Myriad of problems with formerly healthy, athletic teen

[Kathy]

My now 15 y/o son, about whom I have posted in the heart forum, has suffered a marked deterioration in his usual perfect athletic health. We first noted HTN in 8-98 during an EBV, strep C infection. A good resting BP would be @150/90+ with paroxysmal bursts as high as 186/128, 170/110, etc. Cardiac testing in 8-99 indicated LVH, rt. atrial enlargement. EKG=RBBB, LVH. Stress test=inverted T-waves upon standing, etc. A 24 hr. urine for catechols elevated at 131 (high normal 80) 5 days following "attack." Renin elevated at 10.3 (high normal 3). Endocrine w/u  9-99 revealed sexual precosity (full puberty age 8). Thyroid tests, tests for 11-hydroxylase deficiency, etc., apparently normal. Has hair distribution, sexual development of 28-30 y/o man. Had MIBG scan for extra-adrenal pheo; left adrenal enhanced thrice more than right but no tumor seen. 5-HIAA for carcinoid syndrome (high normal 5) was 4 on 11-1-99; 3 wks. later elevated at 11.8. Spent 12 days at Mayo; autonomic reflex testing "somewhat" abnormal. Past 3 weeks, pupils are always dilated, frequently fixed and often non-reactive to light; past 1 week they are different sizes. Attending physician at Mayo freaked when he first saw it but ophthalmological exam normal so they decided this was "normal" for him. He also has attacks of anger over things that would never have bothered him before. MRI of brain supposedly normal 10-21-99. Oddly enough, on tilt table testing, we found his BP is now very low (124/45)and heart rate is brady when lying down, but upright it reverts to HTN and he is often tachy again, as before. Renal angiogram with venous sampling was done; supposedly normal, although he does have newly discovered bilat abdominal bruits which they are saying are "normal" for him. He has lost 27# since late 8-99, yet eats like a horse. CT scan of chest, abdomen, pelvis supposedly normal also. (All scans were performed in Chicago.) Since 8-99, he has developed profuse inappropriate sweating, whether in airconditioning or outside in cold weather. Also, since age 8 when he had the rapid puberty (pubic hair, etc.) he has developed a bright red flushing of the lower half of his facial cheeks. In addition, in past 1-1/2 wks., he had periorbital edema. He started on Lopressor, 50 mg. BID on 10-25-99. I want to reduce the nighttime dosage to 25 mg. as his BP and HR are going so low, but Mayo says no, local docs who have cared for him 6 yrs. say yes. They agree with me that NONE OF THIS IS NORMAL FOR HIM. They are very concerned; I am beside myself. The child goes downhill every day; how can any of this be "normal?" I am very concerned about the eyes; many things could have happened between the time of the MRI and the ophthalmologic exam. Anisocoria has many causes, I realize, including increased intra-cranial pressure. Why is everything dismissed as normal when none of it ever happened prior to August of 1999? Child is a top athlete in 3 sports; Mayo is going to fax a release for him to return to varsity football (starting quarterback) and basketball (forward taking charges to draw fouls). Do you have any suggestions for me, please? I know my son, I have worked in medicine for 18 years, and myself, along with his local physicians, know darned good and well that none of this is normal for this wonderful young man. I would be eternally grateful if you could shed some light on this situation. It is destroying our lives, and he is changing before my very eyes; his pants fall off without a belt (waist went from 36 to 31-3/4 in. in 6 wks. and weight still dropping. Thank you so much.

