Urinary 17-hydroxycorticosteroids Research Articles

Perioperative stress dose steroid management of children with classical congenital adrenal hyperplasia: Too much or too little?

Children with congenital adrenal hyperplasia (CAH) are at risk for adrenal crises in the perioperative period and require higher doses of glucocorticoids. However, there are no specific protocols detailing the appropriate stress dosing required for children with CAH undergoing surgery with anesthesia. To evaluate CAH patients using our current hydrocortisone stress dose surgical protocol. We hypothesized that current clinical protocols may overestimate the endogenous response to perioperative stress. 14 children with CAH scheduled to have genital surgery and a control group of 10 unaffected children scheduled to have cardiac or urologic surgery (of a similar duration) were evaluated in a prospective observational study. Urinary free cortisol (UFC) and urinary 17-hydroxycorticosteroids (17-OHCS) per body surface area were measured in the postoperative period. UFC levels were significantly higher in CAH patients (115.8±24.6nmol/m2) than in controls (26.5±12.2nmol/m2), P<0.05.17-OHCS levels were also higher in CAH patients than in controls (6.5±0.5nmol/m2 vs. 3.4±0.5nmol/m2), P<0.05). In the immediate postoperative period, urinary cortisol and its metabolites are significantly higher in pediatric CAH patients receiving stress dose corticosteroids compared to controls. Results suggest that the amount of hydrocortisone given during our stress dose protocol may be higher than physiologic needs. Future dynamic studies are needed to determine appropriate perioperative and postoperative cortisol requirements in pediatric CAH patients in order to develop optimal stress dose regimens.

Analysis of RIG-I-mediated innate immune response in rats with Kidney-Yang Deficiency Syndrome and its change following Yougui pill administration

Kidney-Yang Deficiency Syndrome (KYDS) is closely bound up with the immune response of immunocompromised patients. The study is to investigate whether retinoic acid-inducible gene-I (RIG-I)-mediated innate immune responseparticipates in the development of KYDS in rats and evaluate the effect of Yougui pill (YGP) on the response in KYDS rats. KYDS rats were induced by intramuscular injection of hydrocortisone at the dose of 10 mg/kg/d for 15 days. YGP at concentrations of 2.43 g/kg/d and 4.86 g/kg/d were administered intragastrically to KYDS rats for 30 days. The results showed that the body weight, urinary 17-hydroxycorticosteroid (17-OHCS) level, spleen size and spleen index in KYDS rats were significantly decreased compared with healthy control rats, while YGP treatment reversed them towards normal level in a dose-dependent manner. Moreover, KYDS challenge not only strikingly increased the mRNA and protein expression levels of RIG-I, tripartite motif containing 25 (TRIM25), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) but also markedly enhanced the endogenous RIG-I polyubiquitination levels. Whereas, YGP treatment effectively reversed this tendency in a dose-dependent manner. In conclusion, these findings revealed that RIG-I-mediated innate immune response was closely bound up with the development of KYDS. And YGP exhibited certain anti-inflammatory effects on KYDS rats via inhibiting the RIG-I-mediated innate immune response.

Subjective symptoms and physiological measures of fatigue in air traffic controllers

This study measured the correlation between fatigue and physiological stress symptoms in 102 air traffic controllers (ATCs) in Taiwan. The subjects were asked to complete a fatigue questionnaire and physiological measurement before and after work. The study results showed that nearly 50% of the subjects felt tired and weary after work. However, according to the results of the critical flicker frequency test, all ATCs performed better after work, and the strength of masculine index fingers improved. The systolic and diastolic blood pressure decreased after work. In addition, the levels of urinary 17-hydroxycorticosteroids (17-OHCS) at the pre-shift and post-shift stages were 1.91 ± 1.01 mg/g cr. and 1.50 ± 0.95 mg/g cr., respectively. This study indicated that, while the ATCs' subjective ratings showed possible work-induced fatigue, it did not affect their physiological response. The findings suggested that ATC is a stressful job, and that complaints regarding excess work stress should be taken seriously. Subsequently the study proposed appropriate intervention strategies to address the identified problems. Relevance to industryThis paper presents the subjective and objective measures of fatigue in ATCs. Recommendations are proposed with respect to potentially viable countermeasures to reduce the impact of fatigue in ATC operations, and achieve a broader understanding of the causal factors for fatigue in ATC.

