RESUMO
AIMS: The purpose of this study was to identify the number of pregnancies affected by pre-gestational diabetes in the Republic of Ireland; to report on pregnancy outcomes and to identify areas for improvement in care delivery and clinical outcomes. METHODS: Healthcare professionals caring for women with pre-gestational diabetes during pregnancy were invited to participate in this retrospective study. Data pertaining to 185 pregnancies in women attending 15 antenatal centres nationally were collected and analysed. Included pregnancies had an estimated date of delivery between 1 January and 31 December 2015. RESULTS: The cohort consisted of 122 (65.9%) women with Type 1 diabetes and 56 (30.3%) women with Type 2 diabetes. The remaining 7 (3.8%) pregnancies were to women with maturity-onset diabetes of the young (MODY) (n = 6) and post-transplant diabetes (n = 1). Overall women were poorly prepared for pregnancy and lapses in specific areas of service delivery including pre-pregnancy care and retinal screening were identified. The majority of pregnancies 156 (84.3%) resulted in a live birth. A total of 103 (65.5%) women had a caesarean delivery and 58 (36.9%) infants were large for gestational age. CONCLUSIONS: This audit identifies clear areas for improvement in delivery of care for women with diabetes in the Republic of Ireland before and during pregnancy.
Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/terapia , Cuidado Pré-Concepcional/estatística & dados numéricos , Resultado da Gravidez/epidemiologia , Gravidez em Diabéticas/terapia , Aborto Espontâneo/epidemiologia , Adulto , Aspirina/uso terapêutico , Cesárea , Auditoria Clínica , Atenção à Saúde , Parto Obstétrico , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Retinopatia Diabética/diagnóstico , Feminino , Macrossomia Fetal/epidemiologia , Ácido Fólico/uso terapêutico , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Recém-Nascido , Bombas de Infusão Implantáveis , Insulina/uso terapêutico , Sistemas de Infusão de Insulina , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Irlanda/epidemiologia , Nascido Vivo/epidemiologia , Programas de Rastreamento , Metformina/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Gravidez , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos , Natimorto/epidemiologia , Complexo Vitamínico B/uso terapêuticoRESUMO
Introduction This case series describes the diagnosis of the first case of community transmission of SARS-CoV-2 in the Republic of Ireland. Cases Case 1: A 25 year old male presented with dyspnoea, cough and high fevers for 4 days. He was commenced on broad-spectrum antimicrobials and oxygen therapy. His respiratory function deteriorated in spite of these measures and he required mechanical ventilation. CT showed left upper lobe consolidation as well as multifocal ground-glass opacification. Case 2: A 43 year-old male presented with headache and was found incidentally to have pneumonia. He was recently diagnosed with pituitary apoplexy secondary to an adenoma with resultant pituitary insufficiency but MRI brain was stable. His respiratory function deteriorated in spite of antibiotics and he required mechanical ventilation. CT showed likely atypical infection with resultant ARDS. Outcome Both underwent nasopharyngeal RT-PCR testing for SARS-CoV-2. Patient 2 was positive. Patient 1 was extubated and made a good recovery. Patient 2 was transferred to another centre for ECMO therapy. He died 27 days after transfer. Conclusion Given the atypical presentations in generally otherwise young and healthy individuals, the decision was made outside of national guidance to perform testing for SARS-CoV-2. This diagnosis had far-reaching implications for the SARS-CoV-2 pandemic within Ireland.
Assuntos
Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Adulto , Betacoronavirus , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Tosse/virologia , Dispneia/virologia , Evolução Fatal , Febre/etiologia , Humanos , Irlanda/epidemiologia , Masculino , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2 , Tomografia Computadorizada por Raios XRESUMO
Idiopathic isolated ACTH deficiency, congenital or acquired, is rare. It may be found in association with primary hypothyroidism. Here we describe four cases of acquired idiopathic isolated ACTH deficiency illustrating its importance and variable presentation. All cases had a structurally normal pituitary gland and persistently normal residual pituitary function. Three cases had co-existing primary hypothyroidism. We discuss the protean presentation of this rare but important condition, its treatment, associations, and possible aetiologies.
