Long-term Glucocorticoid Replacement Research Articles

7560 Using a Single Pre-test Cortisol Level To Reduce The Need For Dynamic Testing For Adrenal Insufficiency In A Southeast Asian Population

Abstract Disclosure: V. Ramadoss: None. L. Tan: None. A.E. Teo: None. K. Lazarus: None. K. Meeran: None. D. Deepak: None. L. Ong: None. C. Khoo: None. P. Eng: None. Introduction: The Short Synacthen Test (SST) is widely used in clinical practice to assess Adrenal Insufficiency (AI). Despite its relative ease of administration, Synacthen use is limited by its availability and its administration demands supervision by experienced staff, resulting in increased testing cost. A single measurement of serum cortisol has been shown to predict AI, but the suggested threshold varies according to the patient cohort studied, assay variation and the prevalence of the condition relative to the size of population tested. This study aims to (a) identify a threshold cortisol level to screen for AI in a South-East Asian population and (b) to determine the utility of a stimulated 60-minute cortisol level in the diagnosis of AI. Methods: This is a retrospective analysis of SSTs (250 micrograms) performed in our institution between 28th February 2022 to 28th February 2023. Serum cortisol in our institution was measured by Abbott Alinity analysers. We defined a normal response as a stimulated cortisol value of ≥ 420nmol/L at either 30-minutes, 60-minutes, or at both time points. Logistic regression analysis was performed to predict normal responses based on baseline cortisol level. Results: Median cortisol level at baseline, 30-minutes, and 60-minutes after Synacthen stimulation were 254 (IQR 191-320) nmol/L, 499 (IQR 415 -585) nmol/L, 574 (IQR 476 -662) nmol/L respectively. A total of 785 SSTs were performed, out of which 83.1% were normal and 16.9% were abnormal. Of the 785 SSTs, 55 (7.0%) would have failed if only the 30-minute cortisol was assessed without the 60-minute value, whereas 10 (1.4%) would have failed if only the 60-minute cortisol was assessed without the 30-minutes value. An early morning basal cortisol (0800am to 1200pm) cut-off of <300nmol/L identified subnormal cortisol with 95.0% sensitivity and an afternoon cortisol (1200pm to 1700) of < 312nmol/L achieved 95.2% sensitivity. A basal cortisol level of < 100nmol/L will confirm AI with 97.3% specificity. Using a basal cortisol level of ≥ 300nmol/L, 94.8% of individuals go on to pass the SST. Use of this basal cortisol value would avoid 252 (32.1%) SSTs. Conclusion: A single measurement of basal cortisol of ≥ 300nmol/L has the potential to exclude AI with 95% sensitivity on Abbott Alinity platform in our cohort of patients. Using a threshold cortisol level of 300nmol/L, at least 32% of the SSTs could be avoided. This would have improved patients experience with cost savings implications. Furthermore, a stimulated 60-minute cortisol level identifies 55 (7%) of individuals who would otherwise be misclassified as AI, thereby avoiding unnecessary long-term glucocorticoid replacement. Presentation: 6/1/2024

Bone Microarchitecture and Volumetric Mineral Density Assessed by HR-pQCT in Patients with 21- and 17α-Hydroxylase Deficiency.

