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Biomedical subjects

C H Shackleton

Publications and source records attributed to C H Shackleton.

At least 145 records · Page 8Linked to original sources
PubMed1979

Metabolism of radiolabeled corticosterone in an adult with the 17 alpha-hydroxylase deficiency syndrome.

[4-14C]Corticosterone was administered to a woman with the 17 alpha-hydroxylase deficiency syndrome and urine was collected for 72 h. Sixty-three percent of the radioactivity was eliminated on the first day, 10.3% on the second, and 3.8% on the third, making a total recovery of 77%. On the first day, 85% of the recovered radioactivity was in the glucuronide conjugates of corticosterone, 10.6% was in the sulfate form of this steroid, and 3.9% was in the free forms of the steroid. On the following 2 days, the proportion of labeled glucuronides and free steroids decreased and that of labeled sulfates increased. On the first day of collection, the major radiolabeled metabolites were 21-hydroxylated steroids (e.g. allo-tetrahydrocorticosterone and 5 alpha- and beta-pregnane-3 alpha,11 beta,20 alpha,21-tetrol), but by the third day, at least 75% of the excreted activity was associated with 21-deoxysteroids, such as 3 alpha,20 alpha-dihydroxy-5 alpha (and beta)-pregnan-11-one and 5 alpha- and beta-pregnane-3 alpha,11 beta,20 alpha-triol. Bacterial metabolism in the intestinal tract is responsible for the dehydroxylation. 6 alpha-Hydroxytetrahydrocorticosterone was tentatively identified among several new metabolites of corticosterone.

Adrenal Hyperplasia, Congenital↗
PubMed1979

Deficient 3 beta-hydroxy-5-ene steroid secretion by newborn infants.

Congenital adrenal hypoplasia is reported in two siblings. The first died at 16 months of purulent bronchopneumonia after a history of adrenal insufficiency. No gross adrenal tissue was found at autopsy and urinary steroids were not excreted in detectable amounts before death. In a subsequent uncomplicated pregnancy, extremely low estrogens were recorded in the last trimester. Analysis of steroids in the urine of the neontate by gas chromatography revealed virtual absence of 3 beta-hydroxy-5-ene steroids. These suggest hypoplasia of the fetal adrenal cortex. Metabolites of cortisol were excreted in normal amounts and responded adequately to ACTH stimulation. Neonatal hyponatremia was associated with subnormal excretion of corticosterone and aldosterone metabolites. It is proposed that in the perinatal period, the fetal zone is required for mineralocorticoid synthesis, possibly by providing essential precursor steroids, e.g. 21-hydroxypregnenolone.

Adrenal Insufficiency↗
PubMed1978

Analysis of glucocorticoid metabolites in the neonatal period: catabolism of cortisone acetate by an infant with 21-hydroxylase deficiency.

The urinary excretion of 27 individual 17-hydroxycorticosteroids by a female infant with 21-hydroxylase deficiency was studied using gas chromatography on an open-tubular column and combined gas chromatography-mass spectrometry. Samples were analysed from days 1, 3 and 4 of life, before cortisone acetate treatment commenced on day 6, and on days 9 and 192, during treatment. The pattern of metabolites before and after treatment showed similarities with extensive reductions at positions 3 and 20 of the steroid nucleus and hydroxylations at positions 1 and 6. The following new glucocorticoid metabolites were identified: 1beta,3alpha,17alpha,21-tetrahydroxy-5alpha(andbeta)-pregnane-11,20-dione; 3alpha,6xi,17alpha,21-tetrahydroxy-5xi-pregnane-11,20-dione (2 epimers); 1beta,3alpha,17alpha,20alpha(andbeta),21-pentahydroxy-5beta-pregnan-11-one, and 3alpha,6xi,17alpha,20alpha (andbeta),21-pentahydroxy-5beta-pregnan-11-one. These steroids comprised 50% of the total metabolites on day 9, but only 20% on day 192. They have also been detected in the urine of normal neonates.

17-Hydroxycorticosteroids↗
PubMed1978

15alpha-Hydroxyoestriol and other polar oestrogens in pregnancy monitoring.

Although oestriol measurements are well established for the assessment of 'at risk' pregnancies, there are a number of other oestrogens, excreted during pregnancy, which contain additional hydroxyl groups and might be more sensitive indicators of the condition of mother or fetus. Some of these result from the action of hydroxylases possibly present only in the fetus and others from maternal hydroxylations. We review the evidence for the biosynthesis of these polar oestrogens, summarise methods of measurement, and compare values obtained in normal and pathological pregnancies. There is as yet insufficient evidence to enable their potential value to be confirmed.

Catechols↗
PubMed1978

Comparison of oestriol in mother and fetus during labour and in the baby at birth.

The progressive rise in pregnancy of oestriol values and their significance in assessing fetal viability is well known, although the exact function of this increase is not understood. In considering the problem it was thought that further information of oestriol levels in mother, fetus and newborn could prove of value. The mean cord plasma oestriol was lower in small-for-dates than in normal cases, but in both groups it was ten times higher than in the relative maternal peripheral veins. In pooled capillary fetal scalp samples the mean oestriol was slightly higher in normal compared with small-for-dates cases. The use of gas chromatography--mass spectrometry was investigated and shown to give an accurate measurement of plasma oestriol levels. The expense of this procedure may be offset by its ability to determine simultaneously the nature and amount of other steroids present.

