Evidence Of Adrenal Insufficiency Research Articles

FRI234 A Pregnancy With Two Special Surprises A Baby And A Nonhemorrhagic Adrenal Infarction During Pregnancy

Abstract Disclosure: S. Idriss: None. N. Barua: None. I. Jamal: None. A. Jabiev: None. Introduction: Unilateral Acute adrenal infarction (AAI) is a rare cause of acute abdomen in pregnancy, with a reported incidence of 1.3%. It usually presents with sudden, severe, and unremitting flank pain. The most common cause of AAI is adrenal vein thrombosis. We present a 26-year-old pregnant female who presents with right flank and back pain, found to have AAI without hemorrhage. Case: 26-year-old female Primigravida without significant past medical history presented to the emergency room at 33 weeks of gestation with sudden onset of RUQ flank and back pain. She was afebrile and normotensive. Physical exam was positive for right flank point tenderness. She underwent multiple investigations including an abdominal US which did not reveal an acute pathology. She was admitted and started on opioids which failed to control her pain. An abdominal MRI was obtained subsequently revealing 4.6cm right adrenal gland lesion suspicious for AAI without hemorrhage and normal left adrenal gland. The pain was poorly controlled warranting Dilaudid drip and repeat imaging/CT showed adrenal gland mass with density of 41-52 HU suspicious for lipid poor adenoma versus adrenal hematoma on CT scan. Initial AM Cortisol level was 46 ug/dl, then it trended down to 31.7. DHEAS was low at 94.2 ug/dl. Plasma metanephrines and normetanephrines were normal. Course was complicated with hypotension and worsening pain on day 10 of admission, repeat MRI showed increase in right adrenal lesion size and cystic transformation, containing some T2 hypointense septations and debris without notable intrinsic T1 hyperintensity to suggest blood products, and restricted diffusion which is a finding compatible with AAI. Repeat AM Cortisol and DHEAS were low at 12 and 61.3 respectively. Despite normal left adrenal gland, clinical picture was consistent with adrenal insufficiency and she was started on stress steroids. Thrombophilia workup was negative. She ultimately underwent c-section on day 13 of admission. She was discharged on physiologic dose of steroids with a pending repeat MRI and outpatient follow up. Discussion: Adrenal glands, especially with preexisting nodules are predisposed to micro-vascular thrombosis and infarction during procoagulable states. Pregnancy is a hypercoagulable state that predisposes patients to thrombotic events. The relative risk of thrombosis is 5-6 times higher in pregnant than non-pregnant females of the same age. Our patient had evidence of adrenal insufficiency and required steroid replacement. Anticoagulation was not started due to possible subtle hematoma on CT scan on initial imaging. Follow up imaging is planned. Conclusion: Adrenal infarction is a rare cause of abdominal pain during pregnancy, and if missed, it can result in devastating clinical consequences for the mother and the child. Adrenal insufficiency if found should be addressed to prevent circulatory collapse. Presentation: Friday, June 16, 2023

Three-month tapering and discontinuation of long- term, low-dose glucocorticoids in senior patients with rheumatoid arthritis is feasible and safe: placebo-controlled double blind tapering after the GLORIA trial

ObjectiveThe randomised placebo-controlled GLORIA (Glucocorticoid LOw-dose in RheumatoId Arthritis) trial evaluated the benefits and harms of prednisolone 5 mg/day added to standard care for 2 years in patients aged 65+...

Early-Onset Virilization May Rarely be Due to an Adrenocortical Neoplasm

Background: Adrenocortical tumors are rare neoplasms of childhood; most of which are functional in childhood, producing excess hormones. Virilization, precocious puberty, and Cushing's syndrome are common presenting features. Clinical Description: A 6-year-8-month-old girl presented with features of virilization, which started appearing at 2 ½ years of age. The mother gave a history of progressive enlargement of the clitoris with the development of pubic, axillary, and facial hair over the years. There was no history of perinatal complications, features of adrenal insufficiency, atypical external genitalia at birth, or family history of malignancy. On examination, she had features of heterosexual peripheral precocious puberty. The hormonal investigation was suggestive of cortisol and androgen excess. Radiologically, she had an adrenal tumor appearing like adrenocortical carcinoma (ACC)-large size, high noncontrast Hounsfield units, and poor washout. Management and Outcome: As virilization was not present since birth and there was no evidence of adrenal insufficiency, therefore, the possibility of congenital adrenal hyperplasia was unlikely. Investigations revealed that the testosterone levels were much higher than other adrenal androgen precursors like dehydroepiandrosterone sulfate. This was a clinical clue to the well-differentiated and benign nature of the tumor although radiologically it appeared like ACC. The child underwent en bloc resection of the mass, and histopathology was suggestive of a benign adrenocortical adenoma. Seven days after surgery, the serum testosterone had dropped substantially. Conclusion: This case creates awareness about the possibility of an adrenocortical neoplasm in a child with early-onset virilization, which can be diagnosed correctly by following a step-wise, logical sequence of investigations.

