Risk of Gallstone Disease in Primary Hyperparathyroidism: A Systematic Review and Meta-analysis.

OBJECTIVE: Apart from renal stones, primary hyperparathyroidism (PHPT) has been linked to the occurrence of gallstone disease (GSD). Nevertheless, the association is not consistent across all studies. The present systematic review and meta-analysis aims to collate the hitherto available evidence and provide a pooled estimate of the association between GSD and PHPT. METHODS: PubMed/MEDLINE, Embase, and Web of Science databases were systematically searched from inception till May 10, 2023 for observational studies reporting the prevalence of GSD (in terms of absolute numbers) in patients with PHPT. The pooled prevalence of GSD and odds ratio with 95% CI of the occurrence of GSD in patients with PHPT as compared to age- and sex-matched controls were calculated. Subgroup analysis was performed based on patient ethnicity (Indian/Caucasian). Statistical analysis was carried out using R version 4.2.2. Random-effects model with Hartung-Knapp adjustment was used for analyses. RESULTS: A total of 7 observational studies were included, pooling data from 15 949 patients with PHPT. The pooled prevalence of GSD in patients with PHPT was 16% (95% CI: 7%, 25%, I2 = 99%), being 13% (95% CI: 0%, 66%, I2 = 76%) in Indians, and 17% (95% CI: 4%, 31%, I2 = 99%) in Caucasians. Data consolidated from 3 studies showed that the pooled odds ratio of occurrence of GSD in patients with PHPT compared to controls was 1.77 (95% CI: 1.60, 1.97, P < .001, I2 = 0%). CONCLUSIONS: GSD is more prevalent in patients with PHPT than in the general population. Thus, PHPT may be considered an additional risk factor for GSD.

Mineralocorticoid receptor antagonists with sodium-glucose co-transporter-2 inhibitors in heart failure: a meta-analysis.

BACKGROUND AND AIMS: To investigate the cardiovascular effects of sodium-glucose co-transporter-2 inhibitors (SGLT2i) with concomitant mineralocorticoid receptor antagonist (MRA) use in heart failure (HF) regardless of ejection fraction (EF) and explore the risk of MRA-associated adverse events in individuals randomized to SGLT2i vs. placebo. METHODS: PubMed/MEDLINE, Web of Science, Embase, and clinical trial registries were searched for randomized controlled trials/post-hoc analyses evaluating SGLT2i in HF with or without MRA use (PROSPERO: CRD42023397129). The main outcomes were composite of first hospitalization or urgent visit for HF/cardiovascular death (HHF/CVD), HHF, and CVD. Others were all-cause mortality, composite renal and safety outcomes. Hazard ratios (HR)/risk ratios were extracted. Fixed-effects meta-analyses and subgroup analyses were performed. RESULTS: Five eligible studies were included, pooling data from 21 947 people with HF (type 2 diabetes mellitus, n = 10 805). Compared to placebo, randomization to SGLT2i showed a similar reduction in HHF/CVD and HHF in people who were or were not using MRAs [HHF/CVD: hazard ratio (HR) 0.75; 95% confidence interval (CI) 0.68-0.81 vs. HR 0.79; 95% CI 0.72-0.86; P-interaction = .43; HHF: HR 0.74; 95% CI 0.67-0.83 vs. HR 0.71; 95% CI 0.63-0.80; P-interaction = .53], with a suggestion of greater relative reduction in CVD in chronic HF people randomized to SGLT2i and using MRAs irrespective of EF (HR 0.81; 95% CI 0.72-0.91 vs. HR 0.98; 95% CI 0.86-1.13; P-interaction = .034). SGLT2i reduced all-cause mortality (P-interaction = .27) and adverse renal endpoints regardless of MRA use (P-interaction = .73) despite a higher risk of volume depletion with concomitant MRAs (P-interaction = .082). SGLT2i attenuated the risk of mild hyperkalaemia (P-interaction < .001) and severe hyperkalaemia (P-interaction = .051) associated with MRA use. CONCLUSIONS: MRAs did not influence SGLT2i effects on the composite of HHF/CVD, HHF or all-cause mortality; however, findings hinted at a more pronounced relative reduction in CVD in chronic HF patients regardless of EF who were randomized to SGLT2i and receiving an MRA compared to those randomized to SGLT2i and not receiving MRAs. SGLT2i attenuated the risk of MRA-associated treatment-emergent hyperkalaemia. These findings warrant further validation in well-designed randomized controlled trials.

