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Biomedical subjects

M H Connors

Publications and source records attributed to M H Connors.

At least 19 recordsLinked to original sources

Pubertal growth in IDDM is determined by HbA1c levels, sex, and bone age.

OBJECTIVE: In cross-sectional studies of subjects with IDDM, the relationship between suboptimal pubertal growth, glycemic control, and abnormal insulin-like growth factor I (IGF-I) levels has proved difficult to define. The objective of this study was to examine these relationships in a longitudinal prospective study. RESEARCH DESIGN AND METHODS: A total of 46 children (23 boys) were measured every 3 months, and their bone age was assessed annually. Blood samples were obtained for HbA1c, IGF-I, and C-peptide. Growth data were compared with national standards, and IGF-I data were compared with a parallel longitudinal study of normal schoolchildren. Data were analyzed as SD scores (mean +/- SD). RESULTS: The onset of puberty was not delayed, although in the girls, bone age was advanced (bone age, 11.48 +/- 1.01 years vs. chronological age, 10.93 +/- 0.86 years [mean +/- SD]; P = 0.04). The timing of peak height velocity (PHV) was normal in both sexes, but the magnitude was reduced in girls (PHV SDS = -0.56 +/- 0.90, P < 0.02), and reductions in height SDS between diagnosis and final height were observed (P = 0.014). At PHV, IGF-I levels were reduced in both sexes, and there were no sex differences in HbA1c levels and insulin doses. IGF-I SDS correlated with insulin dose (r = 0.47, P = 0.004) but not with PHV SDS, whereas HbA1c correlated negatively with PHV SDS in both sexes (r = -0.35, P = 0.03). In a stepwise multiple regression analysis, the major determinants of PHV SDS were HbA1c (P = 0.04), sex (P = 0.0007), and bone age (P = 0.01). CONCLUSIONS: We conclude that the magnitude of the pubertal growth spurt is related to HbA1c levels in both sexes, but it is reduced only in girls. This sexual dimorphism cannot be explained by differences in IGF-I levels and may relate to the bone age advance at the onset of puberty in the girls.

Body Height↗

Growth in the diabetic child.

Insulin has an important role in the GH:IGF-I axis, and its absence leads to major endocrine disturbances, particularly during puberty. Rapid growth in the prediabetic phase occurs and may be a risk factor. Final height reflects gender and the age of onset more than specific growth factors. The influence of hepatic insulin on IGF-I bioactivity has important implications in diabetic adolescents.

Adolescent↗

Expansion and shrinkage of central nervous system tumor coinciding with human growth hormone therapy: case report.

OBJECTIVE AND IMPORTANCE: The influence of human growth hormone (hGH) therapy on the recurrence rates of childhood central nervous system tumors is controversial. Because growth hormone has the ability to increase cell proliferation, it is recommended that hGH therapy wait until central nervous system lesions are inactive and antitumor therapy complete, usually 1 to 2 years. CLINICAL PRESENTATION: We report the enlargement and decrease in size of a hypothalamic pilocytic astrocytoma in a 12-year-old boy after two trials of hGH. Partial resection and radiation of the tumor were performed at 3 years of age, with no change noted over the next 9 years. His height was less than the 5th centile with midparental height at the 90th to 95th centiles. Growth velocity was 3.3 cm/yr. Bone age was normal and there were no signs of puberty. There was no GH response to clonidine and L-dopa testing. INTERVENTION: Volume measurements were performed on gadolinium enhanced tumor images. Growth rate increased to 11.7 cm and the tumor volume increased 230% over the 12 months of hGH therapy. Significant tumor shrinkage (42%) and growth deceleration occurred within the 3 month interval of stopping hGH. Tumor volume again increased (134%) and decreased (22%) after restarting and then stopping hGH. No evidence of tumor necrosis or alteration in ventricular size was found. The patient was asymptomatic. CONCLUSION: These observations indicate that tumor size change is associated with the metabolic response to hGH therapy. It is unclear whether the volume increase represents altered blood-brain or selective blood-tumor barrier permeability, growth factor receptors, and/or tumor cell growth.

