Author: Karthik Balachandran

Endocrinologist. Jipmerite through and through. Data science enthusiast.Loves reading and writing about the intersection of technology and medicine.

Do debates actually harm medicine?

It was during the second year of DM , I was exposed to an interesting kind of academic activity in a conference -the medical debate. The issue in question was a thorny one – with conflicting data. The speakers were excellent and put forth brilliant points for and against the motion. As it so happened, they were both comparable not just in their credentials as doctors but also in their public speaking and debating skills.
As I attended more conferences, it soon became clear the debates were a fixture in many medical conferences and were eagerly awaited by the audience. The speakers in turn tried to do as much justice to the topic as possible. Unfortunately there were some problems

  • Some speakers were better than others – and their point of view was more likely to resonate with the audience
  • Even if the speakers were convinced of the other person’s argument to some extent, it soon became a contest in hyperbole

Most importantly it became a contest between individuals and not ideas. This is of course, entirely predictable to anyone who knows how the human mind works. We back people with ideas, not just ideas. Arjuna vs Karna, Tesla vs Edison, Steve Jobs vs Bill Gates – we revel in the great individual rivalries. You might scoff at this rather ridiculous over simplification. After all, the attendees of conferences are highly educated people, not given to emotional support of one speaker or the other.
Unfortunately, education doesn’t make us immune to biases and blind spots. The nature of the debate means that, the speakers have little incentive to expound on the gray areas and are forced to make emphatic statements in front of an audience baying for certainty. Medical science is rife with uncertainty and it is this uncertainty that make it interesting. To dissect the gray zone in which the debate occurs, the speakers and the audience need to know a lot of details. Some of these details like statistics are boring to the average listener ,but is at least available in public domain. Others are effectively hidden from the prying eyes of the public and are probably sleeping safe in the digital vaults of the companies that conduct the studies.
The need for certainty of the average audience member and the near universal reluctance to dig deeper into difficult topics makes it much harder to convey the nuances involved. At the end of the day, the audience are at risk of taking home the message they understand / like the best – setting the stage for eloquence based medicine. So I wondered, if the non-specialist audience could be influenced by the better speaker in the debate, would it make sense for the companies to ask for a particular speaker to speak for their product? Perhaps I’m being too cynical – I will leave it to your judgment. The moderator of the debate should be a person with impeccable credentials and should be able to rise above the need to simply give the audience some satisfying soundbites. Luckily in most debates this is the case – but not always.
More than posters, oral paper presentations and invited orations, debates spark enormous interest. With great popularity,comes great responsibility. Sometimes, I wonder if the moderator should make slide – instead of , or after the rebuttal. People remember what they see – so this should probably tilt the balance towards the truth (if one is known).

After every debate, I’m reminded of the final scene in the Kamal movie Nayagan, where the don’s grandson asks him a very simple question “Neenga nallavara,kettavara? (Are you a good man or bad man?)” – to which Kamal replies ‘I don’t now”. Some audience are like Kamal’s grandson – hoping for a simple answer to a very complex and nuanced question. I wish we had Kamals to tell them the truth.


The T-score tamasha

Elderly people fracture when they fall, more often than the youngsters. In order to know who is at high risk, so that we can intervene before the fracture, doctors measure how much bone a person has. This is called bone mineral density (we also need to measure bone quality, not just quantity – but that’s a post for another day)

Bone mineral density is measured by a machine called DEXA.(dual energy xray absorptiometry). What we are measuring is the content of the mineral per unit volume. However only have two dimensional measurement – so we express it as gm /cm2.
Now imagine this – you are checking blood glucose and want to know if it’s normal. You have a value and if it exceeds a particular number, you have diabetes. Unfortunately in bone density, we don’t compare the g/cm2 units . Instead we have two unwieldy scores called T scores and Z scores. The T score is (to put simply) as measure of how far away from the avg bone density of a person in the prime of youth. The Z score is a measure of how far away from your peer group (age). Both these change depending on who you take as reference.
In 1994, the WHO defined osteoporosis as T score of less than /equal to -2.5. This means that approx 1/100 people in their 30s have a bone density as low. Pretty simple.
Unlike bone density, no other parameter in modern medicine is compared to the values in the youth. We don’t say only 1 in 1/100 young women have higher waist circumference (thankfully), even though many biological parameters get worse with aging.

