STRAIGHT FROM THE HOUSESTAFF – the April 2015 UT Southwestern Internal Medicine Journal Watch! They have summarized important issues in clinical practice, from alcoholic hepatitis to which medications to use for stroke prevention in afib. Make sure to take the EKG challenge at the end! You will have to view this post on our website to access the PDF. There is a quick run down of the topics below:
- Extended report: Prediction of cardiovascular risk in rheumatoid arthritis: performance of original and adapted SCORE algorithms. Dr. Brian Skaug reviewing Arts, et al. Ann Rheum Dis. 2015 Feb 17. pii: annrheumdis-2014-206879. doi: 10.1136/annrheumdis-2014-206879
- Trial of Early, Goal-Directed Resuscitation for Septic Shock [The Protocolised Management in Sepsis (ProMISe) Trial]. Dr. James Galloway reviewing Mouncey PR et al. N Engl J Med. 2015;372(14):1301-11.
- A Randomized Trial of Icatibant in ACE-Inhibitor-Induced Angioedema. Dr. James Galloway reviewing Bas M, et al. N Engl J Med. 2015;372(5):418-25.
All of the work above comes from the IMJW Editorial Board: Jan Petrasek, Brian Skaug, Ben Galloway, Natalia Rocha, Doug Darden, and Jeanney Lew!
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Dr Holick, endocrinologist and mineral metabolism specialist from Boston University, gave us a rousing Grand Rounds about vitamin D deficiency. The recommendations for vitamin D supplementation, which Dr. Holick notes afflicts almost everyone, are below:
However, these dosing recommendations change for patients with obesity, as increased body weight can increase the need for vitamin D up to 2-3 fold. Dr. Holick’s research is prolific, so take a look at a recent article about the need for increased vitamin D dosing in obese patients.
The Importance of Body Weight for the Dose Response Relationship of Oral Vitamin D Supplementation and Serum 25-Hydroxyvitamin D in Healthy Volunteers
Unlike vitamin D recommendations by the Institute of Medicine, the Clinical Practice Guidelines by the Endocrine Society acknowledge body weight differentials and recommend obese subjects be given two to three times more vitamin D to satisfy their body’s vitamin D requirement. However, the Endocrine Society also acknowledges that there are no good studies that clearly justify this. In this study we examined the combined effect of vitamin D supplementation and body weight on serum 25-hydroxyvitamin (25(OH)D) and serum calcium in healthy volunteers. We analyzed 22,214 recordings of vitamin D supplement use and serum 25(OH)D from 17,614 healthy adult volunteers participating in a preventive health program. This program encourages the use of vitamin D supplementation and monitors its use and serum 25(OH)D and serum calcium levels. Participants reported vitamin D supplementation ranging from 0 to 55,000 IU per day and had serum 25(OH)D levels ranging from 10.1 to 394 nmol/L. The dose response relationship between vitamin D supplementation and serum 25(OH)D followed an exponential curve. On average, serum 25(OH)D increased by 12.0 nmol/L per 1,000 IU in the supplementation interval of 0 to 1,000 IU per day and by 1.1 nmol/L per 1,000 IU in the supplementation interval of 15,000 to 20,000 IU per day. BMI, relative to absolute body weight, was found to be the better determinant of 25(OH)D. Relative to normal weight subjects, obese and overweight participants had serum 25(OH)D that were on average 19.8 nmol/L and 8.0 nmol/L lower, respectively (P<0.001). We did not observe any increase in the risk for hypercalcemia with increasing vitamin D supplementation. We recommend vitamin D supplementation be 2 to 3 times higher for obese subjects and 1.5 times higher for overweight subjects relative to normal weight subjects. This observational study provides body weight specific recommendations to achieve 25(OH)D targets.
