Large Doses Of Glucocorticoids Research Articles

Expert consensus on prevention and treatment strategies for osteonecrosis of femoral head during the prevention and control of novel coronavirus pneumonia (2020)

Novel coronavirus pneumonia is a new type of respiratory infectious disease that has rapidly spread in many countries or regions around the world. The World Health Organization (WHO) named it "coronavirus disease 2019 (COVID-19)". Glucocorticoids (GC) have certain application value in patients with COVID-19, but they need to be used with caution and strict indications and dosage. Application of large doses of GC can also cause osteonecrosis of femoral head (ONFH). On the basis of the latest literature and evidence-based medical evidence on the fight against COVID-19 epidemic and steroid ONFH diagnosis and treatment, the Bone Circulation and Osteonecrosis Professional Committee, Shockwave Medical Specialty Committee of Chinese Research Hospital Association organized Chinese bone necrosis related experts to jointly write this consensus, focusing on the prevention strategy and the protective management measures in the ONFH diagnosis and treatment process during the prevention and control of COVID-19, which can provide reference for hospitals at all levels to carry out early prevention and treatment of ONFH.

Clinical diagnosis and treatment recommendations for immune checkpoint inhibitor-related adverse reactions in the nervous system.

Immune checkpoint inhibitors (ICIs) can cause adverse reactions in the nervous system. The incidence rate is 0.1%–12% and 80% of nervous system adverse reactions occur within the first four months of application. ICIs can cause diseases of various parts of the nervous system including central nervous system diseases such as aseptic meningitis, meningeal encephalitis, necrotizing encephalitis, brainstem encephalitis, transverse myelitis, etc., and peripheral neuropathy such as cranial nerve peripheral neuropathy, multifocal nerve root neuropathy, Guillain‐Barré syndrome, spinal nerve root neuropathy, myasthenia gravis, myopathy, etc. For these complications of the nervous system, diagnosis could be difficult. Physicians require a specific collection of nervous system symptoms and signs, combined with supplementary examinations including imaging, cerebrospinal fluid cytology, EEG or electromyography in order to exclude infection or malignant tumor before reaching a final diagnosis. With regard to treatment, ICIs should be discontinued in severe cases, and large doses of glucocorticoid or gamma globulin administered, and supportive treatment may be necessary. If severe adverse reactions of the nervous system occur, the prognosis could be poor.

1137A life support based comprehensive treatment regimen dramatically lowers the in-hospital mortality of patients with fulminant myocarditis —- a multiple center study

Abstract Background Fulminant myocarditis (FM) is characterized by rapid onset and progression to cardiac and circulatory failure. It has high mortality; however, patients may benefit from short-term circulatory support. This study evaluated the therapeutic efficacy of a life support–based comprehensive treatment regimen (LSBCTR) for FM and demonstrated that it saved the lives of FM patients. Methods One hundred and fourteen FM patients were recruited from January 2007 to October 2017 were divided into two groups: those who received LSBCTR (65 cases), including management of fluids and nutrients, use of antiviral drugs and large doses of glucocorticoids (methylprednisolone over 200 mg) and immunoglobulins, continuous renal replacement therapy (CRRT), and life support (artificial positive pressure respiration, intra-aortic balloon pump [IABP] with or without extracorporeal membrane oxygenation [ECMO]), and those who received traditional methods (74 cases). The primary endpoints were in-hospital death and length of hospital stay for survivors. Results Of the population, 41 patients (36.0%) died in the hospital. In-hospital mortality rates were 3.0% (2/65) for the LSBCTR group and 52.7% (39/74) for the traditional treatment group (P<0.001). Early life support (IABP with or without ECMO and a respirator) and early applications of CRRT, antiviral therapy, and sufficient doses of glucocorticoids and immunoglobulins individually contribute to the efficiency of reducing in-hospital mortality. Vasoactive agents did not improve prognosis, especially noradrenaline, which dramatically increased the incidence of death. Conclusion Our data described comprehensive treatment for patients with FM that can dramatically reduce in-hospital mortality. Its generalization and application in clinical practice will efficiently save lives. Clinical Trial: NCT03268642.

