A Great Case of Twists and Turns

Dear Bloggers

This case is a great example of how to work up a Medical Patient and it shows how being too specialised in ones approach can cause the physician to lose sight of the bigger picture. This case wins by the fact that a senior doctor did not lose focus of all the medical problems and considered a unifying diagnosis under the principles of William of Okham, so-called Okham's Razor.

Case

An elderly gentleman was admitted into a hospital with a 6 month history of Gynaecomastia.

He had noticed breast enlargement and tenderness six months previously at which time it was noted that it was probably due to the spironolactone used for his heart failure and the drug was subsequently stopped. He had no galactorrhoea.

However, the gynaecomastia did not improve, so his local hospital measured the serum prolactin level which was found to be mildly raised (approximately 1.5 x normal) and he was sent to another hospital for more intensive investigation.

However, one week before admission to the next hospital, whilst walking, he developed sudden onset of lower back pain. The pain remained even at night and stopped him from sleeping. He was then having difficulty walking because of it.

On further questioning, Body Systems Review revealed a problem with urination as it took him some 5 minutes to void his urine. Moreover, he had no had an penile erection in 10 years. He had not lost any body hair although he had never had a lot in the past.

Body Systems Review also revealed no loss or change in vision and no headaches, nausea or vomiting.

Previous Medical History included ischaemic heart disease, heart failure, and COPD.

Drugs included furosemide, candesartan, beta-blocker and aspirin plus an H2-blocker.

He was an ex-smoker and drank 2 glasses of wine per day.

On examination, the patient was in severe pain and was lying still in bed but when moving, he screamed in pain.

General inspection showed mild gynaecomastia and loss of skin turgor plus dry skin. Temp 36.5, BP 124/78 (lying)

Cardiovascular examination revealed a pulse of 80 per minute and regular. JVP was raised to the angle of the jaw and showed a systolic 'v' wave consistent with Tricuspid Regurgitation. No murmur could be identified. No leg oedema was seen.

Respiratory examination showed a resp rate of 20/min, SpO2 of 95% on room air, central trachea, slightly hyper-inflated chest and normal vesicular breath sounds throughout the chest fields.

Abdominal examination revealed a slightly distended abdomen that was soft and non-tender with no abdominal masses. Bowel sounds were present. There were no hernial orifices and no AAA. Rectal examination had not been done !!! :-(

Neurological examination of the Lower Limbs was abnormal. Straight leg raising caused pain on the right leg at 70 degrees but immense pain of the left side at only 30 degrees-- a positive test.

The patient was unable to raise legs spontaneously due to pain. Reflexes showed hyper-reflexia throughout in upper and lower limbs but were absent at the ankles. Babinski sign was normal bilaterally. L5 dermatome on the left lower limb revealed loss of sensation (skin sensation below the knee).

CNS examination revealed normal cranial nerves throughout and there was no evidence of bitemporal hemianopia.

Examination of the lower spine was not painful to touch.

Lab data revealed a normal CBC, Normal Na & K but BUN was 50 and Creat 1.6.
Liver function was normal.
Calcium was 10.6 (mildly elevated)
Prolactin level was 1.5 times normal.
Thyroid function was normal
FSH/LH were 20-30 times normal and testosterone was low normal
Cortisol, GH and ACTH were normal.

CXR revealed a small area of scarring at the lateral right upper zone consistent with old TB but no evidence of malignancy.

Clinical Impression From History & Examination and Lab Data

Okay, this patient had in fact been admitted into hospital for a TRH stimulation test because of the raised prolactin. The back problem had not been known about until the patient had been admitted and had complained of the problem.

This patient therefore had several problems

• Gynaecomastia and Hyperprolactinaemia
• Renal Failure
• Hypercalcaemia (mild)
• Back pain of sudden onset with Lower Motor Neurone Signs.
• Probable Tricuspid Regurgitation
• High LH/FSH and low-normal testosterone (testicular failure)
  

In this case, I think the patient has developed gynaecomastia from hyperprolactinaemia and spironolactone. But, the drug was stopped. Prolactin can be raised for several reasons but most people immediately think Pituitary Tumour and do a reflex MRI head scan. Well, in view that the LH / FSH levels are high as well, one might naturally think it to be a pituitary source. However, pituitary adenomas in males present LATE and are usually macroadenomas (>10mm in size) and tend to cause Visual Disturbance. This patient had no obvious visual impairment.
The Raised LH and FSH should have caused a raised testosterone level, but they did not in this case because of the low-normal level (which is inappropriately low) thereby suggesting Testicular Failure.

In Testicular Failure, in response to low testosterone levels, the feedback loop of the pituitary axis is for LH and FSH to rise. Hence, the rise in these levels is unlikely to be due to a tumour. Moreover, LH-FSH secreting pituitary adenomas are rare. Also, prolactin when raised to very high levels e.g. 20x normal with prolactin secreting adenomas, there is inhibition of LHRH and reduction in LH & FSH; hence, in this case, with LH and FSH being high, it was unlikely to be caused by an adenoma. The fact that the other anterior pituitary hormones were left intact goes against panhypopituitarism.

History was important here because on Body System Review, it was elucidated that the patient had had no sexual activity in 10 years due to erectile failure, which again would fit with Testicular Failure. This patient did not offer the information of erectile failure spontaneously, but it was the clever junior doctor that asked the question and the patient then was able to answer to the affirmative.

