Calcitonin (CT), a tumor marker for medullary thyroid cancer (MTC), can be stimulated with pentagastrin or calcium. Because of the unavailability of pentagastrin, basal CT measurement is frequently used for the preoperative diagnosis of MTC. The aim of the study was to define basal serum calcitonin (bCT) cut-off thresholds for diagnosing MTC. Within a retrospective analysis, 114 patients (51 males) were included fulfilling the criteria of an increased preoperative bCT level (> 10 pg/ml) and the criteria of an available postoperative histology analysis. Based on a ROC plot analysis, the cut-off values for the diagnosis of MTC vs. non-malignancy (C cell hyperplasia and goiter) were identified. The most precise bCT thresholds for the identification of MTC were >= 46 pg/ml for males (sensitivity: 93.6 %, specificity: 95.0 %, PPV: 97 %, NPV: 90 %) and >= 35 pg/ml for females (sensitivity: 87.3 %, specificity: 87.5 %, PPV: 98 %, NPV: 50 %). Using these cut-offs, only 6 % of male patients were not identified of having MTC, whereas 5 % were false positive (having instead C cell hyperplasia). In females, the discrepancy was higher since 13 % of female MTC patients were false negative by using the cut-off of >= 35 pg/ml, and 13 % had false positive results (suffering from C cell hyperplasia). Gender-specific bCT cut-offs for the identification of MTC vs. C cell hyperplasia and non-malignancy were defined, which can be used in clinical routine. In female patients, however, the accuracy is much lower compared to males.

We report a case of isolated levothyroxine malabsorption in the course of chronic intestinal giardiasis, leading to severe hypothyroidism. Infection with Giardia lamblia was proved histologically by jejunal biopsy. Treatment with metronidazole resulted in complete elimination of parasites and recovery of regular intestinal thyroid hormone absorption. Stable euthyroidism was accomplished with common replacement doses of orally administered levothyroxine.

To define in a prospective study the prevalence and manifestations of subclinical hypercortisolism in a sizeable group of patients with incidentally detected adrenal adenoma. Such tumour - although usually clinically silent - may cause discrete endocrine dysfunctions.Between 1990 and 1994, 85 consecutive patients with incidentally discovered adrenal adenoma were investigated (54 women, 31 men; mean age 54.1 +/- 13 [24-81] years). In addition to history and clinical examination all patients had a low-dose dexamethasone suppression test (2mg) and their morning basal plasma ACTH concentration was measured. The diagnosis of subclinical hypercortisolism was made if there was inadequate suppression of cortisol after dexamethasone administration, plasma ACTH level was decreased and there were no clinical signs of Cushing's syndrome.Five of the patients fulfilled the criteria of subclinical hypercortisolism (prevalence of 6%). One of them had oligomenorrhoea, another arterial hypertension, and three had mild histological proof of adrenal adenoma. Postoperatively the patient with oligomenorrhoea had normal menstrual cycles, while in all others with subclinical hypercortisolism excision of the tumour had no influence of their clinical state.Subclinical hypercortisolism is rare, but is one of the most common endocrine disorders in patients with incidental adrenal adenoma. It can be diagnosed only by hormonal analysis. Once the latent cortisol excess has been eliminated, those symptoms which are due to hormonal abnormality may regress, but nonspecific signs, such as obesity or hypertension, may not necessarily improve.

We report the case of a 21-year-old man with Mauriac's syndrome, in whom diabetic retinopathy progressed to the proliferative state despite slightly improved glycemic control and completely suppressed sex steroids (by a GnRH agonist). However, a gradual increase in serum IGF-1 from 162 to 482 ng/ml over 9 months clearly preceded retinal deterioration, which responded to panretinal laser coagulation. We conclude that substantial elevation of serum IGF-1 may be another risk factor for the progression of mild diabetic retinopathy to the proliferative state.

To assess the metabolic effects of thyroid disease, body composition was determined by bioimpedance analysis (BIA) in 72 patients with untreated hyperthyroidism (mean age 48.7 +/- 1.9 years) and 26 patients with untreated hypothyroidism (63.8 +/- 3.4 years). Bioelectrical whole body resistance (R) and reactance (Xc) were used for computerized calculation of lean body mass (LBM), body cell mass (BCM), extracellular mass (ECM) and body fat (BF). Compared with age- and sex-matched healthy controls the most sensitive parameter indicating excess thyroid hormone was the ECM/BCM ratio which was markedly elevated in all hyperthyroid subjects. ECM/BCM alteration resulted from marked depletion of BCM with concomitant expansion of ECM. BCM change is thought to be predominantly due to a loss of muscle mass while ECM rise may reflect an increase in extracellular fluids. In contrast, hypothyroidism was characterized by an increase in BF besides a relatively unaffected LBM component. Serum parameters of thyroid function (tri-iodothyronine (T3), free thyroxine, TSH) did not correlate with the determinants of body composition except for a slight inverse relationship between the phase angle (Xc/Rx180 degrees/pi) and T3 concentration in Graves' disease patients. We conclude that hyperthyroidism is primarily accompanied by quantitative as well as qualitative changes in the lean body while considerable fat increase is the most important feature of hypothyroidism. Severity of body composition derangement cannot be predicted from the degree of thyroid dysfunction. BIA could become a useful tool which allows objective determination of even subtle metabolic manifestations of thyroid disease and should, therefore, complement conventional clinical and biochemical assessment.