Astrocytoma↗

Diminished thyroxine-binding globulin in pubertal diabetic children.

OBJECTIVE: To determine the effect of diabetes on thyroid hormone and thyroxine-binding globulin (TBG) concentrations during puberty. RESEARCH DESIGN AND METHODS: Total thyroxine (TT4), free thyroxine (FT4), and TBG levels of 171 thyroid microsomal antibody-negative subjects with normal thyroid-stimulating hormone (TSH) levels were measured and compared with those of nondiabetic adolescents. A random subset of 68 diabetic patients (40 boys and 28 girls) and 51 control subjects (24 boys and 27 girls) were analyzed for puberty-related changes. RESULTS: Most TT4 levels of diabetic subjects (80% of girls and 63% of boys) were below the 50th percentile for the normal range. TT4 increased with age in girls (r = 0.25, P < 0.04) but not in boys. FT4 was within normal limits in both sexes. TBG measurements were below the 50th percentile and 20% were below the 95% CI for both sexes; TT4 correlated with TBG in boys (r = 0.54, P < 0.001) and in girls (r = 0.58, P < 0.001). Duration of diabetes had no effect, whereas TT4 and FT4 levels were higher in girls with the lowest HbA1 levels (r = -0.29, P < 0.01 and r = -0.45, P < 0.01). Levels of TBG were reduced for all male pubertal stages (P < 0.01) and for early and late female pubertal stages (P < 0.01). There was no direct relationship between glucose control or the duration of diabetes and levels of TBG. CONCLUSIONS: Because TT4 levels are low and correlate with the low levels of TBG, it is important to measure free thyroid hormone and TSH levels in diabetic adolescents to establish euthyroidism.

Adolescent↗

"Chordoid" meningeal tumors in young individuals with peritumoral lymphoplasmacellular infiltrates causing systemic manifestations of the Castleman syndrome. A report of seven cases.

Seven young patients ranging in age from 8 to 19 years had surgically removed meningeal neoplasms with a peculiar myxoid-chordoid pattern. The tumors were surrounded by massive polyclonal lymphoplasmacellular infiltrates with follicles and germinal centers. The patients preoperatively manifested iron-resistant hypochromic microcytic anemia, and one of them had dysgammaglobulinemia and stunted growth. After the masses were removed, the blood picture of the patients normalized, and the adolescent with retarded somatic development resumed normal growth, but two patients developed local recurrence with identical histology and again became anemic. It appears that the peritumoral lymphoplasmacellular infiltrates, which in these instances may be regarded as reactive rather than primary cell proliferations, nevertheless brought about the type of systemic manifestations known as the Castleman syndrome, characteristically seen in patients with angiofollicular lymphoid hyperplasia (hamartoma) of soft tissues, or Castleman's tumor. In one of our patients the inflammatory infiltrate extended far into the surroundings of the meningioma, resulting in the erroneous initial diagnosis of "encephalitis" from a needle biopsy of the brain near the tumor.

Adolescent↗

Transient neonatal 'athyreosis' resulting from thyrotropin-binding inhibitory immunoglobulins.

