Are friends for hire a solution to loneliness?

Just out of college, one of my friends quit his good-paying, stable job at a big midwestern company to start a "jack of all trades" handyman business. He and another of our college friends mowed lawns, rebuilt decks damaged by tornadoes, repaired drywall, fixed sprinkler systems, and did other odd jobs. General handyman stuff. 

One day he was called to a house to change light bulbs. This was a common call; it was easier for people to call him than to get their own ladder and defy death above a stairwell. When he finished, the elderly lady who'd called him offered him a glass of water and a seat while she paid the bill. 

"How much would it cost to have you here weekly?" she asked. Again, this wasn't an uncommon request. Many people kept him on retainer and had him come by periodically to do little jobs. My friend eased into his spiel about the packages he had available, and what services were available at each price point. 

"No, no," she said. "How much would you charge just to come by and talk?"

I don't know what happened after this. Every time I heard him tell the story it ended there with all of us groaning about how sad it all was. How sad that an old lady was so lonely that she was willing to give money for company. The reason I bring the story up at all now is that I just read "How to Hire Fake Friends and Family" by Roc Morin in The Atlantic. 

"[Ishii Yuichi]'s 8-year-old company, Family Romance, provides professional actors to fill any role in the personal lives of clients. With a burgeoning staff of 800 or so actors, ranging from infants to the elderly, the organization prides itself on being able to provide a surrogate for almost any conceivable situation."

Some details are heart-wrenching: single moms hiring men to pose as Dad so they aren't discriminated against. Some of them are creepy: one of those single moms has never broken it to her daughter that Yuichi isn't her real dad after eight years. Some of them are downright strange, like this example of surrogacy that seems right out of an Uday and Qusay tale:

"Usually, I accompany a salaryman who made a mistake. I take the identity of the salaryman myself, then I apologize profusely for his mistake. Have you seen the way we say sorry? You go have to down on your hands and knees on the floor. Your hands have to tremble. So, my client is there standing off to the side—the one who actually made the mistake—and I’m prostrate on the floor writhing around, and the boss is there red-faced as he hurls down abuse from above."

Because of the "Romance" in the company name, I suppose, and to head off the inevitable comparison to prostitution, no, Yuichi and his workers do not provide sex. He claims that they aren't even allowed any physical contact besides hand-holding.

I've written several times in the short life of this blog about the dangers of loneliness. I've spoken about it even more. So this post isn't meant to poke fun at the sometimes bizarre social norms like this that crop up in Japan. They may only be bizarre to my western eye. After all, much of what we do in medicine, particularly in palliation, boils down to the act of being present for a person. And sometimes that's the hardest thing of all. My friend didn't take the lady's money for his company. But even if he had, I think we could argue he'd earned it. 

In the words of Yuichi himself, "It feels like work to care for a real person."

Links for Tuesday, November 21, 2017: more on the new HTN guideline, Gymnastics coaches throwing robot shade, the last iron lungs, Germany bans smartwatches, and Raymond Chandler hated US healthcare

Thoughtful post on the new HTN guideline by Dr. Allen Brett

Representative quote: "Consider, for example, a healthy white 65-year-old male nonsmoker with a BP of 130/80 mm Hg, total cholesterol level of 160 mg/dL, HDL cholesterol of 60 mg/dL, LDL cholesterol of 80 mg/dL, and fasting blood glucose of 80 mg/dL — all favorable numbers. The calculator estimates his 10-year CV risk to be 10.1%, making him eligible for BP-lowering medication under the new guideline. To my knowledge, no compelling evidence exists to support drug therapy for this person."

A gymnastics coach says the Boston Dynamics robot flip was a 3.5/5.0

'In a back salto, says Mazloum, “you want to be able to go as high as you can, and you want to be able to land as close to where you take off as possible.” To do that, the gymnast has to squat, throw her arms up by her ears so her body is a straight line (in gymnast-speak, opening the shoulder angle and the hip), then contract into a “closed” position again. By these standards, Atlas’ trick is “not the cleanest flip,” explains Mazloum.

