Database : MEDLINE
Search on : Pituitary and ACTH and Hypersecretion [Words]
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[PMID]: 29330227
[Au] Autor:Ironside N; Chatain G; Asuzu D; Benzo S; Lodish M; Sharma S; Nieman L; Stratakis CA; Lonser RR; Chittiboina P
[Ad] Address:Surgical Neurology BranchNational Institute of Neurological Diseases and Stroke, Bethesda, Maryland, USA.
[Ti] Title:Earlier post-operative hypocortisolemia may predict durable remission from Cushing's disease.
[So] Source:Eur J Endocrinol;178(3):255-263, 2018 Mar.
[Is] ISSN:1479-683X
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:CONTEXT: Achievement of hypocortisolemia following transsphenoidal surgery (TSS) for Cushing's disease (CD) is associated with successful adenoma resection. However, up to one-third of these patients recur. OBJECTIVE: We assessed whether delay in reaching post-operative cortisol nadir may delineate patients at risk of recurrence for CD following TSS. METHODS: A retrospective review of 257 patients who received 291 TSS procedures for CD at NIH, between 2003 and 2016. Early biochemical remission (serum cortisol nadir <5 µg/dL) was confirmed with endocrinological and clinical follow-up. Recurrence was detected by laboratory testing, clinical stigmata or medication dependence during a median follow-up of 11 months. RESULTS: Of the 268 unique admissions, remission was recorded in 241 instances. Recurrence was observed in 9% of these cases with cortisol nadir ≤5 µg/dL and 6% of cases with cortisol nadir ≤2 µg/dL. The timing of hypocortisolemia was critical in detecting late recurrences. Morning POD-1 cortisol <3.3 µg/dL was 100% sensitive in predicting durable remission and morning POD-3 cortisol ≥18.5 µg/dL was 98.6% specific in predicting remote recurrence. AUROC analysis revealed that hypocortisolemia ≤5 µg/dL before 15 h (post-operative) had 95% sensitivity and an NPV of 0.98 for durable remission. Serum cortisol level ≤2 µg/dL, when achieved before 21 h, improved sensitivity to 100%. CONCLUSIONS: In our cohort, early, profound hypocortisolemia could be used as a clinical prediction tool for durable remission. Achievement of hypocortisolemia ≤2 µg/dL before 21 post-operative hours appeared to accurately predict durable remission in the intermediate term.
[Mh] MeSH terms primary: ACTH-Secreting Pituitary Adenoma/surgery
Adenoma/surgery
Hydrocortisone/blood
Neoplasm Recurrence, Local/epidemiology
Neurosurgical Procedures
Pituitary ACTH Hypersecretion/surgery
[Mh] MeSH terms secundary: Area Under Curve
Humans
Kaplan-Meier Estimate
Logistic Models
Neoplasm Recurrence, Local/blood
Postoperative Period
ROC Curve
Remission Induction
Time Factors
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:WI4X0X7BPJ (Hydrocortisone)
[Em] Entry month:1802
[Cu] Class update date: 180220
[Lr] Last revision date:180220
[Js] Journal subset:IM
[Da] Date of entry for processing:180114
[St] Status:MEDLINE
[do] DOI:10.1530/EJE-17-0873

  2 / 1737 MEDLINE  
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[PMID]: 29384929
[Au] Autor:Park SY; Kwak MK; Kim HJ; Park HK; Suh KI; Yoo MH; Jin SY; Yun S; Byun DW
[Ad] Address:Division of Endocrinology and Metabolism, Departments of Internal Medicine.
[Ti] Title:Case report of a bilateral adrenal myelolipoma associated with Cushing disease.
