[Photodynamic diagnostics of bladder carcinoma]. / Photodynamische Diagnostik des Harnblasenkarzinoms.

The question whether conventional cystoscopy should always be performed together with fluorescent diagnostic procedures remains to be answered. The current article presents the current literature dealing with this topic. Particularly for relevant carcinoma in situ lesions of the bladder there is no obvious advantage for photodynamic diagnostics compared to conventional cystoscopy with consistent use of urine cytology.

Influence of coronary artery bypass surgery on thyroid hormone parameters.

UNLABELLED: The postoperative period after cardiac surgery with cardiopulmonary bypass (CPB) is associated with a low T3 syndrome, i.e. low T3 and fT3 concentrations in the presence of normal T4 and TSH concentrations. So far, results from studies evaluating thyroid function during and after CPB are rather conflicting. We therefore evaluated prospectively thyroid function in 28 patients before, during and up to 3 days after coronary artery bypass surgery. We could demonstrate the most significant changes in thyroid hormone concentrations on day 1 after CPB (low T3 and fT3 concentrations, elevated rT3 concentrations in the presence of a significant fall of TSH). T3 fell from 1.93 to 0.6 nmol/1 and fT3 from 5.5 to 1.42 pmol/1. Those patients with low cardiac output syndrome after surgery had significantly lower T3 concentrations than patients without this complication. Moreover, those patients, who already had significant lower T3 values prior to CPB, also demonstrated low T3 concentrations on day 1 after CPB. Cortisol usually has a suppressive effect on TSH secretion. However, the effect of cortisol on TSH in patients undergoing CPB seems to be not that important: those patients with high endogenous cortisol concentrations on day 1 after CPB had similar TSH values to those patients with only slightly elevated cortisol concentrations. Also, the application of high doses of catecholamines seems to have only minor effects on TSH secretion, because those patients requiring high doses of dopamine over a prolonged time period had essentially the same TSH values after CPB. Patients who had been exposed preoperatively to high doses of iodine did not demonstrate significantly different thyroid hormone concentrations. IN CONCLUSION: We could demonstrate that CPB induces a low T3 syndrome up to 3 days after surgery. Those patients with low T3 concentrations prior to surgery demonstrate postoperatively a more severe degree of nonthyroidal illness (NTI). Catecholamines and cortisol seem to have only minor effects on the TSH secretion after CPB. The influence of a previous iodine contamination is negligible.

Association of primary hyperparathyroidism and non-medullary thyroid cancer.

OBJECTIVE: To assess the prevalence of differentiated thyroid cancer among patients with primary hyperparathyroidism (pHPT) and to describe our experience in its treatment. DESIGN: Retrospective study. SETTING: Teaching hospital, Germany. SUBJECTS: 322 patients who were operated on for pHPT from 1979-1993 and a control group of 840 patients operated on for nodular goitre during the same time period. INTERVENTIONS: All patients with non-occult cancer were treated by complete thyroidectomy and adjuvant radioiodine. MAIN OUTCOME MEASURES: Prevalence of differentiated thyroid cancer, morbidity and mortality. RESULTS: No patient died. 120 of the 322 patients had simultaneous thyroid resection for either nodular goitre of solitary adenoma; 9 patients had differentiated thyroid cancer (3% of the whole group, or 8% of the group that had thyroid resections). The prevalence among the control group during the same time period war 4%, which is not significantly different. There were 4 occult papillary cancers, 3 papillary stage T2N0 tumours, 1 T2N1 tumour, and 1 follicular tumour. Among the 9 patients with cancer 1 developed transient and 1 permanent paralysis of the laryngeal nerve. Among the 120 patients who had thyroid resections, 45 (38%) developed transient hypocalcaemia and of the 202 operated on for pHPT alone the corresponding figure was 63 (31%). There were 2 postoperative haemorrhages, and 3 wound infections. All patients were alive and free of disease after a mean follow up of 62 months. CONCLUSION: Though the morbidity of combined thyroid and parathyroid surgery is slightly higher than after operations for pHPT alone we recommend that the indications should not be too rigid because of the benefit that can accrue to patients from the diagnosis of an asymptomatic malignant tumour.

Non-invasive measurement of thyroidal iodine content (TIC) by X-ray fluorescence analysis (XFA).