Here’s Mazloum’s critique: Atlas didn’t quite get to that open position, “so it didn’t really get the full vertical that we look for. That’s why it went backwards a little bit.”'

The last of the iron lungs

Get your kids vaccinated for polio, folks.

Germany has banned smartwatches for kids

If I understand this correctly, it is not because smartwatches cause kids to be distracted monsters (although I don't doubt that that statement is at least a little bit true). The decision stems from the capability of bad guys to hack in and monitor the location of little Dick and Jane:

You have to wonder who thought attaching a low-cost, internet-enabled microphone and a GPS tracker to a kid would be a good idea in the first place. Almost none of the companies offering these “toys” implement reasonable security standards, nor do they typically promise that the data they collect—from your children—won’t be used be used for marketing purposes. If there ever was a time to actually sit down and read the terms and conditions, this was it.
Get your shit together, parents.

Asking parents to destroy them might be a bit of an overreaction, though.

Raymond Chandler paints a dark picture of American healthcare in a newly-discovered story

The title, "It’s All Right – He Only Died," sounds like the title of a video residencies would show interns to convince them that quality improvement and patient safety are part of their job.

The doctor who turned away the patient, Chandler writes, had “disgrace[d] himself as a person, as a healer, as a saviour of life, as a man required by his profession never to turn aside from anyone his long-acquired skill might help or save”.


Should young, healthy people with type 1 diabetes take statins?

I encountered this question a couple months ago in a consult and intended to blog about it then, but relatively little trial data was available. I would have essentially been giving my own off-the-cuff opinion. That's very unsatisfying to me, and probably to the reader.

As background: we tend to think of type 1 diabetes as more a need for hormone replacement (insulin) than as a disease state requiring the complex management that type 2 diabetes requires. That is to say that type 1 diabetes, for all the unpleasantness it causes for people, is easier on the blood vessels as a general rule than type 2 diabetes. The ADA has a statement in its guideline that "For patients with diabetes aged <40 years with additional atherosclerotic cardiovascular disease risk factors, consider using moderate-intensity or high-intensity statin and lifestyle therapy." It's a category C recommendation, meaning it's mostly opinion and has a less-than-spectacular evidence base. It also doesn't differentiate between type 1 and type 2 diabetes. Similarly, a joint statement by the ADA and the AHA states that "Adults with T1DM who have abnormal lipids and additional risk factors for CVD (eg, hypertension, obesity, or smoking) who have not developed CVD should be treated with statins." Both statements argue against the routine use of statins in young healthy type 1 diabetics.

But a recent study from the New England Journal helps us with the question of statins in kids, and throws in ACE inhibitors for good measure. Investigators led by M. Loredana Marcovecchio and Scott T. Chiesa randomized 443 kids between 10 and 16 years with type 1 diabetes and urine albumin-to-creatinine ratios in the upper third of "normal" to some combination of ACE inhibitor, statin, and placebo. Creatinine is a consistently excreted product of muscle metabolism that serves as a nice comparator for other things the kidney excretes. So even if you drink a lot of water and dilute the amount of albumin in your urine, we can look at it compared to the similarly diluted creatinine and see if you're excreting too much.

Anyway: the investigators used a 2 x 2 trial design, meaning that there were ultimately four groups: placebo-placebo, placebo-ACEi, placebo-statin, and ACEi-statin. The statin was atorvastatin 10 mg daily, and the ACEi was quinapril 10 mg daily (after titration). They were most interested in the change in albumin excretion (that is, how much protein spilled through the kidneys into the urine). They assessed this according to that same measure, the albumin-to-creatinine ratio in the urine, from three early-morning urine samples obtained every 6 months over about two and a half years. They also looked at secondary outcomes like the new development of microalbuminuria (that is, the new appearance of protein in the urine), worsening of eye disease, changes in kidney function, blood lipid levels, and measures of cardiovascular risk. For the cardiovascular risk, they did ultrasounds of the carotids to measure the thickness of the vessels (carotid intima–media thickness) and measured levels of high-sensitivity C-reactive protein and asymmetric dimethylarginine in the blood. Both of these are generic markers of vascular risk.

