Diagnóstico de endocrinopatía congénita en neonatos con ictericia prolongada e hipoglucemia / Diagnosis of congenital endocrinological disease in newborns with prolonged jaundice and hypoglycaemia

Introducción: La asociación de ictericia neonatal prolongada e hipoglucemia recurrente puede ser secundaria a una patología endocrinológica subyacente. La insuficiencia hipofisaria y la insuficiencia adrenal primaria son las principales patologías que se deben descartar. Material y métodos: Se analizaron retrospectivamente las características clínicas y de laboratorio de 13 pacientes derivados a la división de endocrinología del Hospital de Niños Ricardo Gutiérrez entre los años 2003 y 2008 con ictericia neonatal e hipoglucemia secundaria a insuficiencia hipofisaria en 12 pacientes y en uno a insuficiencia adrenal primaria. Resultados: Todos los pacientes tuvieron hipoglucemia en el periodo neonatal. En 10 pacientes la hiperbilirrubinemia fue de predominio directo y 6 pacientes presentaron elevación de transaminasas. La insuficiencia hipofisaria fue múltiple en los 12 pacientes. El tratamiento de remplazo hormonal normalizó la función hepática, resolvió la ictericia en todos los niños y ninguno requirió biopsia hepática. Los episodios de hipoglucemia también cedieron al iniciar el tratamiento sustitutivo. Conclusiones: El binomio ictericia prolongada o colestásica e hipoglucemia recurrente exige descartar insuficiencia hipofisaria múltiple e insuficiencia suprarrenal primaria. La terapia sustitutiva correspondiente resuelve el problema colestásico en la mayor parte de los casos, así como los problemas derivados de la hipoglucemia recurrente y las deficiencias hormonales(AU)

Introduction: The association of prolonged neonatal jaundice and hypoglycaemia may be secondary to an endocrinological disease. Pituitary insufficiency and primary adrenal insufficiency are the most likely endocrine diseases that need to be ruled out. Material and methods: We retrospectively analysed the clinical and laboratory characteristics of thirteen patients referred to the Hospital de Niños Ricardo Gutiérrez between years 2003 and 2008 due to prolonged neonatal jaundice and hypoglycaemia secondary to pituitary insufficiency in twelve patients, and in one secondary to primary adrenal insufficiency. Results: All patients had a history of neonatal hypoglycaemia. Ten patients had conjugated hyperbilirubinaemia and six also had elevated transaminases. Combined pituitary hormone deficiency was observed in the twelve hypopituitarism patients. Hormonal replacement normalised liver function and resolved the prolonged jaundice in all the patients. None of them underwent liver biopsy. Hypoglycaemia also remitted after hormonal therapy. Conclusions: Prolonged or cholestatic jaundice associated with neonatal hypoglycaemia is highly likely to be due to pituitary hormone deficiency or primary adrenal insufficiency. Early diagnosis and treatment of these children reverts the prolonged jaundice and prevents morbidity and mortality due to recurrent hypoglycaemia and hormone deficiencies(AU)

[Diagnosis of congenital endocrinological disease in newborns with prolonged jaundice and hypoglycaemia]. / Diagnóstico de endocrinopatía congénita en neonatos con ictericia prolongada e hipoglucemia.

INTRODUCTION: The association of prolonged neonatal jaundice and hypoglycaemia may be secondary to an endocrinological disease. Pituitary insufficiency and primary adrenal insufficiency are the most likely endocrine diseases that need to be ruled out. MATERIAL AND METHODS: We retrospectively analysed the clinical and laboratory characteristics of thirteen patients referred to the Hospital de Niños Ricardo Gutiérrez between years 2003 and 2008 due to prolonged neonatal jaundice and hypoglycaemia secondary to pituitary insufficiency in twelve patients, and in one secondary to primary adrenal insufficiency. RESULTS: All patients had a history of neonatal hypoglycaemia. Ten patients had conjugated hyperbilirubinaemia and six also had elevated transaminases. Combined pituitary hormone deficiency was observed in the twelve hypopituitarism patients. Hormonal replacement normalised liver function and resolved the prolonged jaundice in all the patients. None of them underwent liver biopsy. Hypoglycaemia also remitted after hormonal therapy. CONCLUSIONS: Prolonged or cholestatic jaundice associated with neonatal hypoglycaemia is highly likely to be due to pituitary hormone deficiency or primary adrenal insufficiency. Early diagnosis and treatment of these children reverts the prolonged jaundice and prevents morbidity and mortality due to recurrent hypoglycaemia and hormone deficiencies.