[So] Source:Medicine (Baltimore);96(52):e9455, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:RATIONALE: Adrenal myelolipomas are rare benign tumors, composed of a variable mixture of mature adipose tissue and hematopoietic tissue. These tumors are frequently detected incidentally and are usually asymptomatic, and hormonally inactive. PATIENT CONCERNS: During a routine health checkup, a 52-year-old man was found to have a tumor on the bilateral adrenal glands. Abdominal computed tomography revealed a well-defined, heterogeneously enhanced bilateral adrenal mass, suggesting a myelolipoma. DIAGNOSES: The hormonal evaluation revealed adrenocorticotropic hormone (ACTH) dependent Cushing syndrome. INTERVENTIONS: The patient underwent left adrenalectomy, and transsphenoidal resection of a pituitary mass. The final diagnosis was adrenal myelolipoma associated with Cushing disease. OUTCOMES: Growth of right adrenal myelolipoma was detected during the 7-year follow-up. There were enhancing pituitary lesions in repeat magnetic resonance imaging of the sellar region, which implies persistent or recurrent pituitary adenoma. This case reinforces relationship between Cushing disease and adrenal myelolipoma. LESSONS: To the best of our knowledge, this is the first reported pathologically confirmed bilateral adrenal myelolipoma associated with Cushing disease. This report supports the idea that ACTH is associated with the development of adrenal myelolipoma.
[Mh] MeSH terms primary: Adrenal Gland Neoplasms/complications
Adrenal Gland Neoplasms/diagnosis
Myelolipoma/complications
Myelolipoma/diagnosis
Pituitary ACTH Hypersecretion/complications
Pituitary ACTH Hypersecretion/diagnosis
[Mh] MeSH terms secundary: Adrenal Gland Neoplasms/surgery
Adrenalectomy
Humans
Male
Middle Aged
Myelolipoma/surgery
Pituitary ACTH Hypersecretion/surgery
[Pt] Publication type:CASE REPORTS; JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180209
[Lr] Last revision date:180209
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:180201
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009455

  3 / 1737 MEDLINE  
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[PMID]: 28819015
[Au] Autor:Andreescu CE; Alwani RA; Hofland J; Looijenga LHJ; de Herder WW; Hofland LJ; Feelders RA
[Ad] Address:Department of Internal MedicineErasmus Medical Center, Rotterdam, The Netherlands Corina.Andreescu@uzbrussel.be.
[Ti] Title:Adrenal Cushing's syndrome during pregnancy.
[So] Source:Eur J Endocrinol;177(5):K13-K20, 2017 Nov.
[Is] ISSN:1479-683X
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Cushing syndrome (CS) during pregnancy is a rare condition with only a few cases reported in the literature. Misdiagnosis of CS is common because of overlapping features like fatigue, weight gain, striae and emotional changes that can occur during normal pregnancy. Changes in maternal hormones and their binding proteins complicate assessment of glucocorticoid hormone levels during gestation. CS during pregnancy is most frequently due to an adrenal adenoma and to a lesser degree to adrenocorticotropic hormone (ACTH) hypersecretion by a pituitary adenoma. Furthermore, aberrant expression of luteinizing hormone (LH) receptors in the adrenal cortex has been suggested to be involved in the pathogenesis of adrenal CS during pregnancy. We report three pregnant women with ACTH-independent Cushing's syndrome and an adrenal tumor. After uncomplicated delivery, patient 1 underwent testing for aberrant hormone receptor expression by the adenoma. Cortisol responses were found after administration of luteinizing hormone-releasing hormone (LHRH), human chorionic gonadotropin (hCG), glucagon, vasopressin and a standard mixed meal. All patients were treated with laparoscopic adrenalectomy. Adrenal tumor tissue of two patients showed positive immunohistochemical staining of LH receptors. Considering the cortisol responses to LHRH and hCG, and the development of CS during pregnancy in these patients, it is likely that ACTH-independent hypercortisolism was induced by the pregnancy-associated rise in hCG levels that activated aberrantly expressed LH receptors in the adrenal adenoma. Remarkably, adrenal adenomas may simultaneously express multiple aberrant receptors and individual ligands may play a role in the regulation of cortisol production in CS during pregnancy.