PSAT038 A Case of Spontaneous Atraumatic Unilateral Adrenal Hemorrhage

Abstract Background Adrenal hemorrhage is a rare disorder with an incidence of 0.1 to 1% for which a cause is identified in most cases. It is usually classified as traumatic or atraumatic, unilateral or bilateral and can result in serious consequences such as adrenal crisis and death if not diagnosed and treated properly. We describe a patient with an atraumatic unilateral adrenal hemorrhage without a known coagulopathy Case presentation: A 51-year-old man with history of COPD and Reynaud's phenomenon presented to the hospital for severe right upper quadrant pain. CT of the abdomen demonstrated a right adrenal hemorrhage of 5.2×4.0×2.6 cm in size, for which Endocrinology was consulted. The patient denied recent trauma or anticoagulation use. Physical examination exhibited generalized abdominal tenderness, without hypotension, or symptoms of acute adrenal insufficiency. Biochemical evaluation showed an AM Cortisol level of 14.3 ug/dL (4.2 - 22.4 ug/dL) and ACTH 67.1 pg/mL (7.2 - 63.3 pg/mL). MRI abdomen showed a decrease in size of the hemorrhage measuring 3.1×1.7×5.2 cm. He was referred to Hematology/Oncology to evaluate for coagulopathy which was unrevealing. About one month from hospital discharge, the patient reported voice hoarseness and was diagnosed with moderately differentiated keratinizing squamous cell carcinoma of larynx. Ten months later PET-CT scan showed hypermetabolic laryngeal mass with bilateral cervical lymphadenopathy without evidence of adrenal gland metastasis with resolution of adrenal hemorrhage, indicative that the hemorrhagic episode is unrelated to this newly diagnosed malignancy. Discussion Adrenal hemorrhage is a rare disorder that overall is associated with a 10-20% mortality rate, it is usually classified as traumatic and no traumatic. Most times it is caused by secondary disorders such as trauma, surgery, anticoagulants, infections, but in rare instances is idiopathic. Clinical manifestations of adrenal hemorrhages vary depending on extension of the hemorrhage and early diagnosis is crucial for better outcomes. As per current guidelines, assessment for adrenal insufficiency including hemodynamics, biochemical evaluation and imaging is paramount. To date, clear etiology of primary adrenal hemorrhage is lacking. This case demonstrated an unusual presentation of idiopathic unilateral adrenal hemorrhage without evidence of adrenal insufficiency. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Hypercortisolism in patients with cholestasis is associated with disease severity

BackgroundCholestasis might lead to an impairment of adrenal function as suggested by in vitro and in vivo data as well as by clinical findings. Bile acid and adrenal steroid metabolism not only share the receptors farnesoid X receptor (FXR) and the G protein-coupled bile acid receptor 1 (TGR5), but supraphysiological bile acid levels were found to stimulate steroidogenesis independent of FXR and TGR5. Our previous experimental findings revealed that mice fed bile acids or subjected to common bile duct ligation develop hypercortisolemia. We thus aimed to assess adrenal gland function in patients with cholestasis.MethodsAdrenal gland function was assessed in 36 patients with cholestasis and in 32 patients without cholestasis by measuring total serum cortisol, adrenocorticotropic hormone (ACTH), as well as the increase of cortisol 20 and 30 min after administration of 1 µg of ACTH. Bile acid levels and bile acid pool composition were determined by high-resolution mass spectrometry.ResultsPatients with cholestasis per definition had markedly elevated levels of alkaline phosphatase (AP), bilirubin and serum bile acids. Baseline cortisol and maximum cortisol after ACTH stimulation were significantly higher in patients with cholestasis compared to controls. Increase of cortisol after ACTH stimulation and ACTH did not differ. In the cholestasis group, baseline cortisol correlated with bilirubin but not with AP, total serum bile acids and levels of conjugated and unconjugated bile acid species. Patients with duration of cholestasis < 6 months (n = 30) had significantly higher baseline cortisol levels than those with long standing cholestasis (> 6 months), together with higher bilirubin levels.ConclusionsWe find no evidence of adrenal insufficiency in non-cirrhotic patients with cholestasis. In contrast, patients with cholestasis show hypercortisolism associated with disease severity as mirrored by levels of bilirubin. Lack of ACTH increase in cholestasis suggests a direct effect of cholestasis on adrenals and not on the pituitary gland. Further studies are needed to elucidate the mechanism of cortisol elevation in patients with cholestasis and its clinical significance.