Citation: Ekwaru JP, Zwicker JD, Holick MF, Giovannucci E, Veugelers PJ (2014) The Importance of Body Weight for the Dose Response Relationship of Oral Vitamin D Supplementation and Serum 25-Hydroxyvitamin D in Healthy Volunteers. PLoS ONE 9(11): e111265. doi:10.1371/journal.pone.0111265
We know PCSK9 inhibitors can dramatically lower LDL cholesterol, but does it affect one’s actual health? Through extensive research, including at UT Southwestern, PCSK9 has become a potential target for lowering cholesterol with the hopes of reducing risk for stroke and heart attack. This week in The New England Journal Of Medicine, two research studies published showed reduction in cardiovascular events with the use of PCSK9 inhibitors. The results were also presented at this year’s American College of Cardiology Conference in San Diego, CA. The studies looked at evolocumab and alirocumab and is causing a lot of excitement in the medical community and making national headlines including The New York Times. Both drugs could become approved by the FDA by the end of this summer. Future trials are underway with larger cohorts as these two studies were not designed to primarily look at cardiovascular outcomes but the drug’s ability to lower LDL cholesterol. Check out the two studies below by clicking on the links below:
Review of the Physiology
- CRH –> pituitary ACTH –> adrenals to make glucocorticoids, mineralcorticoids and androgens
- Adrenal Gland
- Cortex makes cortisol, adrenal androgens and aldosterone
- Glomerulosa (aldosterone – salt)
- Fasciculata (cortisol – sugar)
- Reticularis (androgens – sex)
- Medulla makes epinephrine
- Autoimmune (Addison’s disease)
- Polyglandular syndromes
- Granulomatous infections (sarcoid, fungal infections, etc)
- Infiltrative diseases (HIV, CMV, amyloid)
- High ACTH
- Rapid withdrawal of exogenous steroids
- Low or inappropriately normal ACTH
Signs and Symptoms
Acute adrenal insufficiency/adrenal crisis can be an endocrine emergency!
- All causes: weakness, weight loss, NV, fatigue, vague abd pain, hypercalcemia (20%)
- Primary: hypotension and hyperpigmentation, hyperkalemia and hyponatremia (due to affecting both the aldo and cortisol)
- Secondary: hypotension but not associated with hyperkalemia (because aldo is still released by the renin-angiotension response)
- If acute AI suspected with s/sx of shock, must give steroids right away – Dexamethasone will not interfere with cortisol test but will affect ACTH.
- If stable, check Cosyntropin stim test
- Check baseline cortisol
- Give 0.25 mg cosyntropin
- Recheck cortisol at 30 and 60 mins
- Expected stimulation >18-20
- Check ACTH
- Check aldo level
- Expected findings:
- Low stim test
- High ACTH
- Low aldo
- Secondary or tertiary
- Low stim test
- Low or normal ACTH
- Normal aldo
- Acute adrenal insufficiency (ADRENAL CRISIS!)
- General idea: this is a medical emergency! High fatality rate if not treated (approaching 100%). If adrenal crisis is suspected, start treatment before labs have resulted!
- IV Fluids: 2-3 L NS or d5NS bolus as quickly as possible to correct hypotension and hyponatremia. Continue IVF for the next 24-48 hours or until stabilization.
- Dexamethasone: use if cosyntropin stim test has NOT been performed, as it does not interfere with the measurement of plasma cortisol. Give 4 mg decadron IV q12h.
- Hydrocortisone: use if the diagnosis has already been made or decadron is not available. Give 100mg q6h for 2-3 days.
- Continue IV steroids for 2-3 days or until stabilization – then taper to PO hydrocortisone.
- Needed only in primary adrenal insuffi ciency
- Not needed if hydrocortisone dose >50 mg per 24 h, as this will activate the mineralcorticoid receptor
- Chronic adrenal insufficiency:
- Glucocorticoid: hydrocortisone split into 2-3 doses daily, with 2/3 in the AM and 1/3 in the PM. Aim for the lowest possible steroid dose to relieve signs and symptoms.
- Primary adrenal insufficiency: start on 20–25 mg hydrocortisone per 24 h
- Secondary adrenal insufficiency: 15–20 mg hydrocortisone per 24 h
- Increase to stress dose for acute illnesses
- Mineralcorticoid: Needed only in primary adrenal insufficiency, and not if total hydrocortisone dose is greater than 50mg/day.
- Fludrocortisone oral 0.05-0.1 mg/day (lower dose may be sufficient in patients receiving hydrocortisone).
- Sex Steroids: consider in patients who complain of decreased energy, sexual dysfunction, or impaired mood despite optimum replacement therapy with glucocorticoids and mineralocorticoids.
- Start with DHEA 25–50 mg as a single morning dose
- Charmandari, Evangelia et al. Adrenal insufficiency. The Lancet , Volume 383 , Issue 9935, 2152 – 2167.
- Arlt, Wiebke et al. Adrenal insufficiency. The Lancet , Volume 361, Issue 9372 , 1881 – 1893.
- Jadoul, et al. Mineralocorticoids in the management of primary adrenocortical insufficiency. Journal of Endocrinological Investigation. February 1991, Volume 14, Issue 2, pp 87-91.