How did this happen?

Back in the 1990s, when DEXA machines became commercial, only three companies were making the machines. They still do. Norland, Hologic and GE. Let’s take a detour and see how a DEXA machine works. It is surprisingly similar to an Xray. X rays are passed from the top and are received at the bottom. The patient lies down in the middle. If the patient’s bone block more X rays from reaching the receiver, we conclude she has more bone. Or bone mineral. Pretty simple right? Well not quite.
From this generalization, we need to convert the attenuation( the loss of xrays while passing through the patient) into an estimate of bone density. Since the patient isn’t a skeleton, the Xrays pass through other stuff like muscles, fat and organs, each of which cause some attenuation. This is also why we can calculate the fat and muscle mass with a DEXA machine. The algorithms which convert this attenuation into the bone mineral density estimate – in gm/cm2 are complex and proprietary.
Because of this proprietary algorithms, the same person’s bone mineral density when measured by a GE Lunar would be, say 6% higher than the same bone mineral density measured by a Hologic machine. Now that’s like saying you measure tomatoes by two balances and one shows 1 kg and the other shows a little more. The natural tendency is to ask which is right? Or perhaps work towards standardizing the measurement.
To standardize measurement, the companies had to work together on the innards of the DEXA machine. Alas – they didn’t. Instead, they decided to bring in a statistical definition based on T and Z scores.

Ever since, the doctor community adopted what the big corporate boys decided. Unfortunately not all doctors like numbers (I know some who absolutely detest math). This has caused a situation where just to interpret a bone density measurement, you need to deal with unwiedly concepts like mean, standard deviation, scores etc. As a side effect, it has made doctors learn these concepts well and think about how their population varies compared with the Caucasians. (a thinking that’s almost never seen when interpreting any other test).

When a change comes, it brings both good stuff and bad stuff along. The yin and yang, the dark and light always exist together. It’s upto us to focus on the good.

Walking beer factories !

Let’s start with a fundamental question – do you need to drink to get drunk? The surprising answer is no. Our body can make ethanol, thus making us walking beer factories. This phenomenon of endogenous ethanol production is called Auto-Brewery.

Auto-brewery is fascinating and very few doctors would think about this when encountering a patient who they think is drunk. Imagine the plight of a teetotaler trying to persuade the doctor that he is drunk,but not because he drank 🙂

How does this happen?

While very little is known about the auto-brewery syndrome, the following are considered necessary for its development

  1. High carbohydrate intake
  2. Prolonged stay of the food in the gut due to
    1. Gut dysmotility
    2. Surgical alteration , creating a ‘vat’
  3. Colonization by organizations which cause fermentation of carbohydrates
    1. Candida spp
    2. Sacharomyces cerevisiae – both due to prolonged antibiotic therapy


  • Medical
    • Chronic -The above 3 conditions tend to coexist in one of the commonest patient groups- obese diabetics. They may have autonomic dysfunction leading to intestinal dysmotility. Many of these patients also have Non Alcoholic Fatty liver disease -NAFLD. If a subgroup of these patients have endogenous ethanol production, their liver disease may well be ‘alcoholic’. There is very little data to support or refute this claim. In a study of blood alcohol levels, the diabetic patients were found to have 5 times as much BAC (blood alcohol concentration) as non diabetics (1). While the authors conclude that this is not enough to be picked up in routine breath analyser tests, the implications of such long standing increased BAC on liver are intriguing, to say the least.
    • Acute- Acute alcohol intoxication has been reported in a patient who hasn’t touched alcohol in 30 years (2) ! Some cases of metabolic encephalopathy in which no apparent cause is forthcoming may be due to ethanol intoxication from endogenous production. However we must be careful to rule out the usual suspects and should only entertain this diagnosis if BAC is high in a teetotaler or abstinent patient.
  • Medico legal
    • It is unlikely that endogenous ethanol production is severe enough to cause positive breath analyser test in cases of drunken drive (3). This line of argument also doesn’t hold much water in the courts if the published medico legal literature is anything to go by.

