Aspectos genéticos do hipotireoidismo congênito

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cistoadenoma mucinoso do apêndice: relato de caso

O cistoadenoma mucinoso do apêndice ceca l, um tipo de mucocele do apêndice, é uma neoplasia benigna caracterizada pela metaplasia focal ou difusa do epitélio superficial da mucosa, associada à dilatação do apêndice e produção de muco para a luz apendicular. No presente estudo os autores relatam um caso de cistoadenoma mucinoso do apêndice observado em uma mulher de 65 anos de idade, com dor e massa palpável no quadrante inferior direito do abdome, cujo quadro teve início há 1 ano. O diagnóstico de cistoadenoma do apêndice foi suspeitado através da ultrassonografia e tomografia computadorizada do abdome, e confirmado pelo exame histopatológico. A paciente também apresentava cálculos na vesícula biliar e um cisto renal à direita. A laparotomia foi indicada sendo realizada a apendicectomia, a colecistectomia e a exérese do cisto renal. Na presente discussão esperamos contribuir para o diagnóstico precoce dessa doença e a melhor compreensão de sua classificação e patogenia.

Possible association between Carney complex and multiple endocrine neoplasia type 1 phenotypes

Complexo de Carney (CNC) e neoplasia endócrina múltipla tipo 1 (MEN1) são formas de neoplasias endócrinas múltiplas de herança autossômica dominante. O diagnóstico do CNC ocorre quando dois critérios maiores (lentiginose, doença nodular pigmentosa primária das adrenais, mixomas cardíacos e cutâneos, acromegalia, neoplasia testicular, carcinoma de tireóide) são observados e/ou um critério maior associado a um critério suplementar (familiar afetado, mutação do gene PRKAR1A) ocorre. Por outro lado, o diagnóstico de MEN1 dá-se pela detecção de dois ou mais tumores localizados na glândula hipofisária, paratireóide e/ou células pancreáticas. O presente caso descreve um homem de 55 anos, com diagnóstico de acromegalia, hiperparatireoidismo primário e carcinoma papilífero de tireóide, exibindo critérios diagnósticos para as duas condições descritas. Embora possa ter ocorrido apenas uma associação esporádica, ou a acromegalia per se tenha predisposto ao carcinoma papilífero, novos mecanismos moleculares podem estar envolvidos.

Time-dependent effects of lead on rat reproductive functions

The effects of exposure to lead on endocrine function and the reproductive parameters were studied in pubertal rats treated with 1.0 g l(-1) lead acetate in drinking water for 20 days (subacute group) or 9 months (chronic group) in addition to i.v. injections of lead acetate (0.1 mg 100 g(-1) body wt.) every 10 (subacute group) or 15 days (chronic group). Although basal levels of testosterone were higher both in plasma and in testes of acutely intoxicated animals, the circulating levels of luteinizing hormone (LH) were not affected in either group, nor was the LH-releasing hormone content of the median eminence. The density of [I-125]LH/human chorionic gonadotrophin (hCG) binding sites in testicular homogenates was reduced by saturnism in both groups, concomitant with a significantly increased apparent affinity constant of the hormone-receptor complex. These data can be viewed as the result of a mixture of specific lead toxicity (e.g. at the enzyme level) with other more general actions (e.g. at the level of the hypothalamus-pituitary-testicular axis).

THE EFFECT OF TUBEROINFUNDIBULAR DOPAMINERGIC-NEURONS ON PROLACTIN AND ALPHA-MELANOCYTE STIMULATING HORMONE-RELEASE

The effect of tubero-infundibular dopaminergic neurons (TIDA) on the release of prolactin (PRL) and alpha-melanocyte stimulating hormone (alpha-MSH) was studied in median eminence-lesioned (MEL) male rats (N = 6-28). Plasma PRL and alpha-MSH levels were significantly elevated 2 (86.1 +/- 19.8 and 505.1 +/- 19.1 ng/ml), 4 (278.7 +/- 15.5 and 487.4 +/- 125.1 ng/ml), 7 (116.2 +/- 16.2 and 495.8 +/- 62.6 ng/ml) and 14 (247.3 +/- 26.1 and 448.4 +/- 63.8 ng/ml) days after MEL when compared to sham-operated control animals (55.5 +/- 13.4 and 56.2 +/- 6.1 ng/ml, respectively). MEL altered plasma PRL and alpha-MSH levels in a differential manner, with a 1.5-to 5.0-fold increase in PRL and an 8.0-to 9.0-fold increase in alpha-MSH. The increase of alpha-MSH levels occurred abruptly and remained constant from days 2 to 14. These observations indicate that TIDA plays an important role in the pituitary release of PRL and alpha-MSH and provide evidence that the release of the two hormones occurs in a differential manner.

