Isolated central hypothyroidism: Underlying pathophysiology and relation to antidepressant and antipsychotic medications-A multi-centre South Wales study.

OBJECTIVE: Isolated biochemical central hypothyroidism is a presentation we are experiencing more frequently as endocrinologists, with variation in levels of investigation between physicians. We therefore conducted research to investigate the final diagnosis and clinical outcome of patients across multiple hospitals in South Wales with biochemical isolated central hypothyroidism; namely to establish whether this isolated biochemical picture was clinically significant. We also analysed whether there is an association between this biochemical picture and treatment with antidepressant and antipsychotic medications, and how common this is. DESIGN: We performed a retrospective observational study of patients across nine different hospitals in South Wales. We analysed patients referred to endocrinology at each site over a 6-year period with unexplained isolated biochemical central hypothyroidism. MATERIALS AND METHODOLOGY: 1022 individual patients' thyroid function test results were identified from our biochemical database using our inclusion criteria. After exclusion criteria were applied, 71 patients' results were analysed as to the final pathophysiology of their central hypothyroidism. RESULT: Of the 71 patients included in the study, none were found to have any clinically significant pathology on pituitary imaging. On reviewing their medications, 46/71 (65%) were found to be taking psychotropic medications. CONCLUSIONS: Our study strongly suggests isolated central hypothyroidism, in the absence of other pituitary hormone dysfunction or visual field defect, does not require further investigation, saving resources as well as sparing patients unnecessary anxiety. It also strongly supports a relationship between patients taking psychotropic medications and biochemical isolated central hypothyroidism, an association only described in a very limited amount of literature before this, and further supporting our previous single-centre study findings. The mechanism behind this is likely to be the suppression of thyrotropin secretion via antagonism of the dopamine-serotoninergic pathway. In our opinion, patients found to have isolated biochemical central hypothyroidism who are taking psychotropic medications can therefore be regarded to have a recognised cause for this biochemical finding and do not require further radiological investigation.

Central hypothyroidism related to antipsychotic and antidepressant medications: an observational study and literature review.

Objective: To investigate the final diagnosis and clinical outcome of patients referred to endocrinology in our district general hospital with biochemical isolated central hypothyroidism (CeH), and whether there is an association between this biochemical picture and treatment with antidepressant and antipsychotic medications. Methods: We performed a retrospective observational study of patients referred to endocrinology with unexplained biochemical isolated CeH over a 5-year period. Results: Of the 29 patients included in the study, 4 were found to have a partially empty or empty sella and 1 to have a bulky pituitary gland which was deemed to be an incidental radiological finding. No patients had any clinically significant pathology. On reviewing their medications, 18/29 (62%) were found to be on psychotropic medications. Conclusions: Our study suggests a relationship between patients on psychotropic medications and biochemical isolated CeH, an association only described in a very limited amount of literature prior to this. The mechanism behind this may be suppression of TSH secretion via antagonism of the dopamine-serotoninergic pathway. Determining a correlation between psychotropic medications and isolated CeH could lead to the avoidance of further radiological investigations and unnecessary anxiety for patients. However, a larger observational study is needed to provide further evidence to support/refute our finding.

Method-specific serum cortisol responses to the adrenocorticotrophin test: comparison of gas chromatography-mass spectrometry and five automated immunoassays.

OBJECTIVE: The serum cortisol response to the adrenocorticotrophin (ACTH) test is known to vary significantly by assay, but lower reference limits (LRL) for this response have not been established by the reference gas chromatography-mass spectrometry (GC-MS) method or modern immunoassays. We aimed to compare the normal cortisol response to ACTH stimulation using GC-MS with five widely used immunoassays. DESIGN, PATIENTS AND MEASUREMENTS: An ACTH test (250 µg iv ACTH1-24 ) was undertaken in 165 healthy volunteers (age, 20-66 years; 105 women, 24 of whom were taking an oestrogen-containing oral contraceptive pill [OCP]). Serum cortisol was measured using GC-MS, Advia Centaur (Siemens), Architect (Abbott), Modular Analytics E170 (Roche), Immulite 2000 (Siemens) and Access (Beckman) automated immunoassays. The estimated LRL for the 30 min cortisol response to ACTH was derived from the 2·5th percentile of log-transformed concentrations. RESULTS: The GC-MS-measured cortisol response was normally distributed in males but not females, with no significant gender difference in baseline or post-ACTH cortisol concentration. Immunoassays were positively biased relative to GC-MS, except in samples from women on the OCP, who showed a consistent negative bias. The LRL for cortisol was method-specific [GC-MS: 420 nm; Architect: 430 nm; Centaur: 446 nm; Access 459 nm; Immulite (2000) 474 nm] and, for the E170, also gender-specific (female: 524 nm; male 574 nm). A separate LRL is necessary for women on the OCP. CONCLUSIONS: Normal cortisol responses to the ACTH test are influenced significantly by assay and oestrogen treatment. We recommend the use of separate reference limits in premenopausal women on the OCP and warn users that cortisol measurements in this subgroup are subject to assay interference.

Does lactate measurement performed on admission predict clinical outcome on the intensive care unit? A concise systematic review.

BACKGROUND: There is a need for practical, efficient and effective prognostic markers for patients admitted to the intensive care unit (ICU) with sepsis, to identify patients at highest risk and guide and monitor treatment. Although many biomarkers and scoring systems have been advocated, none have yet achieved this elusive combination. Most ICUs already use blood lactate concentrations to monitor patients but the evidence base for this application is unclear. METHODS: A systematic review of the last five years of evidence of effectiveness of lactate measurement in prediction of outcome in ICUs was performed. RESULTS: It was found that there is a lack of high-quality evidence, and no specific studies of prognostic accuracy. D- or L-Lactate concentrations measured in plasma, serum, whole blood or colonic washings were raised at admission in almost all patient groups, and were higher in patient groups who had the worst outcomes (in-hospital mortality, sequential organ failure). However, there was significant overlap in individual concentrations measured in those who died within 28 days of admission, or who developed multiple organ failure, and those who did not. For serum L-lactate concentrations, no specific cut-off value capable of predicting in-hospital mortality or sequential organ failure could be recommended. CONCLUSIONS: The evidence reviewed suggested that whole blood, plasma or serum lactate measurement could not provide specific prognostic information for individual patients. There may be a role for monitoring for normalization of serum D- or L-lactate concentrations during goal-directed therapy in the ICU but further good-quality studies are needed. Measurement of the D-lactate stereoisomer shows promise, such that further studies are warranted.