1、Cushings SyndromeGE QianThe First Affiliated Hospital of Chongqing Medical UniversityDepartment of Endocrinology Cushings syndrome is caused by chronic exposure to excess glucocorticoids(cortisol),characterized by truncal obesity,Round face,Plethora,Hirsutism,Violaceous striae,Hypertension,etc.Defin
2、itionThe hypothalamic-pituitary-adrenal axisfeedbackCause of Cushings syndrome1.ACTH-dependent CortisolPituitary ACTHAdrenal hyperplasia Pituitary microadenomas(10mm)Cushings diseaseTumoursEctopic ACTH Lung small cell carcinoma,bronchial carcinoid tumoursEctopic ACTH syndrome2.ACTH-independent Tumor
3、/HyperplasiaCortisolAutocrinePituitary ACTH Adrenal adenomaAdrenal carcinomaMicronodular adrenal hyperplasia(5mm)Cause of Cushings syndromeEpidemiologyCushings disease:Women:men=4:1Ectopic ACTH syndrome:Women:men=1:1Adrenocortical adenoma/carcinoma:Women:men=4:1Pathophysiology and Clinical Signs Met
4、abolism(Glucose,Lipid,Protein)Immune system Blood system Reproductive system Central nervous system 1.Typical habitus Truncal obesity“Moon”face“Buffalo”humpViolaceous striaeBruisability OsteoporosisPlethoraPeculiar distributionof adipose tissueProtein catabolismRed blood cellsTruncal obesity Moon fa
5、cePlethoraBuffalo humpViolaceous striaeViolaceous striae Osteoporosis：vertebral bodies flatten 2.Hypertension,Electrolyte disturbances Water and sodium retention,potassium depletionHypertension,Hypokalemialeft ventricular hypertrophy,heart failure,cerebrovascular accident,etc.3.Impaired glucose tole
6、rance,Diabetes mellitus(Steroid diabetes)Stimulation of hepatic gluconeogenesis，resistance of insulin4.InfectiousInfections of Bacteria,Fungi,VirusesImmunosuppression:functions and numbers of neutrophils,lymphocytes,monocytes,macrophages the anatomical barrier function of the skin5.Sexual dysfunctio
7、nwomen -Amenorrhea or Oligomenorrhea -Virilization:Hirsutism,Acne,MastatrophyInhibition of Gonadotropin,Adrenal androgensmen-Decreased libidoNeurologic changes:decreased strength,headaches,decreased memory and cognitionPsychiatric changes:depression,anxiety,irritabilityHyperpigmentation:Ectopic ACTH
8、 syndrome and severe Cushings disease6.OthersMSH(Melanocyte-stimulating hormone)Melanocyte MelaninPigment黑色素细胞黑色素细胞黑色素黑色素Mechanism of hyperpigmentationACTHThe partial action of MSHMelanin pigment depositionHyperpigmentation4.Manifestationp Hyperpigmentation:Tests1.Plasma cortisol levels 2.24-hour Ur
9、ine free cortisol(UFC)3.Plasma ACTHDiscrimination of ACTH-dependent and-independent Cushings syndromeCushings diseaseEctopic ACTH-syndromeAdrenal adenoma 4.Plasma cortisol circadian rhythmNormal cortisol circadian rhythmPlasma cortisol circadian rhythm of cushings syndromeNormal Cushings syndrome5.D
10、ynamic tests1 mg overnight dexamethasone suppression test(1mg DST)Method:1 mg by mouth,between 23h and 0h,and the measurement of cortisol between 8h and 9h the following morning.Results:Normal:Cortisol50nmol/L Low-dose dexamethasone suppression test(LDDST)Result Normal:Day 3 plasma cortisol 50nmol/L
11、 Method(2mg/day)0800h1600h0000hDay 1 Dexa0.75mg0.75mg0.5mgDay 2Dexa0.75mg0.75mg0.5mg0700h keep 24-hour urineDay 3 0800h measure plasma cortisol and 24-hour urine cortisol 0800h1400h2000h0200hDay 10700h keep 24h urine,measure plasma cortisolDay 2Dexa3 tablets3 tablets3 tablets2 tabletsDay 3Dexa3 tabl
