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PubMed1997

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

OBJECTIVE: 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. DESIGN AND PATIENTS: 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). MEASUREMENTS: 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). RESULTS: 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. CONCLUSIONS: 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).

17-Hydroxycorticosteroids↗
PubMed2001

Effect of exercise training on serum leptin levels in type 2 diabetic patients.

To evaluate the effect of exercise training on serum leptin levels 50 sedentary subjects with type 2 diabetes were enrolled in either 6 weeks of aerobic exercise training with diet therapy (n = 23) or diet therapy alone (n = 27). The training program consisted of walking and cycle ergometer exercise for 1 hour at least 5 times per week, with the intensity of exercise maintained at 50% of maximum oxygen uptake. Serum leptin levels decreased significantly in the exercise training (TR) group (7.2 +/- 3.6 to 4.6 +/- 2.5 ng/mL, P <.05), but not in the sedentary (SED) group (6.9 +/- 3.4 to 5.6 +/- 2.9 ng/mL). Leptin levels standardized for percentage body fat (dividing serum leptin level by percentage body fat) after treatment were lower in the TR subjects compared with the SED subjects. Body weight and percentage body fat decreased in all patients; however, no significant changes were observed in either group. Fasting concentrations of plasma insulin and cortisol and the urinary excretion of 17-hydroxycorticosteroid (17-OHCS) did not differ between the groups either before or after treatment. Fasting plasma glucose and hemoglobin A(1c) (HbA(1c)) improved significantly in both groups, although no significant differences were observed between the groups either before or after treatment. Ventilatory threshold increased significantly in the exercise training subjects. This study demonstrates that exercise training in type 2 diabetic subjects reduces serum leptin levels independent of changes in body fat mass, insulin, or glucocorticoids.

17-Hydroxycorticosteroids↗
PubMed1979

Adrenal-cortical function in patients with medullary carcinoma of the thyroid and pheochromocytoma.

Medullary carcinoma of the thyroid (MCT) is reported to synthesize ACTH. This ACTH is believed to be responsible for the development of Cushing's syndrome in some patients with MCT. To determine the frequency of occurrence of adrenal cortical overactivity in patients with MCT, we measured plasma cortisol concentration and the urinary excretion of 17-hydroxycorticosteroids, 17-ketosteroids and urinary free cortisol in 22 patients with MCT and 7 patients with MCT plus pheochromocytomas. The patients with MCT and MCT plus pheochromocytoma had similar adrenal cortical function to age and sex matched normal subjects. We conclude that adrenal cortical function is usually normal in patients with MCT.

17-Hydroxycorticosteroids↗
PubMed1976

Effect of an oral contraceptive on the lysine-8-vasopressin test in the diagnostic evaluation of pituitary function.

A comparative study was performed on the plasma 11-hydroxycorticosteroids (11-OHCS) responses to lysine-8-vasopressin (LVP) before and during ingestion of an oral contraceptive wieh oestrogenic activity. A total of 19 healthy women with a normal menstrual cycle and normal plasma 11-OHCS content in blood samples at 8 a.m. and 4 p.m. were included in the study. The results show that the mean response of plasma 11-OHCS to the administration of LVP was equal in magnitude before and during ingestion of the contraceptive, although the baseline value of 11-OHCS doubled as a result of the treatment. On the other hand, during contraceptive treatment the increase of plasma 11-OHCS concentration after the administration of LVP was somewhat slower, reaching its peak later than before treatment. The noticeable variation in individual responses of plasma 11-OHCS to LVP increased during the treatment. Three subjects showed weak responses to LVP, although the adrenocortical responses to exogenous ACTH were quite normal. The inidvidual responses to LVP before and during ingestion of an oral contraceptive with oestrogenic activity are discussed.

11-Hydroxycorticosteroids↗
PubMed1976

Effect of glucose on adrenocortical activity of newborn piglets.

Adrenocortical function was followed in newborn piglets fasted for 36 hours and in piglets given only glucose or glucoplastic amino acids during this period. The greatest increase in relative adrenal weight, blood plasma 17-hydroxycorticosteroid (17-OHCS) levels and in the production of 17-OHCS by pig adrenals in vitro as compared with suckled controls was found in fasted piglets followed by amino acid-treated animals. The latter showed no significant differences in blood glucose between the initial and final values. The administration of glucose produced a transient hyperglycemia, failed to prevent the inhibition of body growth, resulted in a reduction in liver weight similar to that seen in fasted animals, and had a marked suppressive effect on the elevation of adrenocortical function. There were no significant differences in the production of 17-OHCS by adrenals in vitro per kg body weight between the glucose-treated and suckled piglets.