Characterization of primary hyperparathyroidism based on target organ involvement: An analysis from the Indian PHPT registry.

BACKGROUND: It has been a matter of debate for long time about the existence of two distinct phenotypes of primary hyperparathyroidism (PHPT) predisposed to either renal or skeletal manifestation. OBJECTIVE: To differentiate characteristics of symptomatic PHPT patients based on the presence of skeletal or renal involvement. DESIGN: Retrospective analysis of data from the Indian PHPT registry. PATIENTS: PHPT patients were divided into four discrete groups: asymptomatic, presenting with renal manifestations alone, skeletal manifestations alone, and both skeletal and renal manifestations. MEASUREMENTS: Clinical, biochemical, and tumour weight and histopathological characteristics of these groups were compared. RESULTS: Of the 229 eligible patients, 45 were asymptomatic, 62 had renal manifestations, 55 had skeletal manifestations, and 67 had both skeletal and renal manifestations. Patients with both skeletal and renal manifestations had higher serum calcium levels than those with isolated skeletal involvement [12.5 (11.1-13.7) mg/dL, 11.2 (10.6-12.3) mg/dL, respectively; p < .05]. Serum alkaline phosphatase (AP), plasma parathyroid hormone (PTH) levels, and parathyroid tumour weight were significantly higher in patients with isolated skeletal, and both skeletal and renal manifestations, compared to the other two groups. A preoperative PTH and AP level of 300 pg/mL and 152 U/L, predicted the risk of developing skeletal involvement with sensitivity and specificity of 71%, 70%, and 69%, 67%, respectively. CONCLUSIONS: We observed distinct skeletal and renal phenotypic subgroups among PHPT patients with characteristic biochemical and hormonal patterns with higher parathyroid disease burden in patients with skeletal complications compared to those with isolated renal manifestation.

Serum uric acid lowering and effects of sodium-glucose cotransporter-2 inhibitors on gout: A meta-analysis and meta-regression of randomized controlled trials.

AIMS: To pool the effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on gout and to investigate the association of these effects with baseline serum uric acid (SUA), SUA lowering, and underlying conditions, such as type 2 diabetes mellitus (T2DM)/heart failure (HF). METHODS: PubMed, Embase, Web of Science, Cochrane Library and clinical trial registry websites were searched for randomized controlled trials (RCTs) or post hoc analyses (≥1-year duration; PROSPERO:CRD42023418525). The primary outcome was a composite of gouty arthritis/gout flares and commencement of anti-gout drugs (SUA-lowering drugs/colchicine). Hazard ratios (HRs) with 95% confidence interval (CI) were pooled using a generic inverse-variance method with a random-effects model. Mixed-effects model univariate meta-regression analysis was performed. RESULTS: Five RCTs involving 29 776 patients (T2DM, n = 23 780) and 1052 gout-related events were identified. Compared to placebo, SGLT2 inhibitor use was significantly associated with reduced risk of composite gout outcomes (HR 0.55, 95% CI 0.45-0.67; I2 = 61%, P < 0.001). Treatment benefits did not differ between trials being conducted exclusively in baseline HF versus those conducted in patients with T2DM (P-interaction = 0.37), but were greater with dapagliflozin 10 mg and canagliflozin 100/300 mg (P < 0.01 for subgroup differences). Sensitivity analysis excluding trials that evaluated the effects of empagliflozin 10/25 mg (HR 0.68, 95% CI 0.57-0.81; I2 = 0%) accentuated the benefits of SGLT2 inhibitors with no between-trial heterogeneity (HR 0.46, 95% CI 0.39-0.55; I2 = 0%). Univariate meta-regression found no impact of baseline SUA, SUA lowering on follow-up, diuretic use, or other variables on their anti-gout effects. CONCLUSION: We found that SGLT2 inhibitors significantly reduced the risk of gout in individuals with T2DM/HF. Lack of an association with SUA-lowering effects suggests that metabolic and anti-inflammatory effects of SGLT2 inhibitors may predominantly mediate their anti-gout benefits.

