Experimentally challenged reactivity of the hypothalamic pituitary adrenal axis in patients with recently diagnosed rheumatoid arthritis

OBJECTIVE: There is evidence that the hypothalamic pituitary adrenal (HPA) axis is subresponsive in patients with rheumatoid arthritis (RA). We assessed HPA axis responses to experimental stressors mimicking daily life challenges in patients with RA to determine whether HPA axis activity is associated with Th1 and Th2 activity. METHODS: ACTH and cortisol responses in reaction to the succession of a bicycle ergometer task, a cold pressor task, and a computerized Stroop Color-Word interference test, as well as basal Th1 and Th2 cell activity, were assessed in 29 patients (21 female, 8 male) with recently diagnosed RA (mean disease duration 29 wks, range 5-69), mean age 55.7 years, none receiving glucocorticoid treatment, and 30 (20 female, 10 male) healthy age and sex matched controls (mean age 54.1 yrs). RESULTS: Mean ACTH and cortisol levels did not differ between the groups (p > 0.10). Patients tended to have a less pronounced ACTH response (F2.50 = 2.7, p = 0.08) and had a significantly smaller cortisol response (P F2.50 = 6.1, p < 0.01) than healthy controls in reaction to the stressors. This difference in cortisol response was reduced, but remained significant when ACTH responsiveness was accounted for by entering it as a covariate (P F2.49 = 3.7, p = 0.03). ACTH and cortisol levels and responses were not associated (all p > 0.19) with basal interferon-gamma and interleukin 4 as reflections of Th1 and Th2 cell activity, respectively. HPA axis activity was not linked to current disease activity. CONCLUSION: Our findings show reduced HPA axis responsiveness in RA patients with recent diagnosis receiving longterm medication that is suggested to be located both at a hypothalamic/pituitary and at an adrenal level. It appears that common HPA axis activity accomplishes low amounts of cortisol release, which makes it difficult to determine an influence of endogenous cortisol changes on the Th1/Th2 balance.     

Low dose (1 microg) adrenocorticotropin stimulation test in the evaluation of hypothalamo-pituitary-adrenal axis in patients with active pulmonary tuberculosis

Adrenocortical function in patients with active pulmonary tuberculosis is a debate of matter. Previous studies related to adrenocortical function in patients with active pulmonary tuberculosis demonstrated a high rate of suboptimal cortisol response to standard dose ACTH (250 microg) stimulation test. The aim of this study was to assess the hypothalamo-pituitary-adrenal (HPA) axis in low dose (1 microg) and standard dose ACTH (250 microg) stimulation tests in the patients with active pulmonary tuberculosis. Twenty-seven patients and 21 healthy subjects were included in the study. Cortisol levels were measured before, 30 and 60 min after ACTH (1 microg or 250 microg iv) injection. Cortisol responses to 1 microg ACTH at 30 and 60 min were significantly higher in the patient group than in the control group (p<0.05). Peak cortisol levels were significantly higher in the patient group than in the control group after both 1 microg and 250 microg ACTH administration (p<0.05). Cortisol responses to 250 microg ACTH at 30 and (at 30 and 60) 60 min were significantly higher in the patient group than in the control group (p<0.05). Peak cortisol levels obtained after 250 microg ACTH and after 1 microg ACTH were similar in the patient group (p>0.05). This study shows that 1 microg ACTH iv gives an equivalent peak cortisol value to 250 microg ACTH in patients with activated HPA axis. The cortisol levels obtained at 08:00, 11:00, 17:00 and 24:00 h were significantly higher in the patients than in the controls. This study clearly shows that HPA axis is activated in active pulmonary tuberculosis rather than underactivated.     

A case of aldosterone-producing adrenocortical adenoma associated with a probable post-operative adrenal crisis: histopathological analyses of the adrenal gland.

