RESUMEN
INTRODUCTION: Chlorpromazine is a commonly used drug in several medical conditions associated with a wide range of side effects. Few cases of hemostatic disorder have been reported in the literature. CASE REPORT: A 39-year-old man had previously been diagnosed with a cavernous malformation of the medulla oblongata. Chlorpromazine was started to treat persistent hiccups. Twenty days later, the patient presented hepatitis and a pruritic rash. Haemostasis tests revealed a prolonged partial thromboplastin time associated with isolated decrease of factor VIII level and anti-factor VIII antibodies. Magnetic resonance imaging revealed recent asymptomatic bleeding. Introduction of eptacog alfa and prednisone allowed clinical and biological improvement as well as a prolonged remission after 12 months of follow-up.
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Hemofilia A , Masculino , Humanos , Adulto , Hemofilia A/inducido químicamente , Hemofilia A/diagnóstico , Hemofilia A/tratamiento farmacológico , Clorpromazina/efectos adversos , Hemorragia , Bulbo RaquídeoRESUMEN
OBJECTIVE: To describe the outcome and tolerance in patients treated with anti-TNFα in severe and refractory major vessel disease in Behçet's disease (BD). METHODS: A multicenter study evaluating 18 refractory BD patients with major vessel involvement [pulmonary artery (nâ¯=â¯4), aorta (nâ¯=â¯4) or peripheral artery aneurysm (nâ¯=â¯1) and/or pulmonary artery (nâ¯=â¯7), inferior vena cava (nâ¯=â¯5), or intra-cardiac (nâ¯=â¯3) thrombosis or Budd Chiari Syndrome (nâ¯=â¯2)] treated with anti-TNFα agents. RESULTS: Vascular remission was achieved in 16 (89%) patients. The 9â¯months risk of relapse was significantly higher with conventional immunosuppressants used prior anti-TNFα agents as compared to anti-TNFα therapy [ORâ¯=â¯8.7 (1.42-62.6), pâ¯=â¯0.03]. The median daily dose of corticosteroids significantly decreased at 12â¯months. Side effects included infection (nâ¯=â¯4) and pulmonary edema (nâ¯=â¯1). CONCLUSION: TNFα-antagonists are safe and might be associated with a decreased risk of relapse at 9â¯months compared to conventional immunosuppressants in BD patients with major vessels disease.
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Adalimumab/uso terapéutico , Antirreumáticos/uso terapéutico , Síndrome de Behçet/tratamiento farmacológico , Infliximab/uso terapéutico , Trombosis/fisiopatología , Adulto , Enfermedades de la Aorta/etiología , Enfermedades de la Aorta/fisiopatología , Síndrome de Behçet/complicaciones , Síndrome de Behçet/fisiopatología , Síndrome de Budd-Chiari/etiología , Síndrome de Budd-Chiari/fisiopatología , Femenino , Cardiopatías/etiología , Cardiopatías/fisiopatología , Humanos , Inmunosupresores/uso terapéutico , Infecciones , Modelos Logísticos , Masculino , Persona de Mediana Edad , Arteria Pulmonar/fisiopatología , Edema Pulmonar , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Trombosis/etiología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Enfermedades Vasculares/etiología , Enfermedades Vasculares/fisiopatología , Vena Cava Inferior/fisiopatología , Adulto JovenRESUMEN
INTRODUCTION: IgA vasculitis is a systemic small vessel leukocytoclastic vasculitis characterized by skin purpura, arthritis, abdominal pain and nephritis. Most of the abdominal complications are due to edema and hemorrhage in the small bowel wall, but rarely to acute secondary pancreatitis. CASE REPORT: Here, we report a 53-year-old woman who presented with acute pancreatitis and, secondarily, developed skin purpura and arthritis at the seventh day of the clinical onset. Biological tests and computed tomographic scan allowed to rule out another cause of pancreatitis and IgA vasculitis was diagnosed as its etiology. The outcome was favorable without any relapse on glucocorticoids. CONCLUSION: Despite its rarity, pancreatitis is a potential life-threatening complication of IgA vasculitis in which the role of glucocorticoids and immunosuppressive drugs remains uncertain. A prompt elimination of other usual pancreatitis etiologies is mandatory to improve the management of the patients.
