Eishth Arab Conferenceon the Peacefulljses of Atomit Enersv Anman.3-7 December2006 Renal Function in Hypothyroidism A. ShukrallaKhalidr, M. I. Ahmedr,H. M. Elfakir,N. Hassanr,S. M. Suliman2 l. SudanAtomic Energy Commission 2. Universityof Khartoum,Faculty of Medicine 4:i'eJJlJJ"a!cfy i,rlsll .ijl!-l ,-L .1,j...' i.te.: ,tgsilt J,ora 6Jt-iA ,ls".i ,t-Yt .tor-o ,lJti ,irtr* u.i 261,.r,1-.r"-. -a;trjr,:t erl-ntt /.iJIl i3t!l fu+^ .1 -c,,Lll esl>lt L.b 4+ls.2 Abstract Background Hypothyroidisminduces significant changes in the functionof organsystems such as the heart,muscles and brain.Renal function is also influencedby thyroid status.Physiological effects include changes in water andelectrolyte rnetabolism, notably hyponatremia, and reliable alterations of renalhemodynamics, including decrements in renalblood flow, renalplasma flow, glomerularfiltration rate (GFR). Objective Renal function is profoundlyinfluenced by thyroid status;the purposeof the presentstudy was to determinethe relationshipbetween renal functionand thyroid status of patientswith hypothyroidism. Designand Patients In 5 patientswith primaryhypothyroidisrn and control group renal functions are lneasuredby serurncreatinine and glomerular filtrationrate (GFR) usingmodified in diet renaldisease (MDRD) fonnula. Result In hypothyroidism,mean serum creatinineincreased aud mean estimatedGFR decreased,compared to the control group mean serum creatininedecreased and meanestimated GFR hicreased.Tlre hy,potliyroid patientsshowed elevated serum creatinine levels (> 1.1mg/dl)compared to control group (p value: .000).In patientsmean estimated GFR decreased, comparedto lneanestimated GFR increasedirr the controlgroup (p value: .002). ConclusionThus the kidney. in additionto thebrain, heart and rnuscle, is an irnportanttarget of the actionof thyroidhormones. LdB, . ^. a+!l ; *i+ ,:Ll crUlL cL; .r.l ,l(ll LnlJ"J {i *l i-lJil oll !i+i ;,sirl .:iLL* ,1,,n ,} a-l;il orA ."':lJ-i .(Prirnary Hypothyroidisrn)!3)i a1a JIJ LiJil irill ,.5U;r a-iF q+JJl a1.300 $'l iJl '-)l+L*iLl'ill d e .C-iYt e+:rll (Age: cL-Jl o L*: J$iiI i i *, lrYl ap;r.ll ; q*!i r3=, ,-r" StSll-l slS.9:Jl3(TSH)+{J:X,t Jl ,.r_r-_,<ll.9d* 9+L!ir+ ulll; 44.2+ 16years) cry"'1au"S i dlljsr {19'0+21.1 (0.4- 4.0)} ,,-+tll .eoJl :p l-ii;^ dXrr{21.6+11.0 (50- 150)}s-*$ll .rrL*ll Lic l'^i-i" otS; (T4);r-S:,xill .(RIA, and tRMA)a+'L-:YlidLiJl .!'A atl:il ,(Creatinine)CrsUFt,(Urea)t:J-dl .r. ,Js dri*" o*G i o+:.tt ; uli 'lasi r. ju dlllr dll ..rs(Glomerular filtration rate (GFR)-lsll d ,r+Sll e-jt bys cL- i,"; csJ tirL iJJSill ,Jsll Lj:t.tJ uS e l-s .(slsll G:1}J i-ijJ ";. .(Age:33 + 9 years)c.,I-* r;o3 i-lJil orA dlJ. eLJl .9rJ s-*ilJl qg.1Jl d1c aHsqJ$ cf ;i-* os 1ln;l ;l plJL +_,!L (1.18+ 0.102( 0.6-l.1mg/dl))o+,rJl Jr-ii erLl'^\l LJ"S$' .abtic.r^+-ll..r# (P < 0'000),_9_r:,* eiD\::l +3; ( 0.78+ 0.094)ot-.r-.^ll *-i "lri* j L;liijl 53 -L-a;;Jl .rJ (GFR).,JSJ|,,l .,++SllC+.jtjl cJ* i-,r-, ,_!J'll oK_r (l 17.35:t 8.49)crt-l-. tl eL,jJL L_,r (61.55 + 9.33)rJl .(p< 0.002.)*r* . sxll ijjuj & !_*^ l;i: ;_l 4,!JJl JJ"-! e-;r LJIJl a-lJJl ou ,",, lr Introduction Hypothyroidism inducessignihcant changes in the function of organ systemssuch as the heart,muscles and brain.u renal function is also influencedby thyroid status.Physiological effects include changesin water and electrolytemetabolism, notably hyponatremia,and reliable alterations of renal hemodynamics.'including decrementsin renal blood flow, renal plasma flow, glomerularfiltration rate (GFR). The cause of the decreasedrenal plasma flow and GFR observed is believedto be principally due to the generalizedhypodynamic state of the circulatorysystem in hypothyroidism.l Most studieson the effect of thyroid hormone on the kidney, however,have been performedin rats.Furthermore, the renal effectsof thyroid hormonesin humanscan be subtle and thereforeoften escapeclinical attention,as the changes in measuredparameters of renal function are often within the normal range. Hypothyroid adults have mildly elevated serum creatinine )/+11i - values and decreasedslomerular filtration rates (GFR)V. Verhelst et al.i found increasedireatinine levels in patientswith (subclinical) hypothyroidismcompared to controlsgroup. GFR can be estimatedfrom serum creatininelevels and creatinine clearanceor measuredby the clearanceof inulin. Leveyet al., in their modification of diet in renal disease(MDRD) study. e introducedan estimationof the GFR basedon multiple regressionanalyses of a large database,which provided a more accurateevaluation of GFR than creatinineclearance or other calculations.The gold standardin these I2sl-iothalamate. determinationswas clearancemeasured using The purpose of the present study was to prospectively evaluate changesin renal function in patientswith primary