Crecimiento a largo plazo de pacientes con raquitismo hipofosfatémico familiar (RHF) / Long term growth in patients with familial hypophosphatemic rikets

El raquitismo hipofosfatémico familiar (RHF) es una condición genética trasmitida en la mayoría de los casos en forma dominante ligada al sexo, que se asocia a un pérdida renal de fosfatos, con secundaria hipofosfatemia, déficit de osificación, incurvación de miembros inferiores y retraso de crecimiento. Objetivo: describir el crecimiento y su relación con el cumplimiento del tratamiento a largo plazo, en un grupo de pacientes seguidos en el Hospital Garrahan por los servicios de Crecimiento y Desarrollo, Nefrología y Endocrinología. Tiempo de observación de 1.0 a 16.4 años. Población y Métodos: N= 30 pacientes (18 mujeres y 13 varones). Se midió la estatura según técnica estandarizada y se trataron los pacientes en forma uniforme con sales de fósforo 1-25 (HO2) vitamina. Se definió incumplimiento del tratamiento como la discontinuidad de la ingesta de sales de fósforo de más de un mes por año. Resultados: La edad mediana de inicio de tratamiento fue 4.92 años (r: 0.7/12.7), talla media: -2.85 Ds (r. -42/6.7) y a la última consulta: 15.04 años (r: 4.66/20.73), talla media: -3.31 Ds (r: -0.70/-6.6). En promedio, los niños crecieron entre 2.8/3.0 DS. Hubo 12 niños que perdieron estatura durante el seguimiento. La mayor proporción del déficit de talla ya estaba presente al diagnóstico. La regresión logística entre pérdida de talla en puntajes z (0.5 DS o más), y cuatro variables independientes (edad al diagnóstico), cumplimiento del tratamiento, sexo y talla al diagnóstico, cumplimiento al tratamiento, sexo y talla al diagnóstico) reveló que sólo las dos primeras están significativamente relacionadas al déficit de crecimiento (P 0.02 y 0.03 respectivamente). Conclusión: la edad tardía al diagnóstico y el incumplimiento del tratamiento se asocian a déficit de crecimiento.

Sertoli cell proliferations of the infantile testis: an intratubular form of Sertoli cell tumor?

We report on six boys with intratubular Sertoli cell proliferations (ISCPs), studied by routine histologic methods, electron microscopy, and immunohistochemistry of anti-müllerian hormone (AMH), inhibin alpha-subunit, 3beta-hydroxysteroid dehydrogenase (3beta-HSD), proliferative cellular nuclear antigen, and p53, and carefully followed for extended periods with periodic clinical examinations, testicular ultrasonographies, and determinations of serum levels of AMH and inhibin B. Peutz-Jeghers syndrome was found in four of six patients, and gynecomastia occurred in five of six patients. One boy had isosexual pseudoprecocity. ISCPs were observed as multiple foci of seminiferous tubules with large and proliferated Sertoli cells replacing germ cells and limited by the basement membrane. Mitotic figures, atypia, and/or interstitial invasion were not observed. Bilateral ISCPs were the only pathologic finding in three patients (patient nos. 1-3) and were associated with a microscopic tumor that resembled a large-cell calcifying Sertoli cell tumor (LCCSCT) in a fourth patient (patient no. 4). In the two remaining patients (patient nos. 5 and 6) ISCPs and LCCSCT were found in both testes. Ultrastructural examination showed large Sertoli cells, with round nuclei, sparse organelles, and some glycogen. Inhibin alpha-subunit immunolocalization was positive in the five patients in whom it was determined (patient nos. 2-6), AMH was positive in those ISCPs associated with tumors (patient nos. 4-6) and negative in isolated ISCPs (patient nos. 2 and 3); 3beta-HSD and PCNA were variable, and p53 was negative in all ISCPs. Patient nos. 1-4 have been followed for 2-19 years. One of them is currently entering puberty, the other two have already completed puberty and have testes of normal size, and the remaining one is an adult with clinically normal testes and sperm production. None of these patients had evidence of tumor development during follow-up as shown by serial ultrasonographies and serum levels of AMH and inhibin B. Patient nos. 5 and 6 who had bilateral ISCPs and LCCSCT were orchidectomized and evolved for 2-10 years after surgery without tumor recurrence. The prognostic significance of ISCPs, particularly when they are the only pathologic finding in a testicular biopsy, is a matter of controversy. Based on the long normal evolution, we recommend a conservative approach to therapy. The bilateral and multicentric character of ISCPs and their association with Sertoli tumors and Peutz-Jeghers syndrome suggest that they represent either proliferative lesions with tumorigenic potential or the intraepithelial stage in the evolution of some testicular Sertoli cell tumors.