Endocrine Follow-up During Post-Acute COVID-19: Practical Recommendations Based on Available Clinical Evidence.

OBJECTIVE: COVID-19 affects multiple endocrine organ systems during the disease course. However, follow-up data post-COVID-19 is scarce; hitherto available limited data suggest that most of the biochemical endocrine dysfunctions observed during acute phase of COVID-19 tend to improve after recovery. Hence, we aim to provide a rational approach toward endocrine follow-up of patients during post-acute COVID-19. METHODS: We performed a literature review across PubMed/MEDLINE database looking into the effects of COVID-19 on endocrine system and subsequent long-term endocrine sequelae. Accordingly, we have presented a practical set of recommendations regarding endocrine follow-up post-acute COVID-19. RESULTS: COVID-19 can lead to new-onset hyperglycemia/diabetes mellitus or worsening of dysglycemia in patients with preexisting diabetes mellitus. Hence, those with preexisting diabetes mellitus should ensure optimum glycemic control in the post-COVID-19 period. New-onset diabetes mellitus has been described post-acute COVID-19; hence, a selected group of patients (aged <70 years and those requiring intensive care unit admission) may be screened for the same at 3 months. Thyroid dysfunction (euthyroid sick syndrome and atypical thyroiditis) and adrenal insufficiency have been described in COVID-19; however, thyroid/adrenal functions usually normalize on follow-up; hence, widespread screening post-acute COVID-19 should not be recommended. Pituitary apoplexy and male hypogonadism have rarely been documented in COVID-19; therefore, appropriate follow-up may be undertaken as per clinical context. Hypocalcemia during COVID-19 is not uncommon; however, routine estimation of serum calcium post-COVID-19 is not warranted. CONCLUSION: The recommendations herein provide a rational approach that would be expected to guide physicians to better delineate and manage the endocrine sequelae during post-acute COVID-19.

Comparison of Profile of Primary Hyperparathyroidism With and Without Type 2 Diabetes Mellitus: Retrospective Analysis From the Indian Primary Hyperparathyroidism Registry.

OBJECTIVE: To describe the prevalence and compare the clinicobiochemical profile of patients with primary hyperparathyroidism (PHPT) with and without type 2 diabetes mellitus (T2DM). METHODS: We conducted a retrospective observational study wherein the details of patients with PHPT with T2DM (PHPT-T2DM) and without T2DM were retrieved from the Indian PHPT Registry (www.indianphptregistry.com) between 2005 and 2019. We compared the clinical, biochemical, and postoperative findings of patients with PHPT-T2DM with age-, sex-, and body mass index-matched patients with PHPT without T2DM (in 1:2 ratio). RESULTS: Of the 464 patients with PHPT, 54 (11.6%) had T2DM. We observed an increase in the prevalence of PHPT-T2DM cases over time; only 7 (7.1%) of the total patients with PHPT had T2DM between 2005 and 2009 that increased to 31 (12.8%) in the last half decade (2015-2019). Patients with PHPT-T2DM had a significantly lower prevalence of nephrolithiasis (18.5% vs 36.1%, respectively; P = .03) and a higher prevalence of pancreatitis (22.2% vs 5.6%, respectively; P = .007) than those without T2DM. Furthermore, intact parathyroid hormone (203 pg/mL [139.8-437.3 pg/mL] vs 285 pg/mL [166-692 pg/mL], respectively; P = .04) and serum creatinine (0.90 mg/dL [0.67-1.25 mg/dL] vs 1.10 mg/dL [0.73-1.68 mg/dL], respectively; P = .03) levels were significantly lower in patients with PHPT-T2DM than those without T2DM. Also, tumor weight tended to be lower in patients with PHPT-T2DM than in the non-T2DM counterparts (1.05 g [0.5-2.93 g] vs 2.16 g [0.81-7.0 g], respectively; P = .06). CONCLUSION: The prevalence of T2DM in Asian Indians with PHPT is 11.6%. Patients with PHPT-T2DM are characterized by a higher prevalence of pancreatitis, a lower prevalence of nephrolithiasis, and lower levels of intact parathyroid hormone/creatinine. Part of the clinical picture can possibly be explained by early detection of PHPT in patients with T2DM consequent to more frequent screening.

