A STUDY ON
“PROGRESSION OF GESTATIONAL THYROID DISORDER TO OVERT THYROID DISORDER AND TO ESTABLISH THE IMPACT OF THYROID
DISORDER ON PREGNANCY OUTCOME”
Dissertation Submitted to
THE TAMIL NADU DR.M.G.R.MEDICAL UNIVERSITY CHENNAI
In partial fulfillment of the regulations for the award of the degree of
M.D. BRANCH – I (GENERAL MEDICINE)
DEPARTMENT OF GENERAL MEDICINE
GOVERNMENT STANLEY MEDICAL COLLEGE, CHENNAI.
THE TAMIL NADU DR. M.G.R.MEDICAL UNIVERSITY TAMILNADU, INDIA
MAY 2020
CERTIFICATE
This is to certify that this dissertation entitled A STUDY ONPROGRESSION OF GESTATIONAL THYROID DISORDER TO OVERT THYROID DISORDER AND TO ESTABLISH THE IMPACT OF THYROID DISORDER ON PREGNANCY OUTCOME submitted by Dr.A.Mohamed Ibrahim to the faculty of General Medicine, The TamilNadu Dr. M.G.R Medical University, Chennai, Tamilnadu, in partial fulfillment of the requirement for the award of M.D DEGREE BRANCH-I (GENERAL MEDICINE) is a bonafide research work carried out by him under my direct supervision and guidance.
Prof. Dr. C. HARIHARAN M.D., Head of the Department, Department of Medicine,
Stanley Medical College and Hospital, Chennai- 1.
PROF. DR.R.SHANTHIMALAR, M.D., D.A., DEAN
Government Stanley Medical College and Hospital, Chennai-1.
CERTIFICATE BY THE GUIDE
This is to certify that Dr.MOHAMED IBRAHIM A, Post Graduate student (May 2017 to April 2020) in the Department of General Medicine, Government Stanley Medical College and Hospital,Chennai-1,has done this dissertation work titled
“A STUDY ON PROGRESSION OF GESTATIONAL THYROID DISORDER TO OVERT THYROID DISORDER AND TO ESTABLISH THE IMPACT OF THYROID DISORDER ON PREGNANCY OUTCOME” under my guidance and supervision in partial fulfillment of the regulations laid down by The Tamilnadu Dr.M.G.R.Medical University, Chennai for M.D.,(General Medicine), Degree examination to be held in May 2020.
Prof. Dr. S.GEETHA M.D., Chief, Medical Unit-4, Department of Medicine,
Stanley Medical College and Hospital, Chennai - 1.
DECLARATION
I, Dr.MOHAMED IBRAHIM A, solemnly declare that the dissertation titled“A STUDY ON PROGRESSION OF GESTATIONAL THYROID DISORDER TO OVERT THYROID DISORDER AND TO ESTABLISH THE IMPACT OF THYROID DISORDER ON PREGNANCY OUTCOME”is a bonafide work done by me at Government Stanley Hospital, Chennai during November 2017 to May 2018 under the guidance and supervision of Prof.Dr.S.GeethaM.D., Professor of Medicine,Government Stanley Hospital, Chennai. I also declare that this bonafide work or a part of this work was not submitted by me or any other for award degree or diploma to any other university, board either in India or abroad.This dissertation is submitted to the Tamilnadu Dr. M.G.R Medical University, towards the partial fulfillment of requirement for the award of M.D. Degree (Branch – I) in General Medicine.
Place: Chennai Signature of the candidate
Date: (Dr.A.MOHAMED IBRAHIM )
CERTIFICATE – II
This is to certify that this dissertation work titled“A STUDY ON PROGRESSION OF GESTATIONAL THYROID DISORDER TO OVERT THYROID DISORDER AND TO ESTABLISH THE IMPACT OF THYROID DISORDER ON PREGNANCY OUTCOME ”of the candidate Dr.A.Mohamed Ibrahim with Registration Number 201711059 for the award of M.D., DEGREE in the branch of BRANCH-I (GENERAL MEDICINE). I personally verified the urkund.com website for the purpose of plagiarism check. I found that the uploaded thesis file contains from introduction to conclusion pages and result showsZERO percentage of plagiarism in the dissertation.
Guide & Supervisor sign with Seal
SPECIAL ACKNOWLEDGEMENT
I gratefully acknowledge and thank PROF. DR.R. SHANTHI MALAR M.D., D.A.,
DEAN
GOVERNMENT STANLEY MEDICAL COLLEGE AND HOSPITAL, CHENNAI.
For granting me permission to utilize the resources of this Institution for my study
ACKNOWLEDGEMENT
I am extremely thankful to our beloved Superintendent Prof.Dr.DHANASEKAR, M.D., Government Stanley HospitalChennai-1, for having granted permission to do this dissertation inGovernment Stanley Hospital, Chennai.
I am very grateful to our Professor and Head of the Department of Medicine Prof Dr.C.HARIHARAN, M.D., for acceptance to do this dissertation.
I am extremely grateful to my unit chief Dr.S.GEETHA, M.D.,and former unit chief Dr.M.ANUSUYA,M.D.,who taught me the basic aspects and clinical skills ininternal medicine which is an essential pre requisite for pursuing any dissertation work.The guidance and encouragement they provided need a special mention.
I recall with gratitude the other unit chiefs and Associate Professors of Department ofMedicine,Prof. Dr.G.RAJAN, M.D., Prof. Dr. C.SRIDHAR M.D., Prof.
Dr.A.SAMUEL DINESH, M.D., Prof.Dr.T.B.UMADEVI M.D.,Prof. Dr.A.RAVI M.D., Prof. Dr. I.ROHINI M.D., Prof. Dr. R.THILAKAVATHY M.D., Prof.Dr.P.MALARVIZHI M.D., Prof. Dr. KALPANA RAMANATHAN M.D., for their valuable guidance.
I am extremely thankful to our Registrar Dr.N.RAVICHANDRAN M.D., and ourUnit Asst. Professors Dr.C.S.GAUTHAMAN M.D., Dr. A.RAMALINGAM M.D.,Dr. S. PRAKASH M.D., Dr.P.BHARANI M.D.,for their valuable suggestions, guidance and support.
I thank Prof. Dr. M.P. SARAVANAN, M.D.,Professor and Head of theDepartment of Biochemistry for providing me with facilities for accurate measurement of the biochemical parameters involved in the thesis work which were very crucial for the study.
I also thank all our patients and their attenders, without whom the study would not bepossible.
I extend my love and gratitude to my family and friends for their immense help forthis study.
I owe my thanks to almighty for successful completion of this study.
LIST OF ABBREVATIONS
TSH Thyroid Stimulating Hormone T3 Tri iodo tyronine
T4 Tetra iodo tyronine
HCG Human Chorionic Gonadotropin
Wks Weeks
PIH Pregnancy induced hypertension IUGR Intra uterine growth restriction NVD Normal vaginal delivery
LSCS Lower segment caesarean section
PPROM Preterm premature rupture of membranes PROM Premature rupture of membranes
LBW Low birth weight
Rx Treatment
GDM Gestational diabetes mellitus HTN Hypertension
PPH Post partumhaemorrage
TABLE OF CONTENTS
S.No CHAPTERS PAGE NUMBER
1 INTRODUCTION 1
2 AIM AND OBJECTIVES OF THE STUDY 5
3 REVIEW OF LITERATURE 6
4 MATERIALS AND METHODS 33
5 STATISTICAL ANALYSIS 39
6 RESULTS 40
7 DISCUSSION 64
8 CONCLUSION 75
9 BIBLIOGRAPHY 85
10 PROFORMA 91
11 ETHICAL COMMITTEE 94
12 PLAGIARISM CERTIFICATE 95
13. INFORMED CONSENT 96
14. MASTER CHART 98
1
INTRODUCTION i
Thyroid hormones have profound variation during the life span and are associated with severe adverse health impacts (1, 2). Pregnancy, as an important reproductive event, has a profound but reversible effect on the thyroid gland and its functions.
Pregnancy is actually a state of excessive stimulation leading to an increase in thyroid size by 10% in iodide sufficient areas and 20-40% -deficient regions (3). Furthermore following the physiological and hormonal changes caused by pregnancy and human chorionic gonadotropin (HCG) the production of thyroxin (T4) and triiodothyronine (T3) increase up to 50% leading to 50% increase in a woman’s daily iodide need, while Thyroid stimulating hormone (TSH) levels are decreased, especially in first trimester (4). In an iodine sufficient area, these thyroid adaptations during pregnancy are well tolerated, as stored inner thyroid iodide is enough; however, in iodine- deficient areas, these physiological adaptations lead to significant changes during pregnancy (5).