Assuntos
Insuficiência Adrenal/complicações , Hipotireoidismo/complicações , Insuficiência Adrenal/epidemiologia , Insuficiência Adrenal/etiologia , Adulto , Idoso , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Hipotireoidismo/epidemiologia , Masculino , Suspensão de TratamentoRESUMO
The management of diabetic gastroparesis resistant to medical therapy is very difficult Gastric electrical stimulation (GES) is a relatively new therapeutic modality which has shown some promise in international trials. It has seen use in four patients in Ireland. Our aim was to determine if GES improved patients' outcomes in terms of duration and cost of inpatient stay and glycaemic control. We reviewed the patients' case notes and calculated the number of days spent as an inpatient with symptomatic gastroparesis pre and post pacemaker, the total cost of these admissions, and patients' average HbA1c pre and post GES. Mean length of stay in the year pre GES was 81.75 days and 62.25 days in the year post GES (p=0.89). There was also no improvement in glycaemic control following GES. GES has been ineffective in improving length of inpatient stay and glycaemic control in our small patient cohort.
Assuntos
Complicações do Diabetes/terapia , Terapia por Estimulação Elétrica/métodos , Gastroparesia/terapia , Complicações do Diabetes/fisiopatologia , Gastroparesia/etiologia , Humanos , Irlanda , Resultado do TratamentoRESUMO
AIMS: Pre-gestational diabetes mellitus (PGDM) is associated with adverse outcomes. We aimed to examine pregnancies affected by PGDM; report on these pregnancy outcomes and compare outcomes for patients with type 1 versus type 2 diabetes mellitus; compare our findings to published Irish and United Kingdom (UK) data and identify potential areas for improvement. METHODS: Between 2016 and 2018 information on 679 pregnancies from 415 women with type 1 Diabetes Mellitus and 244 women with type 2 diabetes was analysed. Data was collected on maternal characteristics; pregnancy preparation; glycaemic control; pregnancy related complications; foetal and maternal outcomes; unscheduled hospitalisations; congenital anomalies and perinatal deaths. RESULTS: Only 15.9% of women were adequately prepared for pregnancy. Significant deficits were identified in availability and attendance at pre-pregnancy clinic, use of folic acid, attaining appropriate glycaemic targets and appropriate retinal screening. The majority of pregnancies (n = 567, 83.5%) resulted in a live birth but the large number of infants born large for gestational age (LGA) (n = 280, 49.4%), born prematurely <37 weeks and requiring neonatal intensive care unit (NICU) admission continue to be significant issues. CONCLUSIONS: This retrospective cohort study identifies multiple targets for improvements in the provision of care to women with pre-gestational DM which are likely to translate into better pregnancy outcomes.