After an average of 2.6 years, no benefits were found within the ACEi group, the statin group, or the ACEi+statin group compared to placebo. Unsurprisingly, the ACEi group had a much lower incidence of new microalbuminuria, but "in the context of negative findings for the primary outcome and statistical analysis plan, this lower incidence was not considered significant (hazard ratio, 0.57; 95% confidence interval, 0.35 to 0.94)." Also unsurprisingly, the use of statins resulted in lower cholesterol levels (including, unfortunately, HDL). But neither drug had significant effects on carotid intima–media thickness, C-reactive protein, kidney function, or progression of eye disease.

So we can take away from this small-ish study that, at least in a short amount of time in pretty healthy twelve-year-olds (the subjects were excluded if they had genetically bad lipid levels; the participants' average A1c was ~8.3% and their average blood pressure was 116/65 mmHg), there was no benefit to statins or ace inhibitors. This study will influence my recommendations to patients and other docs in the future. The kicker, naturally, is that many young people with type 1 diabetes have imperfect blood sugar control. What about those who can't get their diabetes controlled? It's a tougher call in that case, and this study didn't address it. 

The Gingerbread Man: an iStory

“You should go as the Gingerbread Man,” she said. “I'll be the fox!”

“It's kind of played out, isn't it? Women as foxes?” I replied.

She glanced at my leg. “Well, I could go as the old lady or the farmer. But you have to be the Gingerbread Man.”

“You could be Little Red Riding Hood and I could be the Big Bad Wolf,” I offered.

“Meh. It just wouldn't be the same. Don't you think this would be fun? You never want to have any fun with this. Shouldn't we take advantage?” She looked down at me again.

I didn't bother to offer Hansel and Gretel.

On Halloween I wore a brown shirt and pinned up the right leg of my brown pants. I left my prosthetic leg at home. I left my crutches home, too, so I leaned on her all night. When we got home, I was just under a quarter gone.

What do we do with a free testosterone?

Put another way: what's the free testosterone cutoff we should use for initiating treatment in potentially hypogonadal men?

Spoiler alert: maybe 70 pg/mL?

Background: a new paper from Anna Goldman, Shalender Bhasin, Frederick Wu, Meenakshi Krishna, Alvin M Matsumoto, and Ravi Jasuja lays out their thoughts on the state of the science in free testosterone measurement. This is important because we currently operate under a theory of "bioavailable testosterone." That is, we think that only testosterone that is unbound by proteins, the most important one called "Sex Hormone Binding Globulin," or SHBG, has any effect on the testosterone receptor. All the testosterone that's floating around attached to SHBG or other proteins is inert.

But like any other hormone, testosterone's binding to SHBG or other proteins is affected by myriad causes, like obesity, other hormonal disorders, and other conditions or medications. Even the temperature at which it's measured. So guidelines from the Endocrine Society suggest measuring free testosterone levels in men whose total testosterone concentrations are low-ish and in men with conditions or medications that make total testosterone measurements less reliable (like obesity). But those same guidelines rely almost entirely on the total testosterone to determine who needs testosterone therapy. From their 2010 guideline:

