Search PubMed⌕ Search

Biomedical subjects

S K Cunningham

Publications and source records attributed to S K Cunningham.

At least 37 records · Page 2Linked to original sources
PubMed1990

The overnight dexamethasone test is a worthwhile screening procedure.

The overnight low-dose dexamethasone test is a convenient screening procedure for Cushing's syndrome. Claims that the test is associated with a high incidence of 'false positives', rendering it of little value particularly in obese and hospital in-patients, have been investigated in the present study. The data from 100 consecutive subjects undergoing overnight low-dose dexamethasone tests to examine for the possibility of Cushing's syndrome, were reviewed. Cushing's syndrome was identified in four patients, normal suppression of cortisol values occurred in 84 patients and 12 patients exhibited false positive results. Differences in body weights, body mass indices or in-patient status did not distinguish between those subjects with normal suppression of plasma cortisol and those subjects who yielded false positive results. These data indicate that the simple overnight dexamethasone test substituted for the more cumbersome traditional 48-h dexamethasone test in 84 of 96 patients who did not have Cushing's syndrome. Thus the overnight test provides a useful screening procedure but a small percentage of patients, approximately 12.5%, will require additional procedures to exclude Cushing's syndrome.

Adolescent↗
PubMed1988

Plasma pro-opiomelanocortin fragments and adrenal steroids following administration of metyrapone to normal and hirsute women.

The present study was undertaken to characterize further the adrenal abnormalities in the polycystic ovary syndrome (PCOS) and idiopathic hirsutism (IH). We have previously reported the close association of elevated estrone levels with amenorrhea in hyperandrogenemic patients. In addition we have suggested that high estrone levels in PCOS occur as a consequence of the provision of excess substrate, androstenedione, for conversion to estrone. In the present study plasma estrone levels rose following endogenous adrenal stimulation induced using metyrapone; the highest plasma estrone levels achieved were seen in patients with PCOS and occurred later than peak androstenedione levels. These findings are consistent with the hypothesis that elevated estrone levels occurring in PCOS may arise as a consequence of increased adrenal androgen secretion. In addition, we have examined ACTH and other pro-opiomelanocortin (POMC) fragments in an attempt to identify a factor responsible for the excessive adrenal androgen secretion occurring in hirsute patients. Plasma levels of ACTH, and of immunoreactive beta-endorphin and h-lipotropin were not elevated when androgen levels were raised prior to therapy, although these POMC fragments, and also the 16K fragment, rose in response to metyrapone treatment as did androgen levels. Following treatment with dexamethasone there was more profound suppression of the 16K, beta-endorphin and h-lipotropin responses to metyrapone stimulation, than of the ACTH response, as indicated by decreased POMC-fragment/ACTH ratios; this parallels the dissociation of cortisol from androgens in hirsute patients under similar conditions. However, we have not identified a POMC fragment which consistently parallels changes in androgen levels in patients with idiopathic hirsutism or PCOS.

Administration, Oral↗
PubMed1988

Optimisation of total urinary aldosterone estimation: comparison with other laboratory methods for assessment of mineralocorticoid status.

We have demonstrated that conventional methods for measuring total urinary aldosterone (TUA) may markedly and inconsistently underestimate aldosterone output, since under the conditions usually employed (pH 1.0), the hydrolysis of aldosterone conjugates in urine is incomplete. The use of more acidic hydrolysis conditions (pH 0.2) overcomes this problem. However free aldosterone may be damaged at this pH. Therefore to accurately measure TUA output, it is necessary to isolate the undamaged aldosterone chromatographically and to correct for procedural losses based on the recovery of aldosterone tracer added to the urine prior to hydrolysis. We compared a number of laboratory estimates of aldosterone status (including urinary free aldosterone) with the 24-h urinary sodium output in normal subjects, since this provides a good bioassay of aldosterone. Sodium output correlated best with "optimised" 24 h TUA, i.e. hydrolysed at pH 0.2, (r = -0.589, P less than 0.001), and with plasma aldosterone (r = -0.504, P less than 0.005). Both aldosterone in random urine specimens and plasma renin activity correlated poorly with 24-h sodium output. Therefore, while the measurement of optimised TUA excretion provides the best index of aldosterone activity, assay of aldosterone in random specimens of plasma, which is more convenient for patient and laboratory, may be adequate for many clinical purposes.

Adult↗
PubMed1988

Evaluation of an immunoassay for plasma sex hormone-binding globulin: comparison with steroid-binding assay under physiological and pathological conditions.