12、ets3 tablets3 tablets2 tablets0700h keep 24h urine Day 40800h measure plasma cortisol and 24h urine cortisol Method(8mg/day)Result Be suppressed:Day 4 plasma cortisol 50%of the basal levelHigh-dose dexamethasone suppression test(HDDST)Discrimination of the causes of Cushings syndrome by HDDST HDDSTA
13、CTHCushings diseasesuppressedAdrenal adenoma/carcinomaNo Ectopic ACTH syndromeNo Pituitary MRI：microadenomaPituitary MRI：macroadenoma6.Imaging examinationCT：normal adrenal CT：adrenal adenoma7.Inferior petrosal sinus sampling(BIPSS)Discrimination of Cushings disease and Ectopic ACTH syndromeInvasive
14、TestCushings syndrome(CS)suspected24hUFC,Plasma cortisol circadian rhythm,1mg DSTNormalAbnormalLow-dose DSTCS excludedCS confirmedAbnormalDiagnosis1.Step2.Etiologic diagnosisPlasma ACTHHigh-dose DST3.Location diagnosisPituitary enhanced MRIAdrenal enhanced CTChest enhanced CT/Whole body PET-CTCushin
15、gs disease ACTH Suppressed by High-dose DST Pituitary lesions by CT,MRI Bilateral adrenal mild hyperplasia4.Differential diagnosisEctopic ACTH syndrome Plasma ACTH Hypokalaemia,Hyperpigmentation Not suppressed by high-dose DST Chest CT/Whole body PET-CTAdrenal adenoma/carcinoma Adenoma：progressed gr
16、adually Carcinoma：progressed rapidly，evident sign of androgen excess(virilization)Plasma ACTH Not suppressed by high-dose DST Adrenal enhanced CTSurgical treatment Transsphenoidal microsurgery：most widely usedPituitary irradiation post operationHypophysectomy Total adrenalectomyCushings diseaseTreat
17、mentAdrenal neoplasmaLaparoscopic adrenalectomy Hypopituitarism/hypoadrenocorticism -Glucocorticoid and mineralocorticoid replacement Nelsons syndrome:rapid pituitary tumor enlargement and increased pigmentation secondary to high ACTH levels after total adrenalectomy due to Cushings disease -Periodi
18、c pituitary MRI and ACTH measurement -Pituitary irradiation Adverse effects Medical TherapySteroidogenesis inhibitors:Suppression of cortisol productionKetoconazole MetyraponeMitotaneEtomidateCase oneFemale，30-year，Postpartum depression for 6 months，weight gain for 3 months.Physical examination：T36.
19、5C,BP164/116mmHg,Round face,Plethora,bearded jaw,hirsute back,wide violaceous strae,distended abdomen.Tests：-24h UFC 1620.9nmmol -Plasma cortisol circadian rhythm:8 am 754.7nmmol/L 16 pm 647.0 nmmol/L 0 am 671.9 nmmol/L -ACTH(8am)1718.76nmmol/L High-dose DST Plasma cortisol 643.35nmmol/L Urine corti
20、sol 2406.2nmmol/L Not suppressed by both Low-dose and high dose DSTAdrenal CTDiagnosis？Cushings syndromeAdrenal adenoma Treatment AdrenalectomyCase TwoMale，15-year，Growth retardation for 8 years，fatigue and weight gain for 3 months.Physical examination：T36.7C，BP126/96mmHg,“Moon”face,“Buffalo”hump,Vi
21、olaceous striae on bilateral inner thighs.A 2x2cm nodule was touched in thyroid gland,without tenderness,with clear border.Tests：K+3.0mmol/L，Fast plasma glucose(FPG)8.0mmol/L，24h UFC758ug Plasma cortisol circadian rhythm:8 am 1379nmmol/L 16 pm 1379nmmol/L 0 am 1379nmmol/L ACTH(8am)246pg/mL History D
22、ynamic Tests：-Not suppressed by LDDST and HDDST -Thyroid function：TSH 19.8 IU/ml -Calcitonin 243ng/L -Pituitary MRI：Normal -Adrenal CT：Bilateral adrenal hyperplasia -X-ray：Osteoporosis in spine and pelvis -Cervical CT:Thyroid nodule Diagnosis？Medullary thyroid carcinoma Ectopic ACTH syndromeCushings syndromeTreatmentTotal thyroidectomy Harrisons Internal Medicine 17th Edition Harrisons Endocrinology 3rd EditionReference BookThank you
