Cushing's disease in a 5-month infant due to a basophilic microadenoma of the pituitary gland

We report a female patient who developed severe Cushing's disease during the fifth month of life due to a basophilic pituitary adenoma Histological findings showed a basophilic microadenoma of the pituitary gland, leading to the diagnosis of Cushing's disease. The infant died because of untreatable septic shock. The importance of the present report resides in the age of the child at diagnosis, and that it was the necropsy finding of microadenoma which clarified the cause of the Cushing's syndrome, since it was not diagnosed during life. Cushing's disease is most often diagnosed in children older than 7 years, and our patient was only 5 months old when we detected the pituitary adenoma, the earliest case diagnosed so far. Cushing's syndrome in pediatric patients has been rarely reported and most cases are due to functioning adrenal tumors, usually a malignant carcinoma but occasionally a benign adenoma. The present case shows that the pituitary of these patients should be investigated with important implications in terms of therapeutic approaches, such as pituitary radiotherapy, which can cure the patient when treatment is started very soon.     

Prolonged childhood Cushing's syndrome secondary to intralesional triamcinolone acetonide

Intralesional corticosteroids have been used in the treatment of hypertrophic keloid scars for over 40 years. The few complications documented have mostly been local skin changes, viz depigmentation and cutaneous atrophy. Cushing's syndrome following intralesional injection is rare and usually self-limiting following cessation of therapy. This report describes a 9-year-old girl who developed Cushing's syndrome 2-3 weeks after a single treatment with 40 mg triamcinolone acetonide injected into keloids. Features of Cushing's syndrome and a suppressed hypothalamic-pituitary axis were present up to 9 months later. Three years after glucocorticoid injections, features of Cushing's syndrome had largely disappeared. Dosages of intralesional steroids normally recommended for adults are inappropriate for children.     

Second malignant neoplasm in treated Hodgkin's disease. Report of a patient and scope of the problem

The condition of a 6-year-old boy was diagnosed as mixed-cellularity Hodgkin's disease that involved the right side of the neck. Five years after the completion of radiation therapy for the involved area, followed by six courses of chemotherapy with mechlorethamine hydrochloride (nitrogen mustard), vincristine sulfate, procarbazine hydrochloride, and prednisone, he developed cerebral gliosarcoma. Numerous second malignant neoplasms have been reported in adults following treatment for Hodgkin's disease; however, the sequence of events in our patient is a new finding that has not, to our knowledge, been reported previously. While the second malignant tumor may have been induced by prior treatment, direct evidence is lacking.     

Severe valvular toxicity and pericarditis early after radiation therapy in a patient treated for Hodgkin's lymphoma

Hodgkin's disease can be cured in most cases by radiotherapy. However, it can increase the risk of cardiotoxicity. Here, we report a patient with Hodgkin's disease and superior vena cava syndrome who was treated with chemotherapy in combination with radiotherapy. Four months after the initiation of this therapy, she developed progressive dyspnea. Pleural and pericardial effusion, severe mitral regurgitation, moderate aortic insufficiency, and mild tricuspid regurgitation were detected in echocardiography, which suggested heart failure. The patient was then treated with intrapericardial drainage and received dopamine and diuretics for congestive heart failure; she responded well to this treatment and was discharged in good condition. After high-dose mediastinal radiation, cardiologic screening is recommended in order to identify patients with radiation-induced heart disease and to assess their need for treatment and follow-up.     

Hodgkin's disease in association with Down syndrome: a case report

The increased incidence of malignancies, especially acute leukemia, in Down syndrome has been clearly established. The association of Hodgkin's disease with Down syndrome has not been extensively documented, and only a few cases have been reported. We present here a case report of Hodgkin's disease in an 11-year-old female child with Down syndrome. The child presented with a stage IVB nodular sclerotic Hodgkin's disease and died of progressive disease. We also present a brief review of the mechanisms of development of malignancy in Down syndrome.     

