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1.
Endocrine ; 80(1): 20-28, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36255590

RESUMO

PURPOSE: To present a new case series and to review the literature on Carney complex (CNC) with an emphasis on highlighting key clinical features of the disease and pointing out possibilities of shortening the diagnostic process. METHOD: Searches of PubMed, identifying relevant reports up to April 2022. RESULTS: CNC is a rare, autosomally dominant inherited neoplasia -endocrinopathy syndrome with high clinical variability, even among members of the same family. Data on length of diagnostic process are scarce with numerous case series reporting a diagnostic delay of decades. Suggestions to shorten the diagnostic process includes awareness of the multi-faceted clinical presentations of CNC, thorough history taking of index patients and family members and awareness of diagnostic pitfalls. Importantly, unusual symptom combinations should alert the clinician to suspect a rare endocrinopathy syndrome such as CNC. Already present and coming on the horizon are databases and novel phenotyping technologies that will aid endocrinologists in their quest for timely diagnosis. CONCLUSION: In this review, we examine the current state of knowledge in CNC and suggest avenues for shortening the diagnostic journey for the afflicted patients.


Assuntos
Complexo de Carney , Doenças do Sistema Endócrino , Humanos , Complexo de Carney/diagnóstico , Complexo de Carney/genética , Diagnóstico Tardio , Síndrome , Família , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico , Doenças Raras
2.
Horm Metab Res ; 48(9): 571-4, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27300473

RESUMO

Hydrocortisone replacement therapy is a cornerstone in the treatment of adrenal insufficiency (AI). While urinary cortisol has been used as a diagnostic tool for AI, it remains unclear whether it is a useful parameter to monitor hydrocortisone replacement therapy. Aim of this study was to evaluate possible differences in cortisol metabolism between adrenal insufficient patients and healthy subjects and to assess the value of urinary cortisol in AI management. In a case-control study, urinary cortisol excretion was determined in 14 patients with primary and secondary AI receiving hydrocortisone infusions from midnight to 8:00 AM. Results were correlated with serum cortisol levels and compared to urinary values obtained from 53 healthy volunteers. Urinary cortisol excretion in healthy subjects was 14.0±7.8 µg/8 h (range: 0.24-35.4), levels did not differ between 3 groups aged 20-34 years, 35-49 years, and ≥50 years. Patients with AI receiving hydrocortisone infusions demonstrated significantly higher rates of urinary cortisol excretion (51.6±37.8 µg/8 h; range 17.1-120.0, p<0.001); the values correlated with serum cortisol levels (r(2)=0.98). Of interest, patients with secondary AI showed significantly higher serum cortisol levels after hydrocortisone infusion than those with primary AI, conceivably due to residual adrenal function. In conclusion, we showed that: (i) there is a wide inter-individual variability in urinary cortisol excretion rates; (ii) cortisol metabolism in adrenal insufficient patients differs when compared to controls; (iii) there is a strong correlation between urinary and serum cortisol levels; and (iv) urinary cortisol levels despite their variability may help to discriminate between secondary and primary adrenal insufficiency.


Assuntos
Insuficiência Adrenal/tratamento farmacológico , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/urina , Terapia de Reposição Hormonal , Hidrocortisona/administração & dosagem , Hidrocortisona/urina , Insuficiência Adrenal/urina , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
3.
Internist (Berl) ; 57(7): 638-45, 2016 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-27251672

RESUMO

Osteoporosis is the most common clinical disorder of bone metabolism. Treatment decisions should be made on an individual basis, taking into consideration the relative benefits and risks in different patient populations. Drug selection should be based on the form (primary/secondary) and severity of osteoporosis, age, sex, the specific contraindications and precautions for using the various available medications, and existing comorbidities.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Osteoporose/diagnóstico , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Assistência Centrada no Paciente/métodos , Tomada de Decisão Clínica/métodos , Relação Dose-Resposta a Droga , Esquema de Medicação , Monitoramento de Medicamentos/métodos , Medicina Baseada em Evidências , Humanos , Osteoporose/complicações , Fraturas por Osteoporose/etiologia , Resultado do Tratamento
4.
Exp Clin Endocrinol Diabetes ; 123(9): 571-4, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26465705

RESUMO

INTRODUCTION: Headache and depression are common problems in patients with hypothalamic-pituitary disorders (HPD). AIM: To determine the prevalence of headache and depression in patients with HPD and the specific characteristics in affected individuals in comparison to patients with cardiovascular problems (CD). METHODS: Patients with HPD and CD were asked to complete a questionnaire regarding headache and depression. RESULTS: There were no significant differences between the HPD and the CD group. Prevalence of headache was not associated with the treatment modality of pituitary disease, hormone excess syndromes or any hormonal replacement therapy. However, ACTH, TSH and GH deficiency were associated with less headache when compared to patients with adequate secretion. Interestingly, patients who had prior surgery suffered significantly more often from depression. In addition, headache and depression were significantly more common in patients with microadenomas than in macroadenomas. DISCUSSION: The risk for headache and depression is mainly influenced by a combination of factors, but a specific pituitary hormone deficiency may decrease risk for headache.