Early onset of primary hypogonadism revealed by serum anti-Müllerian hormone determination during infancy and childhood in trisomy 21.

Male patients with an extra sex chromosome or autosome are expected to present primary hypogonadism at puberty owing to meiotic germ-cell failure. Scarce information is available on trisomy 21, a frequent autosomal aneuploidy. Our objective was to assess whether trisomy 21 presents with pubertal-onset, germ-cell specific, primary hypogonadism in males, or whether the hypogonadism is established earlier and affects other testicular cell populations. We assessed the functional status of the pituitary-testicular axis, especially Sertoli cell function, in 117 boys with trisomy 21 (ages: 2months-20year). To compare with an adequate control population, we established reference levels for serum anti-Müllerian hormone (AMH) in 421 normal males, from birth to adulthood, using a recently developed ultrasensitive assay. In trisomy 21, AMH was lower than normal, indicating Sertoli cell dysfunction, from early infancy, independently of the existence of cryptorchidism. The overall prevalence rate of AMH below the 3rd percentile was 64.3% in infants with trisomy 21. Follicle-stimulating hormone was elevated in patients <6months and after pubertal onset. Testosterone was within the normal range, but luteinizing hormone was elevated in most patients <6months and after pubertal onset, indicating a mild Leydig cell dysfunction. We conclude that in trisomy 21, primary hypogonadism involves a combined dysfunction of Sertoli and Leydig cells, which can be observed independently of cryptorchidism soon after birth, thus prompting the search for new hypotheses to explain the pathophysiology of gonadal dysfunction in autosomal trisomy.

Height velocity in Argentinean girls with Turner's syndrome.

Height velocities from birth to maturity derived from 1,049 height increments measured over intervals 0.85-1.15 years were studied from a sample of 187 patients with Turner's syndrome (TS) diagnosed on the basis of karyotype. Length of follow up in each girl varied from 1.0 to 11.0 years. Cross-sectional analysis showed a relatively stable growth velocity during pubertal ages. However, longitudinal analysis of individual growth curves showed the existence of a small growth spurt in 37 out of 47 girls with available data during pubertal years. Mean peak height velocity (PHV) of this spurt was 5.7 cm/year, SD 1.34; mean age at PHV was 12.66 years, SD 1.70. Selected percentiles were calculated using the least mean squares (LMS) method. Results show that a small growth spurt in girls with TS may be more frequent than previously thought.

Psychosocial outcome in growth hormone deficient patients diagnosed during childhood.

Social disabilities have been described in GHD patients. The aim of this study was to evaluate the social outcome of a group of adult hypopituitary patients diagnosed and treated during childhood. Seventy patients were interviewed at a mean age of 25.6 years (range 18-50 yr). They answered a semistructured questionnaire and the Beck Depression Inventory test. Patients were compared for academic achievement, marital status and employment with the nearest age sibling. We found high levels of school repeaters, school was often not completed, and around 50% were overprotected by teachers and teased by peers. 32% were unemployed, while 58% of those employed work with their families. 80% still live with their parents; only 16% are married and 9% have children. 44% had no dating experience and 52% had never had sexual intercourse. Depression was common, especially in hypogonadic subjects. Juvenilization was the most common complaint. We did not found differences in maximal educational achievements and levels of employment between patients and siblings, but significantly more married siblings were found. Depression, social isolation and dependent life style were found in GHD patients. Appropriate medical and psychological counseling should be included for patients and their families as part of treatment.

Final height in long-term primary hypothyroid children.

