Carcinoma medular de tiroides: estudio multicéntrico. Presentación y evolución en 219 pacientes / Medullary Thyroid Carcinoma: Clinical Presentation and Outcome in 219 Patients

Ante la baja frecuencia del carcinoma medular de tiroides (CMT), en el Departamento de Tiroides de SAEM nos propusimos realizar un estudio de cohorte, observacional, retrospectivo y multicéntrico. Se incluyeron 219 pacientes con diagnóstico histológico de CMT. El 65 % fueron mujeres, la edad promedio fue de 39 ± 20 años (1 a 84 años); 44-% de los casos fueron familiares. Las formas de presentación más frecuentes fueron nódulo tiroideo (58 %) y pesquisa genética por antecedente familiar (22 %). Si bien la citología tiroidea fue diagnóstica de CMT en el 39 % de los casos, fue determinante de indicación quirúrgica en el 79 %. En el 47 % de los pacientes el diagnóstico de CMT se obtuvo previamente al tratamiento quirúrgico inicial por punción aspiración con aguja fina (PAAF), estudio genético o nivel de calcitonina (CT)). El 65 % se presentó en estadios avanzados (TNM III y IV). El estudio del protoncogen RET se realizó en 162 pacientes (74 %). En el 49 % se observó mutación siendo la más frecuente (76 %) en el codón 634. La forma hereditaria más frecuentemente observada fue el síndrome de neoplasia endocrina múltiple (NEM) 2A (57 % de los casos familiares), seguida por carcinoma medular familiar (25 %) y NEM 2B (13 %). Los casos familiares tuvieron menor edad al diagnóstico y mayor frecuencia de diagnóstico prequirúrgico. Los casos índice tuvieron mayor edad al momento del diagnóstico, mayores niveles de antígeno carcinoembrionario (CEA) y CT prequirúrgicos, mayor proporción de estadios III y IV y mayor porcentaje de evidencia de enfermedad al momento de la última consulta que aquellos detectados por pesquisa. En 143 pacientes (65 %) se obtuvieron registros completos de seguimiento en los que se analizaron los factores relacionados con la evolución. La mediana de seguimiento fue de 44 meses: fallecieron 21 pacientes (14,6 %) y 122 (86 %) viven; 76 de estos (54 %) se encuentran libres de enfermedad. El grupo con evidencia de enfermedad se presentó en estadios más avanzados. Resultaron factores de mayor riesgo para evidencia de enfermedad: sexo masculino, CMT esporádico, niveles elevados de CT prequirúrgicos, estadio IV y presencia de metástasis. Los niveles de CT posquirúrgicos fueron menores en aquellos pacientes que en la evolución final no presentaron evidencia de enfermedad. El principal factor pronóstico de la evolución de los pacientes con CMT fue el estadio de presentación, determinando la importancia del diagnóstico precoz con el fin de poder implementar un tratamiento quirúrgico curativo en estadios menos avanzados.

Due to the low frequency of medullary thyroid cancer (MTC), an observational, cohort, retrospective multicenter study was conducted at the Thyroid Department of the Endocrine and Metabolism Argentine Society (SAEM). We included 219 patients with histologically proven MTC, with a mean age of 39 ± 20 yr (range 1-84 years). Sixty five percent were women and 44% were familial cases. The most common presentations were thyroid nodule (58 %) and genetic screening due to family history (22 %). In 39 % of patients, diagnosis of MTC was made by fine needle aspiration, but cytology led to surgery in 79 %. In 47 % of patients, MTC was diagnosed by cytology, calcitonin (CT) levels or genetic studies prior to initial surgery. Sixty five percent of patients had advanced stages of the disease (TNM III or IV) at diagnosis. Proto-oncogene RET was studied in 162 patients (74 %). In 49% a mutation was reported, most frequently in codon 634 (76 %). Regarding hereditary forms of MTC, MEN 2A was the most frequent (57%), followed by familial MTC in 25 % and MEN 2B in 13 % of cases. Familial cases were younger subjects and had more frequently a pre-surgery diagnosis. Index cases were older, with higher CEA and CT levels, presented in more advanced stages and had more frequently evidence of disease at final assessment than patients who were diagnosed by genetic screening. Follow-up records of 143 patients were analyzed (65%); median time was 44 months; 21 patients died (14.6 %) and 122 survived (86 %), 76 showed no evidence of disease (NED) (54 %). High risk factors for evidence of disease at the final evaluation were: male gender, sporadic MTC, higher CT pre-surgery levels, stage IV and metastasis. Post surgery CT levels were lower in patients with NED. Stage at initial diagnosis was the main prognostic factor in patients with MTC, determining the importance of early detection for performing curative surgery in less advanced stages.

