The Changes in Plasma Cortisol and Urinary Free Cortisol by an Overnight Dexamethasone Suppression Test in Patients with Cushing's Disease.

1988 ◽  
Vol 35 (6) ◽  
pp. 795-802 ◽  
Author(s):  
EMI ODAGIRI ◽  
REIKO DEMURA ◽  
HIROSHI DEMURA ◽  
TOSHIHIRO SUDA ◽  
NAOKO ISHIWATARI ◽  
...  
2014 ◽  
Vol 27 (11-12) ◽  
pp. 1043-1047 ◽  
Author(s):  
Julia Hoppmann ◽  
Isabel V. Wagner ◽  
Gudrun Junghans ◽  
Stefan A. Wudy ◽  
Michael Buchfelder ◽  
...  

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.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Dhivya Pahwa ◽  
Michael Howard Shanik

Abstract Introduction: Cushing’s disease is an abnormal secretion of ACTH from the pituitary that causes an increase in cortisol production from the adrenal glands. Resultant manifestations from this excess in cortisol include multiple metabolic as well as psychiatric disturbances which can lead to significant morbidity and mortality. Case: The patient is a 29 year old woman who presented with fatigue, decreased energy, poor memory and insomnia for 3 months. She noted irregular menses for 4 months. She was referred from her primary doctor for elevated salivary cortisol and DHEA levels. Evaluation revealed BP: 104/76, HR 78, RR 12, BMI 22.7. She was a thin woman without striae, moon face, buffalo hump or bruising. 24 hour urine free cortisol was 90.3 mcg/24hr. One mg dexamethasone suppression test resulted in an AM cortisol of 17.6 ug/dL and ACTH 25 pg/mL. An 8 mg dexamethasone suppression test showed a cortisol level of 1.2 ug/dL with an ACTH <5 pg/mL. The combined results were suggestive of Cushing’s disease. The patient went for MRI of the pituitary which showed a 4 mm hypoenhancing region on the right side of the gland suspicious for a microadenoma. The patient was followed closely and continued to report fatigue and insomnia. Inferior petrosal sinus sampling was performed. Venous blood sampling of ACTH from the periphery at 0 min, 5 min and 15 min were: <5 pg/mL, <5 pg/mL, and <5 pg/mL respectively. On the right at 0 min, 1 min, 5 min, 15 min ACTH levels were: 12 pg/mL, 14 pg/mL, 16 pg/mL, 14 pg/mL. On the left at 5 min and 15 min ACTH measured 8 pg/mL and 7 pg/mL. These findings confirmed the suspicion of a right-sided ACTH-secreting pituitary adenoma. She was referred to a neurosurgeon to evaluate for resection of the adenoma. Due to the ongoing symptoms, the neurosurgical removal of the lesion was expedited and scheduled within several weeks. While awaiting removal the patient sadly took her own life. Conclusion: Aside from the more commonly associated metabolic manifestations of elevated cortisol levels, psychiatric symptoms can be the initial complaint of patients with Cushing’s disease. Symptoms can include fatigue, depressive symptoms, insomnia, and sleep dysregulation. Currently the Endocrine Society Guideline for Cushing’s syndrome does not have any specific recommendations regarding depression screening. Psychiatric complications are a known manifestation of Cushing’s disease. Close follow up and urgent psychiatric referral with the onset of signs of depression or anxiety should be included as part of Cushing’s disease evaluation. Symptoms of mental health disturbances may be subtle and thus all patients with Cushing’s disease should be screened and monitored for underlying psychiatric illnesses. Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5152600/pdf/JMedLife-09-12.pdf


2000 ◽  
Vol 85 (10) ◽  
pp. 3569-3574 ◽  
Author(s):  
Mirella Moro ◽  
Pietro Putignano ◽  
Marco Losa ◽  
Cecilia Invitti ◽  
Caterina Maraschini ◽  
...  