Oral corticosteroid elimination via a personalised reduction algorithm in adults with severe, eosinophilic asthma treated with benralizumab (PONENTE): a multicentre, open-label, single-arm study

No consensus exists on how to reduce oral corticosteroids after the initiation of biologics in severe asthma. The PONENTE trial evaluated the effectiveness and safety of a rapid, individualised steroid-reduction algorithm, including adrenal insufficiency monitoring, after benralizumab initiation. This multicentre, open-label, single-arm study was done at 138 clinical asthma treatment centres across 17 countries. We enrolled adult patients (age ≥18 years) with severe, eosinophilic asthma (blood eosinophil count ≥150 cells per μL at enrolment or ≥300 cells per μL in the previous year) requiring maintenance oral corticosteroids for at least 3 months preceding enrolment. Patients received benralizumab 30 mg (subcutaneous injection) every 4 weeks for three doses, then every 8 weeks thereafter. The oral corticosteroid reduction phase began at week 4 with daily oral corticosteroid dosages reduced by 1-5 mg every 1-4 weeks depending on the starting dosage, asthma control, and adrenal function status. Adrenal function was assessed with an early morning serum cortisol measurement, followed by adrenocorticotropic hormone stimulation when required, once patients achieved a daily oral corticosteroid dosage of 5 mg/day for 4 weeks. Repeat cortisol measurements were taken for patients with evidence of adrenal insufficiency at first testing. Asthma control was assessed with the Asthma Control Questionnaire-6 (ACQ-6) weekly throughout the induction and oral corticosteroid reduction phases. The primary endpoints were the percentage of patients eliminating daily oral corticosteroids, sustained for at least 4 weeks, and the percentage achieving elimination or a daily prednisone or prednisolone dosage of 5 mg or less, for at least 4 weeks, if the reason for no further reduction was adrenal insufficiency. Safety and efficacy analyses included all patients who received at least one dose of benralizumab and were descriptive. We present results after the oral corticosteroid reduction phase; a maintenance phase is ongoing. The trial is registered with ClinicalTrials.gov, NCT03557307. Between April 1, 2018, and Sept 5, 2020, of 705 patients assessed for eligibility, 598 were recruited and all received at least one dose of benralizumab. Overall, 376 (62·88%, 95% CI 58·86-66·76) of 598 patients eliminated oral corticosteroids and 490 (81·94%, 78·62-84·94) of 598 eliminated use or achieved a dosage of 5 mg or less if the reason for stopping the reduction was adrenal insufficiency. Subgroup analysis showed that dosage reductions were achieved irrespective of baseline eosinophil count, baseline oral corticosteroid dosage, or oral corticosteroid treatment duration. Adrenal insufficiency was detected in 321 (60%) of 533 patients at first assessment and in 205 (38%) of 533 patients 2-3 months later. The safety profile was consistent with previous experience. Most patients (448 [75%] of 598) had no asthma exacerbations during the oral corticosteroid reduction phase with an annualised exacerbation rate of 0·63. Of 598 patients, 38 (6%) experienced a total of 46 exacerbations resulting in emergency department or urgent care visits or hospitalisations. Despite a high prevalence of adrenal insufficiency, most patients with eosinophilic asthma treated with benralizumab achieved elimination of oral corticosteroids or maximal possible reduction using a personalised dosage-reduction algorithm. AstraZeneca.