Carcinoma medular de tiroides: estudio multicéntrico. Presentación y evolución en 219 pacientes / Medullary Thyroid Carcinoma: Clinical Presentation and Outcome in 219 Patients

Ante la baja frecuencia del carcinoma medular de tiroides (CMT), en el Departamento de Tiroides de SAEM nos propusimos realizar un estudio de cohorte, observacional, retrospectivo y multicéntrico. Se incluyeron 219 pacientes con diagnóstico histológico de CMT. El 65 % fueron mujeres, la edad promedio fue de 39 ± 20 años (1 a 84 años); 44-% de los casos fueron familiares. Las formas de presentación más frecuentes fueron nódulo tiroideo (58 %) y pesquisa genética por antecedente familiar (22 %). Si bien la citología tiroidea fue diagnóstica de CMT en el 39 % de los casos, fue determinante de indicación quirúrgica en el 79 %. En el 47 % de los pacientes el diagnóstico de CMT se obtuvo previamente al tratamiento quirúrgico inicial por punción aspiración con aguja fina (PAAF), estudio genético o nivel de calcitonina (CT)). El 65 % se presentó en estadios avanzados (TNM III y IV). El estudio del protoncogen RET se realizó en 162 pacientes (74 %). En el 49 % se observó mutación siendo la más frecuente (76 %) en el codón 634. La forma hereditaria más frecuentemente observada fue el síndrome de neoplasia endocrina múltiple (NEM) 2A (57 % de los casos familiares), seguida por carcinoma medular familiar (25 %) y NEM 2B (13 %). Los casos familiares tuvieron menor edad al diagnóstico y mayor frecuencia de diagnóstico prequirúrgico. Los casos índice tuvieron mayor edad al momento del diagnóstico, mayores niveles de antígeno carcinoembrionario (CEA) y CT prequirúrgicos, mayor proporción de estadios III y IV y mayor porcentaje de evidencia de enfermedad al momento de la última consulta que aquellos detectados por pesquisa. En 143 pacientes (65 %) se obtuvieron registros completos de seguimiento en los que se analizaron los factores relacionados con la evolución. La mediana de seguimiento fue de 44 meses: fallecieron 21 pacientes (14,6 %) y 122 (86 %) viven; 76 de estos (54 %) se encuentran libres de enfermedad. El grupo con evidencia de enfermedad se presentó en estadios más avanzados. Resultaron factores de mayor riesgo para evidencia de enfermedad: sexo masculino, CMT esporádico, niveles elevados de CT prequirúrgicos, estadio IV y presencia de metástasis. Los niveles de CT posquirúrgicos fueron menores en aquellos pacientes que en la evolución final no presentaron evidencia de enfermedad. El principal factor pronóstico de la evolución de los pacientes con CMT fue el estadio de presentación, determinando la importancia del diagnóstico precoz con el fin de poder implementar un tratamiento quirúrgico curativo en estadios menos avanzados.(AU)

