8 2 6 Edi tor ia l correspondence The Journal o f Pediatrics May 1991

sleep of color changes, snoring, and excessive sweating should alert the clinician to the possible presence of obstructed breathing epi- sodes.

A Kahn, MD

E. Rebuffat, MD hi. Sottiaux, LP

M.F. Muller, MD A. Bochner, MD

J. Grosswasser, MD Pediatric Sleep Unit

University Children's Hospital B-I020 Brussels, Belgium

Hearing impairment during deferoxamine therapy for thalassemia major

To the Editor." We have read with great interest the article by Cohen et alJ en-

titled "Vision and Hearing During Deferoxamine Therapy," in which the authors concluded that auditory abnormalities do not occur a s commonly as previously thought in patients with thalassemia major, sickle cell disease, or Blackfan-Diamond syn- drome who are receiving deferoxamine therapy.

We report herein our experience with a large series O f patients with thalassemia major who are receiving deferoxamine therapy; we find a much higher incidence of hearing impairment: 309 patients with thalassemia major between 3 and 18 years of age who received regular transfusions designed to maintain minimal hemo- globin levels at about 10.5 gm/dl were assessed for hearing sensi- tivity by measurement of pure-tone air and bone conduction thresholds and B6k6sy tracing (when considered necessary). Bilat- eral sensorineural hearing impairment was diagnosed when air- conducted sound exceeded the threshold of 20 dB HL at frequen- cies greater than 2000 Hz.

Until 1985, all patients received between 40 and 100 mg defer- oxamine per kilogram of body weight by nightly subcutaneous in- fusion for 10 to 12 hours (the dose producing maximal urinary iron excretion from the analysis of dose-response curves); from 1986 onward, they ~'eceived between 40 and 50 mg/kg per day. This dosage reduction was instituted because of the adverse growth ef- fects detected With high doses. 2 Of 309 patients examined, 48 (15.5%) had sensorineural hearing impairment that was symptom- atic in four. There was no difference between patients with neuro- sensory hearing 10ss and those with normal hearing in regard to deferoxamine dosage and ferritin levels (Table). The discrepancy between our data and those of Cohen et al. may be related to our patients' younger age and lower iron accumulation, in comparison with those of the Cohen patients. Our findings indicate that mon- itoring of hearing function should be pursued very accurately in patients receiving deferoxamine treatment, especially in the pres- ence of moderate iron stores.

Table. Sensorineural hear ing loss among pat ients with

thalassemia major

Subjects with Subjects without sensorineural sensorineural hearing loss hearing loss

(n = 48) (n = 100)

Ag e (yr) 11.5 _+ 3 11.7 + 2 Start of transfusional 21 _+ 16 15 + 16

therapy (mo) Start of chelation 53 _+ 25 47 + 23

therapy (mo) Serum ferritin 1516 + 909 1685 _+ 1003

levels (#g/L) Dose of deferoxamine

(mg/kg/day) Before 1986 79 + 13 (60-104) 68 _+ 11 (45-100) After 1986 39 + 4 (31-48) 40 __+ 4 (30-50)

Values (except ranges) are expressed as mean _+ SD.

Francesca Argiolu, MD. Giuseppe Diana, MD

Antonietta Avignone, MD Antonio Cao, MD

Istituto di Clinica e Biologia dell'Eth Evolutiva Universith Studi Cagliari

Sandra Di Ninni, MD Istituto di Clinica Otorinolaringoiatrica

Universith Studi Cagliari 09134 Cagliari, l taly

R E F E R E N C E S

1. Cohen A, Martin M, Mizanin J, Konkle DF, Schwartz E. Vi- sion and hearing during deferoxamine therapy. J PEDIATR 1990;117:326-30.

2. De Virgiliis S, Congia M, Frau F, et al. Deferoxamine-induced growth retardation in patients with thalassemia major. J PE- DIATR 1988;113:661-9.

Reply

To the Editor. We thank Dr. Argiolu and her colleagues for their data regard-

ing hearing abnormalities in a large group of patients with thalassemia major who are being treated with deferoxamine. The modest level of iron overload in the patients from Cagliari speaks to the success of their iron chelation program and the important benefits of treatment with deferoxamine. Although the incidence of sensorineural hearing loss is higher in their patients than in ours, it is considerably lower than the incidence in three other studies, 13 and this remarkable variation among centers suggests that pres- ently unrecognized factors may contribute to auditory toxic effects. As stated in our article, until specific risk factors for toxic effects

Volume 118 Editorial correspondence 8 2 7 Number 5

are identified, all patients receiving deferoxamine should have reg- ular auditory assessments, regardless of drug dose or degree of iron

overload. Alan Cohen, MD

Marie Martin, RN Dan Konkle, PhD

Elias Schwartz, MD Division of Hematology

Children's Hospital of Philadelphia Department of Communication Disorders

Children's Seashore House Departments of Pediatrics and of

Otorhinolaryngology and Human Communication University of Pennsylvania School of Medicine

Philadelphia, PA 19104

R E F E R E N C E S

1. Olivieri NF, Buncic JR, Chew E, et al. Visual and auditory neurotoxicity in patients receiving subcutaneous deferoxamine infusions. N Engl J Med 1986;314:869-73.