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Inmunoglobulina A/efectos adversos , Pancreatitis/diagnóstico , Vasculitis/diagnóstico , Vasculitis/etiología , Enfermedad Aguda , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana EdadAsunto(s)
Ataxia/diagnóstico , Neoplasias Encefálicas/diagnóstico , Calcinosis/diagnóstico , Quistes del Sistema Nervioso Central/diagnóstico , Leucoencefalopatías/diagnóstico , Espasticidad Muscular/diagnóstico , Enfermedades de la Retina/diagnóstico , Telangiectasia Retiniana/diagnóstico , Convulsiones/diagnóstico , Ataxia/complicaciones , Ataxia/tratamiento farmacológico , Bevacizumab/uso terapéutico , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/tratamiento farmacológico , Calcinosis/complicaciones , Calcinosis/tratamiento farmacológico , Quistes del Sistema Nervioso Central/complicaciones , Quistes del Sistema Nervioso Central/tratamiento farmacológico , Angiografía con Fluoresceína , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/tratamiento farmacológico , Hemorragia Gastrointestinal/etiología , Humanos , Leucoencefalopatías/complicaciones , Leucoencefalopatías/tratamiento farmacológico , Imagen por Resonancia Magnética , Masculino , Espasticidad Muscular/complicaciones , Espasticidad Muscular/tratamiento farmacológico , Enfermedades de la Retina/complicaciones , Enfermedades de la Retina/tratamiento farmacológico , Telangiectasia Retiniana/etiología , Convulsiones/complicaciones , Convulsiones/tratamiento farmacológico , Adulto JovenRESUMEN
OBJECTIVES: Benefits of hydroxychloroquine (HCQ) use on physician reported outcomes are well documented in systemic lupus erythematosus (SLE). We assess for the first time the association and predictive value of blood HCQ levels towards health-related quality of life (HRQOL) in SLE. METHODS: Data from the PLUS study (a randomized, double-blind, placebo-controlled, multicentre study) were utilized. Blood HCQ levels were quantified by high-performance liquid chromatography along with HRQOL assessments (Medical Outcomes Study-SF-36) at baseline (V1) and month 7 (V2). RESULTS: 166 SLE patients' data were analysed. Mean (SD) age and disease duration were 44.4 (10.7) and 9.3 (6.8) years. Eighty-seven per cent were women. Mean (SD, median, IQR) HCQ concentrations in the blood at V1 were 660 (314, 615, 424) ng/ml and increased to 1020 (632, 906, 781) ng/ml at V2 (mean difference 366 units, 95% confidence interval -472 to -260, p < 0.001). No significant correlations between HCQ concentrations with HRQOL domains at V1 or V2 were noted. There were no differences in HRQOL stratified by HCQ concentrations. HCQ concentrations at V1 or changes in HCQ concentration (V2-V1) were not predictive of HRQOL at V2 or changes in HRQOL (V2-V1). CONCLUSIONS: No association of HCQ concentrations with current or longitudinal HRQOL were found in SLE.
