Excretion Of 17-ketosteroids Research Articles

Phytoadaptogen reverses the adverse effects of Naftussya bioactive water on dynamic muscle performance in healthy rats

Background.. Muscular performance is considered one of the attributes of health and non-specific resistance. Phytoadaptogens occupy an important place in the arsenal of means of increasing non-specific resistance and stress resistance. Many years of research of the Truskavetsian Scientific School of Balneology have demonstrated the adaptogenic properties of the main therapeutic factor of the resort, Naftussya bioactive water, as well as ozokerite and mineral baths. However, in contrast to the beneficial effect of the latter on stress resistance and the neuro-endocrine-immune complex, the effect on the physical performance is ambiguous. The purpose of this study is to test the ability of phytocomposition to prevent the adverse actotropic effect of Naftussya bioactive water at rats. Material and methods. The experimentt have been carried out at 42 female rats. Rats of the control group for 7 days loaded through a tube with tap daily water (2 mL once), while the animals of the other groups received according to a similar scheme daily water with the addition of 0,1 mL of Balm; bioactive Naftussya water per se or with the addition of 0,1 mL of Balm. The day after completion the course of water loads in the animal determined the urinary excretion of 17-ketosteroids, assessed the mineralocorticoid activity (MCA) by the urine K/Na ratio as well as the state of neutrophil phagocytosis by the number of absorbed latex particles. Results. It was found that the weekly use of Naftyssya bioactive water reduces the duration of swimming of rats to exhaustion by 30% compared to the daily water control. Addition of phytoadaptogen to Naftyssya softens its negative actotropic effect by up to -9%, and adding Balsam to daily water prolongs the maximum duration of swimming compared to the control by 11%. A positive correlation of the swimming test with 17-KS excretion and water diuresis was revealed, but a negative correlation with MCA, spontaneous diuresis and neutrophils phagocytosis. Conclusion. Phytoadaptogen reverses the adverse effects of Naftussya bioactive water on dynamic muscle performance in healthy rats by mitigating the decrease in the excretion of 17-ketosteroids and increased mineralocorticoid activity.

Phytoadaptogen reverses the adverse effects of Naftussya bioactive water on dynamic muscle performance in healthy rats

Background.. Muscular performance is considered one of the attributes of health and non-specific resistance. Phytoadaptogens occupy an important place in the arsenal of means of increasing non-specific resistance and stress resistance. Many years of research of the Truskavetsian Scientific School of Balneology have demonstrated the adaptogenic properties of the main therapeutic factor of the resort, Naftussya bioactive water, as well as ozokerite and mineral baths. However, in contrast to the beneficial effect of the latter on stress resistance and the neuro-endocrine-immune complex, the effect on the physical performance is ambiguous. The purpose of this study is to test the ability of phytocomposition to prevent the adverse actotropic effect of Naftussya bioactive water at rats. Material and methods. The experimentt have been carried out at 42 female rats. Rats of the control group for 7 days loaded through a tube with tap daily water (2 mL once), while the animals of the other groups received according to a similar scheme daily water with the addition of 0,1 mL of Balm; bioactive Naftussya water per se or with the addition of 0,1 mL of Balm. The day after completion the course of water loads in the animal determined the urinary excretion of 17-ketosteroids, assessed the mineralocorticoid activity (MCA) by the urine K/Na ratio as well as the state of neutrophil phagocytosis by the number of absorbed latex particles. Results. It was found that the weekly use of Naftyssya bioactive water reduces the duration of swimming of rats to exhaustion by 30% compared to the daily water control. Addition of phytoadaptogen to Naftyssya softens its negative actotropic effect by up to -9%, and adding Balsam to daily water prolongs the maximum duration of swimming compared to the control by 11%. A positive correlation of the swimming test with 17-KS excretion and water diuresis was revealed, but a negative correlation with MCA, spontaneous diuresis and neutrophils phagocytosis. Conclusion. Phytoadaptogen reverses the adverse effects of Naftussya bioactive water on dynamic muscle performance in healthy rats by mitigating the decrease in the excretion of 17-ketosteroids and increased mineralocorticoid activity.