2
FIGURE: i1 iANATOMICAL iSTRUCTURE iOF iTHYROID iGLAND i
Furthermore, in women who suffered from thyroid dysfunction prior ito pregnancy, the hormonal changes mentioned are magnified, leading to possible adverse pregnancy outcomes if not been treated appropriately. Furthermore, the mode of delivery may additionally have adverse impact on fetal- pituitary- thyroid axis (6).
The prevalence of thyroid dysfunction in pregnant women is relatively high so that overt thyroid dysfunction occurs 2-3% of pregnancies, and subclinical dysfunction in 10% of pregnancies (7) and thyroid autoimmunity is even more prevalent.The second most common endocrinological disorder in pregnancy is thyroid dysfunction.(8) The most common cause of hypothyroidism is primary abnormality in thyroid. In some cases it is also caused by hypothalamic dysfunction.(9) In antenatal women most
3
common causes are Hashimoto's thyroiditis, iodine deficiency, radioactive iodine therapy and surgical removal of thyroid.The commonest cause of hypothyroidism is iodine deficiency. (10)Hashimoto's thyroiditis is the commonest cause in developed countries. The incidence of overt hypothyroidism is 0.3 to 0.5% and subclinical hypothyroidism 2-3%. Thyroid hormone is crucial for normal development of placenta, neuronal Migration.(11) Thyroid hormone is essential for the normal development of the placenta. There is evidence that preeclampsia, placental abruption and preterm labor are all causatively linked to faulty early placentation. (12)Thyroid hormone is important for normal neuronal migration, synaptic transmission and myelination during the early stages of neurodevelopment.(13)The only assumed physiological of iodine is in thyroid hormone isynthesis. Severeiiodine deficiency which causes hypothyroidism is associated with increased incidence of decreased intelligence, congenital anomalies of the fetus and cretinism.(14) Intrauterine growth restriction and fetal distress are more commonly seen in women with significant hypothyroidism. Starting thyroxine treatment in the 1sttrimester(preferably prenatally) may decrease the incidence of complications. Starting treatment after completion of 1st trimester will not eliminate already established fetal neurodevelopmental delay, as during the first trimester fetus completely maternal thyroid hormone for normal brain development.(15) Many changes occur in thyroid physiology during pregnancy. The cutoff values are changed during pregnancy for the diagnosis of hypothyroidism. The symptoms and signs also common for both the conditions. (16)Severe hypothyroidism pregnancy is not common because most of these women are infertile and they also have increased rates of abortions.(17)Not
4
much studies available to see if early thyroxine supplementation and adequate treatment the incidence of complications in pregnant woman with hypothyroidism.(18)My study is to see if diagnosed early and adequately treated hypothyroid women are able to reduce the complications like spontaneous miscarriages, preeclampsia, preterm labor, IUGR, stillbirth, low birth weight babies.(19,20)
5
AIM AND OBJECTIVE OF THE STUDY
PRIMARY OBJECTIVE :
1.To establish the effect of Thyroid Disorder on pregnancy outcomes in the South- Indian population.
2.To check the rate of progression of Gestational Thyroid Disorders into Overt Thyroid Disorders.
SECONDARY OBJECTIVE :
1. Evaluating and treating them would increase the pregnancy outcomes in these patients.
2. An estimate of the rate of Progression to Overt Thyroid Disorder in PostPartum Life
6
REVIEW iOF iLITERATURE i
Overt ihyperthyroidism iduring ipregnancy iwas inot iprevalent iand iwas ireported iin i2 iout iof i1000 ipregnancies i(0.2%), iwhile isubclinical ihyperthyroidism ioccurred iin i1.7% iof ipregnancies iThe imost iprevalent ireason ifor ihyperthyroidism iduring ipregnancy iwas ithe itransient ihyperthyroidism iresulting ifrom ihyperemesis igravidarum i(THHG) idue ito ithe ithyroid istimulation iof ibeta-HCG i; iit iwas imore iprevalent iin iAsian ipopulations icompared ito iEuropeans i(21)
Thyroid idisorder imay ibe ioverlooked iin ipregnancy ibecause iof inonspecific isymptoms iand ihypermetabolic istate iof ipregnancy. iPhysiological ichanges iof ipregnancy ican istimulate ithyroid idisease. iThe iprevalence iof ithyroid idisorder iduring ipregnancy ihas ia iwide igeographic ivariation. iWestern iliterature ishows ia iprevalence iof ihypothyroidism iin ipregnancy iof i2.5% iand ihyperthyroidism iin ipregnancy ihas iprevalence iof i0.1 ito i0.4% i iThere iis ipaucity iof idata ion iprevalence iof ithyroid idisorders iin iIndian ipregnant iwomen, ifew ireports ishow ia iprevalence iof i4.8% ito i11% iamongst iIndian ipregnant ipopulation i(22, i23). iIn iview iof iadverse imaternal iand ifetal ioutcomes iin ipregnant iwomen iwith ithyroid idisorder iand iobvious ibenefits iof iearly idiagnosis iand itreatment, isome iexpert ipanels iall iaround ithe iworld ihave isuggested iroutine ithyroid ifunction iscreening iof iall ipregnant iwomen.(24) i
7
Historical ibackground:
In i2700 iBC, iGoitres i(Latin- igutter), idefined ias ienlargement iof ithe ithyroid igland. iThe ione iwho icoined ithyroid igland i(Greek- ithyroids, ishield-shaped) iis iThomas iWharton iin ithe iyear i1656. iThe ithyroid igland ihas imany ifunctions iranging ifrom iacts ias ia ireservoir iof iblood ito isupply ithe ibrain ito idecorating ithe iwomen’s ineck. iOnce iSeaweed iwas iconsidered ias ia itreatment ifor igoiter.
iKocher iwas iawarded iNobel iPrize iin i1909, ifor ihis igreat iwork ion ithe ipathology, iand isurgery iof itheithyroid igland.In i1874, iWilliam iGull, iGovernor iof iGuy’s iHospital, idescribed imyxedema iand ihe icalled iit i“cretinous istate iin ithe iadult”., iDr. i iDawtrey iDrewitt iin i1883,presented icasein ithe iclinical isociety
iof iLondon,with ithe iclassical isymptoms iof ihypothyroidism. iIn i1891 iGeorge iRedmayne idescribed ithe itreatment iof ihypothyroidism iwith ithyroid iextract.(25,26)
8
EMBRYOLOGY iOF iTHYROID iGLAND i
The ithyroid igland iarises ias ia iprimitive ioutpouching iof iprimitive iforegut iaround ithe ithird iweek iof igestation. iThe ithyroid igland ioriginates iat ithe ibase iof itongue inear ithe iforamen icaecumipharyngeal ianlage iendodermal icells ithicken ito iform ithe imedial ianlage iof ithyroid. iIt idescends iin ithe ineck ianterior ito ithe ihyoid ibone ithe ithyroglossal iduct iconnects ithe imedian ithyroid ianlage
9
itoiforamen icaecum. iFrom ithe iepithelial icells iof ithe ithyroid ianlage, ithe ithyroid ifollicle icells iarise. iThe ipaired ilateral ianlages iarise ifrom ithe i4th ibrachial ipouch iand ifuses iwith ithe imedial ithyroid ianlage. iThey iare ineuroectodermal iin iorigin iand ithey isecrete icalcitonin. iBy i11th iweek iof igestation icolloid iformation ibegins ifrom ithe ithyroid ifollicle.(27,28)
ANATOMY iOF iTHYROID iGLAND i
The ithyroid igland iis ia ibutterfly-shaped iorgan ithat isits iat ithe ifront iof ithe ineck. iIt iis icomposed iof itwo ilobes, ileft iand iright, iconnected iby ia inarrow iisthmus. iThe ithyroid iweighs i25 igrams iin iadults, iwith ieach ilobe ibeing iabout i5 icm ilong, i3 icm iwide, iand i2 icm ithick iand ithe iisthmus iabout i1.25
10
icmiinheight and width. The gland is usually larger in women and increases in size in pregnancy.The thyroid isits near the front of the neck, lying against and around the front of the larynx and trachea. The thyroid cartilage and cricoid cartilage lie just above the gland, below Adam's apple. The isthmus extends from the second to third rings of the trachea, with the uppermost part of the lobes extending to the thyroid cartilage and the lowermost around the fourth to sixth tracheal rings. The thyroid gland is covered by a thin fibrous capsule,which has an inner and an outer layer. The outer layer is continuous with the pretracheal fascia, attaching the gland to the cricoid and thyroid cartilagesvia a thickening of the fascia to form the posterior suspensory ligament of thyroid gland, also known as Berry's ligament. This causes the thyroid to move up and down with swallowing. The inner layer extrudes into the gland and forms the septae that divides the thyroid tissue into microscopic globules.(29,30) Typically, four parathyroid glands,two on each side, lie on each side between the two layers of the capsule, at the back of the thyroid lobes. The infrahyoid muscles lie in front of the gland and the sternocleidomastoid muscle to the side.Behind the outer wings of the thyroid lie the two carotid arteries. The trachea, larynx, lower pharynx and esophagus all lie behind the thyroid. In this region, the recurrent laryngeal nerveand the inferior thyroid artery pass next to or in the ligament.The thyroid is supplied with arterial blood from the superiorthyroid artery, a branch of the external carotid artery, and the inferiorthyroid artery, a branch of the thyrocervical trunk, and sometimes by the thyroid ima artery, branching directly from the subclavian artery.