Due to the low frequency of medullary thyroid cancer (MTC), an observational, cohort, retrospective multicenter study was conducted at the Thyroid Department of the Endocrine and Metabolism Argentine Society (SAEM). We included 219 patients with histologically proven MTC, with a mean age of 39 ± 20 yr (range 1-84 years). Sixty five percent were women and 44% were familial cases. The most common presentations were thyroid nodule (58 %) and genetic screening due to family history (22 %). In 39 % of patients, diagnosis of MTC was made by fine needle aspiration, but cytology led to surgery in 79 %. In 47 % of patients, MTC was diagnosed by cytology, calcitonin (CT) levels or genetic studies prior to initial surgery. Sixty five percent of patients had advanced stages of the disease (TNM III or IV) at diagnosis. Proto-oncogene RET was studied in 162 patients (74 %). In 49% a mutation was reported, most frequently in codon 634 (76 %). Regarding hereditary forms of MTC, MEN 2A was the most frequent (57%), followed by familial MTC in 25 % and MEN 2B in 13 % of cases. Familial cases were younger subjects and had more frequently a pre-surgery diagnosis. Index cases were older, with higher CEA and CT levels, presented in more advanced stages and had more frequently evidence of disease at final assessment than patients who were diagnosed by genetic screening. Follow-up records of 143 patients were analyzed (65%); median time was 44 months; 21 patients died (14.6 %) and 122 survived (86 %), 76 showed no evidence of disease (NED) (54 %). High risk factors for evidence of disease at the final evaluation were: male gender, sporadic MTC, higher CT pre-surgery levels, stage IV and metastasis. Post surgery CT levels were lower in patients with NED. Stage at initial diagnosis was the main prognostic factor in patients with MTC, determining the importance of early detection for performing curative surgery in less advanced stages.(AU)

Programa nacional de bocio nodular (PRONBONO): Estudio multicéntrico de bocio nodular único palpable / National Program for Nodular Goiter (PRONBONO): Multicenter study of single palpable thyroid nodules

Introducción: La presencia de nódulos tiroideos palpables en la población general, es uno de los signos clínicos tiroideos más frecuentes en la práctica diaria. Objetivos: 1) establecer la prevalencia de las distintas patologías en bocio nodular único palpable y analizar sus características y su relación con los resultados citológicos. 2) analizar la existencia de diferencias regionales en Argentina. Pacientes y Métodos: Estudio prospectivo de 739 pacientes con bocio nodular único palpable evaluados entre el 1/1/2000 y el 31/12/2001 en Centros de Buenos Aires, Bahía Blanca, Mendoza y La Pampa. Se recabaron datos de examen clínico, ecografía tiroidea, TSH, ATPO y citología por punción con aguja fina. (PAAF). Fue utilizado para el análisis estadístico Correlación de Pearson, X2 y Test de Fisher. Resultados: la edad (X ± DS) fue 46,3 ± 14 años, 93,1 % eran de sexo femenino. El 1,6 % tenía historia de radiación en cuello y el 29,9 % antecedentes familiares de patología tiroidea. Hallazgos clínicos: disfagia en el 7,9 %, disfonía 3,5 %, crecimiento nodular en los últimos 6 meses 19,2 %, consistencia dura el 24,7 %, fijeza a estructuras adyacentes 1,5 % y adenopatías en el 3 %. Hallazgos bioquímicos: TSH normal en el 81,2 % y ATPO positivos en el 30,3 % de los casos. Características Ecográficas: nódulos sólidos: 53,1 %, hipoecoicos: 63,8 %, microcalcificaciones 10,3 %, halo incompleto: 15 %, multinodular: 30,5 %, tiroides heterogénea: 60,2 % y adenopatías: 3,8 %. Hallazgos citológicos: En el 86,8 % de los casos fue necesario solo una punción para llegar al diagnóstico. Insatisfactorio (excluyendo quiste): 3,2 %: benignos: 77,3 %; sospechosos: 12,6 % y cáncer: 7 % (42 papilar, 2 medular y 3 sin especificar). Una correlación significativa (p<0,02) fue observada entre citología maligna y crecimiento rápido, dureza, fijeza a estructuras vecinas, nódulo sólido, halo incompleto y adenopatías aunque estos parámetros son más frecuentes en números absolutos en nódulos benignos. La mayoría de las cirugías fueron indicadas en base al hallazgo citológico. El diagnóstico histológico de los 96 pacientes que fueron operados mostró 51 carcinomas, de los cuales solo dos tenían citología benigna y 31 adenomas. Conclusión: Los nódulos palpables únicos fueron más frecuentes en mujeres eutiroideas en la edad media de la vida. Un tercio tenía historia familiar de patología tiroidea, similar al porcentaje hallado de ATPO positivos. Por ecografía los nódulos fueron predominantemente sólidos, hipoecoicos, únicos con resto de la glándula tiroides heterogénea. La PAAF fue predominantemente benigna. El crecimiento rápido, la dureza, la fijeza a estructuras adyacentes, el halo incompleto y la presencia de adenopatías fueron relacionados con malignidad, pero la benignidad fue más frecuente. En la mayoría de los pacientes la cirugía fue recomendada por los hallazgos citológicos. Nuestros resultados son similares a los reportados en otras áreas geográficas.

