Manifestations Of Adrenal Insufficiency Research Articles

Clinical case of autoimmune polyglandular syndrome type II

The peculiarities of clinical symptoms and the difficulties of diagnosing have been considered on the clinical example of manifestations of autoimmune polyglandular syndrome type II in a young woman. Autoimmune polyglandular syndrome type II is a rather rare pathology, its prevalence is 1 : 20.000 cases of the population. The diagnosis of this disease is determined by the presence of insufficiency of at least two endocrine glands with mandatory adrenal insufficiency. The second component of the disease can be any autoimmune thyroid disease or type 1 diabetes mellitus, which is also autoimmune in nature, or both conditions. Adrenal insufficiency is the initial manifestation of this syndrome in approximately 50% of patients, occurs simultaneously with autoimmune thyroiditis or type 1 diabetes in 20% of patients, the remaining 30% of patients may have a different sequence of manifest components of autoimmune polyglandular syndrome type II. In this article, special attention is paid to the importance of careful monitoring of patients with at least one autoimmune disorder of endocrine organ. The data presents in detail a history of patient who had only type 1 diabetes and autoimmune thyroiditis for 7 years, and the manifestation of adrenal insufficiency was registered 7 years after the manifestation of the primary components of autoimmune polyglandular syndrome type II. The authors highlighted diagnostically significant changes in laboratory methods. The analysis has been performed for the literature data, related to the disease. The necessary to observe patients regularly for quick diagnosis and to reduce the risk of developing both immediate and delayed complications has been emphasized. Special attention should be paid to the examination of relatives of the first line of kinship among patients with the established diagnosis of autoimmune polyglandular syndrome type II for the presence of possible heredity.

Adrenal insufficiency as part of X-linked adrenoleukodystrophy

X-linked adrenoleukodystrophy (X-ALD) is a severe neurodegenerative metabolic disease with a frequency 1:17,000 in newborn boys. Being a major part of X-ALD with an incidence of 70-80% of patients, adrenal insufficiency (AI) is alife-threatening condition without timely treatment. The possibility of developing AI during the whole disease duration and the absence of any predictive factor for AI joining shows the necessity of studying AI in X-ALD patients to optimize current diagnostic and treatment algorithms. To study diagnostic and therapeutic features of primary adrenal insufficiency due to X-ALD. A retrospective observational comparative study was conducted in 66 male patients, examined and treated in the Pediatric endocrinology department of Endocrinology Research Centre, Research Centre for Medical Genetics, Research and Clinical Institute for Pediatrics of the Pirogov Russian National Research Medical University Detached Structural Unit Russian Children's Clinical Hospital (Moscow, Russia) for 2014-2022. All of patients were diagnosedwith primary AI and a genetically confirmed X-ALD. The median age of X-ALD manifestation was 6.6 years [4.7; 11.1]. The earliest age of AI diagnosis was 1.5 years atthe preclinical stage and 1 year 8 months with clinical symptoms. The renin level was studied in 22.7% at the manifestation of AI (15/66 patients), mineralocorticoid deficiency was found in 7 patients. Family history was positive in 39.4% of patients (n=66), only in 15.1% (10/66 patients) of patients the disease was established at the preclinical stage. In 59.1% (n=66) thecerebral form of the disease (cALD) was established, in 16.6% - adrenomyeloneuropathy (AMN), and in 24.2% - isolated adrenal insufficiency (PAI). Age of AI establishment in the group of patients with AMN (15.6 years) significantly differs from the establishment of AI in patients with cALD (7.4 years, p=0.001) and PAI (5.6 years, p = 0.000). Mineralocorticoid therapy was prescribed simultaneously with glucocorticoid therapy in patients with cALD, in AMN and PAI patients it was added after 11and 7 months, respectively (the differences between AMN and PAI groups were insignificant). Combined hormonal therapy receive 41% of patients with cALD, 54.5% of patients with AMN and 60% of patients with PAI. It is necessary to examine all male patients with AI regardless of the manifestation age to exclude adrenoleukodystrophy, and it is also important to examine patients for the presence of AI regardless of X-ALD manifestation age. The assessment of renin level in the manifestation of AI is also needed toprescribe mineralcorticoid therapy timely. Studying family history is the main method to detect X-ALD at the preclinical stage.

