The role of an acute pasireotide suppression test in predicting response to treatment in patients with Cushing’s disease: findings from a pilot study

✓ 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.

Download Full-text

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

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2014-0230 ◽

2014 ◽

Vol 27 (11-12) ◽

pp. 1043-1047 ◽

Cited By ~ 1

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.

Download Full-text

Cushing’s Disease: The Role of Adrenalectomy and Autotransplantation

Surgical Clinics of North America ◽

10.1016/s0039-6109(16)41741-x ◽

1979 ◽

Vol 59 (1) ◽

pp. 159-165 ◽

Cited By ~ 8

Author(s):

Richard A. Prinz ◽

Marion H. Brooks ◽

Ann M. Lawrence ◽

Edward Paloyan

Keyword(s):

Cushing’S Disease ◽

Cushing's Disease

Download Full-text

Mutation and Expression Analysis of Corticotropin-Releasing Factor 1 Receptor in Adrenocorticotropin-Secreting Pituitary Adenomas1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.83.9.5114 ◽

1998 ◽

Vol 83 (9) ◽

pp. 3327-3331

Author(s):

K. D. Dieterich ◽

E. D. Gundelfinger ◽

D. K. Lüdecke ◽

H. Lehnert

Keyword(s):

Expression Analysis ◽

Cushing’S Disease ◽

Pituitary Adenomas ◽

Messenger Rna ◽

Corticotropin Releasing Factor ◽

Cushing's Disease ◽

Receptor Regulation ◽

R Gene ◽

Acth Secreting

The present study was designed to investigate a possible role of CRF1 receptors (CRF1-R) in the pathogenesis of Cushing’s disease. ACTH-secreting pituitary adenomas and nonsecreting pituitary adenomas have been analyzed for mutations in the CRF1-R gene by PCR and sequencing and been compared with the sequences of normal anterior pituitaries. No mutations affecting the CRF1-R protein have been found in all tumors analyzed. However, we found a significant overexpression of the CRF1-R messenger RNA in ACTH-secreting pituitary adenomas vs. inactive adenomas and normal pituitaries. We conclude that mutations of the CRF1-R are unlikely to be involved in Cushing’s disease. We suggest that the overexpression of the CRF1-R messenger RNA may be related to a disturbed receptor regulation in ACTH-secreting pituitary adenomas.

Download Full-text

MON-LB58 The Use of 11C Methionine PET CT In Localization of ACTH Dependent Cushing’s Disease

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.2273 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Shady Ibrahim ElEbrashy ◽

Ehab ElRefaay ◽

Farouq H Youssef

Keyword(s):

Cushing’S Disease ◽

Transsphenoidal Surgery ◽

Dynamic Mri ◽

Tracer Uptake ◽

Dexamethasone Suppression Test ◽

Cushing's Disease ◽

Pet Ct ◽

Suppression Test ◽

Acth Secreting ◽

Dexamethasone Suppression

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.

Download Full-text

Pleurihormonal Pituitary Adenomas Presenting as Acromegaly

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1227 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A602-A602

Author(s):

Megan Schwehr ◽

Mayumi Endo

Keyword(s):