OBJECTIVE: We studied retrospectively the statural growth and bone maturation of 32 children with primary hypothyroidism in order to relate their final heights to their chronological ages, height deficits and bone ages at the beginning of treatment. Patients were grouped according to age when treatment was started: Group 1 (G1) (n = 17): (15 girls, 1 boy) 3.09 +/- 0.8 yr; Group 2 (G2) (n = 9): (7 girls, 2 boys) 9.1 +/- 1.2 yr, and Group 3 (G3) (n = 6): (5 girls, 1 boy) 13.58 +/- 1.13 yr. At diagnosis G1 and G2 were prepubertal and G3 children were in puberty. In 10 patients of G1, 7 of G2 and 6 (all) of G3 final height was compared with target height. RESULTS: (SDS) Initial height: G1: -3.74 +/- 1.2; G2: -3.94 +/- 1.32; G3 -3.65 +/- 1. Height at onset of puberty: G1: -1.06 +/- 1.1; G2: -2.5 +/- 1.4. Height menarche stage 5: G1: -0.63 +/- 1.1; G2: -1.76 +/- 1.2; G3: -2.6 +/- 1.7. Final height: (whole group) G1: -0.85 +/- 0.91; G2: -1.6 +/- 1.3; G3: -2 +/- 1.5. Final height G1 (n = 10): -1.05 +/- 0.89; G2 (n = 7) 1.2 +/- 1. Target height G1 (n = 10): -1.22 +/- 0.78; G2 (n = 7): -0.8 +/- 1.2; G3 (n = 6): -1.07 +/- 1.5. Initial bone age: G1: -4.9 +/- 0.85; G2: -7.2 +/- 2.6; G3: -4.5 +/- 1.9. Bone age (onset of puberty) G1: -0.26 +/- 1.74; G2: -2 +/- 1.7; Bone age (menarche) G1: 0.09 +/- 0.6; G2: -0.5 +/- 0.6; G3: -0.76 +/- 0.82. CONCLUSION: G1 and G2, prepubertal at diagnosis, reached a normal adult height with respect to target height; G3 did not, the difference being statistically significant (p < 0.04). Puberty plays a decisive role in the incomplete catch-up growth of longstanding hypothyroid patients.

Growth of Argentinian girls with Turner syndrome.

Growth data on 254 patients with Turner syndrome from Argentina-120 with XO karyotype and 134 with other chromosomal abnormalities-were analysed. Birth weight and height were significantly reduced. Ninety patients had received oestrogen treatment from a mean age of 14-0 years (SD 1.2) and 17 patients had spontaneous menarche. Patients who underwent spontaneous menarche had a small growth spurt. Final height was slightly higher (139.8 cm SD 5.6), though not significantly different from the mean adult height of the whole sample (137.9 cm SD 5.7). Mean adult height was 3.73 SD below mean of the normal local population. Mean height velocities from birth to maturity are very similar to those found in other samples. Distance standards were prepared by fitting a fifth-degree polynomial to the interpolated mean heights at each 0.5 year of age, and to the raw SD. Selected centiles were then calculated from the smoothed values. Differences between adult height in local Turner syndrome girls and local normal population are very similar to the same Turner-normal differences described in other communities. Standards presented here are useful for evaluating Turner syndrome patients from Argentina, and may also be used by those with similar growth pattern in their normal population.

Growth follow-up in 100 children with congenital hypothyroidism before and during treatment.

In order to assess the influence of age at onset of treatment on subsequent growth, height, weight, head circumference (HC) and bone age as estimated by Greulich-Pyle and TW2-RUS methods, 100 children with congenital hypothyroidism (CH) were studied before and during adequate treatment up to 5 years of age. The patients were divided into five groups according to age at the start of treatment: Group 1: < 2 months (n = 26); Group 2: 2-3 months (n = 13); Group 3: 3-6 months (n = 21); Group 4: 6-12 months (n = 20); Group 5: 12-24 months (n = 20). Before treatment, groups 1 and 2 differed significantly from the others in height (p < 0.001). With hormone therapy, catch-up growth was observed in groups 3 to 5, but at age 5 years no differences were found between groups. In all groups, height at 5 years of age correlated significantly with children's midparental height (p < 0.002). Bone age was initially retarded in groups 3 to 5, but approximated the chronological age by age 5 years. Initially, HC was less affected than height and remained relatively larger up to age 5 years in all groups. These findings show that thyroid hormone replacement in CH as late as 24 months corrects the short stature and delayed bone age by age 5 years.