A Huge Adrenal Incidentaloma With Suspicious Features and a Complete Cure!

Introduction: Adrenal hemangioma is an extremely rare benign vascular tumor occurring in adrenal glands (~0.01%). Its clinical presentation is usually vague and is frequently discovered as an incidentaloma. These tumors are mostly encountered at 40–70 years of age and are twice as common in women. We report a case of a nonfunctioning large adrenal incidentaloma with suspicious features on imaging. This in fact was an adrenal hemangioma diagnosed postoperatively with histopathology. Case Description: Our patient was 76 year old Hispanic male, active smoker, with medical history significant for well controlled Type 2 diabetes, hyperlipidemia and hypertension. He was seen for evaluation and management of an adrenal incidentaloma discovered on iv contrast enhanced CT performed to investigate recurrent hematuria. Imaging of the abdomen and pelvis revealed a posterior bladder mass measuring up to 2.6 cm and 20.1 cm x 17.1 cm x 20.5 cm left adrenal mass with few punctuate calcifications displacing the left kidney and spleen- findings concerning for adrenal cortical carcinoma. The right adrenal gland unremarkable. Given the size of mass and suspicious features hormonal workup was initiated in preparation for surgery. Workup was unremarkable for Pheochromocytoma {24 hour urine metanephrine 124 (nl: 0–300), normetanephrine 440 (nl: 0–400)}, Cushing syndrome {(negative 1 mg overnight dexamethasone suppression test), ACTH 22 (nl: 7—63)} and hyperaldosteronism (Aldosterone 5, renin 0.7). Patient underwent an uncomplicated total radical left adrenalectomy, he had no evidence of invasive disease. Pathology showed a large entirely encapsulated heterogenous adrenal mass weighing 2300 grams with largely solid (80%) and cystic components. There was hemorrhage and extensive infarcts- findings consistent with a Hemangioma. He recovered well. No evidence of adrenal insufficiency was noted on subsequent follow-ups. He had a normal surveillance CT scan at 6 months. Discussion: Adrenal hemangiomas are difficult to differentiate clinically and radiographically from adrenal cortical cancer. They must be evaluated to exclude hormonal hypersecretion and malignancy. Previous case reports hypothesized that adrenal hemangiomas may have functional hypersecretion due to mass effect on the adrenal parenchyma. There was no evidence of this in our patient. These tumors increase in size overtime. Surgical resection is often necessary to rule out any malignant potential and alleviate symptoms secondary to mass effect. Adrenal hemangiomas though rare and must be considered in the differential diagnosis.

Randomised clinical trial: the safety and tolerability of fluticasone propionate orally disintegrating tablets versus placebo for eosinophilic oesophagitis

APT-1011, a fluticasone propionate orally disintegrating tablet formulation, is under investigation for the treatment of eosinophilic oesophagitis (EoE). To evaluate the safety and tolerability of APT-1011 administered to patients with EoE and to assess the effect on clinical symptoms of EoE, endoscopic appearance and oesophageal eosinophilia. A randomised, double-blind, placebo-controlled, multicentre, phase 1b/2a study was conducted at seven medical centres in the US to evaluate the safety and tolerability of APT-1011 over 8 weeks in adults and adolescents with EoE. Participants were randomised to placebo (n=8), 1.5mg APT-1011 BID (n=8) or 3.0mg APT-1011 QD (n=8). Safety and tolerability were assessed as the primary outcome; histologic and endoscopic measures were assessed as exploratory outcomes. There were no deaths, serious treatment-emergent adverse events (TEAEs), severe TEAEs or discontinuations from the study related to a TEAE. In one participant randomised to 1.5mg APT-1011 BID, a reduction in cortisol was observed, but without evidence of adrenal insufficiency. Compared with placebo, treatment with APT-1011 resulted in greater reductions in oesophageal eosinophil counts, EoE Endoscopic Reference Score, patient global assessment and symptom-based EoE activity index from baseline to end of treatment (Week 8). APT-1011 was safe and well tolerated in adolescents and adults with EoE. Exploratory efficacy outcomes demonstrated improvement in histologic and endoscopic findings as well evidence of symptom improvement. The results of this study support the continued development of APT-1011 for the treatment of EoE (NCT-01386112).