2. Albera R, Pia F, Morra B, et al. Hearing loss and desferriox- amine in homozygous beta-thalassemia. Audiology 1988; 172:207-14.

3. Porter JB, Jaswon MS, Huehns ER, East CA, Hazell JWP. Desferrioxamine ototoxicity: evaluation of risk factors in thalassaemic patients and guidelines for Safe dosage. Br J Haematol 1989;73:403-9.

Stress hyperglycemia re development of diabetes

To the Editor: Vardi et al. (J PEDIATR 1990; 117:75-7) bring up many important

points. Certainly the value of the islet cell antibodies, the insulin antibodies, and the 1- and 3-minute insulin values during the intravenous glucose tolerance test are important considerations in the evaluation of stress hyperglycemia. There are still many ques- tions regarding the best way (if any) to predict the development of

diabetes. We received in the emergency department a 17-month-old child

with 10% hypernatremic dehydration. He had had a grand real seizure 1 hour before admission. He had had moderate vomiting and diarrhea for 1 day before admission and acute continuous vomiting of large amounts for 2 hours before the convulsion. When seen in the emergency department, he was weak and unresponsive. His temperature was 39.7 ~ C, blood pressure 104/74 mm Hg, pulse 190 beats/min, and respirations 30 breaths/min. The spinal fluid was normal except for a glucose value of 198 mg/dt (11 mmol/L). The blood glucose concentration before the initiation of rehydra- tion was 747 mg/dl (41.5 mmol/L); within 20 hours it came down to 92 mg/dl (5.1 mmol/L) with rehydration and without the use of insulin. Initially the urine contained 3% glucose, reducing sub- stances, and protein; in 24 hours, results of urinalysis were nega- tive. The serum C-peptide level obtained at admission was 11.0

ng/ml (0.9 to 4.2 ng/ml). The child was discharged in good con- dition.

His next admission was at the age of 2 years 11 months for eval- uation of fever of unknown origin. (Final diagnosis was streptococ- cal pharyngitis.) At admission, he had a serum glucose concentra- tion of 178 mg/dl (9.9 mmol/L) and the next day a fasting value of 68 mg/dl (3.8 mmol/L). On admission the urine had elevated levels of glucose (1 +) and of reducing substances and protein (3 +); test results were negative within 24 hours. The fasting glycohemo- globin value was 5.3% (4.0% to 8.0%), and the serum C-peptide concentration was 0~4 ng/ml (0.8 to 4.0 ng/ml).

At the age of 3 years 2 months the patient underwent a 5-hour oral glucose tolerance test. The glucose values at baseline, 30 min- utes, and 1, 2, 3, 4, and 5 hours were 67, 99, 99, 112, 110, 57, and 64 mg/dl, respectively. The insulin values for the same times were 1.6, 7.3, 4.0, 4.2, 3.4, <1.6, and 1.6 #U/ml. Insulin antibodies and islet cell antibodies were not detected. The child was then lost to follow-up. On the basis of the failing levels of C-peptide and the low insulin responses tO the oral glucose tolerance test, we can assume that diabetes has now developed, but it did not do so while we were able to observe the child, in spite of the excessive initial hypergly-

cemia. It seems that neither the degree of stress hyperglycemia nor the

presence of insulin antibodies is an accurate predictor of either the development of diabetes or the time Of its appearance. We agree that the detection of islet cell antibodies, insulin antibodies, and HLA types, the insulin responses to intravenously administered glucose, and probably sequential determinations of C-peptide and glycohemoglobin will give us an advantage in the early control of diabetes.

Humberto A. Latorre, MD Director, Pediatric Endocrinology

Tod Children's Hospital Youngstown, OH 44501

Allen Drash, MD Pediatric Endocrinology

Pittsburgh Children's Hospital Pittsburgh, PA 15213

Reply To the Editor:

The reported case of repeated episodes of stress hyperglycemia emphasizes again the point made by us in our article that patients with this entity constitute the group at highest risk for future de- velopment of insulin-dependent diabetes mellitus (IDDM). The patient had an unusually high blood level of glucose on his first ad- mission to the hospital, and a second episode of stress hyperglyce- mia occurred 18 months later. Such a history probably reflects a declining beta-cell mass, with an insufficient response to glucose challenge. This was more clearly demonstrated by a decreasing C- peptide level and low insulin response to an oral glucose tolerance