Autoinmunidad tiroidea: Mecanismos patogénicos comunes y distintivos en tiroiditis de Hashimoto y enfermedad de Graves / Thyroid Autoimmunity: Common and Distinctive Pathogenic Mechanisms in Hashimoto's Thyroiditis and Graves' Disease

Las enfermedades tiroideas autoinmunes (ETA) son los desórdenes más frecuentes que llevan a la disfunción de la glándula tiroidea. Incluyen varias formas clínicas como Tiroiditis de Hashimoto (TH) y Enfermedad de Graves (EG). La relación entre TH y EG ha sido objeto de debate por décadas. Si bien, muy diferentes en su clínica, algunos las consideran los lados opuestos de una misma moneda. En su patogénesis tienen aspectos en común, como la predisposición genética demostrado por la ocurrencia en una misma familia y en un mismo individuo. Sin embargo, diferencias en el microambiente local determinan la diferente expresión fenotípica o el viraje de una a otra patología. El objetivo de esta monografía es investigar similitudes y diferencias entre TH y EG en las distintas etapas que llevan al desarrollo de autoinmunidad. Los autores declaran no poseer conflictos de interés.

Autoimmune thyroid disease (ATD) is the most common disorder that leads to thyroid gland dysfunction. ATD manifests in various clinical forms, such as Hashimoto's Thyroiditis (HT) and Graves' Disease (GD). The relation between HT and GD has been discussed for decades. Even if they greatly differ in their clinical features and treatment, some people believe they are the opposite sides of the same coin. In their pathogenesis, they share some mechanisms, such as genetic susceptibility, shown by the fact that they tend to occur both in the same person and within the same family. However, differences in the local micro-environment can determine the distinct phenotypic expression or the switch from one disease to the other. The aim of this monograph was to investigate similarities and differences between HT and GD at the diverse stages leading to the development of autoimmunity. No financial conflicts of interest exist.

Autoinmunidad tiroidea: Mecanismos patogénicos comunes y distintivos en tiroiditis de Hashimoto y enfermedad de Graves / Thyroid Autoimmunity: Common and Distinctive Pathogenic Mechanisms in Hashimotos Thyroiditis and Graves Disease

Las enfermedades tiroideas autoinmunes (ETA) son los desórdenes más frecuentes que llevan a la disfunción de la glándula tiroidea. Incluyen varias formas clínicas como Tiroiditis de Hashimoto (TH) y Enfermedad de Graves (EG). La relación entre TH y EG ha sido objeto de debate por décadas. Si bien, muy diferentes en su clínica, algunos las consideran los lados opuestos de una misma moneda. En su patogénesis tienen aspectos en común, como la predisposición genética demostrado por la ocurrencia en una misma familia y en un mismo individuo. Sin embargo, diferencias en el microambiente local determinan la diferente expresión fenotípica o el viraje de una a otra patología. El objetivo de esta monografía es investigar similitudes y diferencias entre TH y EG en las distintas etapas que llevan al desarrollo de autoinmunidad. Los autores declaran no poseer conflictos de interés.(AU)

Autoimmune thyroid disease (ATD) is the most common disorder that leads to thyroid gland dysfunction. ATD manifests in various clinical forms, such as Hashimotos Thyroiditis (HT) and Graves Disease (GD). The relation between HT and GD has been discussed for decades. Even if they greatly differ in their clinical features and treatment, some people believe they are the opposite sides of the same coin. In their pathogenesis, they share some mechanisms, such as genetic susceptibility, shown by the fact that they tend to occur both in the same person and within the same family. However, differences in the local micro-environment can determine the distinct phenotypic expression or the switch from one disease to the other. The aim of this monograph was to investigate similarities and differences between HT and GD at the diverse stages leading to the development of autoimmunity. No financial conflicts of interest exist.(AU)

Cosecretion of glycosylated prolactin and non-glycosylated prolactin from childhood to the end of puberty.