Differentiating Cushing’s disease (CD) from pseudo-Cushing (PC) states may still be difficult in current practice. Because desmopressin (1-deamino-8D-arginine vasopressin, DDAVP), a vasopressin analogue, stimulates ACTH release in patients with CD but not in the majority of normal, obese, and depressed subjects, we investigated its ability to discriminate CD from PC states. One hundred seventy-three subjects (76 with active CD, 30 with PC, 36 with simple obesity, and 31 healthy volunteers) were tested with an iv bolus of 10 μg DDAVP. Sixty-one of these subjects also underwent a control study with saline. DDAVP induced marked ACTH and cortisol rises in CD (P < 0.005 vs. saline, for both ACTH and cortisol) but not in PC. A significant ACTH elevation occurred upon DDAVP administration also in normal and obese subjects, but it was much smaller than that observed in patients with CD (P < 0.0001). A peak absolute ACTH increase (≥6 pmol/L), after DDAVP, allowed us to recognize 66 of 76 patients with CD and 88 of 97 subjects of the other groups. The same criterion correctly identified 18 of 20 patients with mild CD (24-h urinary free cortisol ≤ 690 nmol/day) and 29 of 30 PC, resulting in a diagnostic accuracy of 94%, which was definitely higher than that displayed by urinary free cortisol, overnight 1-mg dexamethasone suppression test, and midnight plasma cortisol. In conclusion, the DDAVP test seems to be a useful adjunctive tool for the evaluation of hypercortisolemic patients chiefly because of its ability to differentiate mild CD from PC states.


1983 ◽  
Vol 58 (1) ◽  
pp. 129-132 ◽  
Author(s):  
Lucille W. King ◽  
Kalmon D. Post ◽  
Israel Yust ◽  
Seymour Reichlin

✓ Pituitary-adrenal function in a patient with classical features of Cushing's disease, increased urinary excretion of cortisol, and documented pituitary adenoma was found to be suppressed by dexamethasone in doses even less than those required to inhibit secretion in normal individuals. This response was shown to be due to inappropriately high levels of dexamethasone in plasma, presumed to be the consequence of decreased peripheral clearance. Because the dexamethasone suppression test is so widely used for diagnosis of Cushing's disease, it is important to recognize that this situation can occasionally occur.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Shady Ibrahim ElEbrashy ◽  
Ehab ElRefaay ◽  
Farouq H Youssef

Abstract Background and objective: Hypercortisolism is the hall mark of ACTH Cushing’s syndrome, which is a benign ACTH secreting tumor resulting in high morbidity and mortality. The diagnosis is based on an elevated serum ACTH, elevated 24h urinary cortisol or a non-suppressible ACTH after dexamethasone suppression test. Confirmation of ACTH hypersecretion is followed by localization of the adenoma which can be pituitary in origin or peripheral. Dynamic MRI of the pituitary gland is the gold standard for diagnosis of pituitary tumors, and contrast enhanced CT scan is the gold standard for ectopic lesions which are usually lung tumors. The localization of the lesion is often a challenge because conventional MRI fail to show pituitary lesions and sometimes requiring inferior petrosal sinus sampling to confirm pituitary origin. Transsphenoidal surgery is the treatment of choice for Cushing’s disease, even without MRI evidence of pituitary tumors, if pituitary origin is confirmed by inferior petrosal sinus sampling. This causes increase in the incidence of treatment failure and complications. Thus, the diagnosis of Cushing’s disease urges exploring new diagnostic modalities. In our study we test the sensitivity of 11C methionine PET CT together with dynamic pituitary MRI in localization of ACTH dependent Cushing’s disease. Materials and methods This is an interventional, prospective study, forty-one subjects: newly diagnosed ACTH dependent Cushing’s Syndrome (n=29). (indicated by non-suppressible ACTH on dexamethasone suppression test) or persistent hypercortisolism following transsphenoidal surgery (n=12). 11C methionine PET CT was done in all cases in addition to dynamic pituitary MRI. All patients underwent 11 C-methionine PET-CT in addition to dynamic pituitary MRI This allowed us to determine whether suspected adenomas seen on structural imaging exhibited focal tracer uptake on functional imaging.Inclusion Criteria:• Aged 18 years old or over• Patient with a diagnosed Cushing’s disease confirmed by non-suppressible ACTH on dexamethasone suppression test.• Patient with persistent ACTH dependent Cushing’s disease following transsphenoidal surgery.• Patient not enrolled in other interventional studies.Exclusion Criteria:• Contraindication to MRI• Pregnant woman, breastfeeding RESULTS: Patients with newly diagnosed ACTH dependent Cushing: 24 out of 29 of the cases showed adenoma on dynamic MRI of the pituitary; 5 out of 29 cases failed to showed any lesions on dynamic MRI of the pituitary; Inferior petrosal sampling was done and confirmed pituitary origin in 4 out of 5 and 1 out of 5 was found to have ectopic ACTH secretion. In patients with persistent hypercortisolism following transsphenoidal surgery; 3 out of 12 of the cases showed adenoma on dynamic MRI of the pituitary and 7 out of 12 cases failed to showed any lesions on dynamic MRI of the pituitary and inferior petrosal sampling was done and confirmed pituitary origin in all 12 cases. All 41 cases underwent 11C methionine PET CT scan; 39 patients showed tracer uptake on 11c methionine PET CT scan in the pituitary area, 36 of which had unilateral asymmetrical tracer uptake. All 40 subjects with suspected pituitary lesions were confirmed to be of pituitary origin by histopathological examination of biopsies taken intraoperatively. CONCLUSIONS 11C methionine PET CT has proven to be of very high sensitivity in detecting ACTH secreting adenomas, further studies should be done on a larger scale as this modality can address the pitfalls in localization of ACTH secreting lesions.


