Subnormal alanine aminotransferase values in blood of patients with Crohn disease.

BACKGROUND: It was observed that several patients from the outpatient clinic with Crohn disease (CD) occasionally had subnormal values of alanine aminotransferase (ALAT) in blood. Subnormal ALAT values have previously been reported only in renal failure. METHODS: A retrospective study of clinical chemistry values going back 10 years was conducted in all patients from the outpatient clinic with CD or ulcerative colitis (UC). Exclusion criteria were age >50 years, a daily alcohol consumption, known liver disease or other chronic diseases with a possible effect on liver function (n=42). The remaining patients (n=123) were classified as UC, CD or indeterminate colitis (ID). Eight patients with microscopic colitis (MC) were also included. RESULTS: It was found that 49/50 CD patients had subnormal ALAT on one or several occasions (mean 7 U/L, range 5-9). Only 1/67 patients with UC had subnormal ALAT values. The mean ALAT value in UC was 20 U/L, range 10-40. In IC, 5/6 patients had subnormal ALAT. None of the 8 patients with MC had subnormal ALAT. CONCLUSIONS: The demonstration that subnormal ALAT values are almost entirely seen in CD as compared with UC may have clinical importance and adds to the information on the pathophysiological differences between these two diseases.

[RTH syndrome--resistance to thyroid hormone syndrome]. / RTH-syndromet--resistance to thyroid hormone syndrome.

The RTH syndrome is an instructive example of a receptor resistance syndrome. A typical case history is reported here. The patient had had symptoms for many years and was first diagnosed as having inappropriate secretion of TSH. Pituitary tumour was excluded. The primary symptom was palpitations and the patient was partially thyroidectomized many years ago on suspicion of thyrotoxicosis. She was then given substitutional Eltroxin, but, because of palpitations, the dose was reduced to almost zero, after which the patient contracted symptoms suggesting myxoedema. The thyroid values could not be used for clinical assessment, however the symptoms of myxoedema disappeared when the Eltroxin dose was increased to 75 micrograms/day. When the dose was increased further the heart symptoms became too troublesome. The patient had no signs of underlying heart disease.

[DiGeorge syndrome. An underdiagnosed disease category with different clinical features]. / DiGeorges syndrom--underdiagnostisert sykdomsgruppe med mange fremtredelsesformer.

BACKGROUND: DiGeorge syndrome is estimated to affect one in every 3,000-4,000 live-born individuals. The syndrome is also known as velocardiofacial syndrome (VCFS) and conotruncal anomaly face syndrome (CTFS). The most common clinical features are mental retardation, congenital heart anomalies, primary hypoparathyroidism (with hypocalcaemia), aplasia or hypoplasia of the thymus, and a dysmorphic face. 90% of the affected individuals have a deletion at the long arm of chromosome 22. 80-90% of those deletions are de novo mutations. MATERIAL AND METHODS: This article presents the case of a 32-year-old woman who was diagnosed with DiGeorge syndrome after a grand mal seizure due to hypocalcaemia. The hypocalcaemia was caused by primary hypoparathyroidism. We also give a brief review of the current state of knowledge about DiGeorge syndrome. RESULTS AND INTERPRETATION: DiGeorge syndrome is probably underdiagnosed. A correct and early diagnosis is important in order to prevent medical complications, e.g. hypocalcaemia and hypothyrosis, and to evaluate the patient's overall need of care.

[DiGeorge syndrome. Velocardiofacial syndrome/chromosome 22q11 deletion syndrome]. / DiGeorges syndrom. Velokardiofacialt syndrom/kromosom 22q11-deletionssyndrom.

Patients with a deletion of chromosome band 22q11 are described as having DiGeorges syndrome, velocardiofacial syndrome or chromosome 22q11 deletion syndrome depending on clinical manifestations. The patients have variable severity and combinations of conotruncal heart defects, abnormalities of the ear and palate, facial dysmorphism and mental retardation as well as partial or complete aplasia/hypoplasia of the thymus and endocrine dysfunction, e.g. hypoparathyroidism. The patients may present with impaired immune function, heart failure, hypocalcaemia, facial dysmorphism, impaired hearing and mental retardation. The syndrome, which is a significant cause of heart and craniofacial defects as well as mental retardation, is probably underdiagnosed. In each of the above mentioned phenotypical presentations, chromosome 22q11 deletion syndrome should be considered.

[DiGeorge syndrome diagnosed in a 39-year old woman with chronic hypocalcemia]. / DiGeorges syndrom diagnosticeret hos en 39-årig kvinde med kronisk hypokalcaemi.

