Neonatal autoimmune hypothyroidism: a patient report

BACKGROUND: Acquired primary hypothyroidism in neonates and infants under 3 years of age is very rare. Herein we report the case of an infant female affected by acquired autoimmune hypothyroidism. PATIENT REPORT: The infant was transferred to the Pediatric Clinic, University of Catania, Italy for evaluation of dysmorphic features, growth and motor retardation, and hypothyroidism on laboratory testing. Neonatal screening test for TSH and PKU was negative. An ultrasound scan showed a non-homogeneous thyroid gland which was increased in volume. Based on the laboratory results, the diagnosis of autoimmune hypothyroidism was made and L-thyroxine treatment was initiated at 50 microg/day. CONCLUSIONS: Autoimmune hypothyroidism in infancy is rare, but early recognition and therapy are essential to prevent neurologic damage and growth deficits. In this patient we would like to underline the early age of appearance of autoimmune thyroid disease and the possible onset of pathologic events before birth.     

Hypothyroidism-associated testicular enlargement: is it a form of precocious puberty or not? A case report

In children with untreated hypothyroidism, the onset of puberty is usually delayed, but gonadotropin-independent precocious puberty may occur in children with severe hypothyroidism of long duration. The association of hypothyroidism, delayed bone age and gonadotropin-independent precocious puberty is defined as Van Wyk Grumbach syndrome (VWGS). VWGS has been described mostly in girls, and only seldom in boys. The manifestation of VWGS in boys is only testicular enlargement without substantial Leydig cell stimulation or testosterone secretion. We report a case of testicular enlargement due to obvious hypothyroidism secondary to autoimmune thyroiditis in a boy who presented with obesity. With this case report, we would like to emphasize that VWGS is not a real gonadotropin- independent precocious puberty in boys as it is in girls. Additionally, we would like to emphasize that delayed bone age is a special discriminating feature for differentiation of VWGS from the other causes of precocious puberty.     

Missed congenital hypothyroidism in an identical twin

Newborn screening for congenital hypothyroidism has been remarkably effective, although rare cases of false negative screening have been reported in same sex twins, presumptively due to fetal blood exchange. We report a case in which the diagnosis of congenital hypothyroidism due to thyroid ectopia in a monozygotic twin was delayed by 8 months, with a normal newborn screening TSH level of 11 mIU/L blood (normal < 15 mIU/L) at 2 days of life. This is the first such case since the national New Zealand newborn screening programme introduced screening for congenital hypothyroidism in 1981 (30 years ago). Repeating thyroid studies at 14 days of age in same‐sex twins has been advocated to avoid delayed diagnosis, but given the low risk, may not be cost effective. It is important to maintain a high index of suspicion in same‐sex twin pregnancies of potential congenital hypothyroidism.     

Watch Me Move: A Program For Parents of Young Children With Gross-Motor Delays

Aims: Watch Me Move (WMM) is a 6-week parent education program for caregivers of children with gross-motor delays. The aims are to improve parent-child interaction in a gross-motor context, increase parents' knowledge of behavioral cues and gross-motor development, and decrease perceived parental stress. Methods: Forty mothers of children, 6 months to 3 years of age, with a gross-motor delay participated in a randomized control trial comparing parents who received the WMM program plus standard of care physiotherapy (n = 24) with parents whose children received standard of care physiotherapy (n = 16). Results: Mothers who received the WMM program had significantly higher change scores on two subscales of the Nursing Child Assessment Teaching Scale (NCATS; i.e., cognitive growth fostering, and responsiveness to caregiver) and on the Parent Knowledge Questionnaire assessing knowledge of behavioral cues and gross-motor development. There were no significant group differences on the other four NCATS subscales (i.e., sensitivity to cues, response to child's distress, social emotional growth fostering, and clarity of cues) or the Parenting Stress Index. Conclusions: The addition of WMM to traditional physiotherapy improved aspects of mothers' ability to interact with their children and their knowledge of behavioral cues and gross-motor development.     

Rhabdomyolysis complicating doxylamine overdose

A 16-year-old male presenting with anticholinergic symptoms was found to have hematuria and oliguria. Evaluation of the patient revealed a serum creatinine of 2.2 mg/dl, myoglobinuria, and a creatine phosphokinase (CPK) level of 78, 750 IU/l with 99 percent fraction 3 isoenzyme. A toxic screen showed the presence of doxylamine, an antihistamine of the ethanolamine class, at a level of 75 times therapeutic. The patient did not have a history of trauma or seizures. The extremely high CPK level with the doxylamine overdose suggests that doxylamine may be associated with nontraumatic rhabdomyolysis. This is the first case report of rhabdomyolysis being associated with an antihistamine overdose.     

