome remains to be determined.

Cushing disease: use of perioperative serum cortisol measurements in early determination of success following pituitary surgery

2007 ◽  
Vol 23 (3) ◽  
pp. 1-8 ◽  
Author(s):  
Armand Krikorian ◽  
Dima Abdelmannan ◽  
Warren R Selman ◽  
Baha M Arafah
Keyword(s):  
Sella Turcica ◽  
Pituitary Surgery ◽  
Serum Cortisol ◽  
Serum Cortisol Level ◽  
Current Recommendation ◽  
Cushing Disease ◽  
Acth Deficiency ◽  
Cortisol Levels ◽  
Acth Secreting

✓Despite many recent advances, management of cases of Cushing disease continues to be challenging. After complete resection of ACTH-secreting adenomas, patients develop transient ACTH deficiency requiring glucocorticoid replacement for several months. The current recommendation by many centers, including ours, for patients with ACTH-secreting adenomas is to withhold glucocorticoid therapy during and immediately after adenomectomy until there is clinical or biochemical evidence of ACTH deficiency. A serum cortisol level of less than 2 μg/dl within the first 48 hours after adenomectomy is a reliable biochemical marker of ACTH deficiency and is associated with clinical remission of Cushing disease. Higher serum cortisol levels in the immediate postoperative period should be interpreted with caution. The decision to immediately reexplore the sella turcica should be individualized, taking into account the findings at surgery, the histopathological findings, and the changes in serum cortisol levels as well as the patient's wishes and concerns. Optimal diagnosis and therapy for patients with Cushing disease require thorough and close coordination and involvement of all members of the management team.

scholarly journals Stereotactic radiosurgery for Cushing disease

2004 ◽  
Vol 16 (4) ◽  
pp. 1-7 ◽  
Author(s):  
Stephen J. Hentschel ◽  
Ian E. McCutcheon
Keyword(s):  
Stereotactic Radiosurgery ◽  
Cortisol Level ◽  
Cushing Syndrome ◽  
Latency Period ◽  
Serum Cortisol ◽  
Serum Cortisol Level ◽  
Cushing Disease ◽  
Fractionated Radiotherapy ◽  
Free Cortisol ◽  
Microsurgical Resection

The most common cause of Cushing syndrome is Cushing disease, in which hypercortisolism is produced by a functional adrenocorticotropic hormone–producing adenoma of the anterior pituitary gland. The common therapies available include microsurgical resection, conventional fractionated radiotherapy, and stereotactic radiosurgery (SRS). In this article the authors review the indications, results, and complications associated with SRS in the treatment of Cushing disease. In as many as 90% of patients SRS results in disease remission, which is defined as a normal 24-hour urinary free cortisol level and a normal or subnormal morning serum cortisol level. Although in most patients who are subsequently cured a marked decrease in the serum cortisol level is demonstrated within 3 months after treatment, a biochemical cure may be delayed up to 3 years in some cases. Complications following SRS for pituitary adenomas are uncommon, particularly in patients with microadenomas, which are most commonly seen in Cushing disease. The most common complication is hypopituitarism, which occurs in up to 50% of patients with a mean latency period of 5 years. Radiation-induced optic neuropathy has been reported in less than 2% of cases and induction of a secondary neoplasm in less than 1% of cases. For patients with Cushing disease, the rate of endocrinological cure following SRS appears to be similar to that attained using microsurgical resection. In contrast to surgery, SRS has the benefit of being noninvasive and associated with a very low incidence of diabetes insipidus, although hypopituitarism may be more common with SRS. With continued follow-up patient reviews and additional experience with SRS, it may become possible to make more definitive statements regarding SRS as the initial treatment for patients with Cushing disease.

scholarly journals Unusual Presentation of Cyclic Cushing’s Syndrome

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A163-A164
Author(s):  
Maria del Mar Morales Hernandez ◽  
Jessica Castellanos-Diaz ◽  
Sreevidya Subbarayan
Keyword(s):  
Hip Fracture ◽  
Adrenal Insufficiency ◽  
Cushing’S Syndrome ◽  
Serum Cortisol ◽  
Cushing's Syndrome ◽  
Ectopic Acth ◽  
Free Cortisol ◽  
Definitive Therapy ◽  
Facial Swelling ◽  
Cortisol Levels