To conclude auto-brewery is an interesting medical oddity. As the mechanistic insights are still not very clear, we must be cautious in making this diagnosis. Whether auto-brewery is the culprit in a subset of diabetic patients with neuropathy with NAFLD is not known.

Further reading

  1. Hafez EM, Hamad MA, Fouad M, Abdel-Lateff A. Auto-brewery syndrome: Ethanol pseudo-toxicity in diabetic and hepatic patients. Hum Exp Toxicol. 2017 May;36(5):445–50.

  2. Welch BT, Coelho Prabhu N, Walkoff L, Trenkner SW. Auto-brewery Syndrome in the Setting of Long-standing Crohn’s Disease: A Case Report and Review of the Literature. J Crohns Colitis. 2016 Dec;10(12):1448–50.

  3. Logan BK, Jones AW. Endogenous ethanol “auto-brewery syndrome” as a drunk-driving defence challenge. Med Sci Law. 2000 Jul;40(3):206–15.

Drugs: Do we get what we pay for?

Most doctors are very particular about the insulin dosing : for a good reason. Small changes in insulin dosing can result in undesirable changes in blood glucose. Sometimes we give higher concentration of insulin when patients require a larger dose. One assumption is that the patient has some sort of insulin resistance/secretory defect and that the increased dose will take care of the problem. Endocrinologists also enquire about the insulin storage – and we have all met the occasional patient who has stored insulin in the freezer or made some egregious mistake in the insulin injection technique.

Hitherto, we have assumed that , if you buy a vial of insulin containing 300 Units of insulin, it contains 300 IU of insulin. After all, what could be more natural than this?.

Today I came across a study that challenges one of our most natural beliefs. You can read the paper here.

Study in brief

Carter and Heinemann purchased insulin vials from different pharmacies in the United States. They quantitatively tested the insulin concentration in 18 10-ml vials from two major manufacturers (if you are into diabetes management, you won’t get any brownie points for guessing). They used a standard analytic method – Quadrapole Time-of-Flight (QTOF) mass spectrometry to quantify insulin.

Unfortunately, not even a single sample contained the amount of insulin that it should contain. The concentrations ranged from 13.9 to 94.2 IU/ml ( for an insulin that should contain 95 IU/ml). The lossis slightly better with NPH insulin, as shown below. However NPH throws a different problem – high variability between vials.So a patient might get only 1/6th of the regular insulin that he pays for.Even the lot to lot difference is more – in essence, while we might prescribe some dose of insulin, only God knows what’s going in. ( call it luck if you are an atheist)

What makes this issue even more troublesome is that neither the patient nor the doctor can do anything about it. Even the pharmacist can’t do much about it, because the problem ( as postulated by the authors) is more proximal – perhaps a break in the cold chain.

This study is the first to show such huge loss of insulin at the last link in the cold chain (pharmacy). The study was not done in some remote African village- but in the USA. In a hot country like India, with poor knowledge about storage of insulin, I wonder what the situation will be. There are no similar data for analogue insulins.

We have had similar problems with thyroxine (especially the government supplied ones). Similar issue was noted with Vitamin D preparations in a study conducted by AIIMS.You can access it here.



  1. If the blood glucose control changes from month to month, it may have something to do with the lot to lot variability
  2. Endocrinology is more than just numbers.
  3. Much of our certainty may be ill founded. The numbers we encounter are at best, estimates and approximations.
  4. We need demand better drug quality control – after all our patients are paying for the drug.