The venous blood is drained via superior thyroid veins, draining in the internal jugular
11
vein, and via inferior thyroid veins, draining via the plexus thyreoideusimpar in the left brachiocephalic vein.(31,32,11)
Lymphatic drainage passes frequently the lateral deep cervicallymph nodes and the pre- and paratracheal lymph nodes. The gland is supplied by parasympathetic nerve input from the superior laryngealnerve and the recurrent laryngeal nerve.(33)
THYROID iHORMONE iSYNTHESIS i& iTRANSPORT i
Thyroid hormones are two hormones produced and released by the thyroid gland, namely triiodothyronine (T3) and thyroxine (T4). They are tyrosine-based hormones that are primarily responsible for the regulation of metabolism. T3 and T4 are partially
12
composed of iodine. A deficiency of iodine leads to decreased production of T3 and T4, enlarges the thyroid tissue and will cause the disease known as simple goiter. The major form of thyroid hormone in the blood is thyroxine (T4), which has a longer half- life than T3. In humans, the ratio of T4 to T3 releasedinto the blood is approximately 14:1. T4 is converted to the active T3 (three to four times more potent than T4) within cells by deiodinases (5'-iodine). These are further processed by decarboxylation and deiodination to produce iodothyronine (T1a) and thyroxine (T0a). All three isoforms of the deiodinases are selenium-containing enzymes, thus dietary selenium is essential for T3 production.(34,35)
Metabolism iand iexcretion iof ithyroid ihormone:(32,26)
By iglucuronide iconjugation iand ideiodination, ithe imetabolic iinactivation iof iT3 ioccurs iin ithe iliver, ikidneys iand isalivary iglands iand ithen ithey iare iexcreted iin ibile. iIn ithe iintestines ia imajor ifraction iis ideconjugated iand ireabsorbed iinto ithe ienterohepatic icirculation iand ifinally iexcreted iin iurine.
Mechanism iof iaction(15,37)
T3 ipenetrates ithe icells iand icombines iwith ithe ispecific iDNA isequences iover ithe inuclear ireceptor, ileads ito ide-repression ior idirect iactivation iof igene itranscription iresults iin iexpression iof ipredetermined ipattern iof iprotein isynthesis.
13
Many iof ithe iclinical imanifestations iof ithyroid ihormone-like iBy isensitization iof iadrenergic ireceptors ito icatecholamines ithe iclinical imanifestations iof ithyroid ihormones ilike itachycardia, iarrhythmias, ihypertension, ihyperglycemia, itremor ioccurs.
THYROID iHORMONES iFUNCTIONS i(38,39,40)
Thyroid ihormones iaffect ialmost ievery isystem iin ithe ibody.
iGrowth iand idevelopment
Thyroid ihormones iexert icritical icontrol iover iprotein isynthesis. iThyroid
ihormone ideficiency iaffects imainly ithe inervous isystem iin iearly ifetal ilife. iIn icretinism ithere iis imental iretardation iand ineural ideficit idue ito ipaucity iof isynaptic iformation, idendritic iand iaxonal iramification iand ireduced imyelination.
iOvert ihypothyroidism iin ithe iadult icauses iimpairment iof iintelligence iand islow imovements.
Carbohydrate(CHO) iMetabolism:
Thyroid ihormones istimulate icarbohydrate imetabolism. i iThough ithe iutilization iof icarbohydrates iis iraised idue ito ia iraised iBasal i iMetabolic iRate
14
i(BMR),iglycogenolysis& igluconeogenesis icompensate ifor iit. iIn ihyperthyroidism ithere iis ia istate iof ihyperglycemia
Protein iMetabolism:
The ieffect iof iT4 iover ithe iproteins iis icatabolic. iProlonged iaction iresults iin inegative initrogen ibalance iand itissue iwasting. iHence ithere iis iloss iof iweight iin ihyperthyroidism iand igain iof iweight iin ihypothyroidism. iMucoprotein isynthesis iis iinhibited iby ithyroid ihormones. iDue ito iloss iof iinhibition ithey iaccumulate iin imyxedema.
Lipid iMetabolism i: i(41,42)
T3 iand iT4 ienhance ilipolysis ithrough ilipogenesis iare ialso istimulated.
iMetabolism iof iCholesterol iis iaccelerated ithough iits iconversion ito ibile iacids idominate. iHence ithere iis ihypocholesterolemia iin ihyperthyroidism iand iobesity i& ihypercholesterolemia iin ihypothyroidism.
Calorigenesis:( i42,43)
BMR iis iraised iby istimulating icellular imetabolism iand iresetting ithe ienergy istat ilevel. iBut iBMR iin igonads, iuterus, ispleen, ibrain iand ilymph inodes iare
15
inotisignificantly iaffected. iUncoupling iof ioxidative iphosphorylation iresults iin ireleasing iof iexcess ienergy ias iheat.
Cardiovascular isystem: i(44,45)
Contractility, iheart irate, iand icardiac ioutput iare iall iincreased iwhich iresults iin ia ifast i& ibounding ipulse. iThe iupregulation iof ibeta-adrenergic ireceptors iby ithyroid ihormones iresults iin ipositive ichronotropic iand iinotropic ieffects. iEffects iof icatecholamines iare iaugmented, ihence iatrial ifibrillation, iarrhythmias, iand iangina iare imore icommon iin ihyperthyroidism. iSystolic iblood ipressure iis ioften iraised.
16
Nervous isystem i(46,47)
Thyroid ihormones imaintain ithe inormal ihypoxic iand ihypercapnic idrive iof ithe irespiratory icenter iin ithe ibrain. iThere iis imental iretardation iin icretinism. i i iTremors,hyperreflexia, i& ianxiety iare iseen iin ihyperthyroidism iwhereas isluggishness iis iseen iin ihypothyroidism.
iSkeletal imuscle
T3&T4 iincreases ithe iprotein imetabolism iresults iin ispeed iof imuscle icontraction iand irelaxation. iMuscle iweakness iis iseen iin imyxedema iand itremor, iincreased imuscle itone iis iseen iin ithyrotoxicosis.
Gastrointestinal isystem
T3&T4increase igastric imotility.Constipation is iseenin ihypothyroidism iwhile idiarrhea iis iseen iin ihyperthyroidism.
Haemopoiesis:
Anemia ioccurs iin ihypothyroid ipatients ihence iit iis iproven ithat ithyroid ihormones iplay ia irole iin ihemopoiesis.