Assuntos
Resultado da Gravidez , Gravidez em Diabéticas/diagnóstico , Gravidez em Diabéticas/epidemiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Irlanda , Gravidez , Estudos RetrospectivosRESUMO
Periodontitis is a common, chronic inflammatory disease initiated by bacteria which has an increased prevalence and severity in patients with type 2 diabetes. Recent studies indicate that the co-morbid presence of periodontitis can, in turn, adversely affect diabetic status and the treatment of periodontitis can lead to improved metabolic control in diabetes patients. Current evidence points to a bidirectional interrelationship between diabetes and inflammatory periodontitis. The importance of oxidative stress-inflammatory pathways in the pathogenesis of type 2 diabetes and periodontitis has recently received attention. Given the bidirectional relationship between these two conditions, this review discusses the potential synergistic interactions along the oxidative stress-inflammation axis common to both type 2 diabetes and periodontitis, and the implications of this relationship for diabetic patients.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Estresse Oxidativo/fisiologia , Periodontite/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Humanos , Periodontite/metabolismo , Periodontite/patologiaRESUMO
The purpose of this study was to assess the knowledge diabetic patients have of their risk for periodontal disease, their attitude towards oral health and their oral health-related quality of life (OHRQL). One hundred and one consecutive patients (age range 31-79 years) recruited from a diabetic outpatient clinic participated in the study. Twenty-seven per cent of participants had type 1 diabetes, 66% type 2 and 7% did not know what type of diabetes they had. The length of time since participants were diagnosed as diabetic ranged from 1 to 48 years. Metabolic control of diabetes as determined by HbA1c levels ranged from 6.2% to 12.0% compared with the normal range of 4.5-6.0%. Thirty-three per cent of participants were aware of their increased risk for periodontal disease, 84% of their increased risk for heart disease, 98% for eye disease, 99% for circulatory problems and 94% for kidney disease. Half of the participants who were aware of their increased risk for periodontal disease had received this information from a dentist. Dental attendance was sporadic, with 43% reporting attendance within the last year. OHRQL was not significantly affected by the presence of diabetes in the group surveyed, in comparison with a previous survey of non-diabetic patients. A significant association was found between metabolic control and dentate status. Awareness of the potential associations between diabetes, oral health and general health needs to be increased in diabetic patients.
Assuntos
Atitude Frente a Saúde , Complicações do Diabetes/psicologia , Saúde Bucal , Doenças Periodontais/psicologia , Qualidade de Vida , Adulto , Idoso , Conscientização , Diabetes Mellitus/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Periodontais/complicações , Risco , Inquéritos e QuestionáriosRESUMO
Over the past decade the Australian health care system has moved rapidly toward a greater emphasis on medical care being provided within the community. This trend can only continue as our population ages and levels of chronic and complex illness continue to rise. Primary care now includes: a higher proportion of general practitioners working in group practices supported by practice nurses and allied health professionals- both on site and in the community, increased patient presentations for chronic and complex disease - often compounded by mental health and social issues, and, more hospital in the home, early discharge and similar programmes enabling shared management of sicker patients in the community.
Assuntos
Competência Clínica , Serviços de Saúde Comunitária/tendências , Atenção à Saúde/tendências , Atenção Primária à Saúde/tendências , Austrália , Educação Médica Continuada , Humanos , Assistência ao PacienteRESUMO
Diabetes mellitus is the most common chronic metabolic disease and a major source of morbidity and mortality. Type 2 diabetes (T2D) is by far the most prevalent form of diabetes accounting for around 90% of cases worldwide. In recent years it has become apparent that a diabetes epidemic is unfolding as a result of increasing obesity, sedentary lifestyles and an ageing population. The enormity of the diabetes epidemic raises concern about the total cost to healthcare systems. This study was undertaken to investigate the direct healthcare costs of managing T2D in Ireland. Data was captured on 701 diabetes patients attending four diabetes centres. A bottom-up, prevalence-based design was used, which collected data on hospital resource use and clinical outcome measures over a 12-month period (1999/2000). The study was observational in nature, focusing on usual care of patients with T2D. Although the true prevalence of T2D in Ireland is unknown, conservative estimates are 3.9% for diagnosed diabetes and 6% for both diagnosed and undiagnosed diabetes. Using these figures the annual total direct cost was estimated at 377.2 million euro for diagnosed diabetes and 580.2 million euro for both diagnosed and undiagnosed diabetes. This corresponds to 4.1% and 6.4% of total healthcare expenditure respectively. Hospitalisations were the main driver of costs, accounting for almost half of overall costs, while ambulatory and drug costs accounted for 27% and 25% respectively. Hospitalisation costs were high because 60% of patients had developed complications. The most common microvascular and macrovascular complications were neuropathy and angina respectively. The annual cost of care for patients with microvascular and macrovascular complications were 1.8 and 2.9 times the cost of treating those without clinical evidence of complications respectively. The figure for patients with both types of complications was 3.8. This study shows that T2D is a very costly disease, largely due to the cost of and the management of complications. Many diabetes related complications are preventable, therefore it would appear a cost-effective approach for government to invest in the prevention of T2D and diabetes related complications.
