International Urology and Nephrology 24 (6), pp. 591--596 (1992)
Ultrasonographic Screening of Neonatal Adrenal
Apoplexy GY. J6JART, G. NAGY Department of Paediatry, Toldy Ferenc Hospital, Cegl6d, Hungary (Accepted October 22~ 1991) A total of 1785 newborns were subjected in the course of 14 months to ultrasonographic screening. Adrenal bleeding among those born via caesarean section has not been recorded. Among 1490 born via vagina there were 14 (0.94%) with adrenal apoplexy and 80 were delivered with clavicular fracture (5.37 %). There were 13 with unilateral bleeding. Hormone examination applied to one infant with bilateral bleeding confirmed adrenal insufficiency which normalized after three months. In the aetiology of neonatal adrenal apoplexy the dominant causative role is attributed to birth trauma. Adrenal apoplexy in the newborn is a designation formerly encountered mostly in post mortem reports. It had rarely been diagnosed on the strength o f clinical symptoms, such as palpable abdominal tumour or blood loss [11 ], until the novel method of ultrasonography helped to realize that the lesion, though occurring with increasing frequency, leaves the patient clinically asymptomatic for the most part and tends to heal spontaneously. Ultrasonographic screenings by Rubecz et al. [24] discovered adrenal haemorrhage in 2.9 % o f newborns. This paper reports on the experience gained at our Department since April 1990, when we first introduced ultrasonographic screening on a regular basis to diagnose neonatal adrenal apoplexy. Material and method In the course of 14 months, from April 1990 to May 1991, a total of 1785 children were born in our hospital. All were subjected within 2 to 4 days to ultrasonography by means of a Picker 7000 LSC equipment with convex headpiece of 3.5 M H z frequency. Each child with adrenal haemorrhage was kept under observation until the h a e m a t o m a resorbed. The clavicles were carefully controlled physically at birth and before discharge from hospital. Results Out of 1785 infants 1490 were born by vaginal delivery and 295 by caesarean section. A m o n g the caesareans adrenal bleeding and clavicular fracture have not been recorded. Among the 1490 naturally delivered there were 14 with adrenal VSP, Utrecht Akad~rniai Kiad6, Budapest
592
Jd]6rt, N a y y : N e o n a t a l adrenal apoplexy
apoplexy (0.94 %) and 80 with clavicular fracture (5.37 %). Adrenal bleeding occurred in 7 (8.75 %) of the fracture group and in 7 (0.50%) among the 1410 born with sound clavicula. Fracture on one side and bleeding on the other were encountered in one patient, unilateral fracture and bilateral bleeding in one, and both types of injury on the same side in 5. Average body weight at birth was 3121 g for the non-bleeders and 3356 g for the bleeders. A list o f predisposing factors and associated anomalies is given in Table 1. Table 1 Maternal and foetal anomalies in 14 newborns with adrenal haemorrhage No.
Umbilical cord round neck Labour infirmity, oxytocin infusion Maternal perinatal fever Squeezed shoulder Vacuum extraction Low Apgar score Clavicular fracture of these: brachial plexus paresis Low prothrombin level Icterus
6 3 1 1 1 1 7 1 1 5
Thirteen out of the 14 apoplectic were unilaterally affected (10 right, 3 left) and presented no symptoms. The solitarybilateral bleeder manifested severe hypadrenia. One of the patients developed within two days of birth a mass o f mixed echostructure above the right kidney which we had first mistaken for adrenal haemorrhage but identified on control as neuroblastoma.