Statin use and clinical outcomes in patients with COVID-19: An updated systematic review and meta-analysis.

PURPOSE: Observations studies have shown that prior use of statins is associated with a reduced risk of adverse clinical outcomes in patients with COVID-19. However, the available data are limited, inconsistent and conflicting. Besides, no randomised controlled trial exists in this regard. Hence, the present meta-analysis was conducted to provide an updated summary and collate the effect of statin use on clinical outcomes in COVID-19 using unadjusted and adjusted risk estimates. METHODS: PubMed, Scopus and Web of Science databases were systematically searched using appropriate keywords till December 18 2020, to identify observational studies reporting clinical outcomes in COVID-19 patients using statins versus those not using statins. Prior and in-hospital use of statins were considered. Study quality was assessed using the Newcastle-Ottawa Scale. Unadjusted and adjusted pooled odds ratio (OR) with 95% CIs were calculated. RESULTS: We included 14 observational studies pooling data retrieved from 19 988 patients with COVID-19. All the studies were of high/moderate quality. Pooled analysis of unadjusted data showed that statin use was not associated with improved clinical outcomes (OR 1.02; 95% CI 0.69 to 1.50, p=0.94, I2=94%, random-effects model). However, on pooling adjusted risk estimates, the use of statin was found to significantly reduce the risk of adverse outcomes (OR 0.51; 95% CI 0.41 to 0.63, p<0.0005, I2=0%, fixed-effects model). CONCLUSIONS: Statin use is associated with improved clinical outcomes in patients with COVID-19. Individuals with multiple comorbidities on statin therapy should be encouraged to continue the drug amid the ongoing pandemic.

Glycaemic efficacy and safety of mealtime faster-acting insulin aspart administered by injection as compared to insulin aspart in people with diabetes mellitus: A meta-analysis of randomized controlled trials.

AIMS: To summarize all relevant randomized controlled trials (RCTs) and provide precise effect estimates of glycaemic efficacy/safety of faster-acting insulin aspart administered by injection as compared to insulin aspart in people with diabetes mellitus. METHODS: PubMed/Cochrane Library were systematically searched till October 10, 2020, to identify RCTs with duration ≥16 weeks, evaluating efficacy/safety of mealtime injections of faster aspart compared to insulin aspart in people with type 1 diabetes mellitus and type 2 diabetes mellitus. Studies using faster aspart as continuous subcutaneous insulin infusion were excluded. Continuous and dichotomous outcome variables (expressed as estimated treatment difference and rate ratio in RCTs, respectively) were pooled using generic inverse variance method with fixed/random-effects model. For each outcome variable, subgroup analysis between type 1 diabetes mellitus and type 2 diabetes mellitus was performed. RESULTS: We included five RCTs; three of type 1 diabetes mellitus (n = 1963) and two of type 2 diabetes mellitus (n = 1780). All had low risk of bias. Faster aspart was associated with small but significant improvement in HbA1c than insulin aspart (MD: -0.06%, 95% CI: -0.10, -0.02, p = 0.005, I2  = 19%). HbA1c reduction was statistically significant only in type 1 diabetes mellitus on subgroup analysis (MD: -0.08%, 95% CI: -0.14, -0.02, p = 0.005, I2  = 47%). Besides, faster aspart was associated with reduced postprandial plasma glucose (PPG) increment at 1 h/2 h after meal test and increased 1,5-anhydroglucitol compared to insulin aspart. Early postprandial hypoglycaemic episodes were higher with faster aspart; however, overall and nocturnal hypoglycaemic episodes were not different from insulin aspart. CONCLUSIONS: Faster aspart is associated with reduced HbA1c , PPG increment and comparable overall hypoglycaemic episodes with regard to insulin aspart.