The determination of thyroidal iodine content by X-ray fluorescence analysis is based on the phenomenon that the gamma radiation of Americium-241 excites stable iodine atoms to emit a characteristic fluorescence radiation which is proportional to the amount of iodine present in the gland. To study this, a stationary system has been developed which consists of a 11.1 GBq Am-241 source and a high-purity Germanium detector with spectrum analysator. Lower limit of detectability of this system corresponds to 0.013 mg per ml of thyroid volume measured sonographically; in-vivo precision given as coefficient of variation of duplicate measurements amounts to 12%. The thyroid is exposed with a radiation dose of 60 microSvs per measurement (approximately 5 % of a Tc-99m scan). Studies carried out in 149 volunteers and 173 patients showed a mean iodine concentration of 0.325 +/- 0.134 mg/ml in healthy persons; decreased iodine concentrations were found in euthyroid goitre patients and hyperthyroid patients with focal functional autonomy or Graves' disease. Iodine concentrations correlated negatively with age and goitre volume. The method is well suited for individual follow-up studies exploring different treatment modalities because of its sensitivity, high reproducibility and low radiation exposure.

Hip fractures and the thyroid: a case-control study.

OBJECTIVE: To investigate the prevalence of thyroid illness - especially hyperthyroidism - and exposure to thyroid hormones in patients with hip fracture. DESIGN: A case-control study. SETTING: Two surgical/orthopaedic hospital units and 22 facilities for the aged in a moderately iodine-deficient region of Germany. SUBJECTS: A total of 116 postmenopausal females with hip fracture and 402 postmenopausal female controls. MAIN OUTCOME MEASURES: Hip fracture; thyroid disease confirmed by measurement of serum thyrotropin, total and free thyroxine and triiodothyronine; history of thyroid disease and thyroid medication obtained by a questionnaire. RESULTS: Of the hip fracture patients 4.3% had overt untreated hyperthyroidism, and 6.9% gave a history of past hyperthyroidism (total, 11.2%). The corresponding figures for the controls were 2.0 and 2.7%, respectively (total, 4.7%). 7.8% of the cases had been exposed to levo-thyroxine for 3-29 years, compared to 11.2% of the controls. The odds ratio for hyperthyroidism (present and past) was 2.5 (1.2-5.3, 95% confidence interval), and the odds ratio for levo-thyroxine exposure was 0.67 (0.32-1.41) in the hip fracture patients. CONCLUSIONS: Hyperthyroidism is found 2.5-fold more often in hip fracture patients than in controls. Hence, hyperthyroidism appears to be a significant risk factor for hip fracture and should be investigated by clinical and, when necessary, laboratory means in hip fracture patients. In contrast, no increased risk for hip fracture could be detected after exposure to levothyroxine.

[Simultaneous interventions of the thyroid gland in primary hyperparathyroidism (pHPT)]. / Simultaneingriffe an der Schilddrüse bei primärem Hyperparathyreoidismus (pHPT).

Among 334 neck explorations for primary hyperparathyroidism (pHPT) between 1979 and 1993 120 (33.9%) thyroid operations were performed simultaneously. Histologic examination revealed 40 thyroid adenomas, 43 nodular goiters, 8 thyroiditis and 9 differentiated carcinomas. In 20 cases the indication was doubtful retrospectively, as evaluated by postoperative histology. Of the 9 carcinomas there were 4 small papillary, 3 papillary pT2 No Mo and 2 follicular pT2 No Mo. Perioperative morbidity of the simultaneous operations was not significantly increased compared to the parathyroid exploration alone. We conclude, that pre- and intraoperative thyroid examination should be performed in pHPT and decision for a simultaneous operation should be made generously.

Effectiveness of prophylactic therapy on goiter recurrence in an area with low iodine intake--a sonographic follow-up study.

There is no agreement as to whether or not drug treatment after surgery for nodular goiter is effective in preventing recurrence of goiter. Data about recurrences in areas of marginally low iodine intake (like Germany) vary widely. Therefore, we performed a retrospective study in 104 patients who had been treated surgically because of benign uninodular or multinodular goiter. The mean follow-up period was 6.4 years (minimal 1 year) with at least three examinations. Thyroid ultrasound with volumetric analysis was recorded in each patient. Thirty-two patients did not receive any prophylaxis, 50 patients were treated with L-thyroxine, 17 patients with a combination of L-thyroxine and iodine and 5 patients with iodine alone. Recurrence of goiter was documented in 28.0% of the untreated patients and in 8.9% of the patients on prophylaxis (P < 0.05). The mean increase of thyroid volume was 7.3 ml versus 3.1 ml in patients without versus with prophylactic drug treatment (not significant). No significant correlation was found between the increase of thyroid volume and age of the patients, follow-up time, or initial thyroid volume, respectively. These data clearly demonstrate the effectiveness of prophylactic drug therapy to prevent recurrence of goiter after thyroid surgery in an iodine-deficient area.

