Photovoice como ferramenta de ensino e aprendizado sobre cuidados paliativos / Photovoice as a tool for teaching and learning about palliative care

Resumo: Introdução: O cuidado paliativo foi recentemente incluído no currículo da graduação em Medicina no Brasil, mas a colocação do seu ensino em prática representa um grande desafio. Ensinar cuidado paliativo envolve abordar o sofrimento e o cuidado de questões que vão além dos sintomas físicos, aspectos com os quais os alunos de Medicina estão geralmente pouco acostumados. O Photovoice (PV) é uma ferramenta multifacetada que pode servir ao propósito do trinômio ensino, pesquisa e extensão. Na sua aplicação como instrumento pedagógico, os alunos atuam geralmente como participantes e o docente como facilitador. Os alunos são convidados a tirar fotografias (photo) e narrar essas imagens (voice) atribuindo significado e interpretação dentro de um contexto. Relato de experiência: Um grupo de alunos foi convidado a produzir um trabalho com o tema "Cuidados paliativos na visão de um estudante do terceiro ano de Medicina". O trabalho foi desenvolvido ao longo de 12 encontros semanais sob a forma de rodas de conversa, que versavam sobre materiais previamente enviados aos alunos, como música, vídeos e textos. Cada aluno produziu um PV individual. Os PV preparados pelos alunos se dividiram espontaneamente em três grupos: experiências familiares de cuidados paliativos, experiências profissionais vivenciadas nos cenários de prática da faculdade e desenvolvimento do tema de maneira mais conceitual. Discussão: A despeito das limitações e dificuldades do tema e da metodologia utilizada, o saldo final da experiência foi muito positivo não só pelo aprendizado dos alunos, mas também pela criação de um grande vínculo no grupo, que manifestou profunda gratidão pelo trabalho desenvolvido ao longo do semestre. Conclusão: Diante dos nove PV produzidos, fruto da reflexão individual de cada aluno, percebe-se que cada integrante do grupo foi tocado de uma forma diferente pelo assunto, ainda que todas as reflexões tenham sido realizadas de forma coletiva durante os nossos encontros. A produção dos PV permitiu a externalização de visões diferentes sobre o mesmo assunto de maneira pessoal e humanística, ou seja, percepção do que é cuidado paliativo na visão de um estudante de Medicina do terceiro ano.

Abstract: Introduction: Palliative care was recently included in the undergraduate medical curriculum in Brazil, but putting its teaching into practice represents a major challenge. Palliative care involves intimate contact with suffering and caring for issues that go beyond physical symptoms, aspects generally unfamiliar to medical students. Photovoice (PV) is a multifaceted tool that can support the teaching, research and extension trinomial. In its application as a pedagogical tool, students generally act as participants and the teacher as facilitator. Students are invited to take photographs (photo) and narrate these images (voice) ascribing meaning and interpretation within a context. Experience Report: A group of students was invited to produce a manuscript with the theme "Palliative care from the point of view of a third-year medical student". The work was developed over 12 weekly meetings in the form of conversation circles that dealt with materials previously sent to students such as music, videos and texts. Each student produced an individual PV. Photovoices prepared by the students were spontaneously divided into three groups: family experiences of palliative care, professional experiences in practice scenarios and development of the theme in a more conceptual manner. Discussion: Despite the limitations and difficulties of the theme and the methodology used, the final balance of the experience was very positive, not only in relation to student learning, but also to the creation of a strong bond within the group, which expressed deep gratitude for the work developed over the course of the semester. Conclusion: In view of the nine PVs produced, as a result of each student's individual reflection, it is clear that each member of the group was touched in a different way by the subject, even though all the reflections were presented collectively during our meetings. The production of a PV allowed the externalization of different views on the same subject in a personal and humanistic way, in other words, the perception of palliative care in the view of a third-year medical student.