Recognition of transient forms of neonatal hypothyroidism is difficult because of the urgency of thyroxine treatment. In the present report the first child born to a mother with Graves' disease developed transient hyperthyroidism during the newborn period. The mother underwent radioactive iodine treatment and was maintained euthyroid on l-thyroxine. Two subsequent children were detected by newborn thyroid screen to have low thyroxine and markedly elevated serum thyrotropin (TSH) levels. Technetium 99 metastable and iodine 123 scans at 22 days of age showed the second child to be athyreotic. The third child was not scanned. All three children were nongoitrous at birth. Patients 2 and 3 had continuous TSH suppression with thyroxine therapy for 3 and 4 years. Thyroid function measurements after discontinuation of therapy for 8 weeks were normal, and both children had normal 123I thyroid scans. The mother was found to have potent TSH-binding inhibitory immunoglobulin (TBII) levels in her serum (85.5%). A fourth child with low thyroxine and elevated TSH was born to a mother on a regimen of l-thyroxine for hypothyroidism. 99mTc scan at 26 days of age showed no thyroid tissue and was normal at 3 months. TBII activity was 35% in the maternal serum and absent in the infant's serum. The above laboratory and clinical data are compatible with the blocking nature of TBII, resulting in transient newborn hypothyroidism and an athyreotic appearance on scan. The TBII measurement can be a useful predictor of neonatal hypothyroidism as well as confirm the transient nature of the disease in newborns.

Adult↗

Familial functional anorchism: a review of etiology and management.

Identical male twins with small penes and bilateral unpalpable gonads were unresponsive to human chorionic gonadotropin stimulation. Both infants had elevated levels of gonadotropins. The size of the penis did not meet fully the criteria for micropenis and the organ was responsive to testosterone therapy. The use of primary human chorionic gonadotropin stimulation followed by testosterone measurements is indicated for children with cryptorchidism in whom the etiology of micropenis is in doubt. We report the first observation of anorchism in identical twins.

Chorionic Gonadotropin↗

Lack of seasonal influence on growth hormone therapy.

Variation in linear growth rates with seasonal changes has been attributed to physical activity, sunlight exposure or hormonal influences. We compared the growth hormone (hGH) induced growth rates in 15 hypopituitary children aged 2 to 17 years during two 4-month periods. Subjects did not receive hGH 4 months before the treatment periods. With subjects receiving hGH, comparison of the growth rates during spring-summer (April-August) and fall-winter (October-February) did not differ significantly (8.25 +/- 2.02 vs 8.75 +/- 1.77 cm/yr). Similarly, when growth during these same periods was compared for all subjects while off of hGH therapy, the growth rates were not significantly different in the spring-summer period (3.04 +/- 1.80) than fall-winter period (2.62 +/- 2.97). Rates of growth during therapy exceeded those during periods without therapy (p less than 0.005). These observations indicate that growth rate during therapy with hGH is not influenced by seasonal factors.

Adolescent↗

Blood glucose monitoring in childhood diabetes.

Diabetic complications may result from chronic elevations in serum glucose concentrations and the consequent counter regulatory mechanisms. Maintaining normal glycemic control is beyond the capability of urine testing for glucose. Blood glucose testing has provided the means to more normal glucose management in diabetics. The use of home blood glucose monitoring devices by diabetic children has been very successful. The test gives an immediate reading of blood glucose level, which has allowed both patients and their family members to become more actively involved in the management of diabetes.

Adolescent↗

Adrenocortical responses to adrenocorticotrophin in the hypophysectomized ovine fetus.

Fetal adrenocortical responsiveness to ACTH declines during 90-120 days gestation and fetal pituitary peptides have been implicated in this refractoriness. In these studies the ACTH-induced cortisol responses were measured in 11 ovine fetuses of 114 days gestation. Five animals were hypophysectomized as evidenced by prolonged gestation, pituitary histology, TRH-testing, delayed maturation and decreasing fetal plasma prolactin concentrations (less than 1 ng.ml-1) (P less than 0.005). Resting cortisol concentrations decreased from 22.4 to 8.1 ng.ml-1 in the hypophysectomy group and were not different from the control group (19.6-14.9 ng.ml-1) over the 5 days of study. Responses measured as increments in plasma cortisol concentrations increased equally and successively in both groups. Since pituitary ablation fails to enhance fetal adrenal responsiveness to ACTH we conclude that refractoriness is unlikely to be caused by an inhibitor of pituitary origin.

Adrenal Cortex↗