Case report A primigravida aged 21, admitted in febrile state to the labour ward in the 40th week o f gestation, was given oxytocin infusion to invigorate labour. As the amniotic fluid turned meconic, confinement had to be completed by means of vacuum extraction because the foetus became bradycardiac. Weight at birth was 3250 g, Apgar score 6/8. Left clavicular fracture occurred during delivery. Following treatment, the infant's general condition improved, blood sugar was 0.7 mmol/1, blood count normal, liquor cell count 105/~k. Ceftazidim and glucose infusion upon bacteriologic culture test. Grey discolouration at one day's age, blood pressure 55 mm Hg, blood sugar normal. Right kidney tangibly enlarged (or downward dislocated). Serum electrolysis followed by antibiotic therapy International Uroloyy and Nephrology 24, 1992
Jdjdrt, Nagy : Neonatal adrenal apoplexy
593
including penicillin. A later received laboratory report confirmed fl-haemolytic streptococci in the secretions. Generalized spastic attack at 30 hours abated temporarily upon i.v. administration of diazepam and glycerin. Ultrasonography ruled out cerebral bleeding. Two masses of mixed echostructure, size 37 x 25 x 21 mm over the right and 30 x 21 x 20 mm over the left kidney, were discovered, causing caudad dislocation of the kidneys. Bilateral haemorrhage turned cystose after three days, then gradually dwindled and eventually absorbed after two months. Previous laboratory findings: blood sugar 4.3 mmol/1, serum Na 118, K 5.4, Ca 2.30 mmol/1. Lacking a serum cortisol level tester, we immediately administered 10 ml of Di Adreson F aquosum and 3 70 NaC1 infusion which stopped the spasm. The serum Na level gradually rose, keeping normal after two days without substitution. Prednisolone medication was carried on until two weeks' age. On days 8 and 15 following the last prednisolone dose, serum cortisol level was below 2.5 #g/dl, as characteristic for hypadrenia. Subsequent normal development, asymptomatic without hormone substitute. ACTH provocation test at three-month age showed initial serum cortisol value of 11.4 #g/dl (normal) which rose to 44.5 pg/dl six hours after administration of 0.25 mg Synacten depot. Adrenal funchon normalized.
Discussion
The introduction of ultrasonography has made it easier to diagnose neonatal adrenal bleeding. The congealed haematoma appears on the screen as a solid mass above the kidney, with minor echo-free spots inside. Upon liquefaction the structure becomes cystose, containing small to medium sized coagula. Later the organizing haematoma begins to dwindle and solidify, until it absorbs in a couple of weeks (or months), leaving occasional deposits of calcium. Reflections as to whether adrenal bleeding was the cause of a newborn's death or a secondary process revealed only post mortem, date back to pre-ultrasonographic times, when autopsies had confirmed that 80 % of diagnosed cases occurred in premature infants. Since the introduction of the sonographic technique, ever more cases have been diagnosed in living infants of average or high body weight. Sonographic screenings performed by Rubecz et al. in 1989 [24] established the frequency and the clinical significance of adrenal bleeding. Among 780 deliveries they encountered 25 cases, including 20 apoplectiform bleedings (2.53 %), of which three were bilateral. They lost one patient for diabetic foetopathy, the rest having been symptom-free. Major importance in the aetiology of neonatal adrenal bleeding is attributed to such factors as coagulation disorders, infection, hypoxia and birth injury [17, 19, 24]. One patient (the reported case) showed infection associated with hypoxia as well as natal trauma. Among our patients there was one with coagulation disorder. Tendency for hypoxia may arise when the umbilical cord gets wound round the neck, as happened in six cases, including two who presented foetal International Urology and Nephroloyy 24, 1992
594
J6j6rt, N a y y : Neonatal adrenal a p o p l e x y
bradycardia. One was born with abnormally low Apgar score. The question has to be decided, which of two factors is of greater consequence in respect of adrenal bleeding: the hypoxic condition itself or the birth trauma involved necessarily by the speed to deliver the parturient of a hypoxic foetus. The experience is that premature infants suffer from hypoxia more often than the mature born, yet are less frequently affected by haemorrhage. Heart massage to deal with severe hypoxia may also cause injury. Statements in the literature on the subject confirm that: adrenal bleeding may occur after caesarean section as well [3, 19, 24]; high birth weight is a predisposing factor [23, 25]; adrenal bleeders are born with higher