Adrenal Insufficiency After Unilateral Adrenalectomy in Primary Aldosteronism: Long-Term Outcome and Clinical Impact.

Primary aldosteronism (PA) represents a secondary form of arterial hypertension that can be cured by surgery. Evidence of adrenal insufficiency (AI) was recently found in patients with PA who had undergone unilateral adrenalectomy (uADX). To study the incidence and long-term outcome of postoperative AI after uADX for PA. Prospective registry study (August 2014 until the end of 2018). Tertiary referral center. One hundred consecutive patients undergoing uADX for PA were included. All patients underwent postoperative ACTH stimulation testing. Postoperative ACTH stimulation testing to identify patients with AI. Incidence of patients with postoperative AI and definition of long-term outcome. Twenty-seven percent of patients developed postoperative AI. Of these, 48% had postoperative ACTH stimulation serum cortisol levels ≤13.5 µg/dL (severe AI); 52% were classified into the group with moderate AI (stimulated serum cortisol levels: 13.5 to 17 µg/dL). Patients with severe AI required significantly longer hydrocortisone replacement therapy than the moderate group (median [25th, 75th percentiles]: 353 [294, 476] days; 95% CI: 284 to 322 days; vs 74 [32, 293] days; 95% CI: 11 to 137 days; P = 0.016). One patient with severe AI was hospitalized for an acute adrenal crisis. With a cumulative follow-up of 14.5 years, this produced an incidence rate of 6.9 adrenal crises per 100 patient-years. We suggest performing postoperative ACTH stimulation tests in all patients who undergo uADX for PA.

SUN-487 Incidence and Natural History of Hypophysitis Secondary to Check-Point Inhibitor Therapy at a Tertiary Center

Hypophysitis is a known adverse effect of immune checkpoint inhibitor therapy. These drugs are being increasingly used for treatment of various cancers. Thus, it is crucial to understand the incidence and natural history of hypophysitis to help us improve its management. Aim - To determine the incidence of hypophysitis associated with ipilimumab, nivolumab and pembrolizumab at our center and describe its natural history. Methods – We performed a retrospective study of patients treated with pembrolizumab, nivolumab, ipilimumab or combination of these drugs between Aug 2013 and Jun 2018. Files were reviewed for cancer history and immune related adverse effects. Patients with hypophysitis had their clinical status, biochemistry and treatment documented at 0,1.5, 3, 6, 9 months and at the most recent follow up. Results – Of 115 patients identified, 14 developed hypophysitis. Of these, 8 of 17 patients had received combination ipilimumab and nivolumab, 1 of 6 had received ipilimumab, 4 of 61 had received nivolumab and 1 of 23 had received pembrolizumab. The median time to hypophysitis from initial dose was 98 days. At diagnosis, 78% had thyroid axis involvement, 3/11 had resolved at 6 weeks. Only 50% had a paired ACTH/cortisol requested at diagnosis. 100% had evidence of adrenal insufficiency with no patient recovering their adrenal axis. Gonadal axis was involved in 5/8 at diagnosis and 3/5 had normalized at 6 weeks. All patients received high dose steroids at diagnosis with a large range of time to physiological dosing (4-311 days), median 56. Conclusion –Hypophysitis is a common adverse effect, especially with combination ipilimumab and nivolumab. Most hormone deficiencies present at 6 weeks appear to be permanent. It is important to have early endocrinology involvement to ensure appropriate investigation and management.

