Kenneth Lee Jones

TYPE 2 DIABETES MELLITUS IN MINORITY CHILDREN AND ADOLESCENTS: An Emerging Problem

Type 2 diabetes mellitus is a disease of adults and has been considered rare in the pediatric population. Over the last decade, however, there has been a disturbing trend of increasing cases of type 2 diabetes in children, particularly adolescents, and with a greater proportion of minority children being affected. This article reviews the clinical characteristics of youth with type 2 diabetes, presents the risk factors associated with insulin resistance and type 2 diabetes, discusses treatment options, and projects future directions in research. The ultimate goal is to raise awareness of this challenging entity among healthcare professionals.

Impaired calcitonin secretion in patients with Williams syndrome

Williams syndrome is associated with neonatal hypercalcemia of unclear pathogenesis. To learn more about the hormonal control of calcium metabolism in patients with Williams syndrome, we studied five such children, with intravenous calcium and parathyroid hormone infusions as provocative stimuli. These patients were found to have significantly higher mean baseline calcium concentrations, delayed clearance of calcium after intravenous calcium loading, and blunted calcitonin responses after calcium infusion, compared with a group of seven normal children. No abnormalities of vitamin D metabolite concentrations were found, either before or after parathyroid hormone stimulation. Our studies demonstrate that patients with Williams syndrome have a defect in the synthesis or release of immunoreactive calcitonin. A deficiency of calcitonin may explain the abnormalities of calcium metabolism seen in these patients and can serve as an important endocrine marker for Williams syndrome.

A Validation Study of Early Adolescents’ Pubertal Self-Assessments

This study aimed to determine whether self-assessed puberty is sufficiently reliable and valid to substitute for physician examination when feasibility of physician examination is low (e.g., behavioral research). Adolescents (convenience sample N = 178 endocrinology patients and N = 125 from educational trial; mean age 12.7 and 11.3 years, respectively) participated. Self-assessments were validated against physician Tanner ratings and by associations with bone density, gender, and age. Highest exact agreement between physicians and adolescents was 54% for females’ and 55% for males’ ratings of pubic hair. More than 85% agreement within one stage was obtained for most measures. Significant associations were found for age and bone between adolescents in earlier and later stages of development and for developmental stage between genders for each age group. Results suggest predictive and discriminate validity of self-assessments. Self-assessments may be useful when estimates of pubertal development are sufficient and for studies barred from physician examination.

Non-Insulin Dependent Diabetes in Children and Adolescents: The Therapeutic Challenge

Data are presented comparing non-insulin dependent diabetes mellitus (NIDDM) and insulin dependent diabetes mellitus (IDDM) in youth. Children and adolescents with NIDDM were predominantly Mexican-American, presented less frequently in ketoacidosis, had a greater frequency of family history of diabetes, had higher BMIs (27.4 vs 16.6 kg/m2), and had higher frequency of acanthosis nigricans (67% vs 1.2%). Logistical, social, and cultural challenges facing the physician treating children and adolescents with NIDDM are discussed, and treatment options for NIDDM in youth are briefly reviewed. Clin Pediatr. 1998;37:103-110

Role of obesity in complicating and confusing the diagnosis and treatment of diabetes in children.

The alarming increase in the prevalence of obesity in children in the United States and globally raises major concerns about its future adverse impact on public health. One outcome of this disturbing trend that is already evident is the rapidly increasing incidence of type 2 diabetes at all ages. This disease, once thought to be nonexistent in children, is increasing coincident with obesity. This article addresses the role that obesity plays in type 2 diabetes and also explores its effects on other types of diabetes that occur in childhood. The new challenges for physicians who formulate a differential diagnosis of diabetes in children are discussed. Also examined are modifications of traditional diabetes treatment that can be helpful in combating the insulin resistance associated with obesity and that use medications that are not traditionally used in this age group. Cases are presented to illustrate certain points. An underlying thesis suggests that specific classification may not be as important to the clinician as the understanding of pathophysiologic factors that contribute to hyperglycemia in individual patients. Recommendations are offered to the practitioner for diagnosing and treating the obese child or adolescent with diabetes.

Calcitonin secretion in congenital nongoitrous cretinism.