birth weight than non-bleeders [24] (attested by our own records); high birth weight frequently associates with natal trauma [1, 7, 11, 13] including clavicular fracture [2] and brachial plexus palsy. Bleeding in our own material occurred 18 times as often among the clavicular fractured as among the non-fractured, and one out of every two bleeders was born with fractured clavicle. Factors predisposing for trauma are the relatively big size of the adrenal during the perinatal period - a multiple of what it measures in terms of percentage in later life - and an excess of blood supply. Pressure in the adrenal sinusoids increases with the abdominal pressure and may cause the frail veins to break. Bleeding occasionally starts from the vascular medullary substance. The suprarenal vein discharges on the right direct, on the left via the renal vein, into the vena cava inferior. The fact that right venous pressure is transferred direct onto the minor adrenal veins accounts for the higher (in our material three times as high) frequency of bleeding on the right side. None of these factors accounts for the development of intrauterine haemorrhage [8, 20]. Neonatal adrenal bleeding for the majority is passing symptom-free until the grown mass becomes palpable. The absorbing haematoma is apt to cause jaundice. Five of our 14 patients presented hyperbilirubinaemia, calling for phototherapy. When a haematoma bursts, it may take the appearance of abdominal bleeding or disperse via the retroperitoneum, discolouring the abdominal wall and the scrotal skin [21 ]. Heavy bleeding occasionally produces anaemia - which did not occur in our patients - and shock. Adrenal insufficiency was only found in connection with bilateral haemorrhage [14, 27], but even this went mostly without hypadrenia [1, 5, 6, 7, 13, 15, 24]. Congenital sepsis in one of our patients improved during the first day of life. The grave condition which developed at 30 hours' age was due to electrolyte disorder, which arose in consequence of adrenal insufficiency. At the time we discovered the bleeding, there was no way to perform hormone test. As soon as the infant recovered, we could safely discontinue prednisolone since hypadrenia alone never produces a clinical symptom but leads under the effect of stress (such as caused by sepsis in our patient) to aggravation [18]. After a brief term of steroid therapy (12 days in our case), the adrenal function returned to normal in a matter of days [9, 18], confirming that the low serum cortisol level measured on days 8 and 15 following the last prednisolone dose was a sure hypadrenia indicator [4]. International Urology and Nephrology 24, 1992
Jtjdrt, Nagy : Neonatal adrenal apoplexy
595
Drop in the adrenal function was a transitory sign. At three-month age serum cortisol level proved normal and the adrenal reacted well to ACTH provocation [22]. Klemm et al. [14] and Wagner [27] have recorded similar experience. Black and Williams [1] found that sound tissue was always present in the biopsy samples they had taken from bleeding neonatal adrenal areas. Apparently the adrenal has plentiful regenerative power and its bleeding in the infant is no reason to worry that hypadrenia should develop in later life. In pre-sonographic times most of the infants with adrenal haemorrhage were put to surgery [1, 6, 7, 10]. However, as more and more symptom-free cases of bleeding began to be determined, surgical overactivity appeared pointless since the majority of patients healed spontaneously. Bleeding stops on cessation of the coagulation disorder and the haematoma absorbs. The presence of sound adrenal islets in the extravasation aids the process of regeneration [1 ], so harm may come from removing them. Operation, ultrasound-aided puncture or drainage may be called for when the haematoma has produced compression symptoms due to oversize, or has given rise to an abscess due to infection [19]. Heavy bleeding necessitates transfusion. Hormone replacement is only indicated in the rare instances when clinical and laboratory signs of hypadrenia appear. We applied only glucocorticoids. The electrolyte disorder became normal in response to sodium chloride infusion, without need for mineralocorticoids. Congenital neuroblastoma is not always distinguishable on first examination from neonatal adrenal haemorrhage [6, 26]; hence it is imperative to trace the bleeding by sonography. Differentiation is possible on the ground of catecholamine discharge but *I-MIBG scintigraphy does not exclude error in interpreting a negative result [12]. We kept the patients under watch until resistance has fully ceased, and correctly diagnosed the congenital neuroblastoma we had first mistaken for adrenal haemorrhage.