Influence of Occupational and Environmental Exposure to Low Concentrations of Polychlorobiphenyls and a Smoking Habit on the Urinary Excretion of Corticosteroid Hormones.

The effects of occupational exposure to low concentrations of polychlorobiphenyls (PCBs) on the urinary excretion of corticosteroid hormones were evaluated, taking into account the influence of cigarette smoking. The study included 26 males working as electrical maintenance staff in a steel factory, previously exposed to a mixture of PCBs (exposed workers), and 30 male workers with no occupational exposure to PCBs (controls). Serum PCBs (33 congeners), urinary 17-hydroxycorticosteroids, 17-ketosteroids (KS) and pregnanes, and their respective glucuronidated and sulfonated compounds, were determined for each subject. PCBs were significantly higher in the exposed workers than controls, and were correlated with age. Both the urinary concentrations of the total 17-KS and pregnanes, and those of some single steroids and their glucuronidated compounds, were significantly lower in the exposed workers than controls, but higher in smokers than the non-smokers + ex-smokers. Two-way analysis of variance showed a negative association between serum PCBs and both total glucuronidated 17-KS and total and glucuronidated pregnanes, and a positive association between cigarette smoking and both total and glucuronidated 17-KS. PCBs seem to act as endocrine disruptors by reducing the urinary excretion of corticosteroid hormones, particularly of the glucuronidated fraction. Cigarette smoking could boost these effects of PCBs in smokers.

Macronodular Adrenal Hyperplasia due to Mutations in an Armadillo Repeat Containing 5 (ARMC5) Gene: A Clinical and Genetic Investigation

Inactivating germline mutations of the probable tumor suppressor gene, armadillo repeat containing 5 (ARMC5), have recently been identified as a genetic cause of macronodular adrenal hyperplasia (MAH). We searched for ARMC5 mutations in a large cohort of patients with MAH. The clinical phenotype of patients with and without ARMC5 mutations was compared. Blood DNA from 34 MAH patients was genotyped using Sanger sequencing. Diurnal serum cortisol measurements, plasma ACTH levels, urinary steroids, 6-day Liddle's test, adrenal computed tomography, and weight of adrenal glands at adrenalectomy were assessed. Germline ARMC5 mutations were found in 15 of 34 patients (44.1%). In silico analysis of the mutations indicated that seven (20.6%) predicted major implications for gene function. Late-night cortisol levels were higher in patients with ARMC5-damaging mutations compared with those without and/or with nonpathogenic mutations (14.5 ± 5.6 vs 6.7 ± 4.3, P < .001). All patients carrying a pathogenic ARMC5 mutation had clinical Cushing's syndrome (seven of seven, 100%) compared with 14 of 27 (52%) of those without or with mutations that were predicted to be benign (P = .029). Repeated-measures analysis showed overall higher urinary 17-hydroxycorticosteroids and free cortisol values in the patients with ARMC5-damaging mutations during the 6-day Liddle's test (P = .0002). ARMC5 mutations are implicated in clinically severe Cushing's syndrome associated with MAH. Knowledge of a patient's ARMC5 status has important clinical implications for the diagnosis of Cushing's syndrome and genetic counseling of patients and their families.

Clinical and Genetic Heterogeneity, Overlap with Other Tumor Syndromes, and Atypical Glucocorticoid Hormone Secretion in Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia Compared with Other Adrenocortical Tumors