The raised prolactin from a Prolactinoma, I would expect to be higher and as I say, I would expect some visual disturbance because of the nature of the presentation of pituitary adenomas in men.

However, one obvious cause of hyper-prolactinaemia is Hypothyroidism because of raised TRH in response to low T3/T4 also drives Prolactin release. In this case, all thyroid function was normal. Hence, it was not entirely clear why a TRH stimulation test was being performed at all. Some authorities advocate a TRH stimulation test, but it does not really tell you what or where the problem is. A TRH stimulation test is perhaps more useful when combined with a LHRH and insulin stress test for patients with suspected hypopituitarism, usually performed post-operatively for pituitary adenomas.

Perhaps, the most obvious cause of the Prolactin being elevated was renal failure induced by the Candesartan (ARB) plus furosemide [dry skin, reduced skin turgor].

There are numerous causes of hyperprolactinaemia which are detailed in any good textbook and are beyond the scope of today's talk.

Now, why did this patient get back pain?? Well, hypotestosteronaemia in men can result in osteoporosis. Referring back to the history, this patient was walking when he suddenly developed severe back pain. This suggests either a vertebral fracture or intervertebral disc herniation. One always has to considered serious causes of neurology such as cauda equina syndrome whereby the lower spinal nerves roots become compressed in a lower motor neurone distribution. Even worse is the conus medullaris syndrome with compression of the spinal cord that can lead to permanent paralysis of one or both lower limbs. In such conditions, patients can develop urinary problems such as retention and then overflow and hence, incontinence and the same can occur with the bowel giving constipation and then overflow diarrhoea.

That is why a rectal examination is so important !!! Rectal examination should always be done in patients with back pain and abnormal neurology affecting the lower limbs.

In this situation, it is useful to check TONE by asking the patient to squeeze with their anus on the examiners finger. Loss of tone is an ominous clinical sign. Moreover, checking sensation around the anus for numbness is also suggestive of a compression problem.

Rectal examination is also important in this case to identify possible prostate cancer as it might also account for the prolonged micturition symptoms and if metastatic, could result in a vertebral fracture.

Hence, a senior doctor who saw this patient suggested the possible diagnoses

1. Iatrogenic Renal failure with secondary Hyper-Prolactinaemia
2. Testicular Failure with Hypotestosteronaemia, raised LH and FSH
3. Osteoporotic fracture due to hypotestosteronaemia
4. Lower motor neurone signs of the left lower limb due to nerve impingement syndrome from likely intervertebral disc herniation
   

However, a pituitary adenoma would have needed to be ruled out by MRI head scan but in view of the previous insertion of coronary artery stents, the patient could not have such imaging. A CT head scan was not performed.

Results

Lumbar Xray did confirm a new vertebral disc fracture at the T12 position when compared to Xrays taken several months before and this 'biopsy' of the radiological archives indicated that he had been experiencing back pain for some time, although it had worsened on this admission due to the new fracture.
The ARB and furosemide were stopped with some improvement of the renal failure.
Moreover, PSA and a Myeloma Screen [renal failure, raised calcium and back pain] should also have been checked in view of being elderly and male.
The patient's back pain improved during the admission and there was no weakness of the lower limbs and he was subsequently discharged home for follow-up as an outpatient.

In summary,

1. Not all hyperprolactinaemia is due to an adenoma. Think of more common things e.g. drug induced renal failure, anti-dopaminergic drugs, lung cancer
   
2. In men, consider also osteoporotic fractures not just osteoarthritis.
3. Think of hypotestosteronaemnia, multiple myeloma, prostate cancer and hyperthyroidism as possible causes of vertebral fractures in men.
4. If you find back pain you must examine the neurology of the lower limbs, check sensation and do a rectal examination. Such patients require urgent imaging by Xray and MRI and may require urgent neurosurgery.
5. Remember, drugs can cause renal failure and the drugs should always be examined in detail and if there is a concern that they are the cause, they should be STOPPED. As in this case, the patient also had COPD and was also taking two bronchospasm-promoting drugs !!! e.g. aspirin and a beta-blocker. Other drugs such as ticlopidine / clopidogrel can be used in place of aspirin and beta-blockers used for hypertension can be switched to other classes such as a calcium channel blocker. If used for anti-arrhythmic purposes there are many agents out there that can be used in place of a beta-blocker.
6. Remember to Ask Questions from Body Systems Review- you will find symptoms that the patient never thought were a problem and that they never thought you would ask and it will save your patient and you too.
7. Men with osteoporosis due to hypotestosteronaemia may benefit from testosterone replacement and reduction of fractures with the use of bisphosphonate drugs or the newer recombinant human parathyroid hormone ( teraparatide ), which should be strongly considered in this case. Note: when starting testosterone therapy, prostate cancer should be initially ruled out because hormone therapy can accelerate this type of cancer.
   
8. Most compression neuropathies from intervertebral disc herniation improve with time, but if severe e.g. severe pain, loss of function, then disc surgery should be considered.
   
9. Remember, Rectal Examination, Rectal Examination and finally, Rectal Examination. Never Forget to Do It !!!!!!!!
10. In view that this patient had biochemical evidence of testicular failure, the genitalia should have also been examined. Never forget to examine this area.
    

One excellent reference for principles of history taking (and hence, Body Systems Review) is:
The Patient History: Evidence-Based Approach (Paperback)
by Lawrence M. Tierney & Mark Henderson

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