It is possible that alterations in sex hormone-binding globulin (SHBG) binding capacity are due to changes in binding kinetics rather than changes in concentration and, therefore, the immunoreactivity of SHBG may not reflect the binding activity. In this study an immunoradiometric (IRMA) assay was evaluated and the results compared with those of an established binding capacity assay. The correlation between the results of the IRMA (y) and binding assay (x) for 179 specimens was r = 0.984, y = 0.95x + 5.9. Irrespective of the method used, SHBG values in normal non-pregnant women were significantly (P less than 0.05) higher than those in normal men, hirsute women, women with polycystic ovary syndrome, hyperprolactinaemic women and obese women, and were significantly less than those in pregnant women; SHBG levels in hirsute women rose during treatment with certain anovulants and fell in genetic males during the second decade of life independent of androgen levels or activity. While being technically simpler SHBG-IRMA provides comparable results to the classical binding assay, indicating that immunoreactivity is an excellent index of binding activity.

Adolescent↗
PubMed1985

Altered androstenedione and estrone dynamics associated with abnormal hormonal profiles in amenorrheic subjects with weight loss or obesity.

The present study was designed for exploration of hormonal disturbances underlying common forms of amenorrhea. Polycystic ovary syndrome (PCO) patients and obese amenorrheic subjects had significantly elevated estrone (E1) levels, elevated luteinizing hormone/follicle-stimulating hormone ratios, and an exaggerated luteinizing hormone response to luteinizing hormone-releasing hormone. However, androstenedione (delta 4A), the precursor of E1, was elevated only in PCO. Thus, the E1/delta 4A ratio, which provides an indirect index of aromatase activity in extraglandular sites, was raised in obese subjects as a group but not in PCO subjects. These findings suggest that elevated E1 levels, which give rise to abnormal gonadotropin secretion, arise from increased available androgens in PCO but from an increased effect of aromatase (present in adipose tissue) in obese subjects. Measurement of androgens and the E1/delta 4A ratio provides insights into the relative contributions of hyperandrogenemia and enhanced aromatase activity to the genesis of amenorrhea in these groups. In patients with suppressed estradiol levels associated with hyperprolactinemia or weight loss, follicle-stimulating hormone levels were suppressed, while luteinizing hormone was not elevated. Prolactin excess explains these findings in hyperprolactinemia. Plasma E1 levels and the E1/delta 4A ratio were suppressed in patients with weight loss, possibly as a consequence of reduced adiposity. This finding suggests that hypothesis that a minimum level of E1, dependent upon adequate adiposity, is critical for the normal mature function of the hypothalamic-pituitary-ovarian axis. Abnormal E1/delta 4A ratios, high in obesity-associated amenorrhea and suppressed in weight loss-associated amenorrhea, may provide specific markers for these groups of patients.

Adolescent↗
PubMed1985

The adrenal cortex and virilization.

The physiological control of adrenal androgen secretion has not been definitively established. However, there is evidence to suggest that a dexamethasone-suppressible factor other than ACTH may have a specific role to play. The majority of patients with idiopathic hirsutism (hirsutism associated with regular menstruation) have findings suggestive of adrenal androgen excess, including enhanced androgen responsiveness following administration of metyrapone, and respond to treatment with dexamethasone, 0.5 mg given each night. Patients with idiopathic hirsutism have elevated androgens but normal oestrogen and gonadotrophin levels. In contrast, while patients with polycystic ovary syndrome (PCOS) also demonstrate evidence of adrenal androgen excess, these patients have elevated oestrone levels and gonadotrophin secretion is abnormal. Approximately 50% of patients with PCOS treated with dexamethasone resume regular menstruation. Oestrone excess appears to be primary to the abnormal gonadotrophin secretion and to the development of PCOS. In non-obese patients with PCOS elevated oestrone appears to occur as a consequence of the availability of the excessive amounts of its immediate precursor, androstenedione, an androgen mainly of adrenal origin. Androstenedione is converted to oestrone in fat. Obese amenorrhoeic subjects have normal androstenedione values but elevated oestrone levels with abnormal gonadotrophin secretion as seen in PCOS. These findings indicate that abnormal gonadotrophin secretion is associated with elevated oestrone levels whether these occur as a consequence of excessive adrenal androgen secretion, or the excessive conversion of normal amounts of available androstenedione. Patients with idiopathic hirsutism and elevated androstenedione levels but normal oestrone values appeared to be protected against the development of PCOS by relatively poor conversion of androstenedione to oestrone. It is likely, therefore, that if patients with idiopathic hirsutism gain additional adipose tissue, elevated oestrone levels will result and PCOS will develop. These observations explain the frequent association of PCOS and obesity. There is a close clinical association between elevated androgen levels and hirsutism and between elevated oestrone levels and menstrual disturbances. However, some patients with amenorrhoea but without hirsutism may demonstrate marked elevations of androgens and oestrone, the correction of which leads to the resumption of regular ovulation. This presentation, 'amenorrhoea with cryptic hyperandrogenaemia', is probably explained by diminished sensitivity of androgen receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