[Mh] MeSH terms primary: Cushing Syndrome/blood
Cushing Syndrome/diagnostic imaging
Pregnancy Complications/blood
Pregnancy Complications/diagnostic imaging
[Mh] MeSH terms secundary: Adult
Cushing Syndrome/complications
Female
Humans
Infant, Newborn
Pregnancy
Ultrasonography, Prenatal/methods
[Pt] Publication type:CASE REPORTS; JOURNAL ARTICLE
[Em] Entry month:1710
[Cu] Class update date: 171012
[Lr] Last revision date:171012
[Js] Journal subset:IM
[Da] Date of entry for processing:170819
[St] Status:MEDLINE
[do] DOI:10.1530/EJE-17-0263

  4 / 1737 MEDLINE  
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[PMID]: 28814582
[Au] Autor:Chakraborty PP; Patra S; Biswas SN; Bhattacharjee R
[Ad] Address:Department of Medicine, Midnapore Medical College and Hospital, Midnapore, West Bengal, India.
[Ti] Title:Adrenal myelolipoma(s) as presenting manifestation of subclinical Cushing's disease (eutopic ACTH-dependent Cushing's syndrome).
[So] Source:BMJ Case Rep;2017, 2017 Aug 16.
[Is] ISSN:1757-790X
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Primary adrenal myelolipomas, relatively rare benign tumours of the adrenal cortex are typically unilateral, hormonally inactive and asymptomatic, hence often diagnosed as 'adrenal incidentaloma'. Bilateral adrenal myelolipomas, in particular, may be associated with underlying endocrinopathies associated with elevated circulating adrenocorticotropic hormone (ACTH) concentration. Subclinical cortisol hypersecretion, irrespective of its ACTH dependency, does not manifest typical clinical phenotype of hypercortisolemia, and thus termed subclinical Cushing's syndrome. In this article, hormonal evaluation in a middle-aged woman with diabetes, hypertension and incidentally discovered unilateral adrenal myelolipoma revealed underlying subclinical Cushing's disease. Abdominal CT revealed another tiny focus in the contralateral adrenal gland, probably representing incipient myelolipoma.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1708
[Cu] Class update date: 170817
[Lr] Last revision date:170817
[St] Status:In-Process

  5 / 1737 MEDLINE  
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[PMID]: 28707538
[Au] Autor:Michelle M A; Jensen CT; Habra MA; Menias CO; Shaaban AM; Wagner-Bartak NA; Roman-Colon AM; Elsayes KM
[Ad] Address:1 Department of Diagnostic Radiology, Baylor College of Medicine, Houston, TX, USA.
[Ti] Title:Adrenal cortical hyperplasia: diagnostic workup, subtypes, imaging features and mimics.
[So] Source:Br J Radiol;90(1079):20170330, 2017 Nov.
[Is] ISSN:1748-880X
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Adrenal cortical hyperplasia manifests radiologically as a non-malignant growth, or enlargement, of the adrenal glands, specifically the cortex, although the cortex cannot be definitively identified by conventional imaging. Controlled by the pituitary gland, the adrenal cortex drives critical processes, such as the production of cortisol, mineralocorticoid and sex hormones. Any disruption in the multiple enzymes and hormones involved in these pathways may cause serious or life-threatening symptoms, often associated with anatomical changes in the adrenal glands. Diagnosis and treatment of adrenal cortical hyperplasia requires a thorough clinical evaluation. As imaging has become more robust so has its role in the diagnosis and treatment of adrenal conditions. CT has been the primary modality for adrenal imaging owing to reproducibility, temporal and spatial resolution and broad access. MRI serves a complimentary role in adrenal imaging and can be used to further evaluate indeterminate CT findings or serve as an adjunct tool without the use of ionizing radiation. Ultrasound and fluoroscopy (genitography) are most commonly used in children and foetuses to evaluate congenital adrenal hyperplasia. This article will discuss the clinical presentation, laboratory workup and imaging features of adrenal cortical hyperplasia, both congenital and acquired.