We describe a case of aldosterone-producing adrenocortical adenoma (APA) associated with a probable post-operative adrenal crisis possibly due to subtle autonomous cortisol secretion. The patient was a 46-year-old female who suffered from severe hypertension and hypokalemia. CT and MRI scans revealed a 2-cm diameter adrenal mass. The patient's plasma aldosterone level was increased, and her plasma renin activity was suppressed, both of which findings were consistent with APA. Cushingoid appearance was not observed. Morning and midnight serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels were all within the normal range. Her serum cortisol level was suppressed to 1.9 microg/dl as measured by an overnight 1-mg dexamethasone suppression test, but was incompletely suppressed (2.7 microg/dl) by an overnight 8-mg dexamethasone suppression test. In addition, adrenocortical scintigraphy showed a strong uptake at the tumor region and a complete suppression of the contra-lateral adrenal uptake. After unilateral adrenalectomy, she had an episode of adrenal crisis, and a transient glucocorticoid replacement improved the symptoms. Histopathological studies demonstrated that the tumor was basically compatible with APA. The clear cells in the tumor were admixed with small numbers of compact cells that expressed 17alpha-hydroxylase, suggesting that the tumor was able to produce and secrete cortisol. In addition, the adjacent non-neoplastic adrenal cortex showed cortical atrophy, and dehydroepiandrosterone sulfotransferase immunoreactivity in the zonae fasciculata and reticularis was markedly diminished, suggesting that the hypothalamo-pituitary-adrenal (HPA) axis of the patient was suppressed due to neoplastic production and secretion of cortisol. Together, these findings suggested that autonomous secretion of cortisol from the tumor suppressed the HPA axis of the patient, thereby triggering the probable post-operative adrenal crisis. Post-operative adrenocortical insufficiency should be considered in clinical management of patients with relatively large APA, even when physical signs of autonomous cortisol overproduction are not apparent.     

Corticotropin-releasing hormone receptor expression on normal and tumorous human adrenocortical cells

Corticotropin-releasing hormone (CRH) is not only the principal regulator of the central hypothalamic-pituitary-adrenal (HPA) axis but also exerts direct actions on peripheral tissues. We analyzed the expression of CRH receptors in microdissected preparations of normal human adrenal glands and in adrenocortical and adrenomedullary tumors, employing immunohistochemistry, quantitative RT-PCR of microdissected adrenal tissues, and in situ hybridization. The effect of CRH on adrenal steroidogenesis was tested in adrenal cells. Immunoreactive CRH1R was found primarily within the zona reticularis. In addition, we found a higher expression of CRH type-1 and 2 receptors mRNAs in preparations of adrenal cortices as compared to pheochromocytomas, a 6-fold increase in preparations of clinically unapparent adrenocortical adenomas, and a 10- to 60-fold increase in cortisol-producing adrenal adenomas. Stimulation of the adrenal tumor cell line NCI-H295R with CRH elicited a 1.4-fold increase in DHEA secretion. This result could be reproduced in a culture of primary human adrenocortical cells. We conclude that adrenocortical cells exhibit a higher expression of functional CRH receptors than chromaffin cells and that CRH acts on adrenal DHEA production. The data support the assertion of a direct action of CRH on human adrenocortical cells in addition to an intra-adrenal CRH receptor/adrenocorticotropin system. Enhanced CRH1R expression may be involved in adrenocortical tumorigenesis.     