Birth Weight↗
PubMed1976

Simultaneous estimation of urinary steroids by semi-automated gas chromatography. Investigation of neo-natal infants and children with abnormal steroid synthesis.

Development of a method for multicomponent analysis of urinary steroids on open-tubular columns is described. The urinary steroid conjugates were hydrolysed enzymatically, extracted on Amberlite XAD-2 columns, purified on columns of Sephadex LH-20, then analysed as methyloxime trimethylsilyl ethers on a gas chromatograph on which up to 24 samples may be automatically injected. All major urinary steroids from 17-oxosteroids to cortisol metabolites were analysed and these were quantified relative to internal standards, 5alpha-androstane-3alpha, 17alpha-diol and cholesteryl butyrate added to the samples prior to derivatisation. The precision of the full technique and reproducibility of repetitive automatic solid injection was found to be acceptable for the purpose of profile analysis. Examples of urinary steroid profiles in normal infants and infants with disorders of adrenal steroid production and excretion are given.

Adrenal Gland Neoplasms↗
PubMed1976

Congenital adrenal hyperplasia caused by defect in steroid 21-hydroxylase. Establishment of definitive urinary steroid excretion pattern during first weeks of life.

The steroid excretion of two female infants with congenital adrenal hyperplasia due to 21-hydroxylase deficiency has been studied during the first weeks of life. The techniques used were gas chromatography on an open-tubular column and combined gas chromatography-mass spectrometry using selected ion recording. During the first days of life 3beta-hydroxy-5-ene steroids predominate and the levels found were considerably greater than those found in normal infants. Selected ion recording mass spectrometry permitted detection of pregnanetriol and 11-oxo-pregnanetriol several days before these steroids could be determined with accuracy by conventional gas chromatography. Pregnanetriol and 11-oxo-pregnanetriol were first detected on the third day of life. The results of this investigation demonstrate that 21-hydroxylase deficiency may be indicated during the first week of life by an increased 3beta-hydroxy-5-ene steroid excretion, but the definitive excretion pattern required for firm diagnosis may not develop for several days. The amounts of the definitive steroids excreted may not be sufficient to be detected by the more usual methods for several weeks.

Adrenocortical Hyperfunction↗
PubMed1976

Identification of bile acids in the serum and urine in cholestasis. Evidence for 6alpha-hydroxylation of bile acids in man.

In this qualitative study of the pattern of bile acid excretion in cholestasis, methods are described for the isolation of bile acids from large volumes of urine and plasma. The bile acids were subjected to a group separation and identified by combined gas chromatography-mass spectrometry. The techniques were developed to allow identification of the minor components of the bile acid mixture. Four bile acids that have not previously been described in human urine and plasma were detected, namely 3beta, 7alpha-dihydroxy-5beta-cholan-24-oic acid, 3alpha, 6alpha-dihydroxy-5beta-cholan-24-oic acid (hyodeoxycholic acid), 3alpha, 6alpha, 7alpha-trihydroxy-5beta-cholan-24-oic acid (hyocholic acid) and 3alpha, 7beta, 12alpha-trihydroxy-5beta-cholan-24-oic acid. In addition three C27 steroids were found; 26-hydroxycholesterol and a trihydroxy cholestane, probably 5 beta-cholestane-3alpha, 7alpha, 26-triol were found in the sulphate fraction of plasma and urine. In the plasma sample, a sulphate conjugate of 24-hydroxycholesterol was found. The presence of these compounds probably reflects the existence of further pathways for bile acid metabolism. It is not yet known whether this is a consequence of the cholestasis or whether they are also present in normal man, at much lower concentrations.

Bile Acids and Salts↗
PubMed1976

Multicomponent gas chromatographic analysis of urinary steroids excreted by an infant with a defect in aldosterone biosynthesis.

The urinary steroids excreted by an infant with a salt-wasting syndrome due to a suspected defect in the 18-oxidation of corticosterone have been analysed by gas chromatography-mass spectrometry. The excretion of tetrahydroaldosterone was low (3.5 mug/24 h) whilst the excretion of 3alpha,11beta,21-trihydroxy-5alpha-pregnan-20-one (allo-tetrahydrocorticosterone) and other corticosterone metabolites was high (total about 2 mg/24 h). The excretion of cortisol metabolites was apparently normal for age (total about 2 mg/24 h) but 3alpha,11beta,17alpha,21-tetrahydroxy-5alpha-pregnan-20-one (allo-tetrahydrocortisol) rather than tetrahydrocortisone, was the major component of the group. The excretion of an 18-hydroxycorticosterone metabolite 3alpha,18,21-trihydroxy-5beta-pregnane-11,20-dione (18-hydroxytetrahydroCompound A) was higher than normal for infants of this age (between 50 and 200 mug/24 h), suggesting that the defect was in 18-hydroxysteroid dehydrogenase rather than 1,-hydroxylase. In addition, 18-hydroxytetrahydrocorticosterone, another metabolite of 18-hydroxycorticosterone was tentatively identified and it was found that the rate of excretion of this compound was of similar magnitude to 18-hydroxytetrahydroCompound A. The salt balance of the infant has been sucessfully controlled by salt administration (77 mEq./24 h) and treatment with Fludrocortisone (0.5 mg/day).

18-Hydroxycorticosterone↗