[Mh] MeSH terms primary: Adrenal Glands/diagnostic imaging
Adrenal Hyperplasia, Congenital/diagnosis
[Mh] MeSH terms secundary: Adolescent
Adrenal Glands/pathology
Adrenal Hyperplasia, Congenital/classification
Adrenal Hyperplasia, Congenital/diagnostic imaging
Adrenal Hyperplasia, Congenital/metabolism
Adrenocorticotropic Hormone/blood
Adult
Cushing Syndrome/diagnosis
Diagnosis, Differential
Female
Humans
Hyperplasia/classification
Hyperplasia/diagnostic imaging
Hyperplasia/etiology
Infant, Newborn
Magnetic Resonance Imaging
Male
Middle Aged
Organ Size
Pituitary ACTH Hypersecretion/diagnosis
Steroid 21-Hydroxylase
Tomography, X-Ray Computed
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Nm] Name of substance:9002-60-2 (Adrenocorticotropic Hormone); EC 1.14.14.16 (Steroid 21-Hydroxylase)
[Em] Entry month:1710
[Cu] Class update date: 171019
[Lr] Last revision date:171019
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:170715
[St] Status:MEDLINE
[do] DOI:10.1259/bjr.20170330

  6 / 1737 MEDLINE  
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[PMID]: 28701629
[Au] Autor:Uraki S; Ariyasu H; Doi A; Furuta H; Nishi M; Sugano K; Inoshita N; Nakao N; Yamada S; Akamizu T
[Ad] Address:The 1st Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.
[Ti] Title:Atypical pituitary adenoma with MEN1 somatic mutation associated with abnormalities of DNA mismatch repair genes; MLH1 germline mutation and MSH6 somatic mutation.
[So] Source:Endocr J;64(9):895-906, 2017 Sep 30.
[Is] ISSN:1348-4540
[Cp] Country of publication:Japan
[La] Language:eng
[Ab] Abstract:The mechanism of pituitary tumorigenesis remains largely unknown. Lynch syndrome is an autosomal, dominantly inherited syndrome caused by a defective mismatch repair (MMR) mechanism involved in the development of various tumors at an early age. In this case study, we showed the occurrence of pituitary tumors associated with Lynch syndrome for the first time and performed genetic and immunohistochemical analysis to evaluate the genetic aberrations that might be related to the tumorigenesis and proliferation. A 68-year-old female patient with Lynch syndrome due to mutL homolog 1 (MLH1) gene mutation suffered from hypersecretion of adrenocorticotrophic hormone (ACTH), hypercortisolism and a rapidly progressive pituitary tumor. We performed genetic analysis by whole genome sequencing with genomic DNA of the pituitary tumor and peripheral blood leukocytes, as well as immunohistochemical analysis of MMR proteins. Genetic analysis revealed that the tumor had homozygous gene mutation of MEN1 associated with pituitary tumorigenesis and mutS homolog 6 (MSH6) gene. Furthermore, immunohistochemical analysis showed that MLH1 and MSH6 immunoexpression were negative. We reveal for the first time that MMR abnormality could cause somatic mutation of MEN1 and pituitary tumor occurrence is associated with Lynch syndrome. We suggest that the identified gene mutations, especially those of MSH6 and MLH1 genes, may be involved in the pathogenesis and proliferation of pituitary tumor. The knowledge obtained from our case study is important to elucidate the pathogenesis and proliferation mechanisms of pituitary tumors.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1707
[Cu] Class update date: 171002
[Lr] Last revision date:171002
[St] Status:In-Process
[do] DOI:10.1507/endocrj.EJ17-0036

  7 / 1737 MEDLINE  
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[PMID]: 28685507
[Au] Autor:Langlois F; McCartney S; Fleseriu M
[Ad] Address:Department of Medicine, Endocrinology and Metabolism, University of Sherbrooke, Sherbrooke, QC, Canada.
[Ti] Title:Recent Progress in the Medical Therapy of Pituitary Tumors.
[So] Source:Endocrinol Metab (Seoul);32(2):162-170, 2017 Jun.
