Severe Adrenal Insufficiency Research Articles

Severe adrenal insufficiency complicating budesonide therapy for Crohnʼs disease

Severe adrenal insufficiency complicating budesonide therapy for Crohnʼs disease

IMAGe syndrome: Case report with a previously unreported feature and review of published literature

IMAGe syndrome is a rare condition, first reported by Vilain et al., in 1999, characterized by intrauterine growth restriction, metaphyseal dysplasia, congenital adrenal hypoplasia, and genital anomalies. Patients with this condition may present shortly after birth with severe adrenal insufficiency, which can be life-threatening if not recognized early and commenced on steroid replacement therapy. Other reported features in this condition include, hypercalciuria and/or hypercalcemia, craniosynostosis, cleft palate, and scoliosis. We report on a 7-year-old boy with IMAGe syndrome, who in addition to the features in the acronym also has bilateral sensorineural hearing loss which has not been reported in previously published cases of IMAGe syndrome. We discuss the clinical presentation in our patient and review the literature in this rare multisystem disorder.

Polycystic Ovaries and Adrenal Insufficiency in a Young Pubescent Female with Lipoid Congenital Adrenal Hyperplasia Due to Splice Mutation of the StAR Gene: A Case Report and Review of the Literature

We report a case of Lipoid Congenital Adrenal Hyperplasia (LCAH) secondary to Steroidogenic Acute Regulatory (StAR) gene mutation in an adolescent female with bilateral ovarian cysts. StAR gene defects follow an autosomal recessive mode of inheritance and typically present with severe adrenal insufficiency during infancy. Both sexes can be affected equally. XY males often present with sex reversal, while XX females may develop gonadal failure later in life due to premature loss of ovarian follicles. Recently there have been reported cases of successful fertility outcomes in women with LCAH. In our case report, we describe the clinical, biochemical and molecular analysis of a 16 year-old XX adolescent female who was suspected of having LCAH upon discovery of bilateral ovarian cysts in the context of adrenal insufficiency. Examination of the StAR gene revealed a homozygous splice site mutation. The patient is currently undergoing estradiol therapy to suppress ovarian cyst formation.

Adrenal insufficiency in a haemodialysis patient.

Sir, Abnormalities in the hypothalamic–pituitary–adrenocortical (HPA) axis do not usually lead to severe adrenal insufficiency in haemodialysis (HD) patients. However, drug administration may trigger a paradigm shift. A 67-year-old man receiving HD therapy for 4 years was admitted to our hospital due to a traumatic fracture of the right rib. Treatment with nonsteroidal anti-inflammatory drugs was started on the first hospital day. On the sixth hospital day, the patient's body temperature rose to 38.0°C and he became disoriented. His condition worsened over time. A presumptive diagnosis of viral, fungal or tuberculous meningitis was made. Although the patient was given isoniazid, streptomycin sulfate and fluconazole, the fever and disorientation continued and he fell into a coma. On the 18th hospital day, the patient received mechanical ventilation due to Cheyne-Stokes breathing. Repeated blood cultures were found to be negative. Plasmapheresis was performed, but the patient remained in a coma. Four months from admission, adrenal insufficiency was suspected. Nine days later, the patient's body temperature rose to 40.0°C. A blood culture yielded Serratia marcescens. Antibiotic (short-term) and steroid (long-term) therapies were given. The patient became afebrile and was completely free from the coma and disorientation. We evaluated the HPA axis. Corticotropin-releasing hormone (CRH) induced an ACTH response, but not a cortisol response (Figure ​(Figure1b,1b, c). The dexamethasone suppression test lowered the plasma ACTH level. Magnetic resonance imaging did not disclose any structural abnormalities (data not shown). Plasma levels of the pituitary hormones were within the normal range. Insulin reduced the blood glucose levels; however, the responsiveness of ACTH (Figure ​(Figure1f),1f), cortisol (Figure ​(Figure1f),1f), growth hormone (data not shown) and catecholamine (data not shown) was poor. Adrenal insufficiency with a disturbed hypothalamic regulation was strongly indicated. The HPA axis and hypothalamic abnormalities have been descried in HD patients. Reports on adrenal insufficiency in HD patients are rare and diverse (Table ​(Table1)1) and include cases of tuberculous Addison's disease [1], primary adrenal insufficiency and panhypopituitarism due to systemic AA-amyloidosis [2], isolated adrenocorticotropic hormone deficiency [3] and steroid withdrawal in rejected renal allografts [4]. Fig. 1 Time course of stimulation tests to evaluate the HPA axis. Blood levels of aldosterone (▴-▴), cortisol (•-•) and ACTH (-) shown, as well as described in the text, were measured at the Health Sciences Research Institute, ... Table 1 Cases of adrenal insufficiency in haemodialysis patients Our patient was exposed to multiple predisposing factors, such as trauma, infection and drug administration. In infection, a dysfunction of the HPA axis at the hypothalamus–pituitary level has been observed [5]. Fluconazole is an anti-fungal agent capable of interfering with steroid biosynthesis by inhibiting P450-dependent enzyme synthesis [5] and inducing adrenal insufficiency. Central nervous system symptoms may occur in adrenal failure. Importantly, soon after our patient received anti-fungal therapy, his disorientation worsened. This temporal association strongly indicated that fluconasol worsened the adrenal insufficiency. In conclusion, we have described an HD patient with adrenal insufficiency in whom abnormalities of the HPA axis, especially those at the hypothalamic level, emerged. We should bear in mind the possibility that drug administration may promptly induce severe adrenal dysfunction in HD patients with a background of multiple predisposing factors. Conflict of interest statement. None declared.