Facultative sexuality

Disclaimer: If you are a kid reading this, close this and watch Shin Chan. If you are an adult prude reading this, close this and watch Shin Chan 🙂

A lot of young people come to endocrinologists with hormonal issues. Some of them turn out to be interesting cases. Very few change your world view.
Today I had an interesting discussion with a fellow Endocrinologist. Apparently the number of homosexuals he saw has increased. That seemed unusual and disturbing. What might account for this? Is this a kind of referral bias? Initially I thought this must be because of the decriminalization of homosexuality – the infamous article 377 A. So it is conceivable that a lot of closet homos were revealing their orientation to the world. This is similar to the early detection hypothesis for many common chronic diseases. As in the chronic diseases , there is more to the story.
The endocrinologist told me about the story of some immigrants to Chennai. These men earned around 15000 rupees or less per month. After their monthly expenses, they had hardly any money left to splurge on entertainment. Perhaps they could afford a cigarette or two. These sexually frustrated young men couldn’t afford a girl friend. Nor could they get married, as even the peers in their own companies state categorically that they would never marry these low ballers. It is a known fact that money plays a major role in marriages. Being an underpaid male immigrant to a city is perhaps the least enviable position one can be in.
These men found themselves in a world of Tinder, but could not partake in it.Left with no other option, they found intimacy with their equally frustrated room mates. A form of situational homosexuality. While situational homosexuality is well known in prisons, barracks and other places where access to the preferred gender is absent, it is virtually unknown among free dwelling people. This form of acquired homosexuality doesn’t always stem from a lack of options.
Were these men bisexuals and were identifying as heterosexuals forced into homosexuality ? This is possible because of the heteronormative environment we live in. I wondered whether they tell the doctor this story to earn a victim tag. However, the story was consistent among men who had never met. May be they were telling the truth. They find themselves trapped in a urban prison of their own making and indulge in high risk behaviour. I can no longer see the lodges and the mansions that dot the city landscape in the same way ever again.
I turned to PubMed as usual to see if this has been reported before. I could find a study of homosexual behaviour among Indian men and was shocked to see that only 26% had homosexual tendencies ! This means that vast majority of homosexuals were opportunistic homosexuals /’acquired’ homos. This is exactly the opposite of what is found in the west. The westerners don’t turn to homosexuality because of poverty/lack of heterosexual options.
What does all this have to do with medicine? Because many homosexuals in India aren’t the ‘natural’ ones – at least according to published literature and anecdotal reports, there is perhaps a window of opportunity. Reorientation may well be a reality in some of these cases. (This is a politically thorny issue in the west, but no so much in India). It also means that the traditional conservative fears in the US and other countries aren’t too far fetched – exposure to media/movies/literature that tend to normalize homosexuality can potentially have a tremendous impact on impressionable minds.
How many of these men continue to remain homosexual throughout their lives? Unfortunately we don’t have Indian data on this. Klein sexual orientation grid can be filled up for each of these people and they need to be followed up over a long period of time. In the mean time, these men need to told about the perils they are putting themselves in and should be counseled appropriately.
Sexuality is not set in stone as many of us like to believe. It is more malleable than we care to admit. It is time to realize that there is a rich poor divide even in sexuality – the rich identify in their social media profiles as sapiosexuals, some poor are -well for want of a better word – facultative sexuals.

