Background: TB was once a common cause of primary adrenal insufficiency, it is now most often autoimmune in the developed world, but there are rarely observed infectious causes, including TB, Fungal, and CMV. The extra-adrenal manifestations typically stem from pulmonary TB. When TB invades the adrenals, imaging of the adrenal glands initially shows hypertrophy, which progresses to fibrosis and calcification in almost half the cases. This adrenal hypertrophy is often a key marker for differentiating tuberculous adrenal insufficiency from autoimmune adrenalitis, in which case adrenals are usually atrophied. Case: A 62 year old woman with a history of CKD, hyperlipidemia, and possible heart failure presented to the hospital with a 3 week history of worsening right knee pain. She was initially hypotensive at 68/48. Her hospital course was complicated by renal failure, persistent hypotension, and hyponatremia. She received approximately 5 liters of fluid with no significant hemodynamic response. Initial labs showed sodium of 125 with normal range 135-145 and a creatinine of 3.63 with sodium levels hovering in the low 130’s throughout the next 8 days while systolic pressure remained less than 110. Endocrinology was consulted to evaluate the ongoing hypotension and hyponatremia 5 days into admission. Infectious disease was also consulted after it was later revealed that the patient had a history of TB with a positive ppd in 2014, treated with Isoniazid but she was unable to confidently state whether she completed treatment. Other lab work was remarkable for a positive ppd test, negative HIV, and random cortisol levels of 1.3 and 1.1. Cosyntropin stimulation test was very abnormal with cortisol results of 1.3 and 1.1 at 30 and 60 minute intervals (normal >18). ACTH on day 6 of admission was greater than 2000, consistent with primary adrenal insufficiency. Abdominal CT without contrast on day 11 showed adrenal fullness with nodal calcifications consistent with post-infectious TB. Blood pressure and sodium improved on hydrocortisone 50 mg three times daily. She was discharged on hydrocortisone 20mg in the AM and 10mg in the PM, fludrocortisone 0.1mg daily and the 4 drug combo for TB; Rifampin, Isoniazid, Pyrazinamide, and Ethambutol. Conclusion: This case of primary adrenal insufficiency highlights an atypical cause that is now rare in the developed world. TB causes adrenal destruction in a gradual manner, targeting the medulla and cortex secondarily as illustrated here by this HIV-negative latent TB patient. Tuberculous adrenal insufficiency typically presents in an insidious manner. This case demonstrates the importance of a thorough history and evaluation coupled with the realization that not all primary adrenal insufficiency is autoimmune.

More than 150 years ago, Thomas Addison first described the clinical features and pathogenesis of adrenal insufficiency. At that time, tuberculosis was the most common cause of this disease. The pathway to diagnosis and treatment of Addison's disease has been well described. However, determining the cause of the disorder remains a challenge. It is important to consider recently described infectious agents in the pathogenesis of Addison's disease. Mycobacterial, bacterial, viral, and fungal infections may lead to the development of adrenal insufficiency. Skin, pulmonary, and imaging findings can aid the clinician in making a prompt diagnosis of specific infections, which is crucial because early identification of infectious causes of Addison's disease may enable recovery of adrenal function. This review describes the clinical presentations of the multiple infectious causes of adrenal insufficiency.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22352号 / 医博第4593号 / 新制||医||1042(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 稲垣 暢也, 教授 森田 智視, 教授 柳田 素子 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Massive bilateral adrenal hemorrhage occurring in the postoperative period is an unusual but potentially life-threatening complication of any abdominal operation. The diagnosis is often difficult due to the nonspecific nature of the clinical presentation, which is easily attributable to other more common postoperative conditions. We report a case of bilateral adrenal hemorrhage resulting in acute primary adrenal insufficiency following an otherwise-uncomplicated laparoscopic cholecystectomy, which has not previously been described. An awareness of the possibility of this uncommon condition complicating laparoscopic cholecystectomy may lead to a higher index of suspicion, which is important in timely diagnosis and prompt treatment.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19176号 / 医博第4018号 / 新制||医||1010(附属図書館) / 32168 / 京都大学大学院医学研究科医学専攻 / (主査)教授 小川 修, 教授 柳田 素子, 教授 三森 経世 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