17-alpha-Hydroxyprogesterone↗
PubMed1985

The relationship between sex steroids and sex-hormone-binding globulin in plasma in physiological and pathological conditions.

Physiological and many pathological changes in plasma sex-hormone-binding globulin (SHBG) levels have been attributed to the opposing effects of androgens which lower, and oestrogens which elevate, levels. We examined four clinical situations in which changes in SHBG levels may not be explained by sex steroid alterations. (1) Dexamethasone caused an increase in SHBG levels in hyperandrogenaemic hirsute women whether or not androgens were suppressed. (2) In male patients with untreated isolated gonadotrophin deficiency there was a highly significant correlation between SHBG levels and age, but there was no relationship between the levels of SHBG and those of plasma testosterone, androstenedione or DHEAS. (3) Two 46-XY siblings, phenotypic female subjects with complete androgen insensitivity, demonstrated a marked decline in SHBG levels between the ages of 9-13 and 12-16 years. (4) SHBG was suppressed in obese oligomenorrhoeic women while plasma concentrations of testosterone, androstenedione and oestradiol were normal and that of oestrone was elevated; however, the testosterone:SHBG ratio, an index of free testosterone, was elevated. These observations indicate that the decline in SHBG levels which normally occurs in men during the second decade of life is independent of androgen activity and is under the influence of as yet unidentified factors. Glucocorticoids in small doses under the influence of as yet unidentified factors. Glucocorticoids in small doses increase SHBG levels independently of sex steroid alterations while elevated free testosterone concentration may contribute to suppression of SHBG in obesity.

Adolescent↗
PubMed1984

Variable clinical and hormonal manifestations of hyperandrogenemia.

This study was undertaken to contrast the hormonal profiles in patients with various hyperandrogenemic states in an attempt to correlate clinical manifestations with specific hormonal abnormalities. Patients with idiopathic hirsutism, polycystic ovaries, and a syndrome recently described by us, amenorrhea with cryptic hyperandrogenemia, ie, without hirsutism, participated. Total testosterone, the testosterone: sex-hormone-binding globulin (SHBG) ratio, and androstenedione levels were elevated in each group of patients. SHBG levels were suppressed in patients with idiopathic hirsutism and in patients with polycystic ovaries. In patients with polycystic ovaries or cryptic hyperandrogenemia, plasma estrone levels were elevated and the luteinizing hormone (LH) responses to luteinizing-hormone-releasing hormone (LH-RH) were exaggerated. Estrone is derived from androstenedione under the influence of the enzyme, aromatase. While elevated androstenedione occurred in both patients with polycystic ovaries or idiopathic hirsutism, estrone levels were only elevated in patients with polycystic ovaries. Reduced aromatase activity may have protected patients with idiopathic hirsutism from elevated estrone values and, thereby, from menstrual disturbances. The hormonal profiles in polycystic ovary syndrome and in patients with amenorrhea with cryptic hyperandrogenemia were very similar, with the exception that SHBG levels were high normal in three of five patients with cryptic hyperandrogenemia while estrone values were markedly elevated in these patients. Elevated estrone levels may explain the normal SHBG values, which are usually suppressed in hyperandrogenemic states. While each of the hyperandrogenemic disorders studied has a characteristic hormonal profile, the various clinical manifestations cannot be accounted for solely by abnormalities in circulating hormonal levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Plasma sex hormone-binding globulin levels decrease during the second decade of life irrespective of pubertal status.

