Early hominid enamel hypoplasia.

Enamel hypoplasia in the South African Plio-Pleistocene fossil hominid sample is examined. The Swartkrans hominids are shown to have a higher incidence of hypoplasia than the Sterkfontein hominids. Within the Swartkrans sample, individuals with hypoplasia of the first upper molar have lower-than-expected ages of death. Possible taphonomic explanations for these observations are discussed.     

Genetic analysis of short stature

Short stature is a major concern for patients and their parents, and represents a diagnostic challenge to the clinician. A correct diagnosis is of particular importance in view of the availability of effective, but costly, therapy in a small subset of cases. Many different genetic etiologies of short stature are known. Therefore, chromosome as well as molecular analysis are requisite diagnostic investigations in children with short stature. Particularly in the group of children with idiopathic short stature, possibilities of molecular analysis are often underestimated. Important options are UPD7 and the FGFR3, SHOX, GH1 and GHR genes. Furthermore, analysis of the IGF and IGF1R genes should be considered. We propose a flow chart for molecular analysis in short stature.     

Prevalence and possible etiology of dental enamel hypoplasia

Two hundred black and white adult human skeletons and 200 living black and white children from the greater Cleveland area were examined for evidence of enamel hypoplasia. Enamel hypoplasia, present in varying expressings (pits, lines and grooves), was found to be more prevalent in both skeletal samples, than in the living groups. In the majority of cases, sex differences between white and black males and females through time and space are highly significant for all tooth catagories. Regardless of the mechanisms behind it, prevalence of enamel hypoplasia for both white and black group has significantly declined through time. No evidence suggesting specific etiologies responsible for enamel hypoplasia can be found. In the majority of previously published reports, the etiology is still idiopathic. The reduction in the prevalence of enamel hypoplasia in the groups examined through time may be related to improved nutritional conditions and the elimination or decline of childhood diseases that have been implicated in this condition.     

Hypoplastic area method for analyzing dental enamel hypoplasia

Most analyses of dental enamel hypoplasia compare frequencies of disturbed tooth types, which do not account for variability in the area of affected enamel. An alternate methodology, hypoplastic area, is presented here that accounts for this variability by combining acute and continuous enamel hypoplasia into an interval-level variable. The method compares samples based on individuals, by multiple tooth type variables, or by a single value rather than by tooth types. Use of the hypoplastic area method is illustrated by analyzing human skeletal dentitions in three archaeological samples: Meroitic Nubians from Semna South, Sudan; Anasazi from Navajo Reservoir, New Mexico; and Mogollon from Grasshopper Pueblo, Arizona. Both univariate and multivariate statistical tests are employed to assess variation in defects between individuals and samples. By incorporating measurements of continuous defects, the hypoplastic area method provides information beyond that of frequency data in comparing levels of stress. Flexibility of the method is also discussed. © 1995 Wiley-Liss, Inc.     

Reevaluating Harris lines--a comparison between Harris lines and enamel hypoplasia

This study examines the association between Harris lines and enamel hypoplasia. This association is analyzed in terms of: 1) presence/absence of these markers in each individual, and 2) age of the individuals at the time of Harris lines and enamel hypoplasias formation. Data from two archaeological groups (Azapa-71 and Azapa-140) from northern Chile were analyzed. The results indicate Harris lines and enamel hypoplasias are not associated in terms of presence/absence. Moreover, the estimated age of the individuals at the time of Harris lines and enamel hypoplasia formation shows that these two markers have a very different distribution. While enamel hypoplasias clustered between ages 3 and 5, Harris lines were more commonly formed during the first year of life, as well as during adolescence, which are the periods of most accelerated growth. We propose that Harris lines are a result of a normal, rather than abnormal, saltatory growth process.     