hypothyroidism. We usedan estimationof the GFR basedon a mathematicalequation using serumurea, albumin and creatinine.6 Patientsand Methods Patients The study group comprised 5 patients (females) with primary hypothyroidismand 5 healthy femalesas control group. All patients gave their written informed consent,and the local ethics committee approvedthe studies. The patients were studied at diagnosis;that is TT4 or TSH being between the reference values for hypothyroid patients. The target levels for thyroid hormone and TSH were between the reference ranges(see below). Blood sampleswere drawn in the fasting statefor determinationof TSH, total T3 (TT3), thyroxineconcentration (TT4), semmcreatinine, blood urea nitrogen (BtrN), andalbumin. Methods TSH levels were measuredby an Immunoradiometriassay(IRMA) with a detectionlimit of 0'01 mU/l (normal range 0.44.0 mU/l). Serum TT3 levels (normal range0.8-3.0 nmol/l) and TT4 (range50- 150nmol/l) were assayed by radioimmunoassay(RIA). Serum creatininelevels (normalrange females 0. 6-l.lmg/dl) were assayed using a BioSystems reagents (Creatinine alkaline picrate) and instruments (Spectrophotometer).BLn{ concentration (range i.0- l8mg/dl) was determinedby measuringurea using urease/salycilate which is an enzymaticcolorimetric n-rethod and conveft the urea mass units to those urea nitrogen apply: mgidl x 0.467. Albumin J /) concentrationwas measured(normal range 3.8la.65gldl) using the Bromocresolgreen (BCG) reaction. Equationfor GFR determination(The MDRD formula_is):" GFR (mllrnir1/1'73m2): 170x (P.J*0eeex (ugr)*o'tux (0'762 if patient is female)x (1'180 if patient is black) x (BtN) orTo x (Alb)+0.318 Where Pcr is the serum creatinineconcentration (mg/dl), BIIN the blood urea nitrogen concentration(mg/dl) and Alb the serumalbumin concentration(g/dl)1. Statisticalanalysis Statisticalanalysis of the datawas performed by meansof pairedt-test using SPSSsoftware. A P-value< 0'05 (two-tailed)was considered significant. Results Tablel gives detaileddata, thyroid function, creatinineand estimated GFR. In hypothyroidism,mean serumcreatitrine increased and mean estimatedGFR decreased,compared to the control group mean serum creatininedecreased and mean estimatedGFR Increased.Four out of five hypothyroid patients showed elevated serum creatinine levels (> 1.lmg/dl). One of thosepatients with normalranges, although all patients showed an increasein creatininelevel Comparedto control group(p value: .000),(Fig.1). In the hypothyroidpatients, there was no evidencefor other causesof elevatedserum creatinine levels such as glomerulonephritis.Mean serum urea nitrogen (B[IN) increased and mean serum BIIN of control group decreased(p value: .030), (Fig.2). In hypothyroid patients mean estimated GFR decreased, comparedto mean estimatedGFR increasedin the control group (p value:.002)(Fig. 3). Discussion This study encompassingpatients with hypothyroidismwhich is showssignificant changes in renalfunction. These changes are similar r.vhetherrenal function is expressedas creatinine levels or asestimated GFR. Although our study lacks the use of a gold standardfor the measurementof renal function, the findings are in accordancewith earlier studieson changesin serumcreatinine, estimated GFR values basedon serum creatinine,and GFR measured^by methodsapplying radioactivelylabelled markers(gold standards).rThe measurementof creatinine levels, BLIN, and the estimated GFR shows significant 376 changescompared to controlgroup (with p value0.000, 0.03, and 0.03 respectively).This result similar to that done by Verhelst et ul.), and Stuarl H. etal. Again An increasedserum creatinineand decreased p.lomerularfiltration rate and renal blood flow have been described2'?' The decreasesin renal plasma flow and glomerular filtration rate (GFR) that accompanyhypothyroidism are believed to be related to the generalized hypodynamic state of the circulatory system in hypothyroidism.Elevation of serumcreatinine levels is not generally mentioned as an abnormality that occurs in association with hypothyroidism,although reports of suchan associationexist. The rise in creatininelevels during hypothyroidismwas not associated with abnormalcreatine kinase levels or other evidenceof hypothyroid myopathy or intrinsic renal disease.The findings demonstratedthat very little time is required for the developmentof elevated seruln creatinine levels during the hypothyroid state. The results argue againstthe previouslyheld notion of a net unchangedcreatinine value becauseof a balancebetween the decreasein renal clearanceand a decreasein creatininegeneration. The hypothyroidstate is associatedwith a consistentelevation in the serumcreatinine level, presumablyrelated to a decreasein the GFR. The changesin serum creatininelevels developrapidly and