Due to disturbances in hormones and long-term glucocorticoid replacement therapy (GRT), congenital adrenocortical hyperplasia (CAH) patients are at risk of impaired bone structure and metabolism. This cross-sectional, case-control study aims to investigate for the first time bone microarchitecture features in 21-hydroxylase deficiency (21OHD; N = 38) and 17α-hydroxylase deficiency (17OHD; N = 16) patients using high-resolution peripheral quantitative computed tomography (HR-pQCT) by matching the same sex and similar age [21OHD vs. control: 29.5 (24.0-34.3) vs. 29.6 (25.9-35.2) years; 17OHD vs. controls: 29.0 (21.5-35.0) vs. 29.7 (24.6-35.3) years] with healthy controls (1:3). All patients underwent HR-pQCT scans of the nondominant radius and tibia, and had received GRT. Compared with corresponding controls, 17OHD cases had higher height (P < 0.001), weight (P = 0.013) and similar body mass index (BMI), while 21OHD had lower height (P < 0.001), similar weight and higher BMI (P < 0.001). 17OHD and 21OHD patients demonstrated various significant bone differences in most HR-pQCT indices, suggesting abnormalities in bone microarchitectures from healthy people. Further correlation analyses revealed that some characteristics, such as height and hormones, may contribute to the bone differences in HR-pQCT indices between two diseases. However, treatment dosage and time were not correlated, indicating that the current glucocorticoid doses may be within safety limits for bone impairment. Overall, our study for the first time revealed changes of bone microarchitecture in CAH patients and their potential relations with clinical characteristics. Further longitudinal researches are required to confirm these findings.

ODP631 Infectious Disease Causing Damage Of The Adrenal Glands, A Life Threating Event

Abstract Introduction Primary Adrenal Insufficiency (PAI) is not a common cause of adrenal insufficiency. The most common cause is Addison disease that is an autoimmune condition. Other causes include hemorrhage, infiltration, infections, necrosis and metastasis. We present a rare case of primary adrenal insufficiency caused by disseminated histoplasmosis. Case presentation 87 yo male from the Midwest with a history of HTN, HLD, CAD s/p CABG was admitted to our hospital for fatigue and 15 lbs weight loss. In the ED, he was found to have persistent hypoglycemia (BG in the 50s mg/dl after several vials of D50%). He was admitted to ICU for continuous D10% infusion. His laboratory showed Na 137mmol/L, K 3.7mmol/L. Further work up for hypoglycemia showed BG of 53 mg/dl with C-peptide of 0.92ng/ml and Insulin &amp;lt;1uIU/ml. Due to the concern of non-insulin dependent hypoglycemia, AM cortisol was done which was low7ug/dl. Immediately, he was started on high dose hydrocortisone. Head CT was negative for pituitary lesions. CT showed lung nodules and bilateral peripherally calcified adrenal lesions 3.6 &amp; 2.6 cm homogenous, well defined borders (HU 20-30). Adrenal hormones work up showed normal metanephrines, Aldosterone &amp;lt;1ng/dl and PRA 1.35ng/ml/h (0.25-5.82). ACTH stim test revealed cortisol level of 9. 0 ug/dl, 9.4 ug/dl, and 9.2 ug/dl at baseline, 30min and 1hr respectively with a baseline ACTH of 539. Lung biopsy showed necrotizing granuloma and fungal spores compatible with histoplasmosis. He was started on amphotericin then transition to itraconazole for 1 year. Additionally, the dose of HC was decrease and Fludrocortisone 0.1mg daily was added. He refused adrenal biopsy at that point and wanted to continue current treatment with a plan to repeat imaging in 3 months and possible adrenal biopsy depending on CT results. On follow-up, patient regained weight and hypoglycemia resolved. Repeated adrenal CT showed shrinkage of the adrenal nodules bilateral. He was continued on PAI replacement. Discussion Histoplasmosis is a fungal infection caused by (H. capsulatum), found in soil contaminated with bird or bat droppings. Infection usually limited to respiratory disease in immunocompetent host but may cause disseminated infection in immunocompromised patient which can involve any organ system. Less commonly, disseminated type may occur in an immunocompetent host with the adrenal gland being the most common infected organ. Treatment involves systemic antifungal therapy; ketoconazole or itraconazole for mild-moderate forms and amphotericin B for 12-18 months for severe ones. Relapse rate is high; ∼ 7.5% and most patients require long-term glucocorticoid replacement. Because unrecognized disseminated histoplasmosis accompanying PAI usually results in a high mortality rate, considerable suspicion and appropriate investigations are necessary for correct diagnosis of this rare but treatable disease. Presentation: No date and time listed

Pediatric Adrenal Insufficiency: Challenges and Solutions.