POSSIBLE MECHANISMS FOR REDUCTION OF CIRCULATING CONCENTRATIONS OF PROGESTERONE BY INTERFERON-ALPHA IN COWS - EFFECTS ON HYPERTHERMIA, LUTEAL CELLS, METABOLISM OF PROGESTERONE AND SECRETION OF LH

Experiments were performed to determine the mechanism by which recombinant bovine interferon-alpha(I)1 (rbIFN-alpha) causes an acute reduction in plasma concentrations of progesterone. In experiment 1, administration of a prostaglandin synthesis inhibitor blocked rbIFN-alpha-induced hyperthermia but did not prevent the decline in plasma concentrations of progesterone. The decline in progesterone concentrations caused by rbIFN-alpha was, therefore, not a direct consequence of the associated hyperthermia or of pathways mediated through prostaglandin synthesis. It is also unlikely that rbIFN-alpha acts to increase the clearance of progesterone since injection of rbIFN-alpha did not decrease plasma concentrations of progesterone in ovariectomized cows given an intravaginal implant of progesterone (experiment 2). In experiment 3, rbIFN-alpha did not affect basal and LH-induced release of progesterone from cultured luteal slices, indicating that rbIFN-alpha is unlikely to affect luteal function directly. Injection of rbIFN-alpha did, however, cause a decrease in plasma concentrations of LH in ovariectomized cows (experiment 4) that coincided temporally with the decrease in progesterone concentrations seen in cows having a functional corpus luteum. The present results strongly suggest that rbIFN-alpha acts to reduce secretion of progesterone by interfering with pituitary support for luteal synthesis of progesterone. The finding that rbIFN-alpha can inhibit LH secretion implies that interferon-alpha molecules should be considered among the cytokines that can regulate hypothalamic or pituitary function.

ENDOCRINE INTERACTION BETWEEN ZINC AND PROLACTIN - AN INTERPRETATIVE REVIEW

Zinc plays a very important role in animal and human metabolism. Nowadays, it is one of the most extensively studied trace element, since its sphere of action has been demonstrated to be very broad. From the biochemical standpoint, it controls more than 300 different enzymes, many of them involved with intermediary metabolism, DNA and RNA synthesis, gene expression, and immunocompetence. It also plays a significant role in hormonal homeostasis, since it can interact with almost all hormones. Zn2+ is closely related to the thyroid and steroid hormones, insulin, parathormone, and pituitary hormones, particularly prolactin (PRL). Zn2+ can inhibit PRL secretion within a range of physiologically and pharmacologically relevant concentrations. This property has raised the possibility of clinical applications of zinc. In this article, we review the Literature on the subject in an attempt to provide a comprehensible general view.

Urocortin in the central nervous system of a primate (Cebus apella): Sequencing, immunohistochemical, and hybridization histochemical characterization

The urocortin (UCN)-like immunoreactivity and UCN mRNA distribution in various regions of the nonprimate mammalian brain have been reported. However, the Edinger-Westphal nucleus (EW) appears to be the only brain site where UCN expression is conserved across species. Although UCN peptides are present throughout vertebrate phylogeny, the functional roles of both UCN and EW remain poorly understood. Therefore, a study focused on UCN system organization in the primate brain is warranted. By using immunohistochemistry (single and double labeling) and in situ hybridization, we have characterized the organization of UCN-expressing cells and fibers in the central nervous system and pituitary of the capuchin monkey (Cebus apella). In addition, the sequence of the prepro-UCN was determined to establish the level of structural conservation relative to the human sequence. To understand the relationship of acetylcholine cells in the EW, a colocalization study comparing choline acetyltransferase (ChAT) and UCN was also performed. The cloned monkey prepro-UCN is 95% identical to the human preprohormone across the matched sequences. By using an antiserum raised against rat UCN and a probe generated from human cDNA, we found that the EW is the dominant site for UCN expression, although UCN mRNA is also expressed in spinal cord lamina IX. Labeled axons and terminals were distributed diffusely throughout many brain regions and along the length of the spinal cord. of particular interest were UCN-immunoreactive inputs to the medial preoptic area, the paraventricular nucleus of the hypothalamus, the oral part of the spinal trigeminal nucleus, the flocculus of the cerebellum, and the spinal cord laminae VII and X. We found no UCN hybridization signal in the pituitary. In addition, we observed no colocalization between ChAT and UCN in EW neurons. Our results support the hypothesis that the UCN system might participate in the control of autonomic, endocrine, and sensorimotor functions in primates.