Ovarian Histological Findings in an Adult Patient with the Steroidogenic Acute Regulatory Protein (StAR) Deficiency Reveal the Impairment of Steroidogenesis by Lipoid Deposition

The steroidogenic acute regulatory protein (StAR) is essential for the production of steroid hormones. The mutations in the StAR gene typically cause congenital lipoid adrenal hyperplasia (lipoid CAH), characterized by severe adrenal insufficiency in both sexes and complete female external genitalia in genetic males. Affected 46, XX females feminize at puberty and menstruate but have progressive hypergonadotropic hypogonadism. It has been hypothesized that the cholesterol accumulation in the steroidogenic cells destroys the residual steroidogenic capacity and progressive ovarian failure occurs (two-hit model). Additionally, ovulation and luteinization in the patients is supposed to be impaired. However, those hypotheses have not been confirmed histologically. We examined whether pathological findings of the ovary in a patient of lipoid CAH corresponded with two-hit model, and whether ovulation and luteinization occurred or not in the patient. The ovary in an adult 46, XX female with a homozygous nonsense mutation (Q258X) in the StAR gene was examined. When the patient was age 22 yr, the ovary was resected because of enlargement with polycysts and subsequent torsion. The affected ovary demonstrated remarkable lipoid deposition and changes of the mitochondrial ultrastructure. Immunohistochemical examination showed decrease of steroidogenic enzymes such as P450 cholesterol side-chain cleavage (P450scc). Additionally, we detected corpus albicans in the affected ovary. This is the first detailed report on ovarian histology in an adult 46, XX female with a null type mutation of the StAR gene (Q258X), which indicates the evidence of the impairment of ovarian StAR-independent steroidogenesis by lipoid deposition.

Allgrove syndrome. Cases report.

