Eur J Nucl Med (1985) 10:346-348 European I~11 I ~ l r ' ~ r Journal of I ~ l g l t , . l l ~ U . ~ /

Medicine © Springer-Verlag 1985

Thyroid dysgenesis in monozygotic twins: Variants identified by seintigraphy Richard McLean 1, Neville Howard z and I. Provan C. Murray 1 x Departments of Nuclear Medicine and 2 Endocrinology, Prince of Wales Hospital, Randwick, Australia

Abstract. The unusual occurrence of neonatal hypothyroid- ism in monozygotic twins is reported. Scintigraphy demon- strated that permanent hypothyroidism in one resulted from an ectopic suprahyoid thyroid, while in the other, the transient hypothyroid state was associated with thyroid hemiagenesis. These findings suggest that the anomalies represent variants of the same developmental aberration.

Key words: Neonatal hypothyroidism - Thyroid dysgenesis - Thyroid scintigraphy

Neonatal screening for hypothyroidism has revealed an in- cidence of thyroid dysfunction much greater than suspected from earlier clinical reviews of primary childhood hypothy- roidism (Anonymous 1979). In part, this is due to early detection of pathology that would otherwise present in later years and in part, to recognition of transient thyroid dys- function (Walfish et al. 1979). Thyroid scintigraphy, recom- mended for aetiological classification of detected cases (Fisher 1980a), has been largely responsible for elucidating and understanding these mechanisms.

We consider it appropriate therefore to report identical twins, in whom neonatal hypothyroidism was detected by a routine screening programme, since they were found by scintigraphy to have non-identical structural anomalies of the thyroid and to have differing degrees of associated thy- roid dysfunction.

Case study

Monozygotic male twins were born to a 24-year-old Anglo- Saxon mother, at 38 weeks of pregnancy. The marriage was non-consanguinous and there had been one previous normal pregnancy, resulting in a euthyroid female infant. During this pregnancy, the only medication was Debendox (doxylamine succinate and pyridoxine hydrochloride) for hyperemesis. Twin A was a breech delivery with birth weight of 2990 g and twin B also a breech delivery with birth weight of 2790 g. The placental membranes were indi- cative of monovular twins. At the time of delivery, there was transfusion from twin A to twin B but in the immediate postnatal period, no problems occurred. Blood groups and

Offprint requests to: Professor I.P.C. Murray, Department of Nu- clear Medicine, Prince of Wales Hospital, Randwick, NSW, 2031, Australia

Fig. 1 A, B. Pertechnetate scintigrams of anterior neck regions of twins. A A midline focus is seen cephelad to the normal site in twin A. B Absence of the isthmus and left lobe is shown in twin B

tissue typing for HLA haptotypes A and B were identical. Subsequent progress is documented below.

Twin A

Jaundice was noted on the second day but resolved without treatment. Tube feeding was necessary for 5 days but breast feeding began at 2 weeks. The baby was a slow feeder with a poorly sustained cry and was observed to have one bowel motion daily. Thyroid screening tests, performed at 5 days of age, showed T 4 RIA 33 nmol/1 (less than 10th percentile) and TSH 144 mU/1 (normal less than 40). A full assessment was performed at 3 weeks of age. This revealed a baby of length 49 cm (10th percentile), weight 3.07 kg (10th per- centile) and head circumference 35.5 cm (50th percentile). The pulse rate was 120/min and systolic blood pressure 80 mmHg. Cool skin was noted, as was a widely patent posterior fontanelle. Further findings included 5 cm of he- patomegaly, 2 cm of splenomegaly and an umbilical hernia 1.5 cm in diameter. The radiological bone age was 38 weeks gestation. In vitro tests were repeated and showed T 4 RIA 49 nmol/1 (normal 100-320), T 3 RIA 0.8 nmol/1 (normal 1.39-4.62) and TSH greater than 800 mU/1 (normal less than 20). A technetium thyroid scan (Figs. 1A, 2A) demon- strated a solitary focus of accumulation in the midline in a suprahyoid site.

The diagnosis was neonatal hypothyroidism (moderate- ly severe) with the only thyroid tissue seen in an ectopic suprahyoid site.

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Fig. 2A, B. Corresponding views performed in the right lateral projection. A The solitary focus is seen in the suprahyoid region in twin A. B A normal right thyroid lobe is seen in twin B

Twin B

Jaundice was noted at 2 days of age but this subsided with- out treatment. The baby was breast fed after 2 weeks and, although a slow feeder, had three bowel motions daily. Screening tests at 5 days of age showed T 4 RIA 25 nmol/1 (less than 10th percentile) and TSH 45 mU/1 (normal less than 40). Physical examination at 3 weeks of age revealed an active baby of length 51 cm (50th percentile), weight 3.t7 kg (30th percentile) and head circumference 35 cm (45th percentile). The pulse rate was 120/min and the sys- tolic blood pressure 80 mmHg. Warm skin was noted and the posterior fontanelle was minimally patent. There was 3 cm of hepatomegaly and 2 cm of splenomegaly and the radiological bone age was 40 weeks gestation. In vitro tests showed T~ RIA 135nmol/1 (normal 10~320), T 3 RIA 2.7 nmol/1 (normal 1.39-4.26) and TSH 11 mU/1 (nor- mal less than 20). A technetium thyroid scan (Figs. 1 B, 2B) showed a normal right lobe but absent left lobe and isthmus.

