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Summary objective Iodide transport defect (ITD) is a rare disorder characterised by an inability of the thyroid to maintain an iodide gradient across the basolateral membrane of thyroid follicular cells, that often results in congenital hypothyroidism. When present the defect is also found in the salivary glands and gastric mucosa and it has been shown to arise from abnormalities of the sodium/iodide symporter (NIS). patient We describe a woman with hypothyroidism identified at the 3rd month of life. The diagnosis of ITD was suspected because of nodular goitre, and little if any iodide uptake by the thyroid and salivary glands. Treatment with iodide partially corrected the hypothyroidism; however, long-term substitution therapy with l-thyroxine was started. measurements Thyroid radioiodide uptake was only 1·4% and 0·3% at 1 and 24 h after the administration of recombinant human TSH. The saliva to plasma I− ratio was 1·1 indicating that the inability of the thyroid gland to concentrate I− was also present in the salivary glands. results Analysis of the patient's NIS gene revealed a 15 nucleotide (nt) deletion of the coding sequence (nt 1314 through nt 1328) and the insertion of 15 nt duplicating the first 15 nt of the adjacent intron. The patient was homozygous for this insertion/deletion, while both consanguineous parents were heterozygous. This deletion predicts the production of a protein lacking the five terminal amino acids of exon XI (439–443) which are located in the 6th intracellular loop. COS-7 cells transfected with a vector expressing the mutant del-(439–443) NIS failed to concentrate iodide, suggesting that the mutation was the direct cause of the ITD in this patient. conclusion In conclusion we describe the first Italian case of congenital hypothyroidism due to a new deletion in the NIS gene.

OBJECTIVE Familial glucocorticoid deficiency (FGD) has frequently been associated with tall stature in affected individuals. The clinical, biochemical and genetic features of five such patients were studied with the aim of clarifying the underlying mechanisms of excessive growth in these patients. PATIENTS AND METHODS Five patients with a clinical diagnosis of FGD are described in whom the disorder resulted from a variety of novel or previously described missense or nonsense mutations of the ACTH receptor (MC2-R). All patients demonstrated excessive linear growth over that predicted from parental indices and increased head circumference. RESULTS Growth hormone and IGF-I-values were normal. Growth charts suggest that the excessive growth is reduced to normal following the introduction of glucocorticoid replacement. A characteristic facial appearance including hypertelorism, marked epicanthic folds and prominent frontal bossing was noted. CONCLUSIONS These findings indicate that ACTH resistance resulting from a defective ACTH receptor may be associated with abnormalities of cartilage and/or bone growth independently of the GH–IGF-I axis, but probably dependent on ACTH actions through other melanocortin receptors.

Background Intensive insulin therapy is the gold standard by which Type 1 diabetes is treated. In addition to this therapy, administration of nicotinamide (NA) can be beneficial. This concept is reinforced by the results of a recent meta-analysis of the use of NA in patients with recent-onset Type 1 diabetes. Methods In this study we compared two different doses of NA in 74 patients with duration of Type 1 diabetes