Basic and clinical aspects of intraadrenal regulation of steroidogenesis

The adrenal gland combines essential components of the autonomic nervous system and the HPA axis in close contact. From morphological analyses employing immunohistochemistry, in situ hybridization, the novel technique of laser capture microdissection, and electron microscopy, it has been has shown that the chromaffin cells of the adrenal medulla and the steroid-producing cells of the adrenal cortex are extensively intermingled and functionally interrelated. In in vitro studies, a variety of regulatory factors produced and released by the adrenal medulla were identified as playing an important role in modulating adrenocortical function. An isolated adrenocortical cell deprived of its tissue integrity, input from the nervous system, or intercellular communication with chromaffin, vascular, and immune cells of the adrenal gland, loses its normal capacity to produce glucocorticoids and to adequately respond to the homeostatic challenges of stress. Adrenocortical cells in co-culture with chromaffin cells produced ten times more glucocorticoids than the same number of pure adrenocortical cells and demonstrated marked up-regulation in the mRNA expression of cytochrome p450 enzymes and STAR in the co-culture, while this expression was down-regulated in isolated cells. Transgenic animal models of over-expression or deletion of enzymes involved in catecholamine synthesis, as well as of altered function of components of the HPA axis, provide evidence that the mutual interdependence of the sympatho-adrenal system and the HPA axis at the level of the adrenal gland is of physiologic relevance in vivo. Alterations in intercellular communications, local production of neuropeptides, growth factors and cytokines, and aberrant expression of ectopic receptors on adrenal cells have been implicated in adrenal cell growth, development, hyperplasia, tumor formation, autonomous hormone production, and autoimmune disease. Moreover, we described a direct cellular interaction of lymphocytes with adrenal cells as a novel non-cytokine mediated mechanism of immune endocrine interactions. Highlighting the importance of the extra-pituitary mechanisms of adrenocortical regulation, be them neural or immune, is a worthwhile starting point for a more complete analysis of the human stress system in vivo.     

Characterization of adrenal autonomy in Cushing's syndrome: a comparison between in vivo and in vitro responsiveness of the adrenal gland

We measured cortisol and precursor steroid production in response to ACTH, cholera toxin, and forskolin by the dispersed adrenocortical cells prepared from the adrenal glands of 10 patients with different forms of Cushing's syndrome. The cells prepared from the hyperplastic adrenal glands from 4 patients with Cushing's disease responded in a dose-dependent manner to ACTH, cholera toxin, and forskolin. The adrenal cells prepared from 4 encapsulated adrenal adenomas showed no (n = 2), a lowered (n = 1), or a clear (n = 1) response of cortisol release to ACTH. The cells prepared from the adrenal glands of 1 patient with dysplastic micronodular adrenal glands showed a limited response to ACTH, while the cells from an adrenocortical carcinoma, which secreted very little cortisol per cell, were unresponsive to ACTH, cholera toxin, and forskolin. The reaction of the dispersed adrenal cells from these 10 patients to ACTH, cholera toxin, and forskolin showed a close correlation (P less than 0.001 in all instances). This suggests that the defect in autonomous glands is not located at the level of the ACTH receptor, but, rather, involves the adenylate cyclase complex as a whole or its coupling to cAMP-dependent protein kinase. The release into the medium of the cortisol precursors deoxycortisol, 17-hydroxyprogesterone, and progesterone showed that the four autonomous nodules were characterized by a significantly higher deoxycortisol/cortisol ratio in the medium (P less than 0.01), suggesting a relative blockade of 11 beta-hydroxylase in these adrenal adenomas. This was further substantiated in cells from several adrenals by a significant increase in the release of these precursors in response to ACTH in the absence of a cortisol response. We conclude the following. 1) Adrenal adenoma formation in patients with Cushing's syndrome is accompanied by a parallel decrease in the stimulation of the release of steroid hormones in response to ACTH, cholera toxin, and forskolin. This points to a defect in the adenoma cells beyond the ACTH receptor. 2) Adrenal adenoma formation in patients with Cushing's syndrome is accompanied by a relative blockade of 11 beta-hydroxylase activity. 3) By comparing the preoperative dynamic tests of the pituitary-adrenal axis, the plasma ACTH concentration, the morphology of the adrenal glands, and their in vitro responsiveness, a gradual transition from pituitary to (partial) adrenal autonomy could be recognized in several patients.     