BACKGROUND: Glycosylated prolactin (G-PRL) is considered as the major post-translational modification of prolactin (PRL) showing reduced lactotropic and mitogenic activities compared to non-glycosylated prolactin (NG-PRL). AIM: To evaluate the evolution of G-PRL in normoprolactinemic children and adolescents and to analyze possible variations in glycosylated/total prolactin (T-PRL) ratios. METHODS: T-PRL, G-PRL and NG-PRL were evaluated in 111 healthy female and male children and adolescents (4.1-18 years), classified as group 1 (Tanner I), group 2 (Tanner II-III) and group 3 (Tanner IV-V). G-PRL and NG-PRL were identified by chromatography on concanavalin-A-Sepharose. RESULTS: G-PRL/T-PRL (median-range): females, group 1: 0.59 (0.17-0.77), group 2: 0.56 (0.31-0.78), group 3: 0.60 (0.38-0.79); males, group 1: 0.64 (0.39-0.80), group 2: 0.61 (0.24-0.79), group 3: 0.62 (0.35-0.90); the p value is not significant among the different groups in both genders. G-PRL/T-PRL ratios do not change when comparing low (first quartile) versus high (third quartile) T-PRL levels in the different groups. CONCLUSION: Our study would appear to support cosecretion of G-PRL and NG-PRL from childhood to the end of puberty. Such cosecretion would not be dependent on sex steroid levels. It is important to point out that puberty does not change the proportions of G-PRL and NG-PRL.

Hiperprolactinemia en la población infantojuvenil: un tema vigente / Hyperprolactinaemia in child an adolescent population: a current issue

La hiperprolactinemia constituye la altelaración endocrina más común del eje hipotálamo-hipofisario, aunque su prevalencia en la población infantojuvenil no está aún claramente definida. Además de la Prolactina (PRL) nativa (23Kda), se han descripto numerosas variantes moleculares, algunas de ellas con menor o ausente actividad biológica. Todo proceso que interrumpa la secreción de dopamina, interfiera con su liberación hacia los vasos portales hipofisarios o bloquee los receptores dopaminérgicos de las células lactotróficas, puede causar hiperprolactinemia. Si bien la patología tumoral constituye el diagnóstico de mayor relevancia, los prolactinomas son poco frecuentes en nios y adolescentes, aunque tienen en general una particular presentación clínica: de acuerdo con nuestra experiencia, el retraso puberal puede observarse en aproximadamente el 50% de las pacientes de sexo femenino. En pacientes con hiperprolactinemia asintomática debe evaluarse la presencia de proporciones alteradas de isoformas de PRL. La cromatografía en columna con sephadex G100, la precipitación con suspención de proteína A o con PEG y la ultracentrifugación constituyen los métodos más frecuentemente empleados para la detección de las distintas isoformas de PRL. En nuestra experiencia la B PRL constituyó el 6,6 - 32,6% de la PRL total y la BB PRL contituyó el 40 y el 72% de çesta en este gruo de pacientes. En cuanto al tratamiento por su efectividad y tolerancia, los agonistas dopaminérgicos constituyen la terapia inicial de elección en pacientes en edad pediátrica. La bromocriptina y la cabergolina han sido empleadas y con resultados similares a los de los pacientes adultos.

Controversies in the evolution of paediatric-adolescent varicocele: clinical, biochemical and histological studies.

OBJECTIVE: To study hormonal and histological parameters of paediatric-adolescent varicocele in order to know certain aspects of its natural history, in an attempt to find prognostic markers of testicular damage. DESIGN AND METHODS: In a prospective cross-sectional study, we evaluated 93 children and adolescents with left unilateral varicocele and 29 healthy males as control group. All of them were classified according to Tanner stage. Scrotal Doppler in both testes and GnRH and human chorionic gonadotrophin (hCG) tests were performed in all subjects. Surgery was performed in 28 patients and homolateral testicular biopsy in 18. RESULTS: Hormonal measurements of patients with varicocele were compared with a control group for each Tanner stage. Testicular biopsy specimens were analysed by light and electron microscopy. We only observed statistical differences in Tanner III patients in basal FSH (median and range) controls=1.70 (1.10-3.70) IU/l vs varicocele=4.20 (1.00-7.50) IU/l, P<0.05 and in Tanner IV patients in LH post-GnRH: controls=11.0 (7.50-15.0) IU/l vs varicocele=18.0 (5.10-29.0) IU/l, P<0.05 and in testosterone post-hCG: controls=9.50 (7.7-10.0) ng/ml vs varicocele=12.0 (6.2-23.0) ng/ml, P<0.01. No correlation was found between the various clinical grades of varicocele and hormonal measurements for each Tanner stage. No statistically significant differences were found between pre- and post-operative hormonal findings, either in basal levels or in maximal responses. On the other hand, no morphological abnormalities were observed by electron microscopy in germ cells, tubular wall and interstice. CONCLUSIONS: There appears to be no reliable biochemical marker in children and adolescents that may predict impaired testicular function. A significant size discrepancy between both testes, testicular pain and a hyperresponse to GnRH stimulation should continue to be, for the time being, the indications for surgery.

