Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.820868
Title: Medical treatment and monitoring for disorders of cortisol and adrenocorticotrophin excess and deficiency
Author: Daniel, Eleni
ISNI:       0000 0004 9356 9668
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2020
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Abstract:
Background: Disorders of cortisol secretion have high mortality and morbidity if inadequately treated. Medical treatment is an essential part of patient management and has improved prognosis and morbidity, however, there are unanswered questions about effectiveness, safety, accuracy and monitoring. The hypothesis in this thesis was that medical treatments can restore physiological cortisol and adrenocorticotrophin hormone (ACTH) levels in patients with disorders of cortisol excess and deficiency. Methods: Five studies examined the treatment and monitoring of cortisol secretion disorders. Two studies examined medical treatment of cortisol and ACTH excess, Cushings syndrome (CS) and Nelson’s syndrome (NS), two studies examined new methods for replacing cortisol in children with adrenal insufficiency and one study examined potential for a novel biomarker of cortisol replacement in congenital adrenal hyperplasia (CAH). Results: Study 1, demonstrated that medical therapy with the steroidogenesis enzyme inhibitor metyrapone was effective in restoring eucortisolaemia and reducing hypercortisolaemia in 50-80% of patients with CS. Study 2, demonstrated that medical therapy with pasireotide, a multi-receptor somatostatin analogue, reduced plasma ACTH levels in patients with Nelson’s syndrome. Study 3, showed that it is possible to replace cortisol with hydrocortisone through nasogastric tubes, however, there are variable drug loses due to interaction with the administering equipment and the study provided practical solutions. Study 5, showed that a novel formulation of hydrocortisone granules administered sprinkled on soft food (applesauce or yoghurt) are bioequivalent to granules delivered directly to the back of the tongue. Study 4, showed that haemoglobin and haematocrit are positively correlated with androgen and steroid precursor levels in women with CAH and provide a novel biomarker. Conclusions. Medical therapy for cortisol excess and deficiency can be improved. Metyrapone and pasireotide are effective in improving cortisol and ACTH levels in patients with CS and Nelson’s syndrome, respectively. The replacement of cortisol in paediatric adrenal insufficiency can be done through nasogastric tubes if required and with food to improve accurate dosing in neonates, infants and children. Markers of erythropoiesis may be used as a biomarker to monitor disease control in women with CAH.
Supervisor: Newell-Price, John ; Ross, Richard Sponsor: European Commission
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.820868  DOI: Not available
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