INTRODUCTIONCongenital hypothyroidism is a condition in which aneonate is born with insufficient production of thethyroid hormone . In such children, hypothyroidismwill be absent in-utero and at birth because ofplacental transfer of maternal thyroid hormones tothe foetus, if the mother is euthyroid . Conversely,if the mother has hypothyroidism, such neonateswould have experienced hypothyroidism in-uteroand will be born with features of hypothyroidism .This is the case in endemic cretinism where theunderlying pathology is dietary Iodine deficiency inboth mother and foetus. Iodine is necessary for theproduction of thyroid hormones across all ages.Other aetiological factors for congenitalhypothyroidism are:

- Sporadic thyroid dysgenesis (accounts for85% of cases of congenital hypothyroidismin areas without endemic Iodinedeficiency ).

- Enzymatic defects in thyroid hormonessynthesis (5 different enzymes have beenidentified) .

- Thyrotropin unresponsiveness- Hypothalamo-pituitary disease .- Trans-placental transfer of anti-thyroid

drugs or auto antibodies .- Suppression of foetal hypothalamo-

pituitory-thyroidal axis by trans-placentaltransfer of excess thyroid hormones from athyrotoxic mother .

- Some genetic disorders .Congenital Hypothyroidism (CH) affects 1:4000newborns worldwide . In areas with severe endemicIodine (I ) deficiency e.g. Northern India, theincidence of CH is 75-115 per 1000 live births;whilst in Delhi, Southern India, an area with onlymild I deficiency, the incidence of CH is 6 per 1000

live births . In Zaire, Africa, an area with severeendemic I deficiency, CH occurs in 10% of allneonates, giving an incidence of 100 per 1000livebirths . Conversely, in Pretoria, SouthAfrica, anarea without endemic I deficiency, the incidence ofCH is approximately 1 per 4000 live births .Wereport a case of congenital hypothyroidism in order

1

2,3,4

5,6,7,8

1,9,10

1,9

9

1,9,11

1,9,12

13

14

15

16

16

17

2

2

2

2

Correspondences: DrT A AdesanmiE mail:adetiti26@yahoo.com

to raise the physician's index of suspicion andfacilitate early diagnosis. Diagnosis andcommencement of treatment of CH before 3 monthsof age are essential if such infants are to attain optimalintellectual development .

O.C. is a 4-month-old Nigerian male who presentedwith constipation since birth, slowly progressiveincrease in tongue size since birth, jaundice noticedon second day of life (DOL) and lasted 16 days;progressive noisy breathing of 3½ months durationand feeding difficulties of 2½ months duration.Pregnancy and delivery were uneventful. Birthweight was 2.8kg. Mother, a 34-year-old Igbo womanwho has been residing in Enugu, Nigeria for the past10 years, is a trained nurse and is apparently normal.He was admitted into the NBSCU in 2nd DOL andtreated for NNJ 2 NNS. His progress notes whilst onadmission in the NBSCU were carefully reviewed.No Exchange blood transfusion was done. Jaundicecleared by 16 DOL. No biochemical or clinicalscreening for hypothyroidism was done. Onexamination, he had remarkable macroglossia andwas small for age. His weight was 3.5kg (58%Expected weight for age); OFC was 38cm (lowerlimit of normal for age is 40cm); full length was51cm. Skin was dry and coarse. Breathing was noisy,though dyspnoea and tachypnoea were absent. Hehad a reducible umbilical hernia of 3cm in diameter;bowel sounds were slightly reduced in pitch. He hadnormal male external genitalia with both testes withinthe scrotum. He had reducible bilateral inguino-scrotal hernia (left greater than right); a widenedanterior fontanelle (5cm x 6.5cm), a widenedposterior fontanelle (2cm x 2cm); global hypotoniaand no head control.Thyroid function tests showedmarkedly elevated TSH (Thyroid StimulatingHormone), very low free T (thyroxin) andundetectable free T . This confirmed the diagnosis ofcongenital hypothyroidism. X-rays of the limbs werenot done. Thyroid scan was requested but not done.Results of other investigations are as shown in tableI.He was commenced on Levo-thyroxin 10ug/kg/dayfor life. The starting dose was 10ug/kg/day. This dosewas adjusted as patient gained weight and increasedin age. A review 3 weeks after commencing L-thyroxin showed progressive remarkableimprovement in all clinical parameters. Clinicalphotographs before treatment (figures I & II) and sixweeks after commencement of thyroxin (figures III &IV) are shown.

1,9

o

th

CASE REPORT

4

3

208

Nigerian Journal of Clinical PracticeJune 2009 Vol 12(2):208-211

CONGENITAL HYPOTHYROIDISM - A DELAYED DIAGNOSIS IN ANEONATE. A CASE REPORT

*TA Adesanmi, **GNAdimora, **BN TagboDepartment of Paediatrics,*Emel Hospitals, Festac Town Lagos, **University of Nigeria Teaching

Hospital, Enugu, Nigeria.