Adrenal insufficiency is an insidious diagnosis that can be initially misdiagnosed as other life-threatening endocrine conditions, as well as sepsis, metabolic disorders, or cardiovascular disease. In newborns, cortisol deficiency causes delayed bile acid synthesis and transport maturation, determining prolonged cholestatic jaundice. Subclinical adrenal insufficiency is a particular challenge for a pediatric endocrinologist, representing the preclinical stage of acute adrenal insufficiency. Although often included in the extensive work-up of an unwell child, a single cortisol value is usually difficult to interpret; therefore, in most cases, a dynamic test is required for diagnosis to assess the hypothalamic-pituitary-adrenal axis. Stimulation tests using corticotropin analogs are recommended as first-line for diagnosis. All patients with adrenal insufficiency need long-term glucocorticoid replacement therapy, and oral hydrocortisone is the first-choice replacement treatment in pediatric. However, children that experience low cortisol concentrations and symptoms of cortisol insufficiency can take advantage using a modified release hydrocortisone formulation. The acute adrenal crisis is a life-threatening condition in all ages, treatment is effective if administered promptly, and it must not be delayed for any reason.

Surgical treatment of primary pigmented nodular adrenocortical disease

Objective To discuss the surgical treatment of primary pigmented nodular adrenocortical disease(PPNAD). Methods twenty-four cases of PPNAD were treated in our hospital from January 2005 to December 2017. Clinical data of these patients were reviewed. It included 8 males and 16 females with a mean age of 23 years old (range 14 to 58). 23 cases presented with typical symptoms of Cushing syndrome, 1 case presented with hypertension. Eight cases could be diagnosed with Carney complex. All cases were confirmed as ACTH-independent Cushing syndrome. Adrenal imaging showed bilateral multiple nodules in 11 cases, unilateral multiple nodules in 4 cases, unilateral single mass or nodule in 3 cases, normal adrenals in 6 cases. Results All of the 24 cases received laparoscope unilateral adrenalectomy or laparoscope unilateral mass resection. After the operation, 8 cases underwent secondary operation because of symptom recurrence and the elevated 24-hour urinary free cortisol. Among them, 5 cases received contralateral subtotal adrenalectomy, 3 cases received contralateral total adrenalectomy. Seven cases with a slightly elevated 24-hour urinary free cortisol but a good recovery of Cushing symptoms were followed-up. Nine cases recovered well after the first operation and they didn′t undergo secondary surgical treatment, but 1 of the 9 cases needed glucocorticoid replacement. Conclusions Bilateral adrenalectomy followed with long-term glucocorticoid replacement is the standard treatment of PPNAD. Unilateral adrenalectomy or subtotal adrenalectomy may be suitable for elected patients, but appropriate criteria need to be explored. Key words: Cushing syndrome; Primary pigmented nodular adrenocortical disease(PPNAD); Carney complex

Impact of nasal continuous positive airway pressure for congenital adrenal hyperplasia with obstructive sleep apnea and bruxism

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders in humans. The most frequent CAH variant is 21-hydroxylase deficiency. Patients with 21-hydroxylase deficiency require long-term glucocorticoid replacement treatment. Although sleep disturbance is frequently observed under glucocorticoid replacement treatment, a case of obstructive sleep apnea(OSA) in patients with CAH has not been reported. A 43-year-old man with CAH who complained about sleep disturbance and sleep bruxism was diagnosed as obstructive sleep apnea (OSA) by polysomnography (PSG). Following the introduction of nasal continuous positive airway pressure (nCPAP), his sleep disturbance with symptoms also improved; in addition, he was able to reduce the dose of glucocorticoid replacement therapy without any adverse consequences on his sleep pattern. Physicians who treat a patient with CAH should know the possibility in the existence of OSA in their patients. Because symptoms with OSA in CAH patient may increase the dosage of long-term glucocorticoid treatment for the patient, which may induce several adverse effects including body weight gain on the patient.