[CCF Neuro[P] MD, RPS]

Dear Kathy:



Wow, sounds like a roller-coaster ride with your heart and emotions on the downside of happy.  I am sorry that your son is going through this.  Full puberty at 8 is alittle accelerated and did this fact not prompt his pediatrician into an endocrine workup?  Anyway, the high resolution MRI of the hypothalmus was normal?  The paraneoplastic workup was also negative?  What metabolic workup has been performed?  Was there any abnormality of urine or serum amino acids or organic acids?  Any muscle weakness in all his symptoms?  I am not sure what would drive such a sympathetic response without a hypothalmic lesion, paraneoplastic tumor, primative neuroendocrine tumor, or quarky mitochondrial disorder.  Sounds like things have been thorough.  If they haven't checked for a possible paraneoplastic disorder I would run the panel, including the testis-limbic system antibody.  We have seen some patients with a mitochondrial disorder present with some of the symptoms you indicate your son has, but certainly not all.  It might be worth running a few metabolic labs such as urine and serum organic acids and amino acids.  I would send the urine organic acids to Dr. Richard Kelly at Kennedy-Krieger Institute at Johns Hopkins.  



Sorry, that I was not able to add much.



Sincerely,



CCF Neuro MD

[Kathy]

Thank you for the quick response. Nothing was done at 8 yrs. old because I started my menses at 9, and he had no other symptoms of absolutely anything (he sees a GP). I know full chem profile, lipids, thyroid function, liver/kidney were done as well as renin, aldosterone, deoxycorticosterine, desoxycortisol, cortisol and the 24 hr. urine for catechols, a plasma free for catechols, VMA; I know Mayo repeated most of these but have no idea what else they ordered (they did not make me privy). MRI of brain w/attentuation to pituitary/hypothalamus was normal in Chicago unless Mayo picked up something they didn't mention. What is required in the metabolic work-up and I can find out what was done? And how do I get the samples to Dr. Kelly at Johns Hopkins? I honestly don't care where we have to go, to the moon or Mars, to get my child well, or at least get some answers so that I can make rational and educated decisions about his care. God bless you!!

[CCF Neuro[P] MD, RPS]

Dear Kathy:



Sounds like the metabolic workup did not include a paraneoplastic evaluation.  I think it would not hurt to include this.  It also sounds like they did not do a mitochondrial workup, which is likely not going on, but at this point it wouldn't hurt.  I would get serum and urine free and acylcarnitine, organic acids and amino acids as a baseline beginning.  You can have your physician call Kennedy-Krieger and get the proper forms.  This is the important thing, I would only send the urine organic acid analysis to Dr. Kelly at Kennedy-Krieger.  



Females usually start developing sexually before males (so what else do females do first and better before males), and 8 years old for a male is very unusual.  We often see females starting this young, but it is highly unusual in males.  Do you know his bone age at the time of puberty?  However, at this point, it is an nonentity.



Increased intracranial pressure is usually manifested by papilledoma which the opthalmogolist or neurologist can pick up easily.  Also, he would have neurological signs of nausea and vomiting with his headache, together with blurry vision.



Sorry, I am not much of a help.



CCF Neuro MD

[Kathy]

Thank you so much for the valuable info; I'll get on it right away. Our doc is good about giving me scripts or orders for whatever I come up with which might be beneficial for Jonathan because our docs are lost, too, and they care so much about my son. There was no paraneoplastic testing performed. There is no muscle weakness; the boy is strong as a horse, does 200+ push-ups and 50+ sit-ups nightly to retain muscle and tone. He looks really "buff," as the kids say, but now his appetite is decreasing, also, which could be attributed to a bit of "pseudo depression" over the lack of diagnosis and the loss of so much of his active life, in addition to having lost 27#. One thing I did forget to mention is that, also within the past 3-4 months, the palms of his hands and the soles of his feet are a very definite orange color. Trust me, my son does not eat orange and yellow vegetables, either. The underside of his tongue is of normal color. Mayo termed this "normal" for him, as well. I am sure you can understand my frustration at their decision to term the marked flushing (he is either quite flushed, awake or asleep, or a very unhealthy greyish color in the face, take your pick), and the new onset of the inappropriate profuse perspiration, the pupillary anisocoria, the abdominal bruits, the extremely low BP and HR when supine and the periorbital edema