Assuntos
Depressão , Cefaleia , Doenças Hipotalâmicas , Sistema Hipotálamo-Hipofisário , Doenças da Hipófise , Inquéritos e Questionários , Adulto , Idoso , Idoso de 80 Anos ou mais , Depressão/sangue , Depressão/epidemiologia , Depressão/etiologia , Feminino , Cefaleia/sangue , Cefaleia/epidemiologia , Cefaleia/etiologia , Humanos , Doenças Hipotalâmicas/sangue , Doenças Hipotalâmicas/complicações , Doenças Hipotalâmicas/epidemiologia , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/sangue , Doenças da Hipófise/complicações , Doenças da Hipófise/epidemiologia , Prevalência , Fatores de Risco
6.
Dtsch Med Wochenschr ; 139(10): 483-5, 2014 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-24570194

RESUMO

HISTORY AND ADMISSION FINDINGS: A 51-year-old man presented with progressive tiredness, proximal muscle weakness, hair loss and weight gain for months. The patient showed mild pretibial myxedema and dry skin. Laboratory findings revealed strongly elevated cardiac enzymes as well as marked hypothyroidism. INVESTIGATIONS: The electrocardiogram, echocardiography, abdominal sonography and chest X-ray were unremarkable. Thyroid ultrasound demonstrated features of Hashimoto thyroiditis. TREATMENT AND COURSE: The findings supported the diagnosis of an overt hypothyroidism with myxedema and rhabdomyolysis. After starting levothyroxine and volume substitution laboratory parameters and clinical condition slowly normalized. CONCLUSION: Severe overt hypothyroidism may rarely present primarily as myopathy with myositis and cardiac involvement.


Assuntos
Cardiomiopatias/etiologia , Hipotireoidismo/complicações , Cardiomiopatias/diagnóstico , Cardiomiopatias/tratamento farmacológico , Diagnóstico Diferencial , Eletrocardiografia Ambulatorial , Doença de Hashimoto/complicações , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/tratamento farmacológico , Humanos , Hipotireoidismo/diagnóstico , Masculino , Pessoa de Meia-Idade , Mixedema/complicações , Mixedema/diagnóstico , Mixedema/tratamento farmacológico , Testes de Função Tireóidea , Ultrassonografia
7.
Clin Endocrinol (Oxf) ; 79(6): 760-9, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23941570

RESUMO

Headache is very common in pituitary disease and is reported to be present in more than a third of all patients with pituitary adenomas. Tumour size, cavernous sinus invasion, traction or displacement of intracranial pain-sensitive structures such as blood vessels, cranial nerves and dura mater, and hormonal hypersecretion are implicated causes. The present review attempts to systematically review the literature for any combination of headache and pituitary or hormone overproduction or deficiency. Most data available are retrospective and/or not based on the International Headache Society (IHS) classification. Whereas in pituitary apoplexy a mechanical component explains the almost universal association of the condition with headaches, this correlation is less clear in other forms of pituitary disease and a positive impact of surgery on headaches is not guaranteed. Similarly, invasion into the cavernous sinus or local inflammatory changes have been linked to headaches without convincing evidence. Some studies suggest that oversecretion of GH and prolactin may be important for the development of headaches, and treatment, particularly with somatostatin analogues, has been shown to improve symptoms in these patients. Otherwise, treatment rests on general treatment options for headaches based on an accurate clinical history and a precise classification which includes assessment of the patient's psychosocial risk factors.