Pituitary Adenoma ◽

Cushing’S Syndrome ◽

Cushing’S Disease ◽

Pituitary Adenomas ◽

Brain Mri ◽

Fatty Infiltration ◽

Cushing's Syndrome ◽

Cushing's Disease ◽

Peripheral Muscle ◽

Suppression Test

Abstract Background: Pleurihormonal pituitary adenomas represent 10-15% of all functioning pituitary adenomas1. One of the rarest combinations is ACTH-GH co-secretion with concomitant acromegaly and Cushing’s disease. Clinical Case: 30-year-old female with type 2 diabetes (A1c 11.4%) developed rapidly progressive peripheral neuropathy. Labs revealed a transaminitis. Hepatic ultrasound revealed fatty infiltration of the liver consistent with steatosis. Patient endorsed life-long “chicken legs”, buffalo hump, and easy bruising. She continued to have worsening paresthesias and stated her teeth were “more translucent”. At an endocrinology visit peripheral muscle wasting, atraumatic bruising at the ankles and toes,and striae on the abdomen, shoulders, breasts, and armpits were noted. She had also noted teeth separation and thinning over time and worsening diffuse joint aches. Lab results showed elevated cortisol value of 8.4 mcg/dl after 1 mg dexamethasone suppression test. 24-hour urine cortisol was elevated (87 ug/24 hrs, nl < 45 ug/24 hrs), confirming the diagnosis of Cushing’s syndrome. ACTH was inappropriately normal (56 pg/mL, nl 7.2 – 63 pg/mL), suggesting ACTH dependency. IGF-1 was elevated twice (328 ng/dL and 391 ng/dL, nl <303 ng/dL), and a GH suppression test was abnormal (GH 1.14 ng/mL at 90 minutes) confirming the diagnosis of acromegaly. Brain MRI revealed a cystic pituitary microadenoma (0.5 x 0.5 x 0.6 cm), and the patient underwent surgical resection via transnasal transsphenoidal pituitary surgery with total tumor removal. Immunostaining was positive for only synaptophysin and ACTH. Postoperative diagnosis of Cushing’s disease was made, with formal diagnosis of acromegaly pending improvement in follow-up IGF-1 levels. Literature reviews have revealed very few cases of pleurihormonal pituitary adenomas presenting with concomitant Cushing’s Syndrome and acromegaly. Roca et. al examined 17 studies which described 20 patients with this condition; only 4 presented with symptoms of both acromegaly and Cushing’s disease. In many cases previously reported, the clinical presentation of Cushing’s syndrome was subtle, often with subclinical Cushing’s syndrome, while patients had florid symptoms of acromegaly.1. Conclusion: This Cushing’s predominant case of a GH-ACTH co-secreting tumor is an incredibly rare presentation for this pleurihormonal pituitary adenoma, which is already a rare diagnosis. References: 1.Roca E, Mattogno PP, Porcelli T, Poliani L, Belotti F, Schreiber A, Maffezzoni F, Fontanella MM, Doglietto F. Plurihormonal ACTH-GH Pituitary Adenoma: Case Report and Systematic Literature Review. World Neurosurg. 2018 Jun;114:e158-e164. PMID: 29501516.

Download Full-text

Abstract #456 A Case of Rapid Onset Cushing’s Disease with Aberrant Dexamethasone Suppression Test

Endocrine Practice ◽

10.1016/s1530-891x(20)46800-4 ◽

2019 ◽

Vol 25 ◽

pp. 220-221

Author(s):

Vibhavasu Sharma ◽

Antoni Kafrouni-Gerges

Keyword(s):

Cushing’S Disease ◽

Rapid Onset ◽

Dexamethasone Suppression Test ◽

Cushing's Disease ◽

Suppression Test ◽

Dexamethasone Suppression

Download Full-text

Evaluation of lipid profile and its relationship with blood pressure in patients with Cushing’s disease

Endocrine Connections ◽

10.1530/ec-18-0010 ◽

2018 ◽

Vol 7 (5) ◽

pp. 637-644 ◽

Cited By ~ 3

Author(s):

Lang Qin ◽

Xiaoming Zhu ◽

Xiaoxia Liu ◽

Meifang Zeng ◽

Ran Tao ◽

...

Keyword(s):

Blood Pressure ◽

Lipid Profile ◽

Cushing’S Disease ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Cushing's Disease ◽

Independent Association ◽

Lipids Profile ◽

Restricted Cubic Splines

Introduction The purpose of the study was to describe lipid profile and explore pathogenetic role of LDL-c on hypertension in patients with Cushing’s disease (CD). Hypertension is a common feature in patients with CD. Previous study found low-density lipoprotein cholesterol (LDL-c) uptake in vascular cells might be involved in vascular remodeling in patients with CD. Therefore, we evaluated the relationship between lipid profile and the blood pressure in patients with CD. Methods This retrospective study included 84 patients referred to Huashan Hospital for the evaluation and diagnosis of CD from January 2012 to December 2013. All subjects had detailed clinical evaluation by the same group of endocrinology specialists to avoid subjective influences. Results We found that high LDL-c patients had significant higher body mass index (BMI), systolic blood pressure (SBP), cholesterol (CHO), triglyceride (TG), and apolipoproteinB (apoB) (P < 0.05). An association was detected between SBP values and lipids profile including CHO, TG, LDL-c, apolipoproteinA (apoA), apoB and lipoprotein(a) (LP(a)). After adjustment for all covariates, the LDL-c remained positively associated with SBP. In patients with or without taking statins, patients with LDL-c ≥3.37 mmol/L had higher SBP than patients with LDL-c <3.37 mmol/L. Then, LDL-c was coded using restricted cubic splines (RCS) function with three knots located at the 5th, 50th and 95th percentiles of the distribution of LDL-c. Compared to individuals with 3.215 mmol/L of LDL-c, individuals with 4.0, 4.5 and 5.0 mmol/L of LDL-c had differences of 3.86, 8.53 and 14.11 mmHg in SBP, respectively. Conclusions An independent association between LDL-c and SBP was found in patients with CD. We speculate that LDL-c may be a pathogenic factor for hypertension in those patients.

Download Full-text