Clinical outcomes and cortical reserve in adrenal histoplasmosis-A retrospective follow-up study of 40 patients.

OBJECTIVE: Detailed studies of Addison's disease resulting from disseminated adrenal histoplasmosis (AH) are not available. We describe the presentation and prognosis of AH and cortisol status before and after antifungal therapy. DESIGN: Single-centre retrospective hospital-based study of 40 consecutive adults with AH [39 males; age (mean ± SD) 53 ± 11 years] was conducted between 2006 and 2018. The median duration of follow-up was 2.5 years (range 0.2-12 years). PATIENTS AND METHODS: AH was diagnosed by bilateral adrenal enlargement on CT scan and presence of Histoplasma by histology and/or culture of biopsied adrenal tissue. All patients received oral itraconazole and, if required, amphotericin B as per guidelines. ACTH-stimulated serum cortisol (normal > 500 nmol/L) was measured in 38 patients at diagnosis and re-tested after one year of antifungal therapy in 21 patients. RESULTS: Seventy-three per cent of patients had primary adrenal insufficiency (PAI) and one-third had an adrenal crisis at presentation. HIV antibody was negative in all patients. Of the 29 patients who completed antifungal therapy, 25 (86%) were in remission at last follow-up. Overall, 8 (20%) patients died: three had a sudden death, four had severe histoplasmosis and one died due to adrenal crisis. No patient with PAI became eucortisolemic on re-testing after one year of antifungal therapy. Of the eight patients with normal cortisol at diagnosis, two developed adrenal insufficiency on follow-up. CONCLUSION: All patients with AH tested negative for HIV antibody. While patients achieved a high rate of clinical remission after antifungal therapy, overall mortality was significant. Cortisol insufficiency did not normalize despite treatment.

Effect of vitamin D supplementation, directly or via breast milk for term infants, on serum 25 hydroxyvitamin D and related biochemistry, and propensity to infection: a randomised placebo-controlled trial.

We assessed the effect of vitamin D supplementation on related biochemistry, infection and dentition of the infant. In a double-blind, placebo-controlled trial conducted in Lucknow, India (latitude 26°N), 230 mother -newborn pairs were randomised to receive, for 9 months, 3000µg/month oral vitamin D3 by the mother (group A) or 10µg/d by the infant (group B) or double placebo (group C). All babies received 15 min of sun exposure (unclothed) during massage. Infants' median 25-hydroxyvitamin D (25(OH)D) was lower in group C (median 45·3; interquartile range (IQR) 22-59·5 nmol/l) than in groups A (median 60·8; IQR 41·3-80·5 nmol/l (P7.5µkat/l) was significantly more frequent in group C babies (16 %) than in group A (4 %) or group B (0 %) babies. The number of days with respiratory or diarrhoeal infection by 9 months of age was higher in group C (median 46·5; IQR 14·8-73·3 d) than in group A (median 18·5; IQR 8·8-31·0 d (P<0·01)) or group B (median 13·0; IQR 7·0-28·5 (P<0·05)). We conclude that monthly maternal or daily infant supplementation with vitamin D along with sun exposure is superior to sun exposure alone in maintaining normal infant 25(OH)D at 3·5 months, and provide protection from elevated alkaline phosphatase and infectious morbidity.

BONE MINERAL DENSITY IN PATIENTS WITH ADDISON DISEASE ON REPLACEMENT THERAPY WITH PREDNISOLONE.

OBJECTIVE: In primary adrenal insufficiency (PAI), replacement with prednisolone may result in lower bone mineral density (BMD) compared with hydrocortisone therapy. However, the number of patients studied on prednisolone is small and the results are conflicting. We conducted a cross-sectional study to determine BMD and its relation with therapy in patients on physiologic doses of prednisolone replacement. METHODS: Forty-one consecutive patients (31 males, age [mean ± SD] 50.9 ± 13.0 years), receiving prednisolone (hydrocortisone equivalent [HCE] 13.0 ± 3.0 mg/m(2)) for 104 ± 95 months were studied. BMD was evaluated by dual-energy X-ray absorptiometry and compared with an age- and sex-matched reference group of healthy Indian subjects (n = 677). RESULTS: Among males, BMD Z-scores (mean [95% confidence interval {CI}]) at lumbar spine (-0.42 [-0.80, -0.04]), femoral neck (-0.50 [-0.95, -0.06]) and total hip (-0.58 [-0.90, -0.26]) were significantly lower than the reference population. Z-scores in female patients did not differ from controls. Among postmenopausal females and males >50 years, 43% had osteoporosis (T-score ≤-2.5), as compared with 25% in the reference group (P = .04). There was no correlation between BMD Z-scores and HCE dose or duration of therapy. On multivariate regression analysis, body mass index was the only significant predictor of BMD. A high proportion of males (45%) had low serum testosterone (<300 ng/dL), but there was no correlation between testosterone and BMD. CONCLUSIONS: Male patients with PAI receiving physiologic prednisolone replacement had a small but significant diminution in BMD at all sites.