The Allgrove syndrome (also known as Triple A syndromes), was described by Allgrove et al. in 1978 as a familiar clinical entity of unknown etiology whose characteristic features are adrenal insufficiency, achalasia and alacrima. The usual presentation is during the first 10 years of life with dysphagia or severe adrenal insufficiency, few new cases have been discovered in adults, whose autonomic symptoms and neurological manifestations such as mental retardation, hyperreflexia, nasal speech, anisocoria, ataxia, postural hypotension and sexual dysfunction are predominant. At the Pediatric Endocrinology Service of Hospital Universitario San Vicente de Paúl, Medellín, Colombia, 5 patients have been identified with the clinical features of Allgrove syndrome. All patients have showed both alacrima and adrenal insufficiency. Achalasia has not been diagnosed in one patient, whose symptomatology is highly suggestive to the syndrome. Mental retardation is the most frequent neurological alteration seen. The mean age of presentation for alacrima was 3.8 years, for adrenal insufficiency was 4.7 years and for achalasia was 7.2 years. An interesting finding and occasionally reported is the presence of hypothyroidism, which is subclinic in three patients, transient hypothyroidism in one patient and clinical hypothyroidism in the other one.

Homozygous Disruption of P450 Side-Chain Cleavage (CYP11A1) Is Associated with Prematurity, Complete 46,XY Sex Reversal, and Severe Adrenal Failure

Disruption of the P450 side-chain cleavage cytochrome (P450scc) enzyme due to deleterious mutations of the CYP11A1 gene is thought to be incompatible with fetal survival because of impaired progesterone production by the fetoplacental unit. We present a 46,XY patient with a homozygous disruption of CYP11A1. The child was born prematurely with complete sex reversal and severe adrenal insufficiency. Laboratory data showed diminished or absent steroidogenesis in all pathways. Molecular genetic analysis of the CYP11A1 gene revealed a homozygous single nucleotide deletion leading to a premature termination at codon position 288. This mutation will delete highly conserved regions of the P450scc enzyme and thus is predicted to lead to a nonfunctional protein. Both healthy parents were heterozygous for this mutation. Our report demonstrates that severe disruption of P450scc can be compatible with survival in rare instances. Furthermore, defects in this enzyme are inherited in an autosomal-recessive fashion, and heterozygote carriers can be healthy and fertile. The possibility of P450scc-independent pathways of steroid synthesis in addition to the current concept of luteoplacental shift of progesterone synthesis in humans has to be questioned.

Molecular pathogenesis of lipoid adrenal hyperplasia and adrenal hypoplasia congenita

Congenital lipoid adrenal hyperplasia (lipoid CAH) is the most severe form of CAH in which the synthesis of all gonadal and adrenal cortical steroids is markedly impaired. Lipoid CAH may be caused by the defect in either the steroidogenic acute regulatory (StAR) protein or the P450scc. More than 34 different mutations in StAR gene have been identified. Clinically, most of the patients manifest adrenal insufficiency from 1 day to 2 months of age, but some patient show delayed onset of adrenal insufficiency. Affected 46, XY subjects do not show pubertal development, whereas affected 46, XX subjects undergo spontaneous feminization, breast development and cyclical vaginal bleeding at the usual age of puberty. X-linked adrenal hypoplasia congenital (AHC) is a rare congenital adrenal disorder characterized by severe adrenal insufficiency and hypogonadotropic hypogonadism. More than 80 different several intragenic mutations of DAX-1 have been identified. The failure of pubertal development may be caused by either abnormal hypothalamic or pituitary regulation of gonadotropin secretion. In addition, although the testicular steroidogenesis is largely intact, the functional maturity of Sertoli cells and also spermatogenesis are impaired. The type of mutation does not predict clinical phenotype. Thus, unified mechanism how DAX-1 gene defect gives rise to adrenal insufficiency, hypothalamic/pituitary hypogonadism and impaired spermatogenesis remains established.

Recent advances in the molecular genetics of congenital and acquired primary adrenocortical failure.

