Claudia Nogueira

Acromegaly at diagnosis in 3173 patients from the Liege Acromegaly Survey (LAS) database.

Acromegaly is a rare disorder caused by chronic growth hormone (GH) hypersecretion. While diagnostic and therapeutic methods have advanced, little information exists on trends in acromegaly characteristics over time. The Liège Acromegaly Survey (LAS) Database, a relational database, is designed to assess the profile of acromegaly patients at diagnosis and during long-term follow-up at multiple treatment centers. The following results were obtained at diagnosis. The study population consisted of 3173 acromegaly patients from ten countries; 54.5% were female. Males were significantly younger at diagnosis than females (43.5 vs 46.4 years; P < 0.001). The median delay from first symptoms to diagnosis was 2 years longer in females (P = 0.015). Ages at diagnosis and first symptoms increased significantly over time (P < 0.001). Tumors were larger in males than females (P < 0.001); tumor size and invasion were inversely related to patient age (P < 0.001). Random GH at diagnosis correlated with nadir GH levels during OGTT (P < 0.001). GH was inversely related to age in both sexes (P < 0.001). Diabetes mellitus was present in 27.5%, hypertension in 28.8%, sleep apnea syndrome in 25.5% and cardiac hypertrophy in 15.5%. Serious cardiovascular outcomes like stroke, heart failure and myocardial infarction were present in <5% at diagnosis. Erythrocyte levels were increased and correlated with IGF-1 values. Thyroid nodules were frequent (34.0%); 820 patients had colonoscopy at diagnosis and 13% had polyps. Osteoporosis was present at diagnosis in 12.3% and 0.6–4.4% had experienced a fracture. In conclusion, this study of >3100 patients is the largest international acromegaly database and shows clinically relevant trends in the characteristics of acromegaly at diagnosis.

Oral glucose lowering drugs in type 2 diabetic patients with chronic kidney disease

Chronic kidney disease (CKD) represents a challenge in the treatment of type 2 diabetic patients. Renal impairment may affect drug clearance and other pharmacokinetic processes which can increase toxicity and drug to drug interactions or cause ineffective therapy. There are many oral glucose lowering drugs available for the treatment of type 2 diabetes mellitus (T2DM) with different mechanisms of action and different pharmacokinetic profiles. While all classes may be used in patients with mild renal impairment, therapeutic options for patients with moderate to severe CKD are still limited. This review focuses on the pharmacokinetics, metabolism, and safety of oral glucose lowering drugs in patients with T2DM and CKD.

Permanent neonatal diabetes by a new mutation in KCNJ11: unsuccessful switch to sulfonylurea

Permanent neonatal diabetes (PNDM) can result from activating heterozygous mutations in KCNJ11 gene, encoding the Kir6.2 subunit of the pancreatic ATP-sensitive potassium channels (KATP). Sulfonylureas promote KATP closure and stimulate insulin secretion, being an alternative therapy in PNDM, instead of insulin. Male, 20 years old, diagnosed with diabetes at 3 months of age. The genetic study identified a novel heterozygous mutation in exon 1 of the KCNJ11 gene - KCNJ11:c1001G>7 (p.Gly334Val) - and confirmed the diagnosis of PNDM. Therefore it was attempted to switch from insulin therapy to sulfonylurea. During glibenclamide institution C-peptide levels increased, however the suboptimal glycemic control lead us to restart an intensive insulin scheme. This new variant of KCNJ11 mutation had a phenotypic lack of response to sulfonylurea therapy. Age, prior poor metabolic control and functional change of KATP channel induced by this specific mutation may explain the observed unsuccessful switch to sulfonylurea. Interestingly, C-peptide levels raise during glibenclamide administration support some degree of improvement in insulin secretory capacity induced by the treatment. Understanding the response to sulfonylurea is crucial as successful treatment may be life-changing in these patients.

Low-temperature Raman spectra of the 2-(α-methylbenzylamino)-5-nitropyridine crystal

The polar organic 2-(α-methylbenzylamino)-5-nitropyridine crystal (MBANP) has been studied by Raman spectroscopy at low temperatures (from 300 to 10K). The effect of temperature change on the vibrational spectrum is discussed with the aid of DFT calculations. The behavior of the Raman spectra indicates that MBANP molecules present a different conformation at low temperatures associated with the rotation of the phenyl and pyridine rings. Temperature-dependent X-ray measurements and differential scanning calorimetry (DSC) analysis were utilized as complementary techniques to investigate the structural stability of MBANP crystal.

COMUNICAÇÕES ORAISXIV Congresso Português de Endocrinologia/64a Reunião Anual da SPEDMPorto, 24 a 27 de Janeiro de 2013CO095. CARACTERÍSTICAS CLÍNICAS, ANALÍTICAS, IMAGIOLÓGICAS, TRATAMENTO E OUTCOME NUMA POPULAÇÃO DE DOENTES ACROMEGÁLICOS

variaveis. Apresentam-se resultados dos doentes tratados no nosso servico nos ultimos 16 anos. Metodos: Avaliacao retrospectiva dos 21 doentes (20 mulheres) com DC observados de 1996 a 2011, submetidos a CH. O diagnostico foi confirmado com base nos doseamentos de ACTH, cortisol urinario, provas de supressao com dexametasona (dose fraca e forte) e prova de CRH. A imagiologia hipofisaria por RM foi efectuada em todos os doentes e o cateterismo dos seios petrosos apenas nos casos de dificuldade no diagnostico diferencial. Resultados: A RM hipofisaria revelou macroadenoma (n = 3), microadenoma (n = 13) e ausencia de imagem (n = 5). Seis doentes efectuaram cateterismo dos seios petrosos. Com excepcao de 1 caso (macroadenoma invasivo), a abordagem cirurgica foi trans-esfenoidal, verificando-se cura em 13 doentes (62%). Destes, apos um follow up medio de 4,6 anos, apenas 2 recidivaram. Dos 8 doentes com persistencia da doenca apos CH, 5 foram reoperados, obtendo-se cura em 3, que persiste em 2 casos decorridos mais de 5 anos. Das 3 recidivas apos 1 ou 2 CH, duas ocorreram mais de 10 anos depois. Verificou-se 1 obito no pos-operatorio imediato de um destes casos. Foi efectuada suprarrenalectomia bilateral em 4 doentes e 3 estao sob terapeutica medica. Conclusao: O racio mulheres/homens na nossa serie e muito superior ao descrito na literatura. A taxa de cura apos primeira ou segunda CH (76%) e semelhante a descrita em outros centros. Duas recidivas ocorreram muito para alem dos 2 anos habitualmente referidos, dado verificado pela duracao do follow-up que e maior que o de outras series. A radioterapia nao foi opcao no tratamento dos nossos doentes.