Altered superoxide dismutase-1 activity and intercellular adhesion molecule 1 (ICAM-1) levels in patients with type 2 diabetes mellitus.

Inflammation and oxidative stress are linked to type 2 diabetes mellitus (T2DM). In this work, we analyzed patients' blood markers of antioxidant capacity, oxidative stress and inflammation in individuals with T2DM, in pre-diabetes state (pre-DM) and controls without diabetes. Patients were divided into three groups, according to glycated hemoglobin A1c (HbA1c): <7%, 7-9%, and >9%. Superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities, total thiols, nitric oxide (•NO), tumor necrosis factor alpha (TNF-α) and intercellular adhesion molecule 1 (ICAM-1) levels of the individuals were measured. Plasma SOD activity was higher in T2DM subjects compared to the controls. While total thiols levels were lower in T2DM groups when compared to pre-DM, the values remained unchanged when compared to controls. ICAM-1 levels of T2DM groups were lower than in controls, while GPx activity, •NO, and TNF-α levels were similar among all groups. A positive correlation was found between SOD and HbA1c levels. Concluding, individuals with T2DM present altered SOD activity, total thiols, and ICAM-1 levels, which might contribute to further complications. There is a positive correlation between SOD activity and HbA1c levels. No apparent correlation exists between total thiols and ICAM-1 levels and with any other of the parameters evaluated in this study.

Prevalence of vitamin B12 deficiency in type 2 diabetic patients using metformin: a cross-sectional study / Prevalência de deficiência de vitamina B12 em pacientes diabéticos do tipo 2 usando metformina: um estudo transversal

ABSTRACT: CONTEXT AND OBJECTIVE: The prevalence of vitamin B12 deficiency varies from 5.8% to 30% among patients undergoing long-term treatment with metformin. Because of the paucity of data on Brazilian patients, this study aimed to determine the frequency of B12 deficiency and related factors among Brazilian patients with type 2 diabetes mellitus (T2DM) using metformin. DESIGN AND SETTING: Cross-sectional study at a public university hospital. METHODS: Patients with T2DM and a control group of non-diabetics were included. Serum B12 levels were measured and biochemical B12 deficiency was defined as serum levels < 180 pg/ml. Associations between B12 deficiency and age, duration of T2DM, duration of use and dosage of metformin, and use of proton pump inhibitors (PPIs) or histamine H2 antagonists were determined. RESULTS: 231 T2DM patients using metformin (T2DM-met) and 231 controls were included. No difference in the frequency of PPI or H2-antagonist use was seen between the groups. B12 deficiency was more frequent in the T2DM-met group (22.5% versus 7.4%) and this difference persisted after excluding PPI/H2-antagonist users (17.9% versus 5.6%). The factors that interfered with serum B12 levels were PPI/H2-antagonist use and duration of metformin use ≥ 10 years. Use of PPI/H2-antagonists was associated with B12 deficiency, with an odds ratio of 2.60 (95% confidence interval, 1.34-5.04). CONCLUSIONS: Among T2DM patients, treatment with metformin and concomitant use of PPI/H2-antagonists are associated with a higher chance of developing B12 deficiency than among non-diabetics.