Acknowledgement We owe thanks to Assistant Professor Dr. J~nos S61yom, lind Department of Paediatry, Semmelweis University Medical School, Budapest, for determination of the serum cortisol level and valuable advice.
References 1. Black, J., Williams, D. J. : Natural history of adrenal hemorrhage in the newborn. Arch. Dis. Childh., 48, 183 (1973). 2. Brill, P. W., Krasna, I. H., Aaron, H. : An early rim sign in neonatal adrenal hemorrhage. Am. J. RoentvenoL, 127, 289 (1976). 3. Brill, P. W., Jagannath, A., Winchester, P., Markin, J. A., Zirinsky, K.: Adrenal hemorrhage and renal veinthrombosis in the newborn. MR imaging.Radiology, 170, 95 (1989).
4. Clayton,R. N. : Diagnosisof adrenal insufficiency.Br. Med. J., 298, 271 (1989). 5. Diekerman, J. D., Tampas, J. P, : Adrenal hemorrhage in the newborn. Clin. Pediat., 16, 314 (1977). International Urology and Nephrology 24, 1992
596
J6jdrt, Nagy : Neonatal adrenal apoplexy
6. Ekl6f, O., Mortensson, W., Sandstedt, B. : Suprarenal hematoma versus neuroblastoma complicated by hemorrhage. A diagnostic dilemma in the newborn. Acta Radiol. Diagn., 27, 3 (1986). 7. Enayat, U., Wendler, H., Hubmer, G. : Zur diagnostischen Problematik massiver Nebennierenblutungenin Neugeborenen. Wien. Klin. Wochenschr., 87, 583 (1975). 8. Gotoh, T., Adachi, Y., Nounaka, O., Mori, T., Koyanagi, T. : Adrenal hemorrhage in the newborn with evidence of bleeding in utero. J. UroL, 141, 1145 (1989). 9. Hagg, E., Asplud, K., Lithner, F. : Value of basal plasma cortisol assays in the assessment of pituitary-adrenal insufficiency. Clin. Endocrinol, 26, 221 (1987). 10. Heij, H. A., Taets von Amerongen, A. H., Ekkelkamp, S., Vos, A.: Diagnosis and management of neonatal adrenal hemorrhage. Pediat. Radiol., 17, 391 (1989). 11. Hill, E. E., Williams, J. A. : Massive adrenal hemorrhage in the newborn. Arch. Dis. Childh., 34, 178 (1959). 12. Jacobs, A., Delree, M., Desprechins, B., Otten, J., Ferster, A., Jonckheer, M. H., Mertens, J., Ham, H. R., Piepsz, A. : Consolidating the role of *I-MIBG-scintigraphy in childhood neuroblastoma: Five years of clinical experience. Pediat. RadioL, 20, 157 (1990). 13. Khuri, F. J., Alton, D. J., Hardy, B. E., Cook, G. T., Churchill, B. M.: Adrenal hemorrhage in neonates: Report of 5 cases and review of the literature. J. Urol., 124, 684 (1980). 14. Klemm, W., Bierich, J. R., MiSlker, H., Nolte, K.: Akute Nebennierenblutungen als Geburtskomplikation: Zur Bedeutung der Fr/.ihdiagnose. Monatsschr. Kinderheilk., 124, 106 (1976). 15. Koch, K. I., Corry, O. : Simultaneous renal vein thrombosis and bilateral adrenal hemorrhage. MR demonstration. J. Comput. Assist. Tomogr., 10, 681 (1986). 16. Langer, R., Kaufmann, H. J., St/iblein, W. : Sonographische Befunde der postpartalen Nebennierenblutungen.Monatsschr. Kinderheilk., 133, 812 (1985). 17. Leidig, E. : Sonographie der Nebennierenerkrankungendes Neugeborenen. Ultraschall, 9, 155 (1988). 18. Lightner, E. S., Johnson, H., Corrigon, J. J. : Rapid adrenocortical recovery after shortterm glucocorticoid therapy. Am. J. Dis. Childh., 135, 790 (1981). 19. Mittelstaedt, C. A., Volberg, F. M., Merten, D. F., Brill, P. W. : The sonographic diagnosis of neonatal adrenal hemorrhage. Radiology, 131, 453 (1979). 20. Pinck, R. L., Constantocopoulos, C. G., Felice, A., Ippolito, J., Rubin, B., Haller, J. O.: Adrenal hemorrhage in the newborn with evidence of bleeding while in utero. J. UroL, 122, 813 (1979). 