In a randomized study, prevention of goiter recurrence with L-thyroxine was compared with pure iodide substitution after thyroid surgery for nodular goiter in an iodine-deficient area. Altogether 107 patients were followed up for 52 weeks after thyroid resection. The thyroid volume was determined sonographically. Free thyroxine, total thyroxine, thyrotropin, thyroglobulin, and antibodies to thyroglobulin and thyroid peroxidase were measured. The thyroid volume decreased slightly over the course of a year in the two therapy groups. There was no significant difference between the two groups. Recurrences were seen with both L-thyroxine medication and iodide substitution. The thyroglobulin levels fell significantly over the 52-week follow-up period in the iodide group. Antibody formation was not observed under iodine substitution. In an area of iodine deficiency, substitution with iodide is just as effective as medicating the patients with L-thyroxine for preventing recurrences.

To test the hypothesis that patients with systemic nonthyroidal illness (NTI) and impaired thyroid hormone metabolism most commonly present with the low T3 or low T4 syndrome are in an euthyroid status at the tissue level, we determined serum sex hormone-binding globulin (SHBG) and osteocalcin (OC) as parameters for thyroid hormone availability to liver and bone. Serum SHBG and OC concentrations were measured in 61 severely ill patients with decreased serum levels of either T3 alone (n = 47) or both T3 and free T4 (n = 14). None of the patients had primary thyroid disorder indicated by regular thyroid sonomorphology and normal basal TSH concentrations. Data were compared with values obtained from age- and sex-matched controls without impairment of thyroid hormone physiology. The respective results from the study groups and from control subjects were as follows: low T3 SHBG, 49 +/- 30 nmol/L; low T4 SHBG, 35 +/- 14 nmol/L; control SHBG, 45 +/- 28 nmol/L; low T3 OC, 0.87 +/- 0.75 nmol/L; low T4 OC, 0.75 +/- 0.71 nmol/L; control OC, 0.98 +/- 0.87 nmol/L. SHBG and OC do not differ significantly between NTI patients with low T3 or low T4 syndrome and controls, and no significant relationship was found between thyroid hormone parameters and SHBG or OC, respectively. We conclude that the term euthyroid sick syndrome applied for the condition of systemic NTI associated with reduced circulating thyroid hormone concentrations appears to be appropriate at the level of hepatocytes and osteoblasts. Data are in partial contradiction to the results of previous studies using alternative serum parameters for assessment of peripheral thyroid hormone action (e.g. angiotensin-converting enzyme). Due to the tissue specificity of the biochemical serum markers, conflicting results may be explained by organ-specific differences in local thyroid hormone exposure. In case of doubt, SHBG and OC determinations may help specify peripheral thyrometabolic status in NTI.

OBJECTIVE:To compare the efficacy of iodide (300 micrograms daily) with that of levothyroxine (1.5 micrograms/kg daily) in the treatment of endemic goitre in middle-aged and elderly persons. The possible occurrence of antibodies against thyroid peroxidase and thyroglobulin was also tested.PATIENTS AND METHODS:67 patients (54 women, 13 men; aged over 40 years, average 53.5 years) with endemic goitre, excluding toxic goitre, were randomly treated with either iodine or thyroxine. Every 3 months for one year their thyroid volume was obtained by ultrasound and the activities of thyroid hormone (TH) and thyroid stimulating hormone (TSH) and the concentration of antibodies against peroxidase and thyroglobulin were measured.RESULTS:In patients on levothyroxine the thyroid volume had already markedly decreased after 3 months (P < 0.0001), diminishing by 15.4% at 12 months. Volume reduction in the group on iodine was 16.2% at one year. There was no significant difference between the two medications and no case of antibody production in the iodine group.CONCLUSIONS:Treatment of endemic goitre with iodine alone is efficacious even in middle-aged or elderly patients, toxic goitre having been excluded. There was no evidence of antibody production against thyroid antigens at the stated iodine dosage.