[Is] ISSN:2093-596X
[Cp] Country of publication:Korea (South)
[La] Language:eng
[Ab] Abstract:Management of pituitary tumors is multidisciplinary, with medical therapy playing an increasingly important role. With the exception of prolactin-secreting tumors, surgery is still considered the first-line treatment for the majority of pituitary adenomas. However, medical/pharmacological therapy plays an important role in controlling hormone-producing pituitary adenomas, especially for patients with acromegaly and Cushing disease (CD). In the case of non-functioning pituitary adenomas (NFAs), pharmacological therapy plays a minor role, the main objective of which is to reduce tumor growth, but this role requires further studies. For pituitary carcinomas and atypical adenomas, medical therapy, including chemotherapy, acts as an adjuvant to surgery and radiation therapy, which is often required to control these aggressive tumors. In the last decade, knowledge about the pathophysiological mechanisms of various pituitary adenomas has increased, thus novel medical therapies that target specific pathways implicated in tumor synthesis and hormonal over secretion are now available. Advancement in patient selection and determination of prognostic factors has also helped to individualize therapy for patients with pituitary tumors. Improvements in biochemical and "tumor mass" disease control can positively affect patient quality of life, comorbidities and overall survival. In this review, the medical armamentarium for treating CD, acromegaly, prolactinomas, NFA, and carcinomas/aggressive atypical adenomas will be presented. Pharmacological therapies, including doses, mode of administration, efficacy, adverse effects, and use in special circumstances are provided. Medical therapies currently under clinical investigation are also briefly discussed.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1707
[Cu] Class update date: 170816
[Lr] Last revision date:170816
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.3803/EnM.2017.32.2.162

  8 / 1737 MEDLINE  
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[PMID]: 28614003
[Au] Autor:Geer EB; Shafiq I; Gordon MB; Bonert V; Ayala A; Swerdloff RS; Katznelson L; Lalazar Y; Manuylova E; Pulaski-Liebert KJ; Carmichael JD; Hannoush Z; Surampudi V; Broder MS; Cherepanov D; Eagan M; Lee J; Said Q; Neary MP; Biller BMK
[Ti] Title:BIOCHEMICAL CONTROL DURING LONG-TERM FOLLOW-UP OF 230 ADULT PATIENTS WITH CUSHING DISEASE: A MULTICENTER RETROSPECTIVE STUDY.
[So] Source:Endocr Pract;23(8):962-970, 2017 Aug.
[Is] ISSN:1530-891X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:OBJECTIVE: Cushing disease (CD) results from excessive exposure to glucocorticoids caused by an adrenocorticotropic hormone-secreting pituitary tumor. Inadequately treated CD is associated with significant morbidity and elevated mortality. Multicenter data on CD patients treated in routine clinical practice are needed to assess treatment outcomes in this rare disorder. The study purpose was to describe the burden of illness and treatment outcomes for CD patients. METHODS: Eight pituitary centers in four U.S. regions participated in this multicenter retrospective chart review study. Subjects were CD patients diagnosed at ≥18 years of age within the past 20 years. Descriptive statistical analyses were conducted to examine presenting signs, symptoms, comorbidities, and treatment outcomes. RESULTS: Of 230 patients, 79% were female (median age at diagnosis, 39 years; range, 18 to 78 years). Length of follow-up was 0 to 27.5 years (median, 1.9 years). Pituitary adenomas were 0 to 51 mm. The most common presenting comorbidities included hypertension (67.3%), polycystic ovary syndrome (43.5%), and hyperlipidemia (41.5%). Biochemical control was achieved with initial pituitary surgery in 41.4% patients (91 of 220), not achieved in 50.0% of patients (110 of 220), and undetermined in 8.6% of patients (19 of 220). At the end of follow-up, control had been achieved with a variety of treatment methods in 49.1% of patients (110 of 224), not achieved in 29.9% of patients (67 of 224), and undetermined in 21.0% of patients (47 of 224). CONCLUSION: Despite multiple treatments, at the end of follow-up, biochemical control was still not achieved in up to 30% of patients. These multicenter data demonstrate that in routine clinical practice, initial and long-term control is not achieved in a substantial number of patients with CD. ABBREVIATIONS: BLA = bilateral adrenalectomy CD = Cushing disease CS = Cushing syndrome eCRF = electronic case report form MRI = magnetic resonance imaging PCOS = polycystic ovary syndrome.
