Undiagnosed Adrenal Insufficiency Research Articles

Undertreated and undiagnosed adrenal insufficiency as a premature cause of death in glucocorticoid users

Undertreated and undiagnosed adrenal insufficiency as a premature cause of death in glucocorticoid users

Undiagnosed adrenal insufficiency as a cause of premature death in glucocorticoid users.

It is unknown whether glucocorticoid (GC)-induced adrenal insufficiency may cause premature mortality in GC users. We conducted a retrospective cohort study to investigate if undiagnosed and undertreated GC-induced adrenal insufficiency is a contributor to premature death in GC users. Information on dispensed prescriptions in West Sweden from 2007 to 2014 was obtained from the Swedish Prescribed Drug Register. Cause of death was collected from the Swedish Cause of Death Register. Of 223,211 patients who received oral GC prescriptions, 665 died from sepsis within 6 months of their last prescription. Three hundred of these patients who had died in hospital were randomly selected for further investigation. Medical records were initially reviewed by one investigator. Furthermore, two additional investigators reviewed the medical records of patients whose deaths were suspected to be caused by GC-induced adrenal insufficiency. Of 300 patients (121 females, 40%), 212 (75%) were prescribed GC treatment at admission. The mean age was 76 ± 11 years (range 30-99). Undiagnosed or undertreated GC-induced adrenal insufficiency was considered a probable contributor to death by at least two investigators in 11 (3.7%) patients. In five of these 11 cases, long-term GC therapy was abruptly discontinued during hospitalization. Undiagnosed or undertreated GC-induced adrenal insufficiency was considered a possible contributing factor to death in a further 36 (12%) patients. GC-induced adrenal insufficiency is an important contributor to premature death in GC users. Awareness of the disorder during intercurrent illness and following cessation of GC treatment is essential.

FRI225 Clinical Course Of Late-onset Adrenal Insufficiency Due To Treatment Of Childhood Acute Lymphoblastic Leukemia

Abstract Disclosure: M. Iwabuchi: None. Background: Some people who were treated for cancer during childhood may develop endocrine problems as because of changes in the function of endocrine system. Acute lymphoblastic leukemia is the most common type of cancer and leukemia in children and components of ALL treatment are induction, consolidation, maintenance, and central nervous system prophylaxis. It is recommended that people who had irradiation in a dose of 40 Gy or higher to the central area of the hypothalamic-pituitary axis should have a blood test done to check the cortisol level and should be done yearly for at least 15 years since this complication can occur many years after irradiation. Clinical Case: A man in his 40s was admitted with symptoms of diarrhea, low-grade fever, and drowsiness. The serum sodium level that caused his symptoms decreased to 100 mEq/L and was adequately corrected. Endocrinological examination confirmed the diagnosis of central adrenal insufficiency. Soon after starting hormonal replacement therapy with hydrocortisone, his general conditions improved. After establishing our relationship, he confessed to having a history of ALL in childhood. According to his medical records at the time, he underwent induction therapy with vincristine-prednisone in 1977, maintenance therapy with 6-mercaptopurine, and radiation therapy to the central nervous system of 25 Gy in 1983. In 2023, 40 years have passed since radiation therapy. He was able to lead a normal life on oral hydrocortisone 20 mg/day without recurrence of adrenal insufficiency. Clinical Lesson: A 40-old male survivor of ALL developed adrenal insufficiency in 30 years after cranial irradiation during childhood. Undiagnosed adrenal insufficiency is often the cause of death. We should consider childhood cancer survivors have the risk of a central adrenal insufficiency. The Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers (COG LTFU Guidelines) are a resource for healthcare professionals who provide ongoing care to survivors of pediatric malignancies. The screening recommendations in these guidelines are appropriate for asymptomatic survivors of childhood, adolescent, or young adult cancer presenting for routine exposure-based medical follow-up. It is recommended that people who had irradiation in a dose of 40 Gy or higher to the central area of the hypothalamic-pituitary axis should have a blood test done to check the cortisol level and should be done yearly for at least 15 years since this complication can occur many years after irradiation. This case highlights the importance of long-term follow-up of cancer survivors after irradiation and the delayed presentation of adrenal insufficiency. This is the first report of the subsequent treatment course of late-onset adrenal insufficiency that developed 30 years after irradiation for childhood central nervous system ALL. Presentation: Friday, June 16, 2023

PSAT034 A Case of Adrenal Crisis in Association With a Febrile Response to the bnt162b2 mRNA COVID-19 (Pfizer) Vaccine Heralding a Diagnosis of Primary Adrenal Insufficiency.