Features of the state of neuro-endocrine factors of adaptation under different options of uric acid metabolism in healthy female rats

Background. As part of the project "Physiological activity of uric acid", we previously identified 4 variants-clusters of uricemia and uricosuria both in rats and in humans. It was shown that the clusters differ from each other in the constellation of immunity parameters, which to one degree or another correlate with uricemia and uricosuria. The aim of this study was to identify autonomic and endocrine adaptogenic factors, the combination of which differentiates previously formed quantitative and qualitative variants of uric acid metabolism in rats. Materials and Methods. Experiment was performed on 58 healthy female Wistar rats 220-300 g. The serum and urine levels of the uric acid, calcium, phosphates, sodium and potassium were determined. The neuro-endocrine status evaluated by the HRV parameters; serum levels of the hormones such as corticosterone, triiodothyronine and testosterone; daily excretion of 17-ketosteroides; electrolytes markers of mineralocorticoid, parathyroid and calcitonin activities as well as by the thickness of glomerular, fascicular, reticular and medullar zones of the adrenals. Results. The previously identified four variants-clusters of uric acid metabolism differ from each other by a constellation of 10 neuro-endocrine adaptation factors that reflect the state of glucocorticoid, androgenic and catecholamine functions of the adrenal glands, as well as HRV-marker of vagal tone and electrolyte markers of sympatho-vagal balance as well as calcitonin and parathyroid activities. Classification accuracy is 90%. Uricosuria and uricemia are negatively correlated with HRV-markers of sympathetic tone and circulating catecholamines, the level of corticosterone and the thickness of the fascicular zone of the adrenal cortex secreting them, as well as the level of triiodothyronine and the Ca-P marker of calcitonin activity, on the other hand, they are positively correlated with the HRV marker of vagal tone and urinary excretion of 17-ketosteroids. The rate of determination of neuro-endocrine adaptation factors by uric acid is 62%. Conclusion. Uric acid is naturally associated with the state of autonomous and endocrine adaptation factors in healthy female rats.

Virilización materno-fetal por tumor ovárico de la madre

Los autores han estudiado una mujer de 23 años en los que un tumor de ovario desarrollado durante su tercera embarazo. El tumor era del tipo resto suprarrenal y virilizados tanto para la madre como para el feto, que era una chica seudohermafrodita; la virilización que se produjo en la madre retrocedió tres meses después de la entrega, y la excreción urinaria de testosterona y 17-CS estaban en el rango normal en este punto; sin embargo, un aumento de los 17-Ks se produjo con la inyección de HCG; Los autores postulan que el tumor era dependiente de hormonas, y que los andrógenos secretados fueron capaces de cruzar la placenta y de esta manera a virilizar el feto.

10.1007/s11174-008-2005-1

A complex study of the functional state of the sympathoadrenal system and adrenal cortex in 10–15-year-old children of both sexes was carried out using the indices of daily excretion of adrenaline, noradrenaline, 17-ketosteroids, and 17-hydroxycorticosteroids. A synchronism in the functional activity of the mediator component of the sympathoadrenal system as well as of the androgenic and glucocorticoid functions of the adrenal cortex was observed with age and during pubertal development of children. At the same time, heterochronic maturation was observed in the sex groups: in girls at the age of 10 and 12 years and in boys at the age of 14–15 years. The changes of different direction and intensity in the excretion of the studied hormones and hormonal metabolites were observed in the sex and age groups. A sharp increase in the daily excretion of glucocorticoid metabolites accompanied by a considerable decrease in the age index of noradrenaline secretion was observed in 14-and 15-year-old boys from beginning to end of school year; in addition, an increase in the daily excretion of sex hormones was observed at the age of 15 years. In girls, these indices varied within the age range, which points to a more sophisticated neuroendocrine control of physiological functions in girls during puberty.