17-Hydroxycorticosteroids↗
PubMed1976

[Estimation of free cortisol in urine (author's transl)].

Radio-immunological estimation of free cortisol in urine in a group of normal persons showed a median daily excretion of 42,5 +/- 22,8 mug (n = 31) using radio-loss-labelling, extraction, and thin layer chromatography. After simple extraction the median value was 54.1 +/- 15.3 mug/d (n = 10). Radioimmunological estimation in simple urine extract seems to be sufficient for routine clinical purposes. The estimation of free cortisol in urine permits a better differentiation between normal adrenal function and adrenal hyperactivity than the determination of 17-hydroxycorticosteroids (17-OHCS). This is shown by comparison of 1) the frequency distribution of the basal values of 17-OHCS and free cortisol in normal persons and in Cushing's disease, 2) the suppression effect of dexamethasone on 17-OHCS and free cortisol in Cushing patients, and 3) the stimulatory effect of ACTH on 17-OHCS and free cortisol in normal persons.

17-Hydroxycorticosteroids↗
PubMed1995

A case of iatrogenic growth retardation induced by a corticosteroid-containing anti-allergic drug.

A nine-year old boy developed reduced growth velocity at the age of seven. The peak plasma growth hormone (GH) response to 3,4-dihydroxyphenylalanine, GH-releasing factor and insulin was 10.2, 8.1 and 7.6 micrograms/l, respectively, suggesting that the GH reserve was slightly reduced. Serum cortisol was undetectable and urinary excretion of 17-hydroxycorticosteroid was low (0.22-0.31 mg/day), but there were no physical or biochemical signs of adrenocortical insufficiency. He had taken an anti-allergic drug containing 0.25 mg of betamethasone and 2 mg of d-chlorpheniramine maleate per tablet for about 2 years to treat allergic rhinitis. Catch-up growth occurred when this drug was stopped. The present case suggests that daily administration of 0.25 mg of betamethasone can induce growth retardation and that ingestion of corticosteroid-containing preparations needs to be excluded in children who develop short stature without other symptoms.

17-Hydroxycorticosteroids↗
PubMed1977

Results of treating childhood Cushing's disease with pituitary irradiation.

To determine the usefulness of conventional pituitary irradiation in childhood Cushing's disease, we reviewed the results of this treatment in 15 patients. Twelve were cured (mean plasma cortisol of less than 10 microgram per deciliter and 24-hour urinary 17-hydroxycorticosteroid excretion of less than 7 mg per gram of creatinine) within 18 months, and 10 of the 15 were cured within nine months. Three failures required bilateral adrenalectomy. Growth resumed in 12, with adult heights of 156 to 166 cm. Sexual development proceeded normally in all 15, with normal secondary sexual characteristics and sexual function, and demonstrated fertility in four married adults. Intellectual function appeared normal. Basal and stimulated hormone levels were normal, except for subnormal (5 ng per milliliter or less) growth hormone levels after hypoglycemia in one of 12 patients. There were no complications of therapy and no progressive pituitary enlargement or hyperpigmentation. Pituitary irradiation is safe and effective therapy for childhood Cushing's disease.

17-Hydroxycorticosteroids↗
PubMedDate not supplied

Acute mountain sickness and physiological stress during intermittent exposure to high altitude.

The effect of intermittent exposure to high altitude (4200 m) hypoxia on symptomatology of acute mountain sickness (AMS) was observed, and the relationship between AMS and stress hormone excretion was examined among shift workers at the United Kingdom Infrared Telescope (UKIRT) facility and a control group of sea level residents. Some of the shift workers experienced AMS during their first day at altitude, but had recovered after 5 days residence at altitude. Upon acute exposure to altitude, none of the shift workers reported severe cases of AMS after 5 days residence at sea level, but some reported severe cases after 45 residence at sea level, thus providing some evidence for a 'carry over' of acclimatization for a 5 day period. Reported symptomatology at sea level was predictive of 24 h. excretion rates of adrenaline and 17-hydroxycorticosteroids at high altitude. No good predictors of symptomatology of AMS at high altitude were found using sea level measures alone.

17-Hydroxycorticosteroids↗
PubMed2003

Adrenal insufficiency due to isolated adrenocorticotropin deficiency complicated by autosomal recessive polycystic kidney disease.