Congenital hypothyroidism: causes for delayed initiation of treatment]

The aim of neonatal screening programs for congenital hypothyroidism is to ensure early treatment in order to prevent brain dysfunction. There are several reasons why infants are missed in the screening program. We report on three patients with congenital hypothyroidism, who had a pathological screening result and initiation of therapy was delayed. The first patient had an increased TSH level, but she was missed because of mistakes in the confirmatory serum test. During the follow-up the patient showed typical symptoms of hypothyroidism and got a thyroxine supplementation not before the age of three years. The second patient did not get a therapy before the age of six months because of the noncompliance of the parents and physicians. The third patient had a central hypothyroidism. The neonatal screening-program revealed no measurable TSH activity. Although the child had clinical signs of a severe hypothyroidism diagnosis was not made before the age of 5.5 months. Although different reasons are known for screening errors, all these 3 patients were missed because of failures in the follow-up of a pathological screening result, indicating a poor quality in the follow-up procedure.     

Linear growth in early treated children with congenital hypothyroidism

Length/height was studied from birth to 6 years of age in 103 children with congenital hypothyroidism identified by the Norwegian or Swedish screening programs. We used the "infancy-childhood-puberty (ICP) growth model". This model describes normal linear growth during the first 3 years of life by an infancy component with the addition of a childhood component, the latter acting from the second half of the first year. In comparison with reference children, children with hypothyroidism had reduced growth from 6 to 12 months, and increased growth after 12 months of age. Mean onset of the childhood component of growth was delayed from 8.1 months (SD 1.9) to 10.4 months (SD 2.2) in girls, and from 8.9 months (SD 2.0) to 11.0 months (SD 2.1) in boys. Age at onset of the childhood component was correlated with age at start of treatment ( r = 0.24), and in children with more severe hypothyroidism (pretreatment serum thyroxine <40 nmol/l) inversely correlated with the L-thyroxine dose at start of treatment ( r = -0.40). Change in height standard deviation score from 1 to 3 years of age was correlated with the serum thyroxine concentration at age 1 year ( r = 0.30). The delay in the onset of the childhood component of growth and the association with age at start of treatment and initial L-thyroxine dose indicate that thyroid hormones during the first months of life are essential for normal onset of the childhood component of growth, which otherwise is assumed to be growth hormone-dependent.     

Severe rhabdomyolysis and acute renal failure in an adolescent with hypothyroidism

Hypothyroidism has been reported rarely as the cause of rhabdomyolysis in adults and children. We present here a non-compliant adolescent with a diagnosis of hypothyroidism who developed rhabdomyolysis and acute renal failure with no additional predisposing factor. A 13-year-old girl with a previous history of hypothyroidism due to thyroid hypoplasia presented with generalized myalgia, malaise, vomiting, and oliguria lasting for three days. Neurological examination revealed bilateral marked weakness and tenderness of muscles of both lower and upper extremities. Urine had bloody appearance and urine analysis showed blood reaction with dipstick test, but there were no erythrocytes on microscopic examination. Serum creatine phosphokinase and myoglobin levels were elevated. Thyroid stimulating hormone (TSH) levels were high, and free thyroxine (T4) and triiodothyronine (T3) levels were low, compatible with uncontrolled hypothyroidism. Renal function tests showed acute renal failure. Other causes of rhabdomyolysis such as muscular trauma, drugs, toxins, infections, vigorous exercise, and electrolyte abnormalities were excluded. Hemodialysis was administered for 24 sessions. After L-thyroxine therapy, thyroid function tests normalized, muscle strength improved, serum muscle enzyme levels returned to normal levels, and renal function tests recovered. One must be aware that rhabdomyolysis may develop in a non-compliant patient with hypothyroidism.     

Bilirubin uridine diphosphate glucuronosyltransferase hepatic activity in jaundice associated with congenital hypothyroidism.

Hepatic bilirubin uridine diphosphate glucuronosyltransferase activity was assayed in an infant with prolonged jaundice and congenital hypothyroidism before thyroid therapy. This activity was nil, suggesting a possible delayed maturation of the enzyme. Although further studies will be necessary to confirm this hypothesis, prolonged jaundice associated with congenital hypothyroidism may be due to a delayed maturation of the hepatic glucuronidation of bilirubin.     

