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Background Preoperative blockade with α-blockers is recommended in patients with pheochromocytoma/paraganglioma (PPGL). The data on calcium channel blockade (CCB) in PPGL is scarce. We aimed to compare the efficacy of CCB and α-blockers on intraoperative haemodynamic instability (HDI) in PPGL. Methods In the interim analysis of this monocentric, pilot, open-label, randomized controlled trial, patients with solitary, secretory, and nonmetastatic PPGL were randomized to oral prazosin GITS (maximum 30mg, n=9) or amlodipine (maximum 20mg, n=11). The primary outcomes were the episodes and duration of hypertension (SBP≥160mmHg) and hypotension (MAP<60mmHg) and duration of HDI (hypertension and/or hypotension) as a percentage of total surgical time (from induction of anaesthesia to skin closure). Findings The median (IQR) episodes (2 [1-3] vs. 0 [0-1], p 0·002) and duration of hypertension (19 [14-42] min vs. 0 [0-3] min, p 0·001) and intraoperative HDI duration (22·85±18.4% vs 2·44±2·4%, CI 8·68–32·14%, p 0·002) were significantly higher in the prazosin GITS arm than the amlodipine arm whereas episodes and duration of hypotension did not differ between the two groups. There was no perioperative mortality whereas one patient had intraoperative ST depression on the electrocardiogram. The drug-related adverse effects were pedal edema (1 in amlodipine), dizziness (1 in prazosin GITS), and tachycardia (6 in prazosin GITS and 3 in amlodipine). Interpretation Preoperative blockade with amlodipine is an efficacious alternative to prazosin GITS in preventing intraoperative HDI in PPGL. Larger studies that compare preoperative blockade by amlodipine with other α-blockers like phenoxybenzamine and/or doxazosin in PPGL patients are warranted.

Objectives: To describe Asian Indian patients with 17β hydroxysteroid dehydrogenase 3 (17βHSD3) deficiency and to perform a systematic review to determine the factors influencing gender role in 46,XY disorder of sex development (DSD) due to 17βHSD3 deficiency. Patients and Design:We present the phenotypic and genotypic data of 10 patients (9 probands and 1 affected family member) with 17βHSD3 deficiency from our 46,XY DSD cohort (N = 150; Western India) and a systematic review of 152 probands with genetically proven, index 17βHSD3 deficiency patients from the world literature to identify the determinants of gender role.Results: 17βHSD3 deficiency was the third most common (6%) cause of nondysgenetic 46,XY DSD in our cohort. Five patients each had prepubertal (atypical genitalia) and pubertal (primary amenorrhoea) presentations. Six patients were initially reared as female of whom two (one each in prepubertal and pubertal age) changed their gender role. Ten pathogenic molecular variants (six novel) were observed. In the systematic review, initial male sex of rearing was uncommon (10.5%) and was associated with atypical genitalia, higher testosterone/androstenedione (T/A) ratio and Asian origin. Gender role change to male was seen in 10.3% of patients with initial female sex of rearing and was associated with Asian origin but unrelated to pubertal androgens or molecular variant severity. It has not been reported in patients of European origin. Conclusions:We report the first Indian case series of 17βHSD3 deficiency, the third most common cause of 46,XY DSD, with six novel molecular variants. Distinct geographical differences in the frequency of initial male sex of rearing and gender role change to male in those initially reared as females in 17βHSD3 deficiency were noted which needs further evaluation for the underlying molecular mechanisms.

Objective To describe 46,XY patients with 17α-hydroxylase/17,20-lyase deficiency (17OHD) from our center and perform literature review. Design Retrospective analysis and literature review Patients and measurements: We retrospectively analyzed genetically-proven index cases of 17OHD from our 46,XY disorders of sex development cohort and reviewed similar cases from the literature (n=150). Based on the phenotype, 17OHD probands were classified into combined severe deficiency (n=128), and combined partial deficiency (n=16). Additionally, patients with the apparent isolated 17,20-lyase deficiency (n=7, from 6 families) were noted. Residual enzyme activities with the observed mutant enzymes were arbitrarily divided in two categories as <1% and ≥1%, each for hydroxylase and lyase. Results We present four index cases of 46,XY 17OHD with a complete spectrum of undervirilization and two novel variants in CYP17A1. In the review, the combined severe deficiency was the most common form, with more frequent female sex of rearing, hypertension, hypokalemia, suppressed renin, higher plasma corticotropin, lower serum cortisol and androgens, and higher proportion had <1%/<1% enzyme activity as compared to combined partial deficiency. Immunoassay-measured serum aldosterone was frequently (68.2%) unsuppressed (>5ng/dl). Elevated serum progesterone had high sensitivity for the diagnosis of combined 17OHD, even in combined partial deficiency (83.3%). Among patients with clinical phenotype of combined severe deficiency, 11.5% of patients had partial 17α-hydroxylase and complete 17,20-lyase deficiency (>1%/<1%) and had significantly higher serum cortisol than group with <1%/<1% activity. Conclusion We report the first monocentric case series of Asian-Indian 46,XY patients with 17OHD. We propose that a phenotype of severe undervirilisation with milder cortisol deficiency may represent a distinct subtype of combined severe 17OHD with residual 17α-hydroxylase activity but severe 17,20-lyase deficiency (>1%/<1%), which needs further validation.

Objective Type 2 diabetes mellitus (T2DM) and hypertension commonly coexist; however, underlying primary aldosteronism (PA) can lead to worsening of hypertension, glycemia and cardiovascular risk. We aim to screen patients with T2DM and hypertension for PA by conducting a prospective monocentric study from Western India, which included adults with T2DM and hypertension from the outpatient diabetes clinic. Design Prospective study. Patients and Measurements Patients with an aldosterone renin ratio of ≥1.6 ng/dl/µIU/ml with plasma aldosterone concentration (PAC) ≥ 10 ng/dl were considered to be positive on a screening test. A PAC ≥ 6 ng/dl on seated saline suppression test (SST) was used to confirm the diagnosis of PA. Results Four hundred and eighty‐six patients were included in this study. Seventy‐six (15.6%, 95% confidence interval [CI]: 12.7%–19.1%) patients had a positive screening test with positive confirmatory test in 20 of the 36 (55.5%, 95% CI: 39.3%–71.7%) screen‐positive patients who underwent SST. Patients with positive screening test had a higher proportion of females (65.8% vs. 50%; p = .011), frequent history of hypertensive crises (21.1% vs. 8%; p = .001), uncontrolled blood pressure (51.3% vs. 34.6%; p = .006), diagnosis of hypertension before diabetes (32.9% vs. 21.7%; p = .035) and higher systolic (137.6 ± 6.9 vs. 131.2 ± 17.8 mmHg; p = .004) and diastolic (85.3 ± 11.1 vs. 81.7 ± 10.7 mmHg; p = .007) blood pressures. Patients with positive confirmatory test had longer duration of diabetes (108 [60–162] vs. 42 [24–87] months; p = .012), hypertension (84 [42–153] vs. 36 [15–81] months; p = .038) and higher creatinine (1.16 [1.02–1.42] vs. 0.95 [0.84–1.12] mg/dl; p = .021). Conclusions PA is prevalent (at least 4.1%) in Asian Indian patients with T2DM and hypertension. Further studies are needed to assess the cost‐effectiveness of routine screening.