We describe a 29-old-year Japanese man with autosomal recessive polycystic kidney disease who was frequently hypoglycemic. Insulinoma as a cause of hypoglycemia was denied because the ratio of plasma immunoreactive insulin to glucose was low. Adrenal insufficiency was diagnosed because of the low urinary excretion of 17-hydroxycorticosteroids, and both blunted responses of plasma cortisol to an intravenous injection of adrenocorticotropin and of plasma adrenocorticotropin to an intravenous injection of human corticotropin releasing hormone were observed, although basal plasma concentrations of cortisol and adrenocorticotropin were normal. The elusion profile of plasma sample from our patient chromatographed on a Sephadex G-75 column showed two peaks of (1-39)-ACTH and beta-lipotropin, with no evidence of high molecular weight form of ACTH. The plasma concentrations of thyroid stimulating hormone and growth hormone were within the normal range. These findings indicated that this patient with autosomal recessive polycystic kidney disease was associated with adrenal insufficiency due to isolated adrenocorticotropin deficiency.

17-Hydroxycorticosteroids↗
PubMed1993

Urinary cortisol metabolites in the assessment of peripheral thyroid hormone action: application for diagnosis of resistance to thyroid hormone.

Urinary cortisol metabolites are altered both quantitatively and qualitatively in thyroid dysfunction. This study was conducted to elucidate the usefulness of urinary cortisol metabolites in the assessment of peripheral thyroid hormone action, particularly in the patients with inappropriate thyrotropin secretion. Twenty-four hour urinary 17-hydroxycorticosteroid (17-OHCS) level and gas chromatographical steroid profile were studied in 25 hyperthyroid, 18 hypothyroid, and 24 euthyroid control subjects. Five patients with generalized thyroid hormone resistance and two patients with thyrotropin secreting pituitary tumor were also studied. The ratio of urinary tetrahydrocortisone to tetrahydrocortisol (THE/THF) was significantly elevated in hyperthyroidism (4.58 +/- 1.49) and depressed in hypothyroidism (1.31 +/- 0.55) compared to control (1.93 +/- 0.35). There were good correlations between THE/THF and serum thyroid hormone levels, especially in hypothyroidism. THE/THF can be a good biochemical indicator for deficiency of peripheral thyroid hormone action. Two patients with thyrotropin-secreting tumor showed high THE/THF, which reflected thyroid hormone excess. In contrast, THE/THF in the patients with generalized thyroid hormone resistance was low as compared to high serum thyroid hormone levels. Similar findings were demonstrated with 17-OHCS but discrimination of thyroid hormone resistance was insufficient. Thus, the ratio of the urinary concentrations of cortisol metabolites, THE/THF, appears to be a good marker for peripheral thyroid hormone resistance.

17-Hydroxycorticosteroids↗
PubMed1976

Enzyme induction by enflurane in man.

Concentrations of 6-beta-hydroxycortisol (6-OHF), a polar metabolite of cortisol formed in the endoplasmic reticulum (microsomes) of the liver, and 17-hydroxycorticosteroids (17-OHCS) were measured in the urines of six healthy adult male volunteers exposed to a mean of 9.6 MAC-hours of enflurane anesthesia as an index of possible enzyme induction. The ratio of 6-OHF to 17-OHCS in 24-hour urine specimens collected five days before anesthesia was compared with the ratio of these metabolites in 24-hour urine specimens collected 16 to 18 hours after anesthesia. The ratio of 6-OHF to 17-OHCS increased markedly in five and decreased slightly in one volunteer following anesthesia. The results indicate that enflurane may cause induction of hepatic microsomal enzymes.

17-Hydroxycorticosteroids↗
PubMed1988

Comparison of hypothalamus-pituitary-adrenal axis suppression from superpotent topical steroids by standard endocrine function testing and gas chromatographic mass spectrometry.

We evaluated 38 males who had psoriasis vulgaris for evidence of hypothalamus-pituitary-adrenal axis suppression (HPAS) during treatment with superpotent topical glucocorticosteroids. All men were treated with 49 g per week of either Betamethasone Diproprionate in an optimized vehicle or Clobetasol Proprionate ointment. Three methods used to assess HPAS were compared. Classic 8 a.m. plasma cortisol measurements, urinary-free cortisol, and 17-hydroxycorticosteroid determinations and gas chromatograph-mass spectrometry (GCMS) quantitation of urinary cortisol metabolites were compared. Values for all methods were obtained just prior to therapy and at days 4, 7, 14, and 21 during therapy and at day 28 after treatment was stopped for 7 d. Plasma cortisol measurements correlated well with other measures of HPAS. GCMS determination of urinary cortisol metabolites was slightly more sensitive at detecting HPAS than the other two methods. Persistent HPAS after day 7 was only appreciated by GCMS. Urinary-free cortisol and 17-hydroxycortisol was the least sensitive of the three methods. Analysis of urinary cortisol metabolites by GCMS may be most useful in the monitoring of HPAS resulting from use of topical glucocorticosteroid preparations.

