Subgaleal recurrence of craniopharyngioma of rapid growing pattern.

The purpose of the present clinical case is to remind clinicians that craniopharyngiomas, which are benign neoplasms with a high incidence of local recurrences, may also present ectopic recurrences which may at first go unsuspected. These tumors most commonly arise in the suprasellar region and despite their benign histology, they may infiltrate the surrounding neurovascular structures making total removal challenging. Ectopic recurrences of craniopharyngiomas are very rare. We describe an adult patient with ectopic recurrence of craniopharyngioma, emphasizing unique features of the case presentation and its physiopathological aspects. A 49-year-old male presented with headache and visual field defect and was diagnosed with a suprasellar tumor. He was submitted to neurosurgery and histological examination revealed an adamantinomatous craniopharyngioma. Postoperative magnetic resonance imaging (MRI) showed complete tumor resection. The patient remained asymptomatic with no imaging signs of local recurrence during follow up. Five years after surgery, the patient noticed a rapidly growing lump at the surgical incision site. He reported a mild to moderate local trauma 4 months before. A MRI showed a subgaleal cystic tumor arising in the pathway of the craniotomy. Surgical resection of that cystic lesion was performed and histological examination revealed an adamantinomatous craniopharyngioma. One year later no recurrences have been detected. The case reported has two particular features: the local trauma as a potential trigger for tumor progression and the rapidly growing pattern of the ectopic recurrent tumor. We emphasize that although ectopic recurrences of craniopharyngiomas are rare, they may occur away from the primary tumor and quite late in the follow up of the patient.

Dyskinesia associated with hyperglycemia and basal ganglia hyperintensity: report of a rare diabetic complication.

The syndrome of dyskinesia associated with hyperglycemia and basal ganglia hyperintensity on T1 - weighted MR images is rare and most often affects elderly patients with type 2 diabetes. We report a case of a 79 year-old female patient who presented to the ED with a 12 h history of a left sided hemichoreoathetosis. Laboratory results revealed pronounced nonketotic hyperglycemia [27 mmol/L (486 mg/dL); HbA1c 140 mmol/mol (15 %)] and brain MRI showed bilateral T1 hyperintensity in the basal ganglia, more noticeable on the right side. One week before she had been admitted with a diagnosis of transient ischemic attack consisting in left hemiparesthesia, also with nonketotic hyperglycemia [38.9 mmol/L (700 mg/dL)] and was discharged home with partial correction of her metabolic disturbance. The movement disorder did not improve with adequate glycemic control so haloperidol was started. Six weeks later she was seen on an outpatient basis. She still had minimal residual involuntary movements of the left arm and leg. Laboratory exams revealed a well controlled diabetes mellitus [glycemia 6.0 mmol/L (109 mg/dL), HbA1c 57 mmol/mol (7.4 %)]. In conclusion, the syndrome of dyskinesia associated to hyperglycemia and hyperintensity in the basal ganglia on T1 - weighted MR images is a rare, intriguing and yet incompletely understood complication of diabetes mellitus. The increasing number of reported cases may help to better understand its peculiarities such as the existence of a clear clinical radiological dissociation and to unveil pathophysiological aspects. We suggest the possibility that the metabolic disturbances unmask a previous established asymptomatic striatum vasculopathy.

Educating diabetic patients through an SMS intervention: a randomized controlled trial at a Brazilian public hospital.

