Cause Of Adrenal Insufficiency Research Articles

Indicators of Adrenal Insufficiency in TB-suspect Patients Presenting with Signs and Symptoms of Adrenal Insufficiency at Three South African Hospitals in Pretoria

Background: Primary adrenal insufficiency occurs when the function of the adrenal cortex to produce cortisol is impaired. Infections, such as disseminated Tuberculosis (TB) and malignancies, are the major causes of Adrenal Insufficiency (AI) in developing countries. AI is characterized by specific symptoms, signs, and laboratory findings. Objective: To determine indicators of AI in TB-suspect patients presenting with signs and symptoms of AI. Methods: A cross-sectional study was conducted at the primary health care ward of Dr. George Mukhari Academic Hospital, Jubilee District Hospital, and Odi District Hospital. The population comprised all TB-suspects, from whom a sample of 75respondents was obtained. A researcher administered questionnaire was used to collect data related to their signs, symptoms, and laboratory findings. Results: Of the 75 respondents, 47 (62.37) and 28 (37.3%) were classified as Adrenal Sufficiency (AS) and AI, respectively. The most occurring symptoms were craving for salt, dry, itchy skin, and vomiting (prevalence: 79.7%, 68.1%, and 69.0%, respectively). Signs or symptoms by themselves did not discriminate persons with a high likelihood of AI. However, a fasting serum glucose (≤ 5.25 mmol/L), a positive GeneXpect, a low CD4 count (≤ 274.5 cells/ml), with a combination of signs and symptoms (9.5) constituted a discriminator for AI in TB-suspect patients (87.5% likelihood). Conclusion: A low fasting serum glucose, a positive GeneXpect, a low CD4 count with a minimum of ten signs and symptoms constitute a discriminator for AI in TB-suspect patients, necessitating treatment initiation to save patient lives in laboratory resource-limited settings.

Current Management and Outcome of Pregnancies in Women With Adrenal Insufficiency: Experience from a Multicenter Survey.

Appropriate management of adrenal insufficiency (AI) in pregnancy can be challenging due to the rarity of the disease and lack of evidence-based recommendations to guide glucocorticoid and mineralocorticoid dosage adjustment. Multicenter survey on current clinical approaches in managing AI during pregnancy. Retrospective anonymized data collection from 19 international centers from 2013 to 2019. 128 pregnancies in 113 women with different causes of AI: Addison disease (44%), secondary AI (25%), congenital adrenal hyperplasia (25%), and acquired AI due to bilateral adrenalectomy (6%). Hydrocortisone (HC) was the most commonly used glucocorticoid in 83% (97/117) of pregnancies. Glucocorticoid dosage was increased at any time during pregnancy in 73/128 (57%) of cases. In these cases, the difference in the daily dose of HC equivalent between baseline and the third trimester was 8.6 ± 5.4 (range 1-30) mg. Fludrocortisone dosage was increased in fewer cases (7/54 during the first trimester, 9/64 during the second trimester, and 9/62 cases during the third trimester). Overall, an adrenal crisis was reported in 9/128 (7%) pregnancies. Cesarean section was the most frequent mode of delivery at 58% (69/118). Fetal complications were reported in 3/120 (3%) and minor maternal complications in 15/120 (13%) pregnancies without fatal outcomes. This survey confirms good maternal and fetal outcome in women with AI managed in specialized endocrine centers. An emphasis on careful endocrine follow-up and repeated patient education is likely to have reduced the risk of adrenal crisis and resulted in positive outcomes.

OR25-04 Over 14% of Inpatients with Euvolemic Hyponatremia Have Undiagnosed Adrenal Insufficiency