Introduction: the presence of palpable thyroid nodules in the general population is one of the most common clinical signs of thyroid disease in daily practice. Objectives: 1) To assess the prevalence of pathologies, clinical and cytological findings of single palpable thyroid nodules (SPTN) in Argentina. 2) Analyze the regional differences in Argentina. Methods: Prospective study of 739 patients with STPN were evaluated at centres in Buenos Aires, Bahía Blanca, Mendoza, and La Pampa between 1/1/00 and 12/31/01. Clinical examination, thyroid ultrasound scan (US), TSH, TPOAb and fine needle aspirations (FNA) were performed. Statistics: Pearson Correlation, X2 & Fisher Tests. Results: Age (X ± SD) 46 ± 14ys: 93.1 % were women. Previous history of neck radiation & familial thyroid disease were found in 1.6 and 29.9 % respectively. Clinical findings: dysphagia: 7.9 %; dysphonia: 3.5%; nodule growth: 19.2 %; hard consistence: 24.7 %; fixation to adjacent structure: 1.5 % and lymphadenopathies (ADP): 3 %. Biochemical findings: TSH was normal in 81.2 % & TPOAb+ in 30.3 %. US features: solid: 53.1 %; hypoechoic: 63.8 %; microcalcifications: 10.3 %; incomplete halo: 15 %; more than 1 nodule: 30.5 %; thyroid heterogeneity: 60.2 % and ADP: 3.8 %. Cytology: Only 1 FNA was needed in 86.8%. Unsatisfactory (excluding cysts): 3.2 %; benign: 77.2%; suspicious: 12.6 % and cancer: 7 % (42 papillary, 2 medullary and 3 non specified). A significant correlation (p<0.02) was established between malignant nodules and rapid growth, hard, fixed, solid nodule, incomplete halo and ADP, though these parameters were more frequent (in absolute number) in benign nodules. Surgery was mainly indicated based on FNA results. Histological diagnosis of 96 patients who underwent surgery showed 51 carcinomas, of which only 2 were cytologically benign and 31 adenomas. Conclusion: Palpable single nodules were more frequent in middle aged euthyroid women. One third had familial thyroid pathology, similar to the presence of TPOAb. On US, nodules were predominantly solid, hypoechoic, single with heterogeneous thyroid gland. FNA was predominantly benign. Rapid growth, hard, fixed, solid nodule, incomplete halo and ADP were associated with malignancy, but benignity was more common. In most of the patients surgery was recommended based on cytological findings. Our results are similar to those reported in other geographic areas.

Unexpected peripheral markers of thyroid function in a patient with a novel mutation of the MCT8 thyroid hormone transporter gene.

The specific thyroid hormone transporter, MCT8, located on the X chromosome, has led to the identification a novel syndrome. The objective is to relate phenotype with several tissue-specific thyroid functions. A 1-year-old boy, who had severe psychological damage and low serum T4, had received l-T4 for 3 months. At admission, body length was normal but weight was low. Off therapy, serum TSH was mildly elevated, serum T4 and free T4 were low, and serum T3 and free T3 were high. Direct sequencing of the MCT8 gene revealed a single nucleotide change that resulted in a novel nonsense mutation at codon 261 (Q261X) in exon 3. Since serum T3 was high, peripheral markers of hyperthyroidism were looked for. Bone age was advanced, despite the presence of malnutrition and low T4. Serum SHBG, a marker of thyroid hormone action in liver, was markedly elevated. Markers of skeletal muscle catabolism, ammonemia and lactic acid, were found to be elevated. The phenotype of MCT 8 mutation might be explained by differences in the entry of thyroid hormones into different cells. In the presence of an inactive MCT8 transporter, the high blood T3 levels might not be enough to prevent brain damage early in life, while they seem to be able to induce a postnatal state of peripheral hyperthyroidism in other tissues, such as liver, bone and skeletal muscle.

