Ectopic ACTH-syndrome due to a thymic carcinoid tumor.

Investigating a recently developed Cushing Syndrome, we diagnosed in a 47-year-old woman an ectopic ACTH syndrome due to a metastatic carcinoid tumor, most likely a thymic carcinoid tumor. Combined therapy with sandostatin and nizoral and later on with sandostatin, metopirone and orimeten, was not able to suppress the hypercortisolism. A few weeks after surgical adrenalectomy, clinical deterioration ensued, culminating in the patient's death 7 months after diagnosis.

Real-life radiation burden to relatives of patients treated with iodine-131: a study in eight centres in Flanders (Belgium).

In view of the EURATOM 96/29 [1] regulations, a prospective multicentre study was performed to evaluate the present guidelines given to relatives of patients treated with iodine-131 for both thyroid carcinoma and thyrotoxicosis, based on the real-life radiation burden. This study comprised 166 measurements carried out on a group of 94 relatives of 65 patients. All relatives wore a thermoluminescent dosemeter (TLD) on the wrist for 7 days. Sixty-one relatives agreed to wear another TLD for an additional 7 days. TLD were placed on nine patients' bedside tables. The eight participating centres were arbitrarily divided into three groups according to the period of time they advised their patients to sleep separately. Groups I, II and III respectively advised their patients to sleep separately for 0, 7-10 and 14-21 days. The median dose received by in-living relatives of thyroid carcinoma patients during the 14 days following hospital discharge was 281 microSv (doses to infinity not calculated); the median dose to infinity received by in-living relatives of ambulatory treated thyrotoxicosis patients was 596 microSv, as compared with 802 microSv for in-living relatives of hospitalised thyrotoxicosis patients. In general the children of patients received a significantly (P < 0.1) lower mean dose than their partners. For thyroid carcinoma patients, only two relatives out of 19 (10%) exceeded the EURATOM 96/29 limit of 1 mSv/year. For thyrotoxic patients, 28% of relatives exceeded the EURATOM 96/29 limit, but none of them were relatives of patients who followed guidelines for 21 days. The results of this study indicate that sleeping separately for 7 days, after a period of hospitalisation of 2-3 days, will usually be sufficient for thyroid carcinoma patients. For thyrotoxicosis patients, up to 21 days of sleeping separately could be necessary in order to strictly abide by EURATOM 96/29. Therefore, the authors propose the implementation of a non-rigid dose constraint for people who "knowingly and willingly" help patients treated with 131I, while still following the ALARA principle.

CTLA-4 gene polymorphism confers susceptibility to insulin-dependent diabetes mellitus (IDDM) independently from age and from other genetic or immune disease markers. The Belgian Diabetes Registry.

Apart from genes in the HLA complex (IDDM1) and the variable number of tandem repeats in the 5' region of the insulin gene (INS VNTR, IDDM2), several other loci have been proposed to contribute to IDDM susceptibility. Recently, linkage and association have been shown between the cytotoxic T lymphocyte-associated protein 4 (CTLA-4) gene on chromosome 2q and IDDM. In a registry-based group of 525 recent-onset IDDM patients <40 years old we investigated the possible interactions of a CTLA-4 gene A-to-G transition polymorphism with age at clinical disease onset and with the presence or absence of established genetic (HLA-DQ, INS VNTR) and immune disease markers (autoantibodies against islet cell cytoplasm (ICA); insulin (IAA); glutamate decarboxylase (GAD65-Ab); IA-2 protein tyrosine phosphatase (IA-2-Ab)) determined within the first week of insulin treatment. In new-onset IDDM patients. G-allele-containing CTLA-4 genotypes (relative risk (RR)= 1.5; 95% confidence interval (CI) = 1.2-2.0; P < 0.005) were not preferentially associated with age at clinical presentation or with the presence of other genetic (HLA-DR3 or DR4 alleles; HLA-DQA1*0301-DQB1*0302 and/or DQA1*0501-DQB1*0201 risk haplotypes; INS VNTR I/I risk genotype) or immune (ICA, IAA, IA-2-Ab, GAD65-Ab) markers of diabetes. For 151 patients, thyrogastric autoantibodies (anti-thyroid peroxidase, anti-thyroid-stimulating hormone (TSH) receptor, anti-parietal cell, anti-intrinsic factor) were determined, but association between CTLA-4 risk genotypes and markers of polyendocrine autoimmunity could not be demonstrated before or after stratification for HLA- or INS-linked risk. In conclusion, the presence of a G-containing CTLA-4 genotype confers a moderate but significant RR for IDDM that is independent of age and genetic or immune disease markers.

Etiology of hypercalcemia in a patient with Addison's disease.

A case is reported of a hypercalcemic patient with primary Addison's disease. A combination of increased calcium input into the extracellular space and reduced calcium removal by the kidney accounted for the hypercalcemia. The mechanisms responsible for the reduction in calcium removal were decreased glomerular filtration and increased tubular calcium reabsorption. Both renal factors were secondary to volume depletion and improved rapidly during rehydration with saline infusion. The enhanced calcium mobilization was probably of skeletal origin. It persisted irrespective of volume status until hydrocortisone treatment was instituted. Serum 1,25-dihydroxyvitamin D3 levels were below 10 pg/ml, even after normalization of the glomerular filtration rate, but returned slowly to the normal range during corticosteroid substitution. Serum 25-hydroxyvitamin D3 and parathyroid hormone levels were within the normal range. Our case report therefore demonstrates that physiological amounts of glucocorticoids reduce bone resorption, normalize serum calcium, and restore the production of 1,25-dihydroxyvitamin D3.