All posts by Eric

I am an R1 in the categorical track of the University of Washington Internal Medicine residency program.

Primary care of the transgender patient


In this episode, I interview Jessica Rongitsch, an internist in Seattle specializing in primary care for the LGBTQ community, about hormone management (and other aspects of primary care) for the transgender patient. Although she specializes in trans* care, she believes it is well within the reach of any primary care provider.

Trans* people are at increased risk for depression and suicide, but gender-affirming hormone therapy improves psychological health.


Jessica advises avoiding these terms: “transgendered“, “MTF”, and “FTM”. We should identify people based on their preference, not based on the sex they were designated at birth. If you mis-gender someone, apologize very briefly and then move on.

Developing a supportive clinic environment

Clinic staff should be trained in trans sensitivity and trans competency (CARDEA has resources for this). Evaluate and consider revising your clinic’s forms. Offer recommended cancer screening once you have developed a therapeutic relationship with the patient.

Treatment based on informed consent

Both major guidelines for trans* care, the WPATH and ICATH guidelines, now allow for informed consent as the basis for treatment. There is no longer  a requirement for psychological evaluation or “lived experience” in the desired gender prior to the initiation of gender-affirming hormone therapy.

Absolute and relative contraindications to hormone treatment

Active steroid-responsive malignancies, pregnancy, and current VTE are considered contraindications to starting therapy. Patients with a history of VTE can be treated with the help of a hematologist and anticoagulation.

Effects of feminizing hormone therapy

Prescribing estradiol and spironolactone should suppress testosterone and raise estrogen levels to the normal female range. Patients at high risk for clotting problems should be targeted to the lower end of the normal female range. Expected changes include fat redistribution of the face and body to a more female pattern, breast tissue growth, testicular atrophy, erectile dysfunction, and infertility. Things that will not change include voice, laryngeal prominence (Adam’s apple), and the location of hair growth, although hair characteristics may change. Recommend sperm banking prior to starting treatment. Finasteride 1mg daily can help with alopecia in the early stages of treatment, until testosterone levels are suppressed.

Titrating feminizing hormone therapy

Start spironolactone at 50 mg PO daily (lower if there is baseline hypotension, or not at all if there is hyperkalemia or renal impairment) and estradiol 2 mg SL daily. Alternatively, estradiol can be written as a patch: 0.1 mg patch, changed twice weekly. Spironolactone can be uptitrated in 1-2 weeks if there are no problems with AKI, orthostatic hypotension, or hyperkalemia.

Gradually uptitrate spironolactone until toxicities limit the dosing, or the testosterone level is suppressed below 50 ng/dL, which usually occurs around 200 mg per day of spironolactone in divided doses.

Estradiol sublingual tablets can be uptitrated to 2 mg SL BID. Patches are the safest option in terms of VTE risk, but carry a higher risk of failing to reach normal female levels of estradiol (80-250 pg/mL).

A JAMA article on “Management of Transgenderism” recommends checking testosterone levels (goal < 55 ng/dL) and estradiol levels (100-200 pg/mL) every three months. Also, monitor electrolytes at least that frequently.

Effects of masculinizing hormone therapy

Effects of treatment include alopecia, deepening of voice, facial and body hair, acne, increased muscle mass, clitoral enlargement, cessation of menses, and a shift in body fat from the hips and thighs to the abdomen. Other effects can include polycythemia, weight gain, dyslipidemia, elevated transamonases, irritability, high risk sexual behavior, atrophic vaginitis, and permanent infertility. However, testosterone therapy is not an effective means of pregnancy prevention.

Titrating masculinizing hormone therapy

Testosterone cypionate is FDA approved for other indications as an IM injection, but has been used as a deep SQ injection with greater tolerability. Start with 40 mg injected weekly, and increase every 4-6 weeks to 60 mg and then 80 mg, with 80 mg being a typical dose achieving normal male levels of testosterone, and 100 mg weekly being considered the maximum dose. The target trough level is around 400 ng/dL.

The above JAMA article recommends checking testosterone levels every 2-3 months, CBC and LFT every three months for the first year and then at least annually, and estradiol levels during the first six months.