Incidence and patterning of dental enamel hypoplasia among the Neandertals

Dental enamel hypoplasia (DEH), as an indicator of nonspecific stress during development, provides an assessment of the relative morbidity of past human populations. An investigation of 669 Neandertal dental crowns yielded an overall DEH frequency of 36.0% by tooth (41.9% for permanent teeth; 3.9% for deciduous teeth) and about 75% by individual. These incidences place the Neandertals at the top of recent human ranges of variation in DEH frequencies, indicating high levels of stress during development. The paucity of deciduous tooth DEH and M1 DEH, combined with generally increasing levels of DEH through later calcifying teeth, suggests that the stress was primarily nutritional, beginning at weaning and continuing through adolescence. This supports paleontological and archeological interpretations implying significantly lower effectiveness for Neandertal foraging compared to that of modern humans.     

Adrenal androgens in children with short stature

Recent data suggest that adolescent individuals with growth hormone (GH) deficiency have subnormal levels of adrenal androgens (AA). In order to determine the developmental pattern of AA in GH deficiency and to assess whether AA levels can help identify children with GH deficiency, we measured plasma concentrations of dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S), delta 4-androstenedione (delta 4A), and cortisol in the basal state and during prolonged adrenocorticotropin (ACTH) infusion (8 h) in a group of 34 individuals, 26 males and 8 females, with short stature. Their chronological ages (CA) ranged from 1.75 to 17.5 years (median 10.35 years). The subjects were grouped into two categories according to the results of pituitary testing: group 1 = short, non-GH-deficient (n = 16), and group 2 = GH-deficient, ACTH-sufficient (n = 18). Patients in groups 1 and 2 had similar bone ages (BA: 7.2 +/- 0.7 vs. 7.5 +/- 1.0 years) and Z scores for height (-3.0 +/- 0.2 vs. -3.2 +/- 0.3 units) and height velocity (-2.5 +/- 0.4 vs. -2.6 +/- 0.2 units). For both groups there were significant increases from basal to peak levels for DHEA, DHEA-S, delta 4A and cortisol following prolonged ACTH infusion. Although both basal and peak levels of DHEA-S overlapped in groups 1 and 2 for all CA and BA, levels in group 2 tended to be lower, especially for BA greater than 10 years.(ABSTRACT TRUNCATED AT 250 WORDS)     

Euthyroid hypothyrotropinemia in children of short stature

Unique association of hypothyrotropinemia with euthyroidism was described in 2 children of short stature. Both had a history of intrauterine growth retardation (IUGR), but showed an appropriate growth rate after infancy (5 cm/y). Growth hormone secretion after provocation tests was normal, whereas TSH response to TRH was absent. With a highly sensitive TSH radioimmunoassay (RIA) and a specific RIA for TSH-alpha-subunit, both responded to a high dose of TRH stimulation. Serum thyroid hormones were within the normal range, while prolactin response to TRH was exaggerated. Exogenous thyroxine (T4) supplement in case 1 did not improve his growth rate, indicating absence of hypothyroidism. Case 2 was treated with stanozolol, which accelerated his growth velocity to 8 cm/y. During the treatment, serum T4 gradually decreased to 50% of the initial level, but blunted TSH response to TRH remained unchanged. These results indicate that their thyrotrophs are resistant to TRH stimulation and the pituitary setpoint of TSH release is unusually high. The exact mechanism involved in maintaining euthyroidism despite hypothyrotropinemia remains to be elucidated, but a common history of IUGR appears to play a role in producing this pituitary-thyroid state.     

Novel treatment of short stature with aromatase inhibitors

Estrogens have an essential role in the regulation of bone maturation and importantly in the closure of growth plates in both sexes. This prospective, randomized, placebo-controlled study was undertaken to evaluate whether suppression of estrogen synthesis in pubertal boys delays bone maturation and ultimately results in increased adult height.

A total of 23 boys with constitutional delay of puberty (CDP) received a conventional, low-dose testosterone treatment for inducing progression of puberty. Eleven of these 23 boys were randomized to receive a specific and potent P450-aromatase inhibitor, letrozole, for suppression of estrogen action, and 12 boys were randomized to receive placebo. Estradiol concentrations in the letrozole-treated boys remained at the pretreatment level during the administration of letrozole, whereas the concentrations increased during the treatment with testosterone alone and during spontaneous progression of puberty. Testosterone concentrations increased in all groups, but during the letrozole treatment, the increase was more than fivefold higher than in the group treated with testosterone alone.