Serum thyrotropin (TSH) levels after recombinant human TSH injections in children and teenagers with papillary thyroid cancer.

CONTEXT: In preparation for whole body radioactive iodine scanning, recombinant human TSH (rhTSH) is usually administered as 0.9-mg i.m. injections on 2 consecutive days without regard to age, body size, or other comorbid conditions. OBJECTIVE: Our objective was to determine whether the usual adult rhTSH dosing regimen would result in excessive elevations of serum TSH in children and teenagers with thyroid cancer. DESIGN/SETTING/PATIENTS/INTERVENTIONS: A retrospective review identified 53 children and teenagers with thyroid cancer who underwent whole body radioactive iodine (RAI) scanning over a 12-yr period at two major medical centers (34 after thyroid hormone withdrawal and 19 after rhTSH treatment). MAIN OUTCOME MEASURES: The dynamic time course of changes in serum TSH after rhTSH administration and/or hypothyroid withdrawal was examined. Peak TSH levels were correlated with age, weight, and body surface area. RESULTS: The mean serum TSH at the time of RAI administration was similar in patients undergoing hypothyroid preparation (188 +/- 118 mIU/liter; range, 110-452 mIU/liter) and those treated with rhTSH (134 +/- 75 mIU/liter; range, 32-290 mIU/liter; P = 0.07). Serial determinations after rhTSH injections revealed a mean serum TSH of 268 +/- 76 mU/liter (range, 87-628) at 6 h and 130 +/- 58 mU/liter (range, 67-250) at 24 h after the initial injection, and 361 +/- 78 mU/liter (range 161-524) at 6 h and 134 +/- 44 mU/liter (range, 32-290) at 24 h after the second injection. CONCLUSIONS: The mean TSH levels achieved in children after rhTSH injections are remarkably similar to values previously reported in adults despite marked differences in clinical characteristics between children and adults. These data suggest that dose adjustments are not generally required in children and teenagers undergoing rhTSH stimulation for RAI scanning or serum-stimulated thyroglobulin determinations.

Cancer papilar de tiroides infanto-juvenil: re-evaluación de los factores pronósticos y nueva propuesta de estadificación / Papillary thyroid carcinoma in children and adolescents.A re-evaluation of prognostic factors

El cáncer capilar de tiroide(CaP)es el tumor tiroideo más frecuente en la población infanto-juvenil.Sin embargo no están definidos en este grupo etario los factores predictivos de agresividad.Estudiamos 24 pacientes con CaP entre 1988 y 1999,edades 4,2 a 20 años(19 mujeres,5 varones)En el mismo lapso se operaronn 20 pacientes con adenomas tiroideos,demostrando una altisíma frecuencia de malignidad del 55 por ciento dentro de las neoplasias tiroideas.Los pacientes fueron divididos en dos grupos según la edad al diagnóstico:G1<9 años,n=8 y G2>9 años,n=16.Evaluamos edad,sexo,tamaño del nódulo,adenopatías regionales,infiltración a tejidos vecinos,metástasis hematógenas a distancia,demora diagnóstica,función tiroidea,anticuerpos antitiroideos y tiroglobulina sérica.Conclusiones:la presencia de adenopatías regionales no modifica la evolución favorable del tumor.En cambio la infiltracíon a tejidos vecinos sería un dato clínico de gran peso como predictor de la presencia de metástasis a distancia.Nuestros datos apoyan la propuesta de una nueva estadificación del CaP unificando invasión local y metástasis pulmonares como estadío IV y establecen como los factores pronósticos adversos de mayor peso a la edad y a la invasión local.De esta forma,el exámen clínico permitiría la predicción de la metástasis pulmonares y adecuar el tratamiento a la agresividad del tumor

Cáncer papilar de tiroides infanto-juvenil: re-evaluación de los factores pronósticos y nueva propuesta de estadificación / Papillary thyroid carcinoma in children and adolescents.A re-evaluation of prognostic factors and new staging proposal