Age- and sex-related characteristics and mechanisms of adaptations during the prepubertal and pubertal periods of development

Integrated study of the functional state of the sympathoadrenal system and the adrenal cortex in children of both sexes aged 10–15 years. The study was conducted on the basis of the daily adrenaline, noradrenaline, 17-ketosteroid, and 17-oxycorticosteroid excretion values, which allowed certain synchrony to be established in the manifestation of the activity of the transmitter link of the sympathoadrenal system and the adrenal cortex androgenic and glucocorticoid functions with age, during sexual maturation. The heterogeneous character of maturation was found in the sex groups: in girls at an age of 10 and 12 years and in the boys at an age of 14–15 years. Changes in the excretion of the hormones and hormone metabolites with different directions and rates in the age-sex groups were observed throughout the academic year. In 14- to 15-year-old boys, a sharp increase in the daily excretion of the glucocorticoid metabolites accompanied by a substantial decrease in the age-related noradrenaline excretion values and the sex hormone metabolite values at an age of 15 years was observed. In the girls, these values varied within the age range, which indicates a more perfect character of the neuroendocrine regulation of their physiological functions in the period of sexual maturation.

URINARY excretion of 17-ketosteroids in scurvy.

Urinary Excretion of 17-Ketosteroids in Scurvy Get access Nutrition Reviews, Volume 10, Issue 8, August 1952, Pages 253–254, https://doi.org/10.1111/j.1753-4887.1952.tb01180.x Published: 01 August 1952

Estrogen receptor in breast cancer of the Japanese.

The estrogen receptor was assayed, using the 2,000g supernatant and dextran-coated charcoal method, in 243 tissue samples from human breast cancer, benign breast diseases, macroscopically normal breast tissues, normal uterine myometrium, and uterine myoma. The estrogen receptor was found to be positive in 52.1% of 98 primary breast cancer and in 54.1% of 24 metastatic tumors. The receptor in the breast cancer was found to be similar to that in normal uterine myometrium in the binding character; that is, the dissociation constant of 10(-9) approximately 10(-11) M and number of binding sites of 0 approximately 2,800 fmol/mg protein. There was no correlation between the presence of the receptor and some clinical factors such as menopausal status, age of the patient, urinary 17-ketosteroid excretion, clinical stage of cancer, tumor size, positive or negative axillary lymph node metastasis, histological type, metastatic site of the cancer, or disease-free interval. The estrogen receptor appeared to be retained by metastasis of cancer, and this may lead to the use of the receptor assay with mastectomy specimens for the prediction of response to hormonal therapy in future recurrence of malignancy. Furthermore, it may be possible by this assay to select patients suitable for adjuvant therapy with hormones at the time of mastectomy. A good correlation was found between the presence of the receptor and response to the major endocrine ablation therapy in patients with advanced or metastatic breast cancer. When the receptor was negative in the cancer tissue, the change of response to the endocrine therapy was minimum. On the other hand, if the cancer contained the receptor, approximately 60% of the patients with metastatic or advanced breast cancer responded well to the major endocrine ablation therapy. Thus, the estrogen receptor of breast cancer in Japanese patients appears to bear a close resemblance to that reported in Western patients in its incidence and the correlation to some biological characteristics of the cancer.

Human sympathoadrenal system and adrenal cortex in prepubertal and pubertal periods

A complex study of the functional state of the sympathoadrenal system and adrenal cortex in 10-15-year-old children of both sexes was carried out using the indices of daily excretion of adrenaline, noradrenaline, 17-ketosteroids, and 17-hydroxycorticosteroids. A synchronism in the functional activity of the mediator component of the sympathoadrenal system as well as of the androgenic and glucocorticoid functions of the adrenal cortex was observed with age and during pubertal development of children. At the same time, heterochronic maturation was observed in the sex groups: in girls at the age of 10 and 12 years and in boys at the age of 14-15 years. The changes of different direction and intensity in the excretion of the studied hormones and hormonal metabolites were observed in the sex and age groups. A sharp increase in the daily excretion of glucocorticoid metabolites accompanied by a considerable decrease in the age index of noradrenaline secretion was observed in 14- and 15-year-old boys from beginning to end of school year; in addition, an increase in the daily excretion of sex hormones was observed at the age of 15 years. In girls, these indices varied within the age range, which points to a more sophisticated neuroendocrine control of physiological functions in girls during puberty.