Auricular Cartilage Calcification and Adrenal Insufficiency

A healthy 60-year-old man presented to the emergency department with profound hypotension 1 day after sustaining a minor hand laceration with minimal blood loss. Physical examination revealed stiffness in both ears, and calcification of the ears was subsequently revealed on computed tomography (Panel A, arrows) and radiography (Panel B, arrows). The patient's hemodynamic status improved promptly after administration of antibiotics and glucocorticoids, and he recovered with support from the intensive care unit. Throughout his 20-day hospital stay, bacterial cultures remained negative. Subsequent detailed investigations showed adrenal insufficiency resulting from autoimmune hypophysitis, with isolated failure to secrete corticotropin. Long-term glucocorticoid-replacement therapy . . .

Hormone therapy in rheumatic diseases

Steroid hormones are deeply involved in the pathophysiology of immune-mediated rheumatic diseases and used for their treatment. Purpose of the review is to update on recent roles and mechanisms of action of important steroid hormones such as glucocorticoids, estrogens, and D hormone (vitamin D) in order to optimize their therapeutical use. Endogenous glucocorticoids are characterized by a circadian rhythm of production that must be respected in case of exogenous low-dose long-term glucocorticoid replacement therapy of rheumatic diseases. Estrogens are enhancers of the humoral immune response and increase cell proliferation. Therefore, estrogens represent a risk factor for the development of autoimmunity and their therapeutical use must be avoided in patients with active immune-mediated diseases. Vitamin D, as synthesized in the skin from cholesterol, is a real steroid hormone (D hormone). The immunosuppressive activities of D hormone are reduced in chronic rheumatic diseases, as low plasma levels of the hormone are evident and justify its therapeutical use. The optimization of the therapeutical use of steroid hormones such as glucocorticoids, estrogens or D hormone is now possible following recent basic and clinical research achievements.

Modified‐release hydrocortisone for circadian therapy: a proof‐of‐principle study in dexamethasone‐suppressed normal volunteers

All existing long-term glucocorticoid replacement therapy is suboptimal as the normal nocturnal rise and waking morning peak of serum cortisol is not reproduced. To test whether it is possible to reproduce the normal overnight rise and morning peak in serum cortisol using an oral delayed and sustained release preparation of hydrocortisone (Cortisol(ds)). Six healthy normal male volunteers attended on two occasions, in a single-dose, open-label, nonrandomized study. Endogenous cortisol secretion was suppressed by administration of dexamethasone. Cortisol(ds) (formulation A or B) was administered at 2200 h on day 1. Blood samples for measurement of cortisol were taken from 2200 h every 30 min until 0700 h, then hourly until 2200 h on day 2. Fifteen body mass index (BMI)-matched control subjects had serum cortisol levels measured at 20-min intervals for 24 h. Serum cortisol profiles and pharmacokinetics after Cortisol(ds) were compared with those in controls. Formulations A and B were associated with delayed drug release (by 2 h and 4 h, respectively), with median peak cortisol concentrations at 4.5 h (0245 h) and 10 h (0800 h), respectively, thereby reproducing the normal early morning rise in serum cortisol. Total cortisol exposure was not different from controls. For the first time we have shown that it is possible to mimic the normal circadian rhythm of circulating cortisol with an oral modified-release formulation of hydrocortisone, providing the basis for development of physiological circadian replacement therapy in patients with adrenal insufficiency.