Background- The commonest cause of euvolemic hyponatremia (EvHNa) is the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The diagnosis of SIADH requires the exclusion of secondary adrenal insufficiency (AI) and untreated hypothyroidism. Studies have suggested about 4% of unselected patients presenting to the emergency room with EvHNa have undiagnosed SAI.1 Among patients admitted to specialized endocrine units this prevalence maybe as high as 20%.2Objective- To study the prevalence of undiagnosed AI among inpatients with EvHNa admitted to general medical wards. Methods- This was a prospective, single centre observational study conducted among inpatients with EvHNa. EvHNa was defined as patients with a serum sodium (Na) <135 mEq/L, with no clinical evidence of dehydration or fluid excess, and a urine spot Na >30mmol/L. In addition patients with recent vomiting, renal failure, recent diuretic use, uncontrolled hyperglycemia and patients with history of use of oral or parenteral steroids in the last 6 months were excluded. Adrenal functions were assessed by a modified porcine ACTH stimulation test which has been described recently by Nair et al. A cut off cortisol value of <18mg/dl after 60 minutes of ACTH injection was used to diagnose AI.3Results- One hundred and forty one (141) patients were included after informed consent and all underwent a modified ACTH stimulation test. They had a mean age of 58 years and 52.3% (n=74) were males. Modified ACTH stimulation testing suggested 20/141 (14.2%) had undiagnosed AI. The mean age among those with AI was 55.2 years. In only 25% (5/20) AI was suspected based on clinical presentation by the treating physician. Despite excluding patients with documented steroid use, the commonest cause of AI (9/20) was secondary AI due to exogenous steroid use including high potency inhaled steroids (5/9) and the use of undocumented steroids or steroid containing medicaments by alternative practitioners (4/9). Hypopituitarism was diagnosed as the cause of AI in 5 patients, which included unsuspected Sheehan’s syndrome in post menopausal women (3/5), non functioning pituitary adenoma (1/5) and lymphocytic hypophysitis (1/5). Despite primary AI not commonly presenting as EvHNa, 3/20 patients had primary AI and in the remaining 3 patients the aetiology of AI remained unclear. Conclusions- Undiagnosed AI is much more common in our country among inpatients presenting with EvHNa to medical units. This increase is primarily driven by inhaled and undocumented exogenous steroid use and undiagnosed Sheehan’s syndrome. An assessment of the hypothalamic-pituitary-adrenal axis is mandatory before making a diagnosis of SIADH. References -(1) Diederich et al. Eur J Endocrinol 2003; 148: 609-617. (2) Cuesta et al. Clin Endocrinol (Oxf) 2016; 85: 836-844. (3) Nair A et al. Eur J Endocrinol. 2019 Oct 1. pii: EJE-19-0558.R2.

SAT-206 A Sweet and Salty Milieu: The Utility of CT in Bilateral Adrenal Hemorrhage

Introduction: Bilateral adrenal hemorrhage (BAH) is seldomly recognized as a cause of adrenal insufficiency due to nonspecific clinical manifestations within the milieu of major concurrent illnesses. CT abdomen is the investigation of choice to evaluate acute adrenal crisis.Clinical Case: A 68 year old female with systemic lupus erythematosus, anti-phospholipid antibody syndrome (APS) complicated by multiple strokes, on warfarin, and recent hip fracture presented with confusion, lethargy, fever, and cough. On exam she was febrile, tachycardic, tachypneic, disoriented with right sided hemiparesis, and crepitations on lung auscultation. Lab results were significant for leukocytosis of 14K/uL, hemoglobin (Hb) 9.9g/dL, INR 3.8, azotemia, normal electrolytes, and glucose 67mg/dL. Blood and urine cultures were negative. Anti-dsDNA, C3, and C4 were normal. CT chest showed right lower lobe infiltrates and bronchial debris. She was treated with antibiotics and bronchoscopy with mucus plug removal. Her lethargy and confusion persisted. MRI brain was negative for acute event. Hb fell to 7g/dL; managed conservatively with i.v. iron. CT abdomen showed BAH both measuring 3.5x3.5cm; AM cortisol was 5.5 mcg/dL. Warfarin was reversed with vitamin K; hydrocortisone 50mg q8h was started with improvement in her mental status. ACTH levels were <5pg/ml; ACTH stimulation testing was deferred as steroids were started emergently. Repeat CT showed stable BAH, AM cortisol increased to 19.4mcg/dL, and Hb stable at 8g/dL. She was discharged on hydrocortisone 10mg twice daily.Discussion: Trauma, corticotropin stimulation during stress, anticoagulation therapy, and APS inducing adrenal venous thrombosis have been identified as risk factors that predispose to BAH. There is a lack of consensus regarding normal cortisol levels in critical illness. Fluctuations in serum cortisol levels are frequent and not necessarily indicative of definite injury to the adrenal gland. CT abdomen, the investigation of choice in the acute setting, has a heterogeneous, high density appearance; the presence of an underlying adrenal mass cannot be excluded. BAH appears as diminished attenuation of the adrenal gland with respect to the adjacent tissues, along with thickening of the ipsilateral crura due to retroperitoneal extension of blood (1). MRI has a greater accuracy for identifying BAH in comparison to CT as it can discern adrenal hematoma from adjacent necrotic tissue and determine the acuity of the hematoma.Conclusion: The nonspecific clinical manifestations of BAH are frequently inseparable from those of the concurrent major illness. The diagnosis requires a high index of suspicion, initiation of prompt steroid replacement, and confirmation by CT abdomen.

