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Objectives: To investigate the significance of ACE gene insertion/deletion (I/D) polymorphism in the frequency of autoimmune manifestations in sarcoidosis., Design: In patients with sarcoidosis the ACE gene I/D polymorphism was detected with PCR on genomic DNA. The patients with sarcoidosis were divided according to the presence (n = 30) or absence (n = 32) of autoimmune manifestations. The former group was subdivided into thyroid autoimmunity (n = 10), gluten immune reactivity (n = 10) and gastric autoimmunity (n = 17)., Settings: The patients were recruited at the Department of Pulmonary Medicine, and the study was conducted at the Department of Endocrinology, University of Lund, Malmö University Hospital, Malmö, Sweden., Subjects: Sixty-two patients with documented sarcoidosis (30 females, 32 males, median age/range at diagnosis of sarcoidosis 31.5/19-75 years, median age/range at study 47.5/22-81 years) were examined. A total of 107 healthy unrelated subjects without sarcoidosis (60 females, 47 males, median age/range at study 58/40-82 years) served as controls., Results: S-ACE values were significantly increased in patients compared to controls (P = 0.00001). The same was true in the subgroup of sarcoidosis patients with associated autoimmunity compared with those with isolated sarcoidosis (P = 0.0328). A significant association was seen between ACE gene polymorphism (II, ID, DD genotypes) and S-ACE levels in both patients and controls according to the order II < ID < DD. The observed genotype frequency distributions in the different study groups agreed the Hardy-Weinberg equilibrium without significant differences between the patients and the controls. Within the group with autoimmune manifestations the DD genotype was significantly over-represented in X-ray stage III compared to the other X-ray stages (P = 0.0181) and a significant increase in the DD genotype in X-ray stage III (P = 0.035) in the group with autoimmune manifestations compared to isolated sarcoidosis was detected., Conclusion: We confirmed that the S-ACE levels corresponded to the order II < ID < DD in patients with sarcoidosis as well as in healthy controls. S-ACE levels were significantly higher in sarcoidosis patients with autoimmune manifestations. The frequency of the DD genotype was significantly increased in patients with autoimmune manifestations and major granuloma mass (X-ray stage III). The ACE D allele in its homozygous form may confer susceptibility for autoimmune manifestations in sarcoidosis, possibly via the high levels of S-ACE it encodes.

Objectives: To study whether there is an increased fracture incidence following thyrotoxicosis., Design: A case-control study., Setting: Malmö University Hospital, Malmö, Sweden., Subjects: All patients (n = 333) from the population of Malmö who were treated for thyrotoxicosis for the first time during the 5-year period 1970-74. A total of 618 controls were selected from the local municipality registry in Malmö. For each case the aim was to randomly select two age- and gender-specific controls, alive in 1993 and born the same year and month as the case., Main Outcome Measures: Fracture incidence, Results: Comparing survivors, there were no differences in the percentage of individuals with fractures (all, fragility, non-fragility) between the patients and the controls. Comparing all individuals and including all fractures, the percentage of individuals with fractures in the entire female patient group (24.6%) was lower (P < 0.05) than in female controls (33.1%). There was a similar but non-significant pattern between male patients and controls. The mean number of all fractures was lower in male patients than in controls (P < 0.05), but no significant difference was noted between female patients and controls. For fragility fractures, there were no significant differences in the percentage of individuals with fractures or in the mean number of fractures between female or male patients and controls., Conclusion: In conclusion we found no increased incidence of fragility fractures in patients with previous thyrotoxicosis as compared with controls. Our results do not support the suggestion that screening for osteoporosis should be performed in patients with previous thyrotoxicosis.