Hiccups as the first presentation of secondary adrenal insufficiency associated with advanced cervical cancer.

SummaryHiccups are a common symptom characterized by intermittent spasmodic contraction of the diaphragm. Most hiccups are transient, but some are refractory. Patients with intractable hiccups often have abnormalities of the diaphragm, medulla oblongata, and lesions affecting nerve fibers connecting them. Moreover, electrolyte abnormalities, including hyponatremia, are frequently observed in patients with intractable hiccups. Adrenal insufficiency (AI) is one of the causes of hyponatremia. However, hiccups are not commonly the first presentation. Herein, we describe a case of a 45-year-old woman complaining of refractory hiccups. The patient was initially diagnosed with hiccups associated with cervical cancer metastasis to the liver and peritoneum. The administration of chlorpromazine did not have a beneficial effect on her hiccup. Fasting hypoglycemia and hyponatremia were later found. Her serum cortisol level was low without an elevation of adrenocorticotropic hormone level. MRI of the pituitary gland showed metastatic lesion in the pituitary gland and stalk. Thus, the patient was diagnosed with secondary AI due to cervical cancer metastasis to the pituitary gland and stalk. Administration of hydrocortisone improved her hiccups with the normalization of serum sodium level. Therefore, differential diagnosis in advanced cancer patients with hiccups should include AI-induced hyponatremia.Learning pointsHiccups could be the first manifestation of adrenal insufficiency (AI).Hiccups in patients with AI are often mediated by hyponatremia.Hyponatremia is less frequent in secondary AI than in primary AI. However, hyponatremia can result from increased antidiuretic hormone due to loss of cortisol.The differential diagnosis should include AI-induced hyponatremia if hiccups occur in patients with advanced cancer, as metastasis to adrenal gland or pituitary gland could cause AI.

Особливості перебігу гострих респіраторно-вірусних інфекцій у дітей раннього віку з тимомегалією

Вступ. Особливості перебігу гострої респіраторної вірусної інфекції (ГРВІ) у дітей із збільшеною загрудинною залозою пов’язані з наявністю у хворих більш чи менш значного імунодефіцитного стану та дисгормонозу з проявами наднирникової недостатності. Мета — вивчити особливості перебігу гострих респіраторних вірусних інфекцій та дослідити функцію наднирникових залоз у дітей раннього віку з тимомегалією. Матеріал та методи. У клінічні дослідження було залучено 41 дитину з тимомегалією, хвору на ускладнені форми ГРВІ, віком від 1 місяця до 3 років. Етіологічна розшифровка ГРВІ проводилася методом парних сироваток. Вміст кортизолу в плазмі крові визначався імуноферментним методом. Групу порівняння становили 36 дітей із тимомегалією без проявів ГРВІ впродовж не менше 3 місяців. Результати. Аналіз анамнестичних даних хворих із тимомегалією показав, що більшість із них зазнали впливу несприятливих умов на різних етапах антенатального, інтранатального та постнатального розвитку. Аналіз даних про розміри загрудинної залози вказав на те, що 3–4-й ступінь тимомегалії частіше спостерігався в дітей з ознаками стенозуючого ларинготрахеїту (75,0 %). У 23,5 % хворих на обструктивний бронхіт тимомегалія була 1-го ступеня, у решти — 3-го та 4-го. При необструктивному варіанті ураження бронхів відмічена протилежна тенденція: найменший ступінь збільшення загрудинної залози діагностовано в 62,5 %, а 3-й та 4-й — у 37,5 % хворих (р < 0,05). Найменша забезпеченість кортизолом спостерігалася в гострому періоді стенозуючого ларинготрахеїту (409,4 ± 10,2 нмоль/мл проти 537,7 ± 11,5 нмоль/мл у групі порівняння; р < 0,05). У гострому періоді ГРВІ, що ускладнилася бронхітом, рівень кортизолу не підвищувався і становив 432,3 ± 32,3 нмоль/мл). У групі хворих на пневмонію зареєстровано вірогідне, можливо, компенсаторне підвищення рівня кортизолу (787,3 ± 2,0 нмоль/мл, р < 0,05). При обструктивному бронхіті в гострому періоді відзначена тільки тенденція до збільшення концентрації кортизолу в крові (562,9 ± 18,9 нмоль/мл). Неоднорідним було й відновлення функції кори наднирникових залоз під час одужання дітей раннього віку з тимомегалією. Найбільш значно до фізіологічних показників наблизилися діти, які одужували від гострого бронхіту. Забезпеченість кортизолом хворих на пневмонію на момент одужання практично не відрізнялася від вихідного рівня дітей із ти­момегалією. Найбільш швидко кількість кортизолу збільшувалася в динаміці стенозуючого ларинготрахеїту (до 528,5 ± 22,6 нмоль/мл). Висновок. Діти з тимомегалією становлять групу ризику за розвитком бронхолегеневих ускладнень гострих респіраторно-вірусних інфекцій.