Plasma calcitonin (CT) was measured in the basal state and/or during provocative tests of hormone secretion in 11 children with congenital non-goitrous cretinism (CNC), in 1 girl with a lingual thyroid, and in 11 normal children. Basal and stimulated CT concentrations were significantly lower in the patients with CNC than in the normal subjects. Mean basal CT (+/- SE) was 41 +/- 4 pg/ml in the normal children, 24 +/- 3 pg/ml in the children with CNC, and 20 +/- 2 pg/ml in the patient with the lingual thyroid. The mean incremental CT responses to calcium infusion were 7.0 +/- 2 pg/ml in the children with CNC, 6.0 pg/ml in the patient with the lingual thyroid, and 146 +/- 47 pg/ml in the normal children. The children with CNC also demonstrated a significant delay in the return of the total serum calcium to basal level after the calcium infusion. The mean incremental CT response after infusion of pentagastrin was 7.6 +/- 2 pg/ml in the children with CNC, 10.0 pg/ml in the child with the lingual thyroid, and 34.4 +/- 11 pg/ml in the normal children. These data indicate that CT deficiency is present in children with CNC and suggest that the deficiency is a consequence of the defective embryologic development of the thyroid gland.

Nocturnal melatonin levels are unaltered by ovarian suppression in girls with central precocious puberty

Girls with central precocious puberty were utilized as a model in which to study the melatonin secretory response to ovarian suppression. Eight girls with central precocious puberty documented by clinical and endocrine characteristics, including sleep-entrained augmentation of luteinizing hormone (LH) pulsatility, were investigated. Nocturnal (6:00 P.M. to 9:00 A.M.) plasma melatonin levels were measured hourly by a sensitive and specific radioimmunoassay before and after gonadotropin-ovarian downregulation with gonadotropin-releasing hormone (GnRH)-agonist. Although nocturnal melatonin elevations varied widely between girls, patterns within the same individual were remarkably reproducible and unaltered before and after treatment. Although estrogens have been shown to modulate melatonin synthesis and secretion, in this model, reduction of estrogen levels was not associated with alterations in plasma melatonin concentrations.

Hypopituitarism in association with postaxialpolydactyly

We report four patients, three boys and one girl, with polydactyly and hypopituitarism. All patients had postaxial polydactyly and subnormal growth hormone responses to standard provocative stimuli. Three of these patients had a family history of polydactyly and few other abnormalities. The remaining patient had a major malformation syndrome including a CNS hamartomatous tumor and early death; this patient had no family history of polydactyly. We believe that the association of postaxial polydactyly with hypopituitarism and possible CNS hamartomatous tumors is an important clinical consideration in the evaluation of children with suspected growth hormone deficiency.

Theca function in polycystic ovaries of a patient with virilizing congenital adrenal hyperplasia

The steroidogenic activity of purified theca interstitial cells (TIC) from polycystic ovaries of a patient with virilizing congenital adrenal hyperplasia due to 21-hydroxylase deficiency was studied in serum-free medium. The results show that CVAH TIC have high intrinsic basal androgen secretory activity that is dramatically stimulated by hCG, insulin, and lipoproteins, particularly HDL. Accordingly, the results support the hypothesis that TIC may contribute to the development of polycystic ovaries in CVAH patients, perhaps by mechanisms independent of the adrenal glands.

THE CUSHING SYNDROMES

The 10 years since this journals last review of CS have seen extraordinary advances in our understanding of many aspects of its causes, diagnosis, and treatment. The spectrum of what are now called the Cushing syndromes has expanded considerably to include CD, multiple sources of ectopic ACTH secretion, and an apparent autoimmune cause. Improved assays of ACTH and the availability of CRF have provided new insight into the physiology and pathophysiology of the HPA axis and new tools for diagnosis of CS, especially in combination with selective catheterization and sampling. New imaging technology has improved our visualization of pituitary adenomas and has provided powerful methods for identifying tumors ectopically secreting ACTH and primary adrenal tumors. Finally, the refinement of transsphenoidal surgery and its success in treating CD have provided a safe and effective therapy for this disease. For those occasional patients who require medical therapy, drugs are available that decrease steroid biosynthesis. We now have a much better understanding of a fascinating disease process and are able to diagnose and treat it more correctly. One is impatient to see which new pieces of this puzzle will fall into place over the next ten years.