17
Reproduction:
Hypothyroid iwomen ihave ioligomenorrhea i& iinfertility. iHence iit iis iproven ithat ithyroid ihormones iare iessential ifor ithe imaintenance iof ipregnancy iand ilactation.(43,44,45,47)
Thyroid iPhysiology iiniPregnancy (48,49,50)
There iis ia ilot iof ichanges iin ithyroid iphysiology ioccur iduring ipregnancy.
iIodination iof ityrosine iresidues iin ithyroglobulin ileads ito iform imono ior idi iiodo ityrosine i(MIT&DIT) iwhich iare ithen icoupled ito iform iT4 iand iT3.The imajor iportion iof iT4 iis ibound ito icirculating itransport iproteins ilike ithyroxine-binding ipre ialbumin i(TPBA), ialbumin i& ithyroxine-binding iglobulin i(TBG i). iOnly i0.04% iof itotal iT4 iis ifree iand iit iis ithe iphysiologically iactive ihormone. iTSH iwhich iis isecreted iby ianterior ipituitary iincreases ithe isynthesis iand irelease iof ithyroid ihormone ifrom ithyroid igland.TBG iproduction iis iincreased iby iestrogen iduring ipregnancy. iThere iis iincreased ibinding iof iT4,increased imetabolism iby ithe iplacenta& iincreased irenal iclearance ileads ito ia igreater idemand ifor ithe iproduction ito imaintain ifree iT4 ilevels.The itotal iT4 ilevel iis igreater ithan ithe inormal inonpregnant ilevels. iThere ialso iincreased iplacental itransfer iof iiodine ito ithe ifetus iresults iin iincreased idemand ifor imaternal iiodine ito imaintain
18
itheinormal ithyroid ihormone iproduction.HCG ihas icommon ialpha isubunit ilike iTSH iand iunique ibeta isubunit. iHence iHCG ihas ia iweak iTSH ilike iactivity iand iit istimulates ithyroid igland iresults iin idecreased iTSH ilevel iand iincreased iT4 ilevels. iMolar ipregnancy, imultiple ipregnancies, ihyperemesis igravidarum iall ithese iconditions iare iassociated iwith iincreased iHCG ilevels iand ilead ito iincreased istimulation iof ithe ithyroid igland iresult iin itransient ifirst- itrimester ithyrotoxicosis. i
Once iHCG ireturns ito ia isteady-state ilevel iTSH ialso irebound ito inormal inonpregnant ilevels. iHence ithere iis ian iincrease iin iTSH i& imild idecline iin ifree iT4 iafter ithe ifirst itrimester. iThat iis iwhy iTSH i& iFT4 ilevels ishould ibe iinterpreted iwith icaution ifor ieach itrimester.
Cut ioff ivalues ifor iTSH iin ipregnancy:
Because iof ithe isuppressive ieffect iof iincreased ithyroxin iand iincreased iTSH iexcretion, iTSH iis ikept iat iits ilowest iminimal ilevel iin inormal ipregnancy.TSH ilevel iis i0.1-1.6 imIU/ml iand ithyroxin ilevel iis iraised ione iand ia ihalf itimes iin ithe ieuthyroid ipregnancy istate.
In i2005 iSpencer iET ial istudied ithat iS.TSH i>2.5 imIU/ml iin i1st itrimester ishows iT4 ideficiency.
19
In i2005 iGreen iWL idid ia istudy iwhich isays ithe inormal irange iof iTSH iis i0.5to i2.5mIU/ml(6)Prof. iLadenson isaid ithat iadequate ireplacement ishould ibe igiven iwhen iTSH iis i> i2.5 imIU/ml iand i/or ithe ilower iT4 ilevel iin ipregnancy.
Thyroid iphysiology iin ithe ifetus iand ineonate:
Between i8 iand i10 iweeks iof igestation istarts ito iconcentrate iiodine iand ito isynthesis ithyroid ihormone ialong iwith ithe isynthesis iof iTSH. iAlthough iaround12 ito i14 iweeks iof igestation ipituitary ithyroid iaxis iis icompletely ideveloped iits ifunction iis iminimal iand ionly iaround i20 iweeks isudden isurge iin ithe ifetal iTSH ioccurs. iAnd itill i28 iweeks iTSH ilevels icontinue ito iincrease itill iit ireaches ia iplateau iand iremains iat ithe isame ilevel itill iterm igestation.
WEEKS iOF iPREGNANCY i(51,52)
20
The imajor ifetal ithyroid ihormone iis iT4and ithe ilevel iof iT3 iis iquite ilow iThroughout ithe ipregnancyRT3 ilevels iare iparallelly ielevates iwith ithe irise iof iT4. iThus ithe ifetus igoes ifrom ia istate iof irelative iT3 ideficiency ito iT3 ithyrotoxicosis iduring idelivery. iBy i48-72 ihours ithe iTSH ivalues irise irapidly iand ithen ifall ito ibaseline ilevels. iThe iT3 iand iT4 ilevels iincrease iin iresponse iand ireach ithe ipeak ilevels iby i24hrs iand iby i24-48 ihrs iof iage irespectively.
iThe ihyperactivity iof ithyroid itakes iabout i3-4 iweeks ito icompletely idisappear.
These ichanges imainly ioccur idue ito ithe iTRH isurge iand iprolactin isurge. iThese ithyroid ichanges iare iprotective imechanisms iagainst ithe irapid ientry iof ineonate ito ithe icold ienvironment iduring idelivery. iDuring ithe ifirst i72 ihrs iof ilife iRT3 ilevels ireach ipeak ilevels ithen iit ireturns ito ithe ibaseline ilevel iat i12 iweeks.
Summary iof ifetal iand ineonatal ithyroid ichanges: i( i17,53,54)
1. By i10-13 iwks iof igestation iTSH iand iT4 istart iappearing 2. By i20 iwks iTSH i&T4levels ireach ian iabrupt irise
3. At iterm iT4 irapidly iincreases iand iexceeds imaternal ivalues
4. T3 ilevels iincrease, ibut ivalues iare irelatively ilow iwhich iis isimilar ito ihypothyroid iadults
5. RT3 ilevels iexceed inormal iadult ilevels
21
6. The ifetal ivalues iof ilow iT3 iand ihigh iRT3 iis isimilar ito ithe ivalues iseen iin icalorie ideprivation
7. TSH ipeaks iat i30mins, ifollowed iby ia iT3 ipeak iat i24 ihrs iand ia iT4 ipeak iat i24- i48hrs iafter ibirth.
8. Raised iRT3 ilevels ipersist ifor i3-5 idays ithen iplateau idown ito inormal ilevelsby2 iWks.
Overt ihypothyroidism; i(55,56)
It iis icharacterized iby iincreased iTSH iand ilow iT4 ilevels i.the iincidence iis i0.3 i- 0.5%. iovert ihypothyroidism iis iassociated iwith ianemia, imiscarriage, ipreeclampsia, iplacental iabruption, ipreterm ilabor, iPostpartum ihemorrhage, ineonatal irespiratory isyndrome.In i1969, iJones iWS iet ial idid ia istudy iin ithe iAmerican iJournal iof iObstetrics iand iGynaecology iwhich isays ithat ipreterm ideliveries iwere imore icommon iin ipregnant iwomen iwith ilow ithyroxine ilevels.Leung iAS iet ial iin i1993 idid ia istudy iin i1993 iand ifound ithat iovert ihypothyroidism iassociated iwith ian iincreased iincidence iof ipreeclampsia iand ilow ibirth iweight ibabies. i iPop iVJ iet ial istudied ithat ifetal idemises iwere iincreased iin ipregnant iwomen iwith iTSH i> i10mIU/ml. iIn i1988. i(57)
22
Davis iet ial ifollowed i25 ihypothyroid iwomen iin iwhich i16 iwere iovert ihypothyroid iand i12 ihad isubclinical ihypothyroidism iand iconcluded ithat imothers iwith iovert ihypothyroidism iare iat iincreased irisk ifor ipreeclampsia, ipreterm ilabor, iabruption iplacentae, ipostpartum ihemorrhage,stillbirth, iand icardiac idysfunction.(58)
ACOG ipractice ibulletin ion ithyroid idisease iin ipregnancy iin i2001 istates ithat iuntreated ihypothyroid iwomen iare imore iprone ito ipre-eclampsia iand iinadequate itreatment iresults iin ilow ibirth iweight ibabies.(26)
Prummel iMF, iet ial ipublished iin ithe iArchives iof igynecology iand iobstetrics ithat igestational ihypertension, iIUGR, iand iIntrauterine ifetal idemise iwere imore icommon iin iwomen iwith iovert ihypothyroidism.(59)
A icouple iof istudies ihave ishown ilow ithyroxine iconcentration iin iearly ipregnancy ican ibe iassociated iwith ithe ilow iintelligent iquotient iof ichildren iat i7 iyears iof iage. iR. iNegro, iG iet ial iin i2004 ireviewed ithe iliterature ion ithe irole iof ithyroid ihormone iin itrophoblast ifunction iand ifetal ineurodevelopment. iThey
iconcluded ithat iclose iscrutiny iof imaternal ithyroid ihormones ito
iensure(60)adequate ihormone ilevels iin iearly ipregnancy iare iof iprime iimportance iin ipreventing imiscarriage iand ineurodevelopmental ideficits iin iinfants(67,15)
23
Only ia ifew ireports iare iavailable ion ithe ipregnancy ioutcome iin ihypothyroid ipregnant iwomen iwho iare ileft iuntreated. iThese idata ishow ithat iadequate ithyroxine ireplacement igreatly iimproves ibut idoes inot itotally isuppress ithe ifrequency iof iobstetric icomplications.(8)
Subclinical iHypothyroidism(43,44)
By idefinition, iit iis ia icondition iin iwhich iTSH iis ielevated, ibut iFT4 iis inormal.
