Long-Term Follow-Up Data of Tumor-Induced Osteomalacia Managed with Surgery and/or Radiofrequency Ablation from a Single Center.

Data on radiofrequency ablation (RFA) in tumor-induced osteomalacia (TIO) are restricted to case reports (~ 11 patients) and long-term follow-up data are further scarce. We describe our experience on managing TIO from a tertiary care center in India. Retrospective study of patients with localized TIO was performed and clinical, biochemical, treatment and follow-up details were retrieved. Normalization of serum phosphorus in absence of phosphate supplementation was defined as remission. Of 33 patients (23 males), 24 patients underwent surgery as first-line treatment, and early remission, delayed remission (> 1 month for phosphorus normalization) and persistence were observed 12, 3, and 9 patients at a median follow-up of 5 (4-9) years. The gender, age, tumor size, location of tumors and FGF23 levels were not statistically different in patients who were in remission after surgery versus those with persistent disease. Second/third line treatment included conventional medical treatment and/or repeat surgery (n = 3), radiotherapy (n = 3), peptide receptor radionuclide therapy (n = 1), RFA (n = 1). Two patients had transient worsening (weeks) of weakness post-surgery. 10 patients underwent RFA (first-line n = 9); at the last follow-up 5 (4-10) years, 7 are in remission. Two of three persistent disease patients had large tumors (5.6 and 3.6 cm). There were no RFA-related complications except local ulcer in one. Although persistent disease was present in a few patients in both arms, there was no recurrence in either RFA or surgical cohort. RFA provide durable response similar to surgery, persistence requires multi-modality treatment.

Pituitary apoplexy in cushing's disease: a single center study and systematic literature review.

INTRODUCTION: Pituitary apoplexy (PA) in Cushing's disease (CD) is rare with data limited to case reports/series. METHODS: We retrospectively reviewed case records of PA in CD managed at our center from 1987 to 2023 and performed a systematic literature review. RESULTS: We identified 58 patients (44 females), including twelve from our center (12/315 CD, yielding a PA prevalence in CD of 3.8%) and forty six from systematic review. The median age at PA diagnosis was 35 years. The most common presentation was type A (79.3%) and symptom was headache (89.6%), with a median Pituitary Apoplexy Score (PAS) of 2. Median cortisol and ACTH levels were 24.9 µg/dl and 94.1 pg/ml, respectively. Apoplexy was the first manifestation of underlying CD in 55.2% of cases, with 31.1% (14/45) presenting with hypocortisolemia (serum cortisol ≤ 5.0 µg/dl), underscoring the importance of recognizing clinical signs/symptoms of hypercortisolism. The median largest tumor dimension was 1.7 cm (53/58 were macroadenomas). PA was managed surgically in 57.8% of cases, with the remainder conservatively managed. All five PA cases in CD with microadenoma achieved remission through conservative management, though two later relapsed. Among treatment-naïve CD patients with macroadenoma, PA-related neuro-deficit improvement was comparable between surgical and conservative groups. However, a greater proportion of surgically managed patients remained in remission longer (70% vs. 38.5%; p = 0.07), for an average of 31 vs. 10.5 months. CONCLUSION: PA in CD is more commonly associated with macroadenomas, may present with hypocortisolemia, and surgical treatment tends towards higher and longer-lasting remission rates.

Luteinizing hormone ß-subunit deficiency: Report of a novel LHB likely pathogenic variant and a systematic review of the published literature.