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Antirreumáticos/sangre , Hidroxicloroquina/sangre , Lupus Eritematoso Sistémico/sangre , Calidad de Vida , Adulto , Método Doble Ciego , Femenino , Francia , Humanos , Modelos Lineales , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: Blood concentrations of hydroxychloroquine (HCQ) vary widely among patients with systemic lupus erythematosus (SLE). A pharmacokinetic/pharmacodynamic relationship has been found in different situations, and a very low blood concentration of HCQ is a simple marker of nonadherence to treatment. Therefore, interest in blood HCQ concentration measurement has increased, but little is known about factors that influence blood HCQ concentration variability. This study was undertaken to analyze determinants of blood HCQ concentrations. METHODS: We conducted a retrospective analysis of patient data, including data from the Plaquenil Lupus Systemic (PLUS) study, to determine the association of epidemiologic, clinical, and biologic factors with blood HCQ concentrations. Data for nonadherent patients (blood HCQ concentration <200 ng/ml) were excluded. RESULTS: To examine homogeneous pharmacologic data, we restricted the analyses of the PLUS data to the 509 SLE patients receiving 400 mg/day. We found no association of ethnicity or smoking with blood HCQ concentrations and no pharmacokinetic drug-drug interaction with antacids or with inhibitors or inducers of cytochrome P450 enzymes. On multivariate analysis, high body mass index (P = 0.008), no treatment with corticosteroids (P = 0.04), increased time between the last tablet intake and measurement of blood HCQ concentrations (P = 0.017), low platelet count (P < 0.001), low neutrophil count (P < 0.001), and high estimated creatinine clearance (P < 0.001) were associated with low blood HCQ concentrations. In 22 SLE patients with chronic renal insufficiency (median serum creatinine clearance 52 ml/minute [range 23-58 ml/minute]) who received 400 mg/day HCQ, the median blood HCQ concentration was significantly higher than that in the 509 patients from the PLUS study (1,338 ng/ml [range 504-2,229 ng/ml] versus 917 ng/ml [range 208-3316 ng/ml]) (P < 0.001). CONCLUSION: We provide a comprehensive analysis of determinants of blood HCQ concentrations. Because this measurement is increasingly being used, these data might be useful for clinicians.
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Corticoesteroides/uso terapéutico , Antirreumáticos/farmacocinética , Hidroxicloroquina/farmacocinética , Lupus Eritematoso Sistémico/tratamiento farmacológico , Adulto , Antirreumáticos/sangre , Antirreumáticos/uso terapéutico , Índice de Masa Corporal , Creatinina/sangre , Femenino , Humanos , Hidroxicloroquina/sangre , Hidroxicloroquina/uso terapéutico , Recuento de Leucocitos , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/complicaciones , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neutrófilos/citología , Obesidad/complicaciones , Insuficiencia Renal Crónica/complicaciones , Estudios Retrospectivos , Trombocitopenia , Factores de Tiempo , Adulto JovenAsunto(s)
Fiebre/diagnóstico , Fiebre Hemorrágica con Síndrome Renal/diagnóstico , Virus Puumala , Trombocitopenia/diagnóstico , Adulto , Fiebre/virología , Fiebre Hemorrágica con Síndrome Renal/complicaciones , Humanos , Masculino , Virus Puumala/aislamiento & purificación , Trombocitopenia/virologíaRESUMEN
Septic arthritis of the pubic symphysis is uncommon, and usually occurs in patients with predisposing conditions (female incontinence surgery, sports). Staphylococcus aureus and Pseudomonas aeruginosa are the main bacteria responsible of these infections. Streptococcal infections of the pubic symphysis are uncommon. We report three cases of streptococcal infections of the pubic symphysis that occurred in the absence of predisposing condition such as surgery or endocarditis. The diagnosis of septic arthritis was difficult, particularly in one patient who underwent an orchidopexy for a suspected of spermatic cord torsion before diagnosis was corrected. All three patients had a favourable outcome after an antibiotic treatment combining amoxicillin and rifampicin. Septic arthritis of the pubic symphysis should be suspected in patients with sudden groin pain, pubic tenderness and fever to avoid traumatic treatments and useless investigations.
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Artritis Infecciosa/microbiología , Sínfisis Pubiana/microbiología , Infecciones Estreptocócicas/diagnóstico , Adulto , Anciano , Antibacterianos/uso terapéutico , Artritis Infecciosa/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones Estreptocócicas/tratamiento farmacológicoRESUMEN
A 22-year-old patient attended the urological office with unclear bladder symptoms, haemorrhoids and haematuria. Splenomegaly was detected by ultrasound together with the suspicion of a bladder cyst. Computed tomography revealed mesenteric, retroperitoneal and inguinal lymph node swelling. The laboratory diagnostics produced the diagnosis of syphilis. The patient was successfully treated with ceftriaxone and benzylpenicillin benzathine.
