Long-acting porcine ACTH stimulated salivary cortisol reduces the overdiagnosis of adrenal insufficiency compared to serum cortisol in cirrhosis liver.

BACKGROUND: There are no reliable methods in clinical practice to diagnose adrenal insufficiency (AI) in patients with cirrhosis owing to variable cortisol-binding protein levels. This leads to unreliable results in ACTH stimulated serum cortisol test. We aimed to estimate the long-acting porcine (LA)ACTH-stimulated serum and salivary cortisol levels of patients at different stages of cirrhosis using second generation electrochemiluminescence and to determine the prevalence of true adrenal insufficiency in these patients. DESIGN, PATIENTS AND MEASUREMENTS: We included 135 noncritical patients with cirrhosis (45 each from CHILD A, B and C) and 45 healthy controls. Serum and salivary samples were collected at baseline in the morning and at 1 and 2 h after LA-ACTH injection. RESULTS: In healthy subjects, the 2.5th centile of 2 h ACTH stimulated serum and salivary cortisol were 19.8 and 0.97 µg/dL, which were used as cut-offs for defining AI based on serum and saliva respectively. The median (interquartile-range) 2-h stimulated salivary cortisol in Child A, B, C categories and controls were 1.36(1.23-2.38), 1.46(1.18-2.22), 1.72(1.2-2.2) and 2.12(1.42-2.72) µg/dL respectively. Six subjects (4.4%) were diagnosed to have AI based on stimulated salivary cortisol cut-off, whereas 39 (28.9%) cirrhosis subjects had inadequately stimulated serum cortisol. Three patients (symptomatic) required steroid replacement therapy. Hypoalbuminemia was identified as a major risk factor for the misdiagnosis of adrenal insufficiency by serum cortisol-based testing. CONCLUSIONS: Long-acting porcine ACTH stimulated salivary cortisol reduces the overdiagnosis of adrenal insufficiency compared to serum cortisol in cirrhosis liver. Stimulated salivary cortisol is a promising investigation for evaluation of adrenal function in cirrhosis and more studies are required for its further validation before clinical use.

Long-acting porcine ACTH stimulated salivary cortisol in the diagnosis of adrenal insufficiency.

BACKGROUND: Synacthen stimulated salivary cortisol has been previously evaluated and found beneficial in the diagnosis of adrenal insufficiency (AI), especially in situations with altered cortisol-binding protein (CBG) levels. Unfortunately, Synacthen is not marketed in many parts of the world whereas porcine sequence corticotrophin (Acton Prolongatum) is readily available. This study aimed to find the diagnostic accuracy of Acton prolongatum stimulated salivary cortisol test (APSST) compared to the short synacthen test (SST). METHODS: Consecutive outpatients with suspected AI underwent SST initially, followed by APSST after 3 days. For APSST, saliva was collected at 0, 60 and 120 minutes after administering 30 units Acton Prolongatum intramuscularly. Serum and salivary cortisol were estimated using electrochemiluminescence assay. (Cobas e 411, Elecsys Cortisol II kits) RESULTS: Sixty-seven patients with clinically suspected AI were enrolled for the study. Based on SST, 35 patients were classified as having AI [primary AI (n=19) and secondary AI (n=16)] whereas 32 had normal glucocorticoid reserve. The area under receiver operator curve of 0.99 and 0.98 was observed for salivary cortisol values at 60 and 120 minutes, respectively, for APSST. A cut-off value of 18.5 nmol/L (0.67 µg/dL) and 29.3 nmol/L (1.06 µg/dL) at 60 and 120 minutes, respectively, had a sensitivity as well as specificity of 93%-100% in diagnosing AI. CONCLUSION: Salivary cortisol estimation following stimulation using intramuscular porcine ACTH (Adrenocorticotrophic hormone) (30 units) is an economical and accurate alternative to SST in the diagnosis of AI, m and its level of 30 nmol/L or more at 2 hours confirms adrenal sufficiency.

Late-Night Salivary Cortisol in Healthy, Community-Dwelling Asian Indians Assessed by Second-Generation ECLIA.

BACKGROUND: Late-night salivary cortisol (LNSC) is used as a screening test for Cushing syndrome (CS), but there is no community-derived normative data for the normal upper limit in the South Asian population. This study aimed to determine the upper limit of normal (97.5th percentile) for LNSC in an Asian Indian population using a commercially available second-generation electrochemiluminiscence immunoassay (ECLIA). METHODS: LNSC in apparently healthy community-dwelling individuals was assessed by multistage cluster sampling. Healthy individuals age 18 to 60 years from 8 urban and 8 rural clusters of Thiruvananthapuram district were studied. Thirty people from an approximate population of 1000 individuals from each cluster participated in the study. A saliva sample was collected between 11 PM and 12 midnight and analyzed using Roche COBAS-e-411 and ultrasensitive Cortisol II kits the next day. RESULTS: Cortisol values from 474 salivary samples were available for final analysis after exclusion of improperly collected samples. The 97.5th percentile of the LNSC concentrations was 0.25 µg/dL (6.89 nmol/L) (90% CI, 0.23-0.27 µg/dL; ie, 6.34-7.45 nmol/L). In postmenopausal women, median LNSC was significantly higher but the 90% CI for the upper limit of their LNSC (0.28µg/dL or 7.72 nmol/L) overlapped with that of premenopausal women. CONCLUSIONS: This study establishes the normal value of LNSC estimated by second-generation ECLIA in healthy community-dwelling Asian Indian individuals for the first time. Salivary cortisol at 11 pm to 12 am is less than 0.25µg/dL (6.89 nmol/L) in the general Asian Indian population. Menopause causes a significant increase in LNSC and may lead to overdiagnosis of CS if not interpreted carefully.