Prospective evaluation of a protocol for reduced glucocorticoid replacement in transsphenoidal pituitary adenomectomy: prophylactic glucocorticoid replacement is seldom necessary

Most pituitary surgery centres prescribe perioperative glucocorticoids to subjects undergoing transsphenoidal pituitary adenomectomy (TSA), despite reports suggesting this may be unnecessary. Evidence-based guidelines for glucocorticoid use in TSA have recently been published but there are no prospective studies of their utility. To implement and assess a protocol for reduced glucocorticoid replacement for subjects undergoing TSA. Prospective and retrospective cohort study in an Australian pituitary surgery centre. Clinical and biochemical data for 56 TSAs performed for non-ACTH-secreting tumours between March 2004 and April 2006 were prospectively collected and compared with data for 47 TSAs performed between October 2001 and November 2003, before implementation of the protocol. In the prospective cohort, a postoperative days 1-3 morning serum cortisol threshold of 250 nmol/l (91 microg/dl) was used to guide long-term glucocorticoid requirement. Implementation of the protocol was associated with significant reductions in dose and duration of glucocorticoid treatment post TSA in 44 'low-risk' cases (no preoperative glucocorticoid use or evidence of pituitary apoplexy). In two low-risk cases, long-term glucocorticoid replacement was required despite postoperative cortisol greater than 250 nmol/l. Following the remaining 42 low-risk operations, glucocorticoid was not prescribed on hospital discharge on the basis of morning serum cortisol > 250 nmol/l and no clinical evidence of hypocortisolism. None of these 42 cases required glucocorticoid treatment for hypocortisolism following surgery. Short synacthen tests were performed in 35 of these subjects a minimum of 6 months after surgery and were normal. Use of the protocol was not associated with differences in postoperative complications. Reduced glucocorticoid replacement in TSA is safe and reduces patient exposure to glucocorticoids and their potential adverse events. The occurrence of hypocortisolism in two low-risk subjects with serum cortisol > 250 nmol/l highlights the importance of daily clinical assessment when using this protocol.

Endogenous corticosteroid biosynthesis in subjects after bilateral adrenalectomy

Corticosteroids can be synthesized in extra-adrenal tissues but the contribution of this to circulating levels in humans is not known. Previous in vitro studies suggest that the 'hybrid' corticosteroid 18-oxocortisol (18-oxoF) is produced from cortisol by aldosterone synthase. We looked for evidence of extra-adrenal production of this and other corticosteroids in 10 subjects stable on long-term glucocorticoid replacement following bilateral adrenalectomy. In phase 1, patients were maintained on cortisol alone (30 mg/day), in phase 2 dexamethasone (2 mg/day), and in phase 3, both cortisol and dexamethasone. Each phase lasted 3 days. On the last day of each phase, 24-h urine collection was performed for analysis of steroid metabolite excretion [using gas chromatography-mass spectrometry (GCMS)] and plasma aldosterone and renin were measured (by radioimmunoassay). Cortisol metabolite excretion rate [tetrahydrocortisone (THE) + tetrahydrocortisol (THF) + allotetrahydrocortisol (aTHF)] fell from 9169 nmol/24 h in phase 1 to 22 nmol/24 h in phase 2, rising to 6843 nmol/24 h in phase 3. Tetrahydroaldosterone (THAldo) excretion was readily detectable and did not alter significantly between phases (26.5, 23.5 and 28.5 nmol/24 h, respectively; P = 0.474). 18-Hydroxycortisol (18-OHF) excretion was easily detectable in phases 1 and 3 (252.5 and 212 nmol/24 h), falling in phase 2 (12 nmol/24 h). 18-oxoF excretion rates were lower but followed a similar pattern (1.62, 0.085 and 1.785 nmol/24 h in phases 1, 2 and 3, respectively). Significant levels of adrenal steroids are found in adrenalectomized subjects. We speculate that this occurs at extra-adrenal sites or in residual adrenal cortex tissue in an ACTH-independent manner. Our data suggest that aldosterone synthase, acting on cortisol, is the source of 18-oxoF and 18-OHF in these subjects. Further studies of corticosteroid production within adrenalectomized subjects, looking for evidence of adrenal regrowth or residual adrenal tissue, are justified.

Acute management of pituitary apoplexy – surgery or conservative management?