RESUMO: CONTEXTO E OBJETIVO: A prevalência de deficiência de vitamina B12 varia de 5,8% a 30% nos pacientes em tratamento a longo prazo com metformina. Devido à escassez de dados em pacientes brasileiros, este estudo determinou a frequência de deficiência de B12 e fatores relacionados em pacientes brasileiros com diabetes mellitus tipo 2 (DM2) usando metformina. TIPO DE ESTUDO E LOCAL: Estudo transversal em hospital público universitário. MÉTODOS: Pacientes com DM2 e um grupo controle de não diabéticos foram incluídos. Os níveis séricos de vitamina B12 foram dosados e deficiência bioquímica de B12 foi definida como níveis séricos < 180 pg/ml. Foi investigada a associação entre deficiência de B12 e idade, duração do DM2, duração do uso e dose de metformina, uso de inibidores de bomba de prótons (IBP) ou antagonistas dos receptores histamínicos H2 (antagonistas-H2). RESULTADOS: 231 pacientes DM2 usando metformina (DM2-met) e 231 controles foram incluídos. Não houve diferença na frequência de uso de IBP/antagonistas-H2 entre os grupos. Deficiência de B12 foi mais frequente no grupo DM2-met (22,5% versus 7,4%) e essa diferença persistiu após exclusão dos usuários de IBP/antagonistas-H2 (17,9% versus 5,6%). Fatores que interferiram nos níveis séricos de B12 foram: uso de IBP/antagonistas-H2 e duração do uso de metformina ≥ 10 anos. O uso de IBP/antagonistas-H2 associou-se com deficiência de B12, com um risco relativo de 2,60 (95% intervalo de confiança, 1,34-5,04). CONCLUSÕES: Considerando pacientes com DM2, o tratamento com metformina e uso concomitante de IBP/antagonistas-H2 estão associados com maior chance de desenvolver deficiência de B12 quando comparado aos não diabéticos.

Prolactinomas may have unusual presentations resulting from massive extrasellar tumor extension.

The purpose of this case series is to report eight patients with giant prolactinomas emphasizing presentations and a treatment complication. The study group included six men and two women. The median age was 29 years (18-54 years); median serum prolactin level was 4,562 ng/ml (1,543-18,690 ng/ml); three patients (37.5%) had panhypopituitarism; median tumor diameter was 50 mm (41-60 mm). Five patients (62.5%) had visual field defects and three had improvement during treatment; six patients (75%) reached prolactin normalization, with a median time of 10.5 months (7-84 months) and median dose of 2.0 mg/week (1.0 to 3.0 mg/week). One patient presented as a true incidentaloma. One patient presented a cerebrospinal fluid leakage during medical treatment and refused surgery, however this resolved with conservative measures. This case series illustrate a rare subtype of macroprolactinomas, the importance of considering unusual presentations at the diagnosis, the effectiveness of pharmacological treatment and its possible complications.

Prolactinomas may have unusual presentations resulting from massive extrasellar tumor extension / Prolactinomas podem ter apresentações incomuns resultantes de maciça extensão tumoral extrasselar

ABSTRACT The purpose of this case series is to report eight patients with giant prolactinomas emphasizing presentations and a treatment complication. The study group included six men and two women. The median age was 29 years (18–54 years); median serum prolactin level was 4,562 ng/ml (1,543–18,690 ng/ml); three patients (37.5%) had panhypopituitarism; median tumor diameter was 50 mm (41–60 mm). Five patients (62.5%) had visual field defects and three had improvement during treatment; six patients (75%) reached prolactin normalization, with a median time of 10.5 months (7–84 months) and median dose of 2.0 mg/week (1.0 to 3.0 mg/week). One patient presented as a true incidentaloma. One patient presented a cerebrospinal fluid leakage during medical treatment and refused surgery, however this resolved with conservative measures. This case series illustrate a rare subtype of macroprolactinomas, the importance of considering unusual presentations at the diagnosis, the effectiveness of pharmacological treatment and its possible complications.

RESUMO O objetivo desta série de casos é relatar oito pacientes com prolactinomas gigantes enfatizando as formas de apresentação e uma complicação do tratamento. O estudo incluiu seis homens e duas mulheres. A mediana de idade foi 29 anos (18–54); e dos níveis de prolactina foi 4.562 ng/ml (1.543–18.690); três pacientes (37,5%) apresentaram pan-hipopituitarismo; a mediana do máximo diâmetro tumoral foi 50 mm (41–60 mm). Cinco pacientes (62,5%) apresentaram alterações no campo visual e três tiveram melhora durante o tratamento; seis pacientes (75%) alcançaram normalização da prolactina em 10,5 meses (7–84) com dose mediana de cabergolina de 2,0 mg / semana (1,0 a 3,0). Um paciente se apresentou como um verdadeiro incidentaloma. Um paciente apresentou uma fistula liquórica durante o tratamento medicamentoso e recusou correção cirúrgica. No entanto a fistula foi resolvida com medidas conservadoras. Esta série de casos ilustra um subtipo raro de macroprolactinomas, a importância de considerar apresentações incomuns no diagnóstico, a eficácia do tratamento farmacológico e suas possíveis complicações.