ACTH-independent macronodular adrenal hyperplasia (AIMAH) is often associated with subclinical cortisol secretion or atypical Cushing's syndrome (CS). We characterized a large series of patients of AIMAH and compared them with patients with other adrenocortical tumors. We recruited 82 subjects with: 1) AIMAH (n = 16); 2) adrenocortical cortisol-producing adenoma with CS (n = 15); 3) aldosterone-producing adenoma (n = 19); and 4) single adenomas with clinically nonsignificant cortisol secretion (n = 32). Urinary free cortisol (UFC) and 17-hydroxycorticosteroid (17OHS) were collected at baseline and during dexamethasone testing; aberrant receptor responses was also sought by clinical testing and confirmed molecularly. Peripheral and/or tumor DNA was sequenced for candidate genes. AIMAH patients had the highest 17OHS excretion, even when UFCs were within or close to the normal range. Aberrant receptor expression was highly prevalent. Histology showed at least two subtypes of AIMAH. For three patients with AIMAH, there was family history of CS; germline mutations were identified in three other patients in the genes for menin (one), fumarate hydratase (one), and adenomatosis polyposis coli (APC) (one); a PDE11A gene variant was found in another. One patient had a GNAS mutation in adrenal nodules only. There were no mutations in any of the tested genes in the patients of the other groups. AIMAH is a clinically and genetically heterogeneous disorder that can be associated with various genetic defects and aberrant hormone receptors. It is frequently associated with atypical CS and increased 17OHS; UFCs and other measures of adrenocortical activity can be misleadingly normal.

Change of aquaporin-1 in rat models of kidney-yang-deficiency syndrome

To explore the material foundation of kidney-yang-deficiency syndrome. Two kinds of rat models of deficiency of kidney-yang were induced by adenine intragastric administration (model I) and hydrocortisone intramuscular injection (model II). One hundred rats were randomly divided into normal control group, model I group, low-dose model II group, medium-dose model II group and high-dose model II group. After model establishment, contents of serum creatinine (SCr), blood urea nitrogen (BUN), and urine creatinine (UCr) were detected by automatic biochemistry analyzer; freezing point method was used for 24-hour urinary osmotic pressure (Uosm) testing and kaolinite method was used to detect the content of urinary 17-hydroxycorticosteroid (17-OHCS). Expression of aquaporin-1 in renal tissue was observed by using real time reverse transcription polymerase chain reaction. The rats of model groups had the characteristics of kidney-yang deficiency syndrome. The contents of SCr and BUN were significantly higher in model I group than in normal control group and three model II groups (P<0.05), and UCr and Uosm were significantly lower (P<0.05). The level of urinary 17-OHCS and expression of aquaporin-1 in renal tissue were decreased in the model I group (P<0.05) as compared with the normal control group. Compared with the normal control group, the content of SCr was increased and urinary 17-OHCS was decreased in the medium-dose model II group, but the expression of aquaporin-1 was increased in three model II groups with a dose-dependent manner. Aquaporin-1 may be one of the material foundations of kidney-yang-deficiency syndrome.

Dynamic Pituitary MRI has High Sensitivity and Specificity for the Diagnosis of Mild Cushing's Syndrome and should be Part of the Initial Workup

The diagnosis of mild or episodic Cushing's syndrome is difficult. The standard tests include 24-hour urinary free cortisol (UFC), night-time blood, or salivary cortisol measurements, and dexamethasone suppression tests. Imaging studies of the pituitary have not been recommended as part of the initial workup (only to help distinguish pituitary Cushing's disease from the ectopic ACTH syndrome) because of poor sensitivity and specificity. With the development of dynamic pituitary MRI which uses multiple coronal dynamic sequences following gadolinium intravenous contrast, we hypothesized that the sensitivity and specificity would be increased and MRI would provide useful information for the initial diagnosis of Cushing's syndrome. This was a retrospective chart review examining charts from 87 consecutive patients who were evaluated for Cushing's syndrome in a tertiary Endocrinology clinic over a one-year period. Most patients had mild and/or episodic hypercortisolism. Of these patients, 24 eventually were diagnosed with pituitary Cushing's syndrome by biochemical testing (24-h UFC and urinary 17-hydroxycorticosteroids, 11 PM salivary cortisol measurements, evening plasma cortisol), and 22 had the diagnosis of Cushing's syndrome excluded. Dynamic pituitary MRI (1.5 Tesla) was performed on all patients. The reader of the MRI was blind to the diagnosis. Twenty-three of 24 patients had a MRI consistent with a pituitary lesion (21 with a microadenoma, two with pituitary asymmetry). In contrast, only 3 of 20 patients (2 patient did not have MRIs) in the Cushing's excluded group had a pituitary lesion on dynamic MRI. Dynamic pituitary MRI had the highest sensitivity and negative predictive value of any testing modalities and its specificity and positive predictive value were similar to that of other tests. We conclude that almost all patients in this series with Cushing's syndrome have a lesion on dynamic pituitary MRI, a rate much higher than the 50-60% rate reported for non-dynamic MRIs. The false positive rate of 16% in our group of Cushing's excluded patients is similar to the literature value of 10% seen in normal volunteers and is acceptable since MRI is not used solely as a determinant for the diagnosis. While a negative MRI will miss those patients with adrenal or ectopic Cushing's syndrome, those patients can usually be diagnosed by other testing. Thus this preliminary study implies that dynamic pituitary MRI adds valuable information to assist in the diagnosis of Cushing's syndrome and should be ordered as part of the initial workup.

