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.

Octreotide-LAR-associated erythema multiforme in an acromegalic subject: case report

Long-acting somatostatin analogs are often used for treating acromegaly, either as adjuvant to surgery or radiotherapy or, more recently, as a primary therapeutic option. These drugs seem to be reasonably safe, but new adverse effects not yet described may occur during the use of the relatively new long-acting formulations. In this case report, we describe a severe cutaneous reaction (erythema multiforme) in a patient treated with long-acting release (LAR) octreotide, and also discuss the need of previous "testing" with short subcutaneous preparation of octreotide.

Análogos da somatostatina de longa duração são freqüentemente usados no tratamento da acromegalia, como adjuvante à cirurgia ou à radioterapia ou, mais recentemente, como opção terapêutica primária. Essas drogas parecem ser razoavelmente seguras, mas podem ocorrer feitos colaterais ainda não descritos com o uso das relativamente novas formulações de ação prolongada. Neste relato de caso, descrevemos uma reação cutânea grave (eritema multiforme) em uma paciente tratada com octreotide de liberação prolongada (LAR) e discutimos a necessidade de submeter os pacientes previamente a um "teste" com a formulação subcutânea do octreotide de ação rápida.

Treatment of diabetic retinopathy with long-acting somatostatin analogues

In this chapter we will discuss the prevalence of diabetes mellitus and the natural course of diabetic retinopathy. Evidence for the important role of hyperglycaemia as the major risk factor for the development of this specific diabetic complication is described. Large clinical trials have provided information on how the risk for microvascular complications in diabetic patients could be modified Failures of existing preventive strategies and the need for the development of new treatment modalities are described. The important roles of growth hormone [GH] and other growth factors for the development of proliferative retinopathy and their modification by somatostatin as well as somatostatin analogues are discussed as a novel basis for the intervention strategies in proliferative diabetic retinopathy

Effects of octreotide in experimental acute pancreatitis

O octreotide, um analogo sintetico de longa duracao da somatostatina, foi avaliado na prevencao e tratamento da pancreatite aguda experimental induzida pela tecnica da alca duodenal fechada. Quarenta ratos machos da raca Wistar (peso medio de 361 g) foram alocados em quatro grupos. Nos grupos nao-tratado (2), tratado (3) e profilatico (4), induziu-se a pancreatite aguda atraves da tecnica da alca duodenal fechada, enquanto que no grupo controle (1), o procedimento cirurgico foi...

Octreotide: a clinical update

Somatostatin is found in the pancreas and gastrointestinal tract, including the visceral autonomic nervous system, the endocrine D cells and the gut lumen. Somatostatin peptides may act differently at different sites as hormones, as paracrine substances or neurotransmitters. So far not much is known on the physiological effects of somatostatin in the gastrointestinal tract. Somatostatin and octreotide, a synthetic analogue with a longer half-life and higher potency, inhibit the neuroendocrine and exocrine gastrointestinal secretion, intestinal glucose, fat and amino acid transport, intestinal propulsive and gallbladder motility, splanchnic blood flow in volunteers and hepatic venous pressure in cirrhotic patients. The inhibition occurs to various extents depending on the target organ. This review deals with the pharmacological effects of octreotide on different gastrointestinal functions and describes the therapeutic role in different gastrointestinal disorders