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Background: Clinical decision-making is influenced by many factors, including clinicians' perceptions of the certainty around what is the best course of action to pursue., Objective: To characterise the documentation of working diagnoses and the associated level of real-time certainty expressed by clinicians and to gauge patient opinion about the importance of research into clinician decision certainty., Method: This was a single-centre retrospective cohort study of non-consultant grade clinicians and their assessments of patients admitted from the emergency department between 01 March 2019 and 31 March 2019. De-identified electronic health record proformas were extracted that included the type of diagnosis documented and the certainty adjective used. Patient opinion was canvassed from a focus group., Results: During the study period, 850 clerking proformas were analysed; 420 presented a single diagnosis, while 430 presented multiple diagnoses. Of the 420 single diagnoses, 67 (16%) were documented as either a symptom or physical sign and 16 (4%) were laboratory-result-defined diagnoses. No uncertainty was expressed in 309 (74%) of the diagnoses. Of 430 multiple diagnoses, uncertainty was expressed in 346 (80%) compared to 84 (20%) in which no uncertainty was expressed. The patient focus group were unanimous in their support of this research., Conclusion: The documentation of working diagnoses is highly variable among non-consultant grade clinicians. In nearly three quarters of assessments with single diagnoses, no element of uncertainty was implied or quantified. More uncertainty was expressed in multiple diagnoses than single diagnoses., Implications: Increased standardisation of documentation will help future studies to better analyse and quantify diagnostic certainty in both single and multiple working diagnoses. This could lead to subsequent examination of their association with important process or clinical outcome measures.

The development and maintenance of the zones of the adrenal cortex and their steroidal output are extremely important in the control of gluconeogenesis, the stress response, and blood volume. Sonic Hedgehog (Shh) is expressed in the adrenal cortex and signals to capsular cells, which can respond by migrating into the cortex and converting into a steroidogenic phenotype. Delta-like homologue 1 (Dlk1), a member of the Notch/Delta/Serrate family of epidermal growth factor-like repeat-containing proteins, has a well-established role in inhibiting adipocyte differentiation. We demonstrate that Shh and Dlk1 are coexpressed in the outer undifferentiated zone of the male rat adrenal and that Dlk1 signals to the adrenal capsule, activating glioma-associated oncogene homolog 1 transcription in a β1 integrin- and Erk1/2-dependent fashion. Moreover, Shh and Dlk1 expression inversely correlates with the size of the zona glomerulosa in rats after manipulation of the renin-angiotensin system, suggesting a role in the homeostatic maintenance of the gland.

The adrenal gland controls a plethora of crucial physiological functions, and dysfunction is associated with severe morbidity. Because of the vital importance of appropriate adrenal function, the development and function of the gland have been intensively studied, and these investigations have revealed fascinating developmental origins and a remarkable remodeling and regenerative capacity in the adult. This chapter, focusing on the adrenal cortex, will describe our current understanding of the development and maintenance of the adrenal gland, which has been advanced over recent years by the use of sophisticated genetic models in the study of both normal function and disease. This work has shed light on the transcriptional networks and signaling pathways involved in development and maintenance of the gland and in its pathology; these are discussed in the light of the wealth of physiological information gathered in studies of human and rodent adrenal development and function., (© 2013 Elsevier Inc. All rights reserved.)

Unlabelled: A state of insulin resistance is common to the clinical conditions of both chronic growth hormone (GH) deficiency and GH excess (acromegaly). GH has a physiological role in glucose metabolism in the acute settings of fast and exercise and is the only anabolic hormone secreted in the fasting state. We report the case of a patient in whom knowledge of this aspect of GH physiology was vital to her care. A woman with well-controlled type 1 diabetes mellitus who developed hypopituitarism following the birth of her first child required GH replacement therapy. Hours after the first dose, she developed a rapid metabolic deterioration and awoke with hyperglycaemia and ketonuria. She adjusted her insulin dose accordingly, but the pattern was repeated with each subsequent increase in her dose. Acute GH-induced lipolysis results in an abundance of free fatty acids (FFA); these directly inhibit glucose uptake into muscle, and this can lead to hyperglycaemia. This glucose-fatty acid cycle was first described by Randle et al. in 1963; it is a nutrient-mediated fine control that allows oxidative muscle to switch between glucose and fatty acids as fuel, depending on their availability. We describe the mechanism in detail., Learning Points: THERE IS A COMPLEX INTERPLAY BETWEEN GH AND INSULIN RESISTANCE: chronically, both GH excess and deficiency lead to insulin resistance, but there is also an acute mechanism that is less well appreciated by clinicians.GH activates hormone-sensitive lipase to release FFA into the circulation; these may inhibit the uptake of glucose leading to hyperglycaemia and ketosis in the type 1 diabetic patient.The Randle cycle, or glucose-fatty acid cycle, outlines the mechanism for this acute relationship.Monitoring the adequacy of GH replacement in patients with type 1 diabetes is difficult, with IGF1 an unreliable marker.

Androgen-secreting adrenal cancers are extremely rare malignancies, accounting for only a tiny proportion of the total number of women presenting with signs of androgen excess. Estrogen-secreting adrenal cancers are rarer still. Understanding how these tumors work benefits from an appreciation of adrenal steroid biosynthesis, as it is said that secretion in cancers is an anarchic version of normal adrenal function. Selection of patients in whom we should have a high suspicion of a malignancy is vital, so that biochemical investigation and imaging is deployed appropriately. When an adrenal tumor is found to secrete androgens or estrogens to excess, it can be difficult to confirm that it is a cancer, as there is significant overlap in the secretory patterns and imaging appearances of benign and malignant disease. The most reliable indicator of malignancy in these tumors remains the presence of metastases. Treatment is essentially surgical, although the role of mitotane is one undergoing evaluation., (Copyright © 2010 Elsevier Inc. All rights reserved.)