The panelists disagreed on serum testosterone levels below which testosterone therapy should be offered to older men with symptoms. Depending on the severity of clinical manifestations, some panelists favored treating symptomatic older men with a testosterone level below the lower limit of normal for healthy young men [280–300 ng/dl (9.7–10.4 nmol/liter)]; others favored a level less than 200 ng/dl (6.9 nmol/liter). The panelists who favored treating men who had values less than 300 ng/dl were more influenced by the observation that men who have values below that level often have symptoms that might be attributable to low testosterone. The panelists who favored not treating unless the serum testosterone was as low as 200 ng/dl were more influenced by the lack of testosterone treatment effects in randomized clinical trials when subjects had pretreatment values of 300 ng/dl but suggestions of beneficial effects when the pretreatment values were closer to 200 ng/dl. The lack of definitive studies precludes an unequivocal recommendation and emphasizes the need for additional research. [emphasis mine]

No mention of the free testosterone in there. More research needed, they say. Well, Goldman et al have delivered it, in a way. They didn't do any new investigation, so far as I can tell, but they did review the existing literature pretty thoroughly and come up with a series of conjectures. The most important of these clinically is this (my words, not theirs):


Without a harmonized, replicable normal range between laboratories and methods, we cannot set a clinical threshold for free testosterone levels at which we should initiate treatment.


The authors point out that in a study by Le et al, only about a quarter of labs performing free testosterone assays would even confirm that they had performed validation studies on their assay. But seeking a clinically relevant answer, they go on to point out that In the Framingham Heart Study, the lower limit of the normal range for the calculated free testosterone for men between 19 and 40 (defined as the 2.5th %ile) was 70 pg/mL (242.7 pmol/L). They do not endorse this as a threshold. But given the lack of other published thresholds, I think it is at least a start. 

One more point before I wrap up: whatever value you or your doctor use, whether it's free testosterone, bioavailable, or total, the number is only one piece of data. A free testosterone of 70 pg/mL in a young man with normal body hair, normal muscles, and a normal libido would not cause me to treat him. That same level in a man with a known pituitary issue, enlarging breasts, and fatigue would definitely cause me to treat him. And I tend not to recommend checks of testosterone in elderly men, even those with fatigue, unless they have other compelling evidence of hypogonadism. And my opinion is generally in line with that of the Endocrine Society:

We recommend against a general policy of offering testosterone therapy to all older men with low testosterone levels. (1|⊕○○○)

We suggest that clinicians consider offering testosterone therapy on an individualized basis to older men with low testosterone levels on more than one occasion and clinically significant symptoms of androgen deficiency, after explicit discussion of the uncertainty about the risks and benefits of testosterone therapy. (2|⊕○○○)

Why else do I hesitate to give testosterone? In a series of trials in JAMA and JAMA internal Medicine earlier this year, men aged 65 and older with a total testosterone level <275 ng/dL plus either sexual or physical dysfunction or reduced "vitality" were randomized to get either testosterone gel (lotion that absorbs through the skin) or placebo for 1 year. The men who got testosterone developed more coronary plaque than the men on placebo. (This may or may not mean anything; in other observational studies, the rate of heart problems was lower in men prescribed testosterone than in untreated men). 

Importantly for the men who tend to come to me with suspected androgen deficiency, though, the men in these studies had no improvement in memory or other measures of brain function.

Testosterone did slightly improve bone density and bone strength compared with placebo. And testosterone seems to have improved the hemoglobin level (the weight of the oxygen-carrying protein in our blood) in anemic men by 1 g/dl more often than placebo did.

If all that sounds confusing, it's because it is. When I was an endocrine fellow, one of my faculty told me that in almost every case, if you don't know what to do, the correct path is to do nothing. So that's the direction I lean in borderline androgen deficiency cases, whether determined by total or free testosterone levels. I lean toward withholding therapy. 

Are triathlons dangerous?