Abstract Background In the face of the COVID-19 pandemic, messenger RNA (mRNA) vaccines were approved for the first time for use in the general population. Vaccination can trigger a febrile flu-like response that is self-limited in healthy individuals. Febrile illness is a classic trigger of acute adrenal insufficiency in patients who are cortisol deficient, but recognizing this clinical scenario is challenging in patients with undiagnosed adrenal insufficiency. Case Presentation A 24-year-old male presented to an acute care community hospital with fatigue, fever, and vomiting 12 hours after receiving the second dose of the BNT162b2 mRNA Covid-19 (Pfizer) vaccine. He was 6 feet tall, and his weight was 175 pounds. He had a temperature of 103 F, a blood pressure of 88/42 mmHg, and a heart rate of 100 bmp on admission. Hypotension persisted despite aggressive fluid resuscitation and broad-spectrum antibiotics. CT of the chest and CT angiogram of the abdomen and Pelvis did not identify an etiology for his presentation. Over a period of hours, he became obtunded, disoriented, and required vasopressor support. He received 100 mg of IV hydrocortisone followed by 50 mg every 6 hours for treatment of presumed sepsis and was transferred to an intensive care unit. Within 24 hours of starting glucocorticoid therapy, he was awake and oriented, defervesced, and became normotensive. This rapid improvement led to suspicion of adrenal insufficiency as an underlying diagnosis. Further questioning revealed a 4-month history of recurrent nausea, vomiting, severe fatigue, to the point where he had trouble climbing a flight of stairs, and a 40-pound unintentional weight loss. He visited an emergency department 3 times over this period and had outpatient evaluations by gastroenterology and cardiology without identifying a cause. Inpatient evaluation revealed a morning Cortisol of 1.4 ug/dL (n 4.8-19.5 ug/dL), aldosterone <3 ng/dL (n <16 ng/dL), and ACTH 1071 pg/mL (n 7.2-63.3 pg/mL) leading to the diagnosis of primary adrenal insufficiency. He was started on physiologic doses of adrenal replacement hormones and discharged home in stable condition 4 days after his admission date. Conclusions A severe post-vaccination reaction should elicit physicians to look for an alternative diagnosis. Autoimmune adrenalitis is the most common cause of primary adrenal insufficiency and is uniquely associated with a long lag to diagnosis. The diagnosis is often made in the setting of an intervening illness or physiologic stressor when a patient's condition acutely deteriorates. Patients with known adrenal insufficiency should be reminded to address post-vaccination febrile reactions with an increase in glucocorticoid doses. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Prevalence of adrenal insufficiency among patients with euvolemic hyponatremia.

BackgroundThe diagnosis of syndrome of inappropriate anti-diuresis requires the exclusion of secondary adrenal insufficiency (AI) among patients with euvolemic hyponatremia (EuVHNa). Studies have suggested that about 2.7–3.8% of unselected patients presenting to the emergency room with EuVHNa have undiagnosed AI and it is as high as 15% among patients admitted to specialized units for evaluation of hyponatremia.ObjectiveTo study the prevalence of AI among in-patients with EuVHNa in a general medical ward setting.MethodsThis was a prospective, single-center observational study conducted among general medical in-patients with EuVHNa, defined as patients with a serum sodium <135 mmol/L, clinical euvolemia and urine spot sodium >30 mmol/L. Additionally, patients with recent vomiting, current renal failure, diuretic use and those with uncontrolled hyperglycemia were excluded. Adrenal functions were assessed by a modified adrenocorticotropic hormone (ACTH) stimulation test called the Acton Prolongatum™ stimulation test (APST). A cut-off cortisol value of <18 mg/dL after 60 min of ACTH injection was used to diagnose AI.ResultsOne hundred forty-one patients were included and underwent an APST. APST suggested 20/141 (14.2%) had undiagnosed AI. The commonest cause of AI (9/20) was secondary AI because of the use of steroids including inhaled steroids and indigenous medicines contaminated with steroids. In 5 (3.5%) patients hypopituitarism was newly diagnosed. Despite primary AI (PAI) not commonly presenting as EuVHNa, 2/20 patients had PAI.ConclusionsAI is much commoner in our country, among in-patients with EuVHNa primarily driven by exogenous steroid use and undiagnosed hypopituitarism.