Macroprolactinemia in childhood and adolescence: a cause of asymptomatic hyperprolactinemia.

Asymptomatic hyperprolactinemias associated with altered proportions of molecular forms of circulating prolactin (PRL) have been reported in adults. The scarce references available in children and adolescents prompted us to report our experience in the evaluation and follow-up of patients with macroprolactinemia. We studied 5 patients (1 male and 4 females) aged 11.6-18 years with incidentally discovered asymptomatic hyperprolactinemia. Patients underwent repeated evaluations for a period of 3 months to 8 years, and their PRL levels remained elevated (34.4-516 ng/ml). Structural variants of PRL >/=45 kD ranged between 58.9 and 78.6%. Chromatographic profiles showed increases in Big Big PRL in the 5 cases, ranging between 40 and 72% (normal: 9-21%), and in Big PRL in 3 cases, ranging between 30.0 and 32.6% (normal: 5-25%). Little PRL was decreased in all cases, ranging between 20.6 and 41.1% (normal: 50-90%). In conclusion, upon detection of hyperprolactinemia with no clinical manifestations and no alteration of the remaining endocrine functions, macroprolactinemia should be considered as a possible diagnosis. The confirmed absence of functional alterations during the follow-up would favor a no-treatment approach and at the same time avoid repeating imaging studies.

Peripubertal prolactinomas: clinical presentation and long-term outcome with different therapeutic approaches.

UNLABELLED: The evolution of prolactinomas in children and adolescents continues to be controversial. We report on the long-term evolution (2-20 yr) of prolactinomas in 40 patients (29 F, 11 M). In females, the age for the onset of symptoms ranged between 8 and 16 yr and the age at which diagnosis was made ranged from 15 to 19 yr; in males, ages ranged from 8 to 17 yr and from 13.8 to 19 yr, respectively. In females, there was predominance of microprolactinomas (22/ 29) and the symptomatology resulted from functional disorders, whereas in males there was predominance of macroprolactinomas (8/11) and symptoms were caused by tumor mass disorders. Surgery was used as primary therapy in nine patients and as supplemental therapy in six patients. Twenty-four patients were treated primarily with bromocriptine and seven with cabergoline. Of the nine patients treated primarily with surgery, only one achieved gonadotropic axis restoration; in 25/31 patients receiving drug therapy gonadotropic function was restored to normal. Fifteen patients showed complete resolution or substantial shrinkage of tumor. CONCLUSION: In pediatric and adolescent age, there seem to be age- and sex-dependent differences in the clinical presentation of prolactinomas that cannot be accounted for only in terms of time of evolution. Drug therapy can control the disease, normalize prolactin levels and achieve gonadotropic axis restoration in most patients.

Immunoradiometric assay of thyrotropin during the first six months of life.

The aim of this preliminary study was to assess variation in thyrotropin (thyroid-stimulating hormone; TSH) levels using an immunoradiometric assay during the first 6 months of life of normal infants. One hundred and five normal newborns (59 females, 46 males) were evaluated for TSH, triiodothyronine and thyroxine at 48 h of life, and TSH was additionally determined at 15 days (n = 42), 30 days (n = 38), 60 days (n = 24), 90 days (n = 28), and 180 days (n = 30). Complete determinations during the total period of the study were obtained in 17 infants. Samples corresponding to the 48-hour period did not exhibit a normal distribution. In this group, percentile 3 corresponded to 0.9 mU/l, the median to 4.2 mU/l and percentile 97 to 17.7 mU/l. Levels of TSH similar to those of the normal adult population were reached between 30 and 60 days of life. Nevertheless, TSH levels of some of the children remained at higher values for a longer period. In summary, our results suggest that high TSH levels might not always indicate an underlying pathology. A critical evaluation of the normality criteria could avoid unnecessary studies and treatments.