Objectives: The aim of the present study was to explore the frequency of clinical and serological manifestations of gastrointestinal immune reactivity in a large group of Swedish patients with sarcoidosis., Design: In patients with documented sarcoidosis, the presence of pernicious anaemia and coeliac disease was examined. Antibodies to H+/K+ ATPase, gliadin (AGA-IgA/IgG) and endomysium (IgA-EMA) were analysed. In H+/K+ ATPase antibody-positive patients, serum gastrin levels were measured and, when elevated, gastrointestinal biopsy was offered (biopsy performed in 6/9 patients): biopsy was also offered to those with positive EMA or AGA of either class (biopsy performed in 8/12 patients). Subjects from national and local studies were used as controls., Setting: The patients were recruited at the Department of Pulmonary Medicine, and the study was conducted at the Department of Endocrinology, University of Lund, Malmö University Hospital, Malmö, Sweden., Subjects: Of all patients (n = 89) with documented sarcoidosis attending the Department of Pulmonary Medicine between January 1980 and December 1991, 78 [34 females and 44 males; median age at the time of the study, 48 (range 22-81) years; median observation time since the diagnosis of sarcoidosis, 120 (range 1-468) months] were examined., Results: Twenty-nine patients (37.2%) had signs of gastrointestinal immune reactivity. H+/K+ ATPase antibodies were detected in 19 patients (24.4 vs. 4% in controls, P = 0.00015). Serum gastrin levels (median 45, range 22-720 pmol L(-1)) in those patients correlated with antibody titre (r2 = 0.882). Gliadin antibodies were detected in 12 patients (15.4 vs. 8.1% in controls, P = 0.042), of whom 11 (14.1 vs. 4.5% in controls, P = 0.00114) had AGA-IgA alone. One patient had pernicious anaemia and another coeliac disease (EMA-positive)., Conclusion: We have demonstrated a high frequency of gastric autoimmunity and gluten-associated immune reactivity in patients with sarcoidosis, occurring in almost 40% of the cases, the former being the most frequent gastrointestinal immune manifestation. Despite a high frequency of humoral autoimmunity, the frequencies of clinical disease, pernicious anaemia and coeliac disease were not increased as compared with the control population.

Objective and Design: To compare the total and age-specific incidence of thyrotoxicosis, as well as the incidence of the individual types of thyrotoxicosis [i.e. thyrotoxicosis of Graves' type (GD), toxic nodular goitre (TNG) and solitary toxic adenoma (STA)] in Malmö during the years 1988-1990 to those of a previous study in 1970-1974., Setting: The town of Malmö in southern Sweden., Subjects: All patients from the Malmö population treated for thyrotoxicosis (GD, TNG and STA) for the first time during the 3-year period 1988-1990 were included., Results: Overall, 299 (263 females and 36 males) new cases of thyrotoxicosis were diagnosed in 1988-1990, corresponding to a mean annual incidence of thyrotoxicosis of 43.0 per 100,000 inhabitants. The incidence of GD was 22.3, of TNG 16.0 and of STA 4.8 per 100,000 per year. Comparing age- and sex-standardized incidences to the results in 1970-1974, there was a significant increase (P < 0.001) in the mean annual incidence of thyrotoxicosis in the total material as well as in TNG. In addition, there was an increase in GD in females younger than 50 years (P < 0.01), whereas in TNG/STA, an increase was seen in females of 50 years or older (P < 0.001). The incidence figures in males were not significantly changed. There was a higher proportion of smokers in females with GD compared to females with TNG (P < 0.001) and STA (P < 0.05)., Conclusions: The total incidence of thyrotoxicosis, as well as the incidence of GD in females younger than 50 years and the incidence of TNG/STA in females of 50 years or older, has increased in Malmö during the period from 1970 to 1990. The increase was probably caused by several factors such as more sensitive diagnostic tools and GD changes in smoking habits, but additional unknown factors might also be of importance.

Objectives: To study the frequency of islet cell (ICA) and glutamic acid decarboxylase (GAD-Ab) antibodies in patients with hyperthyroidism of different types at diagnosis before treatment and in the euthyroid state following treatment., Setting: Department of Endocrinology, Malmö University Hospital, Malmö, Sweden., Subjects and Design: Blood samples were collected at diagnosis from 129 hyperthyroid patients, and about 6 months later, from 78 of the patients (euthyroid state). Ninety-two patients had Graves' disease (69 females and 23 males, median age 49 years, range 17-85 years), and 37 patients had toxic nodular goitre/solitary toxic adenoma (34 females and three males, median age 69 years, range 24-86 years)., Interventions: Most patients were treated by radioactive iodine following the first blood sample., Main Outcome Measures: ICA and GAD-Ab in serum., Results: At diagnosis of Graves' disease, ICA were detected in two out of 92 (2.2%) patients, two out of 85 (2.4%) without diabetes mellitus and in the euthyroid state in one patient. None of the patients with toxic nodular goitre/solitary toxic adenoma had detectable ICA. At diagnosis of Graves' disease, GAD65-Ab as well as GAD67-Ab were detected in 11 out of 85 (13%) patients without diabetes. As many as six out of 11 GAD67-Ab-positive patients were GAD65-Ab negative. In the euthyroid state, GAD65-Ab were found in six out of 51 (12%) and GAD67-Ab in eight out of 51 (16%) of the non-diabetic Graves' disease patients. The frequencies of GAD65-Ab and GAD67-Ab in toxic nodular goitre/solitary toxic adenoma, diabetes excluded, were 3 and 0%, respectively, in the hyperthyroid state., Conclusion: The frequency of ICA in patients with hyperthyroidism is not increased as compared to the background population. GAD-Ab seems to be associated with Graves' disease and not with hyperthyroidism. The presence of GAD67-Ab in GAD65-Ab negative sera from patients with Graves' disease indicates autoreactivity against a specific GAD67 epitope.