Clinical, hormonal, ovarian, and genetic aspects of 46,XX patients with congenital adrenal hyperplasia due to CYP17A1 defects.

OBJECTIVE: To perform a clinical, biochemical, and molecular evaluation of patients with CYP17A1 defects, including ovarian imaging. DESIGN: Retrospective study. SETTING: Tertiary care center. PATIENT(S): Sixteen patients with congenital adrenal hyperplasia due to CYP17A1 defects with a median chronological age of 20 years and belonging to 10 unrelated families. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical and biochemical parameters, molecular diagnosis, ovarian imaging, and therapeutic management. RESULT(S): Seventy-one percent of patients presented with primary amenorrhea, 50% had no breast development, and pubic hair was absent or sparse in all patients; 88% had high blood pressure at diagnosis. Basal LH and P levels were high, and androgen levels were low in all patients. Ultrasound revealed ovarian enlargement in 68.7% and ovarian macrocysts in 62.5% of patients before treatment; three patients had a previous surgical correction of ovarian torsion or rupture. Molecular analysis revealed inactivating CYP17A1 mutations in all patients. The most prevalent mutation was p.W406R, and one patient bore a novel p.G478S/p.I223Nfs*10 compound heterozygous mutation. Treatment with dexamethasone, estrogen, and P resulted in reduction of ovarian volume. CONCLUSION(S): Amenorrhea, absent/sparse pubic hair, hypertension, and ovarian macrocysts, whichincrease the risk of ovarian torsion, are important elements in the diagnosis of 46,XX patients with CYP17A1 defects. High basal P levels in patients with hypergonadotropic hypogonadism point to the diagnosis of CYP17A1 defects. Fertility can be achieved in these patients with novel reproductive techniques.

Prevalence of vitamin B12 deficiency in type 2 diabetic patients using metformin: a cross-sectional study.

CONTEXT AND OBJECTIVE:: The prevalence of vitamin B12 deficiency varies from 5.8% to 30% among patients undergoing long-term treatment with metformin. Because of the paucity of data on Brazilian patients, this study aimed to determine the frequency of B12 deficiency and related factors among Brazilian patients with type 2 diabetes mellitus (T2DM) using metformin. DESIGN AND SETTING:: Cross-sectional study at a public university hospital. METHODS:: Patients with T2DM and a control group of non-diabetics were included. Serum B12 levels were measured and biochemical B12 deficiency was defined as serum levels < 180 pg/ml. Associations between B12 deficiency and age, duration of T2DM, duration of use and dosage of metformin, and use of proton pump inhibitors (PPIs) or histamine H2 antagonists were determined. RESULTS:: 231 T2DM patients using metformin (T2DM-met) and 231 controls were included. No difference in the frequency of PPI or H2-antagonist use was seen between the groups. B12 deficiency was more frequent in the T2DM-met group (22.5% versus 7.4%) and this difference persisted after excluding PPI/H2-antagonist users (17.9% versus 5.6%). The factors that interfered with serum B12 levels were PPI/H2-antagonist use and duration of metformin use ≥ 10 years. Use of PPI/H2-antagonists was associated with B12 deficiency, with an odds ratio of 2.60 (95% confidence interval, 1.34-5.04). CONCLUSIONS:: Among T2DM patients, treatment with metformin and concomitant use of PPI/H2-antagonists are associated with a higher chance of developing B12 deficiency than among non-diabetics.

