Acta Paediatr 81: 274-6. 1992
CASE REPORT
Thyroid dyshormonogenesis: severe hypothyroidism after normal neonatal thyroid stimulating hormone screening F de Zegherl, M Vanderschueren-Lodeweyckxl, C Heinrichs2, G Van Vliet* and P Malvaux3 Departments of Pediatrics. Universitiesof Leuven‘, Brusselg and Louvain’. Belgium
de Zegher F, Vanderschueren-Lodeweyckx M, Heinrichs C, Van Vliet G, Malvaux P. Thyroid dyshormonogenesis: severe hypothyroidism after normal neonatal thyroid stimulating hormone screening. Acta Prediatr 1992;81 :274-6. Stockholm. ISSN 0803-5253 We report four children who presented no evidence of primary hypothyroidismin the neonatal period, either clinically (normal growth velocity) or biochemically (normal plasma levels of thyroid stimulating hormone and/or thyroid hormone). However, in early childhood, these childrendeveloped severe hypothyroidism due to dyshormonogenesis. We conclude that apparently normal thyroid function in the neonatal period does not preclude the development of severe hypothyroidism due to thyroid dyshormonogenesis later in childhood. 0 Hypothyroidism, infancy. thyroid stimulating hormone
F de Zegher, Department of Pediatrics, University Hospital Gasthuisberg, 3000 Leuven, Belgium
Neonatal thyroid stimulating hormone (TSH) screening programs are remarkably successful in diagnosing congenital hypothyroidism. As a consequence, the exposure of physicians to signs and symptoms of hypothyroidism has decreased considerably. However, physicians should be aware that, in spite of the screening, cases of hypothyroidism will continue to present. Nowadays, young children with hypothyroidism can be classified into two groups: those with congenital hypothyroidism missed by the neonatal screening (false negatives) and those developing hypothyroidism after the neonatal screening (acquired hypothyroidism). The former group includes mainly infants missed due to: human errors (e.g. sample collection, laboratory assay and reporting, physician follow-up); gaps inherent to the screening method (e.g. hypothyroidism of pituitary origin is not detected by TSH screening); and at present unexplained biological causes (e.g. primary hypothyroidism with late TSH rise) ( I , 2). The group with acquired hypothyroidism appears to consist mainly of children with a hypoplastic thyroid gland “decompensating” later in infancy (1-3) and of a few athyroid infants of monochorionic twin pairs, receiving euthyroid blood from the unaffected twin until birth (4, 5 , 6). In this report, we establish thyroid dyshormonogenesis as a third cause of severe hypothyroidism after normal neonatal TSH screening.
Case reports Salient clinical and biochemical data obtained in the neonatal period and at diagnosis are summarized in Table 1. The dietary history of the four children was considered to exclude iodine deficiency.
Case 1 This 12-week-old male infant was referred because of increasing feeding difficulties and a growth decline since the age of six weeks. He was the second child of healthy, unrelated Belgian parents. The maternal grandmother and two maternal aunts were undergoing treatment for a goiter. Neonatal thyroid function screening had been normal (Table 1). Clinical examination revealed discrete signs suggestive of hypothyroidism and a palpable thyroid gland of normal size. After demonstration of severe primary hypothyroidism, presumably due to thyroid dyshormonogenesis (Table I), thyroid hormone replacement therapy was initiated. At the age of six months the infant is thriving.
Case 2 Complaints of lethargy, pallor, abdominal distension and growth arrest prompted referral of this boy at the age of three years. He was the first child of healthy, unrelated, tall Belgian parents. There was no family history of thyroid disease or hearing difficulties. Neonatal TSH screening had been normal. Developmental milestones had been reached in time until the age of one year and had been delayed ever since. Similarly, growth had been normal for parental height until aged one year and had declined thereafter (Fig. I). There were obvious signs of hypothyroidism. Furthermore, clinical examination revealed a homogeneously enlarged thyroid gland and also slightly enlarged testes (volume 4 ml). Psychomotor development was estimated to be delayed by approximately six months. A skull radiograph showed an enlarged sella turcica. After demonstration of severe
275
Dyshormonogenesis after normal TSH screening
ACTA PlEDlATR 81 (1992)
Table 1. Salient data obtained in four children at neonatal thyroid screening and at diagnosis of primary hypothyroidism.