Abstract Introduction: About 20–40% of patients with Cushing’s syndrome present with cyclic Cushing’s Syndrome characterized by episodes of cortisol excess interspersed with periods of normal cortisol secretion. A high degree of suspicion is needed to identify patients with cyclical hypercortisolism. Fluctuations in cortisol levels can make this a diagnostic challenge. Rarely, hypocortisolemia and frank adrenal insufficiency can occur. Case Report: A 77-year-old female with history of Cushing’s syndrome and transsphenoidal surgery with no adenoma identified on pathology presented with fatigue and concern for recurrence with ACTH of 358 pg/mL (6–50 pg/mL) and morning serum cortisol of 41.4 mcg/dL. Brain MRI showed a possible 4 mm pituitary adenoma. However, when she was transferred to our hospital, there was no evidence of hypercortisolism with cortisol of 9.5 mcg/dL, ACTH of 33pg/mL, 24 hr urine free cortisol (UFC) of 4.4ug/d (&lt;45ug/d) and she was discharged home after neurosurgery recommended no surgical intervention. A week later, the patient returned to the hospital with nausea and weakness, and found to have cortisol of 4.4mcg/dL, ACTH of 12 pg/mL and UFC of 2.8 ug/d requiring short course of hydrocortisone for adrenal insufficiency. One year later, she presented with hip fracture, worsening weakness, plethora, and facial swelling. UFC was 1,338.3mcg/24 hr(4.0–50.0 mcg/24 hr), AM serum cortisol 58.8mcg/dL and ACTH 304.7 pg/mL. In addition to severe osteoporosis with hip fracture, she had hypertension and impaired fasting glucose. She was treated with Ketoconazole 200mg daily which was titrated until AM cortisol levels decreased from 58.8 mcg/dL to 20 mcg/dL. Patient was discharged on Ketoconazole with plan to complete a Dotatate scan to evaluate for ectopic ACTH production which resulted negative. Shortly thereafter, she returned with hypotension, nausea, and fatigue. Repeat cortisol level was 2.3 mcg/dL with ACTH of 27.6 pg/ml. Ketoconazole was discontinued and patient was started on hydrocortisone for adrenal insufficiency. Hydrocortisone was gradually tapered off. Pituitary MRI and IPSS are planned for further evaluation. Discussion: Cyclic Cushing’s syndrome is diagnosed with three peaks and two troughs of cortisol production. Diagnosis and treatment are challenging since the cycles of hypercortisolism can occur sporadically and rapid fluctuations in cortisol makes it difficult to localize a source. Cortisol fluctuations can affect quality of life and result in complications such as diabetes, hypertension, and osteoporosis. Prompt identification of the source of the Cyclic Cushing’s syndrome is vital to pursue definitive therapy. However, in 9% of cases, there is no identifiable source. In such cases, medical therapy is warranted.

scholarly journals Perioperative serum cortisol levels in ACTH sufficient and ACTH deficient patients during transsphenoidal surgery of pituitary adenoma

Endocrine ◽  
2018 ◽  
Vol 62 (1) ◽  
pp. 83-89 ◽  
Author(s):  
Henrik Borg ◽  
Peter Siesjö ◽  
Babar Kahlon ◽  
Sigridur Fjalldal ◽  
Eva Marie Erfurth
Keyword(s):  
Pituitary Adenoma ◽  
Transsphenoidal Surgery ◽  
Serum Cortisol ◽  
Cortisol Levels

scholarly journals Impact of Technique on Cushing Disease Outcome Using Strict Remission Criteria