Glucocorticoid replacement regimens for treating congenital adrenal hyperplasia.

Glucocorticoid replacement regimens for treating congenital adrenal hyperplasia.

Primary adrenal lymphoma as a cause of adrenal insufficiency, a report of two cases.

SummaryPrimary adrenal lymphoma (PAL) is a rare cause of adrenal insufficiency. More than 90% is of B-cell origin. The condition is bilateral in up to 75% of cases, with adrenal insufficiency in two of three patients. We report two cases of adrenal insufficiency presenting at the age of 70 and 79 years, respectively. Both patients had negative 21-hydroxylase antibodies with bilateral adrenal lesions on CT. Biopsy showed B-cell lymphoma. One of the patients experienced intermittent disease regression on replacement dosage of glucocorticoids.Learning points:Primary adrenal lymphoma (PAL) is a rare cause of adrenal insufficiency.Bilateral adrenal masses of unknown origin or in individuals with suspected extra-adrenal malignancy should be biopsied quickly when pheochromocytoma is excluded biochemically.Steroid treatment before biopsy may affect diagnosis.Adrenal insufficiency with negative 21-hydroxylase antibodies should be evaluated radiologically.

Beyond the adrenals: Organ manifestations in inherited primary adrenal insufficiency in children.

Primary adrenal insufficiency (PAI) in children is mostly due to genetic defects. The understanding of the molecular genetics of the causes of adrenal insufficiency in the pediatric population has made significant progress during the last years. It has been shown that inherited PAI can lead to certain clinical manifestations and health problems in children beyond the adrenals. Organ dysfunctions associated with different forms of PAI in children include a wide range of organs such as gonads, brain, heart, bone, growth, bone marrow, kidney, skin, parathyroid, and thyroid. Diagnosing the correct genetic cause of PAI in children is therefore crucial to adequately control long-term treatment and follow-up in such patients.

Congenital Adrenal Hyperplasia: Diagnostic Features in a Limited Resource Country, Senegal

Introduction: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive diseases characterized by enzymatic deficiencies in the biosynthesis of adrenal steroids. The most common 21-hydroxylase deficiency is characterized by a cortisol deficiency and an excess of androgens, with or without aldosterone deficiency. In our countries, in the absence of neonatal screening, the diagnosis is most often late leading to life-threatening complications. The aim of this study was to describe the diagnostic features of CAH at the Albert Royer National Children’s Hospital (ARNCH) in Dakar. Patients and method: We conducted a retrospective, descriptive study carried out at the pediatric endocrinology department of ARNCH from 2015 to 2019. All children aged under 15 with a form of CAH were included. Socio-demographic data, family history, clinical and biochemical data at presentation were collected. Patients were noted as presenting with Disorder of Sexual Development (DSD) with dehydration, DSD without dehydration, dehydration without DSD, precocious puberty. The Prader’s scale was used to determine the degree of external virilization. These data were entered and analyzed with Epi Info version 7.2. Results: A total of 32 patients were included, representing 74.41% of the causes of disorder of sexual development (DSD) and 84.21% of the causes of adrenal insufficiency. These were 27 girls (84.37%) and 5 boys (15.63%). The mean age was 19 ± 34.6 months. DSD was the main finding (87.5%). It was associated with dehydration in 22 cases (68.75%). 21-hydroxylase deficiency represented 93.75% of the cases with salt wasting in 73.33% of the cases. Conclusion: The diagnosis of CAH was delayed leading to life-threatening adrenal crises. In the absence of neonatal screening for CAH in Senegal, there is a need to train healthcare workers to recognize neonates with DSD early and refer them timeously for specialist care.

