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An infant treated with synthetic β1–24-corticotrophin (“Synacthen” CIBA) developed antibodies against the biologically active part of the ACTH molecule. Using a radioimmunological method the binding of ACTH to the patient’s serum was identified as an antigen-antibody reaction. The fatal course of an infection in this child might be explained by acute adrenal failure due to blocking anti-ACTH antibodies. The possible danger of introducing antibodies against the biologically active part of the ACTH molecule by long-term treatment is stressed.

Summary A 7 1/2-year-old boy in whom the diagnosis of congenital adrenal hyperplasia was made at age 5 weeks is presented. Treatment with exogenous corticoids was started immediately, but between ages 1 to 4 an Addisonian state intervened. Classical congenital adrenal hyperplasia then reappeared after age 6, following a reduction in corticoid replacement. Suppression of ACTH by exogenous glucucorticoid is suggested as a possible cause of this reversible adrenal failure.

Though pathological studies have shown that administration of adrenal steroids can cause adrenocortical atrophy in experi mental animals (Ingle, 1938 ; Winter et al., 1950 ; Rawls et al., 1954 ; Holub et al., 1959) and in man (Sprague et al., 1950, 1951 ; Salassa et al., 1953 ; Bennett, 1954 : Stoner and Whiteley, 1954), biochemical studies have revealed that the adrenal glands are capable of responding satisfactorily to corticotrophin (A.C.T.H.) stimulation despite many years of steroid therapy (Fredell et al., 1955 ; Larzelere et al., 1957 ; Carreon et al., 1960 ; Andersson and Kjerulf, 1961 ; Robinson et al., 1962 ; Savage et al., 1962 ; Brinck-Johnsen et ed., 1963 ; Treadwell et al., 1963). Even when a subnormal increase in plasma 17-hydroxysteroids (17-OHCS ; cortisol) is found during an infusion of A.C.T.H., a significant increase has been recorded with more prolonged adrenal stimulation (Eik-Nes et al., 1955 ; Christy et al., 1956 ; Sandberg et al, 1957 ; Krusius and Oka, 1958 ; Landon et al., 1965). There do not appear to be any reports on adrenal function during attacks of status asthmaticus in patients receiving long term steroid therapy. The present paper describes the plasma 17-OHCS response to the administration of A.C.T.H. in 17 such patients with status asthmaticus.

The past decade has seen significant advances in our understanding of the genetic aetiology of several forms of adrenal failure that present in infancy or childhood. Several of these disorders affec

We have presented the first documented description of the induction of adrenal failure from invasion by a lymphoma. Although adrenal involvement may be common in this disease, which often involves the retroperitoneum, adrenal failure is still unusual. Our case suggests that clinical suspicion must be heightened when lymphoma is present. In particular, adrenal function tests are indicated for patients who have CT evidence of bilateral adrenal invasion from any source, including lymphoma.

Sir. — Dr Brouhard's editorial "Surreptitious Insulin Administration" in the January issue of AJDC discussed an important cause of unexplained hypoglycemia in the type I diabetic patient. Surreptitious insulin administration be considered seriously in any diabetic with drastically reduced insulin requirements. However, Dr Brouhard failed to mention the possibility of autoimmune adrenalitis presenting similarly. Any type I diabetic patient is at risk for other autoimmune disease as part of an autoimmune polyglandular syndrome. Although adrenal failure is uncommon in the pediatric patient, the life-threatening nature of this condition makes early diagnosis essential. Autoimmune adrenalitis should be considered in all type I diabetics with unexplained hypoglycemia, especially those with other autoimmune diseases (most commonly autoimmune thyroiditis) or a family history of an autoimmune polyglandular syndrome.

A normal plasma cortisol response to exogenous corticotropin has been advanced as a reliable indication of adequate hypothalamic-pituitary-adrenal function in patients suspected of having secondary adrenal failure. We have examined the validity of this diagnostic strategy in five patients who had undergone hypophysectomy and 27 patients recently treated with glucocorticoids. Eleven of the patients had normal adrenal responses to cosyntropin but had subnormal responses when the entire hypothalamic-pituitary-adrenal axis was examined using metyrapone; no patient who responded normally to metyrapone failed to respond to cosyntropin. Inducing hypoglycemia with insulin yielded results concordant with the results induced by metyrapone in four patients tested. A normal cortisol response to corticotropin alone should not be relied on to exclude secondary adrenal insufficiency. To do this it is necessary to demonstrate normal activity of the entire hypothalamic-pituitary-adrenal axis, which can be conveniently examined using metyrapone.