Further Reading

  1. A study on male homosexual behavior

Medicines that kill

I received a frantic call from my agitated cousin a couple of days back. His close relative had been admitted to the ICU with dangerously high blood pressure. The manometer showed 220/120. He had thrown seizures and an MRI was promptly taken. Thankfully it was normal.The man was in his sixties and apart from a stable kidney problem, had been chugging along just fine. Like most people with chronic conditions, he was taking a lot of tablets, including drugs to reduce blood pressure.
I thought he had stopped medicines, but I was assured that wasn’t the case. Something else had gone wrong. So I decided to dig deeper. One week back, the man had a bad headache. Like most of us in that situation, he took a paracetamol and went to sleep. To his chagrin, the damn headache returned with a vengeance next day. Having run out of ideas, he went to a nearby “medical shop” and asked for a tablet. The “shopkeeper” thought that it was his duty to give the strongest headache medicine he had – and he gave a tablet that is commonly used for migraine.
Unfortunately this migraine tablet contains ergot alkaloids – substances that can constrict blood vessels and cause a steep rise in blood pressure, especially in those with hypertension and impaired kidney function. It is akin to throwing petrol on the embers. Predictably, the tablet did its job and the man landed in the ICU with a hypertensive emergency. Sure,the ICU folks controlled his BP and made him alright, but this was a close shave. And it happened too close to me for comfort.
It made me realize, for the zillionth time, that trouble is always around the corner and even the most insignificant things matter when your organs aren’t at their best. It laid threadbare a problem most of us don’t realize – that we don’t have any over the counter drug in India! (technically we do – but you can pretty much get any medicine(except narcotics) over the counter, no questions asked). For the most part, we don’t have pharmacies either. We instead have ‘medical shops’ which will sell medicines, no matter how dangerous they are, without a prescription.
All poor countries are plagued by poor regulation. The problem is compounded in our country by the health seeking behaviour of our patients. They would rather ask a friend or neighbour for a quick fix instead of going to a doctor. Since all medicines are available over the counter, they assume that the drugs are innocuous. Nothing could be farther from truth.

One might think that learning about the drug would solve these problems. However that is wishful thinking. The package insert is generally written in such a small font that if you can read it, you can easily become a fighter pilot. And it is so inscrutable that if you can make sense of it, you should seriously consider becoming a doctor yourself.
Googling isn’t much better either. For factual queries, google is great. However choosing a medicine is a much more involved process. That’s why we spend a decade or more learning about it. It takes a special kind of ignorance to think that this can be learnt by googling for two minutes.
Let me convince you..
Many elderly people are on multiple medications which interact in myriad ways. For example, if you want to know the effect of three drugs on some biological parameter, it is naive to think that the
Total effect = Effect of A+ B +C

In reality, it is more like a function
Total Effect = f(A,B,C…)
Where the dots represents a mix of unknown factors and issues specific to a patient(such as kidney failure). More importantly the nature of this function is unique to each patient.
As doctors,we don’t know the exact effect either.But experience allows us to make a close approximation. As you can see, this process is too complex and too important to be left to some ‘shopkeeper’.
At the end of the day, we are responsible for our health. Self medicating is the easiest way to screw up that health. From drugs for common cold to muscle pain, many common drugs can cause deadly side effects in selected people. Smart people do the right thing – they meet their doctor when their health is at stake. Self medicating is dangerous and stupid.

Moral : Don’t self medicate
Conditions DON’T apply. No exceptions.


