Endocrine Journal 1994, 41(1), 13-18 Adrenal Insufficiency in a Patient with Acquired Immunodeficiency Sy ndrome KoIcHI FUJII, IsAO MORIMOTO, ATSUSHIWAKE, YOHSUKEOKADA, NoBUo INOKUCHI, OsAMUISHIDA, YOIcHIRONAKANO, SUSUMUODA, ANDSUMIYA ETO First Departmento f Internal Medicine,University of Occupational and EnvironmentalHealth, Kitakyushu807, Japan Abstract. A 46-year-old man was admitted because of hypotension and consciousness disturbance. He was a patient with hemophilia B, and diagnosed as having an AIDS-related complex 2 years prior to admission. On admission he had severe hyponatremia. Hormonal studies revealed that he had Addison's disease. Serum cytomegalovirus (CMV) antibody titers were high, and a CMV antigen was detected in his urine, which suggested CMV adrenalitis caused by an active CMV infection. After the administration of hydrocortisone and ganciclovir, his general clinical condition and biochemical test results were back to normal. However, the adrenal dysfunction was irreversible, despite the treatment with ganciclovir. With an increase in the number of AIDS patients, we have to consider adrenal insuffi- ciency due to a CMV infection in patients with AIDS. Key words: Acquired Immunodeficiency Syndrome (AIDS), Cytomegalovirus infection, Adrenal Insuffi- ciency, Addison's Disease. (Endocrine Journal 41:13-18,1994) AUTOPSY reports of acquired immunodeficiency syndrome (AIDS) patients have noted adrenal de- Methods structive lesions associated with a cytomegalovirus (CMV) infection [1-5]. These reports indicate that Plasma aldosterone [8] and plasma renin activity more than 50% of AIDS patients have a various de- (PRA) [9] were measured with a radioimmunoas- grees of CMV adrenalitis. However, few cases say (RIA) kit (Daichi Radioisotope Ltd., Tokyo, Ja- have shown presented clinical and biochemical pan). Plasma cortisol, ACTH and antidiuretic hor- evidence of adrenal insufficiency [6, 7]. The num- mone (ADH) were measured by RIA and urinary ber of AIDS patients is going to increase in Japan. 17-OHCS and 17-KS were by spectrophotometric This is a case of AIDS with primary adrenal insuf- method at Otsuka Assay Laboratories (Tokushima, ficiency (Addison's disease) due to a CMV infec- Japan). CMV antigen was measured by the Shell- tion. Vial method at Mitsubishi-Yuka Bio Laboratories (Tokyo, Japan) [10]. Anti-CMV and anti-adrenal cortex antibodies were measured by ELISA [11] and an indirect immunofluorescence method [12], respectively, at Biomedical Laboratory (Saitama, Received: June 4, 1993 Japan). Accepted: November 8, 1993 Correspondence to: Dr. Isao MORIMOTO, First Depart- An ACTH stimulation test was accomplished by ment of Internal Medicine, University of Occupational and intramuscular injection of ACTH-Z (Cortrosyn-Z, Environmental Health, 1-1 Iseigaoka, Kitakyushu 807, Organon, Tokyo) in a dose of 1 mg/day for 3 con- Japan secutive days. Blood samples were obtained at 14 FUJII et al, 0800 h, before the first injection and 24 h after each observed. Otherwise the results of the physical ex- injection, and urine samples were obtained on days amination were unremarkable. 0, 1, 2 and 3. PRA and aldosterone responses were Laboratory data on admission are shown in evaluated after 20 mg of furosemide iv administra- Table 1. The white cell count was 5200/mm3, lym- tion and 2 h upright while giving a 3 g salt diet for phocytes were 830/mm3. CD4 positive cells were 3 days. An angiotensin II infusion test was per- 8%, and the CD4/CD8 ratio was 0.1. The patient formed by the following method: Angiotensin II had anemia (Hb 11.9 g/dl), hyponatremia (116 (Ciba-Geigy, Switzerland) was infused at a dose of mEq/l), hypokalemia (3.1 mEq/l), an increase in 4 ng/kg/min for 10 min, followed by 10 and then serum muscular enzyme (CK 8010 U/l), 20 ng/kg/min for 10 min. When diastolic blood hypoproteinemia (5.2 g/dl), metabolic acidosis pressure showed an increase of more than 20 (pH 7.28, PCO2 26.8 mmHg, P02160 mmHg, HCO3 mmHg (infusion rate: 20 ng/kg/min), blood 12.6 mEq/l), low plasma osmolarity with inappro- samples were obtained every 10 min for the mea- priately high urinary osmolarity (serum: 247, surement of plasma aldosterone. urine: 282 mOsm/kgH2O). His renal function was normal. The anti-CMV antibody (IgG) titer was in- creased, and a urinary CMV antigen was positive. Case Report Anti-adrenal antibodies were negative. Radio- graphic examinations revealed pulmonary paren- A 46-year-old man was admitted to our hospital chymal and interstitial infiltration. No organisms because of diarrhea, vomiting, consciousness dis- were detected in the sputum. turbance, hypotension, and hyponatremia. He was The results of endocrinological studies are diagnosed as having hemophilia B at the age of 14 shown in Tables 2 and 