COVID-19-associated mucormycosis: An updated systematic review of literature.

In its wake, the COVID-19 pandemic has ushered in a surge in the number of cases of mucormycosis. Most cases are temporally linked to COVID-19; hence, the entity is described as COVID-19-associated mucormycosis (CAM). The present systematic review was undertaken to provide an up-to-date summary of the hitherto available literature on CAM. PubMed, Scopus and Google Scholar databases were systematically searched using appropriate keywords till 14 May 2021, to identify case reports/case series pertaining to mucormycosis in patients with COVID-19. Relevant data extracted included demographic characteristics, comorbidity profile, clinical category of mucormycosis, glucocorticoid use, treatment offered and patient outcome. We identified 30 case reports/case series, pooling data retrieved from 99 patients with CAM. Most cases were reported from India (72%). The majority of the patients was male (78%) and had diabetes mellitus (85%). A prior history of COVID-19 was present in 37% patients with mucormycosis developing after an initial recovery. The median time interval between COVID-19 diagnosis and the first evidence of mucormycosis infection or CAM diagnosis was 15 days. Glucocorticoid use was reported in 85% of cases. Rhino-orbital mucormycosis was most common (42%), followed by rhino-orbito-cerebral mucormycosis (24%). Pulmonary mucormycosis was observed in 10 patients (10%). The mortality rate was 34%; the use of adjunct surgery, which was undertaken in 81% of patients, was associated with better clinical outcomes (p < .001). In conclusion, CAM is an emerging problem necessitating increased vigilance in COVID-19 patients, even those who have recovered. CAM portends a poor prognosis and warrants early diagnosis and treatment.

Clinical, morphological and immunohistochemical analysis of 13 cases of phosphaturic mesenchymal tumor - A holistic diagnostic approach.

BACKGROUND: Phosphaturic mesenchymal tumor-mixed connective tissue (PMT-MCT) is a rare tumor characterized clinically by presence of tumor-induced osteomalacia (TIO), subsequent to elevated fibroblastic growth factor 23 (FGF23) levels. This study aims to analyse the morphological spectrum of PMT along with clinico-pathological correlation and immunophenotype profile of this rare tumor. MATERIALS AND METHODS: Detailed histological analysis of all tumors presenting with TIO over past 7 years was done retrospectively. Immunohistochemistry was performed in all cases for SATB2, STAT6, CD34, FGF23, ERG, S100 and smooth muscle actin (SMA). RESULTS: A total of 13 cases were analysed (8 female and 5 male) with mean age of 39.8 years. Five cases were arising from bone while 4 each from soft tissue and nasal cavity/paranasal sinus. All presented with hypophosphatemia, hyperphosphaturia, elevated serum FGF23 and features suggestive of osteomalacia. Histological examination revealed basophilic 'grungy' calcification seen in 7 (53.8%), osteoid formation in 8 (61.5%), chondroid matrix in 4 (30.8%), adipose tissue in 6 (46.2%), osteoclast-like giant cells in 9 (69.2%) and hemangiopericytomatous (HPC like) blood vessels in 7 cases (53.8%). HPC like vessels and adipose tissue were more common in nasal tumors while calcification was more common in tumors arising from bone. All cases showed immunoreactivity for SATB2 and clinical improvement following resection except one case with residual tumor. CONCLUSION: PMT shows varied histological pattern with various matrix components depending on the site of the tumor. Serum FGF-23 is a useful adjunctive marker for diagnosis.

Metabolic Bone Profile of Healthy Adult North Indian Population from Chandigarh Urban Bone Epidemiological Study (CUBES).