The rarity of pituitary apoplexy renders it a difficult subject for audit; hence there are no evidence-based standards of optimum care for such patients. The key controversy in management relates to the role of acute neurosurgical intervention. In recent years we have adopted a relatively conservative approach towards patients presenting with pituitary apoplexy. Against this background, we aimed to determine whether our less-interventional approach affected long-term clinical outcome in these patients. A retrospective analysis was performed to evaluate clinical presentation, management and clinical outcomes in a cohort of patients who presented acutely with pituitary apoplexy during the period 1994-2004. Data from 33 patients (13 female) were included, with a mean age of 52 (range 27-79) years and mean follow-up duration of 3.7 (0.4-10.1) years. The most common presenting symptoms were headache (97%), visual deficits (82%) and nausea/vomiting (78%). Fifteen patients (46%) underwent transsphenoidal surgery while 18 were managed conservatively. Indications for surgery were deteriorating visual deficit (n = 13), hemiparesis (n = 1) and altered conscious level (n = 1). Eight patients in the surgical group had ocular paresis that resolved in 63% following surgery, and seven had visual field defects with recovery in 57% postsurgery. Conservative management was reserved for patients with absent, or evidence of resolving, visual deficits at presentation. In this group, seven presented initially with ocular paresis and six with visual field defects but all made full recoveries. Of the patients managed neurosurgically, 87% required long-term glucocorticoid replacement and 60% required long-term thyroid hormone replacement. Conservatively managed patients required glucocorticoid replacement in 72% and thyroid hormone replacement in 72% of cases (P = NS between the two groups). Sex steroid replacement was required in 67% and 83% of patients managed neurosurgically and conservatively respectively (P = NS). At latest follow-up one patient in the conservatively managed group had required surgery and one in the surgically managed group had received pituitary radiotherapy, in both instances due to evidence of tumour regrowth on magnetic resonance imaging (MRI). Our findings suggest that patients presenting with pituitary apoplexy in whom visual deficits are stable or improving may be managed expectantly as there is no identifiable deleterious effect on visual or endocrine outcome. One patient from each group experienced tumour regrowth that necessitated further treatment intervention, highlighting the importance of long-term follow-up in patients with pituitary apoplexy.

An assessment of bone mineral density in patients with Addison's disease and isolated ACTH deficiency treated with glucocorticoid.

Glucocorticoid replacement therapy needs to be tailored to individual patient's requirements in order to avoid risk of over or under medication. We measured bone mineral density (BMD) of lumbar spine using dual X-ray absorptiometory in 10 patients with Addison's disease and 5 patients with isolated ACTH deficiency receiving glucocorticoid replacement therapy. We also examined the effect of glucocorticoid replacement on BMD. Decreased %BMD (less than 80% of age-matched controls) was found in 2 female patients who had received hydrocortisone at a dose of 14.8 and 15.4 mg/m(2)/day. In contrast, no patient receiving a hydrocortisone dose of less than 12.4 mg/m (2)/day had decreased %BMD. There was no correlation between %BMD and hydrocortisone dose (mg/m(2)), duration of therapy, or cumulative hydrocortisone dose when treated with appropriate dose of hydrocortisone (<13.6 mg/m(2)). There was also no statistically significant difference in %BMD with age. We concluded that long-term glucocorticoid replacement therapy does not induce bone loss in patients with glucocorticoid deficiency unless an excessive dose of hydrocortisone is given.

Long-term follow-up of bone mineral density in Addison's disease.