Assuntos
Cefaleia/etiologia , Doenças da Hipófise/complicações , Adenoma/complicações , Adenoma/fisiopatologia , Adenoma/cirurgia , Fenômenos Biomecânicos , Agonistas de Dopamina/uso terapêutico , Cefaleia/tratamento farmacológico , Cefaleia/fisiopatologia , Hormônio do Crescimento Humano/metabolismo , Humanos , Apoplexia Hipofisária/complicações , Apoplexia Hipofisária/fisiopatologia , Doenças da Hipófise/fisiopatologia , Doenças da Hipófise/terapia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/fisiopatologia , Neoplasias Hipofisárias/cirurgia , Prolactina/metabolismo , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico
8.
Med Klin Intensivmed Notfmed ; 107(2): 110-7, 2012 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-22349529

RESUMO

Endocrine emergencies during pregnancy can become life-threatening for both mother and fetus. In addition to some pregnancy-linked endocrine disorders, several pre-existing forms of endocrinopathy, such as Grave's disease, type 1 diabetes and adrenal insufficiency might deteriorate acutely during pregnancy. Early diagnosis and management are challenging because the classical symptoms are often modified by pregnancy. Laboratory tests are subject to altered physiological ranges and pharmacological options are limited while therapeutic goals are stricter than in the non-pregnant patient. This article focuses on endocrine emergencies complicating pregnancy.


Assuntos
Emergências , Doenças do Sistema Endócrino/diagnóstico , Complicações na Gravidez/diagnóstico , Insuficiência Adrenal/diagnóstico , Insuficiência Adrenal/terapia , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/terapia , Diagnóstico Diferencial , Diagnóstico Precoce , Doenças do Sistema Endócrino/terapia , Feminino , Doença de Graves/diagnóstico , Doença de Graves/terapia , Humanos , Hipopituitarismo/diagnóstico , Hipopituitarismo/terapia , Recém-Nascido , Gravidez , Complicações na Gravidez/terapia , Gravidez em Diabéticas/diagnóstico , Gravidez em Diabéticas/terapia , Prognóstico , Fatores de Risco
10.
Exp Clin Endocrinol Diabetes ; 119(10): 633-5, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21922454

RESUMO

BACKGROUND: The clinical picture of pituitary abscesses may resemble features of other pituitary pathologies including endocrine deficiencies. The characteristic radiological changes, namely the ring enhancement, may aid in the diagnostic work-up of this very rare condition. CASE REPORT: A 40-year-old patient with longstanding HIV infection presented with headache and fatigue. Testing for pituitary function confirmed panhypopitutarism. MRI scanning demonstrated an inhomogeneous pituitary gland with ring-like enhancement and sphenoid sinus mucosa thickening. Transsphenoidal surgery was performed. Histologically CD68 positive macrophages were found supporting the diagnosis of infectious hypophysitis. Under hormone replacement therapy and retroviral treatment the patient clinically normalized. CONCLUSION: A pituitary abscess due to infectious hypophysitis is a rare cause of pituitary failure. Diagnostic signs on imaging may help to rapidly distinguish the cause of pituitary deficiency in patients with HIV infection.


Assuntos
Abscesso/complicações , Infecções por HIV/complicações , Hipopituitarismo/complicações , Abscesso/diagnóstico por imagem , Abscesso/fisiopatologia , Abscesso/terapia , Adulto , Antirretrovirais/uso terapêutico , Terapia Combinada , Fadiga/etiologia , Infecções por HIV/tratamento farmacológico , Cefaleia/etiologia , Terapia de Reposição Hormonal , Humanos , Hipofisectomia , Hipopituitarismo/diagnóstico por imagem , Hipopituitarismo/fisiopatologia , Hipopituitarismo/terapia , Imageamento por Ressonância Magnética , Masculino , Hipófise/diagnóstico por imagem , Hipófise/cirurgia , Radiografia , Resultado do Tratamento
13.
Exp Clin Endocrinol Diabetes ; 116(9): 515-9, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18523920

RESUMO

Immunosuppression with subsequent opportunistic infections is a well-recognized complication of severe hypercortisolism. We report a case of fatal pneumocystis jirovecii pneumonia (formerly pneumocystis carinii pneumonia) in a case of ectopic Cushing's syndrome caused by a neuroendocrine carcinoma of the kidney. The 36-year old male patient had consulted a physician because of weight gain. Further endocrine diagnostic work-up revealed ACTH-dependent hypercortisolism of non-pituitary origin. Because of rapid clinical deterioration therapy with metyrapone was initiated. A neuroendocrine carcinoma of the right kidney with regional lymph node infiltration was identified and was suspected to be the source of the ACTH excess. Before any causal therapy could be initiated, the patient developed severe pneumocystis jirovecii pneumonia and died shortly thereafter from multiorgan failure one month after he first consulted a physician. Pneumocystosis has been reported in only a few cases of Cushing's syndrome. There seems to be a relationship between the degree of hypercortisolism and the susceptibility to opportunistic infections. Since ACTH concentrations may be excessively high in ectopic Cushing's syndrome and pneumocystosis may deteriorate as a consequence of decreasing circulating cortisol levels under adrenolytic therapy, prophylaxis against pneumocystis jirovecii infection should be considered.