Naringin regulates bone metabolism in glucocorticoid-induced osteonecrosis of the femoral head via the Akt/Bad signal cascades

PurposeGlucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a common disease following long-term use or large doses of glucocorticoids. The pathogenesis of GIONFH remains controversial, and abnormal bone metabolism caused by glucocorticoids(GCs) may be one of the important factors. Due to its positive effect on bone remodeling, naringin shows potential therapeutic effects in bone metabolism-related diseases. In this study, we hypothesized that naringin regulated bone metabolism in rat GIONFH via the Akt/Bad signal cascades. MethodsIn vitro, a dexamethasone (Dex)- or naringin-treated cell model was used to evaluate the function of naringin. In vivo, methylprednisolone (MPS)-treated rat model was used to evaluate the function of naringin in GIONFH. In vitro, Cell Counting Kit-8 (CCK-8) and Edu staining was used to evaluate the proliferation of osteocytes, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, Annexin V-FITC-PI, and western blotting were used to evaluate the apoptosis of osteocytes. We also verified the effects of naringin on osteogenesis and osteoclastogenesis. In vivo, we used micro-CT (computed tomography), histological, and immunohistochemical analysis to evaluate the effect of naringin. Moreover, the mechanism of naringin regulating the bone metabolism through the Akt/Bad pathway was also investigated using bioinformatics analysis and western blotting. ResultsThe results of in vitro study showed that Akt activated by naringin promoted osteogenesis and osteocyte proliferation; in addition, osteocyte apoptosis and osteoclastogenesis was inhibited by Akt activation and Bad suppression. According to the in vivo study, naringin prevented GIONFH in a rat model as shown by micro-CT scanning and histological and immunohistochemical analysis. ConclusionsTherefore, we concluded that naringin is an effective compound for promoting bone repair and preventing bone loss in rats with GIONFH through Akt/Bad signal cascades.

Clinical analysis of Takayasu's arteritis with cardiomyopathy

The clinical data of 13 patients diagnosed as Takayasu's arteritis with cardiomyopathy in Peking Union Hospital were reviewed. Echocardiography showed cardiomegaly (left chambers mainly), diffuse weakened myocardial wall movement and reduced left ventricular ejection fraction. Dilated cardiomyopathy was diagnosed in two patients. Glucocorticoid and cyclophosphamide were the essential medication for treatment. One patient died, 1 patient was aggravated and the disease condition in remaining 11 patients was stable or improved. Takayasu's arteritis with cardiomyopathy is a rare disease and it attacks younger people. It is difficult to identify at onset, and the disease deteriorates rapidly. Echocardiography should be performed earlier to evaluate the heart function for early diagnosis and treatment. Administration of large dose of glucocorticoid and cyclophosphamide at early stage may improve the prognosis. Key words: Takayasu's arteritis; Cardiomyopathies

CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY IN CHILDREN: DIAGNOSIS AND TREATMENT

Chronic inflammatory demyelinating polyneuropathy (CIDP) in children is a rare autoimmune disease of the peripheral nervous system. The article analyzes current international diagnostic criteria and clinical presentation features of the disease in childhood. The article discusses general principles of CIDP treatment and focuses on the pathogenetic therapies: intravenous immunotherapy using a standard human immunoglobulin (IVIG) with the content of IgG > 95%, prescription of large doses of glucocorticoids and plasmapheresis. It analyzes the recommendations for prioritizing the use of different types of treatment when initiating the therapy and describes the main drug prescription protocols and recommended doses. Two clinical cases of CIDP in children are described. It is shown that the use of adequate doses of IVIG, glucocorticoids and long-term maintenance treatment can completely reverse the symptoms of peripheral lesion, prevent repeated exacerbations of the disease and significantly improve the quality of life.

Efficacy of different doses of glucocorticoid for prevention of postoperative complications in patients undergoing coronary artery bypass grafting: a meta-analysis

Objective To evaluate the efficacy of different doses of glucocorticoid for prevention of postoperative complications in patients undergoing coronary artery bypass grafting (CABG).Methods We searched PubMed,EMBASE,Highwire,CENTREN and its affiliated clinical trial registration data center,Chinese Biomedical Database,and CNKI from 2000 to 2010 for randomized controlled trials involving the efficacy of different doses of glucocorticoid for prevention of postoperative complications in patients undergoing CABG.The quality of the studies was evaluated by the method recommended by Cochrane Collaboration.Evaluation indexes included development of fibrillation,requirement for insulin treatment because of hyperglycosemia,infection,and death (during stay in hospital or within 30 days after discharge from hospital) after operation and mechanical ventilation time.Meta-analysis was conducted using the RevMan 5.1 software.Results Twenty-one randomized controlled trials involving 1737 patients were included in our meta-analysis.Different doses of glucocorticoid decreased the risk of fibrillation,and did not increase the risk of various causes-induced infection and death.Moderate and large doses of glucocorticoid increased the risk of requirement for insulin treatment because of hyperglucosemia.Large dose of glucocorticoid resulted in prolongation of ventilation time.Conclusion Different doses of glucocorticoid can decrease the development of postoperative fibrillation without increasing the risk of infection and death,moderate and large doses of glucocorticoid increase the risk of requirement for insulin treatment because of hyperglucosemia and large dose of glucocorticoid increases the risk of prolonged ventilation time in patients undergoing CABG. Key words: Glucocorticoids; Cardiopulmonary bypass ; Postoperative complications ; Meta-analysis