OBJECTIVE: Diabetes mellitus (DM) has a high healthcare system cost worldwide. Educational strategies are important to improve self-care and control this disease. This study aimed to evaluate satisfaction and clinical efficacy of a Short Message Service (SMS) educational intervention in self-care and nutrition at a Brazilian university hospital. METHODS: We conducted a trial of educational intervention and assigned eligible patients with DM to either receive weekly educational SMS for 6 months (intervention group [IG]) or no SMS at all (control group). A satisfaction questionnaire was applied before and after the intervention in both groups. Laboratory (fasting glucose, hemoglobin [Hb] A1c, total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein) and clinical (blood pressure) data were also collected. Data were analyzed using nonparametric tests with the Statistical Package for the Social Sciences. RESULTS: We included 128 patients (64 in each group). Responses to the satisfaction questionnaire with self-care and healthcare professionals from 112 patients revealed an improvement in the perception of receiving information regarding helpful eating habits and in healthy eating behavior and an improvement in satisfaction with their diabetes care in the IG. In the post-intervention period, improved systolic blood pressure and HbA1c levels were observed in the IG as illustrated by delta % (post-intervention minus pre-intervention data divided by pre-intervention data multiplied by 100) reductions of 2.3% and 3.9%, respectively. CONCLUSION: SMS intervention was useful as an educational tool for improving satisfaction and glycemic and blood pressure control of patients with DM observed at a Brazilian university hospital.

Utility of [(18)F] fluoro-2-deoxy-D: -glucose positron emission tomography in the localization of ectopic ACTH-secreting tumors.

Ectopically ACTH producing tumors may be difficult to localize by conventional radiology and functional imaging may be helpful. Case 1: 31-year-old man was diagnosed with ectopic ACTH-dependent Cushing's syndrome (ECS). Thorax CT revealed a 1.3 cm nodular opacity in upper left lobe, suggestive of residual lesion. [(18)F] fluoro-2-deoxy-D: -glucose ([(18)F] FDG) positron emission tomography ([(18)F] FDG PET) scan revealed mild glycolytic metabolic activity. Pathological examination confirmed an ACTH-positive carcinoid tumor. Case 2: 53-year-old woman presented with very rapid onset ECS. Pituitary MRI was normal. Thorax CT revealed no tumoral lesion. Abdominal and pelvic MRI showed images suggestive of hepatic and iliac, femoral and lumbar secondary implants. [(18)F] FDG PET scan revealed intense uptake in uterus, especially cervix, suggesting this to be the primary tumor site. These cases illustrate the role of [(18)F] FDG PET in the investigation of an ECS where conventional imaging studies were not elucidative in the search for a responsible tumor.

Prevalence of discordant GH and IGF-I levels in acromegalics at diagnosis, after surgical treatment and during treatment with octreotide LAR.

BACKGROUND: Acromegalic patients are considered "discordant" if their insulin-like growth factor type I (IGF-I) levels are increased for their age with "safe" growth hormone (GH) levels or if their IGF-I levels are normal for their age with "unsafe" GH levels. The prevalence of discordance in acromegalics has been described to vary from 9.4% to 39%, and it may be observed at diagnosis or during the follow up. OBJECTIVE: To evaluate the prevalence of discordant levels of IGF-I and GH in our acromegalic population. METHODS: Hormonal evaluation was made with an oral glucose tolerance test (OGTT) with the IGF-I being assessed in the basal sample at diagnosis and after 3 months of the adenomectomy. During treatment with octreotide LAR, a GH curve (for the calculation of mean GH) and IGF-I assessment were made every 3 months. RESULTS: Among the 51 patients evaluated at diagnosis, the prevalence of discordance was 13.7% (7/51). Among the 58 patients evaluated after the surgical procedure, eight (13.8%) had discordant GH and IGF-I levels. Among the 42 patients evaluated during treatment with octreotide LAR, the prevalence of discordant GH and IGF-I levels was 33.3% (14/42). Using 1 microg/L as a cut off level for "safe" GH, the prevalence of discordance was 3.9%, 8.6% and 28.6% at diagnosis, after surgery and during treatment with octreotide LAR, respectively. No difference of sex, age or treatment modality was observed among discordant and concordant patients with any GH cut off level. CONCLUSION: We observed a prevalence of discordance similar to that previously described in the literature. We believe that studies evaluating morbidity and mortality in discordant patients are also necessary and will enlighten the true impact of this condition in the follow up of acromegaly.

[Evaluation of glucose metabolism in acromegalic patients before and after treatment with octreotide LAR]. / Avaliação do metabolismo da glicose em pacientes acromegálicos antes e após tratamento com octreotide LAR.