iThe iincidence iof isubclinical ihypothyroidism iis iat ileast i2.5%.Usually iit iis iasymptomatic, ibut ithere iis ievidence iautoimmune ithyroid idisease i(positive iTPO iAbs iand ior iTG iantibodies)in i50-60%(12)
Subclinical ihypothyroidism iwas ifound ito ibe imore icommon iin iwomen idelivering ibefore i32 iweeks. i(12)Pregnancies icomplicated iby isubclinical ihypothyroidism ihad ia i3 ifold iincreased irisk iof ideveloping iplacental iabruption iand i2 ifold iincreased irisk iof ipreterm ilabor icompared ito ieuthyroid iwomen.(22) iGestational ihypertension ialso ioccurred imore icommonly iin ithese iwomen.(23) iEven iraised imaternal iTSH i(high ilevel iof inormal) iis iassociated iwith ineonatal irespiratory idistress, imiscarriage iand ipreterm idelivery(12).
24
The ilikelihood iof ipatients idiagnosed ias ihypothyroid iduring ipregnancy ito icontinue ito ibe ihypothyroid ieven iafter ipregnancy idepends ion ithe iinitial iTSH ivalue. iThe iUnited iStates iPreventive iServices iTaskforce ireported ithat inearly ialmost iall ipatients iwith ian iinitial iTSH i>10 imIU/ml ideveloped iovert
ihypothyroidism iwithin i5 iyears.(33)
ISOLATED iHYPOTHYROXINAEMIA:
It iis idefined ias ia icondition iwith inormal iTSH iand ilow ifT4. iCleary iGoldman iand icolleagues iin i2008 iscreened i10,990 ipatients ifor ithyroid idysfunction. iThey inoted ithat ithe ipresence iof ithis iisolated ihypothyroxinemia iin i1st itrimester iwas iassociated iwith ian iincreased ioccurrence iof ipreterm idelivery iand imacrosomia.
iIts ioccurrence iin i2ndtrimester iwas iassociated iwith igestational idiabetes.(28)
CLINICAL iFEATURES iOF iHYPOTHYROIDISM:
Hypothyroidism ideveloping iin ichildhood iresults iin idelayed idevelopment iand imay ieven icause iabdominal idistension, iumbilical ihernia, iand irectal iprolapse.
iMental iperformance iis idiminished ibut isevere iretardation iis iuncommon.
i
25
In iadults imostly isymptoms iare inonspecific. iThey iinclude iweight igain, ifatigue, iintolerance ito icold, iconstipation iand imenstrual iirregularities ilike imenorrhagia.
Patients iwith imyxedema ihave itypical ifacial ifeatures. iSkin iis iyellowish idue ito ireduced iconversion iof icarotene ito ivitamin iA. iHair ibecomes ibrittle iand ithere iis ialso ia icharacteristic iloss iof ithe iouter itwo-third iof ieyebrow. iUntreated ipatients ican idevelop idementia iwhich iis icalled imyxedema imadness. iThere iis idecreased ilibido iand ifertility iin iboth isexes. iCardiovascular ichanges iinclude ibradycardia, ipericardial ior ipulmonary ieffusions.
Treatment iof iHypothyroidism: iLevothyroxine
Levothyroxine ior iT4 iis ia isynthetic iform iof inormally isecreted iby ithe ithyroid ichiral iL-form. iEdward iCalvin iKendall iits ipure iform ifrom iextracts iof ihog ithyroid iglands iin i1914 isynthesized iby iBritish ichemist iAbsorption iof iL ithyroxine iis iincomplete ivarying ifrom i50-75%.
For itherapeutic ipurposes, iL ithyroxine iis isuperior ito iliothyronine ibecause iof iits ilonger iduration iof iaction. iThe ionly iaccepted iindication ifor ithe iuse iof ilio iis imyxedema icoma iwhere ia iquick iresponse iis iessential.
26
Levothyroxine ishould ibe itaken ion ian iempty istomach iapproximately ihalf ian ihour ibefore imeals. iPatients ishould iavoid itaking ithyroxine ias ithese ican iinterfere iwith ithe iabsorption iof ithis idrug.
According ito ithe iAmerican iThyroid iAssociation, ipregnant iwomen ialready ibeing itreated iwith ithyroxine ihormone ioften irequire ia i30-50% iincrease iin idose ithe ineed ifor idose iincrease istarts ias iearly ias i5 iweeks iGA, iThe iassociation iurges iphysicians ito ibe ivigilant iin iidentifying iand itreating iwomen iwith isubclinical ithyroid idysfunction ibefore iconception.
Edward iCalvin iKendall iof ithe iMayo iclinic ifirst iisolated ithyroxine iin iits ipure iform ifrom iextracts iof ihog ithyroid iglands iin i1914.
Congenital iHypothyroidism:
Congenital iHypothyroidism i(CH) iis ione iof ithe imost icommon ipreventable icauses iof imental iretardation. iThe iincidence iis i1:4000 ilivebirths iand ithe iworldwide iand ithe iincidence iin iIndia iis i1:2500-2800 ilive ibirths. iThyroid idysgenesis iis ithe icommonest icause iattributing ifor ithe imajority iof icases. iCH ican ibe ipermanent ior itransient. iMaternal icytotoxic iantibodies iand igenetic imutations icausing iinactivation iof ithyroid i ireceptor ican ibe ia icause.There iis
iclinical iand iscientific ievidence ithat ihypothyroxinemia icauses
27
ipoorineurodevelopment ioutcomes iin ithe ichildren iof imothers iwith ilow ithyroxine ilevels. i
In ia istudy iby iRoberts iCG iEscobar iet ial iin2004, iit iwas inoted ithat ithe ithyroid ihormone iaccumulates iin ithe icerebral icortex ibefore i20 iweeks.(30)Primary ievidence iof ithe ieffect iof ithe ideficiency iof ithyroid ihormone ion icerebral icortex iwas istudied iby iLavado- iAutric iet ial iini2003.(31) iDefects iin ithyroid ihormone isynthesis iaccount ifor i10% iof iall icases. iThese ican ibe iinherited ias iautosomal irecessive idisorders.(62)
CLINICAL iFEATURES iOF iCONGENITAL iHYPOTHYROIDISM
Untreated isevere icongenital ihypothyroidism ileads ito iirreversible igrowth ifailure iand imental iretardation iEarly isymptoms iinclude ifeeding iproblems, iconstipation, igrowth ifailure iand ihoarse icry iLater ithey idevelop idry iskin iand idecreased igrowth iof inails iand ihair; itooth ieruption iis idelayed iClosure iof ianterior iand iposterior ifontanelles iare idelayed iCardiomegaly imay ibe ipresent.The iother
iclinical ifeatures iare ibroad, iflat inose, ipseudohypertelorism, ipuffy,
imyxedematous ifacies, ilarge, iprotruding itongue, iprolonged ineonatal ijaundice, iprotuberant iabdomen, iumbilical ihernia.
28
Postpartum iThyroiditis i(63)
Postpartum ithyroiditis iis icharacterized iby ilymphocytic iinfiltration iof ithe ithyroid igland.It’s ireported iincidence iis iin iabout i5% i iof ipregnancies(17).It iusually
ioccurs iin ithe i1st imonth iafter idelivery.It istarts ias ia ithyrotoxic iphase ifollowed iby ia iphase iof ihypothyroidism ilasting ifor imonths.