Assuntos
Carcinoma Neuroendócrino/complicações , Síndrome de Cushing/etiologia , Neoplasias Renais/complicações , Pneumocystis carinii , Pneumonia por Pneumocystis/complicações , Hormônio Adrenocorticotrópico/fisiologia , Adulto , Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma Neuroendócrino/patologia , Síndrome de Cushing/complicações , Evolução Fatal , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Metástase Linfática , Masculino , Tomografia Computadorizada por Raios X , Aumento de Peso
15.
J Biol Chem ; 275(40): 30817-25, 2000 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-10882740

RESUMO

The vasodilator-stimulated phosphoprotein (VASP) is a major substrate for cyclic nucleotide-dependent kinases in platelets and other cardiovascular cells. It promotes actin nucleation and binds to actin filaments in vitro and associates with stress fibers in cells. The VASP-actin interaction is salt-sensitive, arguing for electrostatic interactions. Hence, phosphorylation may significantly alter the actin binding properties of VASP. This hypothesis was investigated by analyzing complex formation of recombinant murine VASP with actin after phosphorylation with cAMP-dependent kinase in different assays. cAMP-dependent kinase phosphorylation had a negative effect on both actin nucleation and VASP interaction with actin filaments, with the actin nucleating capacity being more affected than actin filament binding and bundling. Replacing VASP residues known to be phosphorylated in vivo by acidic residues to mimic phosphorylation had similar although less dramatic effects on VASP-actin interactions. In contrast, phosphorylation had no significant effect on VASP oligomerization or its interaction with its known ligands profilin, vinculin, and zyxin. When overexpressing VASP mutants in eukaryotic cells, they all showed targeting to focal contacts and stress fibers. Our results imply that VASP phosphorylation may act as an immediate negative regulator of actin dynamics.


Assuntos
Actinas/metabolismo , Moléculas de Adesão Celular/metabolismo , Proteínas Contráteis , Fosfoproteínas/metabolismo , Animais , Adesão Celular , Linhagem Celular , Núcleo Celular/metabolismo , Clonagem Molecular , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Proteínas do Citoesqueleto , Ensaio de Imunoadsorção Enzimática , Escherichia coli/metabolismo , Glicoproteínas , Células HeLa , Humanos , Ligantes , Metaloproteínas/metabolismo , Camundongos , Proteínas dos Microfilamentos/metabolismo , Modelos Biológicos , Fosforilação , Testes de Precipitina , Profilinas , Ligação Proteica , Proteínas Recombinantes/metabolismo , Ressonância de Plasmônio de Superfície , Fatores de Tempo , Técnicas do Sistema de Duplo-Híbrido , Vinculina/metabolismo , Zixina
16.
FEBS Lett ; 451(1): 68-74, 1999 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-10356985

RESUMO

The vasodilator-stimulated phosphoprotein (VASP) colocalizes with the ends of stress fibers in cell-matrix and cell-cell contacts. We report here that bacterially expressed murine VASP directly interacts with skeletal muscle actin in several test systems including cosedimentation, viscometry and polymerization assays. It nucleates actin polymerization and tightly bundles actin filaments. The interaction with actin is salt-sensitive, indicating that the complex formation is primarily based on electrostatic interactions. Actin binding is confined to the C-terminal domain of VASP (EVH2). This domain, when expressed as a fusion protein with EGFP, associates with stress fibers in transiently transfected cells.


Assuntos
Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Moléculas de Adesão Celular/metabolismo , Fosfoproteínas/metabolismo , Células 3T3 , Animais , Sítios de Ligação , Moléculas de Adesão Celular/genética , Cloretos/metabolismo , Humanos , Compostos de Manganês/metabolismo , Camundongos , Proteínas dos Microfilamentos , Fosfoproteínas/genética , Cloreto de Potássio/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Cloreto de Sódio/metabolismo , Transfecção
17.
J Cell Biol ; 144(6): 1245-58, 1999 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-10087267