AIM OF THE STUDY: To evaluate the glucose metabolism in acromegalic patients before and after treatment with octreotide LAR. PATIENTS AND METHODS: This was a prospective and longitudinal study involving 30 patients from the acromegaly research outpatient clinic of the Endocrinology unit of the HUCFF/UFRJ. They underwent clinical and laboratorial evaluations, with measurements of growth hormone (GH), insulin-like growth factor type I (IGF-I), insulin, proinsulin, C peptide, glycosylated hemoglobin (HbA1c), IGF binding protein type 1 (IGFBP-1) and glucose, during oral glucose tolerance test (OGTT), before and after six months of treatment with octreotide LAR. The Wilcoxon signed-rank test was used and values of 5% were considered statistically significant. RESULTS: We found 16 (54%) patients with normal glucose tolerance, 7 (23%) with impaired glucose tolerance and 7 (23%) diabetics. Twelve patients completed the six-month treatment, out of which three showed worsening of glucose tolerance and two (diabetics) had worse blood glucose control. Whereas there was an increase in waist circumference (p=0.03), there was a decrease in GH (p=0.04), with %IGF-I above the upper limit of reference values (% ULRV) [p=0.001], insulin (p=0.019), C peptide levels (p=0.002) and homeostatic model assessment (HOMA-IR) [p=0.039]. CONCLUSIONS: In this series, treatment with octreotide LAR led to a worsening of glucose tolerance in three non-diabetic patients and worsened glycemic control in two diabetics, in spite of reducing insulin resistance.

Quantitative analysis of somatostatin receptor subtype (SSTR1-5) gene expression levels in somatotropinomas and non-functioning pituitary adenomas.

OBJECTIVE: It is believed that the variable effectiveness of somatostatin analogs in post-surgical management of somatotropinomas and non-functioning pituitary adenomas (NFPA) may be due in part to variable expression of somatostatin receptor isoforms (SSTR1-5), within and between pituitary tumor types. DESIGN AND METHODS: Quantitative real-time RT-PCR was used to compare absolute mRNA copy numbers for all five SSTR isoforms in 23 somatotropinomas and 19 NFPA. RESULTS: Somatostatin receptor subtype 5 mRNA was present at the highest level in somatotropinomas, followed by SSTR2>SSTR3>>SSTR1>>>SSTR4. In contrast, SSTR3 mRNA was present at the highest level in NFPA, followed by SSTR2, while SSTR1, SSTR4, and SSTR5 transcripts were only detectable in select tumors. Among somatotropinomas, a positive correlation was found between SSTR2 mRNA levels and the percent decrease of GH (%GH) after 3 and 6 months of therapy with octreotide long acting repeatable (LAR) (r=0.51 and r=0.66; P=0.05 and P=0.008). Also the percent decrease of IGF-I (%IGF-I) after 3 months of octreotide LAR was negatively correlated with SSTR5 and %IGF-I after 6 months of octreotide LAR was positively correlated with SSTR2. CONCLUSIONS: The present report is a large series examining SSTR mRNA levels in somatotropinomas and NFPA. These initial findings suggest that detailed knowledge of the SSTR mRNA expression profile in somatotropinomas can help to predict the hormonal response to therapy with LAR. Also, it appears that SSTR3 in NFPA may be a potential target for SSTR3 preferential or universal ligands such as pasireotide.

Educating diabetic patients through an SMS intervention: a randomized controlled trial at a Brazilian public hospital