Successful treatment of patients with paraquat intoxication: three case reports and review of the literature

To report on three patients with paraquat (PQ) intoxication surviving after combined therapy with hemoperfusion (HP), cyclophosphamide (CTX), and glucocorticoid. Three patients suffered acute renal failure in a few days after ingesting a lethal amount of PQ. Chest computed tomography (CT) scans revealed obvious pulmonary inflammation, pleural effusion, and fibrous lesions several days after ingestion. HP was performed immediately, followed by large doses of glucocorticoid (methylprednisolone, 500 g/d) and CTX (approximately 4 g). After 50 d of treatments, all three patients were discharged in healthy condition, with chest CT showing small fibrous lesions, exudation, and both lungs clear of auscultation. The protective effect of the lungs may have been due to timely treatment at adequate doses.

Definition, epidemiology and classification of diabetes in children and adolescents

Diabetes mellitus is a group of metabolic diseases characterised by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The abnormalities in carbohydrate, fat, and protein metabolism that are found in diabetes are due to deficient action of insulin on target tissues. If ketones are present in blood or urine, treatment is urgent, because ketoacidosis can evolve rapidly.

FC‐20 Efficacy of griseofulvin for juvenile cellulitis in dogs

Juvenile cellulitis is an uncommon idiopathic granulomatous and pustular disorder with submandibular lymph node involvement that usually occurs in puppies. Currently, large doses of glucocorticoids are the treatment of choice. Griseofulvin is a fungistatic antibiotic that also has immunomodulatory properties and is occasionally used in human patients with idiopathic inflammatory skin disorders. The purpose of this study was to investigate the efficacy of griseofulvin in the treatment of juvenile cellulitis in dogs. Six dogs with juvenile cellulitis were investigated. The diagnosis was based on both clinical features and standard diagnostic procedures, and fungal disorders were carefully ruled out. These dogs were treated with griseofulvin (14.2–34 mg/kg orally, twice daily) without any other treatment. On the basis of clinical observation, the efficacy of griseofulvin was evaluated as excellent (complete resolution within 2 weeks), good (complete resolution within 4 weeks), fair (>4 weeks for complete resolution), and poor (unresolved). Two cases were evaluated as excellent, and four cases were good. All cases were completely resolved within 3 weeks. No adverse reactions were recognized in any of the dogs. In this study, griseofulvin appeared to be effective in the treatment of canine juvenile cellulitis. Although the aetiology remains uncertain, it is postulated that griseofulvin could induce down‐regulatory signals within the lesions. Further investigation is needed to understand the clinical effects of griseofulvin. Funding: Self‐funded.

Bone effects of glucocorticoid therapy.

Since the beginning of pharmacological use of glucocorticoids it has been clear that they have serious adverse effects in bone. Chronic administration of glucocorticoids causes a loss of bone mass and pathological fractures, especially in the skeletal areas that are rich in trabecular bone. In addition to osteoporosis, large doses of glucocorticoids could lead to aseptic osteonecrosis affecting mainly proximal femur.

Adrenal suppression versus clinical glucocorticoid deficiency in the premature infant: no simple answers.