Selective adrenal phlebography is useful in detecting small adrenal tumors. 1-4 However, there are several disadvantages inherent in this technique. First, about 5% of patients are sensitive to contrast media—a factor precluding the use of this method. Second, even in the most experienced hands, it is frequently impossible to direct the catheter into one of the adrenal veins, particularly the right one. Third, the technique requires the availability of a radiologist with great expertise in the manipulation of a catheter. The fourth and major disadvantage is the occasional occurrence of rupture of intra-adrenal capillaries in the course of the procedure, with extravasation of contrast material and hemorrhage into the gland. 5 This complication may result in destruction of all glandular tissue within the capsule. 4,6,7 There have been recent 8-11 reports on the advantages of a new technique, adrenal photoscanning, for the diagnosis of adrenal abnormalities. In the course of

Addison's disease is rare in childhood. In reviewing the literature prior to June, 1945, Jaudon 1 found 12 cases in children aged 10 years or less. Since that time only 12 cases have been reported in the available literature. 2-11 Cases of adrenal failure associated with the adrenogenital syndrome were excluded, as were cases occurring before the age of 2 years, because these appear to be a separate group of patients. 12 Among these 12 cases reported, 5 were associated with hypoparathyroidism or moniliasis or had a sibling with this combination of diseases.8-11 Four of these five occurred in two families in which other cases of "the syndrome of familial juvenile hypoadrenocorticism and superficial moniliasis" 13 occurred. In none of these cases associated with hypoparathyroidism and/or moniliasis was tuberculous involvement of the adrenal found. Tuberculosis is becoming an unusual cause of Addison's disease in childhood, as it has become in

This brief, 538 page, book on diseases of children impresses me as quite a remarkable accomplishment for a single author. The diseases of childhood are well covered, the description of disease excellent, and the therapy clear and precise. The illustrations are good. The treatment and prevention of asthmatic attacks with physiotherapy taught to the mother sounds very encouraging and makes me wonder if good instruction in physiotherapy of diseases of the chest is more easily available in England than it is in many parts of the United States. I like the advice to close the defect of a meningo-myelocele immediately after birth whatever the ultimate prognosis, for leaving an unsightly sack on the babies' backs which may rupture and is always prone to infection has never seemed like good therapy to me. An occasional statement such as that the shock of acute meningococemia is caused by adrenal failure and that

Our objective is to estimate frequencies of mutations in STAR, CYP11A1, NR0B1, NR5A1, MC2R, and MRAP in a cohort of Japanese patients with primary adrenal failure without enzymatic defects. Twenty-one patients were included, who were diagnosed as having primary adrenal failure without enzymatic defect, namely 21-hydroxylase deficiency, 3βHSD deficiency, 11β-hydroxylase deficiency, and P450 oxidoreductase deficiency. Sixteen patients presented with primary adrenal failure before the age of 2 years. Fourteen patients had apparent mineralocorticoid deficiency. Fourteen patients were 46, XY and 7 patients 46, XX. Three had 46, XY disorders of sex development. Mutation analyses of STAR, NR0B1, NR5A1, MC2R, and MRAP were done by PCR-based sequencing and next generation sequencing. In case of no amplification of NR0B1 by PCR, we performed oligonucleotide array CGH. We descried clinical findings in each patients and determined possible genotype-phenotype correlation. Five patients were diagnosed as having DAX-1 deficiency. NR0B1 mutations were found hemizygously in 3 patients (c.116delG, c.846_865del, and p.Q283X). NR0B1 deletions were found in 2 patients (400kb deletion including NR0B1 and 2.4kb deletion of exon 1). Four patients presented with primary adrenal failure in newborn, and the other patient presented at the age of 6 years. STAR mutations were found in 3 patients. One patient was 46, XY, and 2 patients were 46, XX. One patient, who presented with primary adrenal failure in newborn, had c.712delA/p.Q258X. Two patients, who presented at preschool age, had p.Q258X/p.R272C and p.Q258X/p.R188H. No mutations were found in CYP11A1, NR5A1, MC2R, and MRAP. In conclusion, NR0B1 mutations and deletions are relatively common in 46, XY normal male phenotype patients (5/11). STAR mutations might be found in cases, being older than 2 years of age. 3. CYP11A1, NR5A1, MC2R, and MRAP mutations are rare.