ABSTRACT Objective: Diabetes mellitus (DM) has a high healthcare system cost worldwide. Educational strategies are important to improve self-care and control this disease. This study aimed to evaluate satisfaction and clinical efficacy of a Short Message Service (SMS) educational intervention in self-care and nutrition at a Brazilian university hospital. Materials and methods: We conducted a trial of educational intervention and assigned eligible patients with DM to either receive weekly educational SMS for 6 months (intervention group [IG]) or no SMS at all (control group). A satisfaction questionnaire was applied before and after the intervention in both groups. Laboratory (fasting glucose, hemoglobin [Hb] A1c, total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein) and clinical (blood pressure) data were also collected. Data were analyzed using nonparametric tests with the Statistical Package for the Social Sciences. Results: We included 128 patients (64 in each group). Responses to the satisfaction questionnaire with self-care and healthcare professionals from 112 patients revealed an improvement in the perception of receiving information regarding helpful eating habits and in healthy eating behavior and an improvement in satisfaction with their diabetes care in the IG. In the post-intervention period, improved systolic blood pressure and HbA1c levels were observed in the IG as illustrated by delta % (post-intervention minus pre-intervention data divided by pre-intervention data multiplied by 100) reductions of 2.3% and 3.9%, respectively Conclusion: SMS intervention was useful as an educational tool for improving satisfaction and glycemic and blood pressure control of patients with DM observed at a Brazilian university hospital.

Etiologic aspects and management of acromegaly.

Acromegaly is a systemic disease with various etiologies. It can occur as a sporadic or, more rarely, as a familial disease. Numerous complications such as endocrine, cardiovascular, respiratory, metabolic, osteoarticular and neoplastic disturbances occur and must be taken into account when establishing a therapeutic strategy. For this reason, the decision as to a treatment modality of acromegaly must be followed by a thorough evaluation of the patient and once the diagnosis of complications is settled, adequate treatment should be instituted. Follow up of the patients requires periodical re-assessment of complications status.

[Acute test with subcutaneous octreotide as a predictor of the response to treatment with octreotide LAR]. / Teste agudo com octreotide subcutâneo como preditor de resposta ao tratamento com octreotide LAR.

Somatostatin analogues are frequently used to treat acromegaly. To determine the value of the acute test (AT) with subcutaneous (SC) octreotide as a predictor of the response to treatment with octreotide LAR, we analyzed data from 20 patients. For the AT, blood was drawn before and two hours after the SC administration of octreotide for measuring GH. GH levels before and after the AT were 21.9 ng/mL (2.3-143.4) and 3.1 ng/mL (0.3-61.3), respectively. Control of the disease was defined as: GH< 2.5 ng/mL and normal IGF-I anytime during treatment. Sensitivity, specificity, positive and negative predictive values of the AT were 0.9, 0.6, 0.69 and 0.86 for a reduction of 75% of the GH on the test. From our sample we conclude that a 75% reduction of the GH levels during the acute test was able to discriminate patients with a higher or lower chance of responding to treatment.

Truncated somatostatin receptor variant sst5TMD4 confers aggressive features (proliferation, invasion and reduced octreotide response) to somatotropinomas.

The GH/IGF1 response of somatotropinomas to somatostatin analogues (SSA) is associated with their pattern of somatostatin receptor (sst1-sst5) expression. Recently, we demonstrated that expression of a truncated sst5-variant (sst5TMD4) can influence the secretory response of somatotropinomas to SSA-therapy; however, its potential relationship with aggressive features (e.g. invasion/proliferation) is still unknown. Here, we show that sst5TMD4 is present in 50% of non-functioning pituitary-adenomas (NFPA) (n = 30) and 89% of somatotropinomas (n = 36), its expression levels being highest in somatotropinomas > > NFPAs > > > normal pituitaries (negligible expression; n = 8). In somatotropinomas, sst5TMD4 mRNA and protein levels correlated positively, and its expression was directly associated with tumor invasiveness (cavernous/sphenoid sinus), and inversely correlated with age and GH/IGF1 reduction after 3-6 months with octreotide-LAR therapy. GNAS+ somatotropinomas expressed lower sst5TMD4 levels. ROC analysis revealed sst5TMD4 expression as the only marker, within all sst-subtypes, capable to predict tumor invasiveness in somatotropinomas. sst5TMD4 overexpression increased cell viability in cultured somatotropinoma (n = 5). Hence, presence of sst5TMD4 associates with increased aggressive features and worse prognosis in somatotropinomas, thereby providing a potentially useful tool to refine somatotropinoma diagnosis, predict outcome of clinical response to SSA-therapy and develop new therapeutic targets.