[Mh] MeSH terms primary: ACTH-Secreting Pituitary Adenoma/therapy
Adenoma/therapy
Pituitary ACTH Hypersecretion/therapy
[Mh] MeSH terms secundary: 14-alpha Demethylase Inhibitors/therapeutic use
ACTH-Secreting Pituitary Adenoma/complications
ACTH-Secreting Pituitary Adenoma/metabolism
ACTH-Secreting Pituitary Adenoma/pathology
Adenoma/complications
Adenoma/metabolism
Adenoma/pathology
Adolescent
Adrenalectomy
Adult
Aged
Antineoplastic Agents/therapeutic use
Comorbidity
Enzyme Inhibitors/therapeutic use
Ergolines/therapeutic use
Female
Follow-Up Studies
Hirsutism/etiology
Hormone Antagonists/therapeutic use
Hormones/therapeutic use
Humans
Hyperlipidemias/epidemiology
Hypertension/epidemiology
Hypoglycemic Agents/therapeutic use
Ketoconazole/therapeutic use
Male
Metyrapone/therapeutic use
Middle Aged
Mifepristone/therapeutic use
Muscle Weakness/etiology
Muscular Atrophy/etiology
Neurosurgical Procedures
Obesity, Abdominal/etiology
Pituitary ACTH Hypersecretion/complications
Pituitary ACTH Hypersecretion/epidemiology
Pituitary ACTH Hypersecretion/metabolism
Pituitary Irradiation
Polycystic Ovary Syndrome/epidemiology
Retrospective Studies
Somatostatin/analogs & derivatives
Somatostatin/therapeutic use
Striae Distensae/etiology
Thiazolidinediones/therapeutic use
Treatment Outcome
Tumor Burden
Young Adult
[Pt] Publication type:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Name of substance:0 (14-alpha Demethylase Inhibitors); 0 (Antineoplastic Agents); 0 (Enzyme Inhibitors); 0 (Ergolines); 0 (Hormone Antagonists); 0 (Hormones); 0 (Hypoglycemic Agents); 0 (Thiazolidinediones); 05V02F2KDG (rosiglitazone); 320T6RNW1F (Mifepristone); 51110-01-1 (Somatostatin); 98H1T17066 (pasireotide); LL60K9J05T (cabergoline); R9400W927I (Ketoconazole); ZS9KD92H6V (Metyrapone)
[Em] Entry month:1710
[Cu] Class update date: 171012
[Lr] Last revision date:171012
[Js] Journal subset:IM
[Da] Date of entry for processing:170615
[St] Status:MEDLINE
[do] DOI:10.4158/EP171787.OR

  9 / 1737 MEDLINE  
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[PMID]: 28570067
[Au] Autor:Emmerich J; van Koppen CJ; Burkhart JL; Hu Q; Siebenbürger L; Boerger C; Scheuer C; Laschke MW; Menger MD; Hartmann RW
[Ad] Address:Pharmaceutical and Medicinal Chemistry, Saarland University , Campus E8.1, 66123 Saarbrücken, Germany.
[Ti] Title:Lead Optimization Generates CYP11B1 Inhibitors of Pyridylmethyl Isoxazole Type with Improved Pharmacological Profile for the Treatment of Cushing's Disease.
[So] Source:J Med Chem;60(12):5086-5098, 2017 Jun 22.
[Is] ISSN:1520-4804
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Cushing's disease, characterized by elevated plasma cortisol levels, can be controlled by inhibition of 11ß-hydroxylase (CYP11B1). The previously identified selective and potent CYP11B1 inhibitor 5-((5-methylpyridin-3-yl)methyl)-2-phenylpyridine Ref 7 (IC = 2 nM) exhibited promutagenic potential as well as very low oral bioavailability in rats (F = 2%) and was therefore modified to overcome these drawbacks. Successful lead optimization resulted in similarly potent and selective 5-((5-methoxypyridin-3-yl)methyl)-3-phenylisoxazole 25 (IC = 2 nM, 14-fold selectivity over CYP11B2), exhibiting a superior pharmacological profile with no mutagenic potential. Furthermore, compound 25 inhibited rat CYP11B1 (IC = 2 µM) and showed a high oral bioavailability (F = 50%) and sufficient plasma concentrations in rats, providing an excellent starting point for a proof-of-principle study.