Assuntos
Efeitos Psicossociais da Doença , Diabetes Mellitus Tipo 2/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Idoso , Assistência Ambulatorial/economia , Doença Crônica , Complicações do Diabetes/economia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/terapia , Custos de Medicamentos , Feminino , Custos Hospitalares , Humanos , Irlanda/epidemiologia , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
The neuropeptide galanin inhibits glucose-stimulated insulin release in dogs and rodents and has been proposed as having a role in the control of insulin release in humans. The effect of infused galanin on intravenous glucose tolerance in humans was investigated by giving an intravenous glucose tolerance test (0.5 g glucose/kg body wt) alone and with infusions of synthetic porcine galanin at high-dose levels (80 and 160 pmol.kg-1.min-1) to seven healthy male volunteers. The results showed no effect of galanin infusion on plasma glucose or serum insulin, although a rise in serum growth hormone even in the face of the intravenous glucose load confirmed the potent growth hormone-stimulating effect of galanin. These results suggest that caution should be exercised in extrapolating a physiological role for galanin in humans from the results of animal studies.
Assuntos
Glucose/administração & dosagem , Neuropeptídeos/farmacologia , Peptídeos/farmacologia , Animais , Glicemia/análise , Galanina , Teste de Tolerância a Glucose , Hormônio do Crescimento/sangue , Humanos , Infusões Intravenosas , Insulina/sangue , Masculino , Neuropeptídeos/sangue , Peptídeos/sangue , Suínos , Fatores de TempoRESUMO
Gastroparesis refractory to prokinetic agents poses a major challenge to the physician and patient, alike. In the past 5 years, electrical methods to treat gastroparesis have emerged from animal and human experiments to a potentially valuable tool in clinical gastroenterology. One of these methods, known as gastric electrical stimulation (GES), is being increasingly used in specialized centres worldwide, but had never been tried in Ireland. We describe here our experience with the first two implantations of gastric neurostimulators performed in Ireland and the outcome with these 2 patients. Our results at 6 months show reduction in symptoms and improvement in quality of life, which is encouraging and should prompt further evaluation of GES for patients with gastroparesis refractory to medical therapy.
Assuntos
Terapia por Estimulação Elétrica , Gastroparesia/terapia , Adulto , Feminino , Esvaziamento Gástrico/fisiologia , Motilidade Gastrointestinal/fisiologia , Gastroparesia/fisiopatologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The neuropeptides substance P, neuropeptide Y, neurotensin, and vasoactive intestinal peptide are present in normal rat anterior pituitary gland and hypothalamus and can influence the secretion of classical pituitary hormones. We investigated the effects of estrogen manipulation on pituitary and hypothalamic expression of these four peptides by specific RIAs and cDNA probe analysis. Surgical ovariectomy produced a significant rise in the pituitary content of substance P immunoreactivity (IR) (130.2 +/- 4.8 fmol/gland vs. control 29.1 +/- 2.2, P less than 0.001), neuropeptide Y IR (34.9 +/- 3.9 vs. 19.6 +/- 2.0, P less than 0.05) and neurotensin IR (85.1 +/- 8.2 vs. 62.4 +/- 7.2, P less than 0.05), while vasoactive intestinal peptide IR showed a fall (201.2 +/- 18.8 vs. 285.4 +/- 25.9, P less than 0.05). These patterns were reversed with estrogen replacement or high dose estrogen treatment. Changes in peptide content were accompanied by parallel changes in the mRNA for each peptide. Treatment with an antiestrogen (tamoxifen) resulted in no change in substance P, neuropeptide Y, and neurotensin expression, while vasoactive intestinal peptide IR content decreased to below the assay detection limit. Hypothalamic expression of these peptides did not change with any of the treatments. These results indicate that: 1) the control of the pituitary expression of the four peptides under the influence of estrogen occurs predominantly at the level of gene transcription and 2) normalization of the castration induced changes by exogenous estrogen replacement suggests the changes to be mediated by the absence of this steroid. The regulation of the pituitary expression of these peptides by estrogen support the possibility of their having an autocrine or paracrine role.