It iis itypically icharacterized iby ithe ipresence iof iTPO iantibodies ialthough iit’s
ioccurrence iis iwomen iwithout ithese iantibodies ihas ialso ibeen ireported. iThe irisk iis ieven igreater iwhen iTPO iantibodies iare idetected iantenatally.Studies ihave ishown ithat ias imany ias i50% iof iwomen iwho ideveloped ipostpartum ithyroiditis icontinued ito iremain ihypothyroid iat ithe iend iof ithe i1stipostpartum iyear. iThere iis ino icompelling ievidence ito isupport ithe iearly itreatment iof ithis icondition.
Thyroid iantibodies:(64,65)
These itests ido inot idetermine ithe ithyroid ifunction, iinstead, ithey iindicate ithe iunderlying idisorder. iAntithyroglobulin, ianti imicrosomal iand ithyroid-stimulating iimmunoglobulin iare ithe ithyroid iantibodies. iApproximately i80% iof ipatients iwith iHashimoto’s ithyroiditis ihave iraised ithyroid iantibody ilevels.Thyroid iperoxidase( iTPO)antibodies iand iAntiThyroglobulin(TG) iantibodies iare ilinked ito ipregnancy icomplications. iThere iare istudies ito ishow ithat ieuthyroid iwomeniwith
29
irecurrent imiscarriages iand ipreterm ibirth iwere ifound ito ihave iantibodies ito ieither iTPO ior iTG.TPO iantibodies ihave ialso ibeen iimplicated iin ithe idevelopment iof ipostpartum ithyroiditis.Association ibetween iautoimmune ithyroiditis iand iadverse iobstetric ioutcome iindependent iof ithyroid ifunction ihas ialso ibeen iproven iin ianother iprospective istudy iwhere ieuthyroid iTPO iantibody- positive iwomen iwho ireceived ithyroxine isupplementation iin iearly ipregnancy ihad ia ireduced irate iof imiscarriage iand ipreterm idelivery irate(12).Pregnant iwomen iwith iTPO iantibodies iwere ifound ito ihave ithree itimes imore ichances iof iplacental iabruption iwhen icompared iwith iantibody-negative icontrols iin ia istudy iby iAbbassi-Ghanavati iet ial iin i2010.
S. iO. iLeBeau iet ial irevealed ia idecrease iin ithe iintelligent iquotient iof ichildren iaged i5 iyears iwhose imothers iwere iTPO iantibody ipositive iat i32 iweeks iof igestation ieven ithough ithey iwere iactually ieuthyroid.(4)Some ithyroid iautoantibodies icross ithe iplacenta icausing ifetal ithyroid idysfunction.iBut imaternal iHashimoto ithyroiditis iis inot itypically ifound ito ibe iassociated iwith ifetal ithyroid iabnormalities.(65)
I
30
Hypothyroidism iand iInfertility: i(65,18,19)
Infertility iis idefined ias ithe iinability ito iconceive iafter ione iyear iof iintercourse iwithout icontraception i(39). iIn imild idegrees iof ihypothyroidism, iovulation iand iconception ican ioccur, ibut ithe ipregnancies ithat iresult iare icomplicated iby iabortions, istillbirth ior iprematurity i(13).
On ithe iother ihand, isevere ihypothyroidism iis icommonly iassociated iwith iovulatory idysfunction iand, ithus, iinfertility. iHypothyroid iwomen ican ipresent iwith imenstrual iirregularities, iespecially ioligomenorrhoea.
Thyroid iunder ifunction ican ialso iact imore iindirectly, iby ialtering ithe iHPO iaxis, iby ireducing ithe ibinding iactivity iof isex ihormone-binding iglobulin i(SHBG)causing ian iincrease iin iserum-free itestosterone iand iestradiol, iby idecreasing ithe imetabolic iclearance iof iandrostenedione iand iestrone.
Also, iTRH iis ielevated iin ihypothyroidism iwhich icauses ian iincrease iin iprolactin ilevels, iand ia idelay iin iLH irelease ito iLH ireleasing ihormone i(LHRH).
iTreatment iof ithyroid iunder ifunction iwith iL-thyroxine i(L-T4) iusually irestores ia inormal imenstrual ipattern iand ialleviates ithese ipathological imechanisms i(34) i
31
It ihas ibeen irecently irecognized ithat idisturbances iof icognition iand imood idevelop iin iassociation iwith ialteration iin ithyroid imetabolism iin ithe ibrain.
iThere iare ieven ifew ismall istudies ito ishow ithe iconnection ibetween ithyroid idysfunction iand imood idisorders ilike ipostpartum idepression.
Thyroid iDysfunction iand ipregnancy iloss: i(53,54,55)
Normal ithyroid ifunction iis icritical ifor ithe inormal ifunctioning iof ithe igonadal iaxis, ithus iimportant iin imaintaining inormal ireproduction. iGonadal isteroid isynthesis iby ioocytes idepends ion ian iadequate ilevel iof ithyroid ihormones. iT3 imodulates ithe iregulating iaction iof iLH iand iFSH i ion isteroid ibiosynthesis, ithyroid ihormones iincrease iand ienhance iestrogenic iresponses(9).
Hypothyroidism iis iassociated iwith ianovulatory icycles, isubfertility ior iinfertility iAbortion irate ias ihigh ias i60% iin iinadequately itreated iovert ihypothyroid iand i70% iin isubclinical ihypothyroidism(10) iMatsua iet ial ishowed ithat iFree iT3 iand iFree iT4 ivalues iwere isignificantly ilower iin iwomen iwhose ipregnancies iterminated iin iabortions i.(40)
Sapana iC iet ial iin i2005 idid ia icase-control istudy ito iinvestigate ithyroid idysfunction ias ia icausative ifactor ifor iabortions. iThey iperformed ithyroid ifunction itests iin i60 ipatients ihaving ispontaneous imiscarriages iand
32
icomparedithem iwith ithose iof i40 ipregnant iwomen iof isame igestational iage iwho iwere ipresumed ito ireach iterm.They ifound ithat iT3 iand iT4 ivalues iwere isignificantly ilower iand iTSH ivalues iwere isignificantly ihigher iamong ithe iabortion igroup isuggesting ithat isubclinical ihypothyroidism imay ibe iresponsible ifor ispontaneous iabortions(16) iThere iare itheories ithat iconsider iautoimmune ithyroiditis ia iconsequence iof iincreased ilymphocytes iT iactivation. iPatientsiwith iantecedents iof ihabitual iabortions ishow ian iincreased inumber iof iendometrial iT ilymphocytes.(66)
Expression iof ithe iantithyroid iantibodies imay ibe ian iepiphenomenon ithat ireflects ian iautoimmune iimbalance, icausing ithe irejection iof ithe iproduct iof iconception.
iThis ihypothesis iis isupported iby ithe iexistence iof ian iincreased iCD5/20 ilymphocyte ipositivity iin iwomen iwith irecurrent imiscarriage(11).
33
i MATERIALS i iAND iMETHODS i
STUDY iPOPULATION: iNewly idiagnosed ipregnant iwomen iwith iThyroid iDisorder iattending iEndocrinology iOut iPatient iDepartment, iGovt iStanley iHospital, iChennai.
STUDY iAREA: iGeneral iMedicine iDepartment iIn iCollaboration iWith iOG iAnd iEndocrinology
SAMPLE iSIZE: i i100 iPregnant ifemales i SAMPLING iMETHOD: iCohort istudy.
STUDY iDURATION: i6 imonths. iin ithe iyear i2019
INCLUSION iCRITERIA:
1.Lessithan i13 iweeks iof igestation. i 2.Singleton ipregnancy.
3.Primigravida ior imultigravida. i 4.Knownihypothyroid ipatients.
34
iEXCLUSION iCRITERIA:
1.Multifoetal igestation.
2.Known ichronic idisorders ilike idiabetes iand ihypertension, iliver idisorders, irenal idisorders
3.previous ibad iobstetric ihistory iwith ia iknown icause.