Analysis of clinical manifestations and gene mutations of 13 child patients with rare causes of primary adrenal insufficiency

Objective To analyze the clinical manifestations and gene mutations of rare causes of primary adrenal insufficiency (PAI) in childhood. Methods The clinical features, laboratory tests and gene mutation of 13 patients with PAI in our hospital from September 2010 to August 2017 were analyzed retrospectively. Patients with congenital adrenal hyperplasia, X-linked adrenoleukodystrophy with neurological onset or a clear family history, and autoimmune adrenal insufficiency were excluded. Results The median age of 13 cases (12 males, 1 female) was 3 years and 10 months. Medical history or clinical manifestations on the first visit included hyperpigmentation, electrolyte imbalance/salt-wasting crisis, gastrointestinal symptoms, and fatigue, etc. All developments of external genitalia were normal. All cases presented with decreased serum cortisol and increased ACTH levels. Some of the cases showed decreased aldosterone level and plasma renin activity, while 17α-hydroxyprogesterone, testosterone, and androstenedione were in the normal range. Part of cases revealed delayed bone age and adrenal atrophy. Three gene mutations were detected in 13 patients, including NR0B1 gene (9/13), ABCD1 gene (3/13), and CYP11A1 gene (1/13). NR0B1, and ABCD1 gene mutations were pathogenic mutations, consistent with clinical characteristics. CYP11A1 gene mutation was heterozygote, which cannot fully explain the clinical features. Conclusion PAI in childhood presents common clinical manifestations of adrenal insufficiency, e. g. hyperpigmentation and electrolyte imbalance/salt-wasting crisis, but without specificity. Gene mutational analysis is necessary for precise diagnosis and prognosis estimation. NR0B1 and ABCD1 gene mutations were common in childhood with rare causes of PAI. Key words: Primary adrenal insufficiency; NR0B1 gene; Mutation; Children

An Analysis of the Hypothalamic-Pituitary-Adrenal Axis Functions in Cirrhotic Rats in Response to Surgical Stress