Surgical options

Many trans* patients don’t undergo surgery, because they don’t want it or can’t afford it. Although a year of hormone therapy is recommended prior to “top” surgery (breast augmentation or reduction), it is not strictly required. A psychological evaluation by two mental health providers, one being a PhD-level psychologist, is required prior to “bottom” surgery, and waitlists can be long. Options for “bottom” surgery include vaginoplasty, metoidoplasty, and phalloplasty.


I would love it if you could leave a star rating and/or review on iTunes, or leave a comment or question on the website.

Image Credit

Image: Florence and Daniel, 2014, from The _________ High School Yearbook Project, by Evan Baden. Used with the artist’s generous permission. The work can be seen touring nationally in “The Outwin: Amerian Portraiture Today”

Audio Transcript

Transgender care episode transcript


Spack, Norman P. “Management of transgenderism” JAMA, 2013, V309, No5, 478-484.

Other Resources

Fenway Guide to LGBT Health (available at Amazon)

Clinical Care for Transgender and Gender Nonconforming Patients – Free eLearning Module (by CARDEA)

Exploring the Laragh method of treating hypertension


When encountering the patient with shock, we are accustomed to thinking through the possible etiologies and directing treatment accordingly. Is there a deficit of blood volume, such as from hemorrhage? Is the patient excessively vasodilated, as in sepsis or anaphylaxis? Is the shock cardiogenic?

However, when faced with the hypertensive patient, we tend to treat every patient the same, regardless of the underlying etiology. Has the time come for hypertension treatment directed at a patient’s individual pathophysiology? In the first part of today’s episode, Dr, Armando Lindner and I discuss the Laragh method of treating hypertension, which proposes to do just that. In part 2 of the episode, we discuss a few major hypertension trials, and their implications for the most important classes of antihypertensive medications.

Part 1: The Laragh method of treating hypertension

Dr. John Laragh was a clinician and hypertension researcher whose work was groundbreaking in describing the role of the renin-angiotensin axis in hypertension. He summarized his twenty-five lessons on treating hypertension and twelve clinical pearls in a 2001 review that serves as a complete primer on his method (2). A new review published in 2011 (3) provides a briefer and more recent summary.

Volume and Vasoconstriction

The first step in using Laragh’s method is understanding that patients with essential hypertension have an excess of blood volume, vasoconstriction, or both. Via the potent vasoconstricting effects of angiotensin II, the renin-angiotensin axis is largely responsible for causing vasoconstriction. The kidneys control blood volume. If a hypertensive patient has an appropriately suppressed renin level (<0.65ng/mL/hr), this suggests a renin-independent etiology of hypertension causing “low-renin,” a.k.a. “volume-mediated,” or “V-” type hypertension. If renin activity is inappropriately normal (0.65-6.5ng/mL/hr) despite a high blood pressure, or even elevated (>6.5ng/mL/hr), then there is a relative excess of renin causing “medium/high-renin” a.k.a. “vasoconstriction-mediated”, “resistance-mediated,” or “R” type hypertension.

V Drugs and R Drugs

The next key insight into Dr. Laragh’s method is that treatments correctly directed at the patient’s etiology of hypertension will be more effective and less toxic to the patient. Patients with volume-mediated hypertension will benefit most from thiazide and other diuretics, calcium-channel blockers, and alpha blockers (as the latter two cause vasoactive changes in the kidney leading to a diuresis) (12). Patients with medium to high renin levels will benefit from beta blockers, which decrease the production of renin, and ACEi/ARBs, which will block renin’s downstream effects. Patients may have both pathways at play and can certainly benefit from a mix of anti-V and anti-R therapies. In fact, hypertensive patients on more than one drug should be on a “VR combo” unless there is a strong reason to choose another combination (such as ischemic heart disease indicating BB + ACEi therapy, or a suppressed renin level even while taking one anti-V drug such as amlodipine, indicating the addition of a thiazide diuretic).

Determining a patient’s etiology of hypertension

There are three strategies to determine your patient’s renin status in order to direct the optimal therapy.