Precocious puberty in children with tumours of the suprasellar and pineal areas: organic central precocious puberty.

UNLABELLED: During the past 11 y, 115 children younger than 8/9 y of age (female/male) with tumours of the suprasellar or pineal areas were followed in our clinic to study the incidence of precocious puberty. In addition, type of central lesion, clinical characteristics and gonadotropic secretion were studied in order to elucidate the different mechanisms of gonadal activation. A control group of 21 patients with idiopathic precocious puberty and a control group of 10 age-matched patients with suprasellar tumours without precocious puberty were also studied. Precocious puberty associated with organic central lesions was found at diagnosis in 30 patients (26%), in 9 out of 48 patients with glial cell tumours (18.7%), 6 out of 9 patients with germ cell tumours (66.6%), 11 out of 11 patients with hypothalamic hamartomas (100%) and in 4 out of 4 patients with subarachnoid cysts or arachnoidocele (100%). Precocious puberty was not found in any of 36 patients with craniopharyngioma. With the exception of one patient with pineal germinoma, all lesions were localized to the suprasellar area. In all patients with hypothalamic hamartoma, precocious puberty was diagnosed before 4 y of age, while in most patients with the other lesions, it was diagnosed after this age. Height SDS, weight increase and advancement of bone age were similar in both idiopathic and organic central precocious puberty. Maximal LH responses to GnRH in idiopathic and organic central precocious puberty were similar except for germ cell tumours. Patients with suprasellar tumours without precocious puberty had lower maximal LH (but not FSH) responses to GnRH, with the exception of germ cell tumours. In the latter, elevation of serum beta-hCG indicates that this gonadotropin was responsible for gonadal stimulation. In hypothalamic hamartomas, the prepubertal hiatus in the activity of the GnRH pulse generator was absent. The mechanism of this failure in the inactivation of GnRH is unknown. Data suggest that in glial cell tumours and in subarachnoid cysts, an unknown factor, probably secreted by the tumours, advances the tempo of GnRH maturation. Therefore, the aetiology of organic central precocious puberty is multiple and is directly related to location and type of lesion. CONCLUSION: This clinical information suggests that the onset of puberty is not the result of the disruption of a putative pulse generator inhibitory influence but the consequence of secretion of stimulatory substances by the lesions.

Determinación de niveles endogenos de hormona antidiurética en pacientes con enuresis primaria / Determination of endogenous levels of antiduiretic hormone in patients with primary enuresis

El objetivo del presente trabajo fue determinar los niveles de secreción endógenea nocturna en 10 pacientes de nuestro medio con enuresis nocturna. Una vez evaluados, habiendo descartado patología asociada y cumplido los criterios de inclusión (edad > 6 a. frecuencia de enuresis > 3 veces por semana y con cuadro de enuresis primaria no complicada), todos los pacientes fueron institucionalizados en el horario nocturno de 22.00 a 08.00 horas, con un intervalo de 2 horas se realizaron 6 extracciones de sangre venosa. Las 60 muestras (6 muestras por paciente) fueron procesadas con la técnica de radiopinmunoensayo realizando los dosajes de HAD endógena nocturna. Con los valores obtenidos se confeccionaron curvas de clara tendencia horizontal. En ninguno de los 10 pacientes con enuresis se observó el incremento nocturno referido por la bibliografía internacional para pacientes no enuréticos. Se concluye que en el marco de la multifactorialidad en la que se encuentra esta entidad (enuresis) la ausencia de un pico de secreción nocturna de HAD, permite plantear el tratamiento sustitutivo con un análogo sintético de HAD como una alternativa a considerar.