Cytotoxic drug-induced fever: a report on procarbazine-induced hyperpyrexia

A case of hyperpyrexia induced by procarbazine in a child with Hodgkin's disease, neurofibromatosis, and pectus excavatum deformity is presented. After the diagnosis of stage IIIS Hodgkin's disease, combined COPP chemotherapy was initiated. One week later she presented with high fever. After a diagnosis of infection was made, chemotherapy was stopped and antibiotics were given. Nearly the same picture recurred three times after reinstituting chemotherapy. On the fourth occasion, the patient had to be hospitalized because of hyperpyrexia and arrhythmia. There was no obvious reason for fever, and cytotoxic-induced fever was considered. The drugs were given one at a time. When a test dose (10 mg) of procarbazine was given, she developed a high fever with severe nausea and vomiting. The reaction was controlled by antihistaminics and steroids. To our knowledge this is the second report on hyperpyrexia due to procarbazine administration.     

Cushing's syndrome,growth impairment,and occult adrenal suppression associated with intranasal steroids

We have previously described iatrogenic Cushing's syndrome secondary to intranasal steroids. This report further highlights the potential deleterious effects of intranasal steroids. Nine cases (including the original two cases) are reviewed to show the varied clinical manifestations of adrenal suppression caused by intranasal steroids. Four presented with Cushing's syndrome, three with growth failure, while two asymptomatic patients were discovered in the course of pituitary function testing. Four children had dysmorphic syndromes--Down's, Treacher-Collins, CHARGE association, and campomelic dysplasia--reflecting the vulnerability of such children to ENT problems, together with the difficulty of interpreting steroid induced growth failure in this context. Adrenal suppression was seen not only with betamethasone but also with budesonide, beclomethasone and flunisolide nasal preparations. A careful enquiry as to the use of intranasal steroids should be routine in children presenting with unexplained growth failure or Cushing's syndrome. Particular vigilance/awareness is required in children with dysmorphic syndromes.     

Cushing's syndrome, growth impairment, and occult adrenal suppression associated with intranasal steroids.

We have previously described iatrogenic Cushing's syndrome secondary to intranasal steroids. This report further highlights the potential deleterious effects of intranasal steroids. Nine cases (including the original two cases) are reviewed to show the varied clinical manifestations of adrenal suppression caused by intranasal steroids. Four presented with Cushing's syndrome, three with growth failure, while two asymptomatic patients were discovered in the course of pituitary function testing. Four children had dysmorphic syndromes--Down's, Treacher-Collins, CHARGE association, and campomelic dysplasia--reflecting the vulnerability of such children to ENT problems, together with the difficulty of interpreting steroid induced growth failure in this context. Adrenal suppression was seen not only with betamethasone but also with budesonide, beclomethasone and flunisolide nasal preparations. A careful enquiry as to the use of intranasal steroids should be routine in children presenting with unexplained growth failure or Cushing's syndrome. Particular vigilance/awareness is required in children with dysmorphic syndromes.     

Residual or recurrent chest mass in pediatric Hodgkin's disease. A surgical problem?

Controversy surrounds the management of a residual chest mass in patients treated for Hodgkin's disease. Between 1971 and 1985, we treated 22 children, aged 7-18 years, with pathologically proven Hodgkin's disease. Nine had radiographic evidence of mediastinal and/or pulmonary involvement. Following treatment, a residual or new chest mass occurred in three patients, prompting surgical exploration. No histologic subtype of Hodgkin's disease predominated in this group. Two patients had received radiotherapy and chemotherapy, and one had received chemotherapy alone. The erythrocyte sedimentation rate (ESR), uniformly elevated at diagnosis, was normal prior to surgery in all three patients. Gallium scans, also uniformly positive at diagnosis, were negative in two patients but positive in a third, suggesting possible relapse. At operation, however, no patient had recurrent Hodgkin's disease. Pathologic findings were thymic fibrosis, mediastinal pseudocyst, and normal thymus, respectively. We conclude that a chest mass following treatment for Hodgkin's disease may be benign, particularly if disease markers such as ESR have normalized. Moreover, a positive gallium scan does not necessarily indicate recurrent Hodgkin's disease. Although surgical exploration is a prudent policy when there is persistent evidence of residual or recurrent chest mass, our experience suggests that immediate exploration is not mandatory and may be deferred for a period of close continued observation.     

Epstein-Barr virus-associated Hodgkin''s disease in a patient with Wiskott-Aldrich syndrome

Wiskott-Aldrich syndrome is a primary immunodeficiency syndrome in which the majority of malignant complications are non-Hodgkin's lymphoma. We report here a Wiskott-Aldrich syndrome patient who developed Epstein-Barr virus-positive Hodgkin's disease in the bilateral pulmonary hilar lymph nodes. The treatment was successful as the patient achieved a complete response and event-free survival for more than 4 y. CONCLUSION: This case is very rare, but highly suggestive of the immune-mediated mechanisms in the pathogenesis of Epstein-Barr virus-associated Hodgkin's disease in an immunodeficiency patient.     

