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The most relevant risk factors for the development of chronic constipation are neurologic disorders such as Parkinson's disease, immobility, and some drugs, in particular opioids. A proctologic exam and exclusion of red flags form part of the basic assessment. The currently available laxatives are effective and safe, habituation and tolerance (tachyphylaxis) being an exception. Also long-term intake of laxatives is of no concern when taken in recommended doses (no relevant hypokalemia!). Though the newer compounds (e. g., prucalopride, linaclotide, lubiprostone) are not more effective than the older ones, developing new drugs with alternative mode of action is reasonable since there are patients not satisfied with the currently available substances. Macrogol, Bisacodyl, and sodium picosulfate are the laxatives of first choice. Their selection depends on the individual preference of the patient. Opioids often induce constipation which can be ameliorated by laxatives or PAMORAs (peripherally acting µ-opioid antagonists)., Competing Interests: Der Autor hat einen Beratervertrag mit Sanofi Deutschland., (© Georg Thieme Verlag KG Stuttgart · New York.)

History and Clinical Findings: For 4 months a 37-year-old woman had been treated for Hashimoto thyroiditis with L-thyroxine, at first 25, then 50 micrograms. From the moment the higher dose had been started she experienced weakness, dizzy spells, nausea, vomiting, weight loss and hyperpigmentation. Her blood pressure was reduced to about 80/60 mm Hg., Investigation: The cortisol level was 5.4 nmol/l. When adrenocorticotrophic hormone was administered the cortisol level rose inadequately. Serum ACTH was raised to 3993 pg/ml., Treatment and Course: When hydrocortisone was administered (10 mg in the morning plus 5 mg three times daily) her condition immediately improved and L-thyroxine (50 micrograms/d) was now well tolerated., Conclusion: Substitution with thyroid hormone causes an increased cortisol breakdown in the liver. It is likely that this will have accentuated the previously latent cortisol deficiency resulting from adrenal cortical insufficiency (caused by an autoimmune mechanism) thus producing typical addisonian signs.

The validity of fractionation of serum bilirubin into direct and indirect fractions for differentiation of haemolytic and hepatobiliary hyperbilirubinaemia was assessed in 20 patients with haemolysis and 72 patients with hepatobiliary diseases. The groups varied significantly regarding the ratio of direct and total bilirubin (0.45 +/- 0.24 vs. 0.58 +/- 0.18, P less than 0.005). Due to the frequency distribution between both groups in each patient there was an a-priori probability of haemolysis of 22% and of hepatobiliary disease of 78%. Fractionation increased the probability of correct diagnosis from 22% to 55% and from 78% to 91%. Exclusion of patients with a total bilirubin of more than 3 mg/dl (51 mumol/l) increased the probability from 26% to 80% and from 74% to 86%. Thus fractionation of serum bilirubin is a considerable gain for the diagnosis of haemolysis, particularly in relatively low total bilirubin. The more frequent hepatobiliary diseases can be better diagnosed using other laboratory methods. Thus fractionation is useful only when a hepatobiliary disease has been established as unlikely beforehand.

Gastro-oesophageal reflux was examined by taped long-term pH monitoring in 31 healthy subjects (16 men, 15 women; average age 28 years). The following was found: (1) reflux during the day is normal in health subjects, occurring predominantly after meals; (2) healthy persons have practically no reflux at night, after reaching the phase of deep sleep, the decisive difference between the healthy subject and those with reflux concerning the sleep phase, during which the patient with reflux has significantly increased reflux; (3) gastro-oesophageal reflux during the night is dependent upon depth of sleep, while position-dependent reflux was not observed.