CONTEXT: Selective deficiency of ß-subunit of luteinizing hormone (LHB) is a rare disease with scarce data on its characteristics. OBJECTIVES: To describe a male with LHB deficiency and systematically review the literature. DESIGN AND PATIENTS: Description of a male patient with LHB deficiency and a systematic review of LHB deficiency patients published to date (10 males and 3 females) as per PRISMA guidelines. RESULTS: A 36-year-old Asian Indian male presented with infertility. On evaluation, he had sexual maturity of Tanner's stage 3, low testosterone (0.23 ng/ml), low LH (0.44 mIU/ml), high follicle-stimulating hormone (FSH, 22.4 mIU/ml), and a novel homozygous missense likely pathogenic variant (p.Cys46Arg) in LHB. In the molecular dynamics simulation study, this variant interferes with heterodimerization of alpha-beta subunits. Eleven males with pathogenic variants in LHB reported to date, presented at a median age of 29 (17-38) years, most commonly with delayed puberty. Clinical and biochemical profiles were similar to those of our patient. In the majority, testosterone monotherapy modestly increased testicular volume whereas human chorionic gonadotropin (hCG) monotherapy also improved spermatogenesis. In females, oligomenorrhoea after spontaneous menarche was the most common manifestation. Ten pathogenic/likely pathogenic variants (three in-frame deletions, three missense, two splice-site, one nonsense, and one frameshift variants) have been reported in nine index patients. CONCLUSION: We report a novel likely pathogenic LHB variant in an Asian Indian patient. The typical phenotype in male patients with LHB deficiency is delayed puberty with low testosterone, low LH, and normal to high FSH and hCG monotherapy being the best therapeutic option.

Comparison of 4D computed tomography and F-18 fluorocholine PET for localisation of parathyroid lesions in primary hyperparathyroidism: A systematic review and meta-analysis.

Minimally invasive parathyroidectomy (MIP) is the standard of care for primary hyperparathyroidism (PHPT). Four dimensional computed tomography(4DCT) and F-18 Fluorocholine positron emission tomography/computed tomography (FCH PET/CT) localize adenomas accurately to perform MIP. We aimed to conduct a systematic review and metanalysis to evaluate the diagnostic performance of 4DCT and FCH PET/CT scan for quadrant wise localisation in PHPT patients and to do head-to-head comparison between these two modalities. DESIGN, PATIENTS AND MEASUREMENT : After searching through PubMed and EMBASE databases, 46 studies (using histology as a gold standard) of 4DCT and FCH PET/CT were included. RESULTS: Total number of patients included were 1651 and 952 for 4DCT scan (studies n = 26) and FCH PET/CT scan (studies n = 24) respectively. In per patient analysis, FCH PET/CT and 4DCT had pooled sensitivities of 92% (88-94) and 85% (73-92) respectively and in per lesion analysis, 90% (86-93) and 79% (71-84), respectively. In the subgroup with negative conventional imaging/persistent PHPT, FCH PET/CT had comparable sensitivity to 4DCT (84% [74-90] vs. 72% [46-88]). As per patient wise analysis, FCH PET/CT had better detection rates than 4DCT ([92.4 vs. 76.85], odds ratio -3.89 [1.6-9.36] p = .0024) in the subpopulation where both FCH PET/CT and 4DCT were reported. CONCLUSION: Both 4DCT and FCH PET/CT scan performed well in newly diagnosed patients, patients with persistent disease and in those with inconclusive conventional imaging results. FCH PET/CT scan had a higher pooled sensitivity than 4DCT in detecting patients with PHPT in head to head comparison.

Prevalence of primary aldosteronism in type 2 diabetes mellitus and hypertension: A prospective study from Western India.

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.

17ß hydroxysteroid dehydrogenase 3 deficiency in 46,XY disorders of sex development: Our experience and a gender role-focused systematic review.

OBJECTIVES: To describe Asian Indian patients with 17ß hydroxysteroid dehydrogenase 3 (17ßHSD3) deficiency and to perform a systematic review to determine the factors influencing gender role in 46,XY disorder of sex development (DSD) due to 17ßHSD3 deficiency. PATIENTS AND DESIGN: We present the phenotypic and genotypic data of 10 patients (9 probands and 1 affected family member) with 17ßHSD3 deficiency from our 46,XY DSD cohort (N = 150; Western India) and a systematic review of 152 probands with genetically proven, index 17ßHSD3 deficiency patients from the world literature to identify the determinants of gender role. RESULTS: 17ßHSD3 deficiency was the third most common (6%) cause of non-dysgenetic 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 17ßHSD3 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 17ßHSD3 deficiency were noted which needs further evaluation for the underlying molecular mechanisms.