Dehydroepiandrosterone and adrenarche

The first report on increased production of 17-ketosteroids in healthy children before puberty was published by N. Talbot et al. in 1943. F. Albrigth et al. introduced the concept of "adrenarch", which everyone has used for the past 50 years. Later, with the advent of more advanced methods, it was shown that increased excretion of 17-ketosteroids during this development period is due to increased secretion of the adrenal cortex of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS). It must be emphasized that the content of other adrenal androgens - androstenedione and lip-hydroxyandrostenedione - does not increase during the adrenarche period. An increase in their secretion is recorded at the age of 6-8 years, that is, it is somewhat behind the activation of DHEA secretion. It must be remembered that androstenedione is also a product of DHEA metabolism in peripheral tissues. In contrast, lip-hydroxyandrostenedione can form only in the cortical layer of the adrenal gland, which is due to the presence of the corresponding enzyme system, which is localized in the adrenal tissue.

Klinefelter’s syndrome and juvenile chronic arthritis

Klinefelter’s syndrome (KS) is the most common disorder of sexual differentiation in males and the most common disorder of sex chromosomes in humans. In KS, primary male hypogonadism is caused by developmental testicular defects due to the presence of two or more X-chromosomes. The classic karyotype for KS is 47XXY, but the mosaic form, 46XY/47XXY occurs in about 10% of cases. Other extreme variants such as 48XXYY, 48XXXY, and 49XXXXY also exist. It is estimated that the frequency of KS is about 1/500 at conception and 1/1000 at birth due to in utero fetal loss. First described in full by Dr. Harry Klinefelter in 1942 [1], the full syndrome begins to manifest in adolescence and its characteristics include gynecomastia, testicular atrophy, azoospermia and sparse facial and body hair. Increased leg length and armspan are also typical of the syndrome. The phenotypic expression is variable, however, and some individuals are not diagnosed until adulthood. Decreased secretion of androgens, an increased estradiol/testosterone ratio (a relative increase in estrogen effect) and elevated gonadotropin levels are noted in KS. The patients evaluated and described by Dr. Klinefelter demonstrated normal to moderately reduced function of the Leydig cells, increased excretion of follicle-stimulating hormone, and reduced excretion of 17-ketosteroids. As a result of the hormonal abnormalities, clinical findings of hypogonadism, azoospermia, and gynecomastia are noted. Small testes, measuring less than 2–3 cm are the most consistent physical finding. Additional physical features are small phallus and decreased upper to lower body ratio [2]. Laboratory evaluation generally demonstrates elevated FSH and LH and a decreased testosterone levels. KS patients generally need to be started on testosterone replacement therapy at about 12 years of age, with increasing dosages over time that simulate age-appropriate concentrations. Klinefelter’s syndrome has been noted to have an association with several autoimmune diseases including, but not limited to, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), autoimmune diseases of the thyroid, and ankylosing spondylitis (AS). It has been speculated that some of these diseases, which normally show a female predominance, are seen concomitant with KS due to a relative excess of estrogens and lack of androgens in these patients. An association between KS and SLE is well described [3]. It has been suggested that the peripheral venous and arterial vascular abnormalities seen in KS (such as commonly seen leg ulcers) may be related to immune mechanisms involving anticardiolipin antibodies in KS patients [3]. Many reports of KS in association with autoimmune disease reflect a continuing interest in the complex relationship between sex hormones and autoimmune processes. Complicating this question, however, is the ‘‘Take home message’’: Pediatric patients with Klinefelter’s syndrome, a genetic condition characterized by primary male hypogonadism, should be considered at potential risk for the development of autoimmune diseases, including juvenile chronic arthritis.