Introduction The activation of hypothalamic-pituitary-adrenal (HPA) axis through severe diseases and stress courses leads to a rise in circulatory cortisol for an adequate response to stress. This axis is one of the important systems that involve in neuroendocrine response to the surgical stress. Hepatoadrenal syndrome that is a manifestation of adrenal insufficiency (AI) in the course of liver disease is described as insufficient production of steroid hormones mainly cortisol due to primary dysfunction of the adrenal gland or secondary malfunction of the HPA axis to provoke the adrenal gland leading to severe illness and increased mortality. Through this evidence, we presented this question as to whether cirrhotic patients have a greater mortality rate than other patients after surgery and if the HPA axis is partly responsible for this phenomenon. Also how the adrenal gland functions during surgery in cirrhotic rats. We conducted this study to assess the effect of cirrhosis on the HPA axis through surgery in cirrhotic rats by evaluating the changes in serum corticosterone level and blood sugar before, immediately, and 30 minutes after surgery. Method This study was performed in the animal lab approved by the Ethics Committee of Tehran University of Medical Sciences in 2014, on 25 male Wistar rats. Thioacetamide was used for induction of cirrhosis in rats with new method of monitoring weekly changes of rats' weight which had 100% success in procedure and reduction in mortality rate. Laparotomy was performed on all of the rats during 9–12 in the morning within 10–15 minutes. Laparotomy was chosen as surgical stress because of its simplicity and feasibility. Three blood samples were obtained from each rat immediately after inducing anesthesia, immediately after the conclusion of surgery, and 30 minutes after surgery. The plasma concentration of corticosterone was measured with enzyme-linked immunosorbent assay test. P value of 0.05 or less was considered as statistical significance. Result Cirrhotic rat group consisted of 15 rats and control group consisted of 10 rats. There was a significant difference in the mean level of corticosterone and blood sugar between the cirrhotic rat group and control group in the 3 time levels (P=0.044/P < 0.001). Pairwise comparison of mean corticosterone and blood sugar levels between case (mean: 249.359 ± 3.90) and control (mean: 262.40 ± 4.69) showed a significant difference (P=0.04, 95% CI = 0.30–25.79/P < 0.001, 95% CI = 129.62–233.96). Unlike the control group, the level of serum corticosterone was compared in the cirrhotic rat group (group 1) before, immediately, and 30 minutes after surgery, which showed a significant difference in our study (P value = 0.005). However, this result was also significant in comparing the blood sugar in 3 time levels of surgery in the control group (P value < 0.001) but not in the cirrhotic rat group (P value = 0.233). Conclusion There was a significant rise in corticosterone levels during 3 time levels of surgery in cirrhotic rats; nevertheless, this elevation was significantly lower than the control group. Also the mean level of blood sugar was higher in the control group than in cirrhotic rats. However, this difference was significant in comparison with the same times of surgery between the two groups. These results approximately can substantiate our hypothesis that AI in the field of cirrhosis would also affect the response of HPA axis to stress during and after surgery that can be concomitant with higher rate of cardiovascular unsteadiness incidences, deteriorating the severity of illness and rise in mortality rate.

Hyperdehydroepiandrosterone in neonates with hypoxic ischemic encephalopathy and circulatory collapse

Circulatory collapse is a very common complication of the critical illnesses in neonates including neonates with hypoxic ischemic encephalopathy; it can be the end result and cause of death of several conditions. Often, despite treatment with fluid resuscitation and vasopressor agents, circulatory collapse persist, and blood pressure can remain critically low, compromising adequate blood flow to vital organs and brain. Low blood pressure has been associated with increased mortality. To investigate adrenal function in newborn infants who suffer from circulatory collapse during hypoxic ischemic encephalopathy. A total of 30 infants were analyzed in the study: 15 neonates in group A (neonates had hypoxic ischemic encephalopathy with vasopressor resistant hypotension) and 15 neonates in group B (neonates with hypoxic ischemic encephalopathy without vasopressor resistant hypotension). All the studied patients were subjected to history, examinations and laboratory investigation including serum cortisol concentrations and cortisol precursor's levels. The cortisol concentrations did not differ significantly between the two groups: (12.9±4.3) μg/dL and (12.1±2.4) μg/dL in group A and group B, respectively. There are highly significant differences between groups A and B regarding Dehydroepiandrosterone (342.1±101.3) μg/dL, (33.4±16.5) μg/dL, respectively. In this study, we noticed that cortisol concentrations did not differ between both groups in contrast to the expectation that neonates with critical illnesses should have higher cortisol concentrations than normal neonates. However, the marked increase in dehydroepiandrosterone DHEA may cause decrease cortisol function, so those neonates having accumulation of dehydroepiandrosterone may suffer from manifestation of adrenal insufficiency and vasopressor resistant hypotension in spite of normal cortisol level.

