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Context/Aims: Pheochromocytoma and paraganglioma (PPGL) are rare tumors, and data on ambulatory blood pressure monitoring (ABPM) in these patients and the effect of blocking on ABPM parameters is limited. We aimed to describe ABPM parameters in a cohort of PPGL at our center in western India. Methods: Retrospective study of patients with PPGL whose ABPM data was available. Demographic details, secretory status, and ABPM data were retrieved. Coefficient of variability (CV) was calculated as standard deviation/mean in percentage. Results: In the 39 included patients, mean age at presentation was 39.3 ± 14.2 yr; 20 (51.3%) were males, 25 (64.1%) hypertensive, and mean tumor diameter was 5.3 cm. In 18 patients whose baseline ABPM was done without medications, those with nocturnal blood pressure dipping (6/18, 33%) had higher serum metanephrines (median 313.2 vs. 34.7 pg/ml, P = 0.028). Despite normal office blood pressure (BP), 8.9% of systolic BP readings were >140 mmHg, and 1.2% were >160 mmHg. Among 29 patients with both pre and post-block ABPM, mean BP (systolic 121.6 vs. 132.5 mmHg, P = 0.014; diastolic 68.9 vs. 76.4 mmHg, P = 0.005) and percentage of BP readings above 140 mmHg (median 9.4% vs. 24.4%, P = 0.016) were significantly lowered after the preoperative blockade in hypertensive (n = 19) patients, whereas CV was similar. The post-blockade ABPM characteristics were similar in patients blocked with amlodipine or prazosin. Conclusion: ABPM provides additional information about BP characteristics in PPGL. The preoperative blocking decreases the magnitude of BP excursions but does not affect BP variability. [ABSTRACT FROM AUTHOR]

Background: To elucidate the role of various imaging modalities for tumor localization in ectopic ACTH Cushing's syndrome (EAS)., Design and Method: Systematic review of the literature published between January 2015-2024 was performed. Patients (290 EAS patients, 23.8% Occult) who underwent contrast enhanced CT (CECT) and at least one PET/CT-scan ( 68 Ga-SSTR, FDG and/or F-DOPA) were included., Results: The sensitivity for identifying EAS tumor was comparable across CECT (63.1%, n=290), SSTR-PET/CT (58.2%, n=187), and FDG-PET/CT (57.6%, n=191), but was poor for DOPA-PET/CT (30.8%, n=26). Sensitivity for detecting metastasis was also comparable across CECT (78%, n=73), SSTR-PET/CT (85.3%, n=41), and FDG-PET (73.7%, n=38). For localised lesions, sensitivity as per etiology and grade of NET were similar for three scans, with exception of Thymic NET and grade 1 NET where CECT was better than FDG PET/CT. In patients not localised on CECT, sensitivity of SSTR PET/CT was 33.3% (vs. 18.9% FDG-PET/CT) whereas for patients negative on CECT and FDG-PET, sensitivity of SSTR-PET/CT was 15%. In cases where CECT and SSTR-PET/CT failed to localize, the sensitivities of FDG-PET/CT and DOPA-PET/CT were only 5.7% (2/35) and 0% (0/9), respectively. SSTR-PET/CT has a distinct advantage with significantly lesser false positive (FP) lesions (2.6%, mostly in thyroid/or pancreas). In comparison, CECT and FDG-PET/CT had FP ∼11% (mostly in lung and/or mediastinum), most of which were negative on SSTR-PET/CT., Conclusions: As per the current evidence, SSTR-PET/CT can be considered as the scan of choice in EAS evaluation, and further research is needed as one-fourth of the lesions remain occult., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Introduction: Differentiating pheochromocytomas from other adrenal masses based on computed tomography (CT) characteristics remains challenging, particularly in lipid-poor lesions with variable washout patterns. This study evaluated CT features for distinguishing pheochromocytomas in good and poor washout subcohorts., Methods: We prospectively analyzed 72 patients with unilateral lipid-poor adrenal masses. CT protocol included basal, bolus-tracked arterial, early venous (45 seconds postarterial), and delayed (15 minutes postarterial) phases. Masses were categorized into good and poor washout groups. Histopathology provided the final diagnosis. CT characteristics and calculated indices were compared between pheochromocytomas and other masses in each washout