Report of an XX male with hypospadias and pubertal gynecomastia, SRY gene negative in blood leukocytes but SRY gene positive in testicular cells.

Most XX male subjects present an anomalous translocation of the sex-determining region of the chromosome Y (SRY) gene from chromosome Y to chromosome X. Several explanations have been proposed for the differentiation of testicular tissue in the absence of SRY gene. A patient is presented in whom the SRY gene was absent in peripheral leukocytes but present in testicular tissue. This possibility should always be ruled out before diagnosing Y-negative XX maleness.

Endocrine disorders in 66 suprasellar and pineal tumors of patients with prepubertal and pubertal ages.

Tumor oncotypes, initial symptoms and endocrine disturbances before and/or 1 month after surgery were studied in 66 patients with prepubertal and pubertal ages having suprasellar or pineal intracranial tumors. Neoplasms found in patients of prepubertal age were: 15 craniopharyngiomas (CRA), 24 neuroepithelial-cell-derived tumors (NEC), 5 germ cell tumors (GERM) and 4 other lesions (OTHER). In patients of pubertal age, there were 7 CRA, 7 pituitary tumors (PIT), 2 NEC, 1 GERM and 1 OTHER. Approximately 90% of patients had visual abnormalities as one of the initial signs and symptoms, while 59% had increased intracranial pressure. Short stature was observed in only 10% of patients. Before surgery, somatotropic function was found to be deficient (by 2 pharmacological tests) in 90-100% of patients with CRA, PIT or GERM and in 40% of patients with NEC. Overt hypothyroidism was found in 5-25% of CRA, NEC or GERM but in 40% of PIT. Abnormal TSH responses to TRH were observed in 64% of CRA and in 29% of NEC. Low basal serum cortisol was found in 21 or 6% of patients with CRA or NEC, but in 100 or 60% of patients with PIT or GERM, respectively. Diabetes insipidus was diagnosed in 13.6% of all patients. Surgery produced few additional disturbances in endocrine function, except for the incidence of diabetes insipidus which was doubled. Gonadotropic deficiency was found in most patients of pubertal age with CRA and PIT. They were readily differentiated by the high prolactin or growth hormone (GH) levels of the latter.(ABSTRACT TRUNCATED AT 250 WORDS)

Gonadotropin secretion in prepubertal and pubertal primary hypogonadism: response to LHRH.

Plasma LH and FSH were measured before and after LHRH administration in 10 patients with Turner's syndrome, in 7 with anorchia, in 2 castrates, in 18 with Klinefelter's syndrome, and in 11 prepubertal subjects with unilateral cryptochidism used as a control group. Basal LH was elevated in 4 and basal FSH in 8 of 10 patients with Turner's syndrome. Four patients with anorchia showed elevations of LH while FSH had increased in all of them. The two castrates had normal or slightly increased basal LH and definite elevations of FSH. Prepubertal subjects with Klinefelter's syndrome had normal plasma LH and FSH levels, but showed a marked elevation when they developed puberty. After LHRH administration, mean LH increased by 297% and FSH by 81% in Turner's syndrome, while in anorchia LH increased 757% and FSH 104%. After LHRH administration, patients with unilateral cryptorchidism had an LH increment of 316% and a FSH increment of 164%. Patients with prepubertal Klinefelter's syndrome showed elevations of 261% for LH and 221% for FSH after LHRH treatment. Adolescent subjects with Klinefelter's syndrome had an increment of 352% for LH and only 13% for FSH after LHRH administration. We have concluded that patients without functioning gonads fail to suppress gonadotropin secretion even before puberty while the gonads of the prepubertal Klinefelter's syndrome are able to control LH and FSH release. After puberty, in spite of the hypersection of LH and FSH observed in all subjects with agonadism there is a large pituitary reserve of the gonadotropins. We suggest that the relative inability of pubertal patients with Klinefelter's syndrome to increase FSH after LHRH treatment might be due to the presence of an abnormal compound secreted by the gonads.