2013 ◽  
Vol 40 (3) ◽  
pp. 334-341 ◽  
Author(s):  
Hussein Alahmadi ◽  
Michael D. Cusimano ◽  
Kenneth Woo ◽  
Ameen A. Mohammed ◽  
Jeannette Goguen ◽  
...  
Keyword(s):  
Remission Rate ◽  
Serum Cortisol ◽  
P Value ◽  
Cushing Disease ◽  
Repeat Surgery ◽  
Free Cortisol ◽  
Significant Difference ◽  
Morning Serum Cortisol ◽  
Remission Criteria

Background:Cushing disease (CD) constitutes a challenging condition for the pituitary surgeon. Given the variety of factors affecting outcomes in CD, it is uncertain whether the newer endoscopic technique improves the results of surgery.Methods:A review was conducted of CD cases at our institution between 2000 and 2010. Analysis was done to: determine if surgical technique had an effect on outcome, identify the predictors of outcome and provide details of failed cases. Remission was defined as normal postoperative 24-hour urinary free cortisol (24-h UFC), suppression of morning serum cortisol to <50 nmol/L after 1mg of dexamethasone or being dependent on steroid replacement.Results:Forty-two patients met our inclusion criteria. Average follow-up period was 33 months. There were 15 macroadenomas and 27 microadenomas. Seventeen patients had an endoscopic transsphenoidal surgery and twenty-five patients had a microscopic transsphenoidal procedure. Long-term overall remission was achieved in 26 (62%) patients. There was no significant difference in remission rates between the two techniques (p value 0.757). Patient's subjective symptomatic improvement and drop of morning serum cortisol in the postoperative period to less than 100 nmol/L correlated with long-term remission (p value 0.0031and 0.0101, respectively) while repeat surgery was the only predictor of the lack of postoperative remission (p value 0.0008).Conclusions:Revision surgery predicted poor remission rate for CD. Within the power of our study size, there was no difference in outcome between the endoscopic and microscopic approaches. Surgical outcomes should be reviewed in association with remission criteria used in a study.

Use of morning serum cortisol level after transsphenoidal resection of pituitary adenoma to predict the need for long-term glucocorticoid supplementation

2009 ◽  
Vol 111 (3) ◽  
pp. 540-544 ◽  
Author(s):  
Nicholas F. Marko ◽  
Vivek A. Gonugunta ◽  
Amir H. Hamrahian ◽  
Ali Usmani ◽  
Marc R. Mayberg ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Cortisol Level ◽  
Postoperative Period ◽  
Serum Cortisol ◽  
Early Postoperative Period ◽  
Serum Cortisol Level ◽  
Total Serum ◽  
Total Cortisol ◽  
Hpa Function

Object Accurate assessment of the hypothalamic-pituitary-adrenal (HPA) axis is critical for appropriate management of the disease in patients with pituitary adenoma after transsphenoidal resection. The authors examine the role of the morning total serum cortisol level in the early postoperative period as a predictor of long-term HPA function. Methods Morning total serum cortisol was measured in 83 patients on postoperative Day 1 (or Day 2 if the patient received glucocorticoids during surgery) after transsphenoidal surgery for pituitary adenoma. These results were compared with those of definitive assays of HPA function performed at 1–3 months postoperatively, including cortrosyn/synacthen stimulation test (CST), insulin tolerance test (ITT), and metyrapone test (MTT). The ability of the early-postoperative morning cortisol level to predict HPA function was determined using standard confusion matrix calculations and receiver-operator control curve analysis. Results The authors found that an early postoperative morning total cortisol level ≥ 15 μg/dl is a sensitive and accurate predictor of normal HPA function in the postoperative period (sensitivity 80.5%, specificity 66.7%, positive predictive value 96.9%). Conclusions A morning total cortisol level ≥ 15 μg/dl in the early postoperative period after transsphenoidal surgery for pituitary adenomas is a good predictor of normal HPA function. This test has good sensitivity and accuracy and correlates well with the results of additional, definitive assays of HPA function (CST, ITT, and MTT) performed at 1–3 months postoperatively. Accordingly, it is the authors' practice to avoid exogenous perioperative glucocorticoid supplementation in patients with normal preoperative HPA function and postoperative morning total cortisol levels ≥ 15 μg/dl 1–2 days after transsphenoidal pituitary adenomectomy.

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