Cracking Crabs Leading to Vibrio Necrotizing Fasciitis in a Male with Undiagnosed Adrenal Insufficiency

Cracking Crabs Leading to Vibrio Necrotizing Fasciitis in a Male with Undiagnosed Adrenal Insufficiency

PTH-Independent Hypercalcemia in Undiagnosed Adrenal Insufficiency

In contrast to PTH-dependent hypercalcemia, the differential diagnosis of PTH-independent hypercalcemia is extensive. Thorough history and physical examination can help direct the clinician in the right direction and avoid extensive and unnecessary work up.A 27-year-old-female with a medical history significant only for untreated subclinical hypothyroidism was admitted to the hospital for hypercalcemia and acute kidney injury after presenting with dizziness, nausea, vomiting, dyspnea, and multiple syncopal episodes prior to admission. Serum calcium on presentation was elevated to 15.9 (8.5–10.2 mg/dL) with an intact parathyroid hormone level of 3.6 (8.5–75 pg/mL). On initial presentation, she was hypotensive, tachycardic, and was noted to be underweight with a body mass index of 17 kg/m2. The patient’s skin was diffusely hyperpigmented, with increased pigmentation in the creases of her hands and on the sides of her fingers. Further lab evaluation was remarkable for hyponatremia and hyperkalemia as well as an undetectable 8 AM cortisol of <1.0 (7–25 µg/dL), adrenocorticotropic hormone (ACTH) level significantly elevated to >1,250 (6–58 pg/mL), aldosterone <4 (<21 ng/dL), and plasma renin activity elevated to 18 (<0.6–3 ng/mL/h). Antibodies to 21-alpha hydroxylase were positive, confirming a diagnosis of Addison’s disease. Prior to the workup confirming an elevated ACTH and low cortisol levels, the patient was treated with aggressive intravenous fluid repletion and calcitonin with overnight improvement in calcium to 11.4 mg/dL. After the diagnosis of primary adrenal insufficiency was confirmed, she was treated with stress doses of intravenous hydrocortisone then gradually tapered to physiologic doses of oral hydrocortisone and fludrocortisone with resolution of her hypercalcemia by the fourth day of hospitalization.Adrenal insufficiency is a known but uncommon cause of PTH-independent hypercalcemia, but the exact mechanism is unknown. Hypercalcemia is thought to result from a combination of a hypovolemic state seen in adrenal insufficiency which leads to decreased urinary calcium excretion as well as increased bone resorption, which may result from increased serum sclerostin concentrations.Adrenal insufficiency should be considered in the differential of PTH-independent hypercalcemia. This case highlights the improvement in hypercalcemia that is seen with correction of glucocorticoid deficiency, and supports delaying additional work up for other PTH-independent causes until appropriate treatment has been given.

Prevalence of Suppressed Morning Serum Cortisol and Its Relationship With Cumulative Glucocorticoid Exposure in a Moderate-Severe Asthma Patient Cohort