Superior vena cava syndrome in childhood: report of ten cases and review of the literature

Experience with ten children with superior vena cava obstruction is reported. Five patients had non-Hodgkin's lymphoma, two had Hodgkin's disease, two had benign lesions, and one patient was suspected on clinical and radiologic basis to have a lymphoma. The clinical situation at presentation was often critical and required rapid treatment. Radiotherapy and/or chemotherapy were used initially as lymphoma was the most frequent cause of obstruction. Urgent thoracotomy was resorted to when treatment failed. Survival with no evidence of disease for more than 5 years was observed in three children: one had a cystic lymphangioma, another had a mediastinal abscess, and the third had a Hodgkin's lymphoma. Review of the literature from 1951 to 1976 revealed that only 24/150 children reported with superior vena cava obstruction syndrome had mediastinal tumors; the remainder developed the obstruction after surgical procedures on the heart or vena cava.     

Hodgkin lymphoma in a child with sickle cell anemia

There are reports of patients with sickle cell disease who developed hematological malignancies but the relationship between these malignancies and sickle cell disease (SCD) is not yet defined. The co-existence of a hematological malignancy with SCD poses certain challenges for the management of each condition. We describe a 7-year-old boy with sickle cell anemia who developed Hodgkin's lymphoma and the challenges of management. He presented with a 4-year history of bilateral neck swelling and a 2-month history of weight loss and high-grade fever. Histology of a lymph node biopsy was consistent with mixed cellularity Hodgkin's lymphoma. He was treated with five cycles of Cyclophosphamide, Vincristine, Procarbazine and Prednisolone (COPP) and had complete clinical response. Chemotherapy was associated with an increase in frequency of painful crises and complicated by septicaemia. Blood transfusion needs were minimal; apart from the transfusion preceding the first cycle of chemotherapy, there was no need for further transfusion. Myelosuppression was not a problem in the patient; he responded well to antibiotics during the two episodes of septicemia without the use of hemopoetic growth factor. Patients with sickle cell anaemia who develop Hodgkin's lymphoma can be successfully treated with chemotherapy along with supportive management for crises and infections.     

Treatment of Hodgkin's disease stages I and II with chemotherapy alone

Ten previously untreated patients with stages I and II Hodgkin's disease were treated with MOPP chemotherapy alone. Eight of nine evaluable patients went into complete remission (CR). Six remained in CR on the average 82.7 months after induction. Two patients relapsed early and died more than 5 years after entering the study. The patient in whom CR was not achieved died as well. The estimated 10-year survival rate is 51%. This experience adds to the very small number of reports that have appeared describing the results of treatment of patients with early stage Hodgkin's disease with MOPP alone.     

Gastric Perforation in Non-Hodgkin'S Lymphoma

Oral steroids are an important component in the treatment of leukemia and lymphoma in children. Until recently it was widely accepted that treatment with oral steroids carried the risk of gastrointestinal complications, in particular gastric irritation, gastrointestinal ulceration, and hemorrhage. Though spontaneous intestinal perforation has been reported, to our knowledge, spontaneous perforation of the stomach in a child with lymphoma taking oral steroids has not previously been described. Furthermore, this report would appear to contradict recent reports claiming that steroid-induced ulcers do not arise unless the patient is also concurrently receiving nonsteroidal anti-inflammatory drugs.^1,2,3     

Simultaneously occurring alopecia areata and Hodgkin's lymphoma: complete remission of both diseases with MOPP/ABV chemotherapy.

A 43-year-old man presented with simultaneously occurring alopecia areata and stage IIIB nodular sclerosing Hodgkin's disease. Systemic symptoms of Hodgkin's disease were present for 6 months, and rapidly developing patchy hair loss of the scalp was present for 2 weeks prior to presentation. The patient was treated with eight cycles of MOPP-ABV chemotherapy that resulted in complete remission of Hodgkin's-disease. Four months after the completion of chemotherapy, the patient had normal hair regrowth with no evidence of alopecia areata. Alopecia areata may be an autoimmune disease and may respond to chemotherapy.     