Direct Costs of Healthcare among Patients with Deliberate Self-harm: A Pilot Study from a Tertiary Care Hospital in South India.

Background: Deliberate self-harm (DSH) in developing nations has a significant impact on health and economic conditions of patients and families. Materials and methods: This retrospective study aims to study the cost of hospitalization and the factors affecting the cost of medical care. Adult patients with a diagnosis of DSH were included. Results: A total of 107 patients were included with the most common type of poison consumed being pesticides (35.5%) followed by a tablet overdose (31.8%). There was a male preponderance with a mean (SD) age of 30.04 (9.03) years. The median cost of admission was ₹13,690 (USD 195.57); DSH with pesticide increased the cost of care by 67% as compared to non-pesticides. Other factors which increased the cost were need for intensive care, ventilation, use of vasopressors, and development of ventilator-associated pneumonia (VAP). Conclusions: Pesticide-based poisoning is the most frequent cause of DSH. Among different types of DSH, pesticide poisoning is associated with a higher direct cost of hospitalization. How to cite this article: Barnabas R, Yadav B, Jayakaran J, Gunasekaran K, Johnson J, Pichamuthu K, et al. Direct Costs of Healthcare among Patients with Deliberate Self-harm: A Pilot Study from a Tertiary Care Hospital in South India. Indian J Crit Care Med 2022;26(7):836-838.

Prospective study to assess the treatment modalities and fever defervescence in patients with scrub typhus from a tertiary care centre in South India.

BACKGROUND AND OBJECTIVES: Fever defervescence in scrub typhus, a zoonotic bacterial infection is used as a surrogate marker of disease resolution. Failure of fever defervescence prompts clinicians to suspect alternate diagnoses and treatment. In this observational study, various treatment regimens were correlated with clinical outcomes. METHODS: All adult patients with a diagnosed scrub typhus were included; various antibiotic regimens used and clinical outcomes were studied. Data was analyzed using SPSS software for windows 16, with a 2-sided P-value of 0.05 or less was considered statistically significant. RESULTS: In 177 hospitalized patients with scrub typhus, combination therapy (doxycycline and azithromycin) was used in 74 subjects with doxycycline and azithromycin used in 46 and 57 subjects, respectively. Incidence of delayed defervescence was seen in 31.6%, Combination therapy being preferred in sicker patients (SOFA score 8.82). Presence of respiratory dysfunction was associated with a delay in fever defervescence [risk ratio 2.50(1.18-5.3)]. Patients receiving doxycycline did better in terms of oxygen requirement and the presence of hypotension. The overall case fatality rate was 5.6%. The severity of illness rather than the choice of antibiotics predicted the outcome in scrub typhus. INTERPRETATION & CONCLUSION: Combination therapy with doxycycline and azithromycin is the most common regimen used. Incidence of delayed defervescence (31.6%) is increasing despite therapy and the involvement of respiratory dysfunction is an independent predictor of delayed fever defervescence.

46,XX aromatase deficiency: A single-center experience with the varied spectrum and recurrent variants, and a systematic review of hormonal parameters.

BACKGROUND: Aromatase deficiency is a rare disorder, with only a few cases reported in India. We describe a single-center experience in western India, with a systematic review of genetically proven 46,XX aromatase deficiency patients to evaluate hormonal parameters. METHODS: Retrospective review of case records, collating phenotypic and genotypic data and molecular modeling. Systematic review of 46,XX aromatase deficiency, analyzing data on gonadotropins, estrogen and androgens. RESULTS: In the seven patients from our center, presentation was frequent in childhood or adolescence (4/7: delayed puberty or hyperandrogenism), with maternal virilization (4/7), predominance of Prader III/IV (5/7), and initial rearing as females (6/7). Three patients had hypoplastic ovaries. One patient had spontaneous regular menses. We report three novel (p.Arg115Pro, p.Arg192Pro, and c.145+1_145+4delins) and two recurrent variants (p.Val370Met, and c.145+1_145+4delins) in western and northern India, respectively. On systematic review (n=43), gonadotropins were elevated (FSH>LH) across ages (except preterm infants), androgens were elevated in about one-third of cases during childhood and puberty, and estradiol was lower than in controls in mini-puberty and puberty. Spontaneous thelarche and streak ovaries were significantly more frequent in patients with non-truncating and truncating variants, respectively. CONCLUSION: We report uncommon presentations with possible founder variants, and highlight hormonal parameters across ages. Serum FSH levels were elevated except in preterms, and can be used as a diagnostic marker.