21. Putman, M. H. : Neonatal adrenal hemorrhage presenting as a right scrotal mass. JAMA, 261, 2958 (1989). 22. Reynolds, J. W., Turnipseed, M. R., Mirkin, B. L. : Adrenal cortical function in abnormal newborn infants. J. Steroid Biochem., 6, 669 (1975). 23. Rosegger, H., Rollett, H. R., Assun~itegui, M. : Routineuntersuchung des reifen Neugeborenen. Wien. Klin. Wochenschr., 102, 294 (1990). 24. Rubecz, I., Gasztonyi, V., Szauer, E., Kodela, I.: Neonatal adrenal hemorrhage (in Hungarian with English summary). Orv. Hetil., 130, 2519 (1989). 25. Salonen, I. S., Kusitato, R. : Birth injuries. Incidence and predisposing factors. Z. Kinderchir., 45, 133 (1990). 26. Stichnoth, F. A., Kehr, S., Baumer, K. : Kernspintomographie in tier Differentialdiagnose yon Nebennierenblutung und Neuroblastom eines Neugeborenen. Monatsschr. Kinderheilk., 138, 221 (1990). 27. Wagner, A. C.: Bilateral hemorrhagic pseudocyst of the adrenal glands in a newborn. Amer. J. Radiol., 86, 540 (1961).
lnternationat UroloGyand Nephrotogy 24, 1992
Ultrasonographic Screening of Neonatal Adrenal
Apoplexy GY. J6JART, G. NAGY Department of Paediatry, Toldy Ferenc Hospital, Cegl6d, Hungary (Accepted October 22~ 1991) A total of 1785 newborns were subjected in the course of 14 months to ultrasonographic screening. Adrenal bleeding among those born via caesarean section has not been recorded. Among 1490 born via vagina there were 14 (0.94%) with adrenal apoplexy and 80 were delivered with clavicular fracture (5.37 %). There were 13 with unilateral bleeding. Hormone examination applied to one infant with bilateral bleeding confirmed adrenal insufficiency which normalized after three months. In the aetiology of neonatal adrenal apoplexy the dominant causative role is attributed to birth trauma. Adrenal apoplexy in the newborn is a designation formerly encountered mostly in post mortem reports. It had rarely been diagnosed on the strength o f clinical symptoms, such as palpable abdominal tumour or blood loss [11 ], until the novel method of ultrasonography helped to realize that the lesion, though occurring with increasing frequency, leaves the patient clinically asymptomatic for the most part and tends to heal spontaneously. Ultrasonographic screenings by Rubecz et al. [24] discovered adrenal haemorrhage in 2.9 % o f newborns. This paper reports on the experience gained at our Department since April 1990, when we first introduced ultrasonographic screening on a regular basis to diagnose neonatal adrenal apoplexy. Material and method In the course of 14 months, from April 1990 to May 1991, a total of 1785 children were born in our hospital. All were subjected within 2 to 4 days to ultrasonography by means of a Picker 7000 LSC equipment with convex headpiece of 3.5 M H z frequency. Each child with adrenal haemorrhage was kept under observation until the h a e m a t o m a resorbed. The clavicles were carefully controlled physically at birth and before discharge from hospital. Results Out of 1785 infants 1490 were born by vaginal delivery and 295 by caesarean section. A m o n g the caesareans adrenal bleeding and clavicular fracture have not been recorded. Among the 1490 naturally delivered there were 14 with adrenal VSP, Utrecht Akad~rniai Kiad6, Budapest
592
Jd]6rt, N a y y : N e o n a t a l adrenal apoplexy