-

Table I:

Figure I:

Laboratory Results

Photograph of Patient Showing TypicalFascies of Hypothyroidism on Presentation.

Figure 2: Same Patient Showing ProtuberantAbdomen, Umbilical Hernia and Left Inguino-Scrotal Hernia.

Figure: 3

Figure 4

Same Patient Showing MarkedImprovement after 6 Weeks of Thyroxin Therapy.

: Same Patient Showing Regression ofUmbilical Hernia with Thyroxin Therapy.

DISCUSSIONThis case clearly demonstrates delayed diagnosis ofcongenital Hypothyroidism (CH) despite earlypresentation to Paediatricians in a tertiary healthinstitution. Baby O.C. was born in our hospital,presented at the NBSCU on the 2 day of life withjaundice, and also presented a number of times at thenewborn outpatient clinic as the other symptomsevolved, yet the possibility of CH was not considered,until the macroglossia became quite obvious. It isclear therefore, that the absence of a 'typical facies' orgross macroglossia or remarkable global hypotonia orcoarse skin and cry at birth or within the first week oflife contributed to this delayed diagnosis. So did thePhysician's low index of suspicion as the othersymptoms evolved. Unachak et al ,in Thailand,in their review of 48 cases of CH seen over a 13 yearperiod found that when CH was diagnosed within thefirst 3 months of life, the commonest symptoms wereneonatal jaundice (NNJ) lasting 14 days (100%),constipation (85%); typical facies of hypothyroidism

nd

15

>

209Nigerian Journal of Clinical Practice June 2009, Vol.12(2) Congenital Hypothyroidism Adesanmi et al

210

(62.5%), feeding problems (46%). They alsoDocumented delayed diagnosis as follows: 62.5%were diagnosed after 1 year of age, 10.5% between 3months and 1 year of age and 27% were diagnosedbetween 1 month to 3 months of life.Maternalthyroid status also contributes to delayed diagnosisof congenital hypothyroidism. This is because trans-placental transfer of maternal thyroid hormones tothe foetus, as demonstrated by Contempre` B et aland Vulsma et al , supplies the thyroid hormonerequirements of the growing foetus. Thyroxin iscritical for many aspects of brain development e.g.neurogenesis, neuronal migration, axon anddendrites formation, myelination, synaptogenesisand neurotransmitter regulation . Theserequirements evolve over months and are mostcritical in the 2 trimester . Thyroxin (T )production in the foetus starts at about 12 weeksGestational Age (GA), but only reaches significantlevels at about 24 weeks GA. However, maternal Tstill continues to supply part of foetal T requirementtill birth. Up to 30% of T in cord blood is of maternal

origin . Where these fetal thyroxin requirements arenot met, clinical features of hypothyroidism will bepresent in the neonate at birth. But where maternalthyroid hormones have compensated for the foetus'intrinsic thyroxin production deficiency, clinicalfeatures of hypothyroidism will be absent at birth andthe infant will remain apparently normal for variableperiods thereafter or become only mildlysymptomatic sometime during infancy.This may explain why our patient appeared normal atbirth, and the highly suggestive macroglossia andmarked global hypotonia slowly evolved over aperiod of 4 months. Our patient's mother seemedeuthyroid and his 2 year old sister was quite normal.Where maternal hypothyroidism is not due to dietaryI deficiency or thyroid antibodies (TAB), both ofwhich also affect the foetus, fetal thyroid hormoneproduction may be normal and the effects ofintrauterine thyroxin deficiency will be mild .Neonatal screening programmes (TSH assay duringthe 1 week of life) have been successfully used indeveloped countries over the past three decades tofacilitate early diagnosis of CH. Twenty percent ofcases of CH may have normal TSH within the firstweek of life, but serial monitoring will reveal aprogressive increase. This screening is however stilltoo expensive to be carried out routinely in ourenvironment. In resource poor countries, a clinicalscreening method called Neonatal HypothyroidIndex (NHI) has been proposed . A score of > 3/13selects children in whom TSH and T4 must beassayed. It is however unclear whether this NHI isapplicable to preterms. The optimal post-natal age atwhich this clinical screening should be done is also

3

4

1 5

nd 15

4,9

15

st

1

4

4

4

4

2

Unclear.At 4 months of age our patient O.C. who wasa term baby scored 9/13 but at the 2nd day of lifescored 2.5/13 and 3.5/13 at one week of life if bowelmovement once a day is taken as constipation in aneonate being fed with breast milk and infantformula. Constipation as an indicator in this NHIneeds to be clearly defined with respect to patient'sgestational age at birth and diet. There is also quite awide range of “normal bowel habit” in neonates, thedefinition often referring to what is normal for theindividual patient. NHI is an adaptable andsustainable health technology in developingcountries. It is suggested therefore that a modifiedNHI be evolved and correctly used to screen allNigerian newborns as soon after birth as possible tofaci l i ta te ear ly diagnosis of congenitalhypothyroidism. The government, NGO's and othercharitable organisations can also fund routinescreening of all neonates in some specialised centres.