- Arlt, Wiebke et al. The Approach to the Adult with Newly Diagnosed Adrenal Insufficiency. The Journal of Clinical Endocrinology & Metabolism 2009 94:4, 1059-1067
How much prednisone do I give my patient that I am tapering off of solumedrol?! Take a look at the handy chart below to learn more about steroid equivalencies.
Sandeep Mukherjee and Urmila Mukherjee, “A Comprehensive Review of Immunosuppression Used for Liver Transplantation,” Journal of Transplantation, vol. 2009, Article ID 701464, 20 pages, 2009. doi:10.1155/2009/701464
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Dr. Saad Khan, from the UTSW division of Hematology/Oncology, presented an update on the diagnosis and treatment of thyroid cancer. A point important for general internists is the evaluation of incidentally discovered thyroid nodules. The algorithm below may help clarify the diagnostic process:
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STRAIGHT FROM THE HOUSESTAFF – the February 2015 Internal Medicine Journal Watch! They have summarized important issues in clinical practice, from Metformin in CKD to pre-exposure prophylaxis for HIV. There is even an EKG challenge at the end, if you are up for it! You will have to view this post on our website to access the PDF. There is a quick run down of the topics below:
- American Diabetes Association’s Standards of Medical Care in Diabetes – 2015.
- Dr. Jeremy Warshauer reviewing Grant RW, et al. Diabetes Care 2015 Jan;38 Supplement 1
- Metformin in Patients With Type 2 Diabetes and Kidney Disease: A Systematic Review
- Dr. Nicolas Barros reviewing Inzucchi, SE, et al. JAMA 2014; 312(24):2668-2675
- Preliminary analysis of the Very Early Diagnosis of Systemic Sclerosis (VEDOSS) EUSTAR multicentre study: evidence for puffy fingers as a pivotal sign for suspicion of systemic sclerosis
- Dr. Brian Skaug reviewing Minier T, et al. Ann Rheum Dis 2014;73: 2087–2093
- Using drugs to discriminate – adverse selection in the insurance marketplace
- Dr. Ashish Gupta reviewing Jacobs DB and Sommers BD. N Engl J Med. 2015 Jan 29;372(5):399-402
General Internal Medicine
- Disorders of Plasma Sodium — Causes, Consequences, and Correction
- Dr. Nicolas Barros reviewing Sterns, R, et al. NEJM 2015; 372:55-65
- Acid–Base Problems in Diabetic Ketoacidosis
- Dr. Nicolas Barros reviewing Kamel K, et al. NEJM 2015 ; 372:546-554
- A Clinical Practice Guideline From the AABB
- Dr. Nicolas Barros reviewing Kaufman RN, et al. Ann Intern Med. 2015 Feb 3;162(3):205-13
- Association of Albumin-Creatinine Ratio and Cystatin C With Change in Ankle-Brachial Index: The Multi-Ethnic Study of Atherosclerosis (MESA)
- Dr. Ben Jenny reviewing Garimella P, et al. Am J Kidney Dis. 2015;65(1):33-40
- Tenofovir-Based Preexposure Prophylaxis for HIV Infection Among African Women
- Dr. Brad Cutrell and Dr. Nicolas Barros reviewing Marrazzo J, et al. 2015; 372:509-518
- Infectious Diseases Diagnosis and Treatment of C. difficile in Adults: Systematic Review
- Dr. Brad Cutrell and Dr. Nicolas Barros reviewing Bagdasarian N, et al. JAMA 2015; 313(4):398-408
- An interferon-free antiviral regimen for HCV after liver transplantation
- Dr. Jan Petrasek reviewing Kwo et al., NEJM. 2014; Dec 18;371(25):2375-82
- Decreasing Mortality Among Patients Hospitalized with Cirrhosis in the United States From 2002 through 2010
- Dr. Jan Petrasek reviewing Schmidt et al., Gastroenterology. 2015 Jan 23.
- Twelve or 30 Months of Dual Antiplatelet Therapy after Drug-Eluting Stents (DAPT trial)
- Dr. Ben Jenny reviewing Mauri L, et al. N Engl J Med. 2014 Dec 4;371(23):2155-66.
- Dr. Ben Jenny
All of the work above comes from the IMJW Editorial Board (with Dr. Brad Cuttrell): Jan Petrasek, Purav Mody, Nicolas Barros, Ragisha Gopalakrishnan, Jeremy Warshauer, Shetal Patel, Ben Jenny (not Jennings), Vishwanatha Lanka, Brian Skaug, Ashish Gupta, and Roma Mehta!