First things first: I've never done a triathlon. I swim like a St. Bernard. But I've done a lot of endurance bike racing, and I've been at more than one event with a death, the most recent the 2017 Dirty Kanza. So I was interested that in the latest Annals of Internal Medicine, investigators looked into a sudden death database to identify 135 race-related deaths and cardiac arrests in American triathlons between 1985 and 2016. Interestingly, right at two-thirds of deaths and arrests happened in the swim part of races, which usually comes first, before the bike and run. The editorialists spend a lot of energy trying to link swimming to some special form of stress from cold water or other factors that might be extra-dangerous. But to me, the swimming link seems consistent with the finding that in autopsies, about half of subjects had cardiovascular abnormalities, most often old-fashioned atherosclerotic disease. Swimming caught most of these people simply because it was the first event. Had running or cycling come first, I suspect one of them might have been the death leader. I'm not convinced by their observation that most marathoners die toward the end of races; anyone who's seen the scrum at the beginning of a triathlon knows that it's inherently different than the often walking pace seen at the start of a marathon: 

From, triathletes tempting fate.&nbsp;

From, triathletes tempting fate. 

85% of victims were male, but I'm not sure the significance of that number, since >60% of participants (at least in pro Ironman races) are male:



And if you look at total Ironman competitors, the distribution of sex comes much closer to the death/cardiac arrest statistics:


But sex aside, we're forced to see that cardiac arrest and death are not rare among triathletes. Between 2006 and 2016, their incidence was 1.74 per 100,000 participants in the study. The risk of death increased with increasing age, unsurprisingly. Don't let this dissuade you from being more active. The benefits of physical activity far, far outweigh the risks in almost everyone. If you're inactive now and thinking of becoming active, or if you're active now and thinking of doing really hard-core things like triathlon, consider taking the American College of Sports Medicine's new-ish algorithm to your doctor and talking it over before you hit it really hard:


We don't know how really weird stuff like performance enhancing drugs effects this. My suspicion is that it's not good. 

Is it too early for a Halloween reading list?

I picked up a copy of We Have Always Lived in the Castle by Shirley Jackson last week at the library:

You'll be missed, Wichita Public Library. #brutalismforever

You'll be missed, Wichita Public Library. #brutalismforever

It is a Gothic masterwork, and the speculation it allows around the psychopathology of Merricat and the townsfolk who hate her and her sister and uncle is irresistible.

Even though I didn't choose it with the intention of kicking off any kind of Halloween-y creepy reading list, now that I've started The Handmaid's Tale by Margaret Atwood, it seems I've inadvertently waded into Gothic waters. Atwood is incredible, but I'm in the mood for something a little more straightforward. So I've made it official: my next book will be It by Stephen King. I was a voracious King reader as a high-schooler. And a copy of Salem's Lot I found in a call room nightstand once got me through a snowy, slow call night as a resident. I left the book there when I finished, and I have wondered many times since how many residents at Deaconess Medical Center have found that same book and killed a couple hours with it. I know, I know, that King is hardly literary. His is not necessarily the kind of reading that increases empathy, but since It is currently crushing it (see what I did there?) at the box office and in critical reviews, it's time.

Assuming I can get through It's 900+ pages in the next few weeks, what other creepy-crawly books should I attack before All Hallow's Eve?

Once more to the lake for Labor Day

When I read the words in EB White's Once More to the Lake, I ache. His description of the smell of wood, the feel of the water, and the schedule set by the sun gives me a completely unearned sense of nostalgia. Most of my summer (and adult) trips to the lake have been marked by the anodyne scent of an RV air conditioner and the coconut-tainted slip and slide of sunscreen. But I ache for microwaved biscuits and gravy and cheese sandwiches and kool-aid. I can smell the fishy water covering the sandstone shore of Wilson Reservoir. I can see the treeless lunar landscape. 

Wilson Lake Rocktown 2010 (500x375).jpg
Pics from

Pics from

So this is your permission from me--not that you were seeking it--to engage in a Great American Pastime and head to the lake for Labor Day. Do it before the McMansions obliterate any of the charm that EB White talked about:

From &nbsp;Answer? No, I hope.&nbsp;

From  Answer? No, I hope. 


