Switch Patient From Rosigli T Azone?


Question

I am a consultant Endocrinologist from the Kingdom of Bahrain.I would be grateful for your assistance regarging the issues related to the use of Rosiglitazone(Avandia).Is it safe to continue using this drug for my patients?Dr. Yahya Al-Zaman,BSc,MD,FRCP(UK), Bahrain

Response

If a patient without heart disease is on Avandia and is doing well, I would leave them on it, unless they insist on being changed to Actos. In my opinion, the data, when are looked at as a whole, do not show a significant increase in cardiac risk with Avandia. However, given the adverse publicity, I probably would not start any new patient on Avandia - rather I would use Actos. Another question concerns the increased fracture rate with both drugs in post menopausal women. How to deal this problem remains an unanswered question.Ira Goldfine , MD

Possible Carcinoid Tumor


Question

I have recently seen an Indian man, aged 48 years,smoker and social drinker, suffering with hypertension for a long time. Over the last few months, he develops flushing on and off, aggravated during times of anxiety, specially when work pressure escalates.Physical examination reveals, BMI 25, BP 180/100 (both arms), all pulses palpable, systoliv flow murmur at apex. Labs show--- raised urea and high creatinine ( 2.6 mmol/l), fasting glucose 115 mg/dl, and 2 hrs post prandial glucose 166 mg/dl. 24 hrs urinary adrenaline and nor adrenaline and total catecholamine levels normal. 5 HIAA markedly raised. He complained of symptoms of gastritis ---an upper GI endoscopy showed mild antral gastritis. My working diagnosis is Carcinoid tumour

My questions are?

Is the hypertension related to Carcinoid , or is this a separate problem?

  1. I n view of his significant degree of renal impairment, can he undergo localising scans like MIBG, which is available at our centre.
  2. What other hormones should I test?

I shall be very much obliged if you kindly enlighten me about this computer software engineer please Thanking you in anticipation.Dr Sagarika Mukherjee MRCP(UK), MRCP(Ireland), CCST(UK), AMRI Hospital, Calcutta, India

Response

1. It is not clear than this is carcinoid-you say the 5HIAA is very high but of course one would like to see the numbers and be sure there has been adequate preparation such as avoiding serotonin containing foods before doing the urine collection. It would also be wise to get blood serotonin values at the same time.

2. Your patient seem to be evolving diabetes and has IGT by your numbers, These people may have autonomic dysfunction and then get gustatory sweating associated with flushing of the upper half of the body while the lower half remains dry. An autonomic function test would help. Simply the measurement of heart rate variability

3. The gastritis may then be due to altered gastric emptying, but alternatively could be due to atrophic gastritis with the possibility of pernicious anemia. You need a gastrin and gastric pH to determine if this is so. These people then get secondary carcinoid s of the gastric mucosa.

4. up to 50% of patients with carcinoid have hypertension in the absence of Pheochromocytoma. You need to obtain fractionated urine or plasma metanephrines to make this diagnosis and the best measure today for a pheo is the plasma chromogranin A level. The chromgranin molecule is processed to pancreastatin and Vasostatin and the latter is a potent vasoconstrictor so you may not nee to postulate a pheo but simply a carcinoid

5. MIBG scans are usually only helpful if the metanephrine levels are markedly elevated and you need the high affinity tracer 123I MIBG to obtain useful pictures.

Hope this helps, AIV Aaron Vinik, MD

Possible Cushing’s Disease with High Cortisols


Question

I'm Dr. Noor Lita Adam currently doing my endocrine fellowship in University Malaya Medical Center, Kuala Lumpur. I really hope that somebody may help me and give their opinion on this patient that I saw recently. He's a 32 years old Chinese man who was investigated earlier for secondary cause of hypertension in one of private medical center. He is obese with BMI of 32 kg/m2 and has positive family history of hypertension ( mother at age 50+). He is not diabetic. He has no cushingoid features. His 24 H urine cortisol was markely elevated at 8550 nmol/24H ( 79-590). However his overnight dexamethasone test was suppressed < 50 nmol/L. ACTH level was 42 pg/ml ( < 46). MRI pituitary revealed 3mm R adenoma. We performed a low dose dexamethasone suppression test, baseline cortisol was 646 nmol/l and ACTH was 125 pg/ml. His cortisol suppressed to 12 nmol/l and ACTH 10 pg/ml after LDDST. Is it possible to have Cushing's despite a negative LDDST?

Would inferior petrosal sinus sampling helps in getting a right diagnosis?

I appreciate any opinion on this. Thank you, Dr. Noor Lita Adam

Response

Your patient has a urine free cortisol that is 14-fold higher than the upper limit of normal; normal suppression with overnight dexamethasone, however you don’t mention the dose of dexamethasone used. The LDDST suggests a normal HPA axis and suggests “pseudocushings”. The possible reasons for discrepancies between a high urine free cortisol and normal dexamethasone suppression testing are medications which decrease the metabolism of dexamethasone or substances that interefere with the measurement of cortisol. Furthermore the absence of stigmata on clinical presentation with such a high cortisol makes one suspicious of a false reading in the cortisol – or rapid onset of disease. I would do the following:

1.clarify the medications the patient is taking (rule out: carbamazepine, fenofibrate, licorice, carbenoxolone, exogenous hydrocortisone)

2.Repeat a basal urine free cortisol by HPLC to determine if intermediates are elevated.

3.Measure salivary free cortisol at midnight, twice.

4.If still elevated urine free cortisol perform a low dose dexamethasone suppression/CRF stimulation test (0.5 mg q6h for 2 days and on the morning of the 3rd day do CRF stimulation test). Measure dexamethasone level in the blood to confirm levels.

To answer your specific questions:

5.Is it possible to have CD despite a negative LDDST – unlikely, but possible.

6.IPSS would not be helpful here. First you need to confirm there is hypercortisolism and that it is ACTH dependent.

I look forward to hearing more about your patient. Thank you for allowing me to comment.

Roy Weiss ,MD, PhD, FACP, FACE