Adrenal Insufficiency

Adrenal insufficiency means hypo-function of the adrenal cortex, usually glucocorticoid, may be associated with mineralocorticoid and rarely adrenal androgen. It can be categorized into two types: Primary adrenal insufficiency, or Addison’s disease (cortisol low and ACTH high) or secondary/ tertiary adrenal insufficiency due to pituitary or hypothalamic disorders (both cortisol and ACTH are low). Identification of etiology is very important for plan of treatment. The reported incidence of adrenal insufficiency varies greatly depending on the population studied, the test and cut off levels used, and the cause. Many patients may present with adrenal crisis, some of them have subtle symptoms, hyperpigmentation, hypotension, electrolyte imbalance, shock etc. Many of them have iatrogenic adrenal insufficiency with features of Cushing’s syndrome. So, the manifestations of adrenal insufficiency are numerous and nonspecific, and clinicians should have a high index of suspicion and be alert to see important diagnostic clues, such as hyponatremia, hyperkalemia, and hypotension (that are refractory to fluids and vasopressors), diarrhea, weight loss, vomiting, fever etc. without any clear causation. Treatment of adrenal insufficiency is usually life-long, of course based on etiology. Short acting glucocorticoid is better, like hydrocortisone. Patients may be treated with prednisolone. Patients should be provided a “steroid card”. Sometimes it is essential to take patients under “withdrawal protocol”.Birdem Med J 2015; 5(1) Supplement: 43-48

Adrenal Insufficiency In Critically Ill Patients

Adrenal insufficiency means hypo function of the adrenal cortex, usually resulting in low glucocorticoid level and it may be associated with low mineralocorticoid, rarely low adrenal androgen level. It can be categorized into two types: primary and secondary. Primary adrenal insufficiency or Addison's disease is associated with low cortisol and high ACTH level. Secondary/tertiary adrenal insufficiency is due to pituitary or hypothalamic disorders and is associated with both low cortisol and ACTH level. Among critically ill patients (CIP) adrenal insufficiency is not uncommon. The reported incidence of adrenal insufficiency varies greatly depending on the population of critically ill patients studied, the type of test, cut off levels used, and the severity of illness. Several studies have shown increased mortality in patients with very low or very high baseline cortisol levels. Manifestations of adrenal insufficiency in the critically ill patient are numerous and nonspecific, so clinicians are urged to have a high index of suspicion while taking history and doing physical examination and be alert to important diagnostic clues, such as hyponatremia, hyperkalemia, and hypotension, that are refractory to fluids and vasopressor without any clear causation. In current literature there is no consensus level of cortisol (basal/random/stimulated) in critically ill subjects. But it is shown that both high and low cortisol level is associated with increased mortality. In one study Basal Serum Cortisol &lt;414 nmol/L and &gt; 696 nmol/L is shown as indicative of higher risk among critically ill patients. Even with Septicemia or ARDS all subjects don’t suffer from adrenal insufficiency often termed relative adrenal insufficiency or critical illness associated adrenal insufficiency. It has been observed that short term low dose IV hydrocortisone may be beneficial in selective group of patients in intensive care unit (ICU) with critical illness. Diagnosis of adrenal insufficiency associated with critical illness is still challenging for physicians working in ICU. Treatment should be started without delay in emergency situation with Injection Hydrocortisone intravenously or even intramuscularly. Since the condition appears to be common in patients with septic shock, clinicians should have a high index of suspicion for its occurrence in critically ill patients with persistent hypotension despite adequate fluid resuscitation and/or poor hemodynamic response to vasopressor. Adrenal insufficiency associated with other illnesses in ICU are attributed to previous primary or secondary adrenal insufficiency. Treatment with physiologic doses of corticosteroids should be started as soon as possible since short-term treatment carries very few risks and has been shown to decrease both morbidity and mortality. Only suspected cases should be evaluated and could be treated with 100-200 mg Hydrocortisone in divided doses for 5-7 days. Glucocorticoid cannot be recommended as a routine adjuvant therapy in all cases of septic shock or ARDS. But glucocorticoid earned its position among other rescue strategies in subgroups of ICU patients with the highest mortality risk. Steroid use is an art and needs to be used by experienced physician. Otherwise it may do more harm than benefit.Bangladesh Crit Care J March 2015; 3 (1): 27-30

Targeting the annexin 1-formyl peptide receptor 2/ALX pathway affords protection against bacterial LPS-induced pathologic changes in the murine adrenal cortex.