Adrenal tuberculosis in Cushing's disease with bilateral macronodular adrenocortical hyperplasia

Cushing's disease is a disorder of hypercortisolism caused by a pituitary micro- or macro-adenoma. Most patients with Cushing's disease have a bilateral adrenal enlargement, which depends on the duration of the disease, as a result of the long standing ACTH stimulation of both adrenal glands. However, in macronodular adrenocortical hyperplasia (MNH) that is caused by Cushing's disease, if the MNH gains autonomy, a bilateral adrenalectomy, as well as the removal of pituitary adenoma, is often essential. We encountered a patient diagnosed with Cushing's disease with bilateral adrenal tuberculosis simulating MNH. She had taken anti-tuberculosis medications one year prior to admission due to spinal tuberculosis. Sellar MRI revealed a pituitary macroadenoma, but adrenal CT showed enlargement in both adrenal glands that appeared to be MNH. A hormonal study and bilateral inferior petrosal sinus sampling revealed Cushing's disease. Therefore, she underwent trans-sphenoidal surgery of the pituitary mass. The pituitary surgery was successful and the serum cortisol returned to normal range. However, the adrenal mass rapidly enlarged after removing the pituitary tumor without showing evidence of a recurrence or adrenal autonomy of hypercortisolism. Accordingly, a laparoscopic left adrenalectomy was performed to examine the nature of the mass. The resected left adrenal gland was pathologically determined to have a lesion of tuberculosis with some part of the intact cortex. So we assumed that the cause of rapid adrenal enlargement might be due to adrenal tuberculosis. In summary, to the best of our knowledge, this is the first case of Cushing's disease coexisting with both adrenal tuberculosis simulating a bilateral MNH.     

Adrenocortical insufficiency after pituitary surgery: an audit of the reliability of the conventional short synacthen test

BACKGROUND: Assessment of the hypothalamic-pituitary-adrenal (HPA) axis after pituitary surgery is important for appropriate decision making regarding replacement therapy. The synacthen test is often used but is questioned, as time has to elapse for adrenal atrophy to develop. OBJECTIVE: To audit the use of the 250 microg synacthen test after transsphenoidal adenomectomy. METHODS: A retrospective study of 110 patients submitted to first-time transsphenoidal adenomectomy. Anterior pituitary testing was performed preoperatively, 1 week and 1, 3, 6 and 12 months postoperatively. The adrenocortical function was tested by a synacthen test (250 microg synacthen i.v.). RESULTS: Thirty-two out of 71 patients with normal HPA function before surgery developed insufficiency postoperatively, seven patients presenting an insufficient test response after 1 week, 16 after 1 month and nine after 3 months, whereas none became insufficient during the remaining follow-up. Three patients presented symptomatic adrenal insufficiency during the first postoperative week despite a normal test. All of these developed an insufficient test 1 month postoperatively. A 1-week basal plasma cortisol > 400 nmol/l indicated HPA sufficiency, whereas a basal cortisol < or = 100 nmol/l indicated insufficiency when related to the diagnosis based on the 3-month synacthen test. CONCLUSION: This study confirms that the synacthen test is of limited use in the early postoperative phase, because out of 62 patients with normal 1-week postoperative synacthen responses, 23 patients developed a test that was indicative of adrenal insufficiency over 1-3 months. Our results indicate that a large proportion of patients should be considered for hydrocortisone replacement therapy up to 3 months postoperatively followed by reassessment of the HPA axis.     

In vitro responses of focal hyperplastic tissue of the human adrenal zona fasciculata to ACTH.

The temporal cAMP, cortisol and aldosterone responses to ACTH of focal hyperplasia of the zona fasciculata and of normal human adrenocortical tissue were investigated. ACTH significantly increased cAMP levels (1 min) and cortisol output (2 min) in normal adrenal tissue but not in hyperplastic tissue. However, following ACTH treatment cortisol and aldosterone production were depressed in the abnormal adrenal tissue below the untreated or the ACTH stimulated normal adrenal tissue. In addition, basal cortisol and aldosterone production of the hyperplastic adrenal tissue was elevated above that of the normal adrenal tissue. These findings suggest that the cAMP second messenger concept may be only one of several mechanisms in the modulation of human adrenocortical function.     