Adrenal Insufficiency by Adrenoleukodystrophy

The X-linked adrenoleukodystrophy (ALD) is a severe neurodegenerative disorder due to mutations in the ABCD1 gene. Objective: To report a case of a 19-year-old man with adrenal insufficiency due to adrenoleukodystrophy. Method: Case report and literature review. Result: A previously healthy 19-year-old male patient was admitted to the emergency room with nausea and vomiting for 5 days, who progressed to abdominal pain, severe asthenia, and fever (38.5°C). He referred progressive darkening of the skin, oral mucosa, tongue and nail bed of the hands and feet, observed in the last 6 years. Emergency laboratory evaluation showed severe hyponatremia and hyperkalemia, which, together with decreased plasma cortisol, directed the investigation to causes of adrenal insufficiency. High ACTH (Adrenocorticotropic hormone) and very long chain fatty acid levels closed the diagnosis. Discussion: ALD is characterized by progressive demyelination in the central and peripheral nervous system and adrenal insufficiency consequence to the accumulation of very long chain fatty acids (VLCFA) in the adrenal. The overall incidence of ALD is 1:17,000. Adrenal insufficiency may be the first symptom of ALD in boys and adults. The diagnosis is based on the measurement of VLCFA plasma levels. Allogeneic bone marrow transplantation is the only treatment that provides a permanent cure when the procedure is performed at an early stage of brain demyelination, i.e. when patients are asymptomatic, although brain magnetic resonance imaging (MRI) is abnormal. Treatment of Addison’s disease is obligatory, but does not change the course of neurological symptoms.

Renal involvement in adrenal insufficiency (Addison disease): can we always recognize it?

Addison disease is due to the destruction or dysfunction of the entire adrenal cortex. Nowadays, the causes of adrenal insufficiency are autoimmune disease for 70-90% and tuberculosis for 7-20%. Many typical signs and symptoms, such as hyponatremia, hyperkalaemia, or renal insufficiency can represent the reasons for a nephrology consultation, especially in conditions of urgency, and they can easily be confused with other causes. Moreover, the fact that in a short time range we have diagnosed the three cases described as a guide in this review, has aroused our attention as nephrologists on a disease in which we have probably already encountered but without recognizing it. The blood tests showed in all three patients severe electrolyte disorders and acute renal failure which will be discussed in their physiopathogenetic mechanisms. In a peculiar way, these alterations were not controlled with repolarizing solutions, fluid replacement and increased volemia, but only after steroid administration. In conclusion, in this review all the known pathogenic mechanisms causing disorders of nephrological interest in adrenal insufficiency are discussed.

POEMS syndrome: a rare cause of adrenal insufficiency in a young male.

POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein and Skin changes) is a rare multisystemic disease. Clinical presentation is variable, the only mandatory criteria being polyneuropathy and monoclonal gammapathy in association with one major and one minor criterion. Primary adrenal insufficiency is rarely reported. We describe a case of a 33-year-old patient, in whom the presenting symptoms were mandibular mass, chronic sensory-motor peripheral polyneuropathy and adrenal insufficiency. The laboratory evaluation revealed thrombocytosis, severe hyperkalemia with normal renal function, normal protein electrophoresis and negative serum immunofixation for monoclonal protein. Endocrinologic laboratory work-up confirmed Addison's disease and revealed subclinical primary hypothyroidism. Thoracic abdominal CT showed hepatosplenomegaly, multiple sclerotic lesions in thoracic vertebra and ribs. The histopathologic examination of the mandibular mass was nondiagnostic. Bone marrow biopsy revealed plasma cell dyscrasia and confirmed POEMS syndrome. Axillary lymphadenopathy biopsy: Castleman's disease. Gluco-mineralocorticoid substitution and levothyroxine therapy were started with clinical improvement. Autologous hematopoietic cell transplantation (HCT) was planned, cyclophosphamide induction was started. Meanwhile the patient suffered two ischemic strokes which resulted in aphasia and hemiparesis. Cerebral angiography revealed vascular lesions compatible with vasculitis and stenosis of two cerebral arteries. The patient deceased 14 months after the diagnosis. The young age at presentation, multiplicity of manifestations and difficulties in investigation along with the absence of serum monoclonal protein made the diagnosis challenging. We report this case to highlight the need to consider POEMS syndrome in differential diagnosis of peripheral neuropathy in association with endocrine abnormalities even in young patients. POEMS syndrome is considered a 'low tumor burden disease' and the monoclonal protein in 15% of cases is not found by immunofixation. Neuropathy is the dominant characteristic of POEMS syndrome and it is peripheral, ascending, symmetric and affecting both sensation and motor function. Endocrinopathies are a frequent feature of POEMS syndrome, but the cause is unknown. The most common endocrinopathies are hypogonadism, primary hypothyroidism and abnormalities in glucose metabolism. There is no standard therapy; however, patients with disseminated bone marrow involvement are treated with chemotherapy with or without HCT.