Assuntos
Estrogênios/fisiologia , Regulação da Expressão Gênica , Neuropeptídeos/genética , Adeno-Hipófise/metabolismo , Animais , Estradiol/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio Luteinizante/sangue , Hormônio Luteinizante/genética , Neuropeptídeo Y/genética , Neuropeptídeo Y/metabolismo , Neuropeptídeos/metabolismo , Neurotensina/genética , Neurotensina/metabolismo , Hibridização de Ácido Nucleico , Ovariectomia , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos , Substância P/genética , Substância P/metabolismo , Tamoxifeno/farmacologia , Peptídeo Intestinal Vasoativo/genética , Peptídeo Intestinal Vasoativo/metabolismoRESUMO
Neuropeptide Y (NPY), a 36-amino acid member of the pancreatic polypeptide family, was found to be present by RIA and immunocytochemistry in the rat anterior pituitary gland. NPY prohormone messenger RNA (mRNA) was identified in the pituitary by Northern blot analysis. The possible regulation of NPY was examined by determining the effects of thyroid hormone manipulation on peptide synthesis. Three other anterior pituitary neuropeptides, neurotensin (NT), substance P (SP), and vasoactive intestinal peptide (VIP), were studied for comparison. Hypothyroidism was found to significantly increase the pituitary content of NPY, SP, and VIP and their respective mRNAs but to decrease the quantity of NT. Immunocytochemistry revealed very weak NPY immunoreactivity in scattered cells in control rat anterior pituitaries, but in hypothyroid rats a greater number of positive cells were seen, and the staining was relatively intense. These positive cells were identified as a subset of thyrotropes. In T4-induced hyperthyroidism NPY, NT, and VIP levels were unaffected whereas SP concentrations fell considerably. TRH treatment produced a decrease in NT and had no effect on NPY, SP, or VIP. These changes were found only in the pituitary; no net change occurred in hypothalamic peptide and mRNA levels. Since the changes in pituitary peptide and mRNA levels occurred coordinately it appears that regulation by thyroid hormone status occurs, at least in part, directly at the level of gene transcription. The changes in these 4 regulatory peptides in hypothyroidism and their known powerful effects on pituitary function suggest that they may have a significant paracrine or autocrine influence in controlling the alterations in pituitary secretion.
Assuntos
Neuropeptídeo Y/biossíntese , Neuropeptídeos/metabolismo , Adeno-Hipófise/metabolismo , Hormônios Tireóideos/metabolismo , Animais , Northern Blotting , Imunoquímica , Neurotensina/metabolismo , Concentração Osmolar , Ratos , Substância P/metabolismo , Tireoidectomia , Tironinas/sangue , Peptídeo Intestinal Vasoativo/metabolismoRESUMO
Bombesin and gastrin-releasing peptide are homologous peptides which have biological activity in mammals. The distribution of bombesin immunoreactivity in rat, guinea pig, cat, dog, pig, cow, monkey, and human pituitaries was investigated using immunocytochemistry with various different antisera. Polyclonal antisera identified bombesin-immunoreactive (IR) cells in the anterior pituitaries of all species except monkey and human, although positive nerves were present in the human posterior lobe. In contrast, a monoclonal antibody demonstrated bombesin-IR cells in anterior and intermediate lobe (or equivalent) of all species. Both types of antibodies identified the anterior pituitary cells as somatotrophs, which may be significant because bombesin and related peptides influence pituitary growth hormone secretion. Differences in bombesin immunoreactivity were seen in male and female rats, with males having more positive cells, and females showing more intense immunoreactivity in those cells which were positive. Ontogenetic studies in rats revealed that bombesin-IR cells were first seen at birth. The effect of estrogen on bombesin-IR cells was studied using ovariectomized and estrogen-treated female rats. Estrogen treatment decreased very significantly the number of bombesin-IR cells, compared with controls, whereas ovariectomy increased significantly the frequency of bombesin-IR cells, so that the staining pattern began to resemble that seen in normal male rats. No bombesin-IR cells were detected in pituitaries from thyroidectomized rats. These results suggest that immunoreactive bombesin/gastrin-releasing peptide in the pituitary is modulated by endocrine status and this peptide may be involved in paracrine interactions in this tissue.