IntroductionIn recent years there have been many advances in ourunderstanding of the molecular pathogenesis of both congenitaland acquired adrenocortical failure (autoimmune or otherwise).As well as providing some fascinating insights into adrenalgland development and steroid hormone biosynthesis, therecognition of these various distinct disorders, either at aclinical or molecular genetic level, often has implications forthe management of the patient and their immediate family. In thispaper, we review the salient clinical and molecular features of thevarious causes of primary adrenocortical failure (Table 1).Genetics of autoimmune Addison’s diseaseAutoimmune Addison’s disease (AAD) is a chronic disorder ofthe adrenal gland, characterized by insufficiency of adrenocor-tical hormones due to autoimmune destruction of steroidogenicadrenocortical cells (Oelkers, 1996). The cytochrome P450enzymes involved in steroidogenesis, including 21-hydroxylase(Baumann-Antczak et al., 1992; Winqvist et al., 1992), 17-hydroxylase (Krohn et al., 1992) and side chain cleavageenzyme (Winqvist et al., 1993) have been identified as primaryautoantigens in AAD. With the overall decrease in theprevalence of tuberculosis, AAD has emerged as the mostcommon cause of primary adrenal failure in developedcountries (Nerup, 1974; Kong & Jeffcoate, 1994). Nevertheless,AAD is a relatively rare endocrinopathy; recent epidemiologi-cal studies showing an estimated prevalence in the generalEuropean population of about 100 per million (Kong J Laureti et al., 1999).The results of human leucocyte antigen (HLA) typing, takentogether with the clinical heterogeneity of presentation anddifferent modes of inheritance, have suggested distinctpathogenic bases for different forms of AAD. Thus, AADmay occur in isolation, as a manifestation of the autoimmunepolyendocrinopathy type 1 syndrome (APS1), or as part of theautoimmune polyendocrinopathy type 2 (APS2) syndrome(Table 1) (Spinner et al., 1968; Neufeld et al., 1981; Maclaren& Riley, 1986).Autoimmune polyendocrinopathy type 1 syndrome: amonogenic autoimmune disorderIn the autoimmune polyendocrinopathy type 1 (APS1)syndrome, which is also known as the autoimmune poly-endocrinopathy, candidiasis and ectodermal dystrophy(APECED) syndrome, AAD occurs in association withautoimmune hypoparathyroidism, chronic mucocutaneous can-didiasis and other organ-specific autoimmune disorders. Theseinclude type 1 diabetes, primary gonadal failure, perniciousanaemia, chronic active hepatitis and hypothyroidism (Neufeldet al., 1981; Ahonen et al., 1990). The age of onset of AAD inAPS1 is typically between 11 and 15years, although othermanifestations of APS1 (e.g. hypoparathyroidism and candi-diasis) are likely to present at an earlier age. APS1 is amonogenic disorder with autosomal recessive inheritance,affecting both sexes with equal prevalence (Ahonen, 1985),and is rare in most populations. However, because of foundereffects, it is relatively common in the Finnish population andIranian Jews with estimated prevalences of 1/25000 and 1/9000, respectively (Ahonen, 1985; Zlotogora & Shapiro, 1992).Initial genetic studies of APS1 focused on HLA, and noassociation of this disorder with any specific HLA haplotypehas been found (Neufeld et al., 1981; Maclaren & Riley, 1986;Aaltonen et al., 1993; Huang et al., 1996). The gene underlyingAPS1 was subsequently localized on chromosome 21q22 bylinkage analysis (Aaltonen et al., 1994) and identified bypositional cloning (Finnish-German APECED consortium,1997; Nagamine et al., 1997). This gene, designated auto-immune regulator-1 (AIRE-1), encodes a 545 amino acidprotein that has two plant homeodomain (PHD)-type zinc-finger motifs, suggesting a role as a transcription factor(Finnish-German APECED consortium, 1997; Nagamine etal., 1997). AIRE-1 mRNA is expressed in lymphoid tissuesincluding thymus, lymph node and spleen, and possibly also inother tissues including the adrenal cortex (Finnish-GermanAPECED consortium, 1997; Nagamine et al., 1997), whichsuggests that it may have an important role in the developmentof a normal immune response.

Severe Early-Onset Obesity, Adrenal Insufficiency and Red Hair Pigmentation Caused by POMC Mutations in Humans

Severe Early-Onset Obesity, Adrenal Insufficiency and Red Hair Pigmentation Caused by POMC Mutations in Humans

Plasma concentration of cytokine antagonists in patients with HIV infection.