The diagnosis was transient neonatal hypothyroidism; thyroid hemiagenesis.

Discussion

Anomalous development of the thyroid can result in total absence of the gland, in ectopic tissue in a variety of sites or in thyroid hemiagenesis. The presentations may vary from detection in the first days of life with signs of neonatal hypothyroidism to incidental identification in an asympto- matic individual, even at autopsy. While none is common, the abnormalities are being recognised more frequently with the use of scintigraphy supplementing neonatal TSH screen- ing. The value of such screening is now well established with most surveys identifying neonatal hypothyroidism in an incidence of approximately 1:4500. The proportion re- sulting from agenesis or from thyroid ectopia varies but in most centres is about 50% of each (Fisher 1980b).

Ectopic thyroid is usually found cephalad to the normal position and represents failure to descend to the usual loca- tion. Arrest at the foramen caecum results in a lingual thy- roid. In most cases, lingual thyroid will not cause hypothy- roidism and may only be detected if the local hypertrophy is sufficient to produce obstructive symptoms. Indeed, only 15-33% will be hypothyroid (Montgomery 1935; Neinas et al. 1973). Failure to descend beyond a sublingual or su-

prahyoid site, however, is almost always associated with hypothyroidism. This may become apparent in the neonatal period but, in some children, the ectopic tissue may produce sufficient hormone to maintain them precariously euthyroid for a number of years. Finally the metabolic demands for thyroid hormones, particularly that of the growing skele- ton, outstrip that available from the ectopic undeveloped thyroid.

Thyroid hemiagenesis has recently been reviewed in de- tail (Melnick and Stemkowski 1981). Ninety-four patients had been documented in the literature. However, the true incidence is difficult to ascertain since in the majority of these, the abnormality had been identified at surgery or autopsy. Even those cases detected by imaging, with which an incidence of approximately 1:1700 has been reported (Hamburger and Hamburger 1970), usually were being evaluated for some other suspected thyroid pathology. Ade- quate clinical data was only available in 48 patients, 24 of whom were thyrotoxic. Hypothyroidism was present in only two patients, one being a l-year-old child. Of the 94 cases in the literature, the abnormality was detected only in 7 children, although a further 3 children have been re- ported (Hopwood et al. 1976; Abbassi and Auth 1983). The two cases described by Abbassi and Auth were euthyroid but underwent diagnostic scintigraphy because of palpable unilateral neck swelling, supporting the observation that, as with a lingual gland, functioning tissue usually can hy- pertrophy and function adequately for metabolic demands. The actual incidence in children is therefore particularly difficult to ascertain since they are less likely even than adults to undergo scintigraphy which might identify the abnormality incidentally. It is of interest that 75% of the patients reported were female and that in 80% of cases, the left lobe was absent.

The developing thyroid, arising as a diverticulum be- tween the first and second pharyngeal arches, is located in its normal anatomical position by week 8 of gestation and thyroxine is synthesised by the end of the first trimester (Fisher et al. 1970). The stimulus for intra-uterine migration of the thyroid is not known. A malformation of the gland may in itself be responsible. Mechanisms related to lack of stimulation by the pituitary, as earlier suggested (Hub- ble 1953), do appear to have been excluded. However, the role of some humoral factor controlling descent and devel- opment still remains a possibility. The familial occurrence of thyroid dysgenesis which has been described, suggests that such a factor may be genetically controlled. It seems feasible that aberration of this mechanism can result in absence of thyroid development, in abnormal descent or in failure of the original anlage to become bilobed and move bilaterally.

This concept of the varying anomalies having a common aetiology is reflected in the spectrum of clinical presenta- tions in the affected families. Thus, Orti et al. (1971) re- ported three sibs in the one family; one being hypothyroid and having a sublingual thyroid, one euthyroid but with obstructive symptoms caused by a lingual thyroid and the other euthyroid but with very hypoplastic left lobe. In the family reported by Rosenberg and Gilboa (1980), two sibs were hypothyroid with sublingual ectopic glands and a third was euthyroid but with a thyroid hemiagenesis. Sublingual glands were demonstrated in two hypothyroid sibs in one family by Kaplan et al. (1977). In another family described by them, two sibs were hypothyroid, one having a lingual

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gland and the other probably having hypoplastic ectopic tissue above the site of the normal thyroid.

Concordance of dysgenetic cretinism in monozygotic twin pairs was documented by Greig et al. (1966). In one pair, no thyroid tissue could be detected. In the other pair, one had a suprahyoid ectopic focus while in the other, at autopsy, the only thyroid tissue detected was a small rind in the site of the right lobe. These twins therefore probably had defects similar to those we have described. Discordance of thyroid dysgenesis has also been reported (Warkanay and Selkirk 1955; Pickering and Fisher 1958) which raises the possibility that these abnormalities may result by chance. However, in view of the overall incidence of thyroid ectopy and of thyroid hemiagenesis, the statistical odds of chance occurrence of both these abnormalities in monozy- gotic twins must be very high.

In our study, both twins were exposed to Debendox which has been shown to cross the placenta and has been linked with congenital deformities in isolated cases (Com- mittee on Safety of Medicines 1976). However, a causative role has not been proved and although the effect of some other exogenous factor cannot be totally excluded, we do believe that our findings add further weight to the conten- tion that thyroid ectopy and hemiagenesis are variants of the same developmental anomaly which may be genetically determined.

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Received March 24, 1984