Assuntos
Bombesina/análise , Hipófise/metabolismo , Envelhecimento , Sequência de Aminoácidos , Animais , Animais Recém-Nascidos , Bombesina/imunologia , Bombesina/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Pulmão/citologia , Masculino , Mamíferos , Dados de Sequência Molecular , Ovariectomia , Hipófise/citologia , Hipófise/efeitos dos fármacos , Hipófise/crescimento & desenvolvimento , Adeno-Hipófise/citologia , Ratos , Ratos Endogâmicos , Especificidade da EspécieRESUMO
Galanin is widely distributed throughout the rat neural and endocrine system. The highest concentrations are found in the anterior pituitary, and it can influence classical pituitary hormone secretion. The effects of endocrine manipulation on pituitary galanin content, mRNA, and immunostaining have been investigated in the rat. In females, medical (39 +/- 4 fmol/gland), surgical (33 +/- 2), or combined (28 +/- 6) castration resulted in a highly significant decrease in galanin content (control, 223 +/- 14; P less than 0.0001). Estrogen in physiological and pharmacological doses produced a significant increase in galanin content (368 +/- 14 and 373 +/- 13, respectively; P less than 0.01) associated with an increase in galanin mRNA content. In the male, high dose dexamethasone and thyroidectomy caused a fall in galanin content, while galanin mRNA levels showed a rise and fall, respectively. Adrenalectomy caused a rise in galanin content, while adrenalectomy and castration produced a dramatic decrease in tissue galanin content. No change in galanin mRNA was observed in these groups. Galanin immunostaining paralleled the results of tissue content in all groups examined, except in the medically castrated group, in which there was some intragroup variation in staining patterns. In normal and high-dose estrogen-treated females, galanin expression was seen mainly in lactotrophs, with a small number of somatotrophs and thyrotrophs staining. In the male, galanin expression was confined to somatotrophs and thyrotrophs. Galanin mRNA was localized at the cellular level by in situ hybridization. In the normal pituitary only scattered lactotrophs contained message, while in high-dose estrogen-treated animals the number of positive cells, mostly lactotrophs, was vastly increased. Thus, the cellular localization of galanin immunostaining varies between the sexes. Galanin peptide and mRNA levels in the pituitary are powerfully influenced by endocrine status.
Assuntos
Glândulas Endócrinas/fisiologia , Peptídeos/metabolismo , Adeno-Hipófise/metabolismo , Adrenalectomia , Animais , Sequência de Bases , Sondas de DNA , Dexametasona/farmacologia , Feminino , Galanina , Expressão Gênica/efeitos dos fármacos , Hipotálamo/metabolismo , Imuno-Histoquímica , Masculino , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Orquiectomia , Ovariectomia , Peptídeos/genética , Adeno-Hipófise/efeitos dos fármacos , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos , TireoidectomiaRESUMO
Growth hormone (GH) synthesis is known to be impaired by either abnormally high or low levels of thyroid hormone. To determine the effects of these conditions on the central regulation of GH secretion, we have examined their effects on the hypothalamic regulatory peptides GH-releasing hormone (GH-RH) and somatostatin (SRIF). In thyroidectomized rat hypothalamus, a dramatic increase in GH-RH mRNA occurred in parallel with a decrease in peptide content. The significance of this phenomenon is uncertain and might possibly reflect some posttranscriptional derangement of GH-RH synthesis or an increased rate of GH-RH synthesis and release. In the hyperthyroid group, GH-RH showed significant decreases in both peptide and mRNA levels that might possibly reflect a decrease in GH-RH synthesis and secretion. No change was observed in SRIF peptide or mRNA levels in either thyroidectomized or T4-treated animals. As expected, GH mRNA levels in the anterior pituitary were dramatically decreased by thyroidectomy and unaffected by T4 treatment. In addition, in thyroidectomized pituitaries, the mature GH mRNA was observed to alter its structure, increasing in size by approximately 100 nucleotides. This increase in size was found to result from an increase in poly(A) tail length, the significance of which is as yet unclear.