category., Results: The cohort included pheochromocytomas (n = 35), adrenocortical carcinoma (ACC; n = 15), lipid-poor adenomas (n = 13), and metastatic infiltration/infection (n = 9). In the good washout group, pheochromocytomas (n = 15) showed larger diameters (6.00 vs 3.45 cm, P = .001), higher necrosis frequency (73.3% vs 30%, P = .049), and greater arterial attenuation (173.2 vs 74.5 HU, P < .001) compared to adenomas (n = 9). Arterial attenuation provided a high discriminatory value [area under the curve (AUC): 0.967], with 100% sensitivity at 87.6 Hounsfield unit (HU) and 100% specificity at 139.9 HU. In the poor washout group, pheochromocytomas (n = 20) exhibited higher arterial attenuation (99.2 vs 59.2 HU, P < .001; AUC: 0.844) compared to ACC (n = 14), metastatic infiltration (n = 9), and adenomas (n = 4), with 85% sensitivity and 78% specificity at 73.3 HU. Normetanephrine-secreting/nonsecretory pheochromocytomas showed higher arterial enhancement than metanephrine-secreting ones (132.0 vs 90.5 HU, P = .020) within the poor washout group., Conclusion: Arterial phase attenuation on CT has good diagnostic accuracy for differentiating pheochromocytomas from other adrenal masses in both good and poor washout categories, potentially guiding hormonal workup., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Unrelieved cancer pain can seriously reduce patients' quality of life. Hydromorphone based patient-controlled analgesia (PCA) is widely used in surgery. In recent years, it has also gained attention in the field of cancer pain. We report the case of an older patient with refractory pain secondary to colorectal cancer for whom PCA therapy led to improved symptomatic outcomes., Case Description: We present the case of a 79-year-old male with severe pain from advanced colon cancer. After receiving anti-cancer therapy for 7 years, the patient developed pain in the right groin with a pain score of 7/10. The results of whole-body bone imaging suggested the underlying cause to be a pelvic osseous metastasis. Contemporaneous computed tomography (CT) scanning confirmed disease progression in previously noted non-osseous sites of disease. Systemic therapy with bevacizumab, oxaliplatin, and raltitrexed was commenced. For pain palliation, the patient was treated with morphine hydrochloride tablets, morphine hydrochloride injections, compound codeine phosphate and ibuprofen sustained release tablets, incadronate disodium for injection, and oxycodone hydrochloride sustained-release tablets; despite this, his pain remained poorly controlled. The patient was admitted to hospital with a pain score of 8/10. Other symptoms at presentation included fatigue, anorexia, distress and insomnia. A hydromorphone PCA was initiated, which led to a rapid improvement in the patient's pain. The patient died peacefully 17 days later; his family was highly satisfied., Conclusions: Older patients with cancer experience pain in myriad ways. Patients with advanced cancer pain should receive safe, rapid, and effective pain relief. Hydromorphone-based PCA therapies may provide a valuable therapeutic option for individuals with malignant pain., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-713/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Purpose: Data on the polar vessel sign (enlarged feeding vessel terminating in parathyroid lesions) on four-dimensional computed tomography (4D-CT) is limited. We performed a retrospective analysis to determine the prevalence, predictors, and adjunctive utility of polar vessel sign in pre-operative 4D-CT of patients with primary hyperparathyroidism (PHPT)., Methods: One radiologist blinded to the patients' details reported the 4D-CT of eighty-four operated patients with histopathology-proven single-gland PHPT. Two protocols were used to obtain arterial-phase images: timed via bolus tracking (n = 41) or fixed at 20 s after contrast injection (n = 43)., Results: Seventy-one patients were symptomatic for PHPT, with median serum calcium 12.1 mg/dL. On the arterial phase of 4D-CT, 88.1% of lesions had the polar vessel sign, including 7/9 asymptomatic patients, 6/6 parathyroid carcinomas, and 3/4 ectopic(1:mediastinum, 2:thyro-thymic ligament). Predictors