Nonfunctioning giant pituitary adenomas: Invasiveness and recurrence.

BACKGROUND: We report our surgical series of 35 patients with giant nonfunctioning pituitary adenomas (GNFPA). We analyzed the rule of Ki-67 antigen expression in predicting recurrence. METHODS: Thirty-five patients were operated between 2000 and 2010. Suprassellar extension of the tumors were classified according to Hardy and Mohr based on magnetic resonance (MR) studies. Pituitary endocrine function and MR scans were assessed preoperatively and at 1, 6, and 12 months postoperatively. Immunohistochemical studies were based in regard to the expression of the proliferative Ki-67 index and the hormonal receptor for luteinizing hormone, follicle stimulating hormone, growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, and prolactin. Tumors specimens were obtained from 35 patients with GNFPA. Endoscopic transsphenoidal surgery was the approach of choice. RESULTS: Thirty-five patients were submitted to 49 surgeries, 44 (89.8%) were transsphenoidal and 5 (10.2%) were transcranial. The most frequent preoperative complaints were visual acuity impairment and visual field defect in 25 (71.2%) and 23 (65.7%) cases, respectively. Improvement of visual acuitiy and visual field deficit after surgery was seen in 20 (80%) and 17 (73.9%) patients, respectively. Endocrinological deficits were encountered in 20 patients (57.1%). After surgery, 18 patients (51.4%) required hormonal replacement. Three patients had visual symptoms related to pituitary apoplexy and recovered after surgery. The Ki-67 labeling index (LI) ranged from <1% to 4.8%. The rate of recurrence in tumors with Ki-67 <3% was 7.7% (2 patients), Ki-67 >3% was present in 5 patients and the recurrence committed 3 patients. CONCLUSION: In our series, regardless the improvement of visual function and compressing symptoms, 5 patients with expression of Ki-67 LI more than 3% experienced a recurrence.

Sellar and suprasellar mixed germ cell tumor mimicking a pituitary adenoma.

Germ cell tumors (GCT) are a heterogeneous group of lesions whose origin is not well established. Several cases of primary intrasellar germinomas have been reported, however non-germinomatous GCT have rarely been described. We report the case of a young adult male patient with a mixed GCT that presented with a sellar tumor with suprasellar extension. The patient seeked medical attention because of seizures and magnetic resonance imaging evidenced a tumor of the sellar region. Hyperprolactinemia was also present and dopamine agonist therapy was started. As there was a rapid tumor growth and the patient had concomitant central diabetes insipidus and elevated testosterone levels, a GCT was suspected and confirmed by elevated serum concentration of ß-human chorionic gonadotrophin. Patient underwent surgical resection of the tumor and histopathological examination confirmed the diagnosis of a mixed GCT. Chemotherapy was initiated, followed by conventional radiotherapy. In conclusion, although pituitary adenomas respond for the vast majority of sellar tumors, concomitant symptoms such as central diabetes insipidus and rapid tumor growth should raise the suspicion of a diverse diagnosis. The present report intend not only to show a rare case of sellar and suprasellar mixed GCT but also to remind clinicians that if laboratory findings do not fit into patient's diagnosis (such as high testosterone levels in our patient), then the diagnosis should be reviewed.

Impact of gsp oncogene on the mRNA content for somatostatin and dopamine receptors in human somatotropinomas.