Slipped Capital Femoral Epiphysis in Primary Hyperparathyroidism - Case Report with Literature Review.

Primary hyperparathyroidism is not common in children and adolescents. Association of slipped capital femoral epiphysis and hyperparathyroidism is rare. We report the case of a 15-year-old boy who presented with pain in both hips and limping. He was diagnosed to have bilateral slipped capital femoral epiphysis (SCFE) and underwent cancellous screw fixation of both hips. He had proximal myopathy and pain at multiple points over the chest. Examination revealed an emaciated patient with genu valgum, rachitic rosary, Harrison's sulcus, and bony tenderness over the ribs. Investigations showed PTH-dependent hypercalcemia with serum calcium levels reaching >17 mg/dL and electrocardiography showing QTc shortening. Imaging revealed parathyroid adenoma. The work up for multiple endocrine neoplasia syndromes (MEN) was negative. Serum calcium was controlled by medical management and patient underwent expedited surgery. Postoperatively serum calcium levels normalized and patient became better biochemically and clinically including resolution of skeletal changes on follow-up. Only 12 cases of SCFE associated with primary hyperparathyroidism have been reported worldwide till date including the current case. The literature has been reviewed and it indicates that SCFE is associated with late adolescent age and severe hyperparathyroidism (severe bone disease, higher parathormone, serum calcium, and alkaline phosphatase levels).

Long acting porcine sequence ACTH in the diagnosis of adrenal insufficiency.

OBJECTIVES: Injectable tetracosactide hexa-acetate, ACTH 1-24 (Synacthen), is not marketed in many countries including India, whereas Injectable long acting porcine sequence, ACTH 1-39 (Acton Prolongatum®) is easily available and much cheaper. This study aimed to find the diagnostic accuracy of ACTH stimulation test using i.m. Acton Prolongatum® (acton prolongatum stimulation test, APST) in comparison with Synacthen (short synacthen test, SST) for the diagnosis of glucocorticoid insufficiency. METHODS: Subjects with a suspicion of adrenal insufficiency based on clinical features underwent a SST with 250 µg Synacthen followed by APST using 30 units of Acton Prolongatum®. Serum cortisol levels were measured at 60 and 120 min following injection of Acton Prolongatum®. Stimulated peak cortisol of less than 18 µg/dL on SST was considered as adrenal insufficiency. RESULTS: Forty seven patients with mean age of 36.7 ± 14.4 years were enrolled for the study. Based on SST, twenty (n = 20) persons were classified as having adrenal insufficiency, whereas twenty-seven (n = 27) were found to be normal. Area under the curve of APST (at 120 min) was 0.986 when compared to SST, thus proving its high accuracy. A serum cortisol cut off value of 19.5 µg/dL at 120-min following stimulation with Acton Prolongatum® showed a sensitivity of 100% and specificity of 88%. CONCLUSION: ACTH stimulation test using Acton Prolongatum® is an economical and accurate alternative to the short Synacthen test.

Prevalence and Associations of Hypothyroidism in Indian Patients with Type 2 Diabetes Mellitus.

Both type 2 diabetes and hypothyroidism are highly prevalent disorders in the community. The existing data regarding prevalence of hypothyroidism in patients with diabetes comes mostly from small studies. There are only two studies with a sample size of more than 1000 diabetic patients, none of which have been done in South Asians. The present study evaluated patients with type 2 diabetes for presence of hypothyroidism and the clinical factors associated with it. The demographic, anthropometric, clinical, and biochemical parameters of consecutively enrolled patients with diabetes were systematically collected and analyzed. A total of 1152 middle aged patients with type 2 diabetes with a mean duration of diabetes of around 10 years were enrolled. Nearly 40 percent of the patients were obese and overweight, respectively, for South Asian standards and abdominal obesity was seen in around 90% patients. Clinical hypothyroidism (TSH>10 mIU/ml) was present in 113 of patients (9.83%) and another 68 patients (5.9%) had subclinical hypothyroidism (TSH 5-10 mIU/ml). Anemia (odds ratio : 2.19), overweight/obese status (odds ratio 2.07), and known dyslipidemia (odds ratio : 1.99) were found to have independent association with clinical hypothyroidism. HbA1c, abdominal obesity, poor control of hypertension, lipid parameters, microalbuminuria, and renal dysfunction showed no difference among patients with hypothyroidism when compared with euthyroid patients. Subclinical hypothyroid patients had no difference in any of the above analyzed parameters when compared to the euthyroid patients. This study shows that a significant proportion of type 2 diabetes patients suffer from clinical or subclinical hypothyroidism and screening for the same may be appropriate.