Primary adrenal lymphoma: a rare cause of adrenal insufficiency

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Diagnostic search for causes of primary adrenal insufficiency in children

Primary adrenal insufficiency rarely occurs in pediatric practice. The clinical diagnosis of the disease is frequently delayed or missed because of nonspecific symptoms early in the course. Hypocorticism should be differentiated from other diseases with similar symptoms or laboratory changes. Hyponatremia is one of the most consistent laboratory signs of adrenal insufficiency in children, while hyperkalemia is detected in half of patients. Detection of low sodium levels in the absence of hyperkalemia often misleads doctors, leading to false diagnosis of «syndrome of inadequate secretion of antidiuretic hormone». Increased thyroid­stimulating hormone level is characteristic of the manifestation of hypocorticism, meanwhile evaluation of the thyroid status is carried out more frequently than the level of adrenal hormones. Therefore, manifestations of Addison’s disease would be suggested to be the symptoms of hypothyroidism. At the same time, intake of levothyroxine in unrecognized hypocorticism is dangerous, as it can trigger an adrenal crisis.In children genetic causes of chronic adrenal insufficiency are the most prevalent. Hypocorticism in children may be the first manifestation of autoimmune and hereditary diseases with multiorgan lesions, so the precise diagnosis may influence the treatment decisions, further examination of the patient and the range of indicators to be monitored. Searching the cause of adrenal insufficiency in children is often a challenge and requires joint work of specialists in different fields. The article presents a review on the diagnostic search for causes of primary adrenal insufficiency in children of different ages.

An unusual cause of adrenal insufficiency and bilateral adrenal masses.

SummaryPrimary adrenal insufficiency secondary to syphilis is extremely rare, with only five cases being reported in the literature. We report a case of adrenal insufficiency as a manifestation of Treponema pallidum infection (tertiary syphilis). A 69-year-old, previously fit and well Caucasian male was found to have adrenal insufficiency after being admitted with weight loss, anorexia and postural dizziness resulting in a fall. Biochemical testing showed hyponatraemia, hyperkalaemia, and an inadequate response to Synacthen testing, with a peak cortisol level of 302 nmol/L after administration of 250 µg Synacthen. Abdominal imaging revealed bilateral adrenal hyperplasia with inguinal and retroperitoneal lymphadenopathy. He was started on hydrocortisone replacement; however, it was not until he re-attended ophthalmology with a red eye and visual loss 1 month later, that further work-up revealed the diagnosis of tertiary syphilis. Following a course of penicillin, repeat imaging 5 months later showed resolution of the abnormal radiological appearances. However, adrenal function has not recovered and 3 years following initial presentation, the patient remains on both glucocorticoid and mineralocorticoid replacement. In conclusion, this case highlights the importance of considering syphilis as a potential differential diagnosis in patients presenting with adrenal insufficiency and bilateral adrenal masses, given the recent re-emergence of this condition. The relative ease of treating infectious causes of adrenal lesions makes accurate and timely diagnosis crucial.Learning points:Infectious causes, including syphilis, should be excluded before considering adrenalectomy or biopsy for any patient presenting with an adrenal mass.It is important to perform a full infection screen including tests for human immunodeficiency virus, other blood-borne viruses and concurrent sexually transmitted diseases in patients presenting with bilateral adrenal hyperplasia with primary adrenal insufficiency.Awareness of syphilis as a potential differential diagnosis is important, as it not only has a wide range of clinical presentations, but its prevalence has been increasing in recent times.

The Short Synacthen (Corticotropin) Test Can Be Used to Predict Recovery of Hypothalamo-Pituitary-Adrenal Axis Function.

The 250-μg short Synacthen (corticotropin) test (SST) is the most commonly used tool to assess hypothalamo-pituitary-adrenal (HPA) axis function. There are many potentially reversible causes of adrenal insufficiency (AI), but no data to guide clinicians as to the frequency of repeat testing or likelihood of HPA axis recovery. To use the SST results to predict adrenal recovery. A retrospective analysis of 1912 SSTs data. Seven hundred seventy-six patients with reversible causes of AI were identified who had at least two SSTs performed. A subgroup analysis was performed on individuals previously treated with suppressive doses of glucocorticoids (n = 110). Recovery of HPA axis function. SST 30-minute cortisol levels above or below 350 nmol/L (12.7 μg/dL) best predicted HPA axis recovery [area under the curve (AUC) receiver operating curve (ROC) = 0.85; median recovery time: 334 vs 1368 days, P = 8.5 × 10-13]: 99% of patients with a 30-minute cortisol >350 nmol/L recovered adrenal function within 4 years, compared with 49% in those with cortisol levels <350 nmol/L. In the subgroup analysis, delta cortisol (30-minute-basal) best predicted the recovery (AUC ROC = 0.77; median recovery time: 262 vs 974 days, P = 7.0 × 10-6). No patient with a delta cortisol <100 nmol (3.6 μg/dL) and a subsequent 1-year random cortisol <200 nmol/L (7.3 μg/dL) recovered HPA axis function. Cortisol levels across an SST can be used to predict recovery of AI and may guide the frequency of repeat testing and inform both clinicians and patients as to the likelihood of restoration of HPA axis function.