The plasma concentrations of sex hormone-binding globulin (SHBG) and sex steroids determine the nonprotein bound or free steroid fraction, which probably exerts the biological activity of sex steroids. Androgens lower and estrogens raise SHBG levels. The established pubertal fall in SHBG levels occurring in men has been attributed to rising androgen levels. In this study we examined the relationship between plasma SHBG and androgens in four men with untreated isolated gonadotropin deficiency and in two siblings with complete androgen insensitivity. In patients with untreated isolated gonadotropin deficiency there was a highly significant inverse correlation between SHBG levels and age (r = -0.9, P less than 0.001), although testosterone levels did not rise and there was no relationship between SHBG levels and testosterone, androstenedione, or dehydroepiandrosterone-sulfate. Two 46 XY siblings, who were phenotypic females, with complete androgen insensitivity had a marked decline in SHBG levels from 28.0 ng/ml at 9 yr to 17.1 ng/ml at 13 yr and from 15.2 ng/ml at 12 yr to 8.1 ng/ml at 16 yr, respectively. These observations indicate that the fall in SHBG levels during the second decade of life occurs irrespective of androgen activity and is under the control of other unidentified influences.

Adolescent↗
PubMed1983

Plasma sex hormone-binding globulin and androgen levels in the management of hirsute patients.

Hirsutism in women is a manifestation of excessive androgen action. This may be due to excessive exposure, or to increased sensitivity, of peripheral tissues to androgens. The present study was undertaken to estimate the percentage of hirsute patients with hyperandrogenaemia and to examine the effect of correction of hyperandrogenaemia on the clinical presentation. Plasma testosterone, dihydrotestosterone, sex hormone-binding globulin (SHBG) and androstenedione were determined in 58 hirsute patients before and following 3 months therapy with dexamethasone, 0.5 mg nocte. Testosterone expressed as a function of SHBG (testosterone/SHBG) provides an index of the non-protein bound testosterone fraction. Plasma levels of androstenedione were significantly elevated in 28% of hirsute patients, testosterone in 31% and testosterone/SHBG was elevated in 52%. Five per cent of patients had an elevated androstenedione value together with a normal testosterone/SHBG value. A subgroup of 13 hirsute patients with oligomenorrhoea had significantly higher values for androstenedione and testosterone/SHBG than eumenorrhoeic hirsute patients, and plasma testosterone, androstenedione and testosterone/SHBG values were more frequently elevated. In hirsute patients dexamethasone therapy resulted in suppression of plasma testosterone and androstenedione values, a significant increase in plasma SHBG and a marked fall in testosterone/SHBG. Following treatment with dexamethasone hyperandrogenaemia was corrected in 64% of hirsute patients, a decrease in the rate of hair growth or a resumption of a normal menstrual pattern occurred in 70% and concordant hormonal and clinical changes occurred in 79% of patients. These observations indicate that the testosterone/SHBG ratio is a sensitive index of hyperandrogenaemia, the correction of which is associated with clinical improvement.

Adult↗
PubMed1983

Normal cortisol response to corticotropin in patients with secondary adrenal failure.

A normal plasma cortisol response to exogenous corticotropin has been advanced as a reliable indication of adequate hypothalamic-pituitary-adrenal function in patients suspected of having secondary adrenal failure. We have examined the validity of this diagnostic strategy in five patients who had undergone hypophysectomy and 27 patients recently treated with glucocorticoids. Eleven of the patients had normal adrenal responses to cosyntropin but had subnormal responses when the entire hypothalamic-pituitary-adrenal axis was examined using metyrapone; no patient who responded normally to metyrapone failed to respond to cosyntropin. Inducing hypoglycemia with insulin yielded results concordant with the results induced by metyrapone in four patients tested. A normal cortisol response to corticotropin alone should not be relied on to exclude secondary adrenal insufficiency. To do this it is necessary to demonstrate normal activity of the entire hypothalamic-pituitary-adrenal axis, which can be conveniently examined using metyrapone.

Adrenal Insufficiency↗
PubMed1978

Effect of a xanthine oxidase inhibitor on adenine nucleotide degradation in hemorrhagic shock.

Biochemical effects of treatment with a xanthine oxidase inhibitor (allopurinol) were investigated in an experimental hemorrhagic shock procedure. Allopurinol pretreatment abolished the increase in plasma uric acid which occurs in untreated dogs during hemorrhagic hypotension and resulted in a much lesser increase in plasma allantoin. The pancreatic, liver and duodenal adenosine triphosphate (ATP) and total adenine nucleotides of untreated dogs were severely reduced, while those of allopurinol-pretreated dogs were essentially normal 2 h following reinfusion. Pretreatment with allopurinol resulted in a significantly lesser release of the lysosomal enzymes, acid phosphatase and beta-glucuronidase, following reinfusion. When treatment was delayed until after reinfusion, an infusion of hypoxanthine + allpurinol restored normal ATP concentrations. The role of adenine nucleotide breakdown in irreversible shock is discussed.

Acid Phosphatase↗