INTRODUCTION: It has been reported in some series that gsp+ somatotropinomas are more sensitive to somatostatin analogues (SA) and dopamine's actions which may be related to their somatostatin receptor (SSTR) and dopamine receptor (DR) profile. No previous studies have been undertaken to evaluate the SSTR and DR profile related with the gsp status in somatotropinomas. OBJECTIVES: To determine if (1) gsp status is correlated with response to octreotide LAR (LAR) and tumor expression patterns of SSTR1-5 and DR1-5 and (2) cAMP level can directly modulate SSTR and DR mRNA levels. METHODS: Response to SA was evaluated by GH and IGF-I percent reduction after 3 and 6 months of treatment with LAR. Conventional PCR and sequencing were used to identify gsp+ tumors. Quantitative real-time PCR was used to determine SSTR and DR tumor expression. Primary pituitary cell cultures of primates were used to study whether SSTR and DR expression is regulated by forskolin. RESULTS: The response to LAR did not significantly differ between patients with gsp+ and gsp- tumors; however, gsp+ tumors expressed higher levels of SSTR1, SSTR2, DR2 and a lower level of SSTR3. Forskolin increased SSTR1, SSTR2, DR1 and DR2 expression in cell cultures. CONCLUSION: Elevated SSTR1, SSTR2, and DR2 tumor expression may help improve responsiveness to SA and DA therapy; however, this study may not have been appropriately powered to observe significant effects in the clinical response. Elevated cAMP levels could be directly responsible for the upregulation in SSTR1, SSTR2 and DR2 mRNA levels observed in gsp+ patients.

Prevalence of gsp oncogene in somatotropinomas and clinically non-functioning pituitary adenomas: our experience.

The purpose of the present study is to evaluate the prevalence of the gsp oncogene in Brazilian patients harboring somatotropinomas and non-functioning pituitary adenomas (NFPA). Patients and methods Deoxyribonucleic acid was extracted from 54 somatotropinomas and 14 NFPA. Exons 8 and 9 (including codons 201 and 227, respectively) of the GNAS gene were amplified by polymerase chain reaction (PCR). The PCR products were then purified and sequenced using the same primers. Results The gsp oncogene was found in nine tumors (eight somatotropinomas). The prevalence among somatotropinomas was 15% and among NFPA was 7%. The mutation was found in codon 201 in eight tumors and in codon 227 in one tumor (a somatotropinoma). No differences were found in age, sex, GH, and IGF-I levels or tumor volume at diagnosis between gsp+ and gsp- patients. Conclusion We found a lower than expected prevalence of gsp mutations in somatotropinomas and a similar prevalence in NFPA compared to previous studies from other countries.

Somatostatin receptors subtypes 2 and 5, dopamine receptor type 2 expression and gsp status as predictors of octreotide LAR® responsiveness in acromegaly / Expressão dos receptores da somatostatina subtipos 2 e 5 e do receptor da dopamina tipo 2 e gsp status como preditores de resposta ao octreotide LAR® na acromegalia

We present two acromegalic patients in which clinical and molecular data are discussed in regard to their ability to predict long term octreotide LAR® therapy response. Case reports: Patient 1: female, 36 years old at diagnosis. Basal GH and IGF-I at diagnosis were 133 ng/mL and 181 percent above the upper limit of reference values (ULRV), respectively. Growth hormone during acute test with subcutaneous octreotide decreased from 133 to 13 ng/mL. Patient started on primary octreotide LAR® therapy (20mg q28 days) and achieved biochemical parameters of disease control after 6 months. Molecular analysis of tumor fragments: gsp +; quantitative analysis of SSTR (somatostatin receptor) and DR (dopamine receptor) mRNA - SSTR2 23954; SSTR5 2407; DR2 total 17016 copies. Patient 2: male, 38 years old at diagnosis. Basal GH and IGF-I at diagnosis were 120 ng/mL and 114 percent ULRV, respectively. Patient underwent non-curative trans-sphenoidal surgery. Post-operative GH and IGF-I were 112 ng/mL and 137 percent ULRV, respectively. Growth hormone during acute test with subcutaneous octreotide decreased from 112 to 7 ng/mL. Octreotide LAR® therapy (20 mg q28 days) was then initiated. After 6 months of treatment, patient did not attain biochemical control of disease and displayed increased tumor volume. Molecular analysis of tumor fragments: gsp not done; quantitative analysis of SSTR and DR mRNA - SSTR2 416; SSTR5 3767; DR2 total 3439 copies. In conclusion, these two cases illustrate how laboratory data can be conflicting as predictors of octreotide LAR® responsiveness and how molecular analysis of tumor fragments can help explain different behaviors in clinically similar patients.