AIM OF STUDY:To define in a prospective study the prevalence and manifestations of subclinical hypercortisolism in a sizeable group of patients with incidentally detected adrenal adenoma. Such tumour - although usually clinically silent - may cause discrete endocrine dysfunctions.PATIENTS AND METHODS:Between 1990 and 1994, 85 consecutive patients with incidentally discovered adrenal adenoma were investigated (54 women, 31 men; mean age 54.1 +/- 13 [24-81] years). In addition to history and clinical examination all patients had a low-dose dexamethasone suppression test (2mg) and their morning basal plasma ACTH concentration was measured. The diagnosis of subclinical hypercortisolism was made if there was inadequate suppression of cortisol after dexamethasone administration, plasma ACTH level was decreased and there were no clinical signs of Cushing's syndrome.RESULTS:Five of the patients fulfilled the criteria of subclinical hypercortisolism (prevalence of 6%). One of them had oligomenorrhoea, another arterial hypertension, and three had mild histological proof of adrenal adenoma. Postoperatively the patient with oligomenorrhoea had normal menstrual cycles, while in all others with subclinical hypercortisolism excision of the tumour had no influence of their clinical state.CONCLUSIONS:Subclinical hypercortisolism is rare, but is one of the most common endocrine disorders in patients with incidental adrenal adenoma. It can be diagnosed only by hormonal analysis. Once the latent cortisol excess has been eliminated, those symptoms which are due to hormonal abnormality may regress, but nonspecific signs, such as obesity or hypertension, may not necessarily improve.

Objective: To compare the efficacy of iodide (300 mu g daily) with that of levothyroxine (1.5 mu g/kg daily) in the treatment of endemic goitre in middle-aged and elderly persons. The possible occurrence of antibodies against thyroid peroxidase and thyroglobulin was also tested.Patients and methods: 67 patients (54 women, 13 men; aged over 40 years, average 53.5 years) with endemic goitre, excluding toxic goitre, were randomly treated with either iodine or thyroxine. Every 3 months for one year their thyroid volume was obtained by ultrasound and the activities of thyroid hormone (TH) and thyroid stimulating hormone (TSH) and the concentration of antibodies against peroxidase and thyroglobulin were measured.Results: In patients on levothyroxine the thyroid volume had already markedly decreased after 3 months (P < 0.0001), diminishing by 15.4% at 12 months. Volume reduction in the group on iodine was 16.2% at one year. There was no significant difference between the two medications and no case of antibody production in the iodine group.Conclusions: Treatment of endemic goitre with iodine alone is efficacious even in middle-aged or elderly patients, toxic goitre having been excluded. There was no evidence of antibody production against thyroid antigens at the stated iodine dosage.

Objective. Endocrine ophthalmopathy is an autoimmune disorder of the retroorbital space tissues which is generally associated with thyroidal Graves' disease. Its pathogenetical aspects, clinical appearance and diagnostic procedures are reviewed. Therapeutic options include both established and more experimental approaches. Increasing use of intravenously administered immunoglobulin preparations has been noted in a variety of autoimmunologically mediated diseases. We report preliminary data of an observational trial on high-dose immunoglobulin treatment including 10 patients suffering from thyroid eye disease.Methods. Ophthalmopathy which had not been present for longer than 12 month and Graves' disease with an euthyroid metabolic state at the time of the investigation were the inclusion criteria. Therapy was commenced with a high initial immunoglobulin dose of 20 g/d over a period of five days, and 4 further doses of 20 g each were administered at intervals of 4 weeks.Results. No significant decrease was found in the clinical ophthalmopathy index and in thyroid-specific autoantibody levels. The eye muscle index, determined radiologically by orbital computed tomography as a parameter for inflammatory eye muscle involvement, also did not change significantly during therapy.Conclusion. In contradiction to previous reports, our results do not at present allow a general recommendation of high-dose immunoglobulin treatment in thyroid-related ophthalmopathy. Immunoglobulin therapy might be effective in selected patients, but criteria for selection have to be defined.

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

Between April 1986 and July 1995 121 patients have been operated on for C-cell carcinoma with 70 (57.9%) patients presenting a sporadic type and 51 (42.1%) a hereditary type of disease (46/38% MEN IIa and 5/4.1% MEN IIb). Indication for operation in patients with familial disease (MEN II) was in 9 patients (18%) detection of a mutation in the ret protooncogen (group I), in 27 patients (53%) a pathologic biochemical screening (pentagastrin stimulation) (group II), and in 15 patients (29%) the first manifestation in a family (index) (group III). Distribution of stages showed a stage I (T1 N0 M0) in 8/9 (89%) in group I, in 17/27 (63%) in group II, and in 0/15 in group III. In 8 from 9 patients with genetic indication a multifocal microcarcinoma and in one patient a cell-cell hyperplasia could be demonstrated. Accordingly the rate of curative operations with postoperative normalization of basal and pentagastrin stimulated calcitonin levels was 100% (9/9) in group I, 59% (16/27) in group II, and 7% (1/15) in group III. The mean age was 14 (median 12) years in group I, 26 (median 24) years in group II, and 43 (median 40) years in group III). In patients with presymptomatic screening (genetic and biochemical) a thyroidectomy including lymph node dissection of the central compartment was performed as a standard procedure. Postoperative complication rate showed a recurrent nerve palsy of 0 in group I and 4% in group II and a hypoparathyroidism of 0 in group I and 4% in group II. The detection of a mutation correlated with positive histological findings of the disease in all patients. The prophylactic radical operation on the basis of a genetic screening proved to be a safe procedure with curative intention. The early age of manifestation underlines the importance of the genetic screening and the early indication for operation.