Adrenocortical and Pituitary Glucocorticoid Feedback in Abstinent Alcohol‐Dependent Women

Background: The long‐term ingestion of alcohol diminishes hypothalamic–pituitary–adrenal (HPA) axis reactivity in alcohol‐dependent men, potentially altering future relapse risk. Although sex differences in HPA axis functioning are apparent in healthy controls, disruptions in this system have received little attention in alcohol‐dependent women. In this study, we assessed the basal secretory profile of adrenocorticotropic hormone (ACTH) and cortisol, adrenocortical sensitivity in both the presence and absence of endogenous corticotropic pituitary activation, and feedback pituitary glucocorticoid sensitivity to dexamethasone. Methods: Seven women 4‐ to 8‐week abstinent alcohol‐only dependent subjects and 10 age‐matched female healthy controls were studied. All subjects were between 30 and 50 years old, not taking oral contraceptives, and were studied during the early follicular phase of their menstrual cycle. Circulating concentrations of ACTH and cortisol were measured in blood samples collected at frequent intervals from 2000 to 0800 hour. A submaximal dose of cosyntropin (0.01 μg/kg), a synthetic ACTH (1–24), was administered at 0800 hour to assess adrenocortical sensitivity. In a separate session, low‐dose cosyntropin was also administered following high‐dose dexamethasone (8 mg intravenous) to assess adrenocortical sensitivity in the relative absence of endogenous ACTH. In addition, the ACTH response to dexamethasone was measured to determine the pituitary glucocorticoid negative feedback. Sessions were 5 days apart, and blood draws were obtained every 5 to 10 minutes. Results: Mean concentrations and pulsatile characteristics of ACTH and cortisol over 12 hours were not statistically different between the 2 groups. Healthy controls had a somewhat higher (p < 0.08) net peak, but not net integrated, cortisol response to cosyntropin relative to the alcohol‐dependent women. There were no significant group differences in either the ACTH or cortisol response to dexamethasone nor in the net cortisol response to cosyntropin following dexamethasone. Conclusion: Significant differences in pituitary–adrenal function were not apparent between alcohol‐dependent women and matched controls. Despite the small n, it appears that alcohol‐dependent women do not show the same disruptions in HPA activity as alcohol‐dependent men. These findings may have relevance for gender‐specific treatment effectiveness.     

The effect of thyrotoxicosis on adrenocortical reserve

OBJECTIVE: Variations in thyroid function are known to be associated with changes in adrenocortical activity. Previous studies in animals have suggested that long-standing hyperthyroidism may be associated with diminished adrenal functional reserve despite a continuing hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. In humans, there has been no direct assessment of adrenal secretory reserve in clinical thyrotoxicosis. This study aimed to assess adrenocortical reserve in response to low-dose ACTH, following dexamethasone suppression, in patients with severe thyrotoxicosis. DESIGN AND METHODS: Ten patients (four men and six women, 30-45 years) with severe long-standing thyrotoxicosis due to Graves' disease (n=6) or toxic nodular goitre (n=4) were studied at diagnosis and again when in a stable euthyroid state following drug therapy for 8-12 months. All patients underwent ACTH stimulation tests at 0800h with ACTH(1-24) (Cortrosyn; 0.1microg/kg body weight, i.v.) following overnight suppression of the HPA axis with dexamethasone (1mg per os at 2300h). Serum cortisol was assayed at -15, 0, 15, 30, 60 and 90min after the administration of ACTH. RESULTS: The mean (+/-s.d.) peak and delta cortisol responses to ACTH (634.5+/-164nmol/l and 618+/- 196nmol/l respectively), as well as the net area under the response curve (36769+/-12188nmol/lx min) in the hyperthyroid patients were significantly lower compared with the values when the same patients were euthyroid (911+/-157nmol/l, 905+/-160nmol/l and 57652+/-10128nmol/lxmin respectively; P<0.005). Subnormal peak cortisol responses (<500nmol/l) were observed in two severely toxic patients. The findings were independent of the cause of thyrotoxicosis. CONCLUSION: In patients with severe thyrotoxicosis, cortisol secretion in response to low-dose ACTH stimulation, following dexamethasone suppression, is lower in the hyperthyroid than in the euthyroid state. It appears that thyrotoxicosis is associated with subtle impairment of adrenocortical reserve.     