Hypothalamo-pituitary-adrenocortical dysfunction contributes to morbidity and mortality in a high proportion of patients with sepsis. Here, we provide new insights into the underlying adrenal pathology. Using a murine model of endotoxemia (LPS injection), we demonstrate that adrenal insufficiency is triggered early in the disease. LPS induced a local inflammatory response in the adrenal gland within 4 hours of administration, coupled with increased expression of mRNAs for annexin A1 (AnxA1) and the formyl peptide receptors [(Fprs) 1, 2, and 3], a loss of lipid droplets in cortical cells (index of availability of cholesterol, the substrate for steroidogenesis), and a failure to mount a steroidogenic response to ACTH. Deletion of AnxA1 or Fpr2/3 in mice prevented lipid droplet loss, but not leukocyte infiltration. LPS increased adrenal myeloid differentiation primary response gene 88 and TLR2 mRNA expression, but not lymphocyte antigen 96 or TLR4. By contrast, neutrophil depletion prevented leukocyte infiltration and increased AnxA1, Fpr1, and Fpr3 mRNAs but had no impact on lipid droplet loss. Our novel data demonstrate that AnxA1 and Fpr2 have a critical role in the manifestation of adrenal insufficiency in this model, through regulation of cholesterol ester storage, suggesting that pharmacologic interventions targeting the AnxA1/FPR/ALX pathway may provide a new approach for the maintenance of adrenal steroidogenesis in sepsis.

A patient with X-linked adrenal hypoplasia congenital and central precocious puberty caused by a novel NROB1 gene mutation

Objective To explore the possible role of NROB1 gene played in regulating hypothalamic-pituitary-gonad axis(HPGA) by analyzing the clinical and molecular characteristics in a case of central precocious puberty(CPP)with NROB1 gene mutation. Methods Clinical characteristics and direct sequencing of NROB1 gene in the patient were analyzed. Results A 11-month-old boy with manifested premature puberty, enlargement of penis/testes, and penile erection, but without manifestations of adrenal insufficiency was reportd. Clinical diagnosis was adrenal hypoplasia congenita(AHC)with CPP. The NR0B1 gene sequencing revealed a novel mutation in exon 1(913C>T). Conclusion NR0B1 gene mutation may lead to the development of CPP in the patient with AHC. However, the mechanism remains unclear and thus deserves further exploration. (Chin J Endocrinol Metab, 2015, 31: 116-119) Key words: NROB1 gene; Mutation; Adrenal hypoplasia congenital; Central precocious puberty

Morbus Addison

The clinical signs and symptoms of primary adrenal insufficiency are unspecific often causing a delayed diagnosis or even misdiagnosis. In the diagnostic work-up the short synacthen test is regarded as the gold standard. Hydrocortisone and fludrocortisone are the preferred therapy for Addison's disease. The management and surveillance of therapy requires experience and several aspects need to be followed to prevent side effects which might occur due to overtreatment or undertreatment. Very important aspects in therapy are the repeated teaching of the patient and relatives, the issuing of an emergency steroid card and the prescription of a glucocorticoid emergency set. Acute adrenal failure (adrenal crisis), which might be the first manifestation of adrenal insufficiency, is a life-threatening situation requiring immediate glucocorticoid administration and fluid substitution. The most common causes for an adrenal crisis are gastrointestinal infections and fever and discontinuation of glucocorticoid therapy. This article gives an up-to-date overview of diagnostic and therapeutic aspects of Addison's disease.

Diagnosis and Treatment of Adrenal Insufficiency in the Critically Ill Patient

The reported incidence of adrenal insufficiency varies greatly depending on the population of critically ill patients studied, the test and cutoff levels used, and the severity of illness. Several studies have shown increased mortality in patients with very low or very high baseline cortisol levels. Manifestations of adrenal insufficiency in the critically ill patient are numerous and nonspecific, so clinicians are urged to have a high index of suspicion and be alert to important diagnostic clues, such as hyponatremia, hyperkalemia, and hypotension, that are refractory to fluids and vasopressors without any clear causation. Multiple tests have been developed to diagnose adrenal insufficiency, but the most commonly used test in the intensive care unit is the adrenocorticotropic hormone (ACTH) stimulation test. The low-dose ACTH stimulation test has been shown to be more sensitive and specific than the high-dose test; however, the high-dose test is preferred since the low-dose test has not been validated. Although diagnosing adrenal insufficiency continues to be difficult in the critically ill patient, administration of high-dose corticosteroids, defined as methylprednisolone 30 mg/kg/day or more (or its equivalent), over a short period of time provides no overall benefit and may even be harmful; however, administration of low-dose corticosteroids for a longer duration decreases both the amount of the time that vasopressors are required and mortality at 28 days. Hydrocortisone 200-300 mg/day, administered in divided doses or as a continuous infusion, is the preferred corticosteroid in patients with septic shock and should be started as early as possible. For patients in whom the ACTH stimulation test cannot be given immediately, clinicians are urged to consider using dexamethasone until such time that the test can be administered, since, unlike hydrocortisone, it does not interfere with the cortisol test.