RESUMO

Intracellular propulsion of Listeria monocytogenes is the best understood form of motility dependent on actin polymerization. We have used in vitro motility assays of Listeria in platelet and brain extracts to elucidate the function of the focal adhesion proteins of the Ena (Drosophila Enabled)/VASP (vasodilator-stimulated phosphoprotein) family in actin-based motility. Immunodepletion of VASP from platelet extracts and of Evl (Ena/VASP-like protein) from brain extracts of Mena knockout (-/-) mice combined with add-back of recombinant (bacterial or eukaryotic) VASP and Evl show that VASP, Mena, and Evl play interchangeable roles and are required to transform actin polymerization into active movement and propulsive force. The EVH1 (Ena/VASP homology 1) domain of VASP is in slow association-dissociation equilibrium high-affinity binding to the zyxin-homologous, proline-rich region of ActA. VASP also interacts with F-actin via its COOH-terminal EVH2 domain. Hence VASP/ Ena/Evl link the bacterium to the actin tail, which is required for movement. The affinity of VASP for F-actin is controlled by phosphorylation of serine 157 by cAMP-dependent protein kinase. Phospho-VASP binds with high affinity (0.5 x 10(8) M-1); dephospho-VASP binds 40-fold less tightly. We propose a molecular ratchet model for insertional polymerization of actin, within which frequent attachment-detachment of VASP to F-actin allows its sliding along the growing filament.


Assuntos
Actinas/fisiologia , Moléculas de Adesão Celular/fisiologia , Proteínas Contráteis , Proteínas do Citoesqueleto , Proteínas de Ligação a DNA/fisiologia , Listeria monocytogenes/fisiologia , Fosfoproteínas/fisiologia , Actinas/química , Actinas/ultraestrutura , Animais , Sequência de Bases , Sítios de Ligação , Plaquetas/metabolismo , Encéfalo/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/fisiologia , Moléculas de Adesão Celular/genética , Primers do DNA/genética , Proteínas de Ligação a DNA/genética , Listeria monocytogenes/genética , Camundongos , Camundongos Knockout , Proteínas dos Microfilamentos/fisiologia , Microscopia Eletrônica , Modelos Biológicos , Movimento/fisiologia , Fosfoproteínas/genética , Profilinas , Ligação Proteica , Proteínas/genética , Proteínas/fisiologia
18.
Curr Biol ; 8(9): 479-88, 1998 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-9560340

RESUMO

BACKGROUND: Focal adhesion sites are cell-matrix contacts that are regulated by phosphatidylinositol-4,5-bisphosphate (PIP2)-dependent pathways. Vinculin is a major structural component of these sites and is thought to be engaged in multiple ligand interactions at the cytoplasmic face of these contacts. Cytoplasmic vinculin is considered to be inactive due to its closed conformation involving intramolecular head-tail interactions. Recently, the vasodilator-stimulated phosphoprotein (VASP), a substrate of cyclic AMP-dependent or cyclic GMP-dependent kinases and a component of focal adhesion sites, was shown to bind to vinculin. RESULTS: VASP-vinculin complexes could be immunoprecipitated from cell lysates and, using immunofluorescence, both proteins were found to colocalize in nascent focal adhesions. Consistent with the view that vinculin must be activated at these sites, we found that PIP2, levels of which are elevated during the early stages of adhesion, bound to two discrete regions in the vinculin tail, disrupting the intramolecular head-tail interaction and inducing vinculin oligomerization. Vinculin-VASP complex formation was greatly enhanced by PIP2 and both the EVH1 and EVH2 domains of VASP participated in vinculin binding. CONCLUSIONS: Focal contact assembly involves interaction between VASP and vinculin, which is enhanced by PIP2-induced vinculin activation and oligomerization. Given that vinculin and VASP both bind to F-actin, vinculin-VASP complexes might bundle the distal ends of actin filaments in focal contacts. We propose that PIP2-dependent signalling modulates microfilament organization at cellular adhesion sites by regulating vinculin-VASP complexes.


Assuntos
Moléculas de Adesão Celular/metabolismo , Proteínas dos Microfilamentos/fisiologia , Fosfatidilinositol 4,5-Difosfato/fisiologia , Fosfoproteínas/metabolismo , Vinculina/fisiologia , Actinas/metabolismo , Moléculas de Adesão Celular/fisiologia , Comunicação Celular/efeitos dos fármacos , Células HeLa , Humanos , Substâncias Macromoleculares , Proteínas dos Microfilamentos/metabolismo , Modelos Biológicos , Fosfatidilinositol 4,5-Difosfato/metabolismo , Fosfoproteínas/fisiologia , Ligação Proteica/efeitos dos fármacos , Vinculina/metabolismo
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