Apresentamos dois pacientes acromegálicos nos quais dados clínicos e moleculares são discutidos quanto à sua capacidade de predizer a resposta a longo prazo ao tratamento com octreotide LAR®. Relato dos casos: Paciente 1: Feminina, 36 anos de idade ao diagnóstico. GH e IGF-I ao diagnóstico 133 ng/mL e 181 por cento acima do limite superior do valor de referência (LSVR), respectivamente. GH durante o teste agudo com octreotide subcutâneo diminuiu de 133 para 13 ng/mL. Foi iniciado tratamento primário com octreotide LAR® (20 mg q28 dias) e a paciente alcançou os parâmetros bioquímicos de controle de doença depois de seis meses. Análise molecular do tumor: gsp +; análise quantitativa do mRNA de SSTR (receptores de somatostatina) e DR (receptor de dopamina) - SSTR2 23.954; SSTR5 2.407; DR2 total 17.016 cópias. Paciente 2: Masculino, 38 anos de idade ao diagnóstico. GH e IGF-I ao diagnóstico 120 ng/mL e 114 por cento LSVR, respectivamente. Paciente foi submetido à cirurgia trans-esfenoidal não-curativa. GH e IGF-I pós-operatórios 112 ng/mL e 137 por cento LSVR, respectivamente. GH durante o teste agudo diminuiu de 112 para 7 ng/mL. Foi iniciado tratamento com octreotide LAR® (20 mg q28 dias). Após seis meses o paciente não alcançou controle bioquímico e apresentou aumento do volume tumoral. Análise molecular do tumor: gsp não estudado; análise quantitativa do mRNA de SSTR e DR - SSTR2 416; SSTR5 3.767; DR2 total 3.439 cópias. Em conclusão, estes dois casos ilustram como dados laboratoriais podem ser conflitantes enquanto preditores de resposta ao tratamento com octreotide LAR® e como a análise molecular de fragmentos do tumor pode ajudar a explicar comportamentos diferentes em pacientes clinicamente semelhantes.

Somatostatin receptors subtypes 2 and 5, dopamine receptor type 2 expression and gsp status as predictors of octreotide LAR responsiveness in acromegaly.

UNLABELLED: We present two acromegalic patients in which clinical and molecular data are discussed in regard to their ability to predict long term octreotide LAR therapy response. CASE REPORTS: Patient 1: female, 36 years old at diagnosis. Basal GH and IGF-I at diagnosis were 133 ng/mL and 181% above the upper limit of reference values (ULRV), respectively. Growth hormone during acute test with subcutaneous octreotide decreased from 133 to 13 ng/mL. Patient started on primary octreotide LAR therapy (20mg q28 days) and achieved biochemical parameters of disease control after 6 months. Molecular analysis of tumor fragments: gsp +; quantitative analysis of SSTR (somatostatin receptor) and DR (dopamine receptor) mRNA - SSTR2 23954; SSTR5 2407; DR2 total 17016 copies. Patient 2: male, 38 years old at diagnosis. Basal GH and IGF-I at diagnosis were 120 ng/mL and 114% ULRV, respectively. Patient underwent non-curative trans-sphenoidal surgery. Post-operative GH and IGF-I were 112 ng/mL and 137% ULRV, respectively. Growth hormone during acute test with subcutaneous octreotide decreased from 112 to 7 ng/mL. Octreotide LAR therapy (20 mg q28 days) was then initiated. After 6 months of treatment, patient did not attain biochemical control of disease and displayed increased tumor volume. Molecular analysis of tumor fragments: gsp not done; quantitative analysis of SSTR and DR mRNA - SSTR2 416; SSTR5 3767; DR2 total 3439 copies. In conclusion, these two cases illustrate how laboratory data can be conflicting as predictors of octreotide LAR responsiveness and how molecular analysis of tumor fragments can help explain different behaviors in clinically similar patients.