A228 FIRST REPORT OF ADRENAL CRISIS IN TWO PATIENTS WITH EOSINOPHILIC ESOPHAGITIS

Eosinophilic Esophagitis (EoE) is an immune mediated allergic condition affecting the esophagus. Risk factors include male sex and atopy. A treatment option is swallowed corticosteroids (cs). Patients with EoE are at risk for adrenal insufficiency (AI). We screened 14 patients on Oral Viscous Budesonide (OVB) for ≥ 3 months using the low dose ACTH stimulation test and found 6 (43%) had evidence of AI. This was found in patients with and without inhaled cs. Golekoh found 10% of their patients on Fluticasone to have AI. We present 2 cases of adrenal crisis requiring major intervention from the ‘at risk’ screened group. Case 1 17 y.o with atopy and food allergies, diagnosed with EoE in 2011 presenting with vomiting. He was on baseline inhaled cs for asthma and cs nasal spray. OVB was successful at achieving remission and he maintained 0.5 mg po daily. Through routine screening in 2013 he was shown to be at risk of AI with an abnormal ACTH stim test result of 403 nmol/L @ 30 mins. Stress-dose cs management was taught for illnesses and stress. Despite the patient deciding to stop the OVB, he had an abnormal ACTH stim test ≥ 3 months later. Limited follow-up occurred. In June 2016, patient underwent a GA for elective surgery at an outlying hospital. No pre-operative cs were received. In recovery he had hypotension and apnea requiring a Code Blue and ICU admission. At the time, a low cortisol level was documented (44 nmol/L). He responded well to IV Hydrocortisone and was discharged the next day. A subsequent ACTH stim test was abnormal (peak 417 nmol/L). Case 2 17 y.o. ex prem with chronic lung disease, asthma, laryngeal cleft, rhinitis and food allergies. Pre-diagnosis he was on inhaled cs for asthma. He was diagnosed with EoE in 2008 presenting with dysphagia. Initially he was on Fluticasone but in 2012 was switched to 1 mg bid OVB with incomplete histological remission (some symptom improvement). He routinely underwent ACTH stim testing in 2013 and was found to have AI with a peak level of 459 nmol/L. Education was provided for episodes of moderate and severe stress. He remained on the OVB. In the interim he received stress coverage for viral meningitis in 2015 and was weaned off. He switched to Fluticasone and did not have improvement in his ACTH stim testing. In 2016 he had a URTI and took 3 po doses of cs for moderate stress. Despite the oral cs, he continued to evolve with headache, aches and weakness. Upon presentation to emergency he was hypotensive and required IV steroids and fluids. Recently, he has had difficulty weaning the cs and has shown to have low baseline cortisol production necessitating daily cs. Identifying EoE patients with AI is clinically relevant as they are at risk for adrenal crisis as exemplified by these two cases. The risk for AI can be enhanced by the swallowed cs, and can persist post-discontinuation. None

Evaluation of Adrenal Function in Nonhospitalized Patients with Cirrhosis.

Background Patients with cirrhosis and advancing hepatic insufficiency may show various degrees of other organ malfunction, including brain, kidney, and lung. Several studies have also shown a high prevalence of adrenal insufficiency in cirrhotic patients that may cause hemodynamic instability. Materials and Methods In this study we prospectively evaluated adrenal function in a population of nonhospitalized cirrhotic patients. Categorization of liver disease severity was done according to model for end-stage liver disease (MELD) score. Adrenocorticotropic hormone stimulation testing was performed on subjects using 250 μg of synthetic short acting hormone; radio immunoassay was used to measure plasma cortisol levels. Results Of 105 cirrhotic patients, 15.23% had evidence of adrenal insufficiency. These patients were not statistically different from those with normal adrenal function in levels of serum creatinine or bilirubin, MELD score, or presence of cirrhosis related complications. Significant differences were seen in mean international normalized ratio and serum sodium. Patients with a sodium level < 135 mEq/L had a higher rate (31.25%) of adrenal insufficiency. Conclusion Adrenal dysfunction was identified in a population of stable nonhospitalized cirrhotic patients. Our results suggest a possible role for adrenal dysfunction as a contributing factor in hyponatremia in cirrhosis independent of other known factors of neurohormonal activation secondary to systemic vasodilation.

A Rare Case of Primary Bilateral Adrenal Lymphoma

Lymphoma may involve the adrenal glands, but primary lymphoma is rare. Only a few cases have been reported in medical literature. Primary adrenal lymphoma is extremely rare, accounting for <1% of non-Hodgkin lymphomas. We here present a case of a middle-aged female who presented with persistent fever for three weeks. She also reported significant weight loss of more than 10 kgs over the duration of three months. Computed tomography of the thorax and abdomen and pelvis demonstrated bilateral adrenal masses. She underwent short Synacthen test which showed evidence of adrenal insufficiency. She underwent CT-guided adrenal gland biopsy. Histology of adrenal gland biopsy showed features consistent with diffuse large B-cell lymphoma. She was started on R-CHOP chemotherapy and had a good clinical response and remained in complete remission for five months after chemotherapy.

