2 5 2 Henningsson el al. The Journal of Pediatrics February 1993

Acute mercury poisoning (acrodynia) mimicking pheoch romocy toma in an ado lescent

C. Henningsson, MD, PhD, S. Hoffmann, MD, L. McGonigle, MD, FRCP(C), and J. S. D. Winter, MD, FRCP(C)

From the Department of Pediatrlcs, University of Alberta, Edmonton, Alberta, Canada

A 14-year-old boy was seen because of Irritability, Insomnia, lethargy, and pro- fuse sweating, together with hypertension (blood pressure: 160/120 mm Hg), ta- chycardla, and a diffuse erythematous rash with desquamatlon of the palms and soles. Initial biochemical Investigation suggested a diagnosis of pheochro- mocytoma, but subsequently a history of exposure to mercury vapor was obtained. This case emphaslzes the cllnlcal and blochemical similarities between mercury poisoning (acrodynla) and pheochromocytoma. (J PEDIATR 1993;122:252-3)

In the absence of a family history of multiple endocrine

neoplasia (types 2 and 3), neurofibromatosis, or yon Hip-

pel-Lindau disease, making the diagnosis of pheochromo-

cytoma can be difficult. The tumor is particularly rare in the

pediatric age group. I Classic manifestations of pheochro-

mocytoma include paroxysmal headache, pallor, sweating,

palpitations, and anxiety, in association with significant hy-

pertension. Biochemical confirmation depends on the dem-

onstration of increased levels of plasma and urinary cate-

cholamines; diagnostic confidence can be enhanced by the

demonstration that catecholamine levels are not suppressed

by orally administered clonidine. 2 Anatomic localization

can then be accomplished with ultrasonography, computed

tomography, and scanning after administration of m-iodo-

benzylguanidine labeled with iodine 131.

The purpose of this report is to demonstrate that acute

mercury poisoning (acrodynia) can mimic the clinical and

biochemical manifestations of pheochromocytoma, and

should be considered and excluded during the investigation

of suspected cases.

CASE R E P O R T

A 14-year-old boy had been seen by his physician 3 weeks pre- viously with complaints of back pain and was discovered to have tachycardia and a blood pressure of 160/120 mm llg. Laboratory

Submitted for publication June 23, 1992; accepted Sept. 1 !, 1992.

Reprint requests: J. S. D. Winter, MD, FRCP(C), Professor, De- partment of Pediatrics, Section of Endocrinology and Metabolism, 671 lleritage Medical Research Centre, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.

Copyright �9 1993 by Mosby-Ycar Book, Inc. 0022-3476/93/$1.00 + .10 9/22/42499

values included the following: hemoglobin, 18.9 gm/L; calcium, 2.84 mmol/L, uric acid, 489 mmol/L; and albumin, 55 gm/L (all evidence of apparent hemoconcentration). Although the patient's back pain resolved, there was no blood pressure response to ther- apy with nifedipine and phenoxybenzamine. Subsequently a gen- eralized, pruritic erythematous rash developed, with desquamation on the palms and soles. The patient began to have paroxysmal ep- isodes of sweating accompanied, by chills and tremor, to a degree that required a change of bed linen every 2 hours, l ie became in- creasingly irritable, complained of insomnia, and lost 4 kg weight. Initially he had anorexia, but subsequently his appetite became vo- racious, requiring extra meals through the night, tte also com- plained of decreased energy and episodic sensations of heat and cold. Exposure to drugs and toxins was denied, except for occasional use of alcohol. IIe had a history of penicillin allergy. There was no family history of hypertension, pheochromocytoma, or multiple endocrine neoplasia syndromes.

On examination the patient was irritable but in no immediate distress. His blood pressure was 140/100 mm ttg while he was su- pine, 130/60 while sitting, and 90/50 while standing; he was still taking the antihypertensive medications, t ie was afebrile. Ills height was at the 50th percentile and his weight at the 25th. There was a generalized, blanching maculopapular rash, confluent over the trunk, with desquamation on the palms and soles. His thyroid gland was normal and there was no exophthalmos. His cardiovas- cular and neurologie examinations were otherwise normal. His ab- domen was soft, with no abnormal masses, no tenderness, and no bruits.

Laboratory investigation showed normal thyroid function. A di- agnosis of pheochromocytoma appeared to be confirmed by dem- onstration of increased basal plasma and urinary catecholamines, with no evidence of suppression by elonidine, 300 ~tg by mouth (Table I). tlowever, abdominal computed tomographic scans and radiographs of the chest failed to show a tumor, and two separate m-[13q]iodobenzylguanidine scans showed normal adrenal glands and no evidence for extraadrenal pheochromocytoma.