The Midgrowth Spurt in Healthy Children Is Not Caused by Adrenarche

A small transient increase in growth, the midgrowth spurt, has been observed in several growth studies in healthy children around the age of 7 yr. During this time adrenarche (the physiological increase in adrenal androgen secretion) also occurs. Although it is now well established that estrogen, not androgen, has a critical role in the male (and female) pubertal growth spurt, a direct effect of androgens on growth cannot be excluded. In accordance with published observations that growth is frequently accelerated in infants and young children with late-diagnosed 21-hydroxylase deficiency (before adequate androgen suppression), it has been speculated that the adrenarchal increase in adrenal androgen secretion in healthy children could be responsible for the midgrowth spurt. To test this hypothesis we studied long-term serial changes in urinary 24-h excretion rates of dehydroepiandrosterone sulfate and total 17-ketosteroid sulfates in a group of healthy children (n = 12) in which yearly auxological measurements allowed the identification of a midgrowth spurt. Annual measurements of standing height were performed over periods of 6-9 yr before the onset of puberty. All children collected five to seven serial 24-h urine samples (1-yr intervals) each at the time of anthropometric examination. The peak of the midgrowth spurt was found to occur at a mean age of 6.8 +/- 1.0 yr. The average height of the midgrowth peak, i.e. average maximum gain in height velocity, was 0.9 cm/yr. In a peak-centered examination of individual 24-h excretion rates of dehydroepiandrosterone sulfate and 17-ketosteroid sulfates, primarily weak 1-yr changes in adrenal androgens were observed until the peak was attained. Only after the peak did increments in urinary adrenal androgen output become more pronounced. ANOVA performed on the peak-centered dehydroepiandrosterone sulfate and 17-ketosteroid sulfate excretion rates revealed a highly significant overall increase in adrenal androgen secretion from 2 yr before to 2 yr after the midgrowth spurt. After multiple testing, however, significant increments, when compared with the respective preceding androgen excretion levels, were for the first time seen 1 yr after the midgrowth spurt (dehydroepiandrosterone sulfate) or 2 yr later (17-ketosteroid sulfates). In conclusion, our longitudinal analysis of prepubertal growth and urinary adrenal androgen excretion in healthy children disproves the speculation that the midgrowth spurt is primarily caused by the adrenarchal increase in adrenal androgen secretion. However, the present results do not rule out a growth-accelerating effect of clearly higher androgen levels, as in premature adrenarche.

Near 10-year and longer periods modulate circadians: intersecting anti-aging and chronoastrobiological research.

Biological cycles with relatively long and some unusual periods in the range of the half-week, the half-year, years, or decades are being discovered. Their prior neglect constituted a confounder in aging and much other research, which then"flew blind" concerning the uncertainties associated with these cycles when they are not assessed. The resolution of more about 10-year and other cycles, some reported herein, replaces the admission of complete unpredictability, implied by using the label "secularity." Heretofore unaccounted-for variability becomes predictable insofar as it proves to be rhythmic and is mapped systematically to serve as a battery of useful reference values. About 10-year cycles in urinary 17-ketosteroid excretion and in heart rate and its variability, among others, are aligned with cycles of similar length in mortality from myocardial infarction. Associations accumulate between cycles of natural physical time structures, chronomes such as the 10.5-year (circadecennian) Schwabe and the 21-year (circavigintunennian) Hale cycles of solar activity, and chronomes in biota. There are about 50-year (circasemicentennian) cycles in mortality from stroke in Minnesota and in the Czech Republic and also in human morphology at birth, the latter result reducing the likelihood that these cycles are purely human made. Associations among large populations warrant long-term systematic coordinated sampling of natural physical and biological variables of interest for the design of countermeasures against already documented elevated risks of stroke, myocardial infarction, and other catastrophic diseases, notably in elderly adults. New findings will be introduced against the background of the documented value of mapping rhythms in medicine and gerontology. In both these fields, rhythms promise the seeming paradox of better care for less.

