Donald Zimmerman

Attained adult height after childhood asthma: Effect of glucocorticoid therapy

BACKGROUND Although oral and inhaled glucocorticoid therapy may impair growth in children with asthma, the effect of glucocorticoid therapy and asthma on attained adult height has not been extensively studied in representative children in the community. OBJECTIVES The study was designed to compare the attained adult height of children with asthma with the attained adult height of nonasthmatic children and to compare the attained adult height of asthmatic children treated with glucocorticoids with the attained adult height of asthmatic children who did not receive glucocorticoids. METHODS Residents of Rochester, Minnesota, with onset of asthma from 1964 to 1987 and age- and sex-matched non-asthmatic residents of Rochester were studied. Glucocorticoid exposure was assessed from medical records. The mean of 5 stadiometer measurements of adult height, adjusted for sex and parental height, was analyzed. RESULTS One hundred fifty-three patients with asthma (mean age at onset, 6.1 +/- 4.8 years) and 153 age- and sex-matched nonasthmatic subjects were studied. Adult height of patients with asthma (mean age at measurement, 25.7 +/- 5.2 years) was not significantly different from the adult height of non-asthmatic subjects; the overall difference, adjusted for mid-parental height, was -0.20 cm (95% confidence interval from -0.27 to 1.64). The adult height of asthmatic children treated with glucocorticoids was not significantly different from the adult height of patients with asthma not treated with glucocorticoids; the difference after adjusting for mid-parental height was -0.2 cm (95% confidence interval from -0.1 to 0.6). CONCLUSIONS We conclude that the attained adult height of patients with asthma is not different from the adult height of age- and sex-matched nonasthmatic subjects and that the attained adult height of asthmatic children treated with glucocorticoids is not significantly different from the adult height of children not treated with glucocorticoids.

American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in adults and children--2003 update.

The use of growth hormone (GH) in clinical endocrine practice is expanding, and its role in the treatment of various clinical conditions is increasingly appreciated. Concurrently, concerns have been raised about the ethical and economic aspects of GH therapy. The Board of Directors of the American Association of Clinical Endocrinologists (AACE) believed that a systematic review of information and a summary of guidelines for GH use would be timely, useful to clinical endocrinolo-gists, and of interest to both the public and the pharmaceutical companies who manufacture this hormone. Accordingly, in 1998, AACE published an initial review of the subject. Because of subsequent developments in this field, an update seemed warranted. Therefore, we searched for, selected, and synthesized the known information about the safety and efficacy of GH use in clinical practice. The indications for use of GH in adults are now defined more clearly, as are guidelines for diagnosis and dosing. Admittedly, some areas of GH application will remain controversial until more information becomes available. This document consists of recommendations for the clinical use of GH. These guidelines should be used by physicians in conjunction with their best clinical judgment. Periodically, these guidelines will be revised to reflect the latest developments in the use of GH in patients with non-GH-deficient conditions such as Turner syndrome (TS), a clinical condition that is not associated with GH deficiency but is improved by use of GH. As expanded indications and new indications (approved by the US Food and Drug Administration [FDA]) for the use of GH arise, AACE will continue to update this document.

Bisphosphonates for Treatment of Childhood Hypercalcemia

Most clinicians only have a limited experience in treating childhood hypercalcemia with bisphosphonates. We report our experience in the use of intravenous and oral bisphosphonates in a 5-year-old with hypercalcemia secondary to acute lymphocytic leukemia, a 16-year-old with immobilization hypercalcemia, and a 14-year-old with chronic hypercalcemia of unknown cause. Single infusions of 0.5 mg/kg and 1 mg/kg of intravenous pamidronate were administered over 4 hours. No adverse reactions were observed except for hypocalcemia. A dose between 10 and 20 mg of oral alendronate was successfully used to maintain normocalcemia in the patient with chronic hypercalcemia. In our experience, the administration of bisphosphonates has enabled us to achieve normocalcemia in all cases, and in all cases there were no significant side effects. Long-term potential side effects from their use in children during the active phase of growth remain unknown.

