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Resistance to thyroid hormones syndrome is defined as increased thyroxine (T4) and triiodothyronine (T3) concentrations associated with normal or sometimes increased thyrotropin (TSH) concentration. This is usually due to a pathogenic variant with loss of function of the gene coding for thyroid hormone receptor β (THRB). This discrepancy in thyroid hormones (TH) and TSH concentrations is also frequently observed in the presence of analytical interference, notably alteration of TH transport proteins in serum. During 2017, 58 samples were sent to our laboratory in the Angers University Hospital Rare Thyroid and Hormone Receptor Disease Reference Center in order to identify an etiology for discrepant TSH and TH results. We sequenced the genes involved in TH regulation, action and transport (THRB,THRA, SECISBP2, SLC16A, ALB, TTR, SERPINA7). Free T4 and free T3 assay were performed with a second immunoassay (Siemens ADVIA Centaur). A genetic cause of discrepancy in TH and TSH concentrations, with mutation in THRB, was found in 26% of cases (15/58). Biological interference due to TH serum transport protein variant was found in 24% (14/58) of cases. No pathogenic variants were found in the other genes studied. Biological interference was also suspected in 26% of cases without genetic variant, in which the biological discrepancy was not confirmed by a second analytical technique (15/58). Finally, no etiology for the biological discrepancy could be found in 24% of cases (14/58). Clinically, patients in whom biological discrepancy was due to analytic interference were more often asymptomatic, and patients with no identified etiology tended to be older. To limit diagnostic errors associated with the finding of discrepant TSH and TH, we recommend initially conducting a second thyroid function test (TSH, free T4 and free T3) with a different assay, and then screening for a genetic variant in gene coding for thyroid hormone receptor β (THRB) and the TH serum transport proteins (ALB, TTR, SERPINA7)., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Purpose: Some adrenal incidentalomas produce cortisol in mild excess ('subclinical' Cushing's adenomas) and can potentially induce osteopenia. Their diagnosis is usually based on exclusive tumour uptake on adrenal scintigraphy using 131I-6 beta-methyl-iodo-19-norcholesterol and on inadequate cortisol response to dexamethasone (DXM) suppression tests. The aims of the present study were to evaluate bone mineral density (BMD) and metabolic markers of bone turnover in patients with incidentalomas and to test the effect of mild hypercortisolism on bone parameters., Methods: Thirty-five patients (13 men, 22 postmenopausal women, 49-76 years) with unilateral incidentaloma were studied. BMD was measured by dual X-ray absorptiometry. Two biochemical markers of bone formation, serum osteocalcin (BGP) and bone alkaline phosphatase (bALP), and two markers of bone resorption, urinary free deoxypyridinoline (D-Pyr) and urinary carboxy-telopeptide of bone type 1 collagen (CTX), were measured by radioimmunoassay. D-Pyr and CTX were corrected for creatinine excretion., Results: Median values of lumbar and femoral T-score were -1.125 and -0.920, respectively, whereas corresponding Z-score values where normal (0.105 and 0.120, respectively). Thirty-nine percent of patients had low serum BGP values and 3% had low bALP values; 16% showed elevated D-Pyr/creatinine values and 23% increased CTX/creatinine values. Patients both with suppression of the contralateral adrenal on scintigraphy and with an inadequate cortisol response to 1 mg DXM (> 50 nmol/L) (n = 14) presented a lower femoral T-score (P < 0.02) and, to a lesser extent, a lower femoral Z-score (P = 0.11) than other patients (n = 21). The proportion of increased values of CTX/creatinine (42% versus 11%, P = 0.08) also tended to be higher in the first than in the second group of patients. These two groups of patients were similar in terms of age, but tumour size was larger (P < 0.04) and plasma ACTH value was lower (P < 0.02) in patients with scintigraphic and endocrine abnormalities., Conclusion: Subclinical hypercortisolism defined on the basis of scintigraphic and hormonal criteria seems to contribute to bone loss in patients with adrenal incidentaloma. As other possible side effects of mild hypercortisolism, these findings have to be taken into account in the therapeutic management of these patients.