Diagnosis and management of children with adrenal insufficiency

Adrenal insufficiency (AI) is a rare diagnosis. Symptoms may be vague, easily overlooked or attributed to more common childhood diagnoses. Early diagnosis and treatment is essential as untreated AI may present as adrenal crisis, a potentially fatal condition. Adrenal insufficiency may result from lesions at all levels of the hypothalamic pituitary adrenal axis. Accurate diagnosis is essential as the treatment and prognosis of AI differs according to the site and nature of the lesion. Cortisol is secreted in a circadian manner. Cortisol concentrations rise from the early hours of the morning, peak 30 minutes after waking before falling throughout the day and overnight. Childhood AI is treated with hydrocortisone, which has a short half-life, requiring three to four daily doses. Modified release formulations, which achieve a more physiological cortisol profile and require less frequent dosing, are in development and may become available to children. During periods of illness and injury, children with AI are at risk of adrenal crisis. It is essential that parents and carers are educated in the management of ‘sick days’, can recognise symptoms of adrenal crisis and seek medical advice appropriately. In turn, it is essential that medical staff know how to manage an adrenal crisis in children and young people. In this article, we will briefly review the physiology of the hypothalamic pituitary adrenal axis, causes of AI, options for treatment, methods of monitoring for the adequacy of treatment, and finally the treatment of children with AI during illness and surgery.     

Diagnosis of adrenal insufficiency

Cortisol is a glucocorticoid hormone secreted by the adrenal in a circadian manner in response to adrenocorticotropic hormone (ACTH) released from the pituitary, which is turn is stimulated by corticotropin releasing hormone from the pituitary. Cortisol has a critical role in homeostasis. Cortisol deficiency may present with nonspecific symptoms of lethargy, headache, nausea, abdominal pain, symptoms of hypoglycaemia and failure to thrive or weight loss or acutely with adrenal crisis (hypovolaemia, hypoglycaemia and collapse). Adrenal reserve can be assessed by measurements of cortisol in the early morning from late infancy, over 24 hours, or following the administration of a stimulant acting at the level of the pituitary or adrenal. All of the tests of adrenal reserve have limitations and results should always be interpreted in light of clinical features.     

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??Adrenal insufficiency??AI?? is an uncommon clinical disorder that arises from an inadequate basal or stress level of plasma cortisol. The clinical findings of primary adrenal insufficiency??PAI?? are associated with deficient synthesis or release of glucocorticoids and frequent deficiency of mineralocorticoids. The presentation of adrenal insufficiency may be insidious and difficult to recognize??so it is important to diagnose adrenal insufficiency properly??for an unrecognized or untreated disorder sometimes might be fatal. Once suspected??the exact underlying diagnosis needs to be confirmed by a stepwise diagnostic approach??with an open eye for other differential diagnostic possibilities. The definite diagnosis should be supported by laboratory evaluation on the function of adrenocortical and HPA axis.     

Identification of adrenal insufficiency in pediatric critical illness.

OBJECTIVE: To determine physicians' beliefs and practices regarding adrenal dysfunction in pediatric critical illness. DESIGN: Cross-sectional mail survey. SETTING: Canada. PARTICIPANTS: All members of the Canadian Pediatric Endocrine Group and all physicians identified as practicing pediatric intensive care medicine in any of 16 tertiary care teaching centers in Canada. INTERVENTIONS: Three pediatric intensive care physicians and three pediatric endocrinologists reviewed the questionnaire before administration to ensure clarity. We asked participants to report their views on the following: a) the frequency of adrenal insufficiency in pediatric critical illness; b) diagnosis/definition of adrenal insufficiency in pediatric critical illness; and c) the use of empirical glucocorticoids in fluid/vasopressor-resistant hypotension in pediatric critical illness. MEASUREMENTS AND MAIN RESULTS: Forty-six of 57 (80.7%) endocrinologists responded, with 43 participating (75.4%). Among intensivists, 59 of 70 (84.3%) responded with no refusals. Of intensivists, 81.4% believe that adrenal insufficiency occurs sometimes or often in critically ill pediatric intensive care unit patients, whereas 41.8% of endocrinologists believe adrenal insufficiency occurs never or rarely in these patients. Six definitions of adrenal insufficiency were proposed (varying cortisol level vs. peak/increment of cortisol in response to corticotropin), with no consensus on the definition of adrenal insufficiency from the endocrinologists or intensivists. Half (50.9%) of intensivists said they would sometimes or often empirically treat hypotensive pediatric patients with glucocorticoids, whereas 81.0% of endocrinologists would occasionally or never recommend glucocorticoids on this basis. CONCLUSIONS: There is no consensus among pediatric intensivists or endocrinologists as to how often adrenal insufficiency occurs in pediatric critical illness or how to diagnose this condition. Despite this lack of consensus, however, many pediatric intensivists would empirically treat hypotensive patients who they suspect may have adrenal insufficiency. Prospective studies are required to determine the definition, frequency, and appropriate treatment of adrenal insufficiency in critically ill pediatric patients.     