The Journal of Pediatrics Henningsson et al. 2 5 3 Volume 122, Number 2

T a b l e I. Catecholamine values in acute mercury poisoning

Basal value -45 mln

Clonldlne lest

0 mln +120 mln Normal range

Plasma (nmol/L) Norepinephrine 13.80 Epinephrine 3.61 Dopamine 3.29

Urine (nmol/24 hr) Metanephrine 0.60 Catecholamines 5.05

11.16 9.39 15.68 0.66-3.56 1.01 1.01 1.63 <0.34 0.37 0.82 2.01 <0.54

<0.6 0-1.5

Clonidine suppression test: Clonidine, 300 ~g, was given orally at time zero; plasma catecholamioes ,~ere measured at -30, -15, 0, +120, and +180 minutes. Normal response is a 50% fall in catecholamine levels.

The patient's clinical condition rapidly deteriorated, and he be- gan to have hallucinations. At the third review of the history, in re- sponse to direct questions about mercury exposure, he admitted to playing with elemental mercury, with extensive skin contact, and to having been exposed to mercury vapor after the metal had been poured into a portable electric coil heater. Use of the heater con- tinued during visits home from the hospital. Blood and urinary mercury levels were elevated in the boy and his parents (Table II). Because of penicillin allergy, the boy was treated with dimercaprol; although mercury levels and blood pressure returned to normal during the next 4 months, and his symptoms disappeared, he was subsequently readmitted to the hospital with seizures. The mother also had symptoms (tremors, weakness, rash, memory loss, sweat- ing, and palpitations) but no hypertension; the father had mild memory loss. Both parents were treated with penicillamine until their mercury levels returned to normal. Their house had to be stripped and cleaned to prevent further mercury exposure.

D I S C U S S I O N

Since an association with mercury exposure was demon-

strated, 3-5 acrodynia has become a rare disease, largely un-

known to physicians. In the past, many authors pointed to

the clinical similarities between acrodynia and pheochro-

mocytoma; although early catecholamine assays were of

dubious validity, at least two authors reported increased

epinephrine and norepinephrine excretion in acrodynia. 6

Cheek et al. 7 showed that inorganic mercury by injection

can markedly increase sympathetic activity and epinephrine

levels in rats, and would therefore be expected to mimic the

signs and symptoms of pheochromocytoma.

In our patient we were able to document elevated cate-

cholamine levels and to demonstrate that they were not

suppressed by clonidine, findings that would commonly be

considered diagnostic of pheochromocytoma. Only our in-

ability to localize a tumor delayed his planned surgery, and

eventually led to the correct diagnosis of mercury poisoning

by the more mundane process of careful history taking. Ac-

rodynia in an adolescent is virtually unheard of but should

not be entirely unsuspected, given the current recreational

nature of mercury exposure. Indeed, during the past year we

T a b l e II. Mercury levels in acute mercury poisoning

Blood (nmol/L) Urine (nmol/t)

Patient 1 I0 400 Mother 50 920 Father 50 480 Normal range <25 <50

Serum and urine mercury concentrations of the patient and the parents (the only other residents of the household).

have seen three other children in this hospital who had sig-

nificant exposure to elemental mercury. It is ironic, with the

rarity of pheochromocytoma in children, that all current

textbooks on pediatrics or endocrinology devote consider-

able space to this tumor, whereas few even mention acrody-

nia. We believe that mercury poisoning should be consid-

ered initially in any child with signs of sweating, behavioral

change, skin rash, and hypertension, and that pheochromo-

cytoma might be considered in the differential diagnosis.

R E F E R E N C E S

1. Beard CMI Shaps SG, Kurland LT, Carney JA, Lie JT. Oc- currence of pheochromocytoma in Rochester, Minnesota, 1950 through 1979. Mayo Clin Proo 1983;58:802-4.

2. Manneli M, DeFeo b, lL, Pupilli C, et al. Usefulness of basal catecholamine plasma levels and clonidine suppression test in the diagnosis of pheochromocytoma. J Endocrinol Invest 1987; 10:377-82.

3. Zahorsky J. Three cases of erythroedema (acrodynia) in infants. Med Clin North Am 1922;6:97-105.

4. Fanconi G, Schenker P. Uberempfindlichkeitstreaktionen auf Quecksilbermedication im kindesalter mit besonderer beruchsichtigung der calomelkrenkheit, ttelv Paediatr Acta 1947;2(suppl 4):3-46.

5. Warkany J, Hubbard DM. Mercury in the urine of children with acrodynia. Lancet 1948;1:829-30.

6. Farquhar ttG. Mercurial poisoning in early childhood. Lancet 1953;2:1186-7.

7. Cheek DB, Bandy RK, Johnson LR. The effect of mercurous chloride (calomel) and epinephrine (sympathetic stimulation) on rats: the importance of the findings to mechanisms in infan- tile acrodynia (pink disease). Pediatrics 1959;23:302-13.