There is increasing evidence that cytokines contribute to the immunopathogenesis of human immunodeficiency virus (HIV) infection. It may be, therefore, that compensatory rises in circulating cytokine antagonists also occur in HIV infection and that such changes mark disease progression. To test this idea, plasma concentrations of the cytokine antagonists alpha-melanocyte-stimulating hormone (alpha-MSH), interleukin-1 receptor antagonist (IL-1ra), and soluble tumor necrosis factor receptor (sTNFr) were measured in patients of different Centers for Disease Control (CDC) categories of HIV infection and in seronegative controls. Plasma levels of all these cytokine antagonists were higher in HIV-infected patients. IL-1ra and sTNFr concentrations were correlated with indicators of disease activity: positively with plasma neopterin and negatively with CD4+ T lymphocyte counts. alpha-MSH and sTNF r were greater in CDC groups III and IV, whereas IL-1ra was elevated only in the latter group. Because cytokines activate the hypothalamic-pituitary-adrenal axis and adrenal steroids inhibit cytokine production, we measured circulating adrenocorticotropic hormone (ACTH) and cortisol in HIV-infected patients and investigated relations among these hormones, cytokine antagonists, and markers of disease progression. It appears that these physiological modulators of cytokine activity are not closely linked to sTNFr, IL-1ra and alpha-MSH: there were no significant correlations between plasma concentrations of ACTH or cortisol and those of cytokine antagonists, nor were there correlations between hormones and markers of disease progression such as neopterin or CD4+ T cell counts. It is notable that severe adrenal insufficiency was extremely rare (3%) in HIV-infected patients; it was confined to the AIDS group and was consistently secondary to ACTH deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Mineralocorticoid activity of liquorice: 11-beta-hydroxysteroid dehydrogenase deficiency comes of age.

The sodium retention associated with liquorice ingestion has been thought to be due to a direct mineralocorticoid effect, despite the fact that it does not seem to occur in patients or animals with severe adrenal insufficiency. This study in seven normal subjects given liquorice showed that sodium retention is associated with a significant change in cortisol metabolism indicating inhibition of 11-beta-hydroxysteroid dehydrogenase (11 beta-OHSD). Congenital deficiency of this enzyme produces a syndrome of apparent mineralocorticoid excess. It is suggested that in both conditions there is a defect in the renal conversion of cortisol to cortisone by 11 beta-OHSD which results in high intrarenal cortisol levels, acting on type 1 mineralocorticoid receptors to cause sodium retention.

Congenital lipoid adrenal hyperplasia in an eight-year-old phenotypic female.

Congenital lipoid adrenal hyperplasia (CLAH) was described as an invariably fatal disease in infancy manifested by severe adrenal insufficiency with lack of differentiation of the external genitalia in males. A genetic defect in cholesterol desmolase was postulated to be the site of the enzymatic block. However, Degenhart et al. demonstrated by in vitro studies that the defect may be in the cholesterol 20-hydroxylase enzyme. Urinary studies of an 8-yr-old phenotypic female with severe adrenal insufficiency who was found to have bilateral testes were performed with corticotropin stimulation. Analysis of the urines by gas chromatograph-mass spectrometer revealed elevated cholesterol excretion and the absence of additional sterols. The 17-hydroxycorticosteroids were 0; 17-ketosteroids ranged from 0.3 to 0.6 mg per 24 hr. The presence of some 17-ketosteroids suggests that an alternate pathway from cholesterol to dehydroepiandrosterone without formation of C-21 compounds may exist. The absence of urinary chole...

The diagnostic value of sodium tolbutamide in hypoglycemic states.

Intravenous sodium tolbutamide tests were performed in patients with 1) proven insulomas, 2) functional hyperinsulinism, 3) mild diabetes mellitus and associated postprandial hypoglycemia, 4) severe adrenal insufficiency, and 5) liver disease. Healthy subjects were used as controls. Administration of sodium tolbutamide to patients with functioning islet-cell adenomas usually produced a greater degree of hypoglycemia than was observed in the other subjects studied. Of much greater significance, however, were the prolonged periods of hypoglycemia in the insuloma patients. After removal of the insulomas the response to tolbutamide became normal. Persistence of tolbutamide-induced hypoglycemia: 1) is a valuable adjunct in the diagnosis of insuloma, 2) is due, in part, to release of excessive amounts of insulin from the insuloma, and 3) is supportive evidence that the primary mechanism of action of the sulfonylureas is release of pancreatic insulin. From a clinical point of view the intravenous tolbutamide tes...