apoplexy (0.94 %) and 80 with clavicular fracture (5.37 %). Adrenal bleeding occurred in 7 (8.75 %) of the fracture group and in 7 (0.50%) among the 1410 born with sound clavicula. Fracture on one side and bleeding on the other were encountered in one patient, unilateral fracture and bilateral bleeding in one, and both types of injury on the same side in 5. Average body weight at birth was 3121 g for the non-bleeders and 3356 g for the bleeders. A list o f predisposing factors and associated anomalies is given in Table 1. Table 1 Maternal and foetal anomalies in 14 newborns with adrenal haemorrhage No.
Umbilical cord round neck Labour infirmity, oxytocin infusion Maternal perinatal fever Squeezed shoulder Vacuum extraction Low Apgar score Clavicular fracture of these: brachial plexus paresis Low prothrombin level Icterus
6 3 1 1 1 1 7 1 1 5
Thirteen out of the 14 apoplectic were unilaterally affected (10 right, 3 left) and presented no symptoms. The solitarybilateral bleeder manifested severe hypadrenia. One of the patients developed within two days of birth a mass o f mixed echostructure above the right kidney which we had first mistaken for adrenal haemorrhage but identified on control as neuroblastoma.
Case report A primigravida aged 21, admitted in febrile state to the labour ward in the 40th week o f gestation, was given oxytocin infusion to invigorate labour. As the amniotic fluid turned meconic, confinement had to be completed by means of vacuum extraction because the foetus became bradycardiac. Weight at birth was 3250 g, Apgar score 6/8. Left clavicular fracture occurred during delivery. Following treatment, the infant's general condition improved, blood sugar was 0.7 mmol/1, blood count normal, liquor cell count 105/~k. Ceftazidim and glucose infusion upon bacteriologic culture test. Grey discolouration at one day's age, blood pressure 55 mm Hg, blood sugar normal. Right kidney tangibly enlarged (or downward dislocated). Serum electrolysis followed by antibiotic therapy International Uroloyy and Nephrology 24, 1992
Jdjdrt, Nagy : Neonatal adrenal apoplexy
593
including penicillin. A later received laboratory report confirmed fl-haemolytic streptococci in the secretions. Generalized spastic attack at 30 hours abated temporarily upon i.v. administration of diazepam and glycerin. Ultrasonography ruled out cerebral bleeding. Two masses of mixed echostructure, size 37 x 25 x 21 mm over the right and 30 x 21 x 20 mm over the left kidney, were discovered, causing caudad dislocation of the kidneys. Bilateral haemorrhage turned cystose after three days, then gradually dwindled and eventually absorbed after two months. Previous laboratory findings: blood sugar 4.3 mmol/1, serum Na 118, K 5.4, Ca 2.30 mmol/1. Lacking a serum cortisol level tester, we immediately administered 10 ml of Di Adreson F aquosum and 3 70 NaC1 infusion which stopped the spasm. The serum Na level gradually rose, keeping normal after two days without substitution. Prednisolone medication was carried on until two weeks' age. On days 8 and 15 following the last prednisolone dose, serum cortisol level was below 2.5 #g/dl, as characteristic for hypadrenia. Subsequent normal development, asymptomatic without hormone substitute. ACTH provocation test at three-month age showed initial serum cortisol value of 11.4 #g/dl (normal) which rose to 44.5 pg/dl six hours after administration of 0.25 mg Synacten depot. Adrenal funchon normalized.