Successful treatment of meningoencephalitis caused by Mycobacterium avium intracellulare in AIDS.

A wide variety of pathologies afflicting the CNS is see in patients infected with the human immunodeficiency virus. We report the case of relapsing meningoencephalitis caused by Mycobacterium avium intracellulare (MAI) in a homosexual male with the acquired immunodeficiency syndrome in whom repeated use of polymerase chain reaction was required to detect MAI-specific DNA in the cerebrospinal fluid. Successful responses to early empirical antibiotic combination treatment, including the drugs clarithromycin and rifabutin, were demonstrated by clinical, EEG, and CSF improvement during an 8-month period. To our knowledge, this study presents the first known patient with the acquired immunodeficiency syndrome effectively treated for MAI meningoencephalitis and suggests that modern antimycobacterial combination therapy may improve the poor prognosis of CNS infections with nontuberculous mycobacteria.

Antithyroid drug-induced agranulocytosis: clinical experience with ten patients treated at one institution and review of the literature.

The frequency, predisposing factors and course of agranulocytosis (granulocytes < 250/microliter) secondary to antithyroid drugs were studied in a cohort of 1256 continuously treated outpatients with hyperthyroidism during the 15 year period from 1973 to 1987. Two cases of agranulocytosis were detected; the frequency was 0.18% (95%-confidence intervals, 0.0-0.44%). This prevalence appears to be lower than reported in previous studies (up to 1.8%). For other adverse drug reactions, there was a clear-cut relationship to initial thionamide dose and to the body mass index; most reactions occurred during the first weeks of treatment. In addition, eight patients referred for thionamide drug- induced agranulocytosis were studied, and the following results obtained: Methimazole dose in patients with agranulocytosis was almost twice as in other patients (63.3 +/- 19.7 vs 34.3 +/- 29.7 mg daily) suggesting that this complication was related to dose. The interval between start of antithyroid drug treatment and first symptoms of agranulocytosis was 33 days (median; range, 23-55 days); hence, prolonged treatment beyond this period would appear relatively safe. Withdrawal of the causative agent and treatment of infection led to recovery of leukocyte counts within 15 days (median; range, 5-31 days). Two fatal outcomes were seen in referred patients. In one severely hyperthyroid patient with methimazole-induced agranulocytosis, recombinant human granulocyte/macrophage colony stimulating factor induced clinical and hematologic recovery within a few days of administration. In conclusion, agranulocytosis is the most severe side effect of antithyroid drugs. According to our results and a literature review, it occurs almost exclusively during the first ten weeks of treatment and is probably related to the drug dose.(ABSTRACT TRUNCATED AT 250 WORDS)

The long-acting somatostatin analogue octreotide alleviates symptoms by reducing posttranslational conversion of prepro-glucagon to glucagon in a patient with malignant glucagonoma, but does not prevent tumor growth.

A 52-year-old female with metastatic glucagonoma secreting glucagon and chromogranin A was treated with the somatostatin analogue octreotide for 2 years without any additional tumor-reducing interventions. Before therapy plasma glucagon was above 8 micrograms/l (normal < 0.2) and within 2 days 3 x 200 micrograms octreotide daily suppressed plasma glucagon to 2.2-2.5 micrograms/l. Concomitantly, chromogranin A dropped from 0.85 mg/l (normal < 0.1) to 0.2. After 3 weeks the preexisting disabling necrolytic migratory erythema had vanished completely, and weight loss was temporarily stopped. During therapy chromogranin A and plasma glucagon rose, exceeding pretreatment levels after 3 and 14 months, respectively. After 1 year the erythema recurred, responding only transiently to increasing doses of octreotide. The patient died after 2 years of therapy of tumor cachexy despite very high doses of octreotide (4 x 600 micrograms/day). Throughout treatment octreotide did not prevent tumor growth, as demonstrated by computed tomography and sonography. Determination of immunoreactive glucagon before and during octreotide therapy in fractions of plasma samples subjected to gel chromatography revealed a reduction in the ratio of glucagon to preproglucagon from 1.83 (before) to 0.56 (during therapy), indicating inhibition of posttranslational processing of preoproglucagon by octreotide, thereby reducing circulating bioactive glucagon. In summary, octreotide induced a remission of clinical symptoms by inhibiting posttranslational conversion of preproglucagon to glucagon but did not prevent tumor growth. Therefore, octreotide is a valuable therapy for rapid relief of clinical symptoms, thereby improving the possibilities for other tumor-reducing therapies.