Type 2 Pseudohypoaldosteronism: New Insights Into Renal Potassium, Sodium, and Chloride Handling

Type 2 Pseudohypoaldosteronism: New Insights Into Renal Potassium, Sodium, and Chloride Handling

Stress barometer at diagnoses in children with school non-attendance

School non-attendance is a major social problem in Japan. Many children stop attending school for a variety of reasons. The authors previously reported stress barometer values for healthy Japanese children. In this study, the authors examined the stress barometer values of children with school non-attendance. The authors measured stress barometer values, that is, urinary 17-hydroxycorticosteroids (17-OHCS) and 17-ketosteroid sulfates (17-KS-S) in 65 children (40 girls and 25 boys; 7-15 years of age) with school non-attendance, except for pervasive developmental disorder and mental retardation, who attended the outpatient department of Dokkyo University School of Medicine Hospital, Tochigi, Japan, during the past 4 years. A total of 24 (36.9%) of the 65 children had urinary 17-OHCS values above 2SD, and 14 (21.5%) had urinary 17-OHCS below 2SD. In total, 10 (15.4%) children had urinary 17-KS-S values above 2SD, and four (6.2%) had urinary 17-KS-S below 2SD. Five (7.7%) children had urinary 17-KS-S/17-OHCS values above 2SD, and 10 (15.4%) had urinary 17-KS-S/17-OHCS below 2SD. The stress barometer values appear to be clinically useful for evaluating objectively whether children with school non-attendance have emotional stress.

Comprehensive study of urinary cortisol metabolites in hyperthyroid and hypothyroid patients

To further analyse the significance and mutual relationship of thyroid function-linked alterations in cortisol metabolism that have been separately and variously reported. 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). 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. 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.

Tests of Pituitary-Adrenal Suppressibility in the Diagnosis of Cushing??s Syndrome*???

ABSTRACT Past attempts to test suppressibility of pituitary-adrenal function by the use of exogenous corticoids have yielded inconsistent findings in patients with Cushing's syndrome. The present study indicates that, with proper selection of suppressive agent and adjustment of dosage, valuable diagnostic information can be obtained from such tests. Δ1-9α-Fluorocortisol (ΔFF) and its 16α:-methylated analog (dexamethasone) were employed as suppressive agents. At dosage levels of 0.5 mg. every six hours for 8 doses these agents induced almost complete suppression of 17-hydroxycorticoid excretion in all 54 endocrinologically normal subjects tested. In contrast, all 35 of the patients with true Cushing's syndrome who were studied maintained relatively high urinary 17-hydroxycorticoid levels during such treatment. At these low dosages, therefore, the suppressive agents were useful in separating patients with Cushing's syndrome from those with normal adrenal function. Administration of ΔFF or dexamethasone in l...

The low-dose dexamethasone suppression test: a reevaluation in patients with Cushing's syndrome.

Low-dose dexamethasone suppression testing has been recommended for biochemical screening when Cushing's syndrome is suspected. The criterion for normal suppression of cortisol after dexamethasone is controversial. To assess diagnostic utility (sensitivity), we report the results of low-dose dexamethasone suppression testing in 103 patients with spontaneous Cushing's syndrome. There were 80 patients with Cushing's disease (78%), 13 with the ectopic ACTH syndrome (13%), and 10 with cortisol-producing adrenocortical adenomas (10%). Fourteen (18%) of 80 patients with Cushing's disease suppressed serum cortisol to less than 5 micro g/dl (<135 nmol/liter) after the overnight 1-mg test, whereas six patients (8%) actually showed suppression of serum cortisol to less than 2 micro g/dl (<54 nmol/liter). In addition, the 2-d, low-dose dexamethasone suppression test yielded false-negative results in 38% of patients when urine cortisol was used and 28% when urinary 17-hydroxycorticosteroids were used. Serum cortisol after the 1-mg test correlated with baseline urinary free cortisol (r = 0.705, P < 0.001), plasma ACTH level (r = 0.322, P = 0.001), and urinary free cortisol after the 2-d test (r = 0.709, P = 0.001). This study provides evidence that low-dose dexamethasone may suppress either plasma cortisol or urinary steroids to levels previously thought to exclude Cushing's syndrome and that these tests should not be used as the sole criterion to exclude the diagnosis of endogenous hypercortisolism.