Efficacy and safety of burosumab compared with conventional therapy in patients with X-linked hypophosphatemia: A systematic review.

Burosumab, a monoclonal antibody directed against the fibroblast growth factor 23 (FGF23), has been approved for the treatment of X-linked hypophosphatemia (XLH). We conducted a systematic review to compare the efficacy and safety of burosumab versus conventional therapy (phosphorus and calcitriol) on XLH treatment. After a comprehensive literature search on MEDLINE/PubMed and Embase, we found nine studies for inclusion in the analysis. Risk of bias was assessed, and a random-effects model was used to determine the effect size. Clinical, biochemical, and radiological parameters of disease severity before and after treatment were analyzed and expressed in standardized mean difference (SMD). Burosumab resulted in normalization of phosphate homeostasis with an increase in renal tubular phosphate reabsorption and significant resolution of skeletal lesions (change in Thacher's total rickets severity score SMD: -1.46, 95% confidence interval [CI]: -1.76 to -1.17, p < 0.001, improvement in deformities, and decline in serum alkaline phosphatase levels [SMD: 130.68, 95% CI: 125.26-136.1, p < 0.001)]. Conventional therapy led to similar improvements in all these parameters but to a lower degree. In adults, burosumab normalized phosphorus levels (SMD: 1.23, 95% CI: 0.98-1.47, p < 0.001) with resultant clinical improvement. Burosumab treatment was well tolerated, with only mild treatment-related adverse effects. The present review indicates a potential role for burosumab in improving rickets, deformities, and growth in children with XLH. Given its superior efficacy and safety profile, burosumab could be an effective therapeutic option in children. We suggest further studies comparing burosumab versus conventional therapy in children and adults with XLH.

17α-Hydroxylase/17,20-Lyase Deficiency in 46,XY: Our Experience and Review of Literature.

CONTEXT: There are more than 100 pathogenic variants in CYP17A1 that have been identified in patients with 17α-hydroxylase/17,20-lyase deficiency (17OHD). OBJECTIVE: We aimed to describe 46,XY patients with 17OHD from our center and review the literature. METHODS: 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 divided in 2 categories as < 1% and ≥ 1%, each for hydroxylase and lyase. RESULTS: We present 4 index cases of 46,XY 17OHD with a complete spectrum of undervirilization and 2 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. Immunoassay-measured serum aldosterone was frequently (68.2%) unsuppressed (>5 ng/dL). Elevated serum progesterone had high sensitivity for diagnosis of combined 17OHD, even in combined partial deficiency (83.3%). Among patients with clinical phenotype of combined severe deficiency, 11.5% had partial 17α-hydroxylase and complete 17,20-lyase deficiency (>1%/<1%) and had significantly higher serum cortisol than those 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 undervirilization 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.

Low-Dose, Low-Specific Activity 131I-metaiodobenzyl Guanidine Therapy in Metastatic Pheochromocytoma/Sympathetic Paraganglioma: Single-Center Experience from Western India.