Diagnosis and management of neonatal adrenal haemorrhage

Three patients with neonatal adrenal haemorrhage (NAH), presenting with various signs and symptoms, are reported. The role of ultrasonography in diagnosis and management of this entity is emphasized. Conservative management is advocated, once the diagnosis is confirmed. Surgery is indicated only for cases of uncontrollable haemorrhage.     

小儿脓毒性休克的诊断与治疗

小儿脓毒性休克（感染性休克）仍是危重患儿的重要死亡原因，近年来由于对脓毒症及休克的研究不断深入，认识的不断提高，以及循证医学证据的不断出现，关于脓毒性休克的定义、诊断及治疗都有了一些明显的变化，本文就这些变化作一简要介绍。     

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??Congenital adrenal insufficiency ??CAI?? comprises a fairly large group of disorders characterized by low production of glucocorticoids with or without low production of mineralocorticoids. Diagnosis of CAI is often delayed due to its unspecific clinical symptoms??and missed diagnosis of CAI or inadequate treatment thereof may be fatal. Recently??new molecular genetic methods have revealed novel genes underlying CAI and have enhanced the knowledge of those disorders. They have the valid managements. Rational substitute treatment may make the patients avoid critical risk and get normal growth and normal live quality. Therefore??the pathogenetic mechanism should be further investigated. Pediatricians should master the keypoints of clinical diagnosis and treatment and try to avoid the risk due to misdiagnosis.     

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各种应激均可使正常的肾上腺分泌皮质醇增多,可较平时增高2~7倍。严重应激状态下血皮质醇水平可高于1mg/L,以适应机体的需要。凡有原发或继发的、急性或慢性的肾上腺皮质功能减退时,就不能产生正常量的皮质醇,应激时更不能相应地增加皮质醇的分泌,因此产生一系列肾上腺皮质激素缺乏的急性临床表现,包括高热,胃肠紊乱,循环虚脱,神志淡漠、萎靡或躁动不安,谵妄甚至昏迷,称为肾上腺危象。强烈的刺激促使机体出现以交感-肾上腺髓质和下丘脑-垂体-肾上腺皮质功能增强为主要特征的一系列神经-内分泌反应,并由此引起机体各种机能和代谢,甚至结构上…     

Diagnosis and management of pediatric closed head injury

Closed head injury in the pediatric population accounts for almost half of all new cases of traumatic brain injury. The incidence of severe brain injury appears to be less in children as compared to the adult population. Over the past several years, advances in recognition and treatment of traumatic brain injury have led to improved outcomes in both children and adults. It is imperative, therefore, for the pediatric surgeon dealing with head trauma to have an understanding of the common brain injuries in the pediatric population, their early recognition and initial management. In this article, early diagnosis and initial management of the most common forms of pediatric closed head injury are reviewed.     

Tests of adrenal insufficiency

AIM—In suspected adrenal insufficiency, the ideal test for assessing the hypothalamo-pituitary-adrenal axis is controversial. Therefore, three tests were compared in patients presenting with symptoms suggestive of adrenal insufficiency.METHOD—Responses to the standard short Synacthen test (SSST), the low dose Synacthen test (LDST), and the 08:00 hour serum cortisol concentration were measured in 32 patients. A normal response to the synacthen test was defined as a peak serum cortisol of ? 500 nmol/l and/or incremental concentration of ? 200 nmol/l. The sensitivity and specificity of the 08:00 hour serum cortisol concentration compared with other tests was calculated.RESULTS—Three patients had neither an adequate peak nor increment after the SSST and LDST. All had a serum 08:00 hour cortisol concentration of < 200 nmol/l. Eight patients had abnormal responses by both criteria to the LDST but had normal responses to the SSST. Three reported amelioration of their symptoms on hydrocortisone replacement. Twenty one patients had a normal response to both tests (of these, 14 achieved adequate peak and increment after both tests and seven did not have an adequate peak after the LDST but had a normal increment). The lowest 08:00 hour serum cortisol concentration above which patients achieved normal responses to both the LDST and SSST was 500 nmol/l. At this cut off value (compared with the LDST), the serum 08:00 hour cortisol concentration had a sensitivity of 100% but specificity was only 33%. CONCLUSION—The LDST revealed mild degrees of adrenal insufficiency not detected by the SSST. The value of a single 08:00 hour serum cortisol concentration is limited.     