Discussion
The introduction of ultrasonography has made it easier to diagnose neonatal adrenal bleeding. The congealed haematoma appears on the screen as a solid mass above the kidney, with minor echo-free spots inside. Upon liquefaction the structure becomes cystose, containing small to medium sized coagula. Later the organizing haematoma begins to dwindle and solidify, until it absorbs in a couple of weeks (or months), leaving occasional deposits of calcium. Reflections as to whether adrenal bleeding was the cause of a newborn's death or a secondary process revealed only post mortem, date back to pre-ultrasonographic times, when autopsies had confirmed that 80 % of diagnosed cases occurred in premature infants. Since the introduction of the sonographic technique, ever more cases have been diagnosed in living infants of average or high body weight. Sonographic screenings performed by Rubecz et al. in 1989 [24] established the frequency and the clinical significance of adrenal bleeding. Among 780 deliveries they encountered 25 cases, including 20 apoplectiform bleedings (2.53 %), of which three were bilateral. They lost one patient for diabetic foetopathy, the rest having been symptom-free. Major importance in the aetiology of neonatal adrenal bleeding is attributed to such factors as coagulation disorders, infection, hypoxia and birth injury [17, 19, 24]. One patient (the reported case) showed infection associated with hypoxia as well as natal trauma. Among our patients there was one with coagulation disorder. Tendency for hypoxia may arise when the umbilical cord gets wound round the neck, as happened in six cases, including two who presented foetal International Urology and Nephroloyy 24, 1992
594
J6j6rt, N a y y : Neonatal adrenal a p o p l e x y
bradycardia. One was born with abnormally low Apgar score. The question has to be decided, which of two factors is of greater consequence in respect of adrenal bleeding: the hypoxic condition itself or the birth trauma involved necessarily by the speed to deliver the parturient of a hypoxic foetus. The experience is that premature infants suffer from hypoxia more often than the mature born, yet are less frequently affected by haemorrhage. Heart massage to deal with severe hypoxia may also cause injury. Statements in the literature on the subject confirm that: adrenal bleeding may occur after caesarean section as well [3, 19, 24]; high birth weight is a predisposing factor [23, 25]; adrenal bleeders are born with higher birth weight than non-bleeders [24] (attested by our own records); high birth weight frequently associates with natal trauma [1, 7, 11, 13] including clavicular fracture [2] and brachial plexus palsy. Bleeding in our own material occurred 18 times as often among the clavicular fractured as among the non-fractured, and one out of every two bleeders was born with fractured clavicle. Factors predisposing for trauma are the relatively big size of the adrenal during the perinatal period - a multiple of what it measures in terms of percentage in later life - and an excess of blood supply. Pressure in the adrenal sinusoids increases with the abdominal pressure and may cause the frail veins to break. Bleeding occasionally starts from the vascular medullary substance. The suprarenal vein discharges on the right direct, on the left via the renal vein, into the vena cava inferior. The fact that right venous pressure is transferred direct onto the minor adrenal veins accounts for the higher (in our material three times as high) frequency of bleeding on the right side. None of these factors accounts for the development of intrauterine haemorrhage [8, 20]. Neonatal adrenal bleeding for the majority is passing symptom-free until the grown mass becomes palpable. The absorbing haematoma is apt to cause jaundice. Five of our 14 patients presented hyperbilirubinaemia, calling for phototherapy. When a haematoma bursts, it may take the appearance of abdominal bleeding or disperse via the retroperitoneum, discolouring the abdominal wall and the scrotal skin [21 ]. Heavy bleeding occasionally produces anaemia - which did not occur