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Do I need to be an endocrinologist to diagnose Cushing’s disease?
  1. A Jabbar
  1. Diabetes and Endocrine Section, The Aga Khan University, Pakistan; abdul.jabbar{at}

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    Around October 1999, while playing cricket after a long time, I fell down for no apparent reason. The same event happened a month later. Being mainly concerned about unexplained falls, I sought help from neurological colleagues. Two neurologists examined me and both reassured me: “your exam is normal and there is nothing to warrant any further investigations”. I checked my vitamin B12, which was 81.0 pg/ml (normal range 200–900). A combination of B12 deficiency and proximal myopathy could explain my falls. Having put on 4 kg over the past year, I sought advice from an internist. More concerning was that the central weight gain was starting to affect my appearance. The internist ascribed it to middle age spread and having checked my glucose and lipids, referred me to our nutritionist. The nutritionist having seen the results gave a good diet and exercise plan. Following this diet and exercise plan, I developed pain in my left foot and it got so severe that I presented to our radiologist with an x-ray film. On first look, he dismissed it as normal but on closer look identified a hairline fracture in the fifth metatarsal. I was referred to an orthopaedic surgeon who advised me to avoid brisk walks for two weeks.

    I questioned both of them—why did I break my bone? I was told that it may happen with strenuous workouts. Now I started to notice a change in my sleep, mood, and thoughts. I began to wake up about 3–4 am for no good reason and it was difficult to go back to sleep. Though unable to have a good night’s sleep of seven hours, which used to be a “must” for me, I was still full of energy during the day but would develop a headache at the end of a busy clinic. I sought advice from my psychiatric colleague. “It appears like mania or hypomania but why should you have it? Forget it, or if you like you may try some sedatives”. For headache, no recommendation.

    I asked my staff nurse to check my blood pressure in the busy clinic and it was 180/100 mm Hg. Not surprisingly, I got more and more worried and one day while doing an endocrine clinic, decided to investigate myself.

    While asking for routine analyses, I decided to include thyroid function tests and also cortisol. My cortisol (1600 hours) was 588 nmol/l (140–690), then looking back over the past months, it occurred to me that all of these features could be explained by one syndrome, Cushing’s, but for the low B12. I submitted a sample for 24 hour urine cortisol and reviewed the literature for B12 and cortisol. The 24 hour urine cortisol was 1644 nmol/day (110–436).

    I emailed the case to my mentors, Professors A B Grossman and R J M Ross, also mentioning that I had found reports of B12 deficiency producing circadian rhythm abnormalities and dexamethasone non-suppression.1 I was advised to replace B12 and then repeat the tests. The repeat 24 hour urine cortisol was 466 nmol/day and overnight dexamethasone suppression test 66 nmol/l. However, after completing an empiric six injection course over one month, I repeated the same tests and the 24 hour urine low dose cortisol was 1911 nmol/day (110–436) and low dose dexamethasone suppression 295 nmol/l (<50).

    Subsequent investigations and imaging showed pituitary dependent Cushing’s disease. I underwent transsphenoidal selective adenomectomy by a neurosurgeon colleague in my own centre. Postoperatively, I had undetectable cortisol and normal pituitary function.

    This case illustrates the complexity involved in the diagnosis of Cushing’s disease. It also illustrates two points that physicians should be aware of when consulted by other physicians: “treat physicians as patients when they come for advice for medical problems” and “physicians could also develop any illness and should be diagnosed”. The question about B12 deficiency remains unanswered.


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