[Questions and answers on the epidemiology and etiology of goiter]. / Fragen und Antworten zur Epidemiologie und Atiologie der Struma.

Goitre defines any enlargement of the thyroid independent of its cause. Worldwide iodine deficiency is the single most common cause of a goitre. However, before iodine deficiency is established, other thyroid diseases need to be ruled out. Very rarely increased production of TSH (secondary hyperthyroidism) or of hormones with TSH activity (e.g. hCG producing tumours), inborn errors of iodine metabolism, and defects of the thyroid hormone receptor (thyroid hormone resistance) are the cause of a goitre. Furthermore, malignancy of the thyroid and autoimmune disease (e.g. Grave's disease) may lead to a thyroid enlargement. Still, worldwide more than 90% of the 200 million patients with goitre suffer from iodine deficiency. In Germany, as in only few other European countries which lack any nation-wide prophylactic iodine supplementation, goitre is endemic with a prevalence of about 25%. The classical concept on the mechanism of iodine deficiency induced goitre is based on decreased thyroid hormone synthesis in the presence of iodine depletion, which leads to increased production of TSH, stimulating thyroidal growth. Recent in vitro findings using thyroid cell cultures expand this concept by demonstrating that TSH regulates the differentiation and function of thyroid cells and may induce hyperplasia, but not cell proliferation. In contrast to TSH, the locally produced growth factors IGF I (insulin-like growth factor I) and EGF (epidermal growth factor) stimulate thyroid cell proliferation. Intrathyroidal iodine antagonises the effects of IGF I and EGF and simultaneously stimulates transforming growth factor beta (TGF-beta), which inhibits thyroid cell proliferation. Thus, intrathyroidal iodine appears to regulate thyroidal growth by controlling proliferation stimulating (IGF I, EGF) and proliferation inhibiting (TGF-beta) growth factors. Though these new insights fill several gaps of the classical concept on the pathogenesis of endemic goitre, open questions remain.

[Management of the cold thyroid nodule and thyroid malignancy]. / Management des kalten Knotens und des Schilddrüsenmalignoms.

The evaluation and management especially of cold thyroid nodules remains an area of controversy. The past decade has witnessed two important advances. The increased availability of fine-needle aspiration of thyroid nodules has altered the clinician's approach to this disease, and provides for the single most precise method for selecting appropriate patients for surgery. The introduction of high-resolution thyroid ultrasonography provides for anatomic definition that is clearly superior to thyroid scintigraphy. However, radionuclide imaging remains critical for determining the functional status of abnormal thyroid tissue. This review attempts to provide a practical approach to the evaluation and management of the thyroid nodule. Only rare data exists concerning the therapeutic approach of cold thyroid nodules and non-toxic nodular goitre. There seems to be a size-reducing effect by thyroxin-treatment, but no data are reported from iodine deficient areas. Concerning the treatment of differentiated thyroid carcinoma total thyroidectomy combined with eradication of remaining thyroid tissue with iodine 131 is usually preferred. In case of smaller or occult carcinoma various modes of uni- or bilateral subtotal resection are used. Chemotherapy is of little use in treating differentiated thyroid carcinoma and remains as a last possibility if usual approaches are no longer effective. To control local-invasive growth of anaplastic thyroid carcinoma combined treatment with mitoxantrone and hyperfractionated irradiation seems to be a successful approach.

Glucocorticoid-induced osteoporosis: pathogenesis, prevention and treatment, with special regard to the rheumatic diseases.