Adrenocortical function in patients investigated for active tuberculosis.

Previous reports have identified adrenal insufficiency in groups of patients with active pulmonary tuberculosis. To investigate this possibility, serum cortisol levels were measured in consecutive patients admitted to the hospital for investigation of active tuberculosis. Blood was drawn for cortisol determination promptly at the time of hospital admission, in the morning and afternoon before commencing chemotherapy for the suspected tuberculosis, and before the diagnosis was confirmed. Thirty-seven patients were assessed; 19 of these patients were subsequently proven to have active pulmonary tuberculosis, six had pulmonary disease caused by mycobacteria other than tuberculosis, and 12 had radiologic appearance indicating tuberculosis, accompanied by a significant tuberculin skin reaction but with negative sputum cultures and no change in roentgenographic appearance during the course of treatment. In evaluating the adrenocortical function, the morning and afternoon serum cortisol level was measured and the diurnal change in serum cortisol level (the difference between afternoon and morning levels) was calculated. There was no association of either morning cortisol levels or diurnal change in cortisol levels with age, gender, or race. There was no difference among the three groups in either cortisol determination. Although difference in morning cortisol levels between those with extensive as compared with limited disease was not statistically significant (p = 0.349 from analysis of variance), there was a significantly decreased diurnal change in cortisol levels in those with extensive disease as compared with those with limited disease (+2.7 +/- 188.3 vs -259.1 +/- 177.1). We conclude that patients in our hospital with active pulmonary tuberculosis do not exhibit decreased adrenocortical function as compared with groups of patients without active pulmonary tuberculosis.     

Isolated ACTH deficiency confirmed by ACTH radioimmunoassay

A 28 year old woman presented with symptoms and biochemical findings suggesting hypoglycemia. Detailed endocrine investigations indicated secondary adrenocortical insufficiency with no rise in plasma ACTH or plasma cortisol following insulin-induced hypoglycemia or vasopressin infusion. The adrenal glands however produced cortisol normally following prolonged stimulation with depot tetracosactrin. Other anterior pituitary hormones were released normally following appropriate stimulation tests. The literature on isolated ACTH deficiency is briefly reviewed, and this case represents one of the few reports in which the diagnosis has been substantiated by ACTH radioimmunoassays.     

Differential expression and action of Toll-like receptors in human adrenocortical cells

During sepsis, an intact adrenal gland glucocorticoid stress response is critical for survival. Recently, we have shown that Toll-like receptors, particularly TLR2 and TLR4, are crucial in HPA axis regulation following inflammation, establishing a direct link between bacterial and viral ligands and the endocrine stress response. However, the exact role which TLRs play in adrenal homeostasis and malfunction is not yet sufficiently known. Using quantitative real-time PCR, confocal microscopy and the NF-κB reporter gene assay, we aimed to analyse both, expression and function of all relevant TLRs in the human adrenocortical cell line—NCI-H295R and adrenal cells in primary culture. Our results demonstrate a differential expression pattern of TLR1–9 in human adrenocortical cells as compared to immune cells and adrenocortical cancer cells. Consequently, activation of these cells by bacterial ligands leads to differential induction of cytokines including IL6, IL8 and TNF-α. Therefore, Toll-like receptors expression and function is a novel feature of the adrenal stress system contributing to adrenal tissue homeostasis, regeneration and tumorigenesis.     

The influence of sex and gonadectomy on the hypothalamo-pituitary-adrenal axis of the sheep.

