Thrombocytopenia associated with octreotide

A 42-year-old woman with a history of hepatitis C-induced cirrhosis, gastrointestinal bleeding, and alcohol abuse presented to the hospital with hematemesis and melena. Based on our previous experience, octreotide (Sandostatin) therapy was started at 50 mg/hr and continued for 5 days. Platelet count on admission (122 x 10(9)/L) dropped immediately after octreotide therapy was started; upon discontinuation, platelet count began trending up from 72 x 10(9)/L. However, octreotide was not suspected at this point as the cause of thrombocytopenia. In a subsequent admission, octreotide was again administered with a resultant prompt decrease in platelet count. To our knowledge, this is only the second case report of octreotide-induced thrombocytopenia, and the first case of this adverse effect demonstrated by inadvertent rechallenge.     

Expanding uses of octreotide

This chapter reviews the therapeutic use of octreotide in a variety of pancreatic disorders, including acute pancreatitis, in the prevention of postoperative and post-ERCP pancreatitis, in the control of postoperative pancreatic fistulae, and in chronic pancreatitis for the control of pain and of pseudocysts and ascites. The review also discusses the use of octreotide in intestinal disorders of motility, gastrointestinal bleeding, intestinal fistulae and refractory diarrhoea, including the diarrhoeas of AIDS, diabetes, short gut, chemotherapy, ileostomy and gastric surgery. The use of octreotide in neuroendocrine tumours, both for therapy and diagnostic imaging, is reviewed briefly. The paucity of adequately controlled studies in many of these situations is indicated and the potential usefulness of octreotide estimated.     

Treatment of orthostatic hypotension with octreotide

The purpose of this study was to evaluate the therapeutic potential of the somatostatin analog octreotide in patients with orthostatic hypotension. Octreotide was administered sc, and its pressor effect was assessed while the patients were semirecumbent and on the tilt table. We also studied the effect of octreotide on blood pressure while patients walked. The efficacy of therapy was assessed by measuring the duration of walking (walking time) before the onset of hypotension. Low doses of octreotide (0.2-0.4 micrograms/kg) had a pressor effect in all patients with progressive autonomic failure (n = 7), multiple system atrophy (n = 7), and diabetic autonomic neuropathy (n = 8), but not in patients with sympathotonic orthostatic hypotension (n = 6). Larger doses (0.4-1.6 micrograms/kg) resulted in a sustained (greater than or equal to 50 min) increase in blood pressure during walking in four of six patients with progressive autonomic failure and in one of six patients with multiple system atrophy. Some patients in whom octreotide failed to stabilize upright blood pressure had a satisfactory response to the drug after pretreatment with dihydroergotamine (10 micrograms/kg, sc). Patients with diabetic autonomic neuropathy, although sensitive to the pressor effect of octreotide, often developed nausea or abdominal cramps after moderate doses (greater than 1.0 micrograms/kg). These results indicate that the pressor effect of octreotide is sufficiently potent to prevent orthostatic hypotension in some patients with autonomic neuropathy. Others require treatment with both dihydroergotamine and octreotide to achieve a stable upright blood pressure.     

Acute test with subcutaneous octreotide as a predictor of the response to treatment with 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.     

Primary intestinal lymphangiectasia successfully treated with octreotide

A 21-year-old man with diarrhea and edema was admitted to our hospital and diagnosed with protein-losing enteropathy caused by primary intestinal lymphangiectasia. He was placed, in turn, on a low-fat diet, an elemental diet, and, subsequently, fasting therapy with total parenteral nutrition (TPN) support. However, his symptoms were not relieved, but, rather were exacerbated. On the 45th day of hospitalization, octreotide therapy was initiated. After 2 weeks of treatment, his clinical symptoms, as well as hypoproteinemia and hypoalbuminemia, gradually became alleviated. The improvement was confirmed in terms of scintigraphy, endoscopy, and histology of the duodenum. The patient remained healthy until 6 months after the commencement of octreotide treatment, when he discontinued octreotide at his own discretion, at which point the symptoms recurred. Resumption of the drug; however, again brought about remission, which has continued until the present, March 2000. Thus, octreotide therapy is one modality which may be useful for refractory primary intestinal lymphangiectasia. Received: September 24, 1999 / Accepted: May 26, 2000     

Successful treatment of hepatic hydrothorax with octreotide

Hepatic hydrothorax is a rare complication of cirrhosis. Controlling ascites formation is the goal of therapy. We report the case of an adult patient presenting with alcoholic cirrhosis who developed first a symptomatic hydrothorax, refractory to diuretics and fluid and sodium restriction, and then an hepatorenal syndrome. Treatment consisted of chest tube insertion and 5 days' intravenous infusion of octreotide. Complete clinical and biological data were reviewed. Octreotide administration resulted in an increased urinary outflow and sodium output, concomitant with improved renal function. The patient has been free of symptoms after discharge from hospital for a follow-up period of 5 months. This observation raises interesting issues regarding the possible utility of splanchnic vasoconstrictors, reducing portal hypertension, in the treatment of refractory hepatic hydrothorax.     