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Hematuria/diagnóstico , Enfermedades Linfáticas/diagnóstico , Esplenomegalia/diagnóstico , Sífilis/tratamiento farmacológico , Antibacterianos/uso terapéutico , Ceftriaxona/uso terapéutico , Hematuria/tratamiento farmacológico , Hematuria/etiología , Humanos , Enfermedades Linfáticas/tratamiento farmacológico , Enfermedades Linfáticas/etiología , Masculino , Penicilina G Benzatina/uso terapéutico , Esplenomegalia/tratamiento farmacológico , Esplenomegalia/etiología , Sífilis/complicaciones , Sífilis/diagnóstico , Resultado del Tratamiento , Adulto JovenRESUMEN
The hypereosinophilic syndromes (HES), defined by an unexplained and sustained hypereosinophilia, can be associated with heterogeneous hematological conditions. Several molecular mechanisms underlying the eosinophilia, which remained indeterminate for a long time, have been recently identified. These recent advances allowed a better classification of the various forms of HES and the development of targeted therapies. The role of tyrosine kinases, especially PDGFRA, and the efficacy of tyrosine kinases inhibitors dramatically improved the diagnosis and the treatment of myeloproliferative variant of HES. On the other side, eosinophilia can be driven by IL-5 secreting abnormal and often clonal T cell subsets (lymphocytic variant of HES). The crucial role of this cytokine in eosinophil development, activation and survival leads to the assessment of anti-IL-5 monoclonal antibodies which have recently shown to provide a significant corticosteroid sparing effect in FIP1L1-PDGFRA negative HES patients. Despite these major advances, half of HES remains unexplained (idiopathic HES). Some FIPL1-PDGFRA negative patients respond to imatinib, suggesting the role of other tyrosine kinases (or other partners than FIP1L1 in a fusion gene implicating PDGFRA). Development of new biomarkers is needed to help physicians in the diagnosis, classification of HES and in the choice of a targeted therapy.
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Síndrome Hipereosinofílico , Humanos , Síndrome Hipereosinofílico/clasificación , Síndrome Hipereosinofílico/tratamiento farmacológico , Síndrome Hipereosinofílico/fisiopatologíaRESUMEN
Among diagnostic progress over the last three years in internal medicine, Antisynthetase Syndrome is now more easily recognised with the diffusion of laboratory tests for research of antibodies against tRNA synthetases (Anti JO1, anti PL7, Anti PL12). In two third of cases, these antibodies are found despite absence of antinuclear antibodies. Hence, we have to search them specifically in patients with polyarthritis associated with myositis, cutaneous manifestations (Raynaud phenomenom and "mechanic'hands") and interstitial lung disease. Discovery of asymptomatic mutation in the L ferritin coding sequence help us to better understand the "unexplained" hyperferritinemia. Initially described by japonese gastroenterologists, auto immune pancreatitis in fact a part of a systemic sclerosing disease with a biochemical hallmark: in crease of a subclass of immunoglobulins G (IgG4). A new pediatric disease due to a deficiency of the interleukin1 receptor antagonist (multifocal aseptic osteitis, periostitis, stomatitis, disseminated pustulosis) help us to better understand unexplained auto inflammatory diseases. The therapeutic progress is primarily due to an explosion of biological therapies, particularly four of them very useful for internists (in an off label use) : Interleukin 1 inhibitors (anakinra, Canakinumab) to treat some auto inflammatory diseases (cryopirin associated periodic syndromes and deficency of interleukin 1 receptor antagonist), monoclonal antibody against interleukin 5 (mepolizumab) to treat some hypereosinophilic syndromes and Churg and Strauss angiitis, interleukin 6 inhibitiors to treat multifocal Castleman's disease and adult Still disease, a monoclonal antibody against vascular endothelial growth factor (Bevacizumab) to treat hereditary hemorrhagic telangiectasia.