Adrenoleukodystrophy: two case reports

Adrenoleukodystrophy (ALD) is a peroxisomal disorder characterized by the accumulation of saturated very long chain fatty acids (VLCFA) in plasma, various tissues of body and central nervous system. It causes demyelination and adrenocortical insuciency. High levels of very long chain fatty acids are found in tissues and body fluids, resulting from their impaired ?-oxidation in the peroxisomes. The most common form of ALD is an X-linked disorder with various presentations which is caused by mutations in the ABCD1 gene located on Xq28. The gene encodes a transmembrane transporter involved in the importation of very long chain fatty acids into peroxisomes. The phenotypic presentations are highly variable, which may lead to delayed recognition and misdiagnosis, as attention deficit and/or hyperactivity disorder in boys or multiple sclerosis in adults. The most common clinical picture is of a degenerative neurologic disorder appearing in childhood or adolescence and progressing to severe dementia and deterioration of vision, hearing, speech, and gait and death occur within a few years. Many patients have evidence of adrenal insufficiency at the time of neurologic presentation. Hydrocortisone and mineralocorticoid are necessary to treat adrenal insufficiency. High doses of hydrocortisone preoperatively and during recovery are needed for surgery and other stressful illnesses in affected individuals.Here, we described two patients with childhood onset ALD with clinical and laboratory features to illustrate the wide clinical variability of this condition.Bangladesh Med J. 2015 Sep; 44 (3): 168-171

Systemic glucocorticoid therapy and adrenal insufficiency in adults: A systematic review.

ObjectivesThe aim of this systematic literature review was to summarize the current knowledge regarding the prevalence of, time to recovery from, and influence of glucocorticoid dose and duration on glucocorticoid-induced adrenal insufficiency (AI).MethodsEligible studies were original research articles, which included adult patients with an indication for glucocorticoids and measured adrenal function following exposure to systemic glucocorticoids. Searches were performed in Web of Science and MEDLINE, with further articles identified from reference lists. Screening was performed in duplicate. Data were extracted for each group of glucocorticoid-exposed patients within eligible studies. The reported proportion of patients with AI was summarized as median and inter-quartile range. Results were then stratified by daily dose, cumulative dose, duration of exposure and time since last glucocorticoid use. The risk of bias within and across studies was considered: for randomised controlled trials risk of bias was assessed using the tool developed by the Cochrane Collaboration.ResultsOverall, 73 eligible studies were identified out of 673 screened. The percentage of patients with AI ranged from 0% to 100% with a median (IQR) = 37.4% (13–63%). Studies were small—median (IQR) group size 16 (9–38)—and heterogeneous in methodology. AI persisted in 15% of patients retested 3 years after glucocorticoid withdrawal. Results remained widely distributed following stratification. AI was demonstrated at <5 mg prednisolone equivalent dose/day, <4 weeks of exposure, cumulative dose <0.5 g, and following tapered withdrawal.ConclusionsThe heterogeneity of studies and variability in results make it difficult to answer the research questions with confidence based on the current literature. There is evidence of AI following low doses and short durations of glucocorticoids. Hence, clinicians should be vigilant for adrenal insufficiency at all degrees of glucocorticoid exposure.

Adrenoleukodystrophy: Diffusion MRI findings

An 8-year-old boy with laboratory evidence of adrenal insufficiency, and an established diagnosis of X-linked adrenoleukodystrophy was referred to our institution for a follow-up magnetic resonance imaging (MRI) examination. Besides T1 and T2-weighted sequences, a diffusion MRI protocol was added. The “trace” sequence, a single-shot, spin-echo, echo-planar imaging sequence was used, which averages the data from the three (x, y, and z) gradients and which provides automatically generated apparent diffusion coefficient (ADC) maps. The acquisition time was 22 sec with TR = 5700 msec, and TE = 139 msec, and slice thickness was 5 mm. On diffusion MRI b = 1000 sec/mm images revealed high-signal changes similar to that seen in cases of restricted diffusion pattern (Fig. 1a). However, the ADC maps revealed that an elevated diffusion pattern was present in the necrotic regions (2.06 and 1.60 × 10−3 mm/sec). The ADC value of the central necrotic zone was higher (2.06× 10−3 mm/sec) compared to that of the peripheral necrotic zone (1.60 × 10−3 mm/sec), and that of the intermediate zone of active demyelination was lower (1.14 × 10−3 mm/sec) (Fig. 1b). These values were higher than the ADC values of the normal regions of the brain parenchyma.