Strategy 1. Age, race, and comorbidities

First, you can use a patient’s age, race, and comorbidities. Current hypertension guidelines implicitly use this strategy (4,5,7,8,9). Patients older than 60 are generally more likely to have LREH (low renin essential hypertension), and younger patients (30-55) are more likely to have MREH/HREH. Black individuals are more likely to have LREH, hence why multiple guidelines recommend prescribing thiazides for black patients and white patients over 60 years old, while recommending ACE inhibition for younger patients (or B blockade for pregnant younger patients).

Strategy 2. Treatment response

If a patient’s blood pressure drops significantly in response to their treatment, you can assume they were correctly treated, confirming the etiology of their hypertension. If there is little response and they are confirmed to be adherant to the regimen, this might suggest that hypertension is due to the other etiology. Laragh calls this approach diagnosis ex juvantibus – diagnosis by finding which treatment helps.

Strategy 3. Plasma renin activity level

For initial treatment

The plasma renin activity (PRA) assay can help differentiate the etiology of hypertension for individual patients. It costs $30-75 in the United States, and is covered by Medicare. The lab is inaccurate in patients who have not yet ambulated on the day of testing, such as in hospitalized inpatients undergoing a morning blood draw. The test can otherwise be sent at any time of day, and the patient doesn’t need to fast, stop current antihypertensive therapy, or restrict salt intake prior to the test, contrary to prior belief(12).

Recommendations for when to use the plasma renin activity assay vary considerably. Laragh checked the renin activity on the first visit when a patient’s blood pressure is elevated, so that the information was available to help him decide the first antihypertensive drug to prescribe (2). A recent study proposed measuring PRA in those populations with prior probabilities of LREH most approaching 50% (younger black patients and older white patients, using 60 as the age cutoff), but empirically treating other populations based on predicted renin status without using PRA when starting therapy (14). Official guidelines do not make recommendations for ever using plasma renin activity in the routine management of hypertension.

For patients already being treated

There is a small randomized trial suggesting that PRA testing can be helpful in the patient whose hypertension is challenging to control. A small study randomized 39 treated-but-uncontrolled patients to clinical hypertension specialists’ care (CHSC) without the use of PRA, versus 38 patients receiving renin-test guided therapy (RTGT) by those same specialists. Although the rtgt care was provided by specialists, they followed a specific algorithm reproduced in Table 1 of the article, which could easily be used by primary care providers. The study found that blood pressure was controlled in 74% of the rtgt arm vs. 59% in the CHSC arm, although this difference was not statistically significant in this small study. Final numbers of antihypertensive medicatiosn were similar, but the RTGT arm allowed more discontinuation of medications since the RTGT started with more therapies at the time of randomization.

The authors conclude that “the number of [hypertension] specialists is quite insufficient to manage the estimated 17 million treated but uncontrolled hypertensive patients in the US. Accordingly, the RTGT algorithm emerges as a practical and objective biochemical alternative to CHSC that can be used in most clinical settings by a wide range of health-care providers for addressing the public health burden of treated but uncontrolled hypertension.”

Part 2: Antihypertensive medications and trials

Dr. Lindner shared his perspective on a handful of major trials in the treatment of hypertension.


allhat was the major trial in the early 2000s that established diuretics as the primary first-line antihypertensive. However, allhat has been criticized for a design that favored diuretics fro mthe start. Monotherapy failed to treat most patient’s hypertension in the trial, and all patients prescribed a second drug were prescribed beta blockers. A thiazide and beta blocker create a “V/R combo” treatment that is likely more effective for most patients than an “R/R combo” of an ACE inhibitor and beta blocker. Additionally, Dr. Lindner shares concerns in this episode about the excess of metabolic side effects of diuretics that were shown in the trial.


The accomplish trial found that amlodipine performed better than hydrochlorothiazide at reducing cardiovascular events when each was combined with an ACE inhibitor.


ascot-bpla studied English and Scandinavian hypertensive patients with or without diabetes, comparing a calcium channel blocker and ACE inhibitor regimen against a diuretic and beta blocker regimen. It was stopped early due to a decrease in many of cardiovascular complications used as secondary endpoints in the calcium channel blocker and ACE inhibitor group.


accord studied strict versus liberalized blood pressure control in diabetic patients, but the drugs that were used (such as alpha and beta blockers) are no longer considered firstline therapies. It found no benefit to strict control, but it is unclear whether these results would be repeated if current first-line therapies were used. Perhaps outcomes are not just driven by the blood pressure achieved, but by the specific drugs used to achieve that blood pressure.