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Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/inmunología , Medicina Interna/tendencias , Pustulosis Exantematosa Generalizada Aguda/diagnóstico , Pustulosis Exantematosa Generalizada Aguda/inmunología , Aminoacil-ARNt Sintetasas/inmunología , Anticuerpos Monoclonales/uso terapéutico , Artritis/diagnóstico , Artritis/inmunología , Autoanticuerpos/inmunología , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/genética , Biomarcadores/metabolismo , Quimioterapia Combinada , Ferritinas/genética , Humanos , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Interleucina-6/antagonistas & inhibidores , Sobrecarga de Hierro/diagnóstico , Sobrecarga de Hierro/genética , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/inmunología , Mutación , Miositis/diagnóstico , Miositis/inmunología , Osteítis/diagnóstico , Osteítis/inmunología , Pancreatitis/diagnóstico , Pancreatitis/inmunología , Periostitis/diagnóstico , Periostitis/inmunología , Enfermedad de Raynaud/diagnóstico , Enfermedad de Raynaud/inmunología , Estomatitis/diagnóstico , Estomatitis/inmunología , Síndrome , Resultado del TratamientoRESUMEN
OBJECTIVE: Activation of ras proto-oncogenes as a result of point mutations is detectable in a significant percentage of most types of tumour. Similar to neoplasms of other organs, mutations of all three ras genes can be found in thyroid tumours. H-, K- and N-ras mutations have been detected in up to 20% of follicular adenomas and adenomatous nodules which were not functionally characterized. This raises the question as to whether ras mutations are specific for hypofunctional nodules and TSH receptor mutations for hyperfunctioning nodules. DESIGN: To investigate ras and TSH receptor mutations with respect to functional differentiation we studied 41 scintigraphically cold nodules and 47 toxic thyroid nodules. To address the likelihood of a somatic mutation we also studied the clonal origin of these tumours. MEASUREMENTS: Genomic DNA was extracted from nodular and surrounding tissue. Mutational hot spots in exons 1 and 2 of the H- and K-ras gene were PCR amplified and sequenced using big dye terminator chemistry. Denaturing gradient gel electrophoresis (DGGE) was used to verify sequencing results for the H-ras gene and to analyse the N-ras gene because its greater sensitivity in detecting somatic mutations. Clonality of nodular thyroid tissue was evaluated using X-Chromosome inactivation based on PCR amplification of the human androgen receptor locus. RESULTS: Monoclonal origin was detectable in 14 of 23 informative samples from cold thyroid nodules. In toxic thyroid nodules the frequency of clonal tissue was 20 in 30 informative cases. Only one point mutation could be found in the N-ras gene codon 61 (Gly to Arg) in a cold adenomatous nodule which was monoclonal. In toxic thyroid nodules no ras mutation was detectable. CONCLUSION: Our study suggests that ras mutations are rare in solitary cold and toxic thyroid nodules and that the frequent monoclonal origin of these tumours implies somatic mutations in genes other than H-, K- and N-ras.
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Adenocarcinoma Folicular/genética , Genes ras/genética , Mutación/genética , Nódulo Tiroideo/genética , Células Clonales , Electroforesis en Gel de Poliacrilamida/métodos , Femenino , Humanos , Masculino , Reacción en Cadena de la Polimerasa , Receptores de Tirotropina/genética , Cromosoma X/genéticaRESUMEN
The actual frequency of constitutively activating thyrotropin receptor or Gsalpha mutations in toxic thyroid nodules (TTNs) remains controversial as considerable variation in the prevalence of these mutations has been reported. We studied a series of 75 consecutive TTNs and performed mutation screening by the more sensitive method of denaturing gradient gel electrophoresis (DGGE) in addition to direct sequencing. Furthermore, the likelihood of somatic mutations occurring in genes other than that for the thyroid-stimulating hormone receptor (TSHR) and exons 7-9 of the Gsalpha protein gene was determined by clonality analysis of TTNs, which did not harbor mutations in the investigated genes. In 43 of 75 TTNs (57%) constitutively active TSHR mutations were identified. Six TSHR mutations were detected only by DGGE, underlining the importance of a sensitive screening method. Novel, constitutively activating mutations were identified at positions 425 (Ser-->Leu) and 512 (Leu-->Glu/Arg). Furthermore, a new base substitution was detected at position Pro639Ala (CCA-->GCA). Ten of 20 TSHR or Gsalpha mutation negative cases (50%) showed nonrandom X-chromosome inactivation, indicating clonal origin. In conclusion, somatic, constitutively activating TSHR mutations appear to be a major cause of TTNs (57%), while mutations in Gsalpha play a minor role (3%). The mutation negative but clonal cases indicate a probable involvement of somatic mutations other than in the TSH receptor or Gsalpha genes as the molecular cause of these hot nodules.