El cáncer capilar de tiroide(CaP)es el tumor tiroideo más frecuente en la población infanto-juvenil.Sin embargo no están definidos en este grupo etario los factores predictivos de agresividad.Estudiamos 24 pacientes con CaP entre 1988 y 1999,edades 4,2 a 20 años(19 mujeres,5 varones)En el mismo lapso se operaronn 20 pacientes con adenomas tiroideos,demostrando una altisíma frecuencia de malignidad del 55 por ciento dentro de las neoplasias tiroideas.Los pacientes fueron divididos en dos grupos según la edad al diagnóstico:G1<9 años,n=8 y G2>9 años,n=16.Evaluamos edad,sexo,tamaño del nódulo,adenopatías regionales,infiltración a tejidos vecinos,metástasis hematógenas a distancia,demora diagnóstica,función tiroidea,anticuerpos antitiroideos y tiroglobulina sérica.Conclusiones:la presencia de adenopatías regionales no modifica la evolución favorable del tumor.En cambio la infiltracíon a tejidos vecinos sería un dato clínico de gran peso como predictor de la presencia de metástasis a distancia.Nuestros datos apoyan la propuesta de una nueva estadificación del CaP unificando invasión local y metástasis pulmonares como estadío IV y establecen como los factores pronósticos adversos de mayor peso a la edad y a la invasión local.De esta forma,el exámen clínico permitiría la predicción de la metástasis pulmonares y adecuar el tratamiento a la agresividad del tumor

[Early diagnosis of multiple endocrine neoplasia type 2 (MEN 2) by detection of mutated RET proto-oncogene carriers]. / Diagnóstico precoz de neoplasia endocrina múltiple tipo 2 (MEN 2) por la deteccion de portadores de mutaciones en el proto-oncogen RET]

RET proto-oncogene mutation results in a dominant autosomic inherited syndrome (MEN 2) presenting three distinct subtypes: MEN 2A, MEN 2B, and familial medullary thyroid carcinoma (FMTC). Detection of RET proto-oncogene mutation is a predictor before clinical or biochemical evidence of the disease is present and leads to preventive thyroid removal since there is no effective treatment for metastases. The aim of the present study was to characterize mutations in the RET proto-oncogene in affected patients and to identify potential carriers in their families. Two families with FMTC (5 and 6 members), 4 with MEN 2A (5, 5, 4 and 3 members) and 2 with MEN 2B (5 and 1 members), were studied. DNA was obtained from blood samples in all patients and from thyroid or from pheonochromocytoma tissues in patients submitted to surgery. PCR amplification was performed using specific primers for exons 10, 11 and 16, followed by direct sequencing. Mutations at codon 634 in exon 11 were found in 16 subjects with FMTC and MEN 2A: TGC --> CGC (cysteine to arginine) in 9 cases, TGC --> TAC (cysteine to tyrosine) in 3, and TGC --> TTC (cysteine to phenilalanine) in 4. A unique mutation of codon 918 in exon 16, ATG --> ACG (methionine to threonine), was found in both MEN 2B affected patients. The mutations detected in DNA from peripheral blood were the same as those present in DNA extracted from tumor material. RET mutations were detected in all affected patients, confirming the diagnosis, and in 10 members of their families. In five of the carriers total thyroidectomy was performed. Anatomopathological study showed C-cells hyperplasia or in-situ microcarcinoma in two children (9 and 12 y) with no clinical signs of diseases and medullary thyroid carcinoma in three adults, who were previously unaware of the presence of thyroid nodules. The early detection of RET mutation followed by total thyroidectomy may prevent the development of the disease, specially in affected families, and avoid the fatal outcome of delayed medullary thyroid carcinoma diagnosis.

Evaluation of serum total thyroxine and triiodothyronine and their serum fractions in nonthyroidal illness secondary to congenital heart disease. Studies before and after surgery.