Insulin signaling pathways in a patient with insulin resistance of difficult management - a case report.

Insulin signalling pathways were investigated in a 33 year-old woman with immunologic insulin resistance. Her past medical history was remarkable for intermittent use of insulin and allergic reactions to several drugs, and measure of plasma anti-insulin antibodies level corroborated the clinical suspicion of immune mediated insulin resistance (8074 nU/ml - RIA - Ref value: <60). Treatment with several immunosuppressive regimens was tried, however the results were disappointing. Possible subcellular mechanisms of insulin resistance were investigated by performing analysis of insulin receptor and post receptor signaling in skeletal muscle biopsy. The expression of insulin receptor (IR), insulin receptor substrate 1 (IRS-1) and glucose transporter 4 (GLUT-4) was evaluated in total extract from muscle tissue by Western blotting. Basal IR, IRS-1 and GLUT-4 expression was detected, however receptor autophosphorylation was not observed. A study of translocation of GLUT-4 to plasma membrane showed that tissue presented low levels of membrane-associated GLUT-4. When in vitro stimulation was undertaken, tissue was capable to be responsive to insulin. Our results suggest that even though IR expression was normally occurring, IR beta-subunit tyrosine kinase activity in muscle was down-regulated leading to alterations in insulin post receptor signaling. Consistent with normal insulin receptor and post receptor signaling, our results were compatible with decreased insulin binding to IR probably due to neutralization by anti-insulin antibodies. In conclusion, this patient has immunologic insulin resistance and treatment should be based on immunosuppressive drugs as tolerated.

Expression analysis of dopamine receptor subtypes in normal human pituitaries, nonfunctioning pituitary adenomas and somatotropinomas, and the association between dopamine and somatostatin receptors with clinical response to octreotide-LAR in acromegaly.

CONTEXT: Dopamine receptor (DR) and somatostatin receptor subtype expression in pituitary adenomas may predict the response to postsurgical therapies. OBJECTIVES: Our objectives were to assess and compare the mRNA levels of DR1-5 and somatostatin receptors 1-5 in normal pituitaries (NPs), nonfunctioning pituitary adenomas (NFPAs), and somatotropinomas. In addition, we determined whether the level of DR expression correlates with the in vivo response to octreotide-LAR in acromegalic patients. DESIGN AND PATIENTS: Eight NPs, 30 NFPAs, and 39 somatotropinomas were analyzed for receptor mRNA levels by real-time RT-PCR. The DR2 short variant was estimated as the DR2 long/DR2 total (DR2T). The relationship between DR expression and the postsurgical response to octreotide-LAR was assessed in 19 of the acromegalic patients. RESULTS: DR3 was not detected. The relationship between expression levels of DR subtypes in NPs and somatotropinomas was DR2T>>>DR4>>DR5>DR1, whereas in NFPAs, DR2T>>>DR4>>DR1>DR5. The DR2 short variant was the predominant DR2 variant in the majority of samples. In acromegalics treated with octreotide-LAR, DR1 was negatively correlated with percent GH reduction (3 months: r = -0.67, P = 0.002; and 6 months: r = -0.58, P = 0.009), and DR5 was positively correlated with percent IGF-I reduction (3 months: r = 0.55, P = 0.01; and 6 months: r = 0.47, P = 0.04). CONCLUSIONS: DR2 is the predominant DR subtype in NPs, NFPAs, and somatotropinomas. The fact that DR1, DR4, and DR5 are also expressed in many adenomas tested suggests that these receptors might also play a role in the therapeutic impact of postsurgical medical therapies in patients with NFPA and acromegaly. This was supported by the finding that the in vivo response to octreotide-LAR was negatively associated with DR1 and positively associated with DR5.

Prevalence of sleep apnea and metabolic abnormalities in patients with acromegaly and analysis of cephalometric parameters by magnetic resonance imaging.