Assuntos
Hormônio do Crescimento/biossíntese , Sistema Hipotálamo-Hipofisário/metabolismo , Hormônios Tireóideos/metabolismo , Animais , Hormônio do Crescimento/genética , Hormônio Liberador de Hormônio do Crescimento/metabolismo , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos , Somatostatina/genética , Somatostatina/metabolismo , Tireoidectomia , Tiroxina/farmacologiaRESUMO
Localization of calcitonin gene-related peptide (CGRP) expression in the rat anterior pituitary and its changes during ontogeny and after gonadal steroid manipulations were studied by immunocytochemistry, RIA, and in situ hybridization. Colocalization studies and the combined use of immunocytochemistry and in situ hybridization revealed that CGRP immunoreactivity is localized mainly in gonadotropes and alpha- and beta-CGRP messenger RNAs were detected in CGRP-immunoreactive cells. Immunoreactivity for CGRP also was detected in nerve fibers and colocalized with substance P immunoreactivity. Cells immunoreactive to CGRP antiserum were first detected in fetal rats at gestational day 18, and the incidence considerably increased between postnatal days 5 and 14. CGRP immunoreactivity was low in control adults of both sexes and in pregnant and ovariectomized females but increased in lactating, estrogen-supplemented ovariectomized and high-dose estrogen-treated females, and in high-dose estrogen-treated and castrated males. Testosterone supplement suppressed the effect of castration on CGRP immunoreactivity in males. Quantities of extractable immunoreactive CGRP under conditions of estrogen manipulation corresponded well to the immunocytochemical findings (females: controls, 96.4 +/- 13.1 fmol/gland; ovariectomized, 107.6 +/- 19.2; high-dose estrogen-treated, 212 +/- 23.0; estrogen-supplemented ovariectomized, 680 +/- 42.1). The present study suggests that pituitary CGRP is synthesized and stored in gonadotropes, is modulated by gonadal steroids, and may have a functional link with gonadotropins.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina/genética , Adeno-Hipófise/crescimento & desenvolvimento , RNA Mensageiro/genética , Envelhecimento , Animais , Peptídeo Relacionado com Gene de Calcitonina/análise , Diestro , Desenvolvimento Embrionário e Fetal , Estradiol/farmacologia , Feminino , Feto , Imuno-Histoquímica , Hormônio Luteinizante/análise , Masculino , Hibridização de Ácido Nucleico , Orquiectomia , Ovariectomia , Adeno-Hipófise/efeitos dos fármacos , Adeno-Hipófise/embriologia , Gravidez , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Radioimunoensaio , Ratos , Ratos Endogâmicos , Valores de Referência , Testosterona/farmacologiaRESUMO
The multiple endocrine neoplasia (MEN) type 1 and McCune-Albright syndromes share many clinical and biochemical characteristics. This report documents for the first time the occurrence and natural history of the McCune-Albright syndrome in a female with a strong family history of MEN type 1. There may be a functional link between both of these conditions, and there is a need to look for G-protein mutations as a mechanism for disease in MEN type 1.