Inhaled corticosteroids and adrenal insufficiency

Inhaled steroids are safe at normal doses, but beware very high doses, especially of fluticasone     

Primary adrenal insufficiency in childhood and adolescence: advances in diagnosis and management

OBJECTIVES: Primary adrenal insufficiency occurring in childhood and adolescence is due to abnormalities of gland development, gland responsiveness, and steroid biosynthesis or target organ response. Causes include autoimmune Addison's disease, tuberculosis, HIV, adrenoleukodystrophy, adrenal hypoplasia congenita and syndromes including triple A and IMAGe. We aimed to define the causes of adrenal insufficiency for a cohort of children in Melbourne. METHODS: We reviewed the frequency and variety of presentation of primary adrenal insufficiency to the Royal Children's Hospital over the past 10 years through an audit of patient records, collating demographic information, presentation and investigations. RESULTS: Sixteen cases (13 male, 3 female) of primary adrenal insufficiency were diagnosed at this hospital between January 1993 and July 2003. Median age at presentation was 7.7 years (range: birth to 14.8 years). Symptoms at presentation included weakness, increased pigmentation, abdominal pain, nausea, developmental delay or a reduction in school performance. Four patients presented with adrenal crisis. Median adrenocorticotrophic hormone (ACTH) at diagnosis was 246 pmol/L (range 30-969 pmol/L). Autoantibodies were positive in five patients. Five patients had elevation of very long chain fatty acids. Five patients were diagnosed with autoimmune adrenal insufficiency, five with adrenal hypoplasia congenita, five with adrenoleukodystrophy and one with IMAGe syndrome. CONCLUSIONS: A high index of suspicion results in earlier detection and possible prevention of adrenal crisis with a reduction in associated morbidities. Definitive diagnosis is now possible for almost all cases of primary adrenal insufficiency using technologies for screening autoimmunity, adrenoleukodystrophy (ALD) and genetic screening.     

Tests of adrenal insufficiency.

AIM: In suspected adrenal insufficiency, the ideal test for assessing the hypothalamo-pituitary-adrenal axis is controversial. Therefore, three tests were compared in patients presenting with symptoms suggestive of adrenal insufficiency. METHOD: Responses to the standard short Synacthen test (SSST), the low dose Synacthen test (LDST), and the 08:00 hour serum cortisol concentration were measured in 32 patients. A normal response to the synacthen test was defined as a peak serum cortisol of >/= 500 nmol/l and/or incremental concentration of >/= 200 nmol/l. The sensitivity and specificity of the 08:00 hour serum cortisol concentration compared with other tests was calculated. RESULTS: Three patients had neither an adequate peak nor increment after the SSST and LDST. All had a serum 08:00 hour cortisol concentration of < 200 nmol/l. Eight patients had abnormal responses by both criteria to the LDST but had normal responses to the SSST. Three reported amelioration of their symptoms on hydrocortisone replacement. Twenty one patients had a normal response to both tests (of these, 14 achieved adequate peak and increment after both tests and seven did not have an adequate peak after the LDST but had a normal increment). The lowest 08:00 hour serum cortisol concentration above which patients achieved normal responses to both the LDST and SSST was 500 nmol/l. At this cut off value (compared with the LDST), the serum 08:00 hour cortisol concentration had a sensitivity of 100% but specificity was only 33%. CONCLUSION: The LDST revealed mild degrees of adrenal insufficiency not detected by the SSST. The value of a single 08:00 hour serum cortisol concentration is limited.     

Inhaled corticosteroids and adrenal insufficiency.

Inhaled steroids are safe at normal doses, but beware very high doses, especially of fluticasone