There is conflicting evidence regarding the long-term effects of long-term glucocorticoid replacement therapy (GRT) on bone mineral density (BMD) in patients with chronic adrenal insufficiency. Our aim was to evaluate bone turnover and changes in BMD in patients on GRT. We have studied 25 subjects (six men, 19 women; aged 62.4 +/- 11.3 years, duration of disease 21.7 +/- 11.7 years, fasting cortisol 63 +/- 36 nmol/l) on GRT (hydrocortisone 30 mg/day or prednisone 7.5 mg/day). BMD was assessed at the lumbar spine (LS; L2-L4), proximal femur (PF) and ultra distal radius (UR) by dual energy X-ray absorptiometry (DXA). The rates of bone loss were calculated using previous DXA measurements at the LS (48 and 60 months earlier). Serum calcium, phosphate alkaline phosphatase (ALP), bone ALP, serum osteocalcin (BGP), intact parathyroid hormone (PTH) and 25(OH) vitamin D were also measured. BMD [Z-score; 95% confidence interval (95% CI)] was normal at the LS: (-1.15-+0.07); PF: (-0.90-+0.22) and UDR (-0.77-+0.36). No significant differences were found according to the type of replacement therapy or sex. No significant bone loss (g/cm2; 95% CI) was detected at the LS: (-0.021-+0.023). Fifty-six per cent of patients met osteoporotic criteria; a greater proportion of patients treated with prednisone had osteoporosis compared with those an hydrocortisone. All bone markers were in their normal ranges. Patients on long-term therapy do not show accelerated bone loss at the lumbar spine. Nevertheless, a considerable proportion of patients, mainly those treated with prednisone, showed densitometric osteoporosis.

Bone density in young patients with congenital adrenal hyperplasia

One of the major complications of glucocorticoid treatment is bone loss. 21-Hydroxylase deficiency is the most frequent inborn error of steroidogenesis, leading to congenital adrenal hyperplasia (CAH): synthesis of cortisol is impaired and replacement therapy is therefore mandatory. We studied the bone mineral density in a group of patients with congenital adrenal hyperplasia (CAH) on long-term glucocorticoid replacement therapy. We selected 30 Caucasian patients with CAH due to 21-hydroxylase deficiency (mean +/- SD age = 17.45 +/- 2.49 years). 22 patients had the classical CAH form and the remaining 8 had the nonclassical (late-onset) form. The mean duration of therapy was 15.20 +/- 4.04 years. Bone mineral density (BMD) was evaluated with a dual-energy X-ray absorptiometer. BMD was also measured in 73 healthy white volunteers of comparable age (17.35 +/- 2.99 years). BMD values of the spine (sBMD), total body (TBBMD), legs, and arms of CAH patients, adjusted for confounding variables (age, gender, body mass index), did not differ from those of control subjects (p = 0.86; p = 0.17; p = 0.06 and p = 0.26, respectively). sBMD and TBBMD values did not show relationships with the duration of treatment and the dose of corticosteroids. Patients with the classical form of CAH had bone density values comparable with those of patients with the nonclassical form (sBMD: p = 0.33; TBBMD: p = 0.97). Our data show that, despite long-term treatment with glucocorticoids, CAH patients have bone density values comparable with controls.

Regulation of the Glucocorticoid Receptor by Glucocorticoids in Human Mononuclear Leukocytes

We analyzed glucocorticoid receptor binding in peripheral blood mononuclear leukocytes from normal adult males and from females at the follicular and luteal phases. Healthy controls were analyzed before and after 17 days of treatment with two synthetic glucocorticoids: prednisone and an oxazoline derivative of prednisolone (deflazacort). We also studied for comparison 4 patients with adrenocortical insufficiency, two of them on long-term corticoid replacement, and 7 patients with Cushing's syndrome. Using a whole-cell competitive binding assay and 3H-dexamethasone as tracer, normal human mononuclear leukocytes (19 males, 6 females) were found to have 4,529 +/- 1,532 (mean +/- SD) binding sites per cell and a dissociation constant (Kd) of 9.5 +/- 2.3 nM. In Cushing's syndrome the receptor parameters were within the normal range. Cells from patients with untreated Addison's disease had low levels of sites per cell. The number of binding sites increased to normal after long-term glucocorticoid replacement. All the adrenal insufficiency cases had a normal Kd. Finally, following treatment with the synthetic glucocorticoid, deflazacort, the sites per cell were reduced but the Kd remained unchanged. Prednisone had no effects.