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Salivary testosterone (ST) levels were measured in 84 boys aged 7.3-16.2 from the Edinburgh Growth Study. The correlation coefficient between matched plasma/saliva samples was 0.88. Six samples were collected over the course of one day from 0900 to 2100 h each month in the majority of the children for 4 consecutive months. Mean daily ST levels showed a significant rise between each pubertal stage (genital (G) and pubic hair (PH]. The rise in ST became more rapid once a mean testicular volume (MTV) of 10 ml had been reached. The diurnal rhythm was assessed by individual curve fitting on the log scale and by cosinor analysis. A rhythm was present prepubertally and developed into a pattern similar to that of the adult rhythm by stage G3. The monthly rate of rise of ST was greatest at stage G4. A significant rise in ST levels was detectable immediately prior to an increase in MTV to 3 ml. This allowed earlier recognition of the clinical onset of puberty at testicular volume of 3 ml, which in this group occurred at 10.9 (SD 0.9) years. ST is a non-invasive and sensitive method for the serial monitoring of gonadal function in the prepubertal and adolescent boy.

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Cortisol concentrations were determined in matched samples of plasma and saliva from patients and healthy volunteers throughout the course of standard tests of pituitary and adrenal reserve. During insulin tolerance tests the percentage incremental changes in cortisol concentrations in saliva were strictly comparable with those in plasma and showed less inter-subject variance. The clinical decision taken with regard to the integrity of the pituitary-adrenal axis was the same whether plasma or salivary cortisol was measured. In the short tetracosactrin test changes in salivary cortisol reflected those in plasma and patients with loss of adrenal responsiveness would have been diagnosed as such using either measurement. In normal subjects, the circadian rhythm in salivary cortisol concentrations exactly paralleled that in plasma. Absence of the circadian rhythm in cases of hypercortisolism was seen as well in saliva as in plasma. Assays for salivary cortisol therefore provide information which is as clinically useful as that of plasma determinations. Since salivary cortisol concentrations were shown to reflect the free, biologically active fraction in plasma, salivary assay may, in selected cases, provide results of greater diagnostic significance than plasma total concentrations.

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The incidence of post-natal depression is high, and dramatic changes in steroid hormones and prolactin occur in the post-partum period. In an attempt to correlate these events, 147 mothers, six to eight weeks after delivery of a healthy infant, completed standard psychological tests, including the Edinburgh, Montgomery-Asberg, and Raskin scales. They also provided matched samples of plasma for assay of cortisol, oestradiol, progesterone and prolactin, and saliva for assay of cortisol and progesterone. All steroid concentrations were within the appropriate normal ranges. Of the mothers, 14.9% were depressed on all three scales. Significant correlations were seen between depression ratings and salivary progesterone and prolactin. In bottle-feeders, salivary progesterone was positively associated with depression, whereas in breast-feeders it was negatively associated. Plasma prolactin levels were inappropriately low in depressed breast-feeders. These data indicate that differing therapies may be appropriate for depression in breast- and bottle-feeders.

We previously reported the unusual case of a teenage girl stricken with multifocal developmental dysfunctions whose physical development was dramatically delayed resulting in her appearing to be a toddler or at best a preschooler, even unto the occasion of her death at the age of 20 years. Her life-long physician felt that the disorder was unique in the world and that future treatments for age-related diseases might emerge from its study. The objectives of our research were to determine if other such cases exist, and if so, whether aging is actually slowed. Of seven children characterized by dramatically slow developmental rates, five also had associated disorders displayed by the first case. All of the identified subjects were female. To objectively measure the age of blood tissue from these subjects, we used a highly accurate biomarker of aging known as “epigenetic clock” based on DNA methylation levels. No statistically significant differences in chronological and epigenetic ages were detected in any of the newly discovered cases.Our study shows that a) there are multiple children who maintain the façade of persistent toddler-like features while aging from birth to young adulthood and b) blood tissue from these cases is not younger than expected.