4.Those iwho iplan ito ideliver iin ianother ihospital METHODOLOGY i
Pregnant iwomen iwith iThyroid iDisorder iattending iEndocrinology iOutpatient iClinic iat iGovernment iStanley iHospital, iChennai iand ifulfilling iinclusion icriteria iwere ienrolled iin ithe istudy iafter iinstitutional iethics iapproval iand iconsent ifrom ithe istudy isubjects. iA idetailed ihistory iwas itaken, iregarding ithe isymptoms iof ithyroid idisorders, imenstrual ihistory, iobstetric ihistory, ipast imedical ihistory, ifamily ihistory, ipersonal iand isocial ihistory. iGeneral iexamination iwas idone iwith ireference ito ithe igeneral icondition iof ithe ipatient, ibody itemperature; ipulse irate, iblood ipressure, irespiratory irate, iand ithe ifinding iwere irecorded. iSystemic iexamination iof ithe icardiovascular isystem i(CVS), icentral inervous isystem i(CNS), irespiratory isystem iand ithyroid igland iwas idone iand ifindings iwere irecorded. iPer iabdominal iand iper ivaginal iexamination iwas idone iand ifindings iwere irecorded. i i
35
LAB iINVESTIGATION: i
Basic iinvestigations: i iComplete iblood ipicture, iClotting itime, iBleeding itime, iBlood igrouping iand iRh ityping, iRBS, iBlood iurea, iSerum icreatinine, iHIV, iHbsAg iand iComplete iurine iexamination iwere idone. iPregnancy iwas iconfirmed iby iclinical iassessment, ipregnancy itest, iand iultrasonography. i i
BIOCHEMICAL iANALYSIS i
ESTIMATION iOF iFREE iT3
Method-RIA i( iRadio iImmuno iAssay i) i– iIMMUNOTECH iPrague, iCze ich irepublic
Principle-The iThe iradioimmunoassay iof ithe ifree itri-iodothyronine i(T3) iis ia icompetitive iassay idone iby iusing ia ilabeled iantibody. iSamples iand icalibrators iare iincubated iwith ia i125I- ilabeled iantibody ispecific ifor iT3, ias itracer, iin itubes icoated iwith ian ianalog iof iT3 i( iligand i). iThe ifree itri-iodothyronine iand ithe iligand icompete ifor ithe ibinding ito ithe ilabeled iantibody. iThe icontent iin ithe itubes iis iaspirated iafter iincubation iand ibound iradioactivity iis imeasured. iA icalibration icurve iis idesigned iand ivalues iare iascertained iby iinterpolation ifrom ithe icurve.
36
Reagents-Ligand-coated itubes i125I- ilabeled imonoclonal iantibody iCalibrators iControl iserum
Specimen icollection-Blood iwas icollected iin idry itubes ior iin itubes icontaining iEDTA, iin ia ifasting istate. iSerum/Plasma iwas iseparated ifrom icells iby
icentrifugation. iSamples iwere istored iat i2-80C.
Results-Normal irange iof iFree iT3 iwas itaken ias i2.5 i– i5.8 ipM/L.
ESTIMATION iOF iFREE iT4
Method-RIA i(Radio iImmuno iAssay) iPrinciple, iReagents iand iprocedure iare isimilar ito iFree iT3 iestimation.
Results-Normal irange iof iFree iT4 iwas itaken ias i11.5 i– i23 ipM/L.
ESTIMATION iOF iTSH
Method-Solid iPhase iTwo-Site iImmunoRadoMetric iAssay i( iIRMA i) iwith iIRMAK-9 ikit, iBRIT, iMumbai.
Principle
In iIRMA, itwo iantibodies igenerated iagainst idifferent iportions i(epitopes) iof ithe isame iantigen iare iused. iOne iof ithe iantibodies iis ibound ito ia isolid iphase,iwhile
37
ithe iother iis ilabeled iwith i125I. iThus, ithe iantigen ibinds iboth iantibodies iin ia i“
isandwich” ifashion. iThe iradioactivity iin ithe ibound ifraction iis iquantitated iusing ia igamma icounter.
Reagents i-TSH imonoclonal iantibody-coated itubes i125I- iAnti iTSH iWash idiluents.
Specimen icollection-Serum ior iplasma ican ibe iused ifor ithe iassay. iEDTA iplasma iis inot iused.
Specific iInvestigations: iPatients iwill ibe itested ifor iserum iTSH ilevel iand ifT4 ilevel.
iThe ireference iranges iof ithe itest ivalues iused iin ithis istudy iwill ibe ias iper ithe iGuidelines iof ithe iAmerican iThyroid iAssociation ifor ithe iDiagnosis iand iManagement iof iThyroid iDisease iduring iPregnancy iand iPostpartum. iAs iper iRegulation i14.2 iof iATA iGuidelines, iif itrimester-specific iranges ifor iTSH iare inot iavailable iin ithe ilaboratory, ithe ifollowing inormal ireference iranges iare irecommended: i1st itrimester i– i0.1 ito i2.5 im iIU/L, i2nd itrimester i– i0.2 ito i3.0 im iIU/L iand i3rd itrimester i– i0.3 ito i3.0 im iIU/L. iThe inormal ifree iT4 ilevel iis i0.7 ito1.8 ing/ml. iDepending ion ithe ihormonal ivalues, ipatients iwill ibe iclassified iinto i
38
1. Gestational iSubclinical ihypothyroidism: iHigh iserum iTSH ilevel iwith inormal ifT4 ilevel.
2. Gestational i ihypothyroidism: iHigh iserum iTSH ilevel iwith ifT4 iless ithan ithe inormal irange,
3. Gestational iSubclinical ihyperthyroidism: iLow iserum iTSH ilevel iwith inormal i ifT4 ilevel, i i
4. Gestational i ihyperthyroidism: iLow iserum iTSH ilevel iwith i ifT4 imore ithan ithe inormal irange.
i i
Subclinical/ iovert ihypothyroid icases iwill ibe itreated iwith iThyroxine.
iSubclinical/overt ihyperthyroid icases iwill ibe itreated iwith iPropylthoiuracyl.
iEvery i4 iweeks, iTSH ilevel iwill ibe iestimated iand ithe idose iof ithe idrug iadjusted. iThe ioutcome iof ithe ipregnancy iwill ibe ifollowed iup iand idocumented.
i iThe ifollowing ioutcome ivariables iof ithe ipregnancy iin irelation ito ithe ithyroid idisorders iwill ibe istudied: iMode iof iDelivery,Preeclampsia, iAbruptio iplacenta, iPreterm idelivery, iIUGR, iLow ibirth iweight, iStillbirth, iAbortion. i iThe iTSH iand ifT4 ilevels iwill ibe iestimated iat i6 iweeks ipostpartum iand ichecked ifor iprogression ito iovert iThyroid iDisorder.
39
STATISTICAL ANALYSIS:
The collected data will be entered in MS excel, values entered will be checked for inconsistency.
The data will be analyzed using SPSS software. Mean, Standard Deviation and
frequency will be calculated, the chi-square test will be used as a test of significance.
A p-value of < 0.05 will be considered statistically significant
40
RESULTS
TABLE: 1 AGE GROUP
AGE GROUP FREQUENCY PERCENT
18 - 21 Years 17 17.0
22 - 24 Years 33 33.0
25 - 27 Years 24 24.0
28 - 30 Years 20 20.0
Above 30 Years 6 6.0
Total 100 100.0
GRAPH: 1 AGE GROUP
17%
24% 33%
20%
6%
AGE
18 - 21 Years 22 - 24 Years 25 - 27 Years 28 - 30 Years Above 30 Years
41
Table: 1 & Graph 1 shows Totally 100 pregnant women were included in study. 18 - 21 Years were 17 patients 22 - 24 Years were33 patients 25 - 27 Years were
24patients 28 - 30 Years were 20 patients Above 30 Years were 6patients
TABLE: 2 PARITY
PARITY Frequency Percent
1.00 46 46.0
2.00 41 41.0
3.00 13 13.0
Total 100 100.0
42
GRAPH: 2 PARITY
TABLE: 2 & GRAPH 2 shows the parity 1 in 46 cases, 2 in 41 cases, 3 is 13
46%
41%
13%
Parity
1 2 3
43
TABLE :3 THYROID DYSFUNCTION
THYROID DYSFUNCTION
FREQUENCY PERCENT
Subclinical Hypothyroidism 67 67.0
Subclinical Hyperthyroidism
10 10.0
Overt Hypothyroidism 17 17.0
Overt Hyperthyroidism 6 6.0
Total 100 100.0
Table :3 & Graph 3Among 100 case Subclinical Hypothyroidism was 67 cases,Subclinical Hyperthyroidism10 cases, Overt Hypothyroidismseen in 17 cases,Overt Hyperthyroidism was seen in 6 cases
44
GRAPH :3 THYROID DYSFUNCTION
TABLE: 4 MATERNAL COMPLICATION MATERNAL
COMPLICATIONS
FREQUENCY PERCENT
Nil 94 94.0
Preeclampsia 6 6.0
Total 100 100.0
67%
10%
17%
6%
THYROID DYSFUNCTION
Subclinical Hypothyroidism Subclinical Hyperthyroidism Overt Hypothyroidism Overt Hyperthyroidism
45
GRAPH: 4 MATERNAL COMPLICATIONS
Table: 4 & Graph 4 No complications and emergency let outs was observed in maximum patients which were 96%, pre-eclampsia seen in 6 cases
TABLE: 5 DELIVERY OUTCOME
DELIVERYOUTCOME Frequency Percent
Term Delivery 93 93.0
Preterm delivery 1 1.0
Spontaneous abortion 5 5.0
Stillbirth 1 1.0
Total 07 100.0
Term delivery was seen in 93 patients, preterm delivery is seen in only 1 case, spontaneous abortion in 5 cases, stillbirth in 1 case.