Heart-hitting tales of salt and destruction

at this, the Seventy-second Annual Meeting of the Central Society for Clinical Research. The Society has a rich tradition and a proud history that includes landmark studies published in The Journal of Laboratory and Clinical Medicine. In his presidential address to the Society on October 29, 1954, Jerome W. Conn presented a case report: M. W., a 34-year-old woman with a history of documented hypertension, complaints of weakness, and intermittent muscle spasms and laboratory evidence of hypokalemia, hypernatremia, and alkalosis. He termed this hitherto unrecognized and soon to be unraveled entity primary aldosteronism. Conn had arrived at this diagnosis based on research he conducted during the war years and that addressed acclimatization of soldiers in the Pacific Rim to stress—namely, “sodium depletion in normal men under conditions of intense and prolonged sweating while on low levels of sodium intake.” During the course of this work he had found evidence of “continuously increased activity of salt saving steroids...that act like desoxycorticosterone.” Conn concluded that M. W. had a syndrome of chronic mineralocorticoid excess caused solely by adrenal gland overproduction of recently discovered ALDO, given that her urinary excretion of 17-hydroxycorticosteroids and 17-ketosteroids had been consistently normal. At surgery on December 10, 1954, M. W. was found to have a 4-cm cortical tumor of her right adrenal gland. In January 1955, Conn’s lecture appeared in the Journal.1 Months later, the Journal featured Conn’s progress report on M. W. Within 10 days of surgical resection of the tumor, her preoperative derangements in blood and urinary chemistries had normalized, and they remained so for months.2 Conn also reported on biochemical and histopathologic analyses of tissue specimens obtained at the time of surgery. Values for ALDO (per gram of tissue) in the tumor were estimated to be 75 to 150 times those found in beef adrenal gland. Of interest, kidney sections revealed severe arteriosclerosis. Eight years later, Conn would summarize his own experience with 18 cases of primary aldosteronism and cases that had appeared in the literature worldwide.3 Of the 103 cases with proven adrenal adenoma, 50% had mild hypertension while none had malignant hypertension, based on the absence of hemorrhage and exudate by funduscopic examination of the retinal circulation; only 40% had radiographic cardiomegaly. This suggested that a structural remodeling of the heart and vasculature was not an outcome of hyperaldosteronism. However, the decline in blood pressure after surgical resection of the tumor was gradual, often requiring months. This contrasted with the more rapid normalization in electrolyte abnormalities. In patients whose arterial pressure failed to normalize after surgery, Conn suggested that abnormalities in kidney structure, including kidney vasculature, were responsible. These inconsistencies notwithstanding, the then-infrequent FROM THE CHICAGO MEETINGS

Feedsidewards: intermodulation (strictly) among time structures, chronomes, in and around us, and cosmo-vasculo-neuroimmunity. About ten-yearly changes: what Galileo missed and Schwabe found.

The spectrum of biological rhythms is extended far beyond circadians, circannuals, and ultradians, such as 1.5-hourly melatonin and 8-hourly endothelin-1 (ET-1) rhythms by statistics of natality, growth, morbidity, and mortality, some covering decades or centuries on millions of individuals. These reveal infradian cycles to be aligned with half-weekly rhythms in ET-1, weekly and half-yearly ones in melatonin, and even longer--about 50-, about 20-, and about 10-year cycles found in birth statistics. About daily, weekly, yearly, and ten-yearly patterns are also found in mortality from myocardial infarctions; the 10-yearly ones are also in heart rate and its variability; in steroid excretion, an aspect of resistance, for example, to bacteria; and in the genetic changes of the bacteria themselves. Automatic physiological measurements cover years and, in one case, cover a decade; the latter reveal an about 10-year (circadecennial) cycle. ECGs, covering months beat-to-beat, reveal circaseptans, gaining prominence in response to magnetic storms or after coronary artery bypass grafting. A spectrum including cycles from fractions of 1 Hz to circasemicentennians is just one element in biological time structures, chronomes. Chaos, trends, and any unresolved variability are the second to fourth elements of chronomes. Intermodulations, feedsidewards, account for rhythmically and thus predictably recurring quantitive differences and even for opposite treatment effects of the same total dose(s) of (1) immunomodulators inhibiting or stimulating DNA labeling of bone in health or speeding up versus slowing down a malignant growth and thus shortening or lengthening survival time, or (2) raising or lowering blood pressure or heart rate in the vascular aspect of the body's defense. Latitude-dependent competing photic and nonphotic solar effects upon the pineal are gauged by alternating yearly (by daylight) and half-yearly (by night) signatures of circulating melatonin at middle latitudes and by half-yearly signatures at noon near the pole. These many (including novel near 10-yearly) changes, for example, in 17-ketosteroid excretion, heart rate, heart rate variability, and myocardial infarction in us and those galactic, solar, and geophysical ones around us have their own special signatures and contribute to a cosmo-vasculo-immunity and, if that fails, to a cosmo(immuno?) pathology.