Two hour mean GH is not superior to basal GH for the follow-up of acromegalic patients treated with Octreotide LAR.

BACKGROUND: GH secretion, in acromegaly, is characterized by increased basal levels, as well as by increased frequency and amplitude of pulses. Evaluation of disease activity during follow-up of treated patients is frequently done with mean GH levels, although there is no established protocol for sample collection. OBJECTIVE: Determine mean GH value of 5 blood samples collected 30 min apart for 2 consecutive hours in the follow-up of acromegalic patients treated with octreotide LAR. METHODS: Ninety-one GH curves of 44 patients (25 women) were evaluated as were the respective IGF-I values (basal). Normal IGF-I for age and sex was considered standard for control of disease activity. Correlations between basal and mean GH were studied as were correlations between both values and %IGF-I above the upper limit of reference values (%ULRV). RESULTS: Median age of the group was 45.5 years (range 28-73). Twenty-five patients (56.8%) had previous surgery and 7 (15.9%) had both surgery and radiotherapy. A positive correlation was found between mean and basal GH (r=0.953; p<0.001). Both basal and mean GH were correlated to %ULRV (r=0.645 and 0.661; p<0.001 for both). In only 3 of the 91 curves (3.3%) there were discordances between basal GH and IGF-I, however the latter was concordant with mean GH. In 3 other curves there was concordance between basal GH and IGF-I although the latter was discordant with mean GH. CONCLUSIONS: There was no benefit to perform GH curves with the present protocol. It may be due to our established outpatient follow up protocol. The use of more complex protocols and the cost of multiple GH assays should be acknowledged, and probably reserved for patients with basal GH levels between 1 and 5 microg/L with discordant GH and IGF-I.

Sensibilidade, especificidade e valor preditivo dos níveis basais da 17-hidroxiprogesterona no diagnóstico da forma näo-clássica da hiperplasia adrenal congênita por deficiência da 21-hidroxilase / Sensitivity, specificity, and predictive value of baseline 17-hydroxyprogesterone levels in the diagnosis of nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency

A forma näo-clássica da hiperplasia adrenal congênita (HAC) por deficiência da 21-hidroxilase (D21OH) é rastreada com a 17-hidroxiprogesterona basal (17OHPb) e seu diagnóstico confirmado pelo teste do ACTH. Como o nível de 17OHPb que indica a realizaçäo do teste ainda é motivo de discussäo, este estudo teve o objetivo de avaliar este valor no diagnóstico de HAC por D21OH. O teste do ACTH (0,25 mg IV) foi realizado em 87 mulheres de 24,8±0,8 anos com hiperandrogenismo clínico. O valor de 17OHP >1.500 ng/dl após 60min do ACTH foi considerado sugestivo de D21OH, a qual foi diagnosticada em 11 casos (12,6 por cento). Nos outros 76, o teste näo foi compatível com o diagnóstico. A sensibilidade, especificidade e valores preditivos positivo e negativo para 17OHPb >200 ng/dL foram 0,91, 0,62, 0,26 e 0,98, respectivamente. Para 17OHPb >350 ng/dL estes valores foram 0,91, 0,91, 0,59 e 0,99 e para 17OHPb >500 ng/dL foram 0,82, 0,99, 0,9 e 0,97. Os achados clínicos (hirsutismo, irregularidade menstrual e obesidade) e as dosagens de androstenediona e testosterona total foram semelhantes entre os dois grupos. Concluímos que os achados clínicos e os níveis de androgênios näo permitem diferenciar os pacientes com e sem D21OH. Sugerimos realizar o teste do ACTH quando a 17OHPb for >350 ng/dL, valor com alta sensibilidade e bom valor preditivo negativo.