Adrenal cortical and medullar hyperplasia--a retrospective analysis of 6 cases.

The features of the symptoms, laboratory tests and pathological characteristics of adrenal cortical and medullary hyperplasia were studied. In 6 cases of hypercatecholaminenia, plasma norepinephrine (NE), epinephrine (E), catecholamine (CA) and 24-h urinary vanillylmandelic acid (VMA), 17-hydroxycorticosteroid (OHCS) and 17-ketosteroid (KS) were determined. Adrenal glands were examined by CT scan and 131I-MIBG imaging. Pathological examination was performed after operation. The results showed that in 6 cases of hypercatecholaminenia (3 men and 3 women) aged from 34-50 years, the clinical features were just like "pheochromocytoma", for example, episodic headache, perspiration, palpitation, pallor, apprehension, nausea, tremor, anxiety and so on. Plasma levels of CA, NE and E were elevated in all 6 cases. 24-h urinary samples obtained at the onset revealed elevated VMA in 1 case. 24-h urinary cortisol was obviously elevated in all 6 cases. 24-h urinary 17-OHCS, 17-KS was normal. B-type ultrasound, CT, MRI and 131I-MIBG revealed 9 lateral adrenal gland diffuse or nodular enlargement in 6 cases. Pathologic examination showed adrenal cortical and medullary hyperplasia. Clinically, adrenal cortical and medullary hyperplasia resembled "pheochromocytoma". The most significant feature of this disease was both elevated plasma CA and 24-h urinary cortisol obviously. Pathologic examination showed adrenal cortex nodular hyperplasia and medullar diffuse or limit hyperplasia. Whether it is an independent disease or symptoms of the other disease has not final conclusion up till now.

Intermittent Hypercortisolism: A Disorder Strikingly Prevalent After Hypophysial Surgical Procedures

To determine the frequency of intermittent hypercortisolism in a consecutive series of patients with Cushing's disease who underwent hypophysial surgical treatment. Thirty-three patients with hypercortisolism of central origin underwent follow-up at approximately annual intervals for prolonged periods after a transsphenoidal pituitary surgical procedure. Clinical evaluation was done, and urinary steroid measurements, as well as dexamethasone suppression tests in some patients, were performed. Frequently normal but intermittently increased urinary 17-hydroxycorticosteroid or cortisol excretion (or both) was found in six patients postoperatively, associated with intermittently severe hypertension, headaches, and weakness in only one patient. In a seventh patient, intermittently excessive cortisol excretion was clearly evident preoperatively. Because corticoid excretion was variable preoperatively in three of the seven study patients, we conclude that intermittent hypercortisolism is commoner than previous evidence has shown, constitutes an extremely difficult diagnostic problem, and did not result from but failed to be cured by pituitary surgical treatment in 6 of 33 patients (18%). The findings emphasize the need for regular follow-up for several years in all patients with Cushing's syndrome who have undergone a hypophysial surgical procedure. Variable consistency of follow-up might partly explain the wide discrepancies between reports of 80 to 90% and 40 to 60% cure rates after a single hypophysial adenomectomy.

Ectopic adrenocorticotropin syndrome associated with undifferentiated carcinoma of the colon showing multidirectional neuroendocrine, exocrine, and squamous differentiation

We report a rare case of ectopic ACTH syndrome associated with undifferentiated carcinoma of the ascending colon. A 62-year-old woman developed hypokalaemia and metabolic alkalosis associated with markedly elevated serum cortisol and plasma ACTH levels. High-dose dexamethasone (8 mg/day) did not suppress increased urinary 17-hydroxycorticosteroid and 17-keto-steroid excretion. Barium enema and abdominal computerised tomography showed a Borrmann II type tumour in the ascending colon, multiple metastatic nodules in the liver and bilateral enlargement of the adrenal glands. Histological examination of the resected primary colon cancer and metastatic liver tumour showed undifferentiated carcinoma with areas of distinct neuroendocrine, exocrine, and squamous differentiation. ACTH production by the tumour was confirmed by radioimmunoassay and immunohistochemistry. This is a unique case report of carcinoma of the colon with distinct multidirectional differentiation causing ectopic ACTH syndrome.