Addisonian crisis and appendicitis: a case report.

Case Reports1 June 1955ADDISONIAN CRISIS AND APPENDICITIS: A CASE REPORTHELMUT O. HAAR, M.D., MARTIN E. SILVERSTEIN, M.D., XENOPHON C. CALLAS, M.D., ALLAN SMALL, M.D., THOMAS H. MCGAVACK, M.D., F.A.C.P.HELMUT O. HAAR, M.D.Search for more papers by this author, MARTIN E. SILVERSTEIN, M.D.Search for more papers by this author, XENOPHON C. CALLAS, M.D.Search for more papers by this author, ALLAN SMALL, M.D.Search for more papers by this author, THOMAS H. MCGAVACK, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-42-6-1280 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe clinical picture of acute adrenal insufficiency may closely simulate that of acute abdominal inflammatory disease. The term "pseudoperitonitis" has been used to describe this syndrome.3 Therefore, a differential diagnosis between Addisonian crisis and an acute abdominal inflammation can sometimes be very difficult.3, 14Surgical procedures in cases of severe adrenal insufficiency are likely to lead to fatal results.2, 8, 11A careful examination for any manifestation of impending crisis is therefore indicated in every Addisonian patient with symptoms of acute abdominal disease. It is equally important in all persons with chronic abdominal pain for whom surgery is considered necessary...Bibliography1. BartelsJohnson ECC: Surgery in Addison's disease, Lahey Clinic Bull. 7: 200-207, 1952. MedlineGoogle Scholar2. Brezeau I: Med. Romana II, 4: 25, 1947. Google Scholar3. DettreMera GZ: Addison's disease and appendicitis, Wien. klin. Wchnschr. 62: 492, 1950. MedlineGoogle Scholar4. GreeneWaltersRowntree CHWLG: Surgical operations in Addison's disease: successful epididymectomy and orchidectomy for tuberculosis, Ann. Surg. 98: 1013, 1933; and Proc. Staff Meet., Mayo Clin. 7: 238, 1932. CrossrefMedlineGoogle Scholar5. KeyOdellTaylor JARTLW: Failure of cortisone to delay or to prevent the healing of fractures in rats, J. Bone and Joint Surg. 34-A: 665, 1952. CrossrefGoogle Scholar6. Laipply TC: Addison's disease due to cytotoxic contraction of adrenal cortex with sudden death four days after appendicitis, Ohio State M. J. 39: 652, 1943. Google Scholar7. Leavitt P: Addisonian crisis precipitated by acute appendicitis, New York State J. Med. 45: 1987 (Sept.) 1945. Google Scholar8. Moene I: Death after operation for chronic appendicitis in patient, Nord. med. 37: 643 (Mar.) 1948. MedlineGoogle Scholar9. PearsonWestWhitmoreRandall OHCDWFHT: Physiological effect of bilateral adrenalectomy in man, J. Clin. Investigation 31: 653, 1952 (in Soc. Proc.). Google Scholar10. RowntreeSnell LGAM: Clinical experience with Addison's disease, Ann. Int. Med. 3: 6, 1949. Google Scholar11. Rowntree LG: Clinical studies in Addison's disease, 1931, W. B. Saunders Co., Philadelphia. Google Scholar12. SchwartzDerrickPapper HSEM: The influence of anesthesia, operation and obstetrical delivery upon patients with adrenal cortical insufficiency, Surg., Gynec. and Obst. 94: 455, 1952. MedlineGoogle Scholar13. Siebenmann R: Die Wirkung von Desoxycorticosterone acetate (DCA), Ascorbinsaeure und Cortisone (compound E) auf die Formalinarthritis der Ratte, Schweiz. Ztschr. f. Path. u. Bakt. 15: 174, 1952; abstract Am. J. Clin. Path. 22: 998, 1952. MedlineGoogle Scholar14. Soffer L: Diseases of the endocrine glands, 1951, Lea and Febiger, Philadelphia. Google Scholar15. SpraguePowerMasonAlbertMathiewsonHenchKendallSlocumbPolley RGMHHDADRSECCHHF: Observations on the physiologic effect of cortisone and ACTH in man, Arch. Int. Med. 85: 199, 1950. CrossrefGoogle Scholar16. TaubenhausAmromin MSD: The effects of hypophysis, thyroid, sex steroids and the adrenal cortex upon granulation tissue, J. Lab. and Clin. Med. 56: 7, 1952. Google Scholar17. ThornForshamFrawleyWilsonRenoldFredericksonJenkins GWPHTGDLAEDSD: Advances in the diagnosis and treatment of adrenal insufficiency, Am. J. Med. 10: 595, 1951. CrossrefMedlineGoogle Scholar18. ThornDorranceDay GWSSE: Addison's disease—evaluation of synthetic desoxycorticosterone acetate therapy in 158 patients, Ann. Int. Med. 16: 1053, 1946. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y.*Received for publication June 1, 1954.From the New York Medical College, Metropolitan Hospital Research Unit, Welfare Island, New York, N. Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1955Volume 42, Issue 6Page: 1280-1284KeywordsAbdominal painAbdominal surgeryAppendicitisInflammation ePublished: 1 December 2008 Issue Published: 1 June 1955 PDF downloadLoading ...