Non-ventilation during early incubation in combination with dexamethasone administration during late incubation: 1. Effects on physiological hormone levels, incubation duration and hatching events

This study investigated the effect of non-ventilation of the incubator during the first 10 days of incubation and its combination with dexamethasone administration at day 16 or 18 of incubation on hatching parameters and embryo and post-hatch chick juvenile physiology. A total of 2400 hatching eggs produced by Cobb broiler breeders were used for the study. Blood samples were collected at day 18 of incubation, at internal pipping stage (IP), at the end of hatch (day-old chick) and at 7-daypost-hatch for T-3, T-4 and corticosterone levels determination. From 448 to 506 h of incubation, the eggs were checked individually in the hatcher every 2 h for pipping and hatching. The results indicate that non-ventilation during the first 10-day shortened incubation duration up to IP, external pipping (EP) and hatch, had no effect on hatchability and led to higher T-3 levels at IP but lower corticosterone levels at 7-day-post-hatch. The injection of dexamethasone at days 16 and 18 of incubation affected hatching and blood parameters in both the ventilated and non-ventilated embryos differentially and the effect was dependent on the age of the embryo. Dexamethasone increased T-3 levels and T-3/T-4 ratios but the effect was greater with early non-ventilation of eggs. Dexamethasone decreased hatchability but the effect was greater when injected at day 16 and especially in ventilated embryos. The effects of incubation protocols and dexamethasone treatments during incubation were still apparent in the hatched chicks until 7 days of age. The changes in T-3, T-4 and corticosterone levels observed in response to the early incubation conditions and late dexamethasone treatments in this study suggest that incubator ventilation or non-ventilation may influence the hypothalamic-pituitary-adrenal axis (HPA) regulation of stress levels (in terms of plasma corticosterone levels) and thyroid function in the embryo with impact on incubation duration, hatching events and early post-hatch life of the chick. Our results also suggest that some stages of development are more sensitive to dexamethasone administration as effects can be influenced by early incubation protocols. (c) 2006 Elsevier B.V. All rights reserved.

Effect of zinc administration on thyrotropin releasing hormone-stimulated prolactinemia in healthy men

Previous in vitro studies have demonstrated zinc (Zn++) inhibition of basal and of potassium (K+) or thyrotropin-releasing hormone (TRH)-stimulated prolactin (PRL) secretion, in a selective, reversible, and dose-dependent manner. Thus, Zn++ may regulate physiologically pituitary PRL secretion. Furthermore, studies with patients with uremia, cirrhosis or prolactinoma, have shown the coexistence of hypozincemia and hyperprolactinemia and zinc supplementation did not correct hyperprolactinemia in these patients. In normal individuals Zn++ administration produced controversial results on PRL secretion. Here, we investigated whether zinc administration affects TRH-stimulated PRL in healthy men. We found that Zn++ administration does not change the TRH-stimulated PRL. Therefore, in normal conditions, Zn++ does not inhibit TRH-stimulated prolactinemia. In addition, we found that acute increases of blood PRL and TRH do not alter blood Zn++ levels.

Reproductive aspects in female rats exposed prenatally to hydrocortisone

We investigated the effects of hydrocortisone during the prenatal period and its later repercussion on reproductive aspects of female rats. Pregnant rats were treated (s.c.) with hydrocortisone acetate, at 1.5 mg/day on the 17th, 18th, and 19th days of pregnancy. Although the present study was not intended to identify mechanisms of toxicity, the treatment with hydrocortisone in the last period of pregnancy presented no signs of toxicity. The efficacy of the hydrocortisone in reducing the adrenal wet mass and plasma corticosterone levels immediately after delivery in both the treated mothers and in respective pups at birth may indicate impairment of the hypothalamus-pituitary-adrenal axis. In addition, the treatment with hydrocortisone did not interfere in the development of the female descendants until puberty. However, it affected the estrous cycle and fertility, Probably, the prenatal exposure to corticosteroids had altered at least partially the hypothalamus-pituitary-gonadal axis, resulting in the damages observed in adult life. These results indicate that the use of the hydrocortisone at a dose that apparently does not endanger the neonate led to undesirable effects in the adult reproductive phase, resulting in later deleterious alteration of the reproductive physiology in female rats. (C) 2004 Elsevier B.V. All rights reserved.