The extent to which inhaled glucocorticoid exposure (ICS) contributes to risk of adrenal insufficiency (AI) is not fully understood. The aim of this study was to establish the relative contribution of both oral (OCS) and inhaled (ICS) glucocorticoid exposure to risk of AI.82 patients with severe asthma treated with fluticasone propionate (FP) who participated in a 32-week prospective randomised trial INCA SUN, (NCT02307669) were studied. Cumulative ICS exposure was calculated using a unique digital device, which creates an acoustic recording of inhaler adherence and technique. Analysis of this data provides an exact measure of the ICS dose received by each patient. Morning serum samples collected during the final study visit (week 32) were analysed for serum cortisol concentration (cortisol) using Roche Elecsys Cortisol II immunoassay. Participants were then stratified into three groups based on cortisol concentration to predict risk of AI; cortisol < 100nmol/l (high risk), 100–315 nmol/l (indeterminate risk) and > 315 nmol/l (low risk) based on locally derived reference ranges. 21% participants were classified as low risk, 18% as high risk and the remaining 61% at indeterminate risk of AI. Median morning cortisol in the low risk group was ten-fold higher than those in the high risk group (380 vs 38.5 nmol/l, p=0.001). OCS exposure was a significant predictor of risk of AI (OR 1.1 [1.03–1.17] per mg/kg increase in prednisolone exposure, p=0.004)). Participants at high risk were more likely to be on maintenance OCS (33% vs 0%, p=0.015) and had a greater median cumulative OCS exposure over the study period (7.55 vs 0.66 mg/kg prednisolone, p=0.002). ICS exposure was also associated with risk of AI. Participants at high risk AI had a greater adherence to ICS therapy (78% vs 62%, p=0.049) and greater cumulative received ICS dose over the study duration than those at low risk AI (178.2 vs 127.9 mg, p=0.036). ICS exposure remained a significant predictor of AI even when OCS exposure is controlled for (OR 2.49 [1.06–5.82] per 1mg/kg increase in FP exposure). Both the asthma control test (ACT) & asthma quality of life questionnaire (AQLQ) scores correlate with morning cortisol concentration (ACT r=0.2, p=0.068, AQLQ r=0.26, p=0.019). Interestingly, participants with cortisol < 100nmol/l reported worse asthma control (ACT score 16 vs 20, p=0.07) and a lower AQLQ score (4.1 vs 5.8, p=0.02) than the low risk group despite objectively better lung function (FEV1 90.6 vs 77.6% predicted). Our data suggests that both cumulative oral and inhaled glucocorticoid exposure contribute independently to cortisol suppression and risk of AI. The discrepancy between objective (FEV1) and more subjective measures of asthma control (ACT score) in the high risk group suggests that undiagnosed AI, as well as other non-airway co-morbidities, may contribute to the symptom burden experienced by these patients.

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-230 Newly Diagnosed Schmidt’s Syndrome and Steroid Induced Psychosis

In 1926, Schmidt reported the combination of hypothyroidism and adrenal insufficiency (AI) with lymphocytic infiltration of both the thyroid and adrenal glands.1 This syndrome is now known as autoimmune polyendocrine syndrome (APS) type 2, characterized by two of the following three endocrinopathies: type 1 diabetes, autoimmune thyroiditis, and Addison’s disease.2 It may seem surprising that transient relative hypercortisolemia in AI patients at the beginning of treatment results in steroid induced psychosis (SIP). Here, we present a patient who developed SIP after starting steroid for AI.44 year old Caucasian female with bipolar disorder and Hashimoto’s thyroiditis was admitted for generalized weakness, nausea, vomiting and weight loss of about 15 pounds in 3 months. On exam, blood pressure was 93/54 mmHg and pulse rate was 99. Her abdomen and arms looked hyperpigmented. Lab test revealed plasma glucose of 68 mg/dl, serum sodium of 129 mmol/l (133-145), potassium of 4.9 mmol/l (3.6 – 5.2), bicarbonate of 20 mmol/l (22 – 29). TSH was 16.93 mIU/ml (0.4 – 4.00) and FT4 was 0.74 ng/dl (0.7 1.8). CT abdomen and pelvis with contrast was unremarkable. As AI was suspected, cortisol level was checked and low at 0.5ug/dl. Cosyntropin stimulation test (CST) revealed pre-CST cortisol of 0.4 ug/dl, and post CST cortisol of 0.5 ug/dl at 45 min. ACTH was elevated at 514.4 pg/ml (7.2 – 63.3). A diagnosis of Schmidt’s syndrome was made based on elevated 21 hydroxylase of 8.5 U/ml (<1.0) and anti-thyroid peroxidase antibody of 20.5IU/ml (<5.6). Screening for type 1 diabetes and celiac disease was negative. After CST, stress dose hydrocortisone was started and dose was gradually tapered down in a few days. However, five days after steroid therapy, patient was admitted for suicidal ideation and catatonia which resolved quickly with Ativan and steroid taper to physiologic dose.APS type 2 has a prevalence of 1:1000. Clinicians should raise the suspicion for this syndrome in the appropriate context as seen in this patient presenting with classic features of AI. Although SIP in AI patients is not frequently reported, we should be mindful about this potential event especially in patients with underlying psychiatric illness. It is postulated that prolonged hypocortisolism in undiagnosed AI might lead to upregulation of central glucocorticoid receptors and hence glucocorticoid replacement might elicit a relative supraphysiological response in these patients.3

A systematic survey of low S-cortisol levels at the department of clinical chemistry: indications for testing and frequency of undiagnosed adrenal insufficiency

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

The contribution of undiagnosed adrenal insufficiency to euvolaemic hyponatraemia: results of a large prospective single-centre study.

