RESUMO
OBJECTIVE: Between 1940 and 1970, 1.5 million female fetuses were exposed to diethylstilbestrol in utero. Numerous deleterious effects on reproductive anatomic and physiologic characteristics have been documented in these women. However, the effects of this exposure on nonreproductive systems, which may have lifelong consequences as this cohort of women progresses beyond the childbearing years, have received little attention. On the basis of an earlier preliminary observation of altered immune reponse, we hypothesized that diethylstilbestrol-exposed women may show abnormalities in T-cell-mediated immune response. STUDY DESIGN: Thirteen women exposed to diethylstilbestrol in utero were compared with 13 age- and menstrual cycle phase-matched control subjects with respect to the in vitro T-cell response to the mitogens phytohemagglutinin, concanavalin A, and interleukin 2. RESULTS: As compared with controls, tritiated thymidine incorporation by T cells harvested from diethylstilbestrol-exposed women was increased 3-fold over a range of concentrations in response to concanavalin A (P <.001), increased by 50% over a range of concentrations in response to phytohemagglutinin (P <.001), and increased 2-fold in response to the endogenous mitogen interleukin 2 (P <.05). CONCLUSIONS: In vitro evidence suggests that women exposed to diethylstilbestrol have alterations in T-cell-mediated immunity. These changes require further attention with regard to their characterization, their role in the pathogenesis of cancer and autoimmunity, and their presence in normal women exposed to diethylstilbestrol in utero.
Assuntos
Dietilestilbestrol/efeitos adversos , Imunidade/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Adulto , Divisão Celular , Células Cultivadas , Concanavalina A/farmacologia , Feminino , Humanos , Imunidade Celular/efeitos dos fármacos , Interleucina-2/farmacologia , Fito-Hemaglutininas/farmacologia , Gravidez , Estudos Prospectivos , Linfócitos T/imunologia , Timidina/metabolismo , TrítioAssuntos
Feto/metabolismo , Hipófise/metabolismo , Prenhez , Tiroxina/metabolismo , Animais , Feminino , Gravidez , Ovinos , Tri-Iodotironina/metabolismoRESUMO
In view of the reported enhanced sensitivity to iodide-induced hypothyroidism in patients with cystic fibrosis, studies were carried out to determine the possible mechanism of this abnormality. The intrathyroid organification of iodide, as assessed by the iodide-perchlorate discharge test, was normal in patients with cystic fibrosis, strongly suggesting that an organification defect was not present. The serum TSH response to TRH was not significantly different from the response in normal children and adolescents. Serum T4 concentration was normal whereas that of T3 was decreased in patients with cystic fibrosis, strongly suggesting decreased peripheral conversion of T4 to T3, as commonly occurs in nonthyroid illness. Our findings do not delineate the mechanism whereby patients with cystic fibrosis develop iodide-induced hypothyroidism.
Assuntos
Fibrose Cística/fisiopatologia , Glândula Tireoide/fisiopatologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Hipotireoidismo/induzido quimicamente , Iodetos/efeitos adversos , Masculino , Testes de Função Tireóidea , Tireotropina/sangue , Hormônio Liberador de Tireotropina , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
Pseudohypoparathyroidism (pseudo HPT) is the prototype of a group of diseases with end organ unresponsiveness to parathyroid hormone (PTH). Patients with the classic form of this disease have both renal and osseous resistance to PTH. We describe a rare variant of pseudo HPT with classic renal unresponsiveness to PTH but normal skeletal responsiveness to this hormone. The latter patients develop metabolic bone disease in response to depressed calcium and elevated PTH levels. Skeletal abnormalities are histologically and radiologically indistinguishable from renal osteodystrophy and these patients frequently present in childhood with symptoms relating to slipped capital femoral epiphyses. The latter radiologic findings, in the face of normal renal function or the classic somatic features of the syndrome, are highly suggestive of pseudo HPT with normal skeletal responsiveness to PTH.