A 39 year-old woman was diagnosed with DiGeorge's syndrome based on newly diagnosed hypocalcaemia, appearance and history. The patient had congenital cardiovascular malformations, mild mental retardation and ear malformations, and during infancy and childhood suffered from failure to thrive and frequent infections. In children with conotruncal heart malformation, hypocalcaemia and hypoplasia of the thymus in combination it is estimated that chromosome 22q11 deletion is present in almost 100%. The syndrome is probably underdiagnosed.

[A 7-year experience with goiter surgery in an otorhinolaryngologic department. A retrospective study of the the period 1990-1996]. / Syv års erfaring med strumakirurgi i øre-, naese- og halsregi. En retrospektiv undersøgelse fra 1990 til 1996.

The aim of this study was quality assurance and to analyse the frequency of complications following thyroid surgery. The most dreaded surgical complications are permanent injury to the recurrent laryngeal nerve or persistent hypocalcaemia. Our surgical procedure included the use of the surgical microscope in connection with thyroid grand surgery. Our materiel includes 122 patients who underwent surgery for benign thyroid diseases in our department from 1990-1996. In nearly 50% of all cases a lobectomy was performed, reserving resections and subtotal thyroidectomy to special cases. Resections were primarily done in the beginning of the period. The surgical microscope was used as a standard procedure to identify and expose the recurrent laryngeal nerve and the parathyroid glands. Primary thyroid grand surgery in benign disease resulted in permanent unilateral laryngeal nerve palsy in one case or in 0.83% of the patients. When calculated as nerves at risk, the complication rate was reduced to 0.67%. In benign completion surgery the complication rate was 0%. No patient developed persistent hypocalcaemia.

Thyroid hormone treatment aiming at reduced, but not suppressed, serum thyroid-stimulating hormone levels in nontoxic goitre: effects on bone metabolism amongst premenopausal women.

OBJECTIVES: To study the effects of six months' treatment with either T4 or T3, aiming at reduced but not totally suppressed serum TSH levels, as measured by a third generation TSH assay, on biochemical bone turnover parameters as well as bone mass in patients with nontoxic goitre. DESIGN: Prospective randomized study with a matched control group, not blinded. SETTING: Two University Hospital Clinics in Copenhagen. SUBJECTS AND INTERVENTION: Twenty-four consecutive premenopausal women with moderate sized nontoxic goitre. Fourteen patients randomized to T4 or T3 treatment for six months with monthly titration of the dose, aiming at TSH values between 0.005 and 0.2 mUL(-1). Ten controls. MAIN OUTCOME MEASURES: Serum parathyroid hormone (PTH), serum procollagen I C-terminal propeptide (PICP), serum alkaline phosphatase, serum osteocalcin, u-pyridinoline, u-deoxypyridinoline, u-hydroxyproline. Bone mass (BMD) at the lumbar spine and at both femoral necks. RESULTS: Serum TSH was generally kept within the desired interval. There was no difference in any marker of bone metabolism between the effects of T4 and T3. Consequently, these groups were combined in order to evaluate the effect of thyroid hormones on the bone and mineral metabolism. Thyroid hormone treatment resulted in increased levels of serum ionized calcium (Ca) (P=0.02), serum alkaline phosphatase (P=0.007), serum-PICP (P=0.003), serum osteocalcin (P=0.02) and urinary excretion of deoxypridinoline (P=0.03) compared to untreated controls. Bone mass did not change. CONCLUSION: Six months treatment with either T4 or T3 of premenopausal women with nontoxic goitre, aiming at reduced but not totally suppressed TSH values, resulted in biochemical signs of increased bone turnover, whereas bone mass remained unaltered. No differences were found between the effects of T4 or T3 treatment.

Development of hyperthyroidism in nodular goiter and thyroid malignancies in an area of relatively low iodine intake.

A high incidence of toxic nodular goiter has recently been described in areas of relatively low iodine intake. We studied the development of hyperthyroidism in nodular goiter and thyroid malignancies in an area of relatively low iodine intake (median 87 micrograms/h). The material comprised a total of 557 patients admitted to our department in the period 1978-88. The follow-up material consisted of 214 patients with a median age of 55 yr (19-86). Eighty-eight percent were females. The period of observation was 33 months (1-205). All patients had technetium thyroid scans, serum T3, serum T4, T3 uptake test and serum TSH performed. TRH tests were performed in 58 patients. During the follow-up period 45 initially euthyroid patients became hyperthyroid (18%). The incidence increased with age, and the median age in the group, who developed hyperthyroidism, was 65 yr. An estimated minimal incidence of toxic nodular goiter was 23/100,000/yr. Contrary to previous assumption, hyperthyroidism developed frequently in elderly patients with nodular goiter in a low iodine intake area. Thyroid cancer was found in 13 patients corresponding an estimated incidence of 1.5/100,000/yr. The cancer incidence was very low compared to other nordic countries with high iodine intake. This finding may suggest a possible influence of iodine intake on the incidence of thyroid cancer.