OBJECTIVES: To review factors associated with development of osteoporosis in patients with rheumatic diseases, as well as the preventive and therapeutic measures. DESIGN: A MEDLINE literature search. RESULTS: 1 Pathogenesis. Rheumatoid arthritis in itself causes reduction of bone mass; this process can be aggravated by glucocorticoid treatment. With glucocorticoid treatment, bone mineral density decrease is most pronounced during the first months of treatment. There is no agreement on the effects of daily dose, cumulative dose, and duration of glucocorticoid treatment on the rate of bone loss. However, with treatment by low doses (< 10 mg of prednisone equivalent per day), bone loss appears to be minimal or even undetectable compared to controls. Alternate day treatment, or treatment with steroid 'pulses' have not been shown to protect from bone loss. 2 Prevention and treatment. Prophylactic and therapeutic measures for glucocorticoid-induced osteoporosis include calcium supplementation, vitamin D in physiological doses and oestrogen in perimenopausal female patients. Efficacy has not always been shown in this particular indication but is extrapolated from other forms of osteoporosis. Limited data exist on treatment with anabolic steroids, calcitonin (with an additional analgesic effect) and biphosphonates and reduction of fracture rates has not yet been investigated. At present, there is insufficient evidence to show that altered steroid molecules can dissociate adverse effects on bone from clinically desirable effects. CONCLUSION: In view of the paucity of study data, prophylaxis and therapy of glucocorticoid-induced osteoporosis should receive more attention in future clinical studies.

Tissue- and subunit-specific regulation of G-protein expression by hypo- and hyperthyroidism.

Thyroid hormone status has profound effects on signal transduction in various tissues throughout the body. Therefore, we quantified the signal transducing G-proteins in the rat heart, cerebral cortex, vas deferens and liver by immunoblotting and pertussis toxin labeling in response to chemically induced hypothyroidism (treatment with propylthiouracil) and hyperthyroidism (treatment with triiodothyronine). Levels of the pertussis toxin (PTX) substrates Gi alpha and Go alpha in the heart and vas deferens were inversely correlated with thyroid hormone levels, i.e. Gi alpha and Go alpha were decreased or unchanged in hyperthyroid rats and increased in hypothyroid rats compared to control animals. The cerebral cortex and liver expression of PTX substrates Gi alpha and Go alpha was not affected by changes in thyroid hormone. Regulation of Gs alpha protein was more complex in that Gs alpha was unaffected in the other tissues tested. Expression of G-protein beta-subunits was not affected by thyroid status in the heart, liver, or cerebral cortex. Our results suggest that tissue- and G-protein-specific factors are involved in the regulation of G-protein subunits by thyroid hormone. Moreover, cardiac expression of Gs alpha is upregulated by increases or decreases in the normal level of thyroid hormone.

Long-term follow-up in patients with autonomous thyroid adenoma.

A group of 375 untreated euthyroid patients with solitary autonomous adenoma of the thyroid were studied in a long-term follow-up (observation period 52.8 (mean)/46 (median), range 3-204 months). During the period of observation, 133 (34.2%) of all initially untreated patients underwent treatment (surgery, radioiodine, antithyroid medication) because of hyperthyroidism, mechanical problems, or at the patient's request. Sixty-seven patients developed hyperthyroidism resulting in a mean incidence of 4.1% per year. The incidence of hyperthyroidism increased during follow-up (3% in the first seven years, 10% in the following years). Age, sex, nodule size, initial scintigraphic appearance and the TRH test were of no individual prognostic value in predicting hyperthyroidism. Eleven of 14 patients with untreated hyperthyroidism became euthyroid without treatment during the time of follow-up. After iodine excess (by history or elevated iodine levels in urine, N = 45), 14 patients (31%) developed hyperthyroidism. In conclusion, we recommend a definitive treatment of autonomous adenoma at least in patients with advanced age, concomitant diseases and a higher probability of iodine exposure.

Effect of small doses of iodine on thyroid function during caloric restriction in normal subjects.

It is well recognized that starvation and malnutrition are associated with a low-T3 syndrome in man. A similar condition has been observed after intake of a low carbohydrate hypocaloric diet. However, little is known about the influence of iodine on these conditions. Therefore, we evaluated the effect of iodine supplementation on thyroid function before and after a short-term intake of a low carbohydrate diet in normal subjects residing in an iodine-deficient area. The study was performed in 16 young euthyroid, nonobese volunteers (11 males, 5 females). The subjects were placed on a low carbohydrate (800 kcal) diet for 4 days. Eight subjects received 500 micrograms iodine (oral) daily beginning 4 weeks before diet. The control group (n = 8) received no iodine. After iodine supplementation, iodine excretion increased from 52 to 405 micrograms iodine/g of creatinine. Total T4 showed a slight but significant increase (104.2 nmol/l vs. 115.8 micrograms/dl; p < 0.001); fT4 was unchanged. The intake of the hypocaloric low carbohydrate diet resulted in a striking decrease in both total and free T3 and an increase of rT3 irrespective of iodine supplementation. T4 and fT4 were not affected in either group. During diet, iodine administration resulted in a decrease of basal TSH from 2.3 to 1.2 mU/l (p < 0.05), delta TSH from 10.3 to 4.5 mU/l (p < 0.01) and delta T3 (T3 180 min after TRH) from 0.7 to 0.3 nmol/l (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Basophilic leukocytes in hypothyroidism.