Hypertension during pregnancy, with and without specific hypotensive treatment. II. The growth and development of the infant in the first year of life

The growth and development of three groups of infants were prospectively assessed from birth to 12 mth. In two groups the mothers had been hypertensive before the 28th wk of gestation; one group was randomly allocated to specific hypotensive therapy, the other group was allocated to no specific treatment. The third group was a sample of the hospital population. General health, and the incidence of sight and hearing problems did not differ. Infants in the treated hypertensive group had had more perinatal problems, and there was an excess of infants with relatively small heads for their gestational age at birth. At 6 mth their heads were still smaller than the hospital sample, but by the age of 1 yr the difference was no longer present. The neurological status of infants in the untreated hypertensive group was less favourable in the neonatal period, and there was still an excess of infants in this group rated questionable on neurological assessment at the age of 12 mth. In both hypertensive groups there was an excess of infants with delayed fine-motor function at 6 mth, and in the untreated group there was an excess with delayed gross-motor function at 12 mth compared with the hospital sample. Our varied findings draw attention to the dangers of assessing the effects of different pregnancy conditions in terms of neonatal mortality and morbidity alone. Our date indicate that follow-up should extend for longer than 12 mth when the effects of adverse pregnancy factors and their management are under consideration. Further evaluation will be made when these children are 4 yr old.     

CEREBELLAR-ATAXIC SYNDROME IN CHILDREN AND ADOLESCENTS WITH HYPOTHYROIDISM UNDER TREATMENT

ABSTRACT. Animal experiments and observations on quantitative growth of human cerebellum suggest a critical period when its development is particularly vulnerable to hypothyroidism. Sixty-seven patients aged 7–24 years with hypothyroidism under long-term treatment were examined for ataxic symptoms. These were found in 24 of 39 patients (60%) hypothyroid before or during the third month of life. Only 4 of 18 patients (20 %) hypothyroid later had cerebellar symptoms. Such symptoms could be evidence for the onset of hypothyroidism before or during the 3rd month of life. Seventeen (80%) of mentally retarded patients had cerebellar symptoms compared with 11 (30%) of 45 attending normal school. Even retrospecitvely, these data might permit a more accurate prognosis of further mental development in hypothyroid children.     

Contributions of bone maturation measurements to the differential diagnosis of neonatal transient hypothyroidism versus dyshormonogenetic congenital hypothyroidism

AIM: To a) evaluate the contribution of bone maturation in the diagnosis of neonatal transient hypothyroidism versus dyshormonogenetic congenital hypothyroidism in full-term newborns, and b) use bone maturation to test the hypothesis that neonatal transient hypothyroidism is perinatal in onset. MATERIALS AND METHODS: The study included 20 patients with dyshormonogenetic and 43 with transient hypothyroidism. Thyroid function and measurements of the distal femoral epiphysis area, obtained at the time of first confirmatory diagnosis, were compared between the two groups. The epiphysis area in two control groups with normal thyroid function was also measured and compared with that in patients with transient hypothyroidism, at age 1-3 d (control A), or at the age when normal thyroid function was confirmed (control B). RESULTS: Mean epiphysis area was 0.04 cm2 in patients with dyshormonogenetic versus 0.22 cm2 in patients with transient hypothyroidism (p < 0.0001). An area <0.05 cm2 was limited to patients with dyshormonogenetic hypothyroidism. Conversely, a normal area (>0.2 cm2) was only observed in patients with transient hypothyroidism. Mean epiphysis areas in control A (0.20 cm2) and in patients with transient hypothyroidism were similar (p = 0.37), consistent with perinatal onset of transient hypothyroidism. Mean epiphysis area in control B (0.31 cm2) was significantly greater than in patients with transient hypothyroidism (p < 0.01). CONCLUSIONS: A short duration of hypothyroidism can significantly delay bone maturation. Examination of bone maturation at initial confirmatory evaluation yields important information pertaining to congenital hypothyroidism, not only to predict intellectual development, but also to evaluate the risk of dyshormonogenetic hypothyroidism.     

CONGENITAL HYPOTHYROIDISM: AGE AT START OF TREATMENT VERSUS OUTCOME

ABSTRACT. We studied 27 patients with congenital hypothyroidism by neurological and psychometric methods. 7 healthy siblings served as a control group for the psychometric evaluation. In 7 patients treatment had been started before the age of 1 month and in 10 patients after the age of 3 months. Our findings suggest that the progressive loss of intelligence potential starts from birth but if treatment is begun before the age of 1 month, then intelligence remains within normal range. The neurological damage seems to originate partly before birth, but more serious injuries arise if treatment is delayed beyond the age of 3 months.     