JNC 7 vs. JNC 8

Pertinent to our discussion in this episode, jnc 8 differed from jnc 7 by recommending less stringent blood pressure targets for certain groups. Language about discontinuing ineffective medications is omitted in JNC 8, so one antihypertensive is added after another until the blood pressure is controlled. jnc 8 was not the official statement of any major society, as support was withdrawn from the individuals publishing the guideline, and a dissenting opinion was also published by other members of the committee.


The Laragh method proposes that hypertension is caused by excess blood volume, excess vasocontriction, or both. By directing treatments at the underlying pathophysiology, it is hypothesized that appropriate blood pressure control may be achieved with fewer drugs, and fewer treatment-related toxicities.


Laragh’s recommendations

1.  Laragh J. Laragh’s lessons in pathophysiology and clinical pearls for treating hypertension*. American Journal of Hypertension. 2001;14(9):837–854.

2. Laragh JH, Sealey JE. The plasma renin test reveals the contribution of body sodium-volume content (V) and renin–angiotensin (R) vasoconstriction to long-term blood pressure. American Journal of Hypertension. 2011;24(11):1164–1180.

3. Olson N, DeJongh B, Hough A, Parra D. Plasma renin activity-guided strategy for the management of hypertension. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2012;32(5):446–455.

Hypertension guidelines

4. AV C, GL B, HR B, et al. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: The JNC 7 report. JAMA. 2003;289(19):2560–2571.

5. Dasgupta K, Quinn RR, Zarnke KB, Rabi DM, Ravani P, Daskalopoulou SS, et al. The 2014 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Canadian Journal of Cardiology. 2014;30(5):485–501.

6. Furberg CD, Alderman MH. JNC 8: Shortcomings in process and treatment recommendations. American Journal of Hypertension. 2014;p. 158.

7. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: Report from the panel members appointed to the eighth joint national committee (JNC 8). JAMA. 2014;311(5):507–520.

8. Krause T, Lovibond K, Caulfield M, McCormack T, Williams B. Management of hypertension: summary of NICE guidance. BMJ. 2011;343.

9. Weber MA, Schiffrin EL, White WB, Mann S, Lindholm LH, Kenerson JG, et al. Clinical Practice Guidelines for the Management of Hypertension in the Community. The Journal of Clinical Hypertension. 2014;16(1):14–26.


10. Smith SM, Campbell JD. Cost-effectiveness of renin-guided treatment of hypertension. American journal of hypertension. 2013;26(11):1303–1310.

Comparisons of Age/race vs. PRA-guided strategies

11. Dickerson JC, Hingorani AD, Ashby MJ, Palmer CR, Brown MJ. Optimisation of antihypertensive treatment by crossover rotation of four major classes. The Lancet. 1999;353(9169):2008–2013.

12. Egan BM, Basile JN, Rehman SU, Davis PB, Grob CH, Riehle JF, et al. Plasma Renin Test–Guided Drug Treatment Algorithm for Correcting Patients With Treated but Uncontrolled Hypertension: A Randomized Controlled Trial. American journal of hypertension. 2009;22(7):792–801.

13. Preston RA, Materson BJ, Reda DJ, Williams DW, Hamburger RJ, Cushman WC, et al. Age-race subgroup compared with renin profile as predictors of blood pressure response to antihypertensive therapy. Jama. 1998;280(13):1168–1172.

14. Schwartz GL, Bailey K, Chapman AB, Boerwinkle E, Turner ST. The role of plasma renin activity, age, and race in selecting effective initial drug therapy for hypertension. American Journal of Hypertension. 2013;p. 957–964.

15. Smith SM, Campbell JD. Cost-Effectiveness of Renin-Guided Treatment of Hypertension. American journal of hypertension. 2013;26(11):1303–1310.