Group 3: Strategies for identifying the cause of adrenal insufficiency: diagnostic algorithms

Annales d'Endocrinologie - In Press.Proof corrected by the author Available online since samedi 25 novembre 2017

Rare cause of adrenal insufficiency

A 72-year-old man presented with weight loss, night sweats and haemoptysis and was hypotensive. CT imaging showed rapidly enlarging bilateral adrenal masses, and he was found to have primary adrenal...

Lipoid congenital adrenal hyperplasia by steroidogenic acute regulatory protein (STAR) gene mutation in an Italian infant: an uncommon cause of adrenal insufficiency

BackgroundLipoid congenital adrenal hyperplasia (CAH) (OMIM n. 201710) is the most severe form of congenital adrenal hyperplasia. It is characterized by severe adrenal and gonadal steroidogenesis impairment due to a defect in the conversion of cholesterol to pregnenolone. Affected infants experience salt loss, but glucocorticoid and mineralocorticoid replacement therapy enables long-term survival. Classic lipoid congenital adrenal hyperplasia is relatively common in Japan and Korea but extremely rare in Caucasian populations.Case presentationA female infant of Italian origin came to our attention in late infancy with a clinical picture of acute adrenal insufficiency.The study of the STAR gene revealed two genomic variants c.562C > T and c.577C > T in compound heterozygosity. At the protein level, the two mutations determine the p.Arg188Cys variant (rs104894090) and the p.Arg193Ter variant (rs387907235), respectively. Sanger sequencing was used to confirm the identified variants and to perform familial study. The mother carried the p.Arg188Cys variant, while the father carried the p.Arg193Ter variant.ConclusionTo our knowledge this is the second case of classic lipoid congenital adrenal hyperplasia reported in the Italian population. STAR mutations resulting in lipoid congenital adrenal hyperplasia should be considered all over the world in the differential diagnosis of newborn babies and infants with primary adrenal insufficiency.

Adrenal insufficiency – recognition and management

Adrenal insufficiency is characterised by inadequate -glucocorticoid production owing to destruction of the adrenal cortex or lack of adrenocorticotropic hormone stimulation. In primary adrenal insufficiency, lack of mineralocorticoids is also a feature. Patients can present with an insidious onset of symptoms, or acutely in adrenal crisis, which requires prompt recognition and treatment. Chronic glucocorticoid therapy is the most common cause of adrenal insufficiency. The -diagnosis of adrenal insufficiency is made by -demonstrating low basal and/or stimulated serum cortisol and should be -followed by appropriate investigations to establish the -underlying aetiology. Maintenance glucocorticoid -replacement is usually given as a twice or thrice daily hydrocortisone preparation. Patients with primary adrenal insufficiency also require mineralocorticoid. Regular monitoring for features of under- and over- replacement is essential during follow-up. Patient education is a key feature of management of this condition.

The unresolved riddle of glucocorticoid withdrawal.

Glucocorticoid (GC) therapy is the most common cause of adrenal insufficiency (AI). The real prevalence of AI after GC is unknown but it could involve more than 30% of patients. Some gene variation has been associated with the variability of hypothalamic-pituitary-adrenal (HPA) axis and this issue could contribute to the individual variation of adrenal function after GC treatment. Symptoms and signs of AI are nonspecific and frequently the diagnosis is delayed. Dosage, duration of treatment, administration route and serum cortisol value are not completely useful to predict AI. Clinical estimation of HPA suppression is difficult and biochemical testing is needed to confirm the diagnosis of AI. The different tapering regimens are based on a very low quality of evidence and considering the sizable individual variation, it is improbable that future research will find a secure GC tapering schedule for all patients. The aim of this review is to address the most important aspects in management of GC withdrawal in light of current knowledge.