Objective: This clinical practice guideline addresses the diagnosis and treatment of primary adrenal insufficiency. Participants: The Task Force included a chair, selected by The Clinical Guidelines Subcommittee of the Endocrine Society, eight additional clinicians experienced with the disease, a methodologist, and a medical writer. The co-sponsoring associations (European Society of Endocrinology and the American Association for Clinical Chemistry) had participating members. The Task Force received no corporate funding or remuneration in connection with this review. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to determine the strength of recommendations and the quality of evidence. Consensus Process: The evidence used to formulate recommendations was derived from two commissioned systematic reviews as well as other published systematic reviews and studies identified by the Task Force. The guideline was ...

/pdf/diagnosis-and-treatment-of-primary-adrenal-insufficiency-an-4ilgjyu2yg.pdf

Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline.

It is now generally accepted that vitamin D deficiency is a worldwide health problem that affects not only musculoskeletal health but also a wide range of acute and chronic diseases. However, there remains cynicism about the lack of randomized controlled trials to support the association studies regarding the nonskeletal health benefits of vitamin D. This review was obtained by searching English-language studies published up to April 1, 2013, in PubMed, MEDLINE, and the Cochrane Central Register of Controlled Trials (search terms: vitamin D and supplementation) and focuses on recent challenges regarding the definition of vitamin D deficiency and how to achieve optimal serum 25-hydroxyvitamin D concentrations from dietary sources, supplements, and sun exposure. The effect of vitamin D on fetal programming epigenetics and gene regulation could potentially explain why vitamin D has been reported to have such wide-ranging health benefits throughout life. There is potentially a great upside to increasing the vitamin D status of children and adults worldwide for improving musculoskeletal health and reducing the risk of chronic illnesses, including some cancers, autoimmune diseases, infectious diseases, type 2 diabetes mellitus, neurocognitive disorders, and mortality.

/pdf/vitamin-d-for-health-a-global-perspective-36p410gca6.pdf

Vitamin D for Health: A Global Perspective

Vitamin D deficiency in Europe: pandemic?

Objective:To develop consensus statements for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients.Participants:A multidisciplinary, multispecialty task force of experts in critical care medicine was convened from the membership of the Society of Critical Car

/pdf/recommendations-for-the-diagnosis-and-management-of-2iswoge3f9.pdf

Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine.

http://www.beyondconformity.org.nz/_literature_85253/Influenza_vit_D_Hyponnen

Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors

Data from the International Vitamin D External Quality Assessment Scheme, Graham D. Carter, Richard Carter, Julia Jones, and Jacqueline Berry ( Endocrine Laboratory, Clinical Chemistry Department, Charing Cross Hospital, London, United Kingdom; 2 Sovereign Software Services, Haywards Heath, West Sussex, United Kingdom; 3 Vitamin D Research Group, Medicine, Manchester Royal Infirmary, Manchester, United Kingdom.: * address correspondence to this author at: Endocrine Laboratory, Clinical Chemistry Department, Charing Cross Hospital, Fulham Palace Road, London, W6 8RF, United Kingdom; fax 44-208-846-7007, e-mail julia.jones@imperial.ac.uk)

http://csvlab.com.br/download/25-vit-D-how-accurate-Cl-Chem-11.pdf

How Accurate Are Assays for 25-Hydroxyvitamin D? Data from the International Vitamin D External Quality

The view that the renin–angiotensin–aldosterone system is a defence mechanism that maintains blood pressure only in conditions of volume depletion or sodium restriction1 has been supported by studies with saralasin2,3, a competitive inhibitor of angiotensin II, and teprotide1, an inhibitor of angiotensin converting enzyme that blocks the formation of angiotensin II. However, both saralasin and teprotide will underestimate the role of the renin–angiotensin system because: (1) they have to be given intravenously, thus inhibiting only the short-term effects of circulating angiotensin II; (2) all subjects in these studies were rested for some time before infusion1–3; and (3) saralasin is an agonist4–7 which only inhibits the action of circulating angiotensin II when its level is high. Niarchos et al.8 demonstrated a drop in blood pressure with teprotide in normal subjects on a sodium intake of 150 mmol per day, but this was partly due to one subject fainting. Therefore, none of these studies clearly shows at what stage of volume depletion the system actively maintains blood pressure. By analogy with other biological systems, a gradual increase in the importance of the renin–angiotensin system as sodium is lost is more likely than an all-or-none phenomenon. Using the recently developed oral inhibitors of angiotensin converting enzyme9–11, it is now possible to inhibit the formation of angiotensin II long-term and study human subjects during normal activity. We have now investigated the effect of one such inhibitor, captopril, in normotensive, healthy, male subjects on a normal sodium intake. Our results demonstrate that the renin–angiotensin system maintains blood pressure in these conditions and that the system is an important controller of aldosterone secretion as well as sodium excretion on a normal sodium intake.