Hypothalamic-pituitary-adrenal axis suppression after short-term, high-dose glucocorticoid therapy in children with asthma

Short-term, high-dose oral glucocorticoid therapy is often required for control of acute asthma episodes in children. To evaluate possible hypothalamic-pituitary-adrenal (HPA) axis suppression after such therapy, we studied 11 children with just asymptomatic asthma before and at 3 and 10 days after completion of a five-day course of prednisone (up to 2 mg/kg/day in divided doses, maximum dose = 60 mg/day). HPA axis responsiveness was tested by measuring plasma corticosteroid levels before and after insulin-induced hypoglycemia. When these levels were compared to pretreatment levels, there was a statistically significant blunting of the peak corticosteroid responses to hypoglycemia 3 days after completion of the course of prednisone (p less than 0.001). However, corticosteroid responses were normal in all children 10 days after completion of the course of prednisone. We concluded that a single course of short-term, high-dose glucocorticoid therapy in children with asymptomatic asthma produces only transient (less than 10 days) HPA axis suppression.

Pheochromocytoma in the pediatric age group: Current status

Pheochromocytoma is an unusual tumor in the pediatric age group. Several aspects serve to differentiate children with pheochromocytoma from their adult counterparts. Children have fewer malignant tumors, more extraadrenal tumors, and greater bilaterality and multiplicity of tumor. Similarly, they have an increased incidence of multiple endocrine neoplasia (MEN) and familial disease. The records of 16 children (age 17 years and younger) with pheochromocytoma were evaluated. One newborn died at 36 hours of age, and a 3-year-old died four days after exploratory laparotomy. Of the 14 survivors (with an average follow-up of 8 years), three had manifestations of multiple endocrine neoplasia type 2 and two had familial pheochromocytoma only. One patient had malignant paragangliomas. Three patients had bilateral tumors; one of these had MEN. Four patients underwent operation before the use of alpha- and beta-adrenergic blockade was routine at our institution. An additional patient received blockade in preparation for the removal of the pheochromocytoma but was not prepared for preoperative angiography. Hypertensive complications were encountered in four of these five children; in one, this complication was fatal. There were no intraoperative complications in the 12 patients who had received appropriate blocking agents. Eleven of the 14 survivors are currently normotensive without the need for antihypertensive medication. Two patients have medically controlled hypertension, and one continues to have severe hypertension. An overview of this series underscores the characteristic features of pheochromocytoma in the pediatric age group. Angiography has been replaced by high-resolution computed tomography for localization.(ABSTRACT TRUNCATED AT 250 WORDS)

Results of early thyroidectomy for medullary thyroid carcinoma in children with multiple endocrine neoplasia type 2.

Children with multiple endocrine neoplasia type 2 (MEN2) often develop medullary carcinoma of the thyroid (MCT) or its precursor, C-cell hyperplasia. Survival results are improved if malignancy is diagnosed early from the results of plasma immunoreactive calcitonin (iCT) measurement. The effect of early detection and thyroidectomy in children with MEN2 syndrome was determined by reviewing the experience between 1975 and 1985. Seventeen children with MEN2 who were 12 years old or younger underwent a total thyroidectomy for MCT or C-cell hyperplasia. iCT was measured in all patients preoperatively and postoperatively. Of the 17 children, 14 (82%) had MEN2a and 3 (18%) had MEN2b. There were 14 (82%) female and three (18%) male patients; their mean age was 6.97 years (range 1.5 to 12 years). In all patients, the diagnosis of MCT was made from initial elevated levels of iCT after stimulation with pentagastrin. Three patients had clinical evidence of disease preoperatively. All patients underwent a total thyroidectomy and lymph nodes were removed from the central zone; a neck dissection was performed in the three with clinically obvious disease. MCT with C-cell hyperplasia was found in 11 children and C-cell hyperplasia alone in six. Of the 11 with carcinoma, eight had bilateral disease and three unilateral. Six children had bilateral C-cell hyperplasia. All 17 children were alive and feeling well at the time of this report; however, three had evidence of metastatic disease according to iCT measurements. None of the children had recurrent nerve injuries; one had evidence of hypoparathyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic and Environmental Contributions to Phenotypic Components of Metabolic Syndrome: A Population-based Twin Study