In a recent issue of the journal, Karlsson et al. (1) reported their results of a study on the adrenal function of mostly premature infants by means of a low dose (1 mg/1.73 m) ACTH test and a standard, human (h) CRH (CRH) test (1 mg/kg). Infants studied varied in gestational age, exposure to antenatal glucocorticoid therapy, quantity of dexamethasone received postnatally, interval between the last dose of dexamethasone and the time of testing, and presence or not of concurrent hydrocortisone replacement. They concluded that the hCRH test was superior to the low dose ACTH test in detecting adrenal suppression on the basis of being abnormal more frequently than the latter in the same population of patients. By definition, adrenal suppression denotes sustained deficiency of hypothalamic-pituitary-adrenal (HPA) axis function ensuing exposure of the organism to excessive and prolonged administration of exogenous glucocorticoids (2). The mechanism is suprapituitary, and the condition has no real rodent model equivalent, as adrenal suppression in rats has a very limited duration of 1–2 days (3). Generally, clinically important adrenal suppression in children and adults occurs after 2 or more weeks of glucocorticoid therapy, depends on the type of and the schedule of glucocorticoid administration and lasts from days, to weeks, months or, rarely, infinity (2). The susceptibility of human beings to the development of adrenal suppression varies widely, as does the sensitivity of their different tissues to glucocorticoids (4). When one thinks of glucocorticoid suppression, one should clarify an important issue. The HPA axis, through several feedback control loops that influence its regulatory centers in the brain, is constantly attempting to maintain the day-to-day exposure of tissues to cortisol normal. This results in an intraindividual variability of HPA axis activity that is quite narrow, in contrast to the wide interindividual variability of this system. This means that decreased cortisol secretion a day or two after administration of a large dose of glucocorticoid is not but a corrective action of the organism. Such a change would not qualify as adrenal suppression, which is the sustained, risky glucocorticoid deficiency that ensues prolonged, excessive exposure to exogenous or endogenous glucocorticoids (2). The latter has significant morbidity, ranging from hypoglycemia to hypotension, as well as mortality, usually as a result of circulatory collapsus. The third trimester fetus and the premature and full-term infants have a functional HPA axis that responds to the negative feedback by glucocorticoids and can develop clinically significant adrenal suppression (5–7). Our ability to recognize adrenal suppression in infants is a prerequisite to decide whether or not to administer daily and stress-appropriate glucocorticoid coverage. In a full-term infant in which suppression is not complicated by concurrent systemic inflammation, one could employ the tests and criteria established for older children and adults. The rapid standard ACTH test (250 mg/1.75 m BSA) would be the procedure of choice in such an instance, and the criterion of a cortisol response greater than the value of 1.96 sd below the normal child/adult mean at 30 or 60 min would suggest no need for coverage. In the uncomplicated premature infant, a 40% lowering of these limits has been proposed because of a relative hypoactivity of the premie HPA axis when compared with that of full-term neonates (6). An insulin tolerance or a metyrapone test should not be used in these frail populations, as they provide no advantage over the standard ACTH test and might have serious complications. There is very little experience with the low dose ACTH test in infants and its clinical utility in children and adults remains controversial. Although, admittedly, it may be more sensitive than the standard ACTH test in detecting subtler abnormalities of the HPA axis, its true pertinence in helping treat patients that would not be treated on the basis of a standard ACTH test is uncertain. The same is true for the human or ovine CRH tests. Both appear to be more sensitive than the standard ACTH test in detecting subtle HPA axis abnormalities, but again, are such mild disturbances clinically relevant to dictate medical intervention? The study of Karlsson et al. (1) shows that the hCRH test is more sensitive than the low dose ACTH test but the question is: will such data change our approach to treatment? The usefulness of the standard ACTH test goes beyond detecting adrenal suppression in the premature infant after the remission of a disease for which glucocorticoid therapy was administered in the first place. Infants with the systemic inflammation that accompanies the respiratory distress synReceived October 30, 2000. Accepted October 30, 2000. Address correspondence and requests for reprints to: George Chrousos, M.D., National Institutes of Health, 10 Center Drive, Building 10, Room 9D42, Bethesda, Maryland 20892-1583. 0021-972X/01/$03.00/0 Vol. 86, No. 2 The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 2001 by The Endocrine Society

Prednisolone-induced muscle dysfunction is caused more by atrophy than by altered acetylcholine receptor expression.