Double autologous bone marrow transplantation for acute myelogenous leukemia in a patient treated for Hodgkin's disease

A 30-year-old man developed acute myelogenous leukemia nearly 3 years after treatment of Hodgkin's disease with radiation and three chemotherapy combinations. Remission was induced with one cycle of high-dose Ara-C therapy. Three cycles of consolidation chemotherapy were given. The patient then had two autologous bone marrow transplants, the first after conditioning with 5 Gy total body irradiation, the second after Melphalan 140 mg/m2. The procedures were well tolerated, although hematological reconstitution was very slow after the second autotransplant. The patient has been disease-free for over 4 years. Such patients may be more vulnerable to transplant-related complications because of their previous exposure to chemotherapy and radiation, which may damage several organs including the bone marrow. This report demonstrates that patients with secondary acute myelogenous leukemia may tolerate a double autotransplant procedure and achieve durable remissions.     

Familial Cushing's disease with severe weight loss occurring in late childhood

We describe a rare case of familial Cushing's disease occurring in a 7-year-old boy, and 19 years of follow up. Our patient first presented soon after his maternal aunt had been treated for Cushing's disease. The clinical presentation was made complicated by the development of an intercurrent eating disorder resembling anorexia nervosa. This resulted in marked weight loss, and even though serum and urinary cortisol levels were elevated, many of the clinical stigmata of Cushing's disease were absent. Eating disorders are relatively uncommon in boys, and in this case there was an organic cause for the abnormal behaviour. This case shows, furthermore, that even the obesity of Cushing's disease can be overcome by the combination of diet and exercise.     

Gastric Perforation in Non-Hodgkin'S Lymphoma

Oral steroids are an important component in the treatment of leukemia and lymphoma in children. Until recently it was widely accepted that treatment with oral steroids carried the risk of gastrointestinal complications, in particular gastric irritation, gastrointestinal ulceration, and hemorrhage. Though spontaneous intestinal perforation has been reported, to our knowledge, spontaneous perforation of the stomach in a child with lymphoma taking oral steroids has not previously been described. Furthermore, this report would appear to contradict recent reports claiming that steroid-induced ulcers do not arise unless the patient is also concurrently receiving nonsteroidal anti-inflammatory drugs.^1,2,3     

Hodgkin's disease in children: Involvement of lung and pleura

In 160 children with Hodgkin's disease, lung involvement was studied. In 14.4%, lung lesions were diagnosed at the first admission and an additional 7.5% of patients developed lung lesions in the course of the disease. As a rule lung involvement was observed in advanced disease. It has been stated that there is no particular difference in the response to treatment in any particular type of lesion, spread either by contiguity or dissemination. Of all methods of treatment, combination chemotherapy (MOPP programme) showed the best results. In our series of children it was not possible to show any advantage to favour irradiation as against combination chemotherapy in the treatment of lung lesions.     

Glucocorticosteroids and growth hormone secretion under physiological conditions and in states of steroid excess

Cortisol and growth hormone (GH) secretion (spontaneous variations at night and the release induced by insulin hypoglycaemia) were investigated in 69 children and adolescents. Statistical analysis of approximately 600 pairs of cortisol and GH values in this study demonstrated that physiological fluctuations of cortisol do not alter GH secretion.A review of the literature shows that GH secretion is consistently depressed in Cushing's disease of central origin and in Cushing's syndrome due to adrenal carcinoma. When acutely administered, doses higher than 100 mg of cortisol (or equivalent amounts of other steroids) per adult are necessary to block GH secretion and the hormones have to be given several hours previously. In long-term steroid treatment, suppression of GH is observed in only 1 out of 3 patients. The effect apparently does not persist beyond elimination of the last dose, i.e. generally not longer than 12 to 24 h. These data can be taken as a rationale for intermittent or alternating dosage schedules, and for the use of short acting derivatives if long-term, high-dose steroid treatment is necessary in children.It remains to be established whether growth deficiency in exogenous hypercortisolism is due to suppression of GH secretion, decreased production of somatomedins, direct antagonism of the action of somatomedins on growing cartilage, or a combination of these mechanisms.Supported by Deutsche Forschungsgemeinschaft (Mu 254/5)In part presented at the Joint meeting, ESPR, ESPE, WGMM, Rotterdam, 1976Dedicated to Professor H. Bickel on the occasion of his 60th birthday