HORMONAL AND METABOLIC STUDY OF A CASE OF ADIPOSIS-DOLOROSA (DERCUMS DISEASE)

A case of a 43-year-old nonobese woman with adiposis dolorosa (Dercum's disease) is reported. Muscle glucose uptake and oxidation before and after ingestion of 75 g of glucose were similar to control group values, although a greater insulin release (16,578 vs 6,242 +/- 1,136 muU/3 h) occurred simultaneously. In vitro studies of abdominal normal and painful subcutaneous adipose tissue of the patient revealed lower responsiveness to norepinephrine and lack of response to the antilipolytic effect of insulin in the painful adipose tissue (0.98 vs 1.43 muM FFA/10(6) cells at 5.0 muM of norepinephrine). The disease was not correlated with the HLA system and there were no alterations in hormonal secretion at the pituitary, adrenal, gonadal, and thyroid levels. These findings indicate the presence of peripheral insulin resistance in this patient with adiposis dolorosa.

Secretion of metalloendopeptidase 24.15 (EC 3.4.24.15)

The metalloendopeptidase EP24.15 (EC3.4.24.15) is a neuropeptide-metabolizing enzyme present in neural and endocrine tissues, presumably functioning extracellularly, Because the majority of the EP24.15 activity is identified in the soluble fraction of cellular homogenates, suggesting that the enzyme is primarily an intracellular protein, we addressed the issue of how EP24.15 arrives in the extracellular environment, We utilized a model system of neuroendocrine secretion, the AtT20 cell, According to both enzymatic activity and immunologic assays, EP24.15 was synthesized in and released from AtT20 cells. Under basal conditions and after stimulation by corticotropin-releasing hormone or the calcium ionophore A23187, EP24.15 activity accumulated in the culture medium. This secretion was not attributable to cell damage, as judged by the absence of release of cytosolic enzyme markers and the ability to exclude trypan blue dye. Pulse-chase analysis and subcellular fractionation of AtT20 cell extracts suggested that the mechanism of EP24.15 secretion is not solely via classical secretory pathways, Additionally, drugs which disrupt the classical secretory pathway, such as Brefeldin A and nocodazole, blocked A23187-stimulated EP24.15 release yet had no effect on basal EP24.15 release, suggesting differences in the basal and stimulated pathways of secretion for EP24.15. In summary, EP24.15 appears to be secreted from AtT20 pituitary cells into the extracellular milieu, where the enzyme can participate in the physiologic metabolism of neuropeptides.

The implications of microsurgical anatomy for surgical approaches to the sellar region

The knowledge of the normal anatomy and variations regarding the management of tumors of the sellar region is paramount to perform safe surgical procedures. The sellar region is located in the center of the middle cranial fossa; it contains complex anatomical structures, and is the site of various pathological processes: tumor, vascular, developmental, and neuroendocrine. We review the microsurgical anatomy (microscopic and endoscopic) of this region and discuss the surgical nuances regarding this topic, based on anatomical concepts.

Pediatric Chronic Sclerosing Sialadenitis: Kuttner Tumor

Chronic sclerosing sialadenitis is an uncommon cause of salivary gland enlargement mainly occurring in the fifth and seventh decade of life. In the Western population, chronic sclerosing sialadenitis has been characterized as an IgG4-related disease. Although rare, this lesion occurs in children. To increase awareness about this entity in the pediatric age group, we report the case of an 11-year-old boy with a hard, 4.0-cm circumscribed mass in the right submandibular gland. Histologically there was marked distortion of the gland architecture by a dense lymphocytic infiltrate and extensive fibrosis with septa that crossed and distorted the gland, leaving atrophic acini and dilated, irregular ducts. The lymphoid infiltrate formed multiple follicles with active germinal centers, numerous plasma cells, and areas with diffuse arrangement. Immunophenotyping showed abundant CD20- and CD3-positive lymphocytes; cytokeratin AE1/AE3 highlighted the distorted architectural pattern; IgG staining showed large numbers of positive cells infiltrating the interstitium and surrounding the atrophic acini and ducts. IgG4 staining revealed a large proportion of positive infiltrating elements. Kuttner tumor belongs to the group of IgG4-related sclerosing diseases. The differential diagnosis includes pleomorphic adenoma and other salivary gland neoplasms. Its recognition in children is important clinically because this entity is amenable to steroid treatment, and additional work up and follow up is warranted to stave off other IgG4-related diseases/complications.