The syndrome of inappropriate antidiuresis (SIAD) is the commonest cause of hyponatraemia. Data on SIAD are mainly derived from retrospective studies, often with poor ascertainment of the minimum criteria for the correct diagnosis. Reliable data on the incidence of adrenal failure in SIAD are therefore unavailable. The aim of the study was to describe the aetiology of SIAD and in particular to define the prevalence of undiagnosed adrenal insufficiency. Prospective, single centre, noninterventional, observational study of patients admitted to Beaumont Hospital with euvolaemic hyponatraemia (plasma sodium≤130mmol/l) between January 1st and October 1st 2015. A total of 1323 admissions with hyponatraemia were prospectively evaluated; 576 had euvolaemic hyponatraemia, with 573 (43·4%) initially classified as SIAD. (i) Aetiology of SIAD, defined by diagnostic criteria; (ii) Incidence of adrenal insufficiency. Central nervous system diseases were the commonest cause of SIAD (n=148, 26%) followed by pulmonary diseases (n=111, 19%), malignancy (n=105, 18%) and drugs (n=47, 8%). A total of 22 patients (3·8%), initially diagnosed as SIAD, were reclassified as secondary adrenal insufficiency on the basis of cortisol measurements and clinical presentation; 9/22 cases had undiagnosed hypopituitarism; 13/22 patients had secondary adrenal insufficiency due to exogenous steroid administration. In a large, prospective and well-defined cohort of euvolaemic hyponatraemia, undiagnosed secondary adrenal insufficiency co-occurred in 3·8% of cases initially diagnosed as SIAD. Undiagnosed pituitary disease was responsible for 1·5% of cases presenting as euvolaemic hyponatraemia.

Abstract #120: Undiagnosed Adrenal Insufficiency and The Ill Effects of Thyroid Replacement: Increasing Physician Awareness of Coexisting Endocrinopathies

Abstract #120: Undiagnosed Adrenal Insufficiency and The Ill Effects of Thyroid Replacement: Increasing Physician Awareness of Coexisting Endocrinopathies

Cardiogenic Shock: An Initial Presentation of Primary Adrenal Insufficiency

ABSTRACT Objective: To describe a unique case of a young patient with undiagnosed primary adrenal insufficiency presenting with cardiogenic shock that promptly improved with the administration of stress-dose steroids. Methods: We present the clinical history, physical findings, laboratory results, and imaging studies of a young female presenting with cardiogenic shock. The association between adrenal insufficiency and cardiogenic shock and pertinent literature are reviewed. Results: A 19-year-old Caucasian female was found unresponsive at home. She had a history of a 30-kg weight loss over the past year, salt craving, and generalized hyperpigmentation. An echocardiogram showed severe dilation of the left ventricle and global hypokinesis. Despite hydration, vasopressors, extracorporeal membrane oxygenation, intra-aortic balloon pump placement, and empiric antibiotics, she remained hypotensive. Serum cortisol was undetectable. She was started on stress-dose steroids. Her blood pressure subsequently improved and she was weaned off inotropes, was extubated, and had an improvement of her cardiac function. Adrenal antibodies and 21-hydroxylase antibodies were both positive, suggesting that her adrenal insufficiency was autoimmune in nature. She ultimately made a full recovery. Conclusion: Due to nonspecific symptoms on presentation, primary adrenal insufficiency can be challenging to diagnose. Although the presentation of cardiogenic shock in a patient with undiagnosed adrenal insufficiency is considered a rarity, with hypovolemic shock being more common, practitioners should consider adrenal insufficiency in the differential diagnosis for cardiogenic shock and not delay the institution of stress-dose steroids. Abbreviations: CT = computed tomography CVP = central venous pressure GC = glucocorticoid LV = left ventricle

Abstract #1066: Hyperthyroidism with Hepatitis in the Setting of Undiagnosed Adrenal Insufficiency