PMM.81 Conservative management of spontaneous bilateral adrenal haemorrhages in pregnancy

IntroductionSpontaneous adrenal haemorrhage is a very rare condition. To date there have been only 13 reported cases associated with pregnancy.Case historyA 29 year old para 2+5 presented at 38 weeks...

Brief Report: Adrenal autoimmunity in primary Sjögren's syndrome

To evaluate the prevalence of antibodies to 21-hydroxylase (anti-21[OH]), a marker of autoimmune adrenal disease, in a cohort of patients with primary Sjögren's syndrome (SS) and to investigate whether the presence of anti-21(OH) correlates with clinical, serologic, and salivary gland features of the disease. Sera from 63 consecutive patients with primary SS, 32 patients with autoimmune thyroid disease (AITD), and 20 healthy controls were obtained and anti-21(OH) levels were determined by radioimmunoassay. Clinical, serologic, and histopathologic features were recorded, and a short Synacthen test was used to assess adrenal function reserve. Seven available minor salivary gland (MSG) tissue specimens from patients in the primary SS cohort were also assessed for interferon-α (IFNα), BAFF, and interleukin-21 (IL-21) cytokine transcripts, which are all implicated in B cell activation. Anti-21(OH) positivity was detected in 17.5% and 28.1% of primary SS and AITD patients, respectively, and in none of the healthy controls. While no evidence of adrenal insufficiency was detected in any of the patients studied, a blunted rate of increase in cortisol levels was observed in patients with detectable serum autoantibodies against 21(OH), compared to their anti-21(OH)-negative counterparts. A strong correlation between the serum titer of anti-21(OH) antibodies and expression of IFNα, BAFF, and IL-21 messenger RNA in MSG tissues was also detected. Adrenal autoimmunity occurs in almost 20% of patients with primary SS in association with markers of B cell activation. Although the presence of adrenal autoantibodies was not associated with adrenal insufficiency in the present study, there was a blunted adrenal response, suggesting the need for further followup and monitoring of adrenal function in patients with primary SS who are positive for the autoantibodies.

P9 Adrenal Suppression in Difficult Asthma: A Neglected Cause For Concern

IntroductionInhaled corticosteroids (ICS) are the mainstay of treatment in asthma. Whilst they are felt to be safe in low doses, a number of case studies have demonstrated adrenal suppression in...

The postoperative cortisol stress response following transsphenoidal pituitary surgery: a potential screening method for assessing preserved pituitary function

The ability to reliably identify patients with new hypocortisolemia acutely following pituitary surgery is critical. We aimed to quantify the postoperative cortisol stress response following selective transsphenoidal adenomectomy, as a marker for postoperative preservation of functional pituitary gland. Records of 208 patients undergoing transsphenoidal operations for pituitary lesions were reviewed. Patients with Cushing's Disease, preoperative adrenal insufficiency, and those receiving intraoperative steroids were excluded. To quantify the postoperative stress response, the ∆ cortisol index was defined as the postoperative day (POD) 1 morning cortisol minus the preoperative morning cortisol level. The incidence of new hypocortisolemia requiring glucocorticoid replacement upon hospital discharge was also recorded. Fifty-two patients met inclusion criteria. The mean preoperative, POD1, and POD2 cortisol levels were 16.5, 29.2, and 21.8 μg/dL, respectively. Morning fasting cortisol levels on POD1 ranged from 4.2 to 73.0 μg/dL. The ∆ cortisol index ranged from -19.0 to +56.2 (mean +12.7 μg/dL). Five patients (9.6%) developed new hypocortisolemia on POD 1-3 requiring glucocorticoid replacement; only one required long-term replacement. The mean ∆ cortisol in patients requiring postoperative glucocorticoids was -2.8 μg/dL, compared with +14.4 μg/dL in patients without evidence of adrenal insufficiency (p = 0.005). Of the 32 patients (61.5%) with a ∆cortisol >25 μg/dL, none developed postoperative adrenal insufficiency. The postoperative cortisol stress response, as quantified by the ∆ cortisol index, holds potential as a novel and complimentary screening method to predict preservation of normal pituitary function and acute development of new ACTH deficiency following transsphenoidal pituitary surgery.