Do it even though, unlike him, you won't be able to spend a month there. Do it because someday you'll wonder what you've done with your life, and the answer of "I took my [kids/wife/husband/friends/enemies] to the lake once in a while, and we had fun and made memories" is better than "I got high and played a lot of video games."

Happy eclipse day!

Before you see the sun obscured by the moon for yourself, read Annie Dillard's Total Eclipse.

I saw, early in the morning, the sun diminish against a backdrop of sky. I saw a circular piece of that sky appear, suddenly detached, blackened, and backlighted; from nowhere it came and overlapped the sun. It did not look like the moon. It was enormous and black. If I had not read that it was the moon, I could have seen the sight a hundred times and never thought of the moon once.

Follow-up on medical school rank and narcotic prescriptions

I've had several conversations with fellow docs about the NBER paper from last week showing a relationship between medical school rank and narcotic prescriptions. Naturally, the responses I got were pretty skeptical. A recurrent theme I ran across was that the authors didn't pay enough attention to practice setting. 

1. Higher-ranked medical schools tend to produce more students who eventually land in academia, often at higher-ranked medical schools or residency programs.

2. Because of the culture of those high-performing places, characterized by greater access to subspecialists, a slower pace of practice, the presence of trainees to keep you honest and whatnot, you practice more conservatively and without fear of patients firing you for not giving them narcotic prescriptions.

 3. Perhaps people graduating from lesser-ranked schools end up in private practice, where there is more pressure to write a narcotic prescription to all those patients with back pain, just to keep them from 1) firing you, and 2) telling all their friends and family what a crappy, uncaring doctor you are.

4. So the speculated end result is that people graduating from higher-ranked medical schools end up writing fewer narcotic prescriptions than their peers from lower-ranked schools.

I pointed out to several people that the study took into account specialty and location; the relationship held for people in the same specialty and same county. The investigators pontificated on practice setting (noting that DO graduates often take care of a more rural, white population, for instance). But they didn't control for it. So I held my hands up ¯\_(ツ)_/¯ and moved on with my life.

But then I listened to a segment about it on the Weeds podcast today (start at 1:01:25):

UPDATE: I'm having some trouble embedding the audio, so if you can't get it to play, go here:

Sarah, Ezra, and Matthew made note that the relationship held within the same clinic, so I re-visited the paper. I found this: 

Check the footnote. *slaps forehead*

Check the footnote. *slaps forehead*

So the investigators did account for practice setting, but since it was hidden in a footnote, I missed it. 

The take-home from this paper is still kind of hard to identify. I'm not in favor of necessarily checking the LinkedIn page of every doctor you see to check what med school she went to, but there is clearly some kind of relationship between the culture of medical schools and the prescribing behavior of graduates.

The lower-ranked your doctor's medical school, the more likely he'll write you a narcotic prescription

You read that headline right: investigators in an NBER paper found that docs who went to a lower US News-ranked school are more likely to write narcotic prescriptions, and the ones who write narcotic prescriptions are likely to write for more drugs, depending on the ranking of their school. And lordy, those osteopathic schools:

US News publishes several rankings, in topics from research to primary care to women's health. For this paper, the investigators used the "research" ranking, which is difficult to translate into medical student bedside education. After all, some of my best teachers in med school hadn't published a paper in a decade.

Several other take-home points from this. First, at first glance general practitioners write a ton of narcotic prescriptions; their rate on the y-axis is roughly double the overall physician population's. But when you consider that primary care docs perform well over half of all the visits delivered, that number of narc prescriptions looks less impressive.

Second, the effect size, if you're willing to take a leap and go straight to the idea that the quality of research at your medical school somehow has a causative effect on how many hydrocodone prescriptions you write, is huge. Using Harvard as the index school, the schools in the eighties and nineties have graduating docs writing three times as many prescriptions.