Author(s):  
James I. Hudson ◽  
David L. Katz ◽  
Harrison G. Pope ◽  
Margo S. Hudson ◽  
George T. Griffing ◽  
...  

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Christine Mathai ◽  
Jonathan Robert Anolik

Abstract Objective: The objective of this case report is to discuss a case of Cushing’s disease with two ACTH-producing pituitary tumors and emphasize consideration of repeat surgery as a treatment modality for unsuccessful initial surgery. Methods: We present a case of a patient with Cushing’s disease with two ACTH-producing pituitary tumors and a literature review. Results: A 36 year-old female found to have left supraclavicular fossa swelling was screened for Cushing’s syndrome. Midnight salivary cortisol levels elevated at 0.636 ug/dL and 0.316 ug/dL (<0.010–0.090 ug/dL). 24-hour urine cortisol 162 ug/24 hr (0–50 ug/24 hr). 1-mg dexamethasone suppression test 14.0 ug/dL. Serum morning cortisol 26.4 ug/dL with corresponding ACTH 66.7 pg/mL (7.2–63.3 pg/mL). MRI brain with and without contrast showed a 7-mm relatively hypoenhancing lesion of the anterior pituitary gland. 8-mg dexamethasone suppression test 2.7 ug/dL. She underwent transsphenoidal surgery (TSS) and pathology was consistent with a pituitary adenoma staining positive for ACTH. No residual tumor was seen. Postoperative morning serum cortisol 17.0 ug/dL and ACTH 79 pg/mL (9–46 pg/mL). She had repeat TSS and the area of resection was clean with no residual tumor but a second adenoma was found that was not visualized on MRI and was distinct from the initial lesion. Postoperative morning cortisol 0.7 ug/dL and ACTH <9 pg/mL (9–46 pg/mL). Pathology was consistent with pituitary adenoma staining positive for ACTH. She is now on steroids for central adrenal insufficiency. Discussion: First-line treatment for Cushing’s disease is surgical resection of the primary lesion (Nieman LK, Biller BMK, et al. Treatment of Cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2015; 100(8):2807–2831). Remission rates are 73–76% for selectively resected microadenomas but 43% for macroadenomas (Nieman et al. 2015). For patients who undergo a noncurative surgery, second-line therapies include repeat TSS, radiotherapy, medical therapy, and bilateral adrenalectomy. Repeat TSS is recommended particularly in patients who had evidence of incomplete resection or a pituitary lesion on imaging although this was not the case with our patient. Repeat TSS is cited to be successful in about 50–60% of cases (Patil CG, Veeravagu A, et al. Outcomes after repeat transsphenoidal surgery for recurrent Cushing’s disease. Neurosurgery. 2008;63(2):266–270) but carries an increased risk of hypopituitarism and lower likelihood of remission compared to initial surgery. Remission can be achieved more rapidly compared to other second-line treatments. Conclusion: In Cushing’s Disease with unsuccessful initial surgery, consideration for repeat TSS may be considered when there is access to an expert pituitary surgeon.


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