Case 1 Neonatal screening Clinical hypothyroidism Day of screening TSH (mU/I; Nla < 20) T4 (nmol/l; NI 105-220) T3 (nmol/l; NI 1.6-3.7)
5
CASE REPORT
Thyroid dyshormonogenesis: severe hypothyroidism after normal neonatal thyroid stimulating hormone screening F de Zegherl, M Vanderschueren-Lodeweyckxl, C Heinrichs2, G Van Vliet* and P Malvaux3 Departments of Pediatrics. Universitiesof Leuven‘, Brusselg and Louvain’. Belgium
de Zegher F, Vanderschueren-Lodeweyckx M, Heinrichs C, Van Vliet G, Malvaux P. Thyroid dyshormonogenesis: severe hypothyroidism after normal neonatal thyroid stimulating hormone screening. Acta Prediatr 1992;81 :274-6. Stockholm. ISSN 0803-5253 We report four children who presented no evidence of primary hypothyroidismin the neonatal period, either clinically (normal growth velocity) or biochemically (normal plasma levels of thyroid stimulating hormone and/or thyroid hormone). However, in early childhood, these childrendeveloped severe hypothyroidism due to dyshormonogenesis. We conclude that apparently normal thyroid function in the neonatal period does not preclude the development of severe hypothyroidism due to thyroid dyshormonogenesis later in childhood. 0 Hypothyroidism, infancy. thyroid stimulating hormone
F de Zegher, Department of Pediatrics, University Hospital Gasthuisberg, 3000 Leuven, Belgium
Neonatal thyroid stimulating hormone (TSH) screening programs are remarkably successful in diagnosing congenital hypothyroidism. As a consequence, the exposure of physicians to signs and symptoms of hypothyroidism has decreased considerably. However, physicians should be aware that, in spite of the screening, cases of hypothyroidism will continue to present. Nowadays, young children with hypothyroidism can be classified into two groups: those with congenital hypothyroidism missed by the neonatal screening (false negatives) and those developing hypothyroidism after the neonatal screening (acquired hypothyroidism). The former group includes mainly infants missed due to: human errors (e.g. sample collection, laboratory assay and reporting, physician follow-up); gaps inherent to the screening method (e.g. hypothyroidism of pituitary origin is not detected by TSH screening); and at present unexplained biological causes (e.g. primary hypothyroidism with late TSH rise) ( I , 2). The group with acquired hypothyroidism appears to consist mainly of children with a hypoplastic thyroid gland “decompensating” later in infancy (1-3) and of a few athyroid infants of monochorionic twin pairs, receiving euthyroid blood from the unaffected twin until birth (4, 5 , 6). In this report, we establish thyroid dyshormonogenesis as a third cause of severe hypothyroidism after normal neonatal TSH screening.
Case reports Salient clinical and biochemical data obtained in the neonatal period and at diagnosis are summarized in Table 1. The dietary history of the four children was considered to exclude iodine deficiency.
Case 1 This 12-week-old male infant was referred because of increasing feeding difficulties and a growth decline since the age of six weeks. He was the second child of healthy, unrelated Belgian parents. The maternal grandmother and two maternal aunts were undergoing treatment for a goiter. Neonatal thyroid function screening had been normal (Table 1). Clinical examination revealed discrete signs suggestive of hypothyroidism and a palpable thyroid gland of normal size. After demonstration of severe primary hypothyroidism, presumably due to thyroid dyshormonogenesis (Table I), thyroid hormone replacement therapy was initiated. At the age of six months the infant is thriving.
Case 2 Complaints of lethargy, pallor, abdominal distension and growth arrest prompted referral of this boy at the age of three years. He was the first child of healthy, unrelated, tall Belgian parents. There was no family history of thyroid disease or hearing difficulties. Neonatal TSH screening had been normal. Developmental milestones had been reached in time until the age of one year and had been delayed ever since. Similarly, growth had been normal for parental height until aged one year and had declined thereafter (Fig. I). There were obvious signs of hypothyroidism. Furthermore, clinical examination revealed a homogeneously enlarged thyroid gland and also slightly enlarged testes (volume 4 ml). Psychomotor development was estimated to be delayed by approximately six months. A skull radiograph showed an enlarged sella turcica. After demonstration of severe
275
Dyshormonogenesis after normal TSH screening
ACTA PlEDlATR 81 (1992)
Table 1. Salient data obtained in four children at neonatal thyroid screening and at diagnosis of primary hypothyroidism.
Case 1 Neonatal screening Clinical hypothyroidism Day of screening TSH (mU/I; Nla < 20) T4 (nmol/l; NI 105-220) T3 (nmol/l; NI 1.6-3.7)
5