The Accident Within

During my MBBS convocation, our chief guest mentioned something that stuck with me. One of the core qualities of a doctor is tranquility – keeping calm in the face of an emotional storm. It is vital to strike a balance between empathy for the suffering of a fellow human being and the cold rationality of diagnosis, to save the patient. The newbie doctors often wrestle with this duality and as time passes, we get used to it. Soon the patients come to occupy an otherworldly dimension,needing only a careful scrutiny for diagnosis and treatment. This drift comes more easily to some people. I’m one of them. I never considered myself the ‘emotional’ type. As I coasted through medical school, I saw many cases of blood and gore. Perhaps, not as much as a surgeon would – but I had my fair share. As a physician, I had frequent encounters with stories that span the entire spectrum of human existence – from sob stories to tales of triumph. I have felt inspired, happy,sad, annoyed, bored, thrilled – and several shades of grey in between these. Yet I was always unperturbed. About the only thing I never felt often was vulnerability. I wonder if the learned professor who came for my first convocation would be proud of me.
That changed on this fateful Friday.
I had gone to the ICU to see a patient with hypocalcemia ( a condition where the blood calcium level is low). This lowering of calcium can be dangerous and can cause the heart to lose its rhythm. So I ( along with a senior colleague) went to do what was required. The ICU colleagues took us to the patient.
The patient was a thirtyish young man. His life until admission had been pretty ordinary.He had had a child a couple of weeks back (just like me).As a contented young man, he went to sleep. When he woke up, he couldn’t lift his legs. They were painful and swollen. The family quickly realized that his ordinary life had taken an extraordinary turn. They rushed him to the hospital.
Upon arrival, the doctors set out to examine him. They couldn’t find a pulse in both legs. They first thought they were unable to perceive the pulse, because the legs (from hip down) were swollen. Not wanting to take a risk, they escalated to the next step of investigations.
The doctors and the patient were in for a rude shock – the man’s blood vessels supplying the kidney and all vessels below the bifurcation of the largest artery in the body(called aorta) had simply clotted. The clot could also be found in the heart. It was as if someone had foamed his vascular tree below his belly button.
Such a catastrophic event always has a domino effect. And it did. Deprived of their blood supply, the muscles had died ( a process known as necrosis). The dying muscles released their protein contents which had clogged the kidneys, already struggling with precarious blood supply. The body desperately tried to contain the damage and initiated an inflammatory cascade : only to worsen the condition. The dying muscles and the surrounding inflammation in the finite space of his legs were throttling the blood supply further , causing what is called a compartment syndrome. (where the pressure in the compartments of leg is unbearably high). It reminded me of the freak accidents in the Hollywood movie franchise called the “Final Destination”. This time, the freak accident happened within.
It soon became clear to the managing team that they had to make a tough choice – between limb and life. Choosing the lesser evil, they decided to amputate both his lower limbs. The patient was informed of this development and had agreed. Remarkably all of this happened within 3 days!
It was at this stage that I met him. He seemed to be faring reasonably well under disastrous circumstances. Perhaps his brain couldn’t process the gravity of the situation and had gone into hibernation. Mine unfortunately hadn’t and I was, for the first time in a long time, visibly perturbed. Curiously when I saw him, there was no blood in the scene. I still don’t know what triggered that feeling in me. True to my training, I convinced myself it is multifactorial. I couldn’t shake the feeling that this could happen to anyone.
In circumstances such as these, it is generally best to focus on the problem at hand. Well, it is comforting to be in familiar territory of analysis and differential diagnosis. The case could be a fulminant form of a rare connective tissue disease, one that causes arterial clots. Then I realized perhaps the diagnosis didn’t matter at this moment. We name a disease, in the vain hope that it will give us some measure of control over it. Sometimes fate has a different idea.A young man’s life has been irrevocably changed. The entire army of doctors and all the combined man hours of training were no match for the ferocity of the disease. We stood helpless against the furious onslaught on his blood vessels. Of course, the man would live. I wasn’t sure whether to call it living or existence. May be there will be light at the end of the tunnel. May be I was too blind to see it then.
What struck me was that through all this commotion, the man had seemed more calm than me. While I had seen cases which struck a chord, I have never been in a situation where the patient was more calm than me. I must admit I was a little spooked.
Moments like make us ponder about the meaning of life – and realize the meaninglessness of the petty fights, parochial politics and proud oneupmanship. They remind us that nothing is permanent and no one is immune to misery. They urge us to make the most of the moment and in our short life, do something worthwhile.
Life is full of turns. Some we choose. Some are chosen for us. We can wallow in self pity or take charge – after all most of us aren’t this unfortunate.
That day, the fragility of the human life stood in stark contrast with the calm human resilience. An immovable object and an unstoppable force.I chose to focus on the latter.