Abstract #1066: Hyperthyroidism with Hepatitis in the Setting of Undiagnosed Adrenal Insufficiency

Adrenal insufficiency in asymptomatic adrenoleukodystrophy patients identified by very long-chain fatty acid screening

Plasma assay for very long-chain fatty acids has made it possible to perform large-scale screening of at-risk individuals to identify asymptomatic patients with X-linked adrenoleukodystrophy (X-ALD). We evaluated the burden of undiagnosed adrenal insufficiency in 49 such patients (age, 4.5 +/- 3.5 years). Serum adrenocorticotropic hormone (ACTH) and standard-dose ACTH stimulation test were performed at the baseline and followed prospectively until initiation of adrenal replacement therapy (follow-up, 2 +/- 1.7 years). At baseline, 39 (80%) patients had impaired adrenal function, serum ACTH levels were elevated in 34 (69%) patients, and ACTH stimulation test was abnormal in 21(43%) patients. There was a moderate association between Serum ACTH and age at baseline, ( r = 0.32, P = .05). By the end of follow-up, 86% of patients had borderline or overt adrenal insufficiency (age of onset, 4.8 +/- 3.7 years). We detected a high prevalence of unrecognized adrenocortical insufficiency in asymptomatic boys with X-ALD. It is known to be a frequent cause of morbidity and can be prevented by careful monitoring, early identification of impaired adrenal reserve, and timely initiation of therapy. It manifests early and before onset of neurologic symptoms, suggesting X-ALD as a candidate disorder for neonatal screening.

Clarithromycin Therapy for Mycobacterium avium Complex Bacteremia

Letters15 July 1995Clarithromycin Therapy for Mycobacterium avium Complex BacteremiaRichard A. Chaisson and Constance A. BensonRichard A. ChaissonSearch for more papers by this author and Constance A. BensonSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-2-199507150-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Drs. Singh and Yu wonder whether the increased prevalence of gastrointestinal symptoms and worse survival in patients randomly assigned to receive clarithromycin, 2000 mg twice daily, could reflect undiagnosed adrenal insufficiency. We do not believe that the gastrointestinal toxicity observed in the high-dose clarithromycin arm was a result of adrenal insufficiency. Patients were randomly assigned to one of three treatment arms, and we did not observe significant imbalances in patient characteristics by treatment. Gastrointestinal toxicity is a well-known, dose-related complication of macrolide therapy. Earlier studies of high-dose clarithromycin in patients with HIV infection confirmed the higher incidence of ...

NORMAL PUBERTY IN X-LINKED CYTOMEGALIC CONGENITAL ADRENAL HYPOPLASIA (CCAH)

X-linkcd cytomegalic congenital adrenal hypoplasia (CCAH) is regularly associated with hypogonadotropic hypogonadism.3.2 To our knowledge, we are reporting for the first time a boy with well documented X-linked CCAH and normal pubertal development. The patient's brother had died at 5 6/12 years of age from undiagnosed adrenal insufficiency of recent onset due to histologically confirmed CCAH. Our patient developed primary adrenal insufficiency at 6 6/12 years of age, and has been doing well ever since on physiological replacement doses of hydrocortisone and fludrocortisone. At the time of diagnosis, there were negative or normal results for adrenal and other endocrine autoantibodies, very-long-chain fatty acids, serum and urinary glycerol, serum triglycerides, CK, and urinary organic acids. At 15 6/12 years of age, audiomctry was also documented to be normal.3 Spontaneous onset of puberty was evidenced by testicular enlargement and appearance of pubic hair in his 1 1th and 14th years of life, respectively, and by a corresponding growth spun. At 15 8/12 years of age, he had an adult sized phallus, testicular volume of 20 ml, and pubic hair stage IV (Tanner). Serum FSH (4.8/7.2 U/l) and LH (4.9/20 U/l) before and 30′ after LHRH (60 μg/m2 i.v.), a LH night profile (3 peaks up to 7.6 U/l), and serum testosterone (493 ng/dt) were within the normal range for adult males. Although molecular genetic studies have so far failed to identify a deletion on the short arm of the X chromosome in our patient, this unique case of normal puberty in CCAH supports the suggestion2,4 that a separate gene locus for hypogonadotropic hypogonadism is located distal to the glycerol kinase and CCAH genes.