Adrenal crisis presenting as an acute abdomen

We report an interesting case of an ‘acute abdomen’. A 63-year-old female was admitted to the Emergency Department with a brief history of severe diarrhoea and rectal bleeding. Colonoscopic findings were normal. Over the next 24 h she developed lower abdominal pain with distension and became hypotensive. Her blood biochemistry results were sodium 133 mmol.l−1, potassium 5.3 mmol.l−1, urea 10.1 mmol.l−1 and creatinine 186 μmol.l−1 Suspecting peritonitis, surgeons performed a laparotomy which revealed a large quantity of uninfected peritoneal fluid, but no perforation of a viscus. Microbiological screening did not reveal any infection. In spite of all measures, she developed multi-organ failure and died a week later. Her past medical history included a head injury 35 years previously and she was maintained on carbamazepine and sodium valproate for post-traumatic seizures. She was hypothyroid on thyroxine supplementation. About 10 years prior to this admission she underwent Keller's operation on her foot and postoperatively had severe seizures and high fever. A few months later she underwent appendicectomy and had a difficult postoperative recovery with seizures and hyponatraemia (113 mmol.l−1), which was attributed to the syndrome of inappropriate ADH secretion secondary to her anti-epileptic medications. On another occasion she was admitted with tonsillitis and developed features of septic shock with a high fever and persistent hypotension requiring fluids and antibiotics. Her only uneventful hospital visit was for an orthopaedic procedure during which she was given a methyl prednisolone injection into her shoulder joint. At post mortem examination, despite a prolonged and extensive search, the adrenal glands were not identified. The thyroid gland was small and the pituitary fossa was considerably enlarged and the pituitary gland was largely replaced by non-functioning fibrous and calcified tissue. On review it appears complications during her previous hospital admissions could have been manifestations of adrenal insufficiency. The only uneventful hospital stay was when she had a steroid injection in her shoulder, which incidentally provided the steroid coverage during the stressful period. In this case, the adrenal failure could have been the result of the head injury she sustained several years earlier, resulting in damage to the pituitary gland. Against this possibility is the enlarged pituitary fossa found at autopsy. She had also suffered from unexplained episodes of headaches, perhaps due to a necrosed pituitary tumour? Histological examination of the pituitary gland revealed calcified and atrophic tissues. Similar cases have been described in the past where the cause was attributed to autoimmune adrenalitis [1]. Acute gastrointestinal symptoms and persistent unresponsive hypotension should raise the possibility of adrenal insufficiency. As our case demonstrates, missing this diagnosis can lead to unnecessary surgical exploration.

Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) in the Irish Population

To determine the Irish prevalence of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), the AIRE mutations involved and clinical features of this population. All patients were identified through paediatricians and endocrinologists in Ireland. Patients were invited to attend a multidisciplinary clinic. Thirty-one patients (2-56 years), 18 female, were identified from 19 families giving an Irish prevalence of 1:130,000. Twenty-six patients had hypoparathyroidism, 21 had adrenal insufficiency (AI) and 10 of 16 had ovarian failure. Three affected patients have died. Many with hypoparathyroidism were resistant to 1-alpha-vitamin D. Two needed daily PTH injections. Mineralocorticoid deficiency as the first manifestation of AI was common. Chronic intra-oral candidiasis affected 25 patients and three had leukoplakia. Two had keratoconjuntivitis. Of 22 with AIRE gene analysis, three different mutations were identified, one of which is novel. APECED is rare in Ireland. We saw a significant amount of non-endocrine disease but no ectodermal dystrophy. AIRE gene analysis reassured many siblings and identified individuals with APECED prior to any symptoms.