in our patients - and shock. Adrenal insufficiency was only found in connection with bilateral haemorrhage [14, 27], but even this went mostly without hypadrenia [1, 5, 6, 7, 13, 15, 24]. Congenital sepsis in one of our patients improved during the first day of life. The grave condition which developed at 30 hours' age was due to electrolyte disorder, which arose in consequence of adrenal insufficiency. At the time we discovered the bleeding, there was no way to perform hormone test. As soon as the infant recovered, we could safely discontinue prednisolone since hypadrenia alone never produces a clinical symptom but leads under the effect of stress (such as caused by sepsis in our patient) to aggravation [18]. After a brief term of steroid therapy (12 days in our case), the adrenal function returned to normal in a matter of days [9, 18], confirming that the low serum cortisol level measured on days 8 and 15 following the last prednisolone dose was a sure hypadrenia indicator [4]. International Urology and Nephrology 24, 1992
Jtjdrt, Nagy : Neonatal adrenal apoplexy
595
Drop in the adrenal function was a transitory sign. At three-month age serum cortisol level proved normal and the adrenal reacted well to ACTH provocation [22]. Klemm et al. [14] and Wagner [27] have recorded similar experience. Black and Williams [1] found that sound tissue was always present in the biopsy samples they had taken from bleeding neonatal adrenal areas. Apparently the adrenal has plentiful regenerative power and its bleeding in the infant is no reason to worry that hypadrenia should develop in later life. In pre-sonographic times most of the infants with adrenal haemorrhage were put to surgery [1, 6, 7, 10]. However, as more and more symptom-free cases of bleeding began to be determined, surgical overactivity appeared pointless since the majority of patients healed spontaneously. Bleeding stops on cessation of the coagulation disorder and the haematoma absorbs. The presence of sound adrenal islets in the extravasation aids the process of regeneration [1 ], so harm may come from removing them. Operation, ultrasound-aided puncture or drainage may be called for when the haematoma has produced compression symptoms due to oversize, or has given rise to an abscess due to infection [19]. Heavy bleeding necessitates transfusion. Hormone replacement is only indicated in the rare instances when clinical and laboratory signs of hypadrenia appear. We applied only glucocorticoids. The electrolyte disorder became normal in response to sodium chloride infusion, without need for mineralocorticoids. Congenital neuroblastoma is not always distinguishable on first examination from neonatal adrenal haemorrhage [6, 26]; hence it is imperative to trace the bleeding by sonography. Differentiation is possible on the ground of catecholamine discharge but *I-MIBG scintigraphy does not exclude error in interpreting a negative result [12]. We kept the patients under watch until resistance has fully ceased, and correctly diagnosed the congenital neuroblastoma we had first mistaken for adrenal haemorrhage.
Acknowledgement We owe thanks to Assistant Professor Dr. J~nos S61yom, lind Department of Paediatry, Semmelweis University Medical School, Budapest, for determination of the serum cortisol level and valuable advice.
References 1. Black, J., Williams, D. J. : Natural history of adrenal hemorrhage in the newborn. Arch. Dis. Childh., 48, 183 (1973). 2. Brill, P. W., Krasna, I. H., Aaron, H. : An early rim sign in neonatal adrenal hemorrhage. Am. J. RoentvenoL, 127, 289 (1976). 3. Brill, P. W., Jagannath, A., Winchester, P., Markin, J. A., Zirinsky, K.: Adrenal hemorrhage and renal veinthrombosis in the newborn. MR imaging.Radiology, 170, 95 (1989).
4. Clayton,R. N. : Diagnosisof adrenal insufficiency.Br. Med. J., 298, 271 (1989). 5. Diekerman, J. D., Tampas, J. P, : Adrenal hemorrhage in the newborn. Clin. Pediat., 16, 314 (1977). International Urology and Nephrology 24, 1992
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J6jdrt, Nagy : Neonatal adrenal apoplexy
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