OBJECTIVES: To determine the prevalence of sleep apnea (SA) and SA syndrome (SAS) in patients with acromegaly and correlate SA with clinical, laboratory, and cephalometric parameters. DESIGN AND METHODS: Prospective and cross-sectional study of 24 patients with active acromegaly evaluated by clinical and laboratory (GH, IGF-I) parameters, polysomnography and magnetic resonance imaging (MRI) of the pharynx. RESULTS: Out of 24 patients, 21 had SA (87.5%), of which 20 (95.3%) had the predominant obstructive type. Median age of these 21 patients was 54 years (range 23-75) and median estimated disease duration was 60 months (range 24-300). The frequency in SA patients of impaired glucose tolerance, diabetes mellitus (DM), and hypertension was 19, 33.3, and 71.4% respectively. Goiter was found in 10 patients (47.6%) and obesity in 18 (90%). Median GH level was 14 mug/l (1.4-198) and median %IGF-I (percentage above the upper limit of normal range of IGF-I) was 181% (-31.6 to 571.2). The prevalence of SAS was 52.4%. Apnea-hypopnea index (AHI) correlated significantly with age, waist circumference, body mass index, and hypopharynx area. The AHI was significantly higher in patients with hypertension and DM. CONCLUSIONS: The prevalence of SA and SAS in acromegaly was similar to the one previously described in other series. Age was a significant risk factor, and hypertension and DM were significantly associated complications of SA. Obesity was also significantly related to SA, as a risk factor, a complication or both. Overall, cephalometric parameters by MRI did not correlate with SA.

Quantitative analysis of somatostatin receptor subtypes (1-5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR.

OBJECTIVE: To determine whether the somatostatin receptor subtype (SSTR) expression profile correlates with hormonal and tumor volume responses to postsurgical octreotide long acting repeatable (OCT LAR) treatment. DESIGN AND METHODS: Quantitative real-time RT-PCR was used to evaluate the absolute mRNA copy numbers for all five SSTR subtypes in 22 somatotropinomas. Response to OCT LAR was studied by hormone levels (GH and IGF-I) and tumor volume (sella turcica magnetic resonance imaging). RESULTS: SSTR5 was present at the highest level followed by SSTR2, SSTR3, SSTR1, and SSTR4 (2327 (1046-5555), 2098 (194-23 954), 97 (0-460), 14 (0-29 480), and 0 (0-652) copies respectively). Positive correlations were found between SSTR2 levels and the percentage decrease of GH and IGF-I after 3 (r=0.49, P<0.027 and r=0.49, P<0.029 respectively) and 6 (r=0.59, P<0.006 and r=0.58, P<0.008 respectively) months of OCT LAR. A negative correlation was found between SSTR5 mRNA levels and the percentage decrease of GH after 3 months of OCT LAR (r=-0.52, P=0.016, n=21). A higher SSTR2/SSTR5 ratio was observed among patients who obtained hormonal control with OCT LAR, when compared with those uncontrolled (2.4 (0.7-10) vs 0.3 (0.1-7.7), P=0.001). A ROC curve analysis showed a SSTR2/SSTR5 ratio of 1.3 as the best predictor of disease control, with a sensitivity of 88% and a specificity of 92% - area under curve, 0.9. A positive correlation was also found between SSTR2 mRNA levels and the percentage decrease in tumor volume after 6 months of OCT LAR (r=0.79, P=0.002, n=12). CONCLUSIONS: Somatostatin receptor subtype 2 mRNA expression levels in somatotropinomas correlate positively with in vivo hormonal and tumor volume responses to OCT LAR.

Avaliação do metabolismo da glicose em pacientes acromegálicos antes e após tratamento com octreotide LAR / Evaluation of glucose metabolism in acromegalic patients before and after treatment with octreotide LAR