INTRODUCTION: Radionuclide therapy is a promising treatment modality in metastatic pheochromocytoma/paraganglioma (PPGL). There is scarce data on 131I-metaiodobenzyl guanidine (131I-MIBG) therapy from the Indian subcontinent. Hence, we aim to study the safety and effectiveness of low-dose, low-specific activity (LSA) 131I-MIBG therapy in patients with symptomatic, metastatic PPGL. METHODS: Clinical, hormonal, and radiological response parameters and side effects of LSA 131I-MIBG therapy in patients with symptomatic, metastatic PPGL were retrospectively reviewed. World health organizations' (WHO) symptomatic, hormonal, and tumor response, and response evaluation criteria in solid tumors (RECIST1.1) criteria were used to assess the response. RESULTS: Seventeen (PCC: 11, sympathetic PGL: 06) patients (15 with disease progression) received low-dose LSA 131I-MIBG therapy. Complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD) were 18% (3/17), 24% (4/17), 18% (3/17), and 41% (7/17), respectively, for WHO symptomatic response; 20% (2/10), 10% (1/10), 30% (3/10), and 40% (4/10), respectively, for WHO hormonal response; and 19% (3/16), 6% (1/16), 31% (5/16), and 44% (7/16), respectively for tumor response based on RECIST1.1. All patients with symptomatic PD and 50% (2/4) with hormonal PD had progression as per RECIST1.1 criteria. Side effects included thrombocytopenia, acute myeloid leukemia, mucoepidermoid carcinoma, and azoospermia in 6% (1/17) each. CONCLUSIONS: Our study reaffirms the modest efficacy and safety of low-dose, LSA 131I-MIBG therapy in patients with symptomatic, metastatic PPGL. Symptomatic, but not hormonal, progression after 131I-MIBG therapy correlates well with tumor progression and should be further evaluated with imaging. In resource-limited settings, anatomic imaging alone may be used to assess tumor response to 131I-MIBG therapy.

Exonic WT1 pathogenic variants in 46,XY DSD associated with gonadoblastoma.

OBJECTIVE: The literature regarding gonadoblastoma risk in exonic Wilms' tumor suppressor gene (WT1) pathogenic variants is sparse. The aim of this study is to describe the phenotypic and genotypic characteristics of Asian-Indian patients with WT1 pathogenic variants and systematically review the literature on association of exonic WT1 pathogenic variants and gonadoblastoma. DESIGN: Combined retrospective-prospective analysis. METHODS: In this study, 46,XY DSD patients with WT1 pathogenic variants detected by clinical exome sequencing from a cohort of 150 index patients and their affected relatives were included. The PubMed database was searched for the literature on gonadoblastoma with exonic WT1 pathogenic variants. RESULTS: The prevalence of WT1 pathogenic variants among 46,XY DSD index patients was 2.7% (4/150). All the four patients had atypical genitalia and cryptorchidism. None of them had Wilms' tumor till the last follow-up, whereas one patient had late-onset nephropathy. 11p13 deletion was present in one patient with aniridia. The family with p.Arg458Gln pathogenic variant had varied phenotypic spectrum of Frasier syndrome; two siblings had gonadoblastoma, one of them had growing teratoma syndrome (first to report with WT1). On literature review, of >100 exonic point pathogenic variants, only eight variants (p.Arg462Trp, p.Tyr177*, p.Arg434His, p.Met410Arg, p.Gln142*, p.Glu437Lys, p.Arg458*, and p.Arg458Gln) in WT1 were associated with gonadoblastoma in a total of 15 cases (including our two cases). CONCLUSIONS: WT1 alterations account for 3% of 46,XY DSD patients in our cohort. 46,XY DSD patients harboring exonic WT1 pathogenic variants carry a small but definitive risk of gonadoblastoma; hence, these patients require a gonadoblastoma surveillance with a more stringent surveillance in those harboring a gonadoblastoma-associated variant.

Preoperative Amlodipine Is Efficacious in Preventing Intraoperative HDI in Pheochromocytoma: Pilot RCT.