Urinary 17-KS and 17-OHCS as markers of endocrine disruption by air pollution in primary school children.

The present study was undertaken to determine the effects of air pollution on urinary excretion of 17-ketosteroids (17-KS) and 17-hydroxycorticosteroids (17-OHCS), which are markers of adrenal cortex functions, in primary school children from five schools with different levels of air pollution. One hundred and twentynine fourth-grade children were included in the study. Urinary excretion of 17-KS and 17-OHCS were significantly lower in male children living in polluted areas than in children living in clean areas. We conclude that adrenal cortex functions before puberty can serve as practical markers of endocrine disruption by environmental factors in epidemiological studies.

Further Studies on the Treatment of Congenital Adrenal Hyperplasia with Cortisone: IV. Effect of Cortisone and Compound B in Infants With Disturbed Electrolyte Metabolism, by John F. Crigler Jr, MD, Samuel H. Silverman, MD, and Lawson Wilkins, MD,Pediatrics, 1952;10:397–413

Three infants with female pseudohermaphrodism attributable to the salt-losing form of congenital adrenal hyperplasia (CAH; adrenogenital syndrome) followed for 14 to 20 months are described in detail. The first infant was admitted at the age of 7 weeks in adrenal crisis and studied intensively during a 557-day hospitalization; the second, an infant 7 weeks of age, was hospitalized for 7½ months; and the third, a 9-week-old infant, was studied over a 5-month period. The effects of cortisone and corticosterone on the suppression of the abnormal adrenals, as reflected in the urinary excretion of 17-ketosteroids (17-KS) and on the electrolyte disturbance as manifested by changes in serum and urinary electrolytes and body weight, are described. Cortisone acetate produced more marked suppression of the adrenal overactivity per milligram (as assessed by the urinary excretion of 17-KS), but less sodium retention than corticosterone. Both steroids, however, improved the electrolyte abnormality significantly. The possible mechanism of action of cortisone on the disturbed electrolyte metabolism is considered. We suggest that cortisone can serve as a substitute for deficient “Na-retaining hormone,” and/or it may act by suppressing secretions of the abnormal adrenals that possibly cause salt loss actively, either from the production of a specific “Na-losing” factor or from an antagonistic action of some of the steroids secreted by the abnormal adrenal gland against those hormones that normally regulate electrolyte metabolism. The studies in the three infants lead us to conclude that the electrolyte disturbance in patients with the salt-losing form of CAH is not merely simple deficiency of the adrenal salt hormone that appears to be associated with the zona glomerulosa of the adrenal cortex. The approach to the initial and long-term management of infants with the salt-losing form of CAH derived from the intensive study of these three infants is described. The critical importance of the use of adequate NaCl and fluids by intravenous administration initially to repair the electrolyte and fluid deficiencies and the hemodynamic abnormalities without the use of deoxycorticosterone acetate (DCA), if possible, in the initial treatment is emphasized because suppression of the adrenal with cortisone seems to alter materially the requirement for DCA. The final combination of the maintenance dose of cortisone acetate (either intramuscularly or orally) after initial high-dose priming, the amount of added NaCl, and the requirements for DCA (as long-acting subcutaneous pellets preferably), however, must be decided in each patient individually. Too high a dose of glucocorticoid resulted in impaired growth and cushingoid features as we described earlier; an inadequate dose of cortisone did not protect the infant from an adrenal crisis and was associated with rapid growth and skeletal maturation and the undesirable clinical signs of excess androgen production.*

Incidentally discovered adrenal mass (incidentaloma): investigation and management of 208 patients.