of polar vessel sign were maximum lesion dimension (2.2 vs. 1.4 cm; P = 0.03), solid-cystic CT morphology (47.3% vs. none; P = 0.004), and bolus tracking-timed arterial phase (55.4% vs. none; P = 0.001). Of these, bolus tracking improved the polar vessel's visualization (100% vs. 76.7%; P = 0.001) independent of lesion dimension and solid-cystic morphology. The latter two predicted polar vessel sign in images obtained at a fixed interval (20 s). A significantly lower proportion of bolus tracking-timed scans had lesion percentage arterial enhancement (PAE) < 128.9% (2/41 vs. 9/43; P = 0.04). Even with suboptimal PAE, the polar vessel helped identify 9/11 lesions., Conclusion: The polar vessel sign demonstrated an additive role to PAE during CT reporting. Bolus tracking is valuable in optimizing vessel and tumor arterial enhancement and is easily incorporated into parathyroid 4D-CT protocol., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To describe the genotype-phenotype characteristics of patients with 21-hydroxylase deficiency from western India and ascertain the prevalence of various phenotypes of 21-hydroxylase deficiency., Methods: Patients with 21-hydroxylase deficiency, diagnosed clinically and biochemically, were prospectively enrolled and classified into salt wasting (SW), simple virilizing (SV), and non-classic (NC) phenotypes and were subjected to genetic testing of CYP21A2 by targeted sequencing and multiplex ligation-dependent probe amplification (MLPA)., Results: Eighty (64; 46, XX) probands with 21-hydroxylase deficiency were analyzed. 41 had SW, 34 had SV, and 5 had NC phenotype. Disease-causing mutations were identified in 158/160 alleles. The common mutations were Deletions/Large Gene Conversions (Del/LGC, 25.6%), p.293-13A/C>G (22.5%), and p.Ile173Asn(18.75%). Exon 6 cluster mutations (Ile236Asn, Val237Glu, Met238Lys) and p.Val282Leu were absent. c.-113G>A+p.Pro31Leu (6.87%) and p.Phe405Ser (2.5%) were rare recurrent mutations with a possible founder effect. Two novel variants (Exon 1, p.Leu49Arg, Exon 8, p.Leu362Ter) were identified and were estimated to have low enzyme activity (<2%)., Conclusion: Del/LGC were the most common mutations identified. The c.-113G>A+p.Pro31Leu and p.Phe405Ser were recurrent variants with possible founder effect. This study also reiterates the low prevalence of NC CAH in Indian cohorts.

Background: The data on Leydig cell hypoplasia (LCH) resulting from biallelic Luteinizing hormone/chorionic gonadotropin receptor (LHCGR) inactivating variants is limited to case series., Methods: We aim to describe our patients and perform systematic review of the patients with LHCGR inactivating variants in the literature. Detailed phenotype and genotype data of three patients from our centre and 85 (46,XY: 67; 46,XX: 18) patients from 59 families with LHCGR-inactivating variants from literature were described., Results: Three 46,XY patients (age 6-18 years) from our center, with two reared as females, had two novel variants in LHCGR. Systematic review (including our patients) revealed 72 variants in 88 patients. 46,XY patients (n = 70, 56 raised as females) presented with pubertal delay (n = 41) or atypical genitalia (n = 17). Sinnecker score ≥3 (suggesting antenatal human chorionic gonadotropin (hCG) inaction) was seen in 80% (56/70), and hCG-stimulated testosterone was low (<1.1 ng/mL) in 77.4% (24/31), whereas puberty/postpubertal age, high luteinizing hormone (LH) (97.6%, 41/42) and low (<1.0 ng/mL) basal testosterone (94.9%, 37/39) was observed in most. Follicle stimulating hormone was elevated in 21/51 of these patients. Variants with <10% receptor function were exclusively seen in cohorts with Sinnecker 4/5 (10/15 vs 0/5, P = 0.033). 46,XX patients (n = 18) presented with oligo/amenorrhea and/or anovulatory infertility and had polycystic ovaries (7/9) with median LH of 10 IU/L (1.2-38)., Conclusion: In summary, this study comprehensively characterizes LHCGR variants, revealing genotype-phenotype correlations and informing clinical management of LCH. In 46,XY LCH patients, pubertal LH inaction is uniform with variable severity of antenatal hCG inaction. Few mutant LHCGR have differential actions for LH and hCG.