CONTEXT: Preoperative blockade with α-blockers is recommended in patients with pheochromocytoma/paraganglioma (PPGL). The data on calcium channel blockade (CCB) in PPGL are scarce. OBJECTIVE: We aimed to compare the efficacy of CCB and α-blockers on intraoperative hemodynamic 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 gastrointestinal therapeutic system (GITS) (maximum 30 mg, n = 9) or amlodipine (maximum 20 mg, n = 11). The primary outcomes were the episodes and duration of hypertension (systolic blood pressure ≥ 160 mmHg) and hypotension (mean arterial pressure < 60 mmHg) and duration of HDI (hypertension and/or hypotension) as a percentage of total surgical time (from induction of anesthesia to skin closure). RESULTS: The median (IQR) episodes (2 [1-3] vs 0 [0-1]; P = 0.002) and duration of hypertension (19 [14-42] vs 0 [0-3] minutes; P = 0.001) and intraoperative HDI duration (22.85 ±â€…18.4% vs 2.44 ±â€…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 2 groups. There was no perioperative mortality. 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). CONCLUSION: 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.

The Utility of 68Ga-DOTATATE PET/CT in Localizing Primary/Metastatic Pheochromocytoma and Paraganglioma: Asian Indian Experience.

Purpose: Pheochromocytoma and paraganglioma (PGL), together called PPGL, are rare tumors with a limited number of studies on the diagnostic performance of 68Ga-DOTA (0)-Tyr (3)-octreotate positron emission tomography-computed tomography (68Ga-DOTATATE PET/CT) from the Asian-Indian subcontinent. Materials and Methods: In this retrospective study, PPGL suspects (n = 87) who had undergone at least contrast-enhanced computed tomography (CECT) and 68Ga-DOTATATE PET/CT, were included. Lesion-wise, patient-wise, and region-wise sensitivities of 68Ga-DOTATATE PET/CT, 18F fluorodeoxyglucose positron emission tomography CT (18F-FDG PET/CT, n = 53), 131I-metaiodobenzylguanidine (131I-MIBG, n = 37), and CECT were compared, and diagnostic performance of 68Ga-DOTATATE PET/CT in the detection of PPGL was calculated. Results: 68Ga-DOTATATE PET/CT had significantly higher lesion-wise sensitivity than 131I-MIBG for both primary (94% vs 75%, P = 0.004) and metastatic disease (85% vs 59%, P = 0.001) and higher sensitivity than CECT for metastatic lesions (83% vs 43%, P = 0.0001). The lesion-wise sensitivity of 68Ga-DOTATATE PET/CT was similar to 18F-FDG PET/CT for both primary tumors (94% vs 85%, P = 0.08) and metastatic lesions (82% vs 84%, P = 0.76) in the whole cohort but tended to be inferior in the head to head comparison. Conclusion: 68Ga-DOTATATE PET/CT had higher sensitivity for detection of PPGL than 131I-MIBG (primary and metastatic) and CECT (metastatic) but similar to 18F-FDG PET/CT (primary and metastatic).

Clinical, Hormonal, Genetic, and Molecular Characteristics in Androgen Insensitivity Syndrome in an Asian Indian Cohort from a Single Centre in Western India.

The study aimed to analyze clinical and hormonal phenotype,and genotype in patients with genetically proven androgen insensitivity syndrome (AIS) from Western India. Index patients with pathogenic variants in the androgen receptor (AR) gene were identified from a consecutive 46,XY DSD cohort (n = 150) evaluated with clinical exome sequencing, and their genetically-proven affected relatives were also included. In sum, 15 index cases (9 complete AIS [CAIS] and 6 partial AIS [PAIS]) were identified making AIS the second most common (10%) cause of 46,XY DSD, next to 5α-reductase 2 deficiency (n = 26; 17.3%). Most patients presented late in the postpubertal period with primary amenorrhoea in CAIS (89%) and atypical genitalia with gynecomastia in PAIS (71.4%). All CAIS were reared as females and 83.3% of PAIS as males with no gender dysphoria. Four of 6 patients with available testosterone to dihydrotestosterone ratio had a false elevation (>10). Metastatic dysgerminoma was seen in 1 patient in CAIS, while none in the PAIS group had malignancy. Fifteen different (including 6 novel) pathogenic/likely pathogenic variants in AR were found. Nonsense and frameshift variants exclusively led to CAIS phenotype, whereas missense variants led to variable phenotypes. In this largest, monocentric study from the Asian Indian subcontinent, AIS was the second most common cause of 46,XY DSD with similar phenotype but later presentation when compared to cases in the rest of the world. The study reports 6 novel pathogenic variants in AR.