Assuntos
Displasia Fibrosa Poliostótica/complicações , Displasia Fibrosa Poliostótica/genética , Neoplasia Endócrina Múltipla/complicações , Neoplasia Endócrina Múltipla/genética , Linhagem , Criança , Feminino , HumanosRESUMO
A characteristic feature of the ectopic ACTH syndrome is a state of mineralocorticoid excess, although the etiology remains obscure. Some forms of endocrine hypertension, such as licorice ingestion, have been explained by cortisol acting as a mineralocorticoid in the setting of inhibition or deficiency of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD). This enzyme is responsible for the conversion of cortisol (F) to hormonally inactive cortisone, and its activity in vivo can be inferred from the ratio of the urinary excretion of tetrahydrocortisol (THF) and its isomer (5 alpha THF) to tetrahydrocortisone. Twenty-two patients with Cushing's syndrome (11 pituitary dependent, 9 ectopic, and 2 adrenal adenomas) and 13 controls were studied. Compared to controls. Cushing's patients had a significant increase (P < 0.001) in the excretion of all principal metabolites of F, secondary to a 5- to 6-fold increase in the cortisol secretion rate [median, 34.0 (range, 13.3-327) mg/day in Cushing's vs. 6.1 (range, 2.5-10.3) mg/day in controls]. The THF plus 5 alpha THF/tetrahydrocortisone ratio was significantly increased in Cushing's syndrome regardless of etiology [mean, 1.81 (range, 1.09-9.99) in Cushing's vs. 0.81 (range, 0.51-1.47) in controls; P < 0.001), indicative of defective 11 beta HSD activity. Furthermore, compared to patients with pituitary-dependent Cushing's, this ratio was significantly higher in patients with the ectopic ACTH syndrome (4.12 vs. 1.49; P < 0.01) and was inversely correlated with serum potassium levels (r = -0.57; P = 0.01; n = 22). One explanation for the mineralocorticoid excess state of the ectopic ACTH syndrome appears to be that cortisol gains inappropriate access to the mineralocorticoid receptor through failure of its normal metabolism by 11 beta HSD. The reason for the defective 11 beta HSD activity is unclear, but it may be secondary to substrate saturation, inhibition by other adrenal steroids, or product inhibition.
Assuntos
Síndrome de ACTH Ectópico/metabolismo , Síndrome de Cushing/metabolismo , Hidroxiesteroide Desidrogenases/metabolismo , Mineralocorticoides/metabolismo , 11-beta-Hidroxiesteroide Desidrogenases , Feminino , Humanos , Hidrocortisona/metabolismo , Masculino , Pessoa de Meia-Idade , Tetra-Hidrocortisol/metabolismo , Tetra-Hidrocortisona/metabolismoRESUMO
Circulating insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) may be risk factors for the development of colorectal cancer. On the other hand, IGF-II and IGFBP-2 are overexpressed in colorectal carcinomas. These contrasting backgrounds led us to investigate the relationship between serum IGF-I, IGF-II, IGFBP-2, and IGFBP-3 and the presence of colorectal adenomas, known precursors of colorectal carcinoma, in 345 volunteers attending a screening flexible sigmoidoscopy trial (entry criteria: healthy, aged 55-64 yr). The most striking finding was an elevated mean serum IGF-II in individuals with adenomas (n = 52) compared with controls (mean difference, 139 ng/mL; 95% confidence intervals, 82, 196; P < 0.0001). Logistic regression adjusting for confounding factors confirmed the significant association between IGF-II and adenoma occurrence (P < 0.0001) and revealed an additional positive association with serum IGFBP-2 (P < 0.0001). However, there was no association found between either serum IGF-I and/or IGFBP-3 and the presence of adenomas. Additionally, in 31 individuals with adenomas in whom levels were determined pre- and postpolypectomy, there was a significant fall in mean IGF-II (P < 0.001) and IGFBP-2 (P < 0.001) after adenoma removal, but no difference in IGF-II and IGFBP-2 concentrations between repeated samples in 20 individuals without adenomas. Immunohistochemical studies demonstrated IGF-II expression in 83% of all adenomas, which contrasted with absent expression in normal colonic expression and hyperplastic polyps. This study has shown for the first time that serum IGF-II may be a tumor marker in individuals with colorectal adenomas. Further studies are needed to validate these relationships in larger populations, including individuals undergoing colonoscopy.