Psychomotor Development of Children with Congenital Hypothyroidism Diagnosed by Neonatal Screening

ABSTRACT. The psychomotor development in 68 children with congenital hypothyroidism diagnosed during the first two years of a nationwide neonatal screening programme in Sweden was assessed during their first three years of life. Replacement therapy with thyroxine was initiated at the age of 15±7 days (mean ± SD). Griffiths tests were performed in 15 patients at the age of 18 months and in 51 patients at 30–47 months. Their developmental quotients did not differ from those of control children, indicating that the psychomotor development in the children with congenital hypothyroidism was normal. In earlier studies of Swedish children with congenital hypothyroidism, diagnosed clinically before the age of three and a half years, the psychomotor development was found to be impaired. In contrast, the patients diagnosed by neonatal screening and given early therapy displayed normal results in Griffiths tests. This indicates that the age at the start of treatment is an important determinant for the prognosis.     

Psychological development of children with hypothyroidism. II. Motor development and psychopathology (author's transl)

In addition to a preceeding report the relation of motor development to ataxia and age at onset of symptoms and therapy as well as psychopathological symptoms in relation to intelligence and sex in 32 children with hypothyroidism are reported.     

Psychomotor development of children with congenital hypothyroidism diagnosed by neonatal screening

The psychomotor development in 68 children with congenital hypothyroidism diagnosed during the first two years of a nationwide neonatal screening programme in Sweden was assessed during their first three years of life. Replacement therapy with thyroxine was initiated at the age of 15 +/- 7 days (mean +/- SD). Griffiths tests were performed in 15 patients at the age of 18 months and in 51 patients at 30-47 months. Their developmental quotients did not differ from those of control children, indicating that the psychomotor development in the children with congenital hypothyroidism was normal. In earlier studies of Swedish children with congenital hypothyroidism, diagnosed clinically before the age of three and a half years, the psychomotor development was found to be impaired. In contrast, the patients diagnosed by neonatal screening and given early therapy displayed normal results in Griffiths tests. This indicates that the age at the start of treatment is an important determinant for the prognosis.     

Cerebellar-ataxic syndrome in children and adolescents with hypothyroidism under treatment.

Animal experiments and observations on quantitative growth of human cerebellum suggest a critical period when its development is particularly vulnerable to hypothyroidism. Sixty-seven patients aged 7-24 years with hypothyroidism under long-term treatment were examined for ataxic symptoms. These were found in 24 of 39 patients (60%) hypothyroid before or during the third month of life. Only 4 of 18 patients (20%) hypothyroid later had cerebellar symptoms. Such symptoms could be evidence for the onset of hypothyroidism before or during the 3rd month of life. Seventeen (80%) of mentally retarded patients had cerebellar symptoms compared with 11 (30%) of 45 attending normal school. Even retrospectively, these data might permit a more accurate prognosis of further mental development in hypothyroid children.     

Gross motor development of Nigerian children.

A prospective study of 320 Nigerian children was undertaken to determine their pattern of motor development by recording the age at attainment of 12 gross-motor milestones. The children were all born full term and were neurologically normal at birth. They were recruited in the first week of life and seen at regular intervals in a well-baby clinic, where their parents were questioned about the ages at attainment of milestones. Results show that most gross-motor milestones were attained at earlier ages by these children than by children studied to establish norms for the traditional tests of motor development that have long been in use. Our findings confirm several previous reports which emphasize the more rapid attainment of motor milestones such as 'sit without support', 'crawl', 'stand well alone' and 'walk well alone' by black as compared with white children. But, conversely, a number of transitional milestones such as 'roll over', 'pull self to stand' and 'stand holding on' were achieved later by children in this study than by their non-African counterparts. Girls in this study were slightly advanced, relative to boys, in their attainment of most milestones. The results of this study have been incorporated into a chart which can be used in well-baby clinics to detect children with motor delay.     

CONGENITAL HYPOTHYROIDISM IN SWEDEN Incidence and Age at Diagnosis

ABSTRACT. A total number of 112 children with congenital hypothyroidism were diagnosed in all Children's Hospitals and Pediatric Wards in Sweden during the 7-year period 1969–1975. Since it may be assumed that all cases of congenital hypothyroidism, which were diagnosed during that period were seen in one of these hospitals, the incidence of congenital hypothyroidism in Sweden can be calculated to be 1:6900 live births. In spite of an efficient National Health Care Program for Infants the diagnosis was delayed until after an age of three months in 52% of the cases. This fact supports the view that mass screening of newborns for congenital hypothyroidism has to be introduced in Sweden. However, the beneficial effects of such a program cannot be fully elucidated until it has been considered whether earlier instituted treatment would have improved the outcome of children in whom a diagnosis was made after 3 months of age.