There is a sex difference in the hypothalamo-pituitary-adrenal (HPA) axis of many species, although there are sparse data on the sheep. In the present study we have compared the HPA axes of intact and gonadectomised adult male and female sheep at the level of the median eminence, pituitary and adrenal glands using a variety of in vitro approaches. The concentration of arginine vasopressin (AVP) was higher (P<0.01) in the median eminence of male than female sheep, and was also elevated by gonadectomy of either sex (P<0.01). The concentration of corticotrophin-releasing factor (CRF) in the median eminence did not differ between the sexes, but was also elevated in both sexes following gonadectomy (P<0.01). Anterior pituitary pro-opiomelanocortin mRNA concentrations were higher (P<0.05) in intact male sheep than in intact females, with the levels in gonadectomised animals of both sexes being intermediate. In contrast to this finding, basal ACTH secretion from anterior pituitary cells was higher (P<0.05) in cultures derived from female sheep than those from males, but gonadectomy was without effect. There was no effect of sex or gonadectomy on in vitro ACTH secretion in response to AVP, CRF or the combination of AVP and CRF, and in all cases the combination of AVP and CRF generated greater (P<0.0001) ACTH secretion than AVP alone. AVP alone was more effective (P<0.01) than CRF alone as an ACTH secretagogue. The adrenal glands were larger (P<0.05) in female than male sheep, with no effect of gonadectomy. Basal cortisol production was greatest (P<0.05) in cultures of adrenal cells from intact male sheep, though ACTH- and 8BrcAMP-induced cortisol production was greater in the cultures of cells from females (P=0.05); there were no effects of gonadectomy. Cultures of adrenocortical cells from male sheep had greater (P<0.05) basal cAMP production, but ACTH-stimulated cAMP production did not differ between any of the groups of animals. These findings show a range of differences in the HPA axis of male and female sheep. Furthermore, they suggest that the heightened activity of the axis in the female occurs primarily due to differences at the level of the adrenal gland, and that greater adrenal responsiveness of female animals is due to differences in the latter stages of steroidogenesis, rather than an effect on ACTH signal transduction at its receptor.     

A case of adrenal tuberculosis complicated with acute exacerbation of adrenal insufficiency during the initial phase of anti-tuberculosis therapy for pulmonary tuberculosis

A 36-year-old male was admitted to our hospital because of adrenal insufficiency. About one month before admission, he was diagnosed as pulmonary tuberculosis and started anti-tuberculosis therapy with isoniazid, rifampicin, ethambutol, and pyrazinamide. On the tenth day, general fatigue, abdominal pain, nausea and diarrhea developed, and laboratory examination showed hyponatremia [126 mEq/l]. Enhanced CT on admission revealed bilateral adrenal mass-like enlargement, and further examination showed high level of plasma ACTH, and low level of cortisol. These findings led to a diagnosis of adrenal insufficiency caused by adrenal tuberculosis. He was treated with hydrocortisone and his signs and symptoms rapidly improved. We suppose adrenal insufficiency became clinically apparent because rifampicin reduced half-life of serum cortisol. Interestingly we observed rapid increase and decrease in size of bilateral adrenal glands on CT scan during the course.     

The potential role of increased adrenal volume in the pathophysiology of obesity-related type 2 diabetes

The hypothalamic-pituitary-adrenal (HPA) axis seems to play an important role in obesity and Type 2 diabetes (DM). The aim of the present study was to determine the adrenal volume in obese patients with DM in comparison to obese non-diabetic patients. Eleven diabetic obese and 19 non-diabetic obese women were sequentially invited to take part in the study. Computed tomography (CT) scan of the abdomen was performed to determine adrenal volume, visceral (VF) and sc fat (SCF). Daily urinary free cortisol (UFC) was used as a measure of integrated cortisol production. In the diabetic patients, hemoglobin A1c was measured as an index of metabolic control. Compared to nondiabetic controls, patients with diabetes had a significantly higher total adrenal volume (4.29+/-1.50 vs 2.95+/-1.64; p=0.03). A highly significant correlation was detected between VF and VF/SCF ratio and total adrenal volume in the whole group (r=0.36, p=0.04 and r=0.48, p=0.008, respectively). This study, therefore, suggests an association between abdominal obesity, enlarged adrenals and Type 2 diabetes. These findings support the hypothesis that an increased activity of the HPA axis in obese subjects may be involved in the pathogenesis of Type 2 diabetes.     