Symptomatic HIV CNS viral escape among patients on effective cART.

OBJECTIVE: The clinical syndrome in symptomatic HIV associated CNS viral escape is poorly defined. We attempted to describe the clinical syndrome, laboratory profile, radiological features and outcomes of HIV infected patients with symptomatic central nervous system (CNS) viral escape in our study. METHODS: This is a retrospective study were adult patients with HIV infection on cART admitted with a diagnosis of CD8 encephalitis or CNS viral escape in a large teaching hospital in South India was identified. RESULTS: The mean age of the eleven patients included in the study was 37.5 years. Most patients had received almost a decade of antiretroviral treatment at diagnosis (mean: 11.18 years). All patients presented with global cerebral syndrome. Cognitive decline, tremors, and headaches were common manifestations. All patients had lymphocytic pleocytosis (mean cell count: 44.63 cells/ml; lymphocyte percentage: 94.81%) with elevated protein (mean: 125.36 mg/dl). All patients were on boosted protease inhibitors (81.8% on Atazanavir and 18.18% Lopinavir). All except one patient was on Tenofovir and lamivudine combination therapy. White matter changes and deep brain nuclei involvement were common. Most patients required a change of cART to regimens with better CNS penetration and suppression of the resistant virus in the plasma and improved. CONCLUSION: CNS viral escape should be considered as a differential among patients on Atazanavir presenting with non-focal cerebral syndrome and CSF lymphocytic pleocytosis.

Efficacy and safety of burosumab compared with conventional therapy in patients with X-linked hypophosphatemia: A systematic review

ABSTRACT Burosumab, a monoclonal antibody directed against the fibroblast growth factor 23 (FGF23), has been approved for the treatment of X-linked hypophosphatemia (XLH). We conducted a systematic review to compare the efficacy and safety of burosumab versus conventional therapy (phosphorus and calcitriol) on XLH treatment. After a comprehensive literature search on MEDLINE/PubMed and Embase, we found nine studies for inclusion in the analysis. Risk of bias was assessed, and a random-effects model was used to determine the effect size. Clinical, biochemical, and radiological parameters of disease severity before and after treatment were analyzed and expressed in standardized mean difference (SMD). Burosumab resulted in normalization of phosphate homeostasis with an increase in renal tubular phosphate reabsorption and significant resolution of skeletal lesions (change in Thacher's total rickets severity score SMD: −1.46, 95% confidence interval [CI]: −1.76 to −1.17, p < 0.001, improvement in deformities, and decline in serum alkaline phosphatase levels [SMD: 130.68, 95% CI: 125.26-136.1, p < 0.001)]. Conventional therapy led to similar improvements in all these parameters but to a lower degree. In adults, burosumab normalized phosphorus levels (SMD: 1.23, 95% CI: 0.98-1.47, p < 0.001) with resultant clinical improvement. Burosumab treatment was well tolerated, with only mild treatment-related adverse effects. The present review indicates a potential role for burosumab in improving rickets, deformities, and growth in children with XLH. Given its superior efficacy and safety profile, burosumab could be an effective therapeutic option in children. We suggest further studies comparing burosumab versus conventional therapy in children and adults with XLH.

An uncommon cause of osteoporosis.

Osteoporosis in the younger age group is an important cause of morbidity. Prolactinoma is an uncommon but reversible cause of osteoporosis. The main mechanisms of osteoporosis in prolactinoma are reduced osteoblast activity and hypogonadism. A high index of suspicion is the key in diagnosis and management of this treatable entity.