Transient Elevation of Serum Growth Hormone Level During Pituitary Apoplexy in Acromegaly

We report a case of acromegaly followed by pituitary apoplexy in which hormonal changes during the course of an acute episode were investigated. Serum growth hormone level increased markedly during the acute phase, and, subsequently, decreased rapidly. Finally, serum growth hormone level remained low and did not respond to stimulation. In contrast, the serum cortisol level remarkably decreased during the most serious stage and returned to the previous level after pituitary apoplexy. The low level of cortisol during the acute phase is compatible with the patient's manifestation of adrenal insufficiency, and hydrocortisone sodium succinate administration improved the critical state of the patient dramatically.

Preoperative Assessment of Adrenal Insufficiency in Glucocorticoid Therapy-Reply

In Reply .—Dr Thygeson asserts that the ACTH test provides the best method of identifying patients at risk of adrenal insufficiency following treatment with glucocorticoids. Thygeson is apparently addressing the specificity of the ACTH test for the possible emergence of intraoperative hypotension rather than sensitivity to the wide spectrum of clinical and biochemical manifestations of adrenal insufficiency. Since the population und[ill] review are patients previously trea[ill] with glucocorticoids and would th[ill] fore be expected to have intact fu[ill] tioning of the renin-angiotensin-[ill] sterone system, the emergence of [ill] potension would be a late event. article by Jasani cited by Thyge[ill] demonstrates that patients with [ill] paired preoperative responses to [ill] poglycemia and/or metyrapone [ill] subnormal cortisol responses dur[ill] surgery; a number of these cas[ill] would not have been identified if [ill] plasma cortisol response to exogen[ill] ACTH had been relied on. The obs[ill] vations that these patients did develop hypotension

Adrenal inhibition in the rat and guinea pig by 2-(p-aminophenyl)-2-phenylethylamine (SK&F 12185)

SK&K 12185 [2-(p-aminophenyl)-2-phenylethylamine] inhibits in vitro corticogenesis by normal rat and guinea pig adrenals stimulated with ACTH, indicating a direct inhibitory effect on the adrenal. The acute and chronic administration of SK&K 12185 prevents the increase in peripheral plasma corticosterone levels of cold stressed rats. The peripheral plasma hydrocrotisone levels of ACTH treated guinea fails to rise following the oral administration of SK&K 12185. Manifestations of adrenal insufficiency are evident by the inability of rats to excrete an acute water load and to survive a cold stress. A natriuresis is evident in the sodium deficient rat which revieved a sodium and water load concomitantly with SK&K 12185. SK&K 12185 is goitrogenic, anethetic or estrogenic.

Adrenocortical insufficiency in infants with the adrenogenital syndrome: A clinical and pathologic study of four cases

<h2>Summary</h2> This paper deals with clinical, chemical, and pathologic observations on fourinfants who presented the picture of adrenal cortical insufficiency in association with bilateral adrenal hypoplasia as shown at autopsy. The condition was found in 0.52 per cent of autopsies done on infants under1 year of age, indicating a higher incidence than is suggested by the literature. The familial pattern which was apparent in two of our patients remains unexplained and requires endocrinologic studies of the mothers of such infants. In our own group and in all eases thus far reported the patients were either female pseudohermaphrodites with a characteristic deformity of the genitalia or else true males. In the latter, external manifestations of virilism are not apparent in early infancy. The presenting clinical features were gastrointestinal symptoms, especiallydiarrhea, vomiting, and dehydration. Serial chemical studies performed in two cases showed a lowering of the"total base," bicarbonate and chloride values in the plasma. The blood sugar levels were found normal in three patients. Anatomic and histologic examination of the adrenals showed diffuse hyperplasia of the cortex with apparent replacement of the zona glomerulosa by eosinophilic cells which often contained fuchsinophil granules. A correlation of these findings with the clinical manifestations is suggested. The physiologic disturbance appears to be one of overproduction with respect to N hormone and underproduction of substances regulating salt and water metabolism. The apparently intact carbohydrate metabolism differentiates these patients from those with true Addison's disease as regards the manifestations of adrenal insufficiency. Further studies of the carbohydrate metabolism in such patients are needed. It is suggested that the administration of DOCA and salt may be a complete substitution therapy in patients exhibiting this syndrome.