Since in the literature basophilia is frequently related to myxedema, we evaluated basophilic leukocytes in patients with hypothyroidism, applying routine techniques used in clinical laboratories. The study included normal persons, untreated patients with hypothyroidism, and euthyroid subjects with hyperlipidemia. The number of circulating basophils was determined by differential counts of Pappenheim stained blood smears. No difference in relative and total basophil counts was detected in patients with hypothyroidism as compared to healthy controls (1.0% and 58.1 basophils/microliters vs. 0.8% and 50.8 basophils/microliters, respectively). The percentage of basophils in myxedema associated with hypercholesterolemia amounted to 1.0%, their absolute number to 57.6/microliters; in hypothyroid patients presenting normal serum cholesterol levels, the relative and absolute numbers of basophilic leukocytes was not statistically different (0.83% and 61.1 basophils/microliters, respectively). We conclude that in patients with hypothyroidism the number of basophils is not statistically different from the values of basophils in healthy controls. Furthermore, the number of peripheral blood basophils in hypothyroidism is not related to the serum cholesterol level.

[Thyroid gland volume and urinary iodine excretion in children 2-16 years of age]. / Schilddrüsenvolumina und Jodurie bei Kindern im Alter von 2-16 Jahren.

Thyroid volume on ultrasound and urinary iodine excretion in relation to creatinine excretion were determined in 252 children (130 boys, 122 girls; mean age 8.7 [2-16] years) from the central Ruhr area of Germany. The data were compared with those published for children of other regions of Germany and Sweden. Mean thyroid volume in the 2-year olds was 2.0 +/- 0.5 ml, in 4-year olds 2.9 +/- 1.1 ml, in 6-year olds 4.2 +/- 1.9 ml, in 9-year olds 5.2 +/- 1.3 ml and in 13-year olds 8.7 +/- 2.4 ml. Mean iodine excretion for the whole group was 101.0 +/- 41.5 micrograms iodine/g creatinine, in the 13-year olds it was 69 +/- 27 micrograms/g. These values are clearly below those of Swedish children on an adequate iodine intake. The thyroid volume measurements agree reasonably well with those published for children in the region of Germany and are clearly above those of the Swedish children. In 69% of cases the thyroid volume was more than 3 S.D. above the mean for Swedish children. The reported data support the demand for a higher iodine intake of the German population.

Conservative and surgical management of incidentally discovered adrenal tumors (incidentalomas).

Of 50 patients with incidentalomas (INC), 18 were adrenalectomized and in 18 patients the INC was left in place. For 14 patients clinical data were insufficient for evaluation. Follow-up investigation of the 18 unoperated subjects 11-101 months (median 32.2) after the diagnosis had been made revealed unchanged size of the INC [initially 2.1 +/- 0.8 cm (mean +/- SD) at follow-up 2.0 +/- 1.0 cm]. Cushing's syndrome developed in one patient, which was not evident at the initial discovery of the INC 32 months before. "Pre-Cushing's Syndrome" was detected in 1 patient and confirmed in a second who had displayed a pathologically high dose dexamethasone suppression test 101 months before. In addition, 3 male patients with a hitherto unknown mild subclinical defect of 21-hydroxylase activity were identified. The remaining 12 patients had normal endocrine activity of their adrenals. Eighteen patients were adrenalectomized with an average tumor size of 3.96 +/- 1.88 cm. Histologically, 10 (52%) adenomas were observed, including 3 with signs of hypercortisolism. Adrenal hyperplasias were observed in 2 patients, metastasis in 1 patient. 31.5% of the INC which were removed were nonmalignant tumors of other than adrenal origin. We conclude that initially endocrinologically inactive adrenal tumors can eventually develop autonomous endocrine activity and therefore need to be reexamined at regular intervals. Conservative management with regular follow-up investigations is the preferable treatment for small incidentalomas when endocrine over-activity has been excluded and no indications of malignancy exist. Based on these observations and the literature a diagnostic and therapeutic strategy is presented.