The inhibition of estrogen synthesis delayed bone maturation. The slower bone maturation in the boys treated with testosterone and letrozole, despite higher androgen concentrations, than in the boys treated with testosterone indicate that estrogens are more important than androgens in regulation of bone maturation in pubertal boys. During the 18 months follow-up, an increase of 5.1 cm in predicted adult height was observed in the boys who received testosterone and letrozole, but no change was seen in the boys who received testosterone alone or in the untreated boys. This finding indicates that an increase in adult height can be attained in growing adolescent boys by inhibiting of estrogen action.     

Linear enamel hypoplasia in gibbons (Hylobates lar carpenteri)

This study describes the expression of linear enamel hypoplasia (LEH), a sensitive dental indicator of physiological stress, in Thailand gibbons (Hylobates lar carpenteri). Previous studies of enamel hypoplasia in hominoids have focused on great apes, with little attention given to the expression of this stress indicator in gibbons. In that gibbons differ from both monkeys and great apes in numerous life history features, LEH expression in gibbons might be expected to show significant differences from both. In this study, 92 gibbon specimens from two sites in Thailand were compared with several samples of monkeys and great apes in their expression of LEH. The intertooth distribution of LEH in gibbons was compared to that of chimpanzees and rhesus monkeys. Gibbon populations from both sites exhibit LEH frequencies intermediate between those of the monkey samples, in which LEH prevalence is usually low, and those of the great ape samples, in which LEH prevalence is high. Gibbons differ significantly from monkeys, but not great apes, in the number of individuals whose teeth record multiple stress events. Multiple episodes of stress are rarely recorded in the teeth of monkeys, while multiple stress events occur with higher frequency in gibbons and great apes. Taxonomic variation in the duration of crown formation, the prominence and spacing of perikymata on dental crowns, life history features, and/or experience of physiological stress may explain these patterns. The intertooth distribution of LEH in gibbons is, for different reasons, unlike that of either chimpanzees or rhesus monkeys. The mandibular canines of gibbons have significantly more LEH than any of their other teeth. Aspects of crown morphology, perikymata prominence/spacing, enamel thickness, and crown formation spans are potential causes of taxonomic variation in the intertooth distribution of LEH.     

The association between Harris lines and enamel hypoplasia in prehistoric California Indians

Hypoplastic defects of tooth enamel and Harris lines in the long bones have been heralded as potentially useful indicators of health conditions in prehistoric populations. Both result from temporary cessation of growth processes due to similar types of disease, malnutrition, or other metabolic insult. An association test for the first six years of life was conducted on a large series of prehistoric California Indians, using femora and canines from young adults. No significant association was found. This is ascribable to differences in etiology and stability.     

Subcutaneous treatment with growth hormone-releasing hormone for short stature

In the present study we report the effects of therapy with growth hormone-releasing factor (1-29)NH2 (GRF) on growth rate, plasma levels of insulin growth factor I (IGF-I) and growth hormone (GH) secretion in 11 children who were selected solely on the basis of their short stature and normal GH secretion on standard provocative tests. All children received GRF for 6 months (5 micrograms/kg body weight subcutaneously) each evening. The 24-hour GH secretory profile was studied before and after 6 months of treatment. Simultaneously, GH secretory responses to single intravenous bolus GRF (1.5 micrograms/kg body weight) were also studied before, during, and 6 months off therapy with GRF(1-29)NH2. Plasma levels of IGF-I were measured before, during (1, 2 and 6 months), and after 6 months off therapy with GRF. Statural growth was measured at 3-month intervals. The peak plasma GH level in response to GRF was 56.04 +/- (SD) 24.46 ng/ml before treatment, and similar results were found after therapy. The 24-hour GH secretory profile did not show differences before, during, and after treatment. Comparably, no differences were found in GH pulse frequency, pulse amplitude, pulse height, pulse increment, pulse area and total area before, and 6 months off therapy with GRF. The increments in serum IGF-I achieved were not significantly different at all intervals studied. All patients increased growth velocities (mean +/- SD, cm/year) in response to GRF therapy. Our results demonstrate that GRF administration was effective in accelerating growth velocity in 11 children without GH deficiency.