16. Turner ST, Schwartz GL, Chapman AB, Beitelshees AL, Gums JG, Cooper-DeHoff RM, et al. Plasma renin activity predicts blood pressure responses to β-blocker and thiazide diuretic as monotherapy and add-on therapy for hypertension. American journal of hypertension. 2010;23(9):1014–1022.

Criticism of the Laragh method

17. Moser M, Izzo JL. Plasma renin measurement in the management of hypertension: the V and R hypothesis.
The Journal of Clinical Hypertension. 2005;7(s8):32–35.

Hypertension trials

18. Dahlöf B, Sever PS, Poulter NR, Wedel H, Beevers DG, Caulfield M, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. The Lancet. 2005;366(9489):895–906.

19. Davis B, Cutler JA, Gordon D, et al. Major outcomes in high risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid Lowering treatment to prevent Heart Attack Trial (ALLHAT). Jama. 2002;288(23):2981–2997.

20. Group AS, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. The New England Journal of Medicine. 2010;362(17):1575.

21. Jamerson K, Weber MA, Bakris GL, Dahlöf B, Pitt B, Shi V, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. New England Journal of Medicine. 2008;359(23):2417–2428.

ALLHAT criticism

23. Laragh JH, Sealey JE. Relevance of the plasma renin hormonal control system that regulates blood pressure and sodium balance for correctly treating hypertension and for evaluating ALLHAT. American Journal of Hypertension. 2003;16(5):407–415. Pressor responses to antihypertensives

Pressor Response to Beta Blockers

24. Alderman MH, Cohen HW, Sealey JE, Laragh JH. Pressor responses to antihypertensive drug types. American
journal of hypertension. 2010;23(9):1031–1037.

Laragh’s website

Episode PDFs

Laragh Method Show Notes (PDF)

Laragh Method Transcript (PDF)

How to start recognizing catatonia

In this episode, I interview Heidi Combs, MD, associate professor of psychiatry at Harborview Medical Center and the course director for the University of Washington’s MS3 clerkship. We discuss the importance of recognizing catatonia in hospitalized patients on medical services, as well as her physical exam for catatonia and approach to treatment. This episode is directed to internists and internists in training, and is likely appropriate for anyone from MS3s to practicing clinicians.

The Importance of Recognizing Catatonia

Estimates of the incidence of catatonia varies, but we are likely grossly under-identifying it by misidentifying it as delirium or pharmacologic over-sedation. It has been estimated to affect up to 4% of patients in medical ICUs and likely affects many hospitalized patients on medical services as well.

Catatonia can develop in the setting of psychiatric disease (bipolar disorder is actually more commonly associated with catatonia than schizophrenia is), medical conditions (the list is long but includes infections, electrolyte disorders, autoimmune conditions and endocrinopathies), or medications (benzodiazepine downtitration or withdrawal, and the addition of antipsychotic agents). It can also develop in patients without any identified risk factors.

The Catatonia Exam

The 23-item Bush Francis Catatonia Rating Scale is used to grade catatonia severity (each item is scored 0-3), and the 14-item Bush Francis Catatonia Screening Instrument is used to screen for catatonia: 3 items is considered a positive screen, and even with 2 items, catatonia should be strongly considered.

First, observe the patient and speak with the patient. Do they have negative motor symptoms: Immobility/stupor  or staring? Do they have positive motor symptoms, such as excitement, grimacing, mannerisms, or stereotypy?

Then speak with the patient. Do they copy what you say (echolalia) or make repetitive statements of their own (verbigeration)? Is there a complete or relative paucity of verbal production or long speech latency? This would classify as mutism.

Examine the patient for rigidity by moving their arm around at the elbow and wrist joints. if they push harder the harder that you push in any direction, this is called negativism, a.k.a gegenhalten. Instead of placing their hand down gently, let go with the arm above the bed, to see if it remains in place (waxy flexibility).

Ask the patient to put their hands out in front of them with the palms down (like checking for pronator draft, but pronated instead of supinated). Instruct the patient NOT to let you move their hand up any further. Then apply gentle upward pressure to the palms. Do they let you easily raise their arms? This is the anglepoise lamp sign, also known as passive obedience or mitgehen.

