County Clinical Emergency Hospital, Arad, Romania,,Vasile Goldis,, Western University of Arad 1 S zeged, 13 december, 2011 CONGENITAL HYPOTHYROIDISM EARLY DIAGNOSED AND TREATED WITHOUT NEWBORN SCREENING PROGRAM Authors: D. Teodorescu MD, Ph.D Assistant Professor D. Burdan MD, PhD, A. Filimon, MD, PhD

The purpose of the presentation The aim of this presentation is to show you a newborn case report with congenital hypothyroidism; in a nonendemic area diagnosticated and treated early without a newborn screening program. 2

M ATERIAL. M ETHOD We present a female newborn case report, 3 weeks old, born in a nonendemic area and diagnosticated with classic hypothyroidism. 3 S.C., female, date of bird , 3400g birth weight, 39 weeks gestational age, who lives in Arad.

H ISTORY Mother- S.M., -32 years old, first level of schooling, - BIII blood group, negative Rh.( without isoimunisation ). - antenatal obesity. She hasn't received any antityroidian treatment and she has never been investigated for any endocrine pathology. Father- S.C., 29 years old, healthy Pregnancy evolution:- GI PI, followed-up by obstetrician, - high obstetrical risk, pre- eclampsia(180/120mmHg).. She has won 25 kilos in body weight. She delivered her baby by C-section, in cranial presentation. The placenta had a normal aspect. 4

T HE NEWBORN The newborn cames from high obstetrical risk pregnancy, Apgar score 8 at 1 and 5 minutes after birth. The newborn was placed into the rooming-in system. 5 On the fourth day of life the neonatal jaundice was intensified, intermittent phototerapy beeing required. The newborn was discharged from the hospital on the fifth day of life, with the regression of the jaundice, breast-fed. Birth was by C-section in cranial presentation

E VOLUTION On the twelfth day of life the newborn was readmitted to the hospital for prolonged neonatal jaundice and a cutaneous infection with Staphylococcus. The clinical examination Pointed out the presence of : -muco-cutaneous jaundice (Kramer 4), -characteristic facial features with macroglossia, - hoarse-sounding cry, - an anormally large distance between the nipples, - protuberant abdomen, - decreased activity and abnormally low muscle tone 6

o The symptomatology was sugestive: - particular face (with half-open mouth, macroglossia) o - prolonged jaundice o - umbilical hernia o - abnormal cry o - hypoton syndrome 7

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P ARACLINICAL INVESTIGATIONS Hb 20,11g% FL (N61%, L28%, M3%, Eo 5%, b 0%) PLT /mm³ C reactive protein – negative Umbilical secretion- Staphylococcus aureus Bilirubin T 11,2mg%, D 2,12 mg%, I 9mg% Calcium 1,24 mmnol/L Glucose 66 mg% TEOAE auditiv test – refer bilateral Abdominal ultrasound - normal finding, without modifications Cranial ultrasound –cvasinormal cerebral finding 9

P ARACLINICAL INVESTIGATIONS TSH- basal thyroid-stimulating hormone - 464,6300µU/ml (0,49-4,67), controlled result in two separate series FT3 Free triiodothyronine – 0,01 pg/ml (normal value 1,45-3,48 pg/Ml) FT4 Free serum thyroxine - 0,18 ng/dl ( 0,71-1,85) - 2,3 pmol/L (9,13- 23,80) (AXSYM analyser,ABBOT reactiv, MEIA method) 10

P OSITIVE DIAGNOSIS Based on the history, clinical examination, and paraclinical investigation there was established the positive diagnosis: 1.Congenital hypothyroidism (congenital myxoedema TSH = 464,630µU/ml.) 2.Cutaneous infection with Staphylococcus aureus 3.Three weeks old newborn. 11

T REATMENT The replacement treatment was early introduced at the moment of the diagnosis, at three weeks of age, in colaboration with the endocrinologist consultant. After the endocrinological consultation, the treatment is Euthyrox LT mg/kg,Euthyrox 100mg tablets- ½ tb per day,mornings, along six weeks. At the discharge of the pacient from the hospital, we recommand endocrinological follow- up. 12

T REATMENT The disease outcome-is favourable under the instituated treatment.The newborn was discharged from the hospital after eight days with the recomandation of endocrinological and laboratory follow-up. The investigations continued in the Timisoara Children Hospital. They found an associated congenital heart disease (patent foramen ovale), 13

BACKGROUND Congenital Hypothyroidism No standardized case definition Defined as inadequate thyroid hormone production Usually characterized by increased thyroid stimulating hormone (TSH) concentration and decreased thyroxin (T4) concentration. Insufficient thyroid hormone impacts brain development; specifically myelination and neuronal connections are impacted o Congenital untreated hypothyroidism is a cause of severe cerebral injury. The incidence of the disease is 1 : newborn. 14

Hypotalamic pituitary-thyroid axis T4 is stimulated by secretion of TSH by the pituitary. Low T4 (negative feedback) causes hypothalamus to secrete thyrotropin releasing hormone (TRH) which stimulates release of TSH thereby stimulating the thyroid gland to increase secretion of T4. When the thyroid does not respond to TSH stimulation (primary CH), due to dysgenesis or dyshormonogenesis, the result is low T4 and high TSH. 15 szeged, 13 december, 2011

Etiology of HC Dysgenesis (thyroid gland developmental defect) Dyshormongenesis (defects in thyroid hormone synthesis) Mutations in thyroid development genes or TSH receptor Defects in hypothalamus or pituitary (central or secondary/tertiary hypothyroidism) ~ rare (1/25,000 – 1/100,000) Iodine deficiency 16

After its evolution, the primary hypothyroidism in newborns is permanent or transient. The primary permanent hypothyroidism includes the anteriorly mentioned dysgenetic or dyshormonogenetic hypothyroidism. Without an adequate treatment at children with HC, growth retardation may develope, which becomes evident at 3-6 months, accompanied by neuro- psychiatryc development disorders and some neurological disabilities. HC can be accompanied by other cardiovascular abnormalities (pulmonary stenosis, atrial and ventricular septal defect) 17 o Some of the congenital hypothyroidism cases have genetic origin. The genetical aspect is polymorf.Some modifications are autosomal recessive inherited

C ONCLUSIONS The case is suggestive for a classic congenital hypothyroidism, early diagnosed, without a newborn screening program. The prognosis of the intellectual was good. The substitutive treatment was early administrated, after the diagnosis was established, at three weeks postnatal age. It is highlighted the importance of the extension of the screening in the whole the country. 18

19 Purpose of Newborn Screening Program to screen for congenital and inherited disorders These disorders may cause severe mental retardation, illness or death if not treated early in life If treated, infants may live relatively normal lifes Results in medical cost savings over time

20 CH Untreated Could cause disorders in:  Growth problems  Developmental delays  Behavioral/emotional problems  Deafness or blindness  Retardation  Seizures  Coma, sometimes leading to death

21 NBS Screening Identification is a multi-step process  Blood specimens from infants are analyzed by the laboratory  If a result is abnormal, laboratory staff notifies case management staff  Case management provides follow-up to assist linking families with appropriate providers to o Confirm the test results and o Ensure the infant has the disorder prior to treatment o Ensure the infant receives appropriate treatment

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