Urinary alpha-ketolic steroid metabolites of cortical hormones administered to subjects with adrenal cortical insufficiency.

The analysis of urinary excretory products following the administration of known compounds is one of the classical methods for the study of their metabolism. The developments inpaper chromatographic (1) and micro-analytic (2) technics and the use of glucuronidase hydrolysis (3) have considerably decreased the difficulties of investigating steroid metabolism by this method. Using these newer technics, we have studied the urinary excretion pattern of the major alpha-ketolic steroids after the administration of the six active adrenal cortical steroids to individuals with severe adrenal cortical insufficiency. We have found, as has been demonstrated for other steroids (4), that the major alpha-ketolic metabolites result from the reduction in ring A of the steroid nucleus to the 3-alpha-hydroxy pregnane derivatives (the socalled tetrahydro form) and that the hydroxyl and ketone groups on carbon atom 11 are interconvertible for corticosterone and 1 1-dehydrocorticosterone as well as for hydrocortisone and cortisone.

Adrenal Function in Chronic Pulmonary Tuberculosis

The frequency, extent and importance of adrenal involvement in pulmonary tuberculosis, and the role of the adrenal in the clinical symptomatology of this disease have been the subject of widely divergent opinions for many years. This lack of unanimity has a variety of reasons, some of fundamental Importance. All too often, judgment as to the presence or absence of adrenal cortical hypo-function has been based solely on clinical criteria such as gastrointestinal disturbances, asthenia, hypotension, and so forth; these symptoms, though usually present in severe adrenal insufficiency, are by no means pathognomonic, and their significance is particularly difficult to interpret in a disease such as tuberculosis where intestinal lesions, malnutrition, and debility are so common. Thorn’ states, as a matter of fact, that the differential diagnosis of Addison’s disease may present great difficulty “in patients with established tuberculosis elsewhere (i.e., not in the adrenal) whose excessive weakness, gastrointestinal symptoms or pigmentation raises the question of adrenal involvement” unless detailed studies of adrenal function are performed. The small, globular heart which forms part of the clinical picture of the now discredited “habitus phthisicus” and which was thought to bear some relationship to the small heart commonly found in Addison’s disease has been shown by us to have no relation to adrenal function, as far as could be judged by available criteria.2 Even isolated biochemical data may be misleading in this problem, for low serum sodium values have been observed in patients with chronic pulmonary tuberculosis but without any evidence of adrenal failure.3 Other biochemical attempts to study adrenal function by highly roundabout means have served only to confuse the picture further. Trautwein,4 studying liver glycogen in tuberculous patients by indirect tests, found that depletion of liver glycogen exists in such patients, and that repletion could be induced by the administration of adrenal cortical substance. This and similar data were considered to be evidence of adrenal cortical insufficiency. Actually, they merely demonstrate well-known physiological effects of adrenal cortical hormones, and can be observed clinically as well as In starved nonadrenalectomized animals. Experiments of this type, then, cannot add to our knowledge of the adrenal status in tuberculosis. Abderhalden and Abderhalden5 claim that certain urinary proteases reflect adrenal cortical activity. On the basis of this measurement, they state that nearly all severe cases, as well as 36 per cent of “mild” cases of tuberculosis show disturbance of adrenal function.