Tell the patient “do not shake my hand. I do not want you to shake it.” Then extend your hand for a handshake. If they shake your hand, or vacillate between extending their arm and bringing it back for an extended period, this is ambitendency.

Without giving instructions, abduct your arm and dramatically shake your head, like a monkey. If the patient copies you, this is echopraxia.

Reach into your pocket, and tell them “Please stick out your tongue so that I can put a pin in it.” If the patient then sticks out their tongue, this is abnormal and is considered automatic obedience.

Two or three positive findings suggests a clinical diagnosis of catatonia, which is reason enough to start a benzodiazepine trial in order to treat obvious cases and help confirm the diagnosis in questionable cases, if the patient has a positive response to treatment. A negative response does not rule out catatonia, since roughly 30% of patients may not improve with benzodiazepines alone, so zolpidem or memantine could also be tried.


You can perform a benzodiazepine trail by giving 1mg of ativan IV, and re-examining the patient roughly 30 minutes later. Many patients require higher doses to achieve a clinical response. You could go to ativan 1mg PO TID after the initial trial, then try 2mg PO TID, 3mg PO TID, 4mg PO TID, up to 6mg PO TID, uptitrating every two doses, and stopping when the patient seems fully treated or sedated.

Have you ever given your patients Ambien (zolpidem) in the morning? Patients with catatonia will actually become more interactive with zolpidem (e.g. 5mg). This is an alternative agent that can be tried if the response to benzodiazepines is incomplete.

For emergent cases, or those not responsive to benzodiazepines, consider ECT.


Carroll, B. T., et al. “Treating persistent catatonia when benzodiazepines fail.”Current Psychiatry 4 (2005): 56-64.

Saddawi-Konefka, D., Berg, S. M., Nejad, S. H., & Bittner, E. A. (2014). Catatonia in the ICU: An Important and Underdiagnosed Cause of Altered Mental Status. A Case Series and Review of the Literature*. Critical care medicine, 42(3), e234-e241.

Weder, Natalie D., et al. “Catatonia: a review.” Annals of Clinical Psychiatry20.2 (2008): 97-107.


Catatonia Episode Transcript

Welcome to OslerCast! A new internal medicine podcast

Launching in early 2015, OslerCast will be an audio podcast which will cover topics relevant to the practice of internal medicine. I will focus on content that is relevant to the resident level all the way up to that of practicing internists, but I also hope that a significant portion will be of interest to MS3s and MS4s as well. I am a medical resident in the categoral track (and clinician educator pathway) of the University of Washington’s Internal Medicine residency program.

I was inspired to create this podcast because of the robust and exciting global discussion that has been building in the fields of emergency medicine and critical care, and has been dubbed “FOAM” or “FOAMed” (that’s free, open-access online medical education). I’ve been listening to incredible medical podcasts such as EMCrit, ERCast, SMART EM, and EM:RAP and thinking “there should be something like this, but for internal medicine!” I’m pleased to say that those behind EM:RAP have created a new podcast called Primary Care:RAP, but since it costs money and most internists aren’t already listening to podcasts, I expect uptake to be unfortunately slow (despite recommending it to my friends).

Central to FOAM’s mission is cultivating asynchronous, contextual education with post-publication peer-review. It’s been effectively harnessing the power of social media platforms to help teach a new generation of physicians. Last year, the FOAMed community even pointed out an error in a NEJM article on decolonization which led to a correction being published, adjusting the intervention’s NNT by a factor of 2. I hope that this podcast will bring even more internists into that vibrant online discussion.

I hope to have more for you here soon. Here’s how you can follow OslerCast going forward, in order from most important to least important:

1.Subscribe to the podcast RSS feed:
I recommend using the DownCast app for iPhone, since I often zone out briefly when listening to podcasts and it has a great 30 second rewind button.

2. Subscribe to this website’s RSS feed:
I recommend an RSS aggregator like Feedly.

3. Follow @OslerCast on twitter.

4. Join the email list.

Welcome to the #FOAM revolution.