We aimed to estimate metabolic bone profile in a large cohort of healthy, adult Indian population to generate reference standards of serum calcium, phosphate and alkaline phosphatase (ALP), 25 (OH) Vitamin D and iPTH, and also to find out the prevalence of Vitamin D deficiency in healthy population. Apparently healthy people in the age group of 20-80 years, residing in the union territory of Chandigarh were chosen. Fasting samples for serum calcium, phosphate, albumin, alkaline phosphatase (ALP), 25 (OH) D and iPTH were collected and were processed on the same day. We recruited 930 healthy subjects from different subsectors of Chandigarh. Final analysis was done for 915 subjects. Out of this, 530 (58%) were women and 385 (42%) were men. The study participants were divided into two groups, less than and more than 50 years for the men and pre and post-menopausal for the women. The serum calcium, phosphate, ALP and iPTH were significantly higher in the post-menopausal women compared to the pre-menopausal women. The median plasma 25 (OH) D in men and women was 12.5 ng/mL and 14.3 ng/mL, respectively. 25 (OH) D deficiency was seen in 65.4% of individuals. 25 (OH) D levels co-related negatively with iPTH levels (r = - 0.4, p < 0.0001), and showed an increasing trend with age. We have thus presented metabolic bone profile of healthy, adult north Indian population. These reference values can be used for diagnosis and monitoring of various MBDs. Vitamin D deficiency is still rampant in our population in spite of increasing awareness.

Weight gain after curative parathyroidectomy predicts increase in bone mineral density in patients with symptomatic primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (PHPT) results in reduction of bone mineral density (BMD) and an increased risk of pathological fractures. Curative surgery does improve BMD; however, the magnitude of rise and predictive factors are highly variable amongst the hitherto available studies. OBJECTIVES: To quantify the magnitude of improvement in BMD after curative surgery in patients with symptomatic PHPT and dissect out the possible clinical and biochemical parameters predicting the BMD rise. METHODS: We conducted a retrospective study of symptomatic PHPT patients undergoing surgery between August 2016 and July 2018. Patients achieving biochemical cure with pre- and post-operative (at least 1 year after surgery) dual-energy X-ray absorptiometry scans performed were included in the study. RESULTS: After exclusion, 63 patients were included in the study (M:F = 2:5; mean age = 44.8 years). At a median interval of 15 months, the median per cent change in BMD (ΔBMD) at lumbar spine (LS), total hip (TH), femoral neck (FN) and one-third distal radius (forearm) was 6.5%, 7.0%, 8.1% and 6.9%, respectively. Following multiple linear regression analysis, baseline BMD was found to inversely predict ΔBMD at LS, TH and forearm. Pre-operative iPTH positively predicted ΔBMD at LS and FN. Interestingly, 82.5% of the patients had a gain in body weight following curative surgery and change in body weight emerged as a significant positive predictor of ΔBMD at all sites. CONCLUSIONS: Curative surgery improves BMD at all sites in patients with symptomatic PHPT. Weight gain following surgery can be used as a positive clinical predictor of BMD rise.

Intracranial Germinoma Masquerading as Secondary Granulomatous Hypophysitis: A Case Report and Review of Literature.

Germinomas are highly immunogenic tumors eliciting a strong peri-tumoral immune response that can spillover into the surrounding healthy tissues. This phenomenon can also occur in intracranial germinomas, manifesting as secondary hypophysitis. Herein, we report a case of 12-year-old-girl presenting with polyuria and polydispsia. She had central diabetes insipidus (CDI) and panhypopituitarism. Imaging revealed a sellar-suprasellar mass with infundibular stalk thickening. Transphenoidal biopsy revealed epithelioid granulomas with immunostaining negative for germinomatous cells. Other causes of hypophysitis were ruled out. Accordingly, she was diagnosed as primary granulomatous hypophysitis and treated with high-dose corticosteroids. Three years later she again presented with headache, vomiting and diminution of vision. Imaging showed a heterogeneous, solid-cystic peripheral rim-enhancing lesion at the same location with involvement of hypothalamus, ependyma and pineal gland. Cerebrospinal fluid beta-human chorionic gonadotropin was markedly elevated, confirming the diagnosis of an intracranial germ cell tumor. She was started on chemotherapy; however, she succumbed to febrile neutropenia. We performed a literature search and found 18 anecdotal cases of secondary hypophysitis associated with intracranial germinomas. There was a slight male preponderance (male:female 5:4). Two-thirds of the cases were below 18 years of age. Polyuria was the most common presenting manifestation (83%). CDI and panhypopituitarism were seen in 89 and 78% cases, respectively. Imaging evidence of pituitary stalk thickening was seen in 12 cases (67%), while pituitary enlargement and/or sellar mass were reported in 11 cases (61%). Pineal involvement was extremely rare, being reported in only 1 case, implying the predilection of suprasellar (rather than pineal) germinomas in causing secondary hypophysitis. Histologically, 82% had lymphocytic hypophysitis, while 18% had granulomatous hypophysitis. Initially, the diagnosis of germinoma was missed in 60% of the cases who were wrongly treated with corticosteroids. To conclude, physicians should make it a dictum that all children and adolescents presenting with CDI and pituitary stalk thickening should be rigorously screened for an underlying intracranial germinoma before labeling them as primary hypophysitis.