Large doses of glucocorticoids can alter muscle physiology and susceptibility to neuromuscular blocking drugs by mechanisms not clearly understood. We investigated the effects of moderate and large doses of prednisolone on muscle function and pharmacology, and their relationship to changes in muscle size and acetylcholine receptor (AChR) expression. With institutional approval, 35 Sprague-Dawley rats were randomly allocated to receive daily subcutaneous doses of 10 mg/kg prednisolone (P10 group), 100 mg/kg prednisolone (P100 group), or an equal volume of saline (S group) for 7 days. A fourth group of rats was pair fed (food restricted) with the P100 rats for 7 days (FR group). On Day 8, the nerve-evoked peak twitch tensions, tetanic tensions, and fatigability, and the dose-response curves of d-tubocurarine in the tibialis cranialis muscle were measured in vivo and related to muscle mass or expression of AChRs. Rate of body weight gain was depressed in the P100, FR, and P10 groups compared with the S group. Tibialis muscle mass was smaller in the P100 group than in the P10 or S groups. The evoked peak twitch and tetanic tensions were less in the P100 group than in the P10 or S groups, however, tension per milligram of muscle mass was greater in the P100 group than in the S group. The 50% effective dose of d-tubocurarine (microg/kg) in the tibialis muscle was smaller in the P10 (33.6 +/- 5.4) than in the S (61.9 +/- 5.0) or the P100 (71.3 +/- 9.6) groups. AChR expression was less in the P10 group than in the S group. The evoked tensions correlated with muscle mass (r(2) = 0.32, P < 0.001), however, not with expression of AChR. The 50% effective dose of d-tubocurarine did not correlate with muscle mass or AChR expression. Our results suggest that the neuromuscular dysfunction after prednisolone is dose-dependent, and derives primarily from muscle atrophy and derives less so from changes in AChR expression. The mechanisms by which chronic glucocorticoid therapy alters neuromuscular physiology and pharmacology are unclear. We suggest that the observed effects are dose-dependent and derive primarily from muscle atrophy and derive less from changes in acetylcholine receptor expression.

Therapeutic effect of glucocorticoid on experimental crescentic glomerulonephritis

Crescentic glomerulonephritis shows active and progressive glomerular changes with rapid deterioration in kidney function. A large dose of glucocorticoid (pulse therapy) is clinically used for the treatment, but its efficacy has not been fully estimated. In this study we assessed the therapeutic effect of a large dose of methylprednisolone (MP) on a rat model of crescentic glomerulonephritis that had been induced in WKY rats by an injection of anti-glomerular basement membrane antibody. The infiltration of CD8+ cells and monocytes was manifest by day 3, protein-uria appeared on days 4 and 5, and cellular crescents were diffusely formed by day 7. The gene expression of MCP-1, a chemokine for monocytes and T lymphocytes, was enhanced within 4 hours and peaked on day 3. Daily administration of MP (30 mg/kg/d) from day 3 through day 6 reduced the gene expression of MCP-1 and the numbers of glomerular leukocytes and largely prevented both crescent formation and proteinuria. When daily MP treatment started on day 7, the numbers of glomerular CD8+ cells and monocytes, crescents, and urinary protein were significantly reduced by day 11. In addition, continuing treatment with a small dose of MP (3 mg/kg/d) begun on day 11 completely prevented the increase in blood urea nitrogen and serum creatinine levels. These results indicate that treatment with a large dose of MP histologically and clinically ameliorates crescentic glomerulonephritis in a rat model, supporting the efficacy of pulse MP therapy for the treatment of the disease in human subjects.

Dual effects of hydrocortisone on exocrine rat pancreas

The acute and chronic effects of hydrocortisone on exocrine pancreatic function were examined in the isolated perfused rat pancreas. In the first part of this study, rats were given subcutaneous injections of hydrocortisone at doses of 1.25, 2.5, 5, and 10 mg/kg body wt once daily for 7 days. Trypsin and lipase secretion in response to 100 pM cholecystokinin-octapeptide was significantly increased in rats with the two highest doses of hydrocortisone compared with controls, irrespective of whether calculated as the total amount of stimulated output of enzymes or related to the secretion of enzyme to the pancreas content. On the other hand, the secretory responsiveness of amylase to 100 pM cholecystokinin-octapeptide was maximal at the 5-mg dose, and decreased with higher doses. In the second part, 100 μM hydrocortisone was superimposed for 20 min on 100 pM cholecystokinin-octapeptide stimulation to examine the acute effects of hydrocortisone on exocrine pancreatic function in the isolated perfused rat pancreas. Addition of hydrocortisone caused a significant inhibition of the secretion of pancreatic juice and amylase. The present study has clearly demonstrated the dual effects of glucocorticoids on the pancreas: inhibition and potentiation. There is a possibility that chronic treatment with large doses of glucocorticoid may sensitize the acinar cells and induce hypersecretion of trypsin and lipase, whereas acute treatment inhibits secretory function of exocrine pancreas.

Effect of Methylprednisolone and Reduced Glutathione on Survival in Mice and Hepatic Energy Metabolism in Rats with Endotoxin Shock

Reduced glytathione (GSH) is the tripeptide of glycine, cysteine and glutamic acid and is widely distributed in the body. FSH has been reported to comprise at least 90% of the nonprotein sulfhydryl (NPSH). Although the role of GSH in the tissue has not been clearly established, it is known to be a cofactor for enzymes, a substrate in detoxifications, and a free radical scavenger.Several investigators have reported that the level of NPSH, mainly GSH, in the tissue was decreased in several types of shock and that exogenous administration of GSH has beneficial effects on shock (1,2). This study was designed to evaluate the effects of GSH on the survival rate in mice and the hepatic energy metabolism in rats after administration of endotoxin. These results were compared with those of methylprednisolone sodium succinate (MP), since many investigators have reported that the large doses of glucocorticoid have beneficial effects in several types of shock in experimental animals and in man (3,4).