Maintenance of blood pressure by the renin-angiotensin system in normal man.

Serum total cortisol has traditionally been used for the interpretation of tests of the hypothalamic-pituitary-adrenal axis. Approximately 80% of total cortisol is bound to cortisol-binding globulin (CBG), and variation in CBG significantly affects serum total cortisol levels. Reliable assessment of hypothalamic-pituitary-adrenal axis reserve is difficult in severely ill patients, because CBG falls substantially during the acute phase response. The free cortisol index (FCI), defined as the ratio of total cortisol/CBG, correlates well with serum free cortisol. We evaluated the FCI in the context of severe stress and the acute phase response by measuring total cortisol and CBG pre- and postoperatively in 31 patients undergoing major elective surgery. Serum total cortisol increased by 55% from 453 +/- 35.2 (mean +/- SEM) nmol/liter (range, 88-882) to 700 +/- 47.2 (range, 294-1631) nmol/liter. Serum CBG decreased by 30% from 45 +/- 1.7 (range, 26.6-64.1) to 31.4 +/- 1.62 (range, 16.1-51.9) mg/liter, but FCI increased by 130% from 10 +/- 0.8 (range, 2-18) to 23 +/- 1.7 (range, 13-58) nmol/mg. In seven patients (23%), postoperative serum total cortisol was less than 500 nmol/liter, but their postoperative CBG levels were significantly lower than levels in the rest of the group (P < 0.01). However, there was no difference in the FCI between this subgroup and the rest of the group. This study demonstrates the importance of CBG measurement and the calculation of FCI for the interpretation of serum total cortisol in situations where CBG changes significantly.

Free cortisol index is better than serum total cortisol in determining hypothalamic-pituitary-adrenal status in patients undergoing surgery.

Objective: Assessment of the hypothalamic ‐ pituitary ‐ adrenal (HPA) axis relies on the interpretation of serum (total) cortisol in response to dynamic tests of the HPA axis. Most cortisol is bound to cortisolbinding globulin (CBG) and serum total cortisol levels are significantly affected by variation in CBG. We hypothesised that CBG variation significantly affects interpretation of dynamic tests of the HPA axis. Design: We investigated the effect of CBG variation on the outcome of the 250mg short Synacthen test (SST) in 30 healthy adults. Methods: Blood was sampled at time 230, 0 (at which point Synacthen was given) and +30 min. CBG and total cortisol were measured at each time-point. Integrity of the HPA axis was confirmed by measurement of urine cortisol. Results: We found that CBG varied significantly within individuals, falling from 51^3: 4t o 43^ 3:2mg=mlOP , 0:0001U on changing from standing to lying. Total cortisol levels strongly correlated with CBGOra 0:88; P , 0:0001U: Thirteen subjects had a +30 min total cortisol ,550 nmol/l. In these subjects, the CBG levels at each time-point were significantly lower compared with subjects who had a +30 min total cortisol of .550 nmol/l OP , 0:05U: To correct for variation in CBG we calculated the total cortisol:CBG ratio and found no significant difference in the +30 min ratio between these two groups. Conclusion: CBG varies significantly within and between individuals. This is accompanied by changes in serum total cortisol large enough to affect the outcome of an SST and, by implication, other tests of the HPA axis.

/pdf/cortisol-binding-globulin-is-important-in-the-interpretation-3qkk6cax2t.pdf

Cortisol-binding globulin is important in the interpretation of dynamic tests of the hypothalamic--pituitary--adrenal axis.

1. Captopril given for 5 days caused a fall in blood pressure in normotensive subjects. The percentage fall in mean supine pressure was greatest on a low sodium diet (10 mmol/day), 19.6%, least on a high sodium diet (350 mmol/day), 11%, and in between on a normal sodium diet (120 mmol/day), 16.5%. 2. Captopril caused a marked fall in plasma aldosterone in normal subjects on all three sodium intakes. 3. Captopril caused an increase in sodium excretion on the normal (120 mmol/day) and low (10 mmol/day) sodium diet but not the high sodium diet. 4. These results suggest that the renin-angiotensin-aldosterone system is a normal mechanism for maintaining blood pressure and aldosterone secretion in normotensive man. The system may also be involved in the maintenance of sodium balance. 5. These results may lead to a better understanding of the role of the renin-angiotensin-aldosterone system in the maintenance or causation of high blood pressure in essential hypertension.

J. Jones

Papers

How Accurate Are Assays for 25-Hydroxyvitamin D? Data from the International Vitamin D External Quality

Maintenance of blood pressure by the renin-angiotensin system in normal man.

Free cortisol index is better than serum total cortisol in determining hypothalamic-pituitary-adrenal status in patients undergoing surgery.

Cortisol-binding globulin is important in the interpretation of dynamic tests of the hypothalamic--pituitary--adrenal axis.

The renin--angiotensin--aldosterone system in the maintenance of blood pressure, aldosterone secretion and sodium balance in normotensive subjects.