3. The basal morning se- and had been treated with Factor IX. An AIDS-re- rum cortisol level was low normal, 110 nmol/l (3.9 lated complex was diagnosed 2 years prior to ad- ug/dl), but the ACTH level was increased at 45.1 mission and he has been given azidothymidine and pmol/l (204.8 pg/ml). Urinary 17-OHCS and didanosine. On admission, his blood pressure was 17-KS were lower than the normal level (2.48, 7.28 70/40 mmHg, with a pulse rate of 70 beats/min. ,umol/day, respectively). Hyporeninemic hypoal- His consciousness level was somnolent. The skin dosteronism was also observed (plasma renin ac- was dry, but the skin pigmentation was not obvi- tivity: 0.06 ng/l/s, aldosterone: <28 pmol/1). ADH ous. Articular contracture on the extremities was was inappropriately high despite low serum osmo- Table 1. Laboratory data on admission ADRENAL INSUFFICIENCY DUE TO AIDS 15 larity. A consecutive 3-day ACTH-Z (1 mg/day, im) loading test showed blunt plasma cortisol and Clinical course (Fig. 1) urinary 17-OHCS responses. PRA and plasma al- dosterone levels remained low despite 20 mg of On admission there was dehydration with furosemide iv administration and 2 h upright pos- hyponatremia due to vomiting, and diarrhea was ture on a low sodium (3 g/day) diet for 3 days. An observed, and saline administration was instituted. angiotensin II loading test was performed (Table However, the hyponatremia did not improve de- 3), but aldosterone response was inadequate. spite the saline administration, and the conscious- ness disturbance continued. Endocrinological data obtained several days later suggested that he had Table 2. Endocrine function on admission adrenal insufficiency. Hydrocortisone (25 mg/day) was administered after adrenal insufficiency was confirmed by an ACTH-Z loading test, and there was marked improvement in his clinical condition. Both serum electrolyte levels and osmolarity were back to normal. As an active CMV infection was suspected because of increased serum anti-CMV antibody (IgG) titer and there was a positive uri- nary CMV antigen, treatment with 300 mg of ganciclovir was instituted. Two weeks after the treatment, the urinary CMV antigen became nega- tive. Low plasma cortisol, high plasma ACTH and hyporeninemic hypoaldosteronism persisted. Re- peated ACTH loading test done after ganciclovir treatment showed no improvement in the adrenal function (Table 3-1). Five months later he had vi- Table 3. Adrenocortical function tests 1. Consecutive 3-day ACTH-Z (1 mg) administration 2. PRA and aldosterone levels to Na restriction (NaCI: 3 g/day), furosemide (20 mg. iv) and upright posture (2 h) loading 3. Aldosterone response to angiotensin II administration 16 FUJII et al. Fig. 1. Clinical course after admission. Hormone levels on days 45 and 90 were obtained 24 h after hydrocortisone adminsitration. ADH, antidiuretic hormone; PRA, plasma renin activity; Aid, aldosterone; ACTH, adrenocorticotropin. sual disturbance and was diagnosed as having renal destruction in AIDS, is recognized in more CMV retinitis. A CMV antigen in urine was posi- than 75% of autopsied AIDS patients with a CMV tive and ganciclovir was administered again. infection [4, 6]. However, most of the cases showed necrosis involving less than 50% of the adrenal cor- tex and clinically evident adrenal insufficiency is Discussion not common in the disorder [5]. AIDS patients of- ten have signs and symptoms suggestive of adre- Various endocrine dysfunction due to an inci- nal insufficiency in their clinical course. Some dental infection has been reported in patients with studies have reported that AIDS patients have nor- AIDS [13, 14]. Katt and Shibata [4] reported that mal [15] or blunt cortisol response to ACTH stimu- half of all AIDS patients show evidence of CMV lation test [13, 16, 17]. In our case, an increase in infection at autopsy. A CMV necrotizing serum anti-CMV antibodies and a positive urinary adrenalitis, which is the most common cause of ad- CMV antigen suggested an active CMV infection. ADRENAL INSUFFICIENCY DUE TO AIDS 17 He also had CMV retinitis during his clinical the adrenal insufficiency seemed to be irrevers- course. Though histological evidence was not ob- ible. In this patient, PRA was low despite tained, CMV adrenalitis was suspected and be- hyponatremia with volume depletion on admis- came clinically apparent under physical stress. sion and did not respond to the stimulation of so- Mycobacterial infections can cause adrenal insuffi- dium depletion, furosemide administration and ciency. Disseminated tuberculosis has been seen in upright posture. Hyporeninemic hypoaldoster- the post-mortem examinations of patients with onism associated with AIDS is reported in previ- AIDS [18], but the clinical course of our patient ous studies