94%
6%
MATERNAL COMPLICATIONS
Nil
Pre eclampsia
46
GRAPH: 5 DELIVERY OUTCOME
TABLE: 6 MODE OF DELIVERY
MODEOFDELIVERY Frequency Percent
LSCS 23 24.0
NVD 71 76.0
Total 94 100.0
In 100 cases,LSCS was seen in 23 cases, NVD in 71 cases
93%
1%
5%
1%
DELIVERY OUTCOME
Term Delivery Preterm delivery Spontaneous abortion Still birth
47
GRAPH: 6 MODE OF DELIVERY
TABLE: 7 PRESENCE OF CONGENITAL ANOMALIES
ANYCONGENITALANOMALIES Frequency Percent
No 99 99.0
Yes ( Cleft lip) 1 1.0
Total 100 100.0
Table: 7 & Graph: 7 In 100 cases, only 1 case had, cleft lip,99 cases dnt show clinically any congenital anomalies
24%
76%
MODE OF DELIVERY
LSCS NVD
48 99%
1%
ANY CONGENITAL ANOMALIES
No
Yes ( Cleft lip)
GRAPH :7 PRESENCE OF CONGENTIAL ANOMALIES
TABLE: 8 TYPES OF THYROID OVER PERIOD
TYPEOFTHYROIDDISORDERINPNPERIOD Frequency Percent
Hyperthyroidism 1 1.0
Hypothyroidism 7 7.0
Nil 92 92.0
Total 100 100.0
GRAPH: 8 TYPES OF THYROID OVER PERIOD
49
Table: 8 & graph: 8 shows In 100 cases, hyperthyroidism was seen in 1 case, 7 had hypothyroidism. 92 cases had normal thyroid function.
1%
7%
92%
TYPE OF THYROID DISODER IN PN PERIOD
Hyperthyroidism Hypothyroidism Nil
50
Overt Subclinical
Entyroid 0
25(2.5%)
6 (0.6%) 200
400 600 800
69 (6.9%) 1000
1200
CLASSIFICATION
TABLE: 9 CLASSIFICATION
CLASSIFICATION Frequency
Euthyroid 69 (6.9)
Subclinical hypothyroid 25 (2.5%)
Overt hypothyroid 6 (0.6%)
Total 100
TABLE: 9 CLASSIFICATION
Table 9 & graph 9 shows the prevalence of hypothyroidism in my study group that is 3.1%
of the totally screened patients 2.5% of them are subclinically hypothyroid, 0.6% of them are overt hypothyroid. Chi sq. & p-value 0.0001 which is significant
51
TABLE: 10 SHOWS MODE OF DELIVERY IN CORRELATION WITH PROGRESSED TO OVERT THYROID DISORDER
PROGRESSEDTOOVERTTHY ROIDDISORDER
Total
No Yes
MODEOFDELIVERY LSCS Count 23 0 23
% 26.4% 0.0% 24.5%
NVD Count 64 7 71
% 73.6% 100.0% 75.5%
Total Count 87 7 94
% 100.0% 100.0% 100.0%
In LSCS group 23 had which is 26.4%.progressed to overt thyroid disorder pearson chi-square=2.450 p=0.118 of p-value which is statistically significant.
52
TABLE: 10 SHOWS BIRTH IN CORRELATION WITH PROGRESSED TO OVERT THYROID DISORDER
PROGRESSEDTOOVERTTHYROIDDI SORDER
Total
No Yes
Birthweightgr oup
<2.5 Kg
Cou nt
52 0 52
% 59.8% 0.0% 55.3
%
>=
2.5K.
G
Cou nt
35 7 42
% 40.2% 100.0% 44.7
%
Total Cou
nt
87 7 94
% 100.0% 100.0% 100.0
%
53
Birth weight <2,5 kg 52 had progressed to an overt thyroid disorder. > 2.5 kg 87had progressed to overt thyroid disorder absent in 7 members.Birth weight >= to 2.5 35 had overt thyroid disorder, absent in 7 members.Pearson Chi-Square=9.364**
p=0.002
54
GRAPH: 10 SHOWS BIRTH IN CORRELATION WITH PROGRESSED TO OVERT THYROID DISORDER
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
No Yes
60%
0%
40%
100% >=2.5 K.G
<2.5 K.g
55
TABLE: 11 SHOWS CONGENITAL ANOMALIES CORRELATION WITH PROGRESSED TO OVERT THYROID DISORDER
PROGRESSEDTOOVERTTHYROI DDISORDER
Total
No Yes
ANYCONGENIT ALANOMALIES
No Count 86 7 93
% 98.9% 100.0% 98.9%
Yes Count 1 0 1
% 1.1% 0.0% 1.1%
Total Count 87 7 94
% 100.0% 100.0% 100.0
%
Table: 11 shows 86 cases have absent of progressed to overt thyroid disorder, 7 had progressed to overt thyroid disorder . In congenital anomalies group. Non had significance progressed to overt thyroid disorder of Pearson Chi-Square=0.081 p=0.776
56
TABLE: 12 SHOWS AGE CORRELATION WITH PROGRESSED TO OVERT THYROID DISORDER
PROGRESSEDTOOVERTTH YROIDDISORDER
Total
No Yes
Age Group
18 - 21 Years Count 16 1 17
% 17.4% 12.5% 17.0%
22 - 24 Years Count 33 0 33
% 35.9% 0.0% 33.0%
25 - 27 Years Count 17 7 24
% 18.5% 87.5% 24.0%
28 - 30 Years Count 20 0 20
% 21.7% 0.0% 20.0%
Above 30 Years Count 6 0 6
% 6.5% 0.0% 6.0%
Total Count 92 8 100
% 100.0% 100.0% 100.0%
57
TABLE: 12 SHOWS AGE CORRELATION WITH PROGRESSED TO OVERT THYROID DISORDER
Table: 12 & graph: 12 shows Totally 100 pregnant women were included in study. 18 - 21 Years were 17 patients 16 doesn’t have progressed to overt thyroid disorder , 1 had incidence of progressed to overt thyroid disorder 22 - 24 Years were33 patientsprogressed to overt thyroid disorder 25 - 27 Years were 24, 17progressed to overt thyroid disorder, 7 doesn’t have progressed to overt thyroid disorder had patients 28 - 30 Years were 20 patients had progressed to overt thyroid disorder patients Above 30 Years were 6patients had progressed to overt thyroid disorder Pearson Chi-Square=19.844** p=0.001
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
No Yes
17% 12%
36%
0%
18%
88%
22%
0%
7%
0%
18 - 21 Years 22 - 24 Years 25 - 27 Years 28 - 30 Years Above 30 Years
58
TABLE: 13 SHOWS PARITY CORRELATION WITH PROGRESSED TO OVERT THYROID DISORDER
PROGRESSEDTOOVERTTHYROI DDISORDER
Total
No Yes
PARITY 1.00 Count 46 0 46
% 50.0% 0.0% 46.0%
2.00 Count 33 8 41
% 35.9% 100.0% 41.0%
3.00 Count 13 0 13
% 14.1% 0.0% 13.0%
Total Count 92 8 100
% 100.0% 100.0% 100.0%
GRAPH 13 & TABLE 13 Parity 1 is 46 had casesprogressed to overt thyroid disorder, 2 is 41, 33 had progressed to overt thyroid disorder cases, 8 hadprogressed to overt thyroid disorder 3 is 13 had progressed to overt thyroid disorder Pearson Chi- Square=12.513** p=0.002