Somatostatin or octreotide in acute variceal bleeding

In patients with cirrhosis, somatostatin or octreotide administration is followed by a transient decrease in the hepatic venous pressure gradient and azygos blood flow. Although no clear-cut changes in variceal pressure are observed and the exact mechanisms of acute hemodynamic changes induced by somatostatin or its derivatives are still unknown, this provided the rationale for its use in patients with variceal hemorrhage. The only known sustained hemodynamic effect of octreotide is to prevent increases in hepatic venous gradient or azygos blood flow in response to food intake. Somatostatin infusion can be as effective as sclerotherapy in the initial control of bleeding esophageal varices in patients with cirrhosis and is associated with fewer complications. Octreotide also seems to be as effective as endoscopic therapy in the control of acute variceal bleeding, although larger studies should be performed before its efficacy and safety profile can be fully evaluated. The combination of somatostatin or long-acting analogues to endoscopic therapy has recently been delineated as one of the most promising approaches in these patients. Early somatostatin administration with repeat boluses, starting several hours before sclerotherapy is combined, eases the endoscopic procedure and reduces bleeding control failure rate. Although two studies also showed that octreotide, when started at the time of sclerotherapy or variceal banding, also improves bleeding control, a conclusion on octreotide use in these patients is premature. Optimal administration schedules and doses of somatostatin or octreotide are still unknown. The safety of octreotide in patients with variceal bleeding, which has recently been challenged, should be assessed in larger trials. Recent data suggesting that octreotide combination to beta-blockers or sclerotherapy may represent a useful approach for long-term prevention of rebleeding in these patients will have to be confirmed.     

Effect of octreotide treatment on Graves' ophthalmopathy

In this study, nine patients with Graves' ophthalmopathy with positive clinical activity score (CAS), who were either unresponsive or not suitable for glucocorticoid treatment, were given 100 microg of octreotide three times daily, subcutaneously, for three months. The mean age was 49+/-13 years. All patients were under either propylthiouracil or methimazole therapy and were euthyroid for at least one month prior to the start of the octreotide treatment. The mean degree of proptosis as measured with the Hertel exophthalmometer decreased slightly after the treatment (22.0+/-3.0 vs 19.6+/-2.4 for the right eye and 22.2+/-1.9 vs 20.2+/-2.2 for the left eye; p<0.05). The mean activity score decreased from 3.2+/-0.8 to 1.7+/-1.1 (p<0.005) and the mean score of eye signs according to the NOSPECS classification showed improvement with octreotide therapy (3.2+/-0.7 vs. 2.2+/-1.4; p<0.05). Seven patients responded favorably to octreotide treatment. In the remaining two no improvement was observed. Four of the responders could be followed up for 20 months after the treatment and all maintained the favorable state of eye findings obtained with octreotide. We conclude that octreotide seems to be a safe and effective drug in Graves' ophthalmopathy, especially in improving soft tissue involvement, and can be used in patients who are unresponsive to glucocorticoid treatment or who cannot use these drugs for some reason.     

Yellow nail syndrome: treatment with octreotide

Introduction: The yellow nail syndrome (YNS) is the triad of ‘yellow’ nails, peripheral oedema and pleural effusions. For diagnosis, which is clinical, at least two of these findings are necessary. Also typical is a long‐standing chronic cough often caused by low‐grade bronchiectases. The pleural effusions often require pleurodesis. The pathogenesis is probably a dysfunction of the lymphatic system ( 1 , 2 ). Octreotide regulates the release of growth hormone and thyrotropin, and also has effects on the gastro‐intestinal tract, where it inhibits glandular secretion, neurotransmission, smooth‐muscle contraction and absorption of nutrients. Adverse effects are nausea, abdominal cramps, diarrhoea, malabsorption of fat and flatulence ( 3 ). Because of the inhibition of absorption of fats and other nutrients, octreotide has been useful in chylothorax from many different causes ( 4 ). The pleural effusion in YNS is usually an exudate, but in rare cases a frank chylothorax. One such case with successful octreotide treatment has been described in the literature ( 5 ). Objective: The aim of this report was to investigate the effect of octreotide treatment on a patient with YNS with pleural exudates not resulting from chylothorax. Methods and results: A 62‐year‐old man with typical YNS presented with bilateral large pleural effusions ( Fig. 1 ). He had suffered from repeated pneumonia for many years, and 10 years earlier mild bronchiectases were diagnosed and yellow nails were noted. From the right pleura, 1750‐mL clear yellowish fluid was removed and a few days later, 1300 mL was removed from the left side. During the next few weeks, repeated thoracocenteses on both sides were necessary for the palliation of his dyspnoea, and the total amount of removed fluid was more than 10 L. The pleural fluid showed a low cholesterol value, 1.2 mmol/L (serum, 3.5), a fairly high albumin level, 19.0 g/L [serum, 25 g/L (normal, 36–45)], and no triglycerides. Octreotide was administered, initially 0.5 mg subcutaneously twice daily to make sure that there were no side effects, then the long‐acting drug, 30 mg given every fourth week. There was a subjective improvement after the first week, and even though he still has pleural effusions bilaterally, he no longer needs palliative thoracocenteses and can live a normal life. His nails are better, as is the oedema. He is satisfied with his treatment and does not wish to have any pleurodesis. The observation time is now 6 months, and no adverse side effects have been seen so far.

Figure 1 Open in figure viewer PowerPoint Yellow nail syndrome. Pitting oedema on the legs, bilateral massive pleural effusions and typical toenails.