Mes travaux ont concerné 1) l'ascite, 2) l'inflammation systémique, et 3) l'identification de la l'insuffisance surrénale au cours de la cirrhose. L'analyse prospective de 515 paracentèses montrait que les taux de complications mineures et majeures étaient respectivement de 8,9% et de 1,6%. La paracentèse évacuatrice (vs. exploratrice) était associée au risque de complication majeure, tandis que l'étiologie alcoolique, la gravité de la cirrhose (Child-Pugh C) et l'intensité de la thrombopénie rendaient plus compte des complications mineures. Les performances de deux bandelettes urinaires (BU) pour le diagnostic de l'infection spontanée du liquide d'ascite (ISLA) étaient excellentes (100 paracentèses testées). Avec un seuil de 125 leucocytes/mm3, les performances de la BU Multistix 8SG affichaient de moins bons résultats dans notre étude multicentrique (2123 paracentèses): sensibilité à 45,3% et VPP à 77,9%. Une élévation persistante de la C-réactive protéine (CRP) >29 mg/L entre JO et J15 prédisait la survie à 6 mois chez 175 patients cirrhotiques (Child-Pugh>7) hospitalisés, indépendamment du MELD, de l'existence de comorbidités extra-hépatiques et d'un carcinome hépatocellulaire. Nous avons montré que les concentrations de cortisol total sérique (CTS) diminuaient avec la dégradation de la fonction hépatique alors que les concentrations du cortisol libre sérique (CLS) et salivaire augmentaient ; cette chute du CTS était en rapport avec une chute des concentrations des protéines porteuses du cortisol [albumine et cortisol binding protein (CBG)] produites par le foie. Nous avons aussi montré que des concentrations élevées de CLS étaient associées à une surmortalité. / My research has been focused on: 1) managing ascitis, 2) the systemic inflammation, and 3) the adrenal insufficiency in cirrhosis. Our prospective analysis of 515 paracentesis showed that the rates of minor and major complications were of 8.9% and of 1.6%, respectively. Therapeutic (vs. diagnostic) paracentesis was associated with risk of major complications, whereas the aetiology related to alcohol, the severity of cirrhosis (Child-Pugh C) and the intensity of thrombopenia were associated with minor complications. The performances of two urinary strips for the diagnosis of spontaneous bacterial peritonitis (SBP) were excellent (100 paracentesis tested). Using the cut-off of 125 leukocytes/mm3, the performances of the Multistix 8SG strip displayed disappointing results in our multicenter study (2123 paracentesis): sensitivity of 45.3% and PPV of 77.9%. A Persistent C-reactive protein (CRP) >29 mg/L within the first 15 days predicted the 6-month mortality in 175 cirrhotic inpatients (Child-Pugh>7), independently of the MELD score, extra-hepatic comorbidities and hepatocellular carcinoma. We demonstrated that concentrations of serum total cortisol (STC) decreased along with the altération of hepatic function while the concentrations of serum free cortisol (SPC) and salivary cortisol increased. The low concentrations of STC in these patients were related to reduced serum concentrations of cortisol-binding proteins [albumin and corticosteroid-binding globulin (CBG)], both synthesized in the liver. Unlike previously reported. we have shown that patients who died at 12 months had high levels of SPC after 1ug of Synacthen, challenging the concept of "hepatoadrenal syndrome".

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13553号 / 論医博第2282号 / 新制||医||1067(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 齋藤 潤, 教授 万代 昌紀, 教授 長尾 美紀 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

Thesis (PhD)-- Stellenbosch University, 2013. / ENGLISH ABSTRACT: Although the effect of inhaled corticosteroids (ICS) on the hypothalamic- pituitary-adrenal axis (HPA) has been regarded as a “benign physiological response”, a survey published in 2002 suggested that adrenal crisis is more common in asthmatic children on ICS than previously thought. Relying on clinical features to detect chronic adrenal insufficiency secondary to corticosteroids may not be wise, as these are non-specific and can therefore easily be missed. Accurate biochemical assessment of the whole axis to detect subclinical HPA suppression (HPAS) is thus desirable. A review of the literature indicates that basal adrenal function tests, including plasma cortisol profiles, do not identify which children can appropriately respond to stress. There is no evidence to suggest that the degree of the physiological adjustment of the HPA to ICS and/or nasal steroids (by reducing basal cortisol production), predicts HPAS. Cortisol profiles should therefore only be used to demonstrate differences in systemic activity of various ICS and delivery devices. Only two tests, considered as gold standard adrenal function tests [the insulin tolerance test (ITT) and the metyrapone test] can assess the integrity of the whole axis. / AFRIKAANSE OPSOMMING: Die outeurs van ´n opname wat in 2002 gepubliseer is stel voor dat ´n bynierkrisis meer algemeen by asmatiese kinders, wat inhalasie kortikosteroïede ontvang, voorkom as wat voorheen gedink is. Dit is strydig met die gevestigde opvatting dat die effek van IKS op die hipotalamiese-hipofise-bynier-as (HHB) ’n “goedaardige fisiologiese reaksie” is. Die kliniese kenmerke van kroniese bynierontoereikendheid sekondêr tot die gebruik van kortikosteroïede (KS) is nie-spesifiek en gevolglik onbetroubaar. ´n Akkurate biochemiese toets van subkliniese HBB onderdrukking (HHBO) sou gevolglik waardevol wees. ´n Literatuur oorsig toon dat toetse van basale bynierfunksie, insluitend plasma kortisol (K) profiele, nie kinders uitken wat toepaslik op stres sal reageer nie. Daar is geen bewyse dat die graad van fisiologiese aanpassing van die HHB, soos aangedui deur laer K-vlakke, na die gebruik van IKS en/of nasale steroïede (NS), HHBO voorspel nie. Serum K profiele is dus slegs van waarde om die sistemiese aktiwiteit van verskillende IKS en toedieningsstelsels te ondersoek. Slegs twee toetse, naamlik die insulien toleransie toets (ITT) en die metyrapone -(MTP)-toets (wat beide as die goue standaard van bynier funksie beskou word), kan die integriteit van die hele as meet. / Stellenbosch University / Medical Research Council / SA Thoracic Society / Harry Crossley Foundation / Red Cross Children’s Hospital.