REFERENCES1. Azubuike, JC.

2. De Escobar GM, Obregon J, Escobar delRey.

3. Contempre` B, Jaunlaux E, Calvi R,Jurkovic D, Campbell S, Escobar GM.

4. Vulsma T, Gons MH, De Vijilder JJ.

5. Mann EB, Brown JF, Serumian, SA

6. Pop VJ, kujpens JL, VanBaar AL et al.

Endocrine and metabolicd isorders . In : J .C. Azubuike, K.E.ONkangineme (eds). Paediatrics and Child healthin a tropical region. Owerri, Nigeria. Africaneducational services 1999: 456-473.

Is neuropsychological developmentrelated to maternal hypothyroxinaemia?Journal of Clinical Endocrinology andMetabolism. 2000; 85: 3975-87.

Detection of thyroid hormone in humanembryonic cavities during the 1st trimester ofpregnancy. Journal of Clinical Endocrinologyand Metabolism 1993; 77: 1719-22.

Maternalt ransfer of thyroxin in Congeni ta lHypothyroidism due to a total organificationdefect or thyroid dysgenesis. New England,Journal of Medicine, 1989; 321: 13-16.

. Maternalhypothyroxinaemia: Psycho-neurologicaldeficits of progeny. Annals of ClinicalLaboratory Science. 1991; 21: 227-339.

Lowmaternal free thyroxin concentration in earlypregnancy are associated with impairedpsychomotor development in infancy. Clinicalendocrinology 1999; 50: 149-155.

Nigerian Journal of Clinical Practice June 2009, Vol.12(2) Congenital Hypothyroidism Adesanmi et al

Nigerian Journal of Clinical Practice June 2009, Vol.12(2) Congenital Hypothyroidism Adesanmi et al 211

7. Hadden JE, Palomaki GE, Allan WC, et a

8. Smith BJ, Kok JH, Vulsma T, Brist JM,Boer K, Wierringa WM.

9. DiGeorge AM, LaFranchi S.

10. Grasberger H, Ringkananout U, CroxsonM, Refetoff S.

11. Redaideh AM, Nusier M, El-Akawi Z,Jaradat D.

lMaternal thyroid deficiency duringp r e g n a n c y a n d s u b s e q u e n tneuropsychological development of thechild. New England Journal of Medicine.1999; 341: 549-55.

Neurologicdevelopment of the newborn and young childin relation to maternal thyroid function. ActaPaediatrica 2000; 39: 291-5.

Disorders ofthe Thyroid Gland. In: Nelson W.E, BehrmanR.E, Kliegman R.M, Arvin A.M. (eds)Nelson Textbook of Paediatrics 15th edition.1996;1587-99.

Resistance to thyroidhormone in a patient with thyroiddysgenesis. Thyroid 2005; 15 (7): 730-3.

Precocious puberty withcongeni tal hypothyroidism. NeuroEndocrinology Letter 2005; 26 (3):253-6.

12. La Franchi S.

13. Kempers MJ, Van Tijn DA, VanTrotsenburg AS, Vijilder JJ, Wiedijle BM,Vulsma T.

14. Morend JC, Bikker H, Kempes MJE,Trotsenburg PV, Baas F, De-Vijlder JJM,Vulsma T, Ris-Stalpers C

15. S mal l r id ge R C , L a de ns on PW

17. Bernstein RE, Opt HJ, Hitzeroth W.

Congenital hypothyroidism:etiologies, diagnosis and managementThyroid, 1999; 9: 735-40.

Central hypothyroidism occurs ininfants of mothers with hyperthyroidism dueto Graves disease during their pregnancies.Clinical thyroidology 2004; 16 (1): 10.

. Inactivatingmutations in the gene for thyroid oxidase 2(THOX2) and congenital hypothyroidism.New England Journal of Medicine 2002; 347(2): 95-102.

.H y p o t h y r o i d i s m i n P r e g n a n c y :Consequences to neonatal health. Journal ofClinical Endocrinology and Metabolism.2001; 86 (6): 234-53.

diseases.

Neonatal screening for CongenitalHypothyroidism:Adecade review, includingSouth Africa. South African MedicalJournal. 1988; 73 (6): 339-43.

16. Delange FH, Hetzel B. The thyroid and itshttp://www.thyroidmanager.org/th

yr oidbook.htm 2004.