Introduction: Pituitary apoplexy (PA) is a rare clinical syndrome due to acute/subacute pituitary hemorrhage and/or infarction; data on PA in functioning pituitary adenoma (FPA) is scarce., Methods: A retrospective record-review of details of PA in non-functioning (NFPA) and FPA managed at tertiary endocrine center., Results: 93 patients [56 males; 33.3% FPA: 5 acromegaly, 14 prolactinoma, and 12 Cushing's Disease (CD)] diagnosed with PA were included. Median age was 40 years, with younger age of presentation in FPA. Type A (acute) [49.5%] and headache (78.5%) were the commonest presentations, with PA being the initial manifestation in 98.4% of NFPA. Median (range) Pituitary Apoplexy Score (PAS) was 2 (0-8). Median tumor diameter was 2.5 cm, with larger tumors in FPA (3.2 cm vs. 2.3 cm). 29 (46.7%) NFPA-PA and 14 (45.2%) FPA-PA patients [71% prolactinoma, 33% in CD, and none in acromegaly] were conservatively managed. In the NFPA cohort, those managed surgically had significantly higher PAS (4 vs. 1) and larger tumor size (2.6 vs. 1.8 cm); however, both arms had comparable recovery of neuro-visual, radiological, and hormonal outcomes. In FPA cohort, CD and acromegaly required definitive treatment, whereas prolactinomas were effectively managed (clinical and biochemical recovery) with oral cabergoline and glucocorticoids. Matching PAS cohorts (to overcome allocation bias for management approach) in macroadenomas (excluding prolactinoma) showed comparable neuro-deficit and hormonal recovery between surgical and conservative approaches., Conclusion: PA in FPA has distinct features and management issues. Carefully selected patients (PAS guided) in NFPA with PA for conservative management have comparable outcomes to surgery., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Surgical oncology patients have a high symptom burden and increased risk of morbidity. The aim of palliative care is to evaluate and treat the patient in a holistic manner focusing on the unique attributes of each patient. This goal-concordant approach could help surgical patients cope with the stress and uncertainty that often accompany serious illness and surgery, improving overall outcomes. This qualitative analysis sought to explore whether unmet specialist palliative care or end-of-life needs exist in this population., Methods: Qualitative interviews were completed with a subset of participants in a randomized, controlled trial of a specialist palliative care intervention for patients undergoing abdominal oncologic surgery. The interview guide sought to elicit respondents' perceptions of palliative care and end-of-life needs perioperatively and postoperatively. Recurring themes were identified by two independent coders., Results: Analysis of 47 interview transcripts revealed few serious concerns about end-of-life issues, however appreciation for the supportive presence offered by palliative care was present. Among participants who received specialist palliative care, many found the intervention helpful, but few were able to articulate issues that the intervention improved., Conclusion: These findings suggest low levels of unmet palliative care needs among this population, which is consistent with the results of the parent trial. Targeting patients with a higher symptom burden perioperatively may allow for improved symptom management and better adherence to the treatment plan postoperatively, as well as be a more focused use of specialist palliative care clinicians' efforts., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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.

Objective: Lipoid congenital adrenal hyperplasia (LCAH) is caused by mutations in STAR. A systematic review of phenotype-genotype correlation and data on testicular histology in LCAH patients is unavailable. We aim to describe our experience and provide phenotype-genotype correlation. DESIGN, PATIENTS AND MEASUREMENTS: Retrospective review of three genetically proven LCAH patients from our centre and per-patient data analysis from a systematic review of 292 probands. The phenotypic subgroups of 46,XY were Group A (typical female genitalia), Group B (atypical genitalia) and Group C (typical male genitalia)., Results: We report three new LCAH probands from India, all diagnosed post-infancy with preserved gonadal function and one novel variant. The systematic review reports 46,XY to 46,XX LCAH ratio of 1.1 (155:140). Patients with 46,XY LCAH in Group A were diagnosed in infancy (116/117) and had higher mineralocorticoid involvement than Group C (96.4% vs. 75%, p = 0.035), whereas Group C had preserved gonadal function. Hyperplastic adrenals are noted in ~60% of LCAH diagnosed with primary adrenal insufficiency in infancy. There was no report of gonadal germ cell cancer and rare reports of germ cell neoplasia in situ in adolescents, especially with intraabdominal gonads. Two-thirds of LCAH probands were East-Asian and 11/16 regional recurrent variants were from East Asia. There was minimal overlap between variants in Groups A (n = 55), B (n = 9) and C (n = 8). All nonsense and frameshift and most of the splice-site variants and deletion/insertions were present in Group A., Conclusions: We report three new cases of LCAH from India. We propose a phenotype-derived genotypic classification of reported STAR variants in 46,XY LCAH., (© 2024 John Wiley & Sons Ltd.)