OBJETIVO: Avaliar o metabolismo da glicose em pacientes acromegálicos antes e após o tratamento com octreotide LAR. PACIENTES E MÉTODOS: Este foi um estudo longitudinal e prospectivo com 30 pacientes do ambulatório de pesquisa em acromegalia do Serviço de Endocrinologia do Hospital Universitário Clementino Fraga Filho da Universidade Federal do Rio de Janeiro (HUCFF/UFRJ). Eles foram submetidos à avaliação clínica e laboratorial com dosagens de hormônio do crescimento (GH), fator de crescimento semelhante à insulina tipo I (IGF-I), insulina, pró-insulina, peptídeo C, hemoglobina glicosilada (HbA1c), proteína de ligação do IGF tipo 1 (IGFBP-1) e a um teste oral de tolerância à glicose (TOTG), antes e após seis meses de tratamento com octreotide LAR. Foi aplicado o teste dos postos sinalizados de Wilcoxon e o critério de determinação de significância adotado foi o nível de 5 por cento. RESULTADOS: Encontraram-se 16 pacientes (54 por cento) com tolerância normal à glicose, sete (23 por cento) com intolerância à glicose e sete (23 por cento) com diabetes melito (DM). Doze pacientes completaram os seis meses de tratamento, sendo que houve piora da tolerância à glicose em três e piora do controle glicêmico dos dois pacientes diabéticos. Houve aumento da circunferência abdominal (p = 0,03) e queda do GH (p = 0,04), por cento IGF-I acima do limite superior do valor de referência ( por centoLSVR) (p = 0,001), insulina (p = 0,019), peptídeo C (p = 0,002) e do modelo de avaliação homeostática (HOMA-IR) (p = 0,039). CONCLUSÕES: Nesta série, o tratamento com octreotide LAR acarretou piora da tolerância à glicose em três pacientes não-diabéticos e piora do controle glicêmico em dois diabéticos, apesar da diminuição da resistência insulínica (RI).

AIM OF THE STUDY: To evaluate the glucose metabolism in acromegalic patients before and after treatment with octreotide LAR. PATIENTS AND METHODS: This was a prospective and longitudinal study involving 30 patients from the acromegaly research outpatient clinic of the Endocrinology unit of the HUCFF/UFRJ. They underwent clinical and laboratorial evaluations, with measurements of growth hormone (GH), insulin-like growth factor type I (IGF-I), insulin, proinsulin, C peptide, glycosylated hemoglobin (HbA1c), IGF binding protein type 1 (IGFBP-1) and glucose, during oral glucose tolerance test (OGTT), before and after six months of treatment with octreotide LAR. The Wilcoxon signed-rank test was used and values of 5 percent were considered statistically significant. RESULTS: We found 16 (54 percent) patients with normal glucose tolerance, 7 (23 percent) with impaired glucose tolerance and 7 (23 percent) diabetics. Twelve patients completed the six-month treatment, out of which three showed worsening of glucose tolerance and two (diabetics) had worse blood glucose control. Whereas there was an increase in waist circumference (p=0.03), there was a decrease in GH (p=0.04), with percentIGF-I above the upper limit of reference values ( percent ULRV) [p=0.001], insulin (p=0.019), C peptide levels (p=0.002) and homeostatic model assessment (HOMA-IR) [p=0.039]. CONCLUSIONS: In this series, treatment with octreotide LAR led to a worsening of glucose tolerance in three non-diabetic patients and worsened glycemic control in two diabetics, in spite of reducing insulin resistance.

Etiologic aspects and management of acromegaly

A acromegalia é uma doença sistêmica com diversas etiologias. A grande maioria dos casos se manifesta de forma esporádica, e uma minoria tem transmissão familiar. Além disso, a acromegalia pode ser acompanhada de várias complicações como alterações endócrinas, cardiovasculares, respiratórias, metabólicas, osteoarticulares e neoplásicas que devem ser consideradas quando a estratégia de tratamento for estabelecida. O acompanhamento dos pacientes requer reavaliações periódicas do status das complicações. Neste artigo serão abordados os aspectos etiológicos e o manejo da acromegalia.