Between April 1986 and July 1995 121 patients have been operated on for C-cell carcinoma with 70 (57.9 %) patients presenting a sporadic type and 51 (42,1 %) a hereditary type of disease (46/38 % MEN IIa and 5/4.1% MEN IIb). Indication for operation in patients with familial disease (MEN II) was in 9 patients (18 %) detection of a mutation in the ret protooncogen (group I), in 27 patients (53 %) a pathologic biochemical screening (pentagastrin stimulation) (group II), and in 15 patients (29 %) the first manifestation in a family (index) (group III). Distribution of stages showed a stage I (T1 N0 M0) in 8/9 (89 %) in group I, in 17/27 (63 %) in group II, and in 0/15 in group III. In 8 from 9 patients with genetic indication a multifocal microcarcinoma and in one patient a cell-cell hyperplasia could be demonstrated. Accordingly the rate of curative operations with postoperative normalization of basal and pentagastrin stimulated calcitonin levels was 100 % (9/9) in group I, 59 % (16/27) in group II, and 7% (1/15) in group III. The mean age was 14 (median 12) years in group I, 26 (median 24) years in group II, and 43 (median 40) years in group III). In patients with presymptomatic screening (genetic and biochemical) a thyroidectomy including lymph node dissection of the central compartment was performed as a standard procedure. Postoperative complication rate showed a recurrent nerve palsy of 0 in group I and 4 % in group II and a hy poparathyroidism of 0 in group I and 4 % in group II. The detection of a mutation correlated with positive histological findings of the disease in all patients. The prophylactic radical operation on the basis of a genetic screening proved to be a safe procedure with curative intention. The early age of manifestation underlines the importance of the genetic screening and the early indication for operation.

OBJECTIVE:Recent studies have indicated that the syndrome of congenital adrenal hyperplasia due to 21-hydroxylase deficiency is closely associated with the development of benign adrenocortical tumours. Tumour formation is thought to be a consequence of ACTH hypersecretion which results from the lack of glucocorticoid synthesis. The aim of this study was to evaluate 21-hydroxylase activity in patients with an incidentally discovered adrenal mass ('incidentaloma') without a history of congenital adrenal hyperplasia. DESIGN:A prospective study of 52 patients admitted to a single hospital. PATIENTS:Fifty-two consecutive subjects (mean age 56.0 years, range 24-81 years) with an incidentally discovered adrenal tumour were studied. MEASUREMENTS:The 21-hydroxylase reserve was assessed by intravenous bolus administration of 1-24 ACTH (tetracosactrin) with measurement of basal and stimulated serum 17 alpha-hydroxyprogesterone (17-OHP) concentrations. Impaired 21-hydroxylase activity was defined as an exaggerated 17-OHP response, with a 17-OHP increment exceeding 7.9 nmol/l. Basal and stimulated cortisol concentrations, and basal ACTH were also measured. RESULTS:Baseline levels of 17-OHP were normal in 44 and elevated in 8 subjects. In 37 patients (71.2%), the 17-OHP increment following ACTH administration exceeded 7.9 nmol/l, demonstrating mildly decreased 21-hydroxylase activity. In these subjects, the peak serum 17-OHP correlated with the tumour diameter. In the patients with apparently normal 21-hydroxylase activity, no significant correlation was found between 17-OHP concentrations and tumour size. All patients had a stimulated serum cortisol above 550 nmol/l reflecting intact adrenal glucocorticoid reserve. There were no other differences between the group with exaggerated and the group with normal 17-OHP increment. The tumours were removed from two women with augmented 17-OHP responses and this was followed by normalization of 17-OHP dynamics. CONCLUSIONS:Biochemical evidence for partial 21-hydroxylase defiency is a common finding in patients with an adrenal incidentaloma, even in the absence of a congenital adrenal hyperplasia history. Exaggerated 17-OHP increment is not accompanied by decreased adrenal glucocorticoid reserve. Normalization of the 17-OHP response after surgical treatment suggests that the phenomenon results from reduced 21-hydroxylase activity in the tumour, which retains ACTH responsiveness.