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Poster presented at: BES2017 2’ Much of a Problem with Hypoglycaemia N Sukumar 1 , H Venkataraman 1 , J Ayuk 1,2 1 Department of Endocrinology, University Hospital Birmingham, 2 University of Birmingham • Endocrine referral: 2x hypoglycaemic episodes in non-diabeGc paGent • 88 year old man • AdmiIed under oncology 4 weeks previously with pulmonary oedema and blocked ureteric stent 11 days aLer palliaGve trabeciGdine • Nocturnal hypo – CBG 1.2 when found unrousable from sleep, IV glucose given • PaGent denied any symptoms when quesGoned Case Overview • MetastaGc malignant fibroma of pelvis • CT (10/16): 16cm pelvic mass with small volume lung nodules • Histology (12/16): solitary fibrous tumour, STAT6 posiGve, Ki67 30 • For palliaGve chemotherapy only • Bilateral hydronephrosis, ureteric stents: 01/17 • Bilateral nephrostomies: 03/17 (for blocked stent and worsening AKI) • Decompensated heart failure, NYHA Class 3 • Drug history è Bisoprolol 2.5mg OD, ForGsip liquid TDS, Hyoscine butylbromide PRN, Midazolam S/C PRN, Oxynorm IV PRN, Paracetamol 1g QDS • Social history è lives alone, independent ADLs unGl diagnosis -ReGred machinist -Non smoker, occasional whiskey Past medical history • IniGal invesGgaGons:- • AddiGonal blood tests requested during next hypo prior to treatment ênext night • CBG 2.7 mmol/l – bloods sent off Test (units) Result Normal range Urea (mmol/L) 22.5 3.4 – 8.0 Crea6nine (umol/L) 352 60 - 126 eGFR (ml/min) 13 Cor6sol (nmol/L) 412 > 350 TSH (mIU/L) 1.85 0.3 – 4.5 Inves?ga?ons Test (units) Result Normal range Glucose (mmol/L) 2.2 3.5 – 11 Insulin (pmol/L) < 10 >20 C-pep<de (nmol/L) 380 IGF-I (nmol/L) 7.1 4.6 – 23.4 IGF-II (nmol/L) 137.2 IGF-II: IGF-I ra<o 19.3 <10 • Started Prednisolone 10mg BD è 5mg BD on discharge Ini$al blood glucose chart Post-steroid blood glucose chart Management Causes of hypoglycaemia Insulin mediated Non-insulin mediated Drugs vExogenous insulin vInsulin secretagogues Drugs vAlcohol vPentamidine, quinine, indomethacine Insulinoma CriGcal illness vHepaGc / renal / cardiac failure vSepsis FuncGonal beta-cell disorders (nesidoblastosis) vNoninsulinoma pancreaGc hypoglycaemia vPost gastric bypass ‘dumping syndrome’ Hormone deficiency vCorGsol vGlucagon / adrenaline Insulin autoimmune hypoglycaemia Non-islet cell tumour Accidental / surrepGGous hypoglycaemia Discussion Non-islet cell tumour hypoglycaemia • ComplicaGon of certain malignancies resulGng in symptomaGc severe hypoglycaemia (usually in fasGng state) • ~130 case reports / small series in English language medical literature in last 30 years 1 • Occur with < 5% of solitary fibrous tumours Pathophysiology • Tumours of mesenchymal or epithelial origin 1 • Solitary fibroma / fibrosarcoma or mesothelioma (22%) • Hepatocellular carcinoma (17%) • Hermangiopericytoma (7%) • Adrenal carcinoma, phaeochromocytoma • 2/3 retroperitoneal, 1/3 thoracic • 70% of tumours >10 cm in diameter 2 • ‘Big’ IGF-II formed from abnormal processing of pro IGF-II in tumours with aberrant gene transcripGon / expression Mechanism of hypoglycaemia Diagnosis • Key feature is êêglucose/insulin/C-pepGde/-hydroxybutarate PLUS é free IGF-II, IGF- II:IGF-I raGo, pro IGF-II levels Management • GlucocorGcoids • Suppresses producGon + increase clearance of IGF-II • Used in ~25% of cases • Typically 30 – 60mg /day needed • Recombinant GH • CauGon re: possible effect on tumour growth • IGF-II producGon by tumour • Acts on insulin receptor to é glucose uGlisaGon in muscle + ê gluconeogenesis • Suppresses insulin, glucagon and GH release • InfiltraGon of hepaGc Gssue by tumour • DestrucGon of adrenal glands by tumour / haemorrhage References 1. Bodner TW et al. (2014) Management of non-islet cell tumor hypoglycemia: a clinical review. JCEM; 99(3): 713-22 2. Fukuda I et al. (2006) Clinical features of insulin-like growth factor-II producing non-islet-cell tumour hypoglycemia . Growth Horm IGF Res; 16(4): 211-6 EP-049 Nithya Sukumar Clinical biochemistry

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Poster presentedat:

BES2

017

2’MuchofaProblemwithHypoglycaemiaNSukumar1,HVenkataraman1,JAyuk1,2

1DepartmentofEndocrinology,UniversityHospitalBirmingham, 2UniversityofBirmingham

•  Endocrinereferral:2xhypoglycaemicepisodesinnon-diabeGc

paGent•  88yearoldman•  AdmiIedunderoncology4weekspreviouslywithpulmonary

oedemaandblockeduretericstent11daysaLerpalliaGvetrabeciGdine

•  Nocturnalhypo–CBG1.2whenfoundunrousablefromsleep,IVglucosegiven•  PaGentdeniedanysymptomswhenquesGoned

CaseOverview

•  MetastaGcmalignantfibromaofpelvis•  CT(10/16):16cmpelvicmasswithsmallvolumelungnodules•  Histology(12/16):solitaryfibroustumour,STAT6posiGve,Ki6730•  ForpalliaGvechemotherapyonly

•  Bilateralhydronephrosis,uretericstents:01/17•  Bilateralnephrostomies:03/17(forblockedstentandworseningAKI)•  Decompensatedheartfailure,NYHAClass3• DrughistoryèBisoprolol2.5mgOD,ForGsipliquidTDS,HyoscinebutylbromidePRN,MidazolamS/CPRN,OxynormIVPRN,Paracetamol1gQDS• Socialhistoryèlivesalone,independentADLsunGldiagnosis

- ReGredmachinist- Nonsmoker,occasionalwhiskey

Pastmedicalhistory

•  IniGalinvesGgaGons:-

•  AddiGonalbloodtestsrequestedduringnexthypopriortotreatment ênextnight

•  CBG2.7mmol/l–bloodssentoff

Test(units) Result NormalrangeUrea(mmol/L) 22.5 3.4–8.0Crea6nine(umol/L) 352 60-126eGFR(ml/min) 13Cor6sol(nmol/L) 412 >350TSH(mIU/L) 1.85 0.3–4.5

Inves?ga?ons

Test(units) Result NormalrangeGlucose(mmol/L) 2.2 3.5–11Insulin(pmol/L) <10 >20C-pep<de(nmol/L) 380IGF-I(nmol/L) 7.1 4.6–23.4IGF-II(nmol/L) 137.2IGF-II:IGF-Ira<o 19.3 <10

•  StartedPrednisolone10mgBDè5mgBDondischargeIni$albloodglucosechart Post-steroidbloodglucosechart

Management

Causesofhypoglycaemia Insulinmediated Non-insulinmediatedDrugsv Exogenousinsulinv Insulinsecretagogues

Drugsv Alcoholv Pentamidine,quinine,indomethacine

Insulinoma CriGcalillnessv HepaGc/renal/cardiacfailurev Sepsis

FuncGonalbeta-celldisorders(nesidoblastosis)v NoninsulinomapancreaGchypoglycaemiav Postgastricbypass‘dumpingsyndrome’

Hormonedeficiencyv CorGsolv Glucagon/adrenaline

Insulinautoimmunehypoglycaemia Non-isletcelltumourAccidental/surrepGGoushypoglycaemia

Discussion

Non-isletcelltumourhypoglycaemia•  ComplicaGonofcertainmalignanciesresulGnginsymptomaGcseverehypoglycaemia

(usuallyinfasGngstate)•  ~130casereports/smallseriesinEnglishlanguagemedicalliteratureinlast30years 1

•  Occurwith<5%ofsolitaryfibroustumoursPathophysiology•  Tumoursofmesenchymalorepithelialorigin1

•  Solitaryfibroma/fibrosarcomaormesothelioma(22%)•  Hepatocellularcarcinoma(17%)•  Hermangiopericytoma(7%)•  Adrenalcarcinoma,phaeochromocytoma

•  2/3retroperitoneal,1/3thoracic•  70%oftumours>10cmindiameter2•  ‘Big’IGF-IIformedfromabnormalprocessingofproIGF-IIin tumourswithaberrant

genetranscripGon/expressionMechanismofhypoglycaemiaDiagnosis•  Keyfeatureisêêglucose/insulin/C-pepGde/-hydroxybutaratePLUSéfreeIGF-II,IGF-

II:IGF-IraGo,proIGF-IIlevelsManagement

•  GlucocorGcoids•  SuppressesproducGon+increaseclearanceof

IGF-II•  Usedin~25%ofcases•  Typically30–60mg/dayneeded

•  RecombinantGH•  CauGonre:possibleeffectontumourgrowth

•  IGF-IIproducGonbytumour•  ActsoninsulinreceptortoéglucoseuGlisaGonin

muscle+êgluconeogenesis•  Suppressesinsulin,glucagonandGHrelease

•  InfiltraGonofhepaGcGssuebytumour•  DestrucGonofadrenalglandsbytumour/haemorrhage

References1.  BodnerTWetal.(2014)Managementofnon-isletcelltumorhypoglycemia:a

clinicalreview.JCEM;99(3):713-222.  FukudaIetal.(2006)Clinicalfeaturesofinsulin-likegrowthfactor-IIproducing

non-islet-celltumourhypoglycemia.GrowthHormIGFRes;16(4):211-6

EP-049Nithya Sukumar

Clinical biochemistry

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