Asunto(s)
Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Mutación/genética , Receptores de Tirotropina/genética , Nódulo Tiroideo/genética , Sustitución de Aminoácidos/genética , Composición de Base , Clonación Molecular , Codón/genética , Análisis Mutacional de ADN/métodos , Compensación de Dosificación (Genética) , Electroforesis en Gel de Poliacrilamida , Frecuencia de los Genes , Humanos , Desnaturalización de Ácido Nucleico , Reacción en Cadena de la Polimerasa , Receptores de Tirotropina/químicaRESUMEN
Iodine deficiency is the most important etiological factor for euthyroid endemic goiter. However, family and twin pair studies also indicate a genetic predisposition for euthyroid simple goiter. In hypothyroid goiters several molecular defects in the thyroglobulin (TG), thyroperoxidase (TPO), and Na+/I- symporter (NIS) genes have been identified. The TSH receptor with its central role for thyroid function and growth is also a strong candidate gene. Therefore, we investigated a proposita with a relapsing euthyroid goiter and her family, in which several members underwent thyroidectomy for euthyroid goiter. Sequence analysis of the complementary DNA (cDNA) of the TPO and TSH receptor genes revealed several previously reported polymorphisms. As it is not possible to exclude a functional relevance for all polymorphisms, we opted for linkage analysis with microsatellite markers to investigate whether the candidate genes are involved in the pathogenesis of euthyroid goiter. The markers for the genes TG, TPO, and NIS gave two-point and multipoint logarithm of odds score analysis scores that were negative or below 1 for all assumed recombination fractions. As no significant evidence of linkage was found, we conclude that these candidate genes can be excluded as a major cause of the euthyroid goiters in this family. In contrast, we have found evidence for linkage of familial euthyroid goiter to the recently identified locus for familial multinodular nontoxic goiter (MNG-1) on chromosome 14q. The haplotype cosegregates clearly with familial euthyroid goiter. Our results provide the first confirmation for MNG-1 as a locus for nontoxic goiter.
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Proteínas Portadoras/genética , Mapeo Cromosómico , Ligamiento Genético , Bocio Nodular/genética , Bocio/genética , Yoduro Peroxidasa/genética , Proteínas de la Membrana/genética , Simportadores , Tiroglobulina/genética , Adolescente , Adulto , Anciano , Northern Blotting , Cromosomas Humanos Par 14/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hibridación de Ácido Nucleico , Linaje , Receptores de Tirotropina/genética , RibonucleasasRESUMEN
Familial pituitary tumors are rare. Only 45 cases in 20 families with acromegaly have been reported. A third of the cases (30%) is related to multiple endocrine neoplasia type 1 (MEN 1). We report two cases of acromegaly in one family with pituitary macroadenomas. A 46-year-old woman with elevated serum growth hormone (GH) and insulin-like growth factor (IGF-1) and a failure to supress GH in the glucose tolerance test underwent transsphenoidal surgery 4 years ago. Three years later her 24-year-old son also presented with typical signs of acromegaly. A pituitary macroadenoma was identified by MRT and he also underwent transsphenoidal surgery. There were no symptoms of McCune-Albright syndrome or other forms of endocrine hyperfunction in the two patients. In an attempt to identify the molecular etiology of the tumours DNA was extracted from paraffin fixed tissue from both patients. Exon 7 to 13 of the Gsp-protein and exons 1 to 10 of the menin gene were amplified by PCR. Although Gsp mutations have been identified in 40% of somatotroph tumors, direct sequencing of the PCR products showed no mutations in exons 7 to 13 of Gs alpha. Moreover no mutations were found in exons 1 to 10 of the menin gene. Therefore, molecular causes other than Gsp or menin gene mutations have to be considered as the molecular etiology of acromegaly in this family.