[Calcium blood changes in septic conditions. A review]. / Calciumaendringer i blodet ved septiske tilstande. En oversigt.

Hypocalcemia has been reported in critically ill patients over the last 10-15 years, however, measurements of Ca2+ in blood have not yet became routine in the treatment of severely ill patients. In order to stress the importance of calcium in such patients, a review of calcium changes in septic conditions is presented. In vitro studies show that the intracellular calcium metabolism is disturbed in these patients, and that the changes in extracellular calcium are probably secondary to the intracellular changes. Parathyroid hormone secretion is inappropriate in septic patients. The reason for this is unknown. Administration of calcium parenterally does not seem to affect the prognosis, however calcium seems to be beneficial in patients with hypotension. Since the level of Ca2+ in blood may have prognostic significance in septic patients, measurements of Ca2+ in blood should be used routinely in these patients, in order to point out "risk" patients as early as possible.

Comparative aspects of iodine conservation in mammals.

1. Comparative aspects of iodine conservation in mammals were studied on the basis of published data on kidney and thyroid weights and function. 2. Very small mammals possessed an efficient reabsorption of iodide to compensate for the high glomerular filtration rate (GFR). 3. Humans and mammals of a similar and larger size had "lost" the ability to reabsorb iodide efficiently. 4. Very large mammals are protected against renal loss of iodide due to the relatively low GFR. 5. Thyroid weights in relation to body weight were highest in humans suggesting that humans and other mammals of a similar size are especially susceptible to iodine deficiency.

The basis for common reference intervals for serum potassium.

In order to investigate the relevance of the currently used lower reference limit for S-Potassium in Danish hospital laboratories, analytical bias in the measurement of S-Potassium was compared with the lower reference limit in each of 52 Danish hospital laboratories. The acceptable bias range was estimated according to Gowans et al on the basis of the result of two different reference sample groups. The estimated acceptable 0.95 bias range was 0.24 mmol/L, so the observed bias range of 0.23 mmol/L was within this limit. As all preanalytical errors tend to increase the measured S-Potassium, all acceptable bias should be in the direction of decreasing the measured value. It can be concluded that analytical performance allows for more uniform (even common) reference interval(s) in all Danish and perhaps Nordic hospital laboratories, provided that preanalytical errors can be controlled.

Reference intervals based on hospitalized 'healthy' patients and medical students in relation to analytical bias for serum potassium.

The reliability of reference intervals for measurements of serum (S)-potassium in Danish hospital laboratories was investigated (i) by estimation of reference interval based on two different, healthy subpopulations and (ii) by comparison of reference intervals for S-potassium with analytical bias in each of 52 Danish laboratories. (i) The reference values from 227 hospitalized 'healthy' patients were obtained during the period 1979 to 1987 from the first-drawn serum specimen from the hospitalized patients, who were later discharged from the hospital without a diagnosis. The estimated 0.95 reference interval was 3.34 to 4.52 mmol l-1. The other reference sample group consisted of 314 medical students from whom blood was collected in the period from 1983 to 1987. Here the estimated reference interval was from 3.44 to 4.53 mmol l-1. The concentration values from both reference sample groups were corrected for analytical bias (+0.05 mmol l-1). (ii) The 52 Danish laboratories revealed a considerable variability in reference intervals which, regarding the lower reference limit, ranged from 3.2 to 3.7 mmol l-1 in strong contrast to the analytical bias (ranging from -0.08 to +0.15 mmol l-1) in 50 laboratories (two outliers). There was no relationship between lower reference limit and analytical bias in the individual laboratories. It is concluded that analytical performance allows for more uniform (even common) reference intervals throughout the Danish and perhaps Nordic hospital laboratories.

Ionized calcium in blood: studies on patients with pulmonary disease.

A new automatic ionized calcium analyser ICA 2 (Radiometer, Copenhagen, Denmark) was used for studies of ionized calcium (cCa2+) in the arterial blood of patients with a compensated respiratory acidosis due to chronic lung disease. The data for 16 patients showed an unexpectedly high level of variation in cCa2+ (range, 1.01-1.25 mmol l-1) despite the fact that there was only a small degree of variability in pH (range, 7.38-7.51). cCa2+ was not correlated with pH as has been observed in acute respiratory disturbances. A highly significant negative correlation was found between cCa2+ and base excess (BE) (r = -0.81, P less than 0.0001), and between cCa2+ and carbon dioxide tension (PCO2) (r = 0.71, P less than 0.002). These correlations differed from those reported previously in acute respiratory disturbances. CCa2+ showed a significant positive correlation with oxygen tension (PO2) (r = 0.71, P less than 0.002). It is concluded that cCa2+ in arterial blood from patients with chronic lung disease is correlated with acid-base and gas quantities in an entirely different manner to that observed in acute acid-base disturbances in normal adults.