Adrenocortical Tumors in Children: A Report of 12 Cases

Adrenocortical tumors in children are extremely rare, accounting only for 0.3-0.4% of all neoplasms in this age. Most frequently they secrete hormones, resulting in virilization, Cushing's syndrome or feminization, while the non-functioning ones are unusual. The authors describe 12 cases observed in 13 years (1976-1989), with a mean age of 5 years. 9 cases showed virilization, 4 presented with Cushing's syndrome and in 5 patients an abdominal mass was palpable. One case was affected by Beckwith-Wiedemann's syndrome. I.V. urography was performed in 8 patients, arteriography in 4 and since 1982 all patients were submitted to abdominal sonography and CT scan or MR imaging. Urinary 17-ketosteroids, 17-hydroxycorticoids and serum testosterone and cortisol were tested in all children. Dexamethasone suppression test was performed in 7. All patients were treated with surgery which seems to be the most suitable treatment, while the real effectiveness of treatment by drug therapy with suppressors of steroidogenesis is not confirmed in children. Histopathological examination showed typical features of adenoma in 5 cases, of adenocarcinoma in 4, while three cases revealed border line forms classified as "atypical adenomas". At the moment 10 patients are alive with a follow-up ranging from 18 months to 14 years, while 2 children with adenocarcinoma are dead.

Biochemical effects of Catha edulis, cathine and cathinone on adrenocortical functions

Catha edulis is a plant that grows in certain areas of East Africa and the Arab Peninsula. The stimulating properties of fresh material were described more than seven centuries ago and today the habit of inducing a state of euphoria and subjective well-being by chewing Catha edulis prevails among the inhabitants of these regions. Oral administration of this plant and its active constituents (cathine and cathione) on experimental animals might have stimulating effects on adrenocortical function. This was indicated by the significant decrease in adrenal cholesterol, ascorbic acid, glycogen, and the increase in adrenal phosphorylase activity. In addition, the level of urinary 17-hydroxycorticosteroids and plasma free fatty acids were increased.

Clinical Experience of Incidentally Discovered Adrenal Tumor with Particular Reference to Cortical Function

We reviewed 14 male and 9 female patients with adrenal tumor discovered incidentally by imaging studies in an attempt to assess adrenal function, mainly cortical function. Pathological diagnosis consisted of cortical adenoma in 12 patients, cortical nodular hyperplasia in 2, medullary hyperplasia in 1, cavernous hemangioma in 1, metastatic tumor in 4 and cyst in 2. Another adrenal cyst was diagnosed by percutaneous puncture. In all patients peripheral levels of plasma cortisol and aldosterone were normal. Plasma catecholamine levels were also normal except for 1 patient with medullary hyperplasia who had equivocal elevation. Among the patients with cortical adenoma and hyperplasia, however, 5 of 10 (50%) had excessive excretion of 24-hour urinary 17-hydroxycorticosteroids, 4 of 13 (31%) had a loss of plasma cortisol circadian rhythm and 7 of 14 (50%) had insufficient suppression on the dexamethasone test. Furthermore all patients had an increased ipsilateral uptake that was not suppressed after dexamethasone on 131iodine-adosterol scintigraphy, while a diminished contralateral uptake was noted in 5 of 15 (33%). Postoperatively, hypertension decreased to normal in 2 of 3 patients and impaired glucose tolerance was improved in 1 of 2. Two patients with cortical adenoma who exhibited a loss of plasma cortisol circadian rhythm experienced postoperative adrenal insufficiency.These data indicate that a considerable number of incidentally discovered adrenal tumors are not nonfunctioning particularly in reference to glucocorticoid secretion, and adrenalectomy seems to be beneficial in some of those patients with hypertension or impaired glucose tolerance.

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.