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      How should we interrogate the hypothalamic-pituitary-adrenal axis in patients with suspected hypopituitarism?

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      BMC Endocrine Disorders
      BioMed Central

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          Abstract

          Hypopituitarism is deficiency of one or more pituitary hormones, of which adrenocorticotrophic hormone (ACTH) deficiency is the most serious and potentially life-threatening. It may occur in isolation or, more commonly as part of more widespread pituitary failure. Diagnosis requires demonstration of subnormal cortisol rise in response to stimulation with hypoglycemia, glucagon, ACTH(1-24) or in the setting of acute illness. The choice of diagnostic test should be individualised for the patient and clinical scenario. A random cortisol and ACTH level may be adequate in making a diagnosis in an acutely ill patient with a suspected adrenal crisis e.g. pituitary apoplexy. Often however, dynamic assessment of cortisol reserve is needed. The cortisol response is both stimulus and assay- dependent and normative values should be derived locally. Results must be interpreted within clinical context and with understanding of potential pitfalls of the test used.

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          Most cited references49

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          Autoimmune hypophysitis.

          Autoimmune (lymphocytic) hypophysitis is a rare disease that should be considered in the differential diagnosis of any nonsecreting pituitary mass, especially when occurring during pregnancy or postpartum. We have analyzed 370 articles published from January 1962 to October 2004 and identified a total of 379 patients with primary lymphocytic hypophysitis. The present review synthesizes the clinical and research data reported in this body of scientific literature.
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            Diagnosis of adrenal insufficiency.

            The cosyntropin stimulation test is the initial endocrine evaluation of suspected primary or secondary adrenal insufficiency. To critically review the utility of the cosyntropin stimulation test for evaluating adrenal insufficiency. The MEDLINE database was searched from 1966 to 2002 for all English-language papers related to the diagnosis of adrenal insufficiency. Studies with fewer than 5 persons with primary or secondary adrenal insufficiency or with fewer than 10 persons as normal controls were excluded. For secondary adrenal insufficiency, only studies that stratified participants by integrated tests of adrenal function were included. Summary receiver-operating characteristic (ROC) curves were generated from all studies that provided sensitivity and specificity data for 250-microg and 1-microg cosyntropin tests; these curves were then compared by using area under the curve (AUC) methods. All estimated values are given with 95% CIs. At a specificity of 95%, sensitivities were 97%, 57%, and 61% for summary ROC curves in tests for primary adrenal insufficiency (250-microg cosyntropin test), secondary adrenal insufficiency (250-microg cosyntropin test), and secondary adrenal insufficiency (1-microg cosyntropin test), respectively. The area under the curve for primary adrenal insufficiency was significantly greater than the AUC for secondary adrenal insufficiency for the high-dose cosyntropin test (P 0.5) for secondary adrenal insufficiency. At a specificity of 95%, summary ROC analysis for the 250-microg cosyntropin test yielded a positive likelihood ratio of 11.5 (95% CI, 8.7 to 14.2) and a negative likelihood ratio of 0.45 (CI, 0.30 to 0.60) for the diagnosis of secondary adrenal insufficiency. Cortisol response to cosyntropin varies considerably among healthy persons. The cosyntropin test performs well in patients with primary adrenal insufficiency, but the lower sensitivity in patients with secondary adrenal insufficiency necessitates use of tests involving stimulation of the hypothalamus if the pretest probability is sufficiently high. The operating characteristics of the 250-microg and 1-microg cosyntropin tests are similar.
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              Hypothalamic-pituitary dysfunction after radiation for brain tumors.

              Patients with brain tumors who are treated with radiation frequently have growth hormone deficiency, but other neuroendocrine abnormalities are presumed to be uncommon. We studied endocrine function in 32 patients (age, 6 to 65 years) 2 to 13 years after they had received cranial radiotherapy for brain tumors. The doses of radiation to the hypothalamic-pituitary region ranged from 3960 to 7020 rad (39.6 to 70.2 Gy). Nine patients also received 1800 to 3960 rad (18.0 to 39.6 Gy) to the craniospinal axis. Serum concentrations of thyroid, gonadal, and pituitary hormones were measured at base line and after stimulation. Nine patients (28 percent) had symptoms of thyroid deficiency, and 20 patients (62 percent) had low serum total or free thyroxine or total triiodothyronine concentrations. Of the 23 patients treated only with cranial radiation, 15 (65 percent) had hypothalamic or pituitary hypothyroidism. Of the nine patients who also received spinal (and thus direct thyroid) radiation, three (33 percent) had evidence of primary thyroid injury. Seven of the 10 postpubertal, premenopausal women (70 percent) had oligomenorrhea, and 5 (50 percent) had low serum estradiol concentrations. Three of the 10 men (30 percent) had low serum testosterone concentrations. Overall, 14 of the 23 postpubertal patients (61 percent) had evidence of hypogonadism. Mild hyperprolactinemia was present in 50 percent of the patients. Responses to stimulation with corticotropin-releasing hormone and corticotropin were normal in all patients except one, who had panhypothalamic dysfunction. However, serum 11-deoxycortisol responses to the administration of metyrapone were low in 11 of the 31 patients (35 percent) tested. Three of the 32 patients, (9 percent) had no endocrine abnormalities, 9 (28 percent) had an abnormal result on tests of thyroid, gonadal, prolactin, or adrenal function, 8 (25 percent) had abnormalities in two axes, 8 (25 percent) in three axes, and 4 (12 percent) in all four axes. Cranial radiotherapy in children and adults with brain tumors frequently causes abnormal hypothalamic-pituitary function. The most frequent changes are hypothyroidism and gonadal dysfunction, although subtle abnormalities in adrenal function may also be present.
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                Author and article information

                Contributors
                +353-1-8093000 , +353-1-8376982 , amaragha@beaumont.ie
                Journal
                BMC Endocr Disord
                BMC Endocr Disord
                BMC Endocrine Disorders
                BioMed Central (London )
                1472-6823
                17 June 2016
                17 June 2016
                2016
                : 16
                : 36
                Affiliations
                [ ]Division of Endocrinology, Beaumont Hospital, Dublin, Ireland
                [ ]RCSI Medical School, Dublin, Ireland
                Article
                117
                10.1186/s12902-016-0117-7
                4912809
                27316460
                ebf7a52f-48f8-433b-a958-7c223d0f24e5
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 10 May 2016
                : 6 June 2016
                Categories
                Review
                Custom metadata
                © The Author(s) 2016

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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