My first thought when I read this was that docs who went to lower-ranked schools may end up on places where they're more compelled to write narcotic prescriptions: places with high poverty, or a large blue-collar workforce, for instance. But the investigators accounted for that, and found that the relationship persisted even within the same county:

I can't help but try to apply this research to myself, even though I'm an endocrinologist and therefore mostly shielded from the narcotic game, and even though I see relatively few patients nowadays. But here we go. I attended the University of Kansas, which is comfortably ensconced in a tie at number 65 on the research list:

Oof. Medical school got a lot more expensive in the last couple decades.

Oof. Medical school got a lot more expensive in the last couple decades.

So where would I live in the narc prescribing graph?

Riiiiiiiiight about there. It's a wonder I'm not a bonafide narcotic prescribing machine.&nbsp;

Riiiiiiiiight about there. It's a wonder I'm not a bonafide narcotic prescribing machine. 

What's unsaid in this list is that KU has three campuses (two at the time of my training). And it further goes without saying that the training in Wichita, Salina, or Kansas City may have subtle differences that would lead to slightly different physician performance or behavior. Furthermore, it would be interesting to see the research repeated with residency or fellowship training as the independent variable, since those are the years when trainees really fall into a groove of prescribing habits. If I were held to the standard of my internship with a University of Washington program, I'd be compared to the folks at the skinny end of the graph:

Go dawgs.

Go dawgs.

But if my fellowship training at UNC-Chapel Hill were the standard, I'd be in a nice, comfortable happy medium between the narc-crazed sixties and the narc-stingy pre-teens:

The take-home from this isn't that we should all check our doctors' CVs before we go see them, in fear of them hooking us on oxycodone. It's just that schools who inhabit the lower tiers of medical research need to do a better job of teaching narcotic prescribing. 

And obviously, the take-home for patients is to be very, very careful about requesting narcotics for pain. They don't work as well as we think they do, and the potential for harm is huge. 

I found this link, fwiw, via

Hormonal diseases in literature

I have three favorite pieces of endocrinology-themed fiction.

The short story "Baster" by Jeffrey Eugenides, was featured on this week's New Yorker Fiction podcast. It is in his collection of short stories Fresh Complaint, to be released this fall. "Baster" was adapted into the movie The Switch with Jason Bateman and Jennifer Aniston, but only the first half of the movie, where Wally obsesses over Kassie's impending insemination and eventually switches his own specimen for her better-looking donor's, is drawn from the story. The rest of the movie, dealing with Wally's growing affection for his neurotic son and his eventual confession, are new. 

My absolute favorite piece of endocrinology-related fiction is Middlesex, also by Jeffrey Eugenides.

It tells the story of consanguinous parents of a child born with 5-alpha reductase deficiency, a hormonal disorder in which male children do not make enough of the active male hormone dihydrotestosterone.

The red line is the enzyme defect we're talking about here. Image from Wikipedia.&nbsp;

The red line is the enzyme defect we're talking about here. Image from Wikipedia. 

This causes them to be very feminized at birth, with a micropenis and undescended testicles. They were often raised female before the disorder was well-known. But at the onset of puberty, people with the disorder suddenly and sometimes dramatically get male features. Callie (later Cal) is the narrator, and his gender identity evolves in parallel with the family's experience in immigrating from Asia Minor to Detroit, then to San Francisco. It's fantastic.

Finally, the novel The Amazing Adventures of Kavalier and Klay, by Michael Chabon, has a clever endocrinologic twist at the beginning. 

It starts off with one of the main protagonists, Josef Kavalier, escaping to New York from Prague, Czechoslovakia by being concealed inside the coffin of the Golem of Prague, a clay mannequin, by his magic teacher, Kornblum. The giant clay mannequin is clothed in the suit of a giant obtained from a deceased patient of Josef's endocrinologist father. It's the first of several escapes by Joe in the book (first from Nazi Europe, then from poverty, then from Antarctica, then from loneliness). The book concludes with (spoiler alert) Sammy, his best friend and cousin, escaping from life as a closeted homosexual. Haunting book.