Pendular See-Saw Nystagmus: A Rare Presenting Manifestation of Craniopharyngioma.

Pendular see-saw nystagmus is an extremely rare form of nystagmus characterised by cyclical movement of the eyes with a conjugate torsional component and a disjunctive vertical component. Intorsion and elevation of one eye is accompanied by simultaneous extorsion and depression of the contralateral eye. Most commonly it results from a suprasellar/parasellar mass compressing the meso-diencephalic region. Herein, we report a case of a 5-year-old girl who presented with pendular see-saw nystagmus secondary to a craniopharyngioma. The nystagmus resolved following excision of the lesion.

UTILITY OF A SINGLE LATE-NIGHT PLASMA CORTISOL AND ACTH FOR THE DIAGNOSIS OF CUSHING SYNDROME.

OBJECTIVE: To evaluate the diagnostic efficacy of various screening tests for the diagnosis of Cushing syndrome (CS). METHODS: Thirty-five patients with CS and 16 patients of pseudo-CS were enrolled. Assessment of 24-h urinary free cortisol (UFC), late-night salivary cortisol (LNSC), overnight dexamethasone suppression test (ONDST), late-night plasma cortisol (LNPC), and adrenocorticotropic hormone (ACTH) on outpatient basis, and during sleep as well as in awake state after 48 hours of hospital admission. RESULTS: We found that 24-h UFC performed the best among the screening tests with sensitivity, specificity and areas under the curve (AUCs) of 96.0%, 99%, and 0.988, respectively, at a cut-off of 144.6 µg/24 h. A cut-off of 10.5 nmol/L for LNSC had sensitivity 85.7%, specificity 88.2%, and an AUC of 0.897. A cut-off of 412.4 nmol/L for LNPC on outpatient basis had sensitivity 88.2%, specificity 91.2%, and an AUC of 0.957. Cut-offs of 215 and 243.3 nmol/L for LNPC during sleep and awake states after acclimatization had sensitivity, specificity, and an AUC of 94.1%, 88.2%, and 0.958, respectively. An ONDST cut-off of 94.6 nmol/L provided sensitivity, specificity, and an AUC of 96.0%, 99.03% and 0.995, respectively. A cut-off of 30.3 pg/mL for late-night ACTH on outpatient basis had sensitivity 67.6%, specificity 99.9%, and an AUC 0.796.A cut-off of 22.6 pg/mL for ACTH during sleep state after acclimatization had sensitivity, specificity, and an AUC of 73.5%, 99.2%, and 0.827, respectively. CONCLUSION: UFC is the best screening test for CS. Furthermore, single measurements of LNPC and ACTH help to establish the diagnosis and ACTH dependency of CS in the majority of patients with CS. ABBREVIATIONS: ACTH = adrenocorticotropic hormone AUC = area under the curve CRH = corticotropin-releasing hormone CS = Cushing syndrome ECLIA = electrochemiluminescence immuno-assay LDDST = low-dose dexamethasone suppression test LNPC = late-night plasma cortisol LNSC = late-night salivary cortisol ONDST = overnight dexamethasone suppression test RIA = radio-immuno assay UFC = urinary free cortisol.