ACTIVITY OF DESOXYCORTICOSTERONE ACETATE IN PROPYLENE GLYCOL BY ORAL AND INTRAVENOUS ROUTES IN ADRENALECTOMIZED DOGS, AND ITS EFFECT ON THE CARDIAC ARHYTHMIA OF ADRENAL INSUFFICIENCY

THE SUBLINGUAL ADMINISTRATION of desoxycorticosterone acetate in propyleneglycol was introduced recently by Anderson, Haymaker and Henderson (1) in the treatment of Addison's disease. They found this method to be as effective as subcutaneous or intramuscular injections of the hormone in oil, while the ingestion of tablets of desoxycorticosterone acetate was of no value. It seemed desirable to test the effectiveness of this material in a laboratory animal. Adrenalectomized dogs were chosen for the investigation since a study had been made on the maintenance of such animals by injections of desoxycorticosterone acetate in oil and this would provide a basis for comparison (2). Oral administration of desoxycorticosterone acetate in propylene glycol was undertaken on dogs previously maintained by daily injections of hormone and the value of intravenous injections of the same material was invests gated in dogs suffering severe adrenal insufficiency.

Relative Effectiveness of Several Methods of Administering Desoxycorticosterone Acetate1

SUCCESSFUL HORMONE THERAPY depends in a large measure upon three factors, a) a satisfactory hormone preparation of uniform potency, b) moderate cost of adequate therapy and c) a convenient and effective method of administering the hormone. Desoxycorticosterone acetate, a synthetic adrenal cortical hormone, has been employed successfully in the treatment of patients with severe adrenal cortical insufficiency (1). The crystalline hormone preparation ensures uniform potency and it is possible to maintain an effective concentration of hormone by means of a single, daily intramuscular injection of the hormone in oil or by the subcutaneous implantation of pellets of crystalline hormone at intervals of 12 to 14 months. Furthermore, most patients can afford the cost of synthetic hormone therapy. Limiting factors in the exclusive use of desoxycorticosterone therapy are its deficiency in the ‘carbohydrate regulating factor’ of the adrenal cortex and the care which must be exercised in the administration of this pre...

Acid Intoxication of Adrenal Insufficiency in Dogs.

Recent work on the blood chemistry of dogs and cats suffering from adrenal insufficiency suggests the probability that the adrenal cortex secretes a hormone which in some manner controls the normal functioning of the kidney. Several investigators1 report marked nitrogen retention following adrenal removal. Swingle2 and Swingle and Eisenmann3 demonstrated phosphorus retention, and the existence of an uncompensated non-volatile acidosis in severe adrenal insufficiency. The acidosis was considered to be due to retention of the acid end products of normal metabolism.Owing to the difficulty of bleeding cats repeatedly, and the fact that considerable quantities of blood are necessary for analysis, the writer made a detailed investigation of the acid intoxication following adrenal removal in dogs.Adult male and non-pregnant dogs were employed, an interval of 5 to 10 days elapsing between operations. Longer intervals were not found to prolong the survival period, the average survival period to date being 5½ to 6 ...