Serum thyroid hormones, serum thyroxine-binding proteins and serum thyroid hormone fractions have been measured in children with congenital heart disease before and after open cardiac surgery. Twenty prepubertal patients, mean (+/- SD) age 3.6 +/- 3.7 yr, were studied before, immediately after, and 24 and 48 h after surgery. A control group of 6 normal prepubertal children was also studied in basal conditions. Serum TSH was normal in all samples collected. Significantly low mean levels of serum TBG (261 +/- 57 vs 456 +/- 71 nmol/L in normals), serum TBPA (2692 +/- 1119 vs 5999 +/- 2226 nmol/L), serum TBG-bound T4, serum TBPA-bound T4, serum TT3, serum TBG-bound T3 and free T3 were found before cardiac surgery in the patients. While serum binding proteins did not change after surgery, significant decrements in serum TT4, serum TBG-bound T4, serum TT3, serum TBG-bound T3, serum albumin-bound T3 and free T3 were observed after surgery. Free T4 and albumin-bound T4 remained normal. Our study shows that many features of nonthyroidal illness were present in our patients before surgery. In this context, the stress of surgery induced further alterations in several parameters of thyroid metabolism. It is concluded that the changes occurring in this model of chronic, as well as acute, nonthyroidal illness reflect adaptative changes, rather than altered thyroid function, as shown by normal serum free T4, serum albumin-bound T4 and serum TSH.

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)

Thyroid dysfunction in Hodgkin's disease.

Radiotherapy to the neck and/or polychemotherapy late effects on the thyroid were investigated in 51 patients (34 males and 17 females) with Hodgkin's disease. Except for two untreated, recently diagnosed patients, all were studied after 1 to 105 months (median, 27.5 months) of completion of polychemotherapy. Age ranged from 6.2 to 36.6 years (median, 13.6 years). Patients were divided according to treatment into four groups: (A) patients treated with CVPP (cyclophosphamide, vinblastine, procarbazine, and prednisone); (B) 22 patients treated with CVPP plus radiotherapy (median radiation dose to the thyroid, 3000 cGy); (C) seven patients with ACOP/BVP (adriamycin, cyclophosphamide, vincristine, prednisone, bleomycin, vinblastine, procarbazine); and (D) seven patients treated with different polychemotherapy protocols, four of whom also received radiotherapy. Elevated basal and/or post-TRH, -TSH levels were found in the following: Group A: two of 12 patients (17%); Group B: 11 of 22 (50%); Group C: four of seven (57%); and Group D: two of seven (28%). Positive antimicrosomal thyroid antibody titers (AM Ab) were found in the following: Group A: three of 12 patients (25%); Group B: six of 21 (28%), Group C: two of seven (28%); and Group D: one of six (17%). Of 46 patients studied, 12 (26%) had positive AM Ab; 37 of 46 patients were younger than 20 years of age, 11 (30%) of whom had positive AM Ab versus 4% in the normal population (P less than 0.001). Two recently diagnosed, untreated patients had either high TSH response to TRH or positive AM Ab. In conclusion, higher frequency of thyroid dysfunction was observed in patients receiving radiotherapy (50% versus 27%). Prevalence of positive AM Ab, apparently unrelated to therapy, was higher in young patients than in the normal population. A predisposition to autoimmune thyroid disease seems to be present in these patients, but it is not possible to discern how lymphoma and thyroiditis are interrelated.

Long-term endocrine sequelae after surgery, radiotherapy, and chemotherapy in children with medulloblastoma.

Thirteen children with medulloblastoma, were studied after 2 to 62 months off radiotherapy and chemotherapy with methotrexate and BCNU. Ages at time of study ranged from 2.3 to 15.7 years. Eleven patients, followed for a mean of 22 months, showed a significant decrease of height score, whereas nine patients had deficient growth hormone (GH) response to provocative tests. Clinical pubertal progression was normal in all patients, and three of five girls with advanced pubertal development had menarche. No evidences of gonadotropin disturbances were found in five patients whereas seven had raised basal follicle-stimulating hormone (FSH) level or FSH response to luteinizing hormone-releasing hormone (LH-RH). Abnormalities in thyrotrophin (TSH) secretion were found in 9 of 13 patients. This study shows that poor growth and GH deficiency were frequent in our patients. The high frequency of thyroid disturbances observed point out the need of evaluating thyroid function for adequate replacement therapy. Perhaps modification of adjuvant chemotherapy in the future can diminish drug-induced gonadal damage.