Background: Hospitals often lack bereavement programs. Bereaved families often navigate grief support on their own. This problem was complicated by the early COVID-19 pandemic. Objective: Describe a cost neutral pilot to support next of kin (NOK) of deceased patients from our communicable disease response unit (CDRU) and palliative care unit (PCU). Design: Ad hoc pilot leveraging chaplains and a social worker (SW) to call NOK for grief support using a templated guide, referring interested NOK to bereavement support agencies. Setting/Subjects: NOK of patients who died in the CDRU and PCU at a metropolitan, quaternary care, hospital over five months. Results: One hundred eighty-six patients died. Eighty-one NOK were called, 51 calls were considered complete. Fourteen NOK accepted a referral for bereavement support. Conclusions: This cost neutral pilot successfully connected 81 NOK with either a pilot chaplain or SW for bereavement support. Fourteen NOK accepted referral for a community bereavement resource.

Vitamin D is mainly produced in the skin (cholecalciferol) by sun exposure while a fraction of it is obtained from dietary sources (ergocalciferol). Vitamin D is further processed to 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D (calcitriol) in the liver and kidneys, respectively. Calcitriol is the active form which mediates the actions of vitamin D via vitamin D receptor (VDR) which is present ubiquitously. Defect at any level in this pathway leads to vitamin D deficient or resistant rickets. Nutritional vitamin D deficiency is the leading cause of rickets and osteomalacia worldwide and responds well to vitamin D supplementation. Inherited disorders of vitamin D metabolism (vitamin D-dependent rickets, VDDR) account for a small proportion of calcipenic rickets/osteomalacia. Defective 1α hydroxylation of vitamin D, 25 hydroxylation of vitamin D, and vitamin D receptor result in VDDR1A, VDDR1B and VDDR2A, respectively whereas defective binding of vitamin D to vitamin D response element due to overexpression of heterogeneous nuclear ribonucleoprotein and accelerated vitamin D metabolism cause VDDR2B and VDDR3, respectively. Impaired dietary calcium absorption and consequent calcium deficiency increases parathyroid hormone in these disorders resulting in phosphaturia and hypophosphatemia. Hypophosphatemia is a common feature of all these disorders, though not a sine-qua-non and leads to hypomineralisation of the bone and myopathy. Improvement in hypophosphatemia is one of the earliest markers of response to vitamin D supplementation in nutritional rickets/osteomalacia and the lack of such a response should prompt evaluation for inherited forms of rickets/osteomalacia., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Fanconi renotubular syndromes (FRTS) are a rare group of inherited phosphaturic disorders with limited Indian as well as global data on this condition. Here, we describe the experience of a single Endocrinology center from Western India on FRTS., Materials and Methods: Comprehensive clinical, biochemical, radiological, management, and genetic details of FRTS patients managed between 2010 and 2023 were collected and analyzed., Results: FRTS probands had mutations (eight novel) in six genes [CLCN5 (n = 4), SLC2A2 (n = 2), GATM, EHHADH, HNF4A, and OCRL (1 each)]. Among 15 FRTS patients (11 families), rickets/osteomalacia was the most common (n = 14) presentation with wide inter- and intra-familial phenotypic variability. Delayed diagnosis (median: 8.8 years), initial misdiagnosis (8/11 probands), and syndrome-specific discriminatory features (8/11 probands) were commonly seen. Hypophosphatemia, elevated alkaline phosphatase, normal parathyroid hormone (median: 36 pg/ml), high-normal/elevated 1,25(OH) 2 D (median: 152 pg/ml), hypercalciuria (median spot urinary calcium to creatinine ratio: 0.32), and variable proximal tubular dysfunction(s) were observed. Elevated C-terminal fibroblast growth factor 23 in two probands was misleading, till the genetic diagnosis was reached. Novel observations in our FRTS cohort were preserved renal function (till sixth decade) and enthesopathy in FRTS1 and FRTS3 families, respectively., Conclusion: Our findings underscore frequent under- and misdiagnosis of FRTS; hence, a high index of suspicion for FRTS in phosphopenic rickets/osteomalacia, with early consideration of genetic testing