The increasing prevalence of metabolic syndrome (MS) poses a serious public‐health problem worldwide. Effective prevention and intervention require improved understanding of the factors that contribute to MS. We analyzed data on a large twin cohort to estimate genetic and environmental contributions to MS and to major MS components and their intercorrelations: waist circumference (WC), systolic (SBP) and diastolic blood pressure (DBP), fasting plasma glucose (FPG), triglycerides (TGs), and high‐density lipoprotein–cholesterol (HDL‐C). We applied structural equation modeling to determine genetic and environmental structure of MS and its major components, using 1,617 adult female twin pairs recruited from rural China. The heritability estimate for MS was 0.42 (95% confidence interval (CI): 0.00–0.83) in this sample with low MS prevalence (4.4%). For MS components, heritability estimates were statistically significant and ranged from 0.13 to 0.64 highest for WC, followed by TG, SBP, DBP, HDL‐C, and FPG. HDL‐C was mainly influenced by common environmental factors (0.62, 95% CI: 0.58–0.62), whereas the other five MS components were largely influenced by unique environmental factors (0.32–0.44). Bivariate Cholesky decomposition analysis indicated that the clinical clustering of MS components may be explained by shared genetic and/or environmental factors. Our study underscores the importance of examining MS components as intercorrelated traits, and to carefully consider environmental and genetic factors in studying MS etiology.

Endocrine manifestations of craniopharyngioma

RationaleDue to the proximity of craniopharyngiomas to the hypothalamus and pituitary gland, most children and adolescents presenting with these tumors will exhibit significant endocrine dysfunction. After treatment, these impairments can become a major cause of morbidity and mortality.MethodsThe postoperative course of children undergoing surgery for craniopharyngioma is reviewed.ConclusionEven if hormone levels seem to be adequate in the short term after treatment, deficiencies may develop over years and need to be monitored closely.

Hashimoto thyroiditis associated with thyroid cancer in adolescent patients

Three girls had Hashimoto thyroiditis and thyroid cancer. Cervical exploration revealed a follicular carcinoma in one, an oxyphilic cell carcinoma in another, and a papillary carcinoma in the third. These cases add clinical and pathologic data to the previously debated concept that Hashimoto thyroiditis coexists with thyroid carcinoma.

Radiation therapy for diabetes insipidus caused by Langerhans cell histiocytosis

Hypothalamic-pituitary radiation therapy has been the standard treatment for the diabetes insipidus of Langerhans cell histiocytosis. The goal of this study was to assess the role of radiation therapy in Langerhans cell histiocytosis-associated diabetes insipidus and to compare the results with nonirradiated controls. Forty-seven patients with pathologically confirmed Langerhans cell histiocytosis were diagnosed with diabetes insipidus between 1950 and 1989 and were treated at the Mayo Clinic. These patients were divided into two groups on the basis of treatment for the diabetes insipidus: The first group (radiation group) included 30 patients (28 of whom were evaluable for response) who received hypothalamic-pituitary radiation therapy, and the second group (control group) included 17 patients who did not. A partial response to treatment was defined as a reduction in vasopressin dosage or improvement in computed tomography (CT) or magnetic resonance imaging (MRI). A complete response was defined as no further need for vasopressin therapy or normalization of CT or MRI. End points analyzed included treatment response, patient characteristics, morbidity, dose-response relationship, and survival. Patient characteristics of the two groups were similar except for age and lung involvement, both of which were significantly less in the radiation group. Thirty-six percent of patients (10 of 28) in the radiation group responded to hypothalamic-pituitary radiation therapy (22% complete response and 14% partial response), whereas none in the control group responded. Five of the six complete responders were irradiated within 14 days of the diagnosis of diabetes insipidus. The mean dose used in the responding and nonresponding patients was 11.2 and 10 Gy, respectively. Three of five patients (60%) treated with more than 15 Gy responded compared to seven of 23 (30%) treated with less than 15 Gy. Eight of the 10 responders (80%), compared to 16 of 35 nonresponders (46%), were female. Only one in 20 patients with concomitant lung histiocytosis responded. Complications of therapy may include insufficiency in other hypothalamic-pituitary axes in the treated patients. Actuarial survivals at 5, 10, 20, and 40 years for the entire group were 80%, 78%, 75%, and 65%, respectively, with a median follow-up in living patients of 14.7 years.