Objectives: To study whether an association between polyglandular autoimmune (PGA) syndrome type III [including autoimmune thyroid disease (ATD) and insulin-dependent diabetes mellitus (IDDM)], coeliac disease and sarcoidosis, exists., Design: In patients with documented sarcoidosis, the presence of the disease constellation of ATD, IDDM and coeliac disease was examined., Setting: The patients were recruited at the Department of Pulmonary Medicine, and the study was conducted at the Department of Endocrinology, Lund University Clinics, General Hospital, Malmö, Sweden., Subjects: Of all patients (n = 89) with documented sarcoidosis attending the Department of Pulmonary Medicine between January 1980 and December 1991, 78 patients (44 males, 34 females: median age at the time of the study 48 years, range 22-81 years: median observation time since the diagnosis of sarcoidosis 120 months, range 1-468 months) were examined in the present study., Results: Amongst the 78 patients with documented sarcoidosis, one female patient was found with PGA syndrome type III, coeliac disease and sarcoidosis., Conclusions: This present patient further indicates the existence of an association between polyglandular autoimmune (PGA) syndrome type III, coeliac disease and sarcoidosis. To determine whether this disease constellation might constitute a new syndrome, further studies on larger groups of patients with sarcoidosis are demanded.

Cardiac pheochromocytoma is a rare tumour and may be difficult to localize. We present a 32-year-old male with a cardiac pheochromocytoma that was successfully resected. An initial unenhanced CT did not reveal the tumour. MIBG-scintigraphy indicated the location, but to get full information, a dynamic contrast-enhanced CT of the chest during adequate alpha and beta blockade was essential. ECG-gated MRI gave further information about the anatomical details.

The incidence of recurrence and of hypothyroidism was determined in all new patients treated for thyrotoxicosis during the period 1970-1974 in an unselected, well-defined urban population. A total of 309 patients were followed up for a median time period of 108 (1-192) months. There was a cumulative incidence of 51% recurrence in patients who were treated with antithyroid drugs for Graves' thyrotoxicosis, whereas after surgery or radioiodine treatment there were few recurrences, but 32% and 78% cumulative incidences of hypothyroidism. There were no recurrences after surgery or radioiodine treatment in patients with toxic multinodular goitre or solitary toxic adenoma, but 29% and 40% cumulative incidences of hypothyroidism following radioiodine treatment. Late hypothyroidism occurred after surgery for Graves' thyrotoxicosis, and in all groups treated with radioiodine. Thus it is advisable that all patients with Graves' thyrotoxicosis, regardless of treatment, and all patients with toxic multinodular goitre or solitary toxic adenoma treated with radioiodine, should be followed up for many years, and probably for life.

During a 5-year period, 333 new cases of thyrotoxicosis were diagnosed in a well-defined urban population of 258,000 inhabitants in southern Sweden without a history of endemic goitre. This corresponds to a mean annual incidence of thyrotoxicosis of 25.8/100,000. The incidence of Graves' disease was 17.7, the incidence of toxic nodular goitre was 5.4 and that of solitary toxic adenoma was 2.7/100,000/year. The peak age-specific incidence of Graves' disease was 32.6/100,000/year (age group 60-69 years), and that of toxic nodular goitre and solitary toxic adenoma was 31.5/100,000/year (age group over 80 years).