17-Hydroxycorticosteroids↗
PubMed1986

D-glucaric acid excretion in critical care patients--comparison with 6 beta-hydroxycortisol excretion and serum gamma-glutamyltranspeptidase activity and relation to multiple drug therapy.

The incidence of increased drug metabolism activity as a consequence of multiple drug therapy at a surgical intensive care ward has been studied non-invasively by determinations of daily urinary D-glucaric acid (GA) excretion rates. Among 165 randomly selected patients, GA excretion was stimulated in 76 cases (= 46%). Exploratory data analysis showed that increases in GA excretion are primarily due to administration of barbiturates (pentobarbitone, Nembutal), miconazole (Daktar) and, to a lesser extent, neuroleptics. Surprisingly, the large number of simultaneously administered additional drugs failed to increase GA excretion. Urinary 6 beta-hydroxycortisol (6 beta-OHF) and 17-hydroxycorticosteroid (17-OHCS) excretion rates were correlated in 34 patients with GA excretion; patients not receiving known enzyme inducers showed low GA values but high 6 beta-OHF and 17-OHCS values, however, with a ratio of 6 beta-OHF/17-OHCS in the normal range. Patients receiving high dose pentobarbitone treatment failed to exhibit significantly increased 6 beta-OHF and 17-OHCS or 6 beta-OHF/17-OHCS values. Miconazole treatment resulted in a significantly increased ratio of 6 beta-OHF/17-OHCS. gamma-Glutamyltranspeptidase activity in serum showed no correlation with GA excretion (n = 91).

17-Hydroxycorticosteroids↗
PubMed2006

Comprehensive study of urinary cortisol metabolites in hyperthyroid and hypothyroid patients.

OBJECTIVE: To further analyse the significance and mutual relationship of thyroid function-linked alterations in cortisol metabolism that have been separately and variously reported. PATIENTS AND MEASUREMENTS: Twenty-four-hour urine samples from 21 patients with hyperthyroidism (Graves' disease), 16 patients with hypothyroidism (Hashimoto's thyroiditis), 21 healthy age- and sex-matched controls for hyperthyroidism, and 16 healthy age- and sex-matched controls for hypothyroidism were evaluated for 6beta-hydroxycortisol (6beta-OHF), tetrahydrocortisol (THF), tetrahydrocortisone (THE), allo-tetrahydrocortisol (allo-THF), urinary free cortisol (UFF), urinary free cortisone (UFE) and 17-hydroxycorticosteroid (17-OHCS). RESULTS: Urinary 17-OHCS, THE and allo-THF levels increased considerably in hyperthyroid patients compared to the controls, while UFF and THF showed no difference between the two groups. Urinary 6beta-OHF was significantly lower in the hyperthyroid patients than in the controls. Both the urinary allo-THF + THF/THE and the UFF/UFE ratios were significantly lower in the hyperthyroid patients than in the controls, whereas only the former was significantly higher in the hypothyroid patients than in the controls. The urinary allo-THF/THF ratio was significantly higher in the hyperthyroid patients and significantly lower in the hypothyroid patients than in the controls. In an analysis of pooled subjects including all groups (n = 64), free T4 levels correlated negatively (P < 0.0001) with the urinary allo-THF + THF/THE ratio but not with the UFF/UFE ratio. The serum levels of free T4 correlated positively (P < 0.0001) with the urinary allo-THF/THF ratio. CONCLUSION: The thyroid hormones seem to affect the total 11beta-HSD activity (allo-THF + THF/THE) more strongly than the renal 11beta-HSD2 activity (UFF/UFE). 5alpha-reductase activity (allo-THF/THF) is also enhanced in hyperthyroidism, while the reduction of urinary 6beta-OHF in hyperthyroidism might be a secondary effect of the altered activity of the total 11beta-HSD and 5alpha-reductase.

17-Hydroxycorticosteroids↗
PubMed1976

Intra-nasal beclomethasone dipropionate in vasomotor rhinitis.

Twenty-one patients with vasomotor rhinitis, with no relevant allergens known, completed a special double-blind trial of beclomethasone dipropionate aerosol (BDA) and placebo intra-nasally. Each patient took 200, 400 and 800 mug BDA and placebo during four consecutive 2-week periods and in different sequences. The symptom scores of the last week of each period of nasal blockage, watery secretion and sneezing were significantly reduced by all doses of BDA as compared with placebo. There were no differences between the effects of the different doses of BDA except for secretion, which was reduced more by using 800 than 200 mug. Cortisol in serum and 17-hydroxycorticosteroids in 24-hour urine were not significantly changed by BDA treatment and no increased frequency of pathogenic bacteria or fungi could be demonstrated in the nasal secretion. For treatment of patients with vasomotor rhinitis, intra-nasal BDA in a daily dose of 200 mug can be recommended when antihistamines, sympathomimetic drugs and sodium cromoglycate are not sufficiently effective.