Incidentally discovered adrenal masses are fairly common, although there are some controversies concerning the results of hormonal investigation (especially DHEAS values) and the methods of management. We summarize our experience in diagnosis, pathological findings and treatment of a large group of patients with incidentally found adrenal tumours. Our study included patients referred to the Department of Endocrinology of the Centre of Post-graduate Medical Education (Warsaw, Poland) during the last 10 years because of an adrenal tumour incidentally found on ultrasound scan. In all cases this was confirmed by computed tomography. There were 208 patients (148 female and 60 male), 14-76 years old. Unilateral adrenal masses were found in 172 patients (right 106, left 66), while bilateral masses were demonstrated in 36 patients. The size of the tumours ranged between 0.8 and 21.0 cm. The most common clinical abnormalities were hypertension (36 cases), obesity (23 cases), diabetes (8 cases), Addison's disease (6 cases). Endocrine tests evaluating pituitary-adrenal function (urinary excretion of 17-hydroxycorticosteroids, 17-ketosteroids and catecholamines, plasma concentrations of ACTH, cortisol, DHEAS, androstendione and testosterone, dexamethasone suppression test and corticotrophin-releasing hormone stimulation test). Cortisol hypersecretion was noted in two patients with coexisting Cushing's disease and high normal 17-OHCS values with lack of dexamethasone suppressibility were found in six other patients with pre-clinical Cushing's syndrome. More common were subtle hormonal abnormalities: low ACTH levels (in 33 out of 98 investigated patients), diminished dexamethasone suppressibility and lack of ACTH response in the CRH test (in two out of 12 patients). Urinary catecholamine excretion was elevated in nine patients. In the group of 85 patients treated by surgery the most frequent pathological findings were: adrenocortical adenoma (21), carcinoma (17), phaeochromocytoma (13), metastatic masses (12) and myelolipoma (10). The size of carcinomas ranged from 3.2 to 20.0 cm, while the size of non-malignant tumours ranged from 1.5 to 21.0 cm. Every patient with an incidentally discovered adrenal mass has to be investigated to detect malignancy and subtle hormonal overproduction, to select the cases for surgical treatment. Most of the adrenocortical carcinomas were > 7.0 cm in diameter. For prophylactic purposes, adrenal incidentalomas > 4.0 cm should be treated by surgery, while the smaller ones could be followed-up (with special care for those between 3.0 and 4.0 cm).

How to learn from patients: Fuller Albright's exploration of adrenal function.

Fuller Albright (1900-1969) was acknowledged as the preeminent clinical and investigative endocrinologist of his day by many of his contemporaries, but his many achievements are all but unknown to the present generation of physicians. This article describes how he used his clinical knowledge and a few tools--the measurement of urinary 17-ketosteroid excretion and the administration of methyltestosterone--to elucidate the major hormonal functions of the adrenal cortex and to clarify the pathophysiology of the Cushing syndrome. In addition, in a tour de force of clinical reasoning, he predicted, 5 years before the event, the discovery of a hormone that would reverse the endocrinologic abnormalities of congenital adrenal hyperplasia. Fittingly, he and pioneer pediatric endocrinologist Lawson Wilkins were the first to treat this disease successfully with cortisone.

Serum 3α-androstanediol glucuronide measurements in children with congenital adrenal hyperplasia

To determine the value of 3 alpha-androstanediol glucuronide (3-AG) measurements in children with congenital adrenal hyperplasia, we compared serum 3AG, 17-hydroxyprogesterone (17-OHP), androstenedione (A), testosterone (T) and dihydrotestosterone (DHT) levels and 24-h urinary 17-ketosteroid (17-KS) excretion in 42 female children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, including 27 with the simple virilizing and 15 with the salt-losing form. Their mean age was 74.5 +/- 48.5 months (range, 6-194 months). Twenty-four-hour urinary 17-KS excretion and serum 3-AG, A, T, DHT and 17-OHP levels were measured in the patients. The values were less than the mean + 2 SD of the control group in 63%, 74%, 67%, 69%, 60% and 31% of the patients, respectively. Serum 3-AG levels correlated with 24-h urinary 17-KS excretion (r = 0.66) and plasma A (r = 0.80), 17-OHP (r = 0.56), T (r = 0.79) and DHT (r = 0.62) levels. We conclude that serum 3-AG is a useful metabolic index in the management of children with congenital adrenal hyperplasia.