Teste agudo com octreotide subcutâneo como preditor de resposta ao tratamento com octreotide LAR® / Acute test with subcutaneous octreotide as a predictor of the response to treatment with octreotide LAR®

Os análogos da somatostatina são muito utilizados no tratamento da acromegalia. Com o objetivo de determinar o valor do teste agudo (TA) com octreotide subcutâneo (SC) como preditor da resposta ao tratamento com octreotide LAR®, analisamos os dados de 20 pacientes. Para o TA, amostras de sangue foram colhidas antes e duas horas após a administração de octreotide SC para a dosagem de GH. Os níveis de GH antes e após o TA foram 21,9 (2,3-143,4) e 3,1ng/mL (0,3-61,3), respectivamente. Foi considerado controle de doença: GH< 2,5ng/mL e IGF-I normal em algum momento durante o tratamento. A sensibilidade, especificidade e os valores preditivos positivo e negativo do TA foram 0,9, 0,6, 0,69 e 0,86 para redução de 75 por cento do GH no teste. Concluímos que, em nossa casuística, um decréscimo de 75 por cento dos níveis de GH no TA teve um bom poder discriminatório entre pacientes com maior e menor chance de resposta ao tratamento.

Resistência insulínica imunológica: apresentação de caso / Immunologic insulin resistance: case report

Resistência insulínica imunológica é uma entidade reconhecida na prática clínica há muitos anos. Sua patogênese está relacionada ao aparecimento de anticorpos anti-insulina, e o tratamento baseia-se em imunossupressão. Apresentamos aqui o caso de uma paciente de 33 anos, com diagnóstico de diabetes desde a infãncia, que referia uso de hipoglicemiantes orais durante a adolescência. Durante o acompanhamento em nosso serviço, a dose de insulina foi progressivamente reduzida até ser substituída por hipoglicemiantes orais. Permaneceu 11 meses com esquema de glibenclamida, mefformina e acarbose até ser internada em coma hiperosmolar não-cetótico. Após internação prolongada, recebeu alta usando insulina NPH, sendo necessário o aumento da dose nos meses subseqüentes. Quando atingiu a dose de 2,7U/Kg/dia, foi investigada e excluída a possibilidade de diabetes secundário, sendo diagnosticada resistência insulínica imunológica. Foram tentados diversos esquemas imunossupressores sem sucesso. A paciente está atualmente em uso de bomba de infusão subcutânea de insulina Lispro, micofenolato mofetil e prednisona com melhora do controle glicêmico.

Avaliaçäo da incidência e do comportamento do câncer de tireóide em pacientes com doença de graves submetidos a tireoidectomia / Incidence and behavior of thyroid carcinoma in patients with graves' disease treated by thyroidectomy

A fim de avaliar a incidência, comportamento, evoluçäo clínica e determinaçäo de possíveis fatores preditivos da associaçäo entre carcinoma de tireóide (CT) e Doença de Graves (DG), analisamos os prontuários de todos os pacientes submetidos à tireoidectomia para tratamento definitivo de DG em 2 hospitais universitários, entre 01/79 e 11/02. Dos 341 pacientes identificados, o exame histológico das peças cirúrgicas revelou CT em 7 (2,1 por cento). A idade dos pacientes do grupo sem CT variou de 13 a 79 anos (mediana: 34) e naqueles com CT variou de 19 a 50 anos (mediana: 29), sem diferença significativa entre os grupos. Havia 293 mulheres (87,7 por cento) e 41 homens (12,3 por cento) no grupo sem CT e 5 mulheres (71,5 por cento) e 2 homens (28,5 por cento) no grupo com CT. O tipo histológico presente em todos os casos foi carcinoma papilífero de tireóide (CPT), sendo um caso de CPT multicêntrico sem acometimento extra-tireoidiano, 2 casos de variante folicular com 8 e 25mm de diâmetro, sem invasäo capsular, um caso de CPT clássico com 15mm de diâmetro e nos 3 restantes, microcarcinoma (<10mm de diâmetro). O acompanhamento dos pacientes variou de 6 a 16 anos, e nenhum apresentou recorrência local da doença, ou metástases à distância. Nesta casuística, a incidência de CT em pacientes operados por DG foi concordante com dados da literatura. Näo observamos agressividade maior do que a usual, talvez pela grande freqüência de carcinomas ocultos