Diabetic ketoacidosis in Denmark: epidemiology, incidence rates, precipitating factors and mortality rates.

The epidemiology of uncontrolled diabetes mellitus was studied in an 11.2% sample of the Danish population (574,696 inhabitants) during a 24-month period. Some 175 admissions in ketoacidosis (heavy ketonuria and plasma bicarbonate below 21 mmol/l) were recorded. Based on prevalence rates from a socio-economically and ethnically comparable Danish county, the annual incidence rate was calculated to be 0.045 per diabetic. The incidence rate of moderate and severe episodes (bicarbonate less than 16 mmol/l) was 0.032 and of severe episodes only (bicarbonate less than 10 mmol/l) 0.017 per diabetic. The major risk group was female teenagers. The total annual frequency of recurrence was 8.7%: 48% of the male episodes were ketoacidosis (DKA) associated with onset of diabetes, against 30% of the female episodes (P = 0.02). All Danish diabetics were at the time of the survey (1978-79) treated with conventional insulin treatment. Annual incidence rate in these established diabetics was 0.028, i.e. three to five times less than reported during treatment with continuous subcutaneous insulin infusion. Mortality of DKA was low, 3.4%, and dependent upon age and precipitating factor but not upon the degree of acidosis. The overall annual mortality rate was 1.5 per 100 diabetics.

[The effect of beta blockers combined with thiazides on serum electrolytes]. / Virkningen af beta-blokkere kombineret med tiazider på serumelektrolytter.

The case reports of a total of 9,670 patients admitted to a medical department were reviewed manually. From this material, all patients receiving treatment with beta-blockers alone, bendroflumethiazide alone or combinations of these were selected. In addition, a control group was selected. The patients should have received treatment for at least seven days and they should not be "ill". Patients receiving treatment with beta-blockers had higher S-K+ (4.2 mmol/l) and lower standard bicarbonate levels (23 mmol/l) than matched controls. Patients receiving treatment with bendroflumethiazide had low S-K+ (3.6 mmol/l) and high standard bicarbonate (26 mmol/l). Patients receiving treatment with both bendroflumethiazide and beta-blocker had low S-K+ (3.4 mmol/l) and the same standard bicarbonate as patients who received bendroflumethiazide alone. A more limited group chosen according to stricter criteria confirmed the above mentioned results. The investigation demonstrated that treatment with both beta-blocker and bendroflumethiazide caused deterioration of the hypokalaemia induced by bendroflumethiazide despite the higher S-K+ during beta-blockade. This may be due to renal excretion of potassium during beta-blockade.

Renal iodide clearance in rabbits.

The purpose of the study was to compare indirect clearance methods based on plasma values and external detection of activity using small skin attached radioactivity detectors with a direct clearance method based on constant infusion and urine collection. The experiments were performed in anesthetized rabbits. The plasma iodide concentration was increased 100 times to prevent thyroid organification of radioactive iodide. [131I]iodide was infused at a constant rate and [125I]iodide was administered iv as a bolus for indirect clearance determination. The ratio between plasma values and external values 125I-activity was constant in all experiments from 15 min after administration of [125I]iodide and throughout the experiment. The results of 7 experiments in 3 rabbits showed a highly significant correlation (r = 0.98) between direct and indirect values within the range of direct clearance values obtained (0.002-0.6 ml.min-1.kg-1. The direct and indirect clearances were measured simultaneously during a 2-h period of steady state. The 95% confidence interval of the mean ratio between direct and indirect clearances was +/- 20% for plasma activity and +/- 26% for externally measured activity. It is concluded that both methods of indirect clearance determination can be applied to rabbits to estimate absolute values of the renal iodide clearance.

Serum calcium and parathyroid function linked to control of respiration.

It is suggested that the plasma concentration of ionized calcium in a complex way is connected to control or respiration in mammals. The level of ionized calcium in plasma is suggested to correlate with the arterial carbon dioxide tension as well as with the arterial oxygen tension. The primary function of the parathyroid glands, which are absent in fish, but develop in land vertebrates, is suggested to be control of plasma calcium and pH in respiratory alkalosis due to hyperventilation.