17-Hydroxycorticosteroids↗
PubMed2003

Relationship between fluvoxamine and stress barometer for nocturnal enuresis.

BACKGROUND: It has been reported recently that fluvoxamine (a selective serotonin reuptake inhibitor) is effective and safe for children with monosymptomatic nocturnal enuresis (MNE). However, the exact mechanism by which fluvoxamine is beneficial in the treatment of MNE remains unknown. One possibility is that it controls emotional stress. METHODS: We divided children with MNE into primary MNE (n = 40) and secondary MNE (n = 7). We measured urinary 17-hydroxycorticosteroids (17-OHCS) and 17-ketosteroid sulfates (17-KS-S) as a stress barometer in children with MNE to evaluate adaptation to emotional stress before and during fluvoxamine treatment. We initially administered fluvoxamine at a dose of 25 mg at bedtime. If patients remained incontinent after 3 weeks, we increased the dose to 50 mg. RESULTS: Fluvoxamine was effective in 26 of 28 children (93%) with primary MNE and an abnormality of the stress barometer and in six of six children (100%) with secondary MNE and an abnormality of the stress barometer. Fluvoxamine was effective in only six of 12 children (50%) with primary MNE and normality of the stress barometer and was not effective in one child with secondary MNE and normality of the stress barometer. CONCLUSIONS: The stress barometer is useful clinically for evaluating the therapeutic effect of fluvoxamine for children with MNE.

17-Hydroxycorticosteroids↗
PubMed2004

Abnormal steroidogenesis in three patients with Antley-Bixler syndrome: apparent decreased activity of 17alpha-hydroxylase, 17,20-lyase and 21-hydroxylase.

BACKGROUND: Antley-Bixler syndrome (ABS) is characterized mainly by abnormal skeletal morphogenesis such as craniosynostosis and radiohumeral synostosis, and by ambiguous genitalia in some cases. The mechanisms resulting in these deformities have not been determined. METHODS: The adrenal and gonadal function of three Japanese ABS patients were evaluated. Patient 1 (17-year-old-male) had bilateral cryptoorchidism, delayed puberty and symptoms of glucocorticoid deficiency. Patient 2 (14-year-old male) and patient 3 (4-year-old female) presented with emaciation. Additionally, patient 3 had partial labial fusion and common urogenital sinus. In each patient, blood sampling for steroid analysis before and after rapid adrenocorticotropic hormone (ACTH) stimulation was carried out. Additionally, urinary steroids were quantified. Molecular analysis of CYP17 and CYP21A2 were also performed. RESULTS: All patients showed elevated basal 17alpha-deoxysteroid levels. Although the 17alpha-deoxysteroid levels further increased after rapid ACTH stimulation, 17alpha-hydroxysteroids including cortisol did not respond, suggesting impaired 17alpha-hydroxylation. Patient 1 and patient 2 showed low adrenal androgen blood levels both before and after rapid ACTH stimulation. Patient 3 showed lower than normal excretions of urinary androgens. Additionally, a prolonged ACTH stimulation in patient 3 failed to elicit significant increase of adrenal androgens. These findings suggested impaired 17,20-lyase activity. In contrast to attenuated 17alpha-hydroxycorticosteroids, notably cortisol, elevated 17alpha-hydroxyprogesterone (17OHP) levels were observed, not only in pubertal patients (1 and 2) but also in prepubertal patient 3, indicating impaired 21-hydroxylation. This assumption was supported by increased urinary 21-deoxycortisol metabolite excretion in patients 2 and 3. With the exception of a heterozygous mutation of CYP17 in one of the patients, other mutations of this gene or CYP21A2 were identified in any of the patients. CONCLUSION: Combined decreased 17alpha-hydroxylation, 17,20-lyase activity and 21-hydroxylation was detected in three ABS patients. Considering that the enzymes responsible are all cytochrome P450 enzymes and that another cytochrome P450 enzyme, lanosterol 14alpha-demethylase, has recently been shown to be impaired in an ABS patient, we speculate that dysfunction of a system which commonly regulates cytochrome P 450 activity may be responsible for the ABS phenotype.

Abnormalities, Multiple↗