[Mh] MeSH terms primary: Drug Evaluation, Preclinical/methods
Isoxazoles/chemistry
Pyridines/pharmacology
Steroid 11-beta-Hydroxylase/antagonists & inhibitors
[Mh] MeSH terms secundary: Administration, Oral
Animals
Biological Availability
Chemistry Techniques, Synthetic
Cytochrome P-450 CYP11B2/antagonists & inhibitors
Drug Stability
ERG1 Potassium Channel/metabolism
Female
Humans
Inactivation, Metabolic
Inhibitory Concentration 50
Pituitary ACTH Hypersecretion/drug therapy
Pyridines/chemical synthesis
Rats, Sprague-Dawley
Toxicity Tests/methods
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (5-((5-methylpyridin-3-yl)methyl)-2-phenylpyridine); 0 (ERG1 Potassium Channel); 0 (Isoxazoles); 0 (KCNH2 protein, human); 0 (Pyridines); EC 1.14.15.4 (Cytochrome P-450 CYP11B2); EC 1.14.15.4 (Steroid 11-beta-Hydroxylase)
[Em] Entry month:1708
[Cu] Class update date: 170811
[Lr] Last revision date:170811
[Js] Journal subset:IM
[Da] Date of entry for processing:170602
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00437

  10 / 1737 MEDLINE  
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[PMID]: 28522647
[Au] Autor:Kiefer FW; Winhofer Y; Iacovazzo D; Korbonits M; Wolfsberger S; Knosp E; Trautinger F; Höftberger R; Krebs M; Luger A; Gessl A
[Ad] Address:Clinical Division of Endocrinology and MetabolismDepartment of Medicine III, Medical University of Vienna, Vienna, Austria.
[Ti] Title: mutation causing pituitary-dependent Cushing disease in a patient with Carney complex.
[So] Source:Eur J Endocrinol;177(2):K7-K12, 2017 Aug.
[Is] ISSN:1479-683X
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:CONTEXT: Carney complex (CNC) is an autosomal dominant condition caused, in most cases, by an inactivating mutation of the gene, which encodes for the type 1 alpha regulatory subunit of protein kinase A. CNC is characterized by the occurrence of endocrine overactivity, myxomas and typical skin manifestations. Cushing syndrome due to primary pigmented nodular adrenocortical disease (PPNAD) is the most frequent endocrine disease observed in CNC. CASE DESCRIPTION: Here, we describe the first case of a patient with CNC and adrenocorticotropic hormone (ACTH)-dependent Cushing disease due to a pituitary corticotroph adenoma. Loss-of-heterozygosity analysis of the pituitary tumour revealed loss of the wild-type copy of , suggesting a role of this gene in the pituitary adenoma development. CONCLUSION: loss-of-function mutations can rarely lead to ACTH-secreting pituitary adenomas in CNC patients. Pituitary-dependent disease should be considered in the differential diagnosis of Cushing syndrome in CNC patients.
[Mh] MeSH terms primary: Carney Complex/genetics
Cyclic AMP-Dependent Protein Kinase RIalpha Subunit/genetics
Mutation/genetics
Pituitary ACTH Hypersecretion/genetics
[Mh] MeSH terms secundary: Adult
Carney Complex/complications
Carney Complex/diagnostic imaging
Humans
Male
Pituitary ACTH Hypersecretion/complications
Pituitary ACTH Hypersecretion/diagnostic imaging
[Pt] Publication type:CASE REPORTS; JOURNAL ARTICLE
[Nm] Name of substance:0 (Cyclic AMP-Dependent Protein Kinase RIalpha Subunit); 0 (PRKAR1A protein, human)
[Em] Entry month:1708
[Cu] Class update date: 170829
[Lr] Last revision date:170829
[Js] Journal subset:IM
[Da] Date of entry for processing:170520
[St] Status:MEDLINE
[do] DOI:10.1530/EJE-17-0227


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