Large doses of glucocorticoid in the treatment of alopecia areata

Severe extensive alopecia areata (totalis) was treated with prednisolone as a single 2 g dose i.v. (22 patients) or 0.5 g daily for 5 days orally (13 patients). Four of the patients responded well, 12 had a poor response and 19 had no response. There was a relapse in some at about 6 months, which could be arrested by a further single i.v. dose, but the risks of this form of therapy are unclear and it cannot be recommended for general use. The clinical response to a single dose of corticosteroid implies, however, that there may be a 'switch' mechanism in certain auto-immune diseases, with an all-or-none response.

Medical Adrenalectomy With Aminoglutethimide

To the Editor.— The recent article by Santen et al (230:1661, 1974) is certainly an excellent and useful contribution in regard to the pharmacology of aminoglutethimide and dexamethasone interaction. There are, however, points that deserve comment. The authors state that large doses of glucocorticoids are established in the treatment of breast cancer. A review of 12 of the cited references fails to establish either the efficacy or the dose response relationship of glucocorticoids (Table). 1-12 In addition, the cited studies did not utilize the now accepted criteria of objective partial remission, ie, greater than or equal to 50% reduction in the product of the two greatest diameters of palpable or measurable lesions. In regard to the response data cited for aminoglutethimide, the earlier series did achieve objective partial remissions in three of nine cases. 13 However, of the 22 patients reported by the authors of the current study, there were

A rapid increase in skin extensibility due to prednisolone.

We have tested the short-term effect of prednisolone on the ability of the skin to withstand a shearing stress, using a specially designed stretching machine. A single intravenous infusion of 2 g prednisolone given to seven patients with alopecia totalis produced an increase in skin extensibility within 2 h which persisted for at least a week. This acute effect could be due to a change in dermal ground substance or to breaking of collagen crosslinks. We suggest that patients receiving very large doses of glucocorticoids should avoid undue exertion during, and for some time after, treatment, since a similar effect might occur in the connective tissue of other organs, such as the aorta.

Iatrogenic Cushing's disease in a boy after misdiagnosis of salt-losing virilizing adrenal hyperplasia: Impaired metyrapone response with failure of catch-up growth

A boy misdiagnosed as having the sodium-losing form of virilizing adrenal hyperplasia was treated with large doses of glucocorticoids and mineralocorticoids from the newborn period until he was more than 4 years of age. He developed iatrogenic Cushing's syndrome and associated glaucoma and dwarfism. The greatest catch-up linear growth took place when the mineralocorticoid had been discontinued and the glucocorticoid was being reduced, but was only of brief duration. Catch-up in skeletal maturation was greatest after complete withdrawal of steroid medication. At this time there was a normal response of urinary corticosteroids to ACTH stimulation and of serum growth hormone and plasma cortisol to insulin hypoglycemia; cortisol production rate was normal. Plasma cortisol values were in the low-normal range and responses to metyrapone were inadequate, suggesting that this boy's massive exposure to adrenocortical steroids had resulted in selective damage to his pituitary ACTH feedback mechanism. Glaucoma resulted in loss of all sight in the right eye. A boy misdiagnosed as having the sodium-losing form of virilizing adrenal hyperplasia was treated with large doses of glucocorticoids and mineralocorticoids from the newborn period until he was more than 4 years of age. He developed iatrogenic Cushing's syndrome and associated glaucoma and dwarfism. The greatest catch-up linear growth took place when the mineralocorticoid had been discontinued and the glucocorticoid was being reduced, but was only of brief duration. Catch-up in skeletal maturation was greatest after complete withdrawal of steroid medication. At this time there was a normal response of urinary corticosteroids to ACTH stimulation and of serum growth hormone and plasma cortisol to insulin hypoglycemia; cortisol production rate was normal. Plasma cortisol values were in the low-normal range and responses to metyrapone were inadequate, suggesting that this boy's massive exposure to adrenocortical steroids had resulted in selective damage to his pituitary ACTH feedback mechanism. Glaucoma resulted in loss of all sight in the right eye.