肾上腺结核的多层螺旋CT诊断

目的 探讨肾上腺结核的多层螺旋CT平扫及增强表现特征,以提高该病的CT诊断水平。 方法 对经临床证实的13例肾上腺结核患者的CT表现特征进行回顾性分析。 结果 13例中,男性8例,女性5例;年龄20～58岁,平均42岁。肾上腺结核累及双侧共12例,单侧1例。肾上腺肿块样增大10例,轻度或中度增大3例,轮廓完整。肾上腺密度均匀增高1例,不均匀增高12例。周边强化11例。4例患者经抗结核治疗后复查CT,其中1例双侧增大的肾上腺体积缩小或恢复正常,其内低密度消失,9例患者行手术治疗,而且术前术后进行了抗结核治疗。早期肾上腺结核 CT 表现为肾上腺体积增大,并见密度不均匀的扁圆形肿块9例,增强扫描后肿块周边强化,其内见线样明显强化的正常肾上腺组织分隔,边缘清楚。晚期肾上腺结核表现为腺体萎缩及钙化4例。8例患者伴有肾上腺外结核,包括肺结核4例、泌尿系结核2例、脊柱结核1例,同时伴有肺结核、左肾结核及脊柱结核1例。 结论 肾上腺结核的CT具有特征性表现,当发现全身多脏器结核,同时发现肾上腺上述影像变化,则要考虑肾上腺结核的诊断,为临床治疗及疗效判断提供指导。     

Immediate postoperative cortisol levels accurately predict postoperative hypothalamic–pituitary–adrenal axis function after transsphenoidal surgery for pituitary tumors

Accurate assessment of the hypothalamic–pituitary–adrenal (HPA) axis is critical for the appropriate management of patients with pituitary adenoma after transsphenoidal surgery. We examine the role of immediate postoperative cortisol levels to assess hypothalamic–pituitary–adrenal axis (HPA) axis function post-operatively. We performed preoperative cortrosyn stimulation test (CST) and measured immediate postoperative serum cortisol levels in 100 patients undergoing 104 transsphenoidal surgeries. These results were compared to those of the CST at 4–6 weeks postoperatively, which served as a measure of HPA axis function. The ability of immediate postoperative, day of surgery (DOS) cortisol levels to predict normal HPA axis function was determined using standard predictive analytic methods and confusion matrix calculations. We found that postoperative, DOS cortisol level ≥15 μg/dL is a sensitive and accurate predictors of normal postoperative HPA axis function, with a sensitivity of 98%, an accuracy of 97%, and a positive predictive value of 99%. Our data suggest that an immediate, postoperative, DOS cortisol level ≥15 μg/dL predicts distant, normal, post-operative HPA axis function following transsphenoidal surgery.     

The hypothalamic-pituitary-adrenal axis in asthmatic children.

Reduced responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis in patients with various chronic allergic inflammatory disorders and a blunted HPA axis response of poorly controlled asthmatics before long-term treatment with inhaled corticosteroids (ICS) have been reported. It seems that pro- and anti-inflammatory cytokines might be involved in the attenuation of cortisol and adrenocorticotropic hormone (ACTH) responses to stress in these patients. Although long-term ICS treatment might produce mild adrenal suppression in some asthmatic children, improvement of adrenal function has been detected in the majority of cases. We postulate that the anti-inflammatory effects of ICS result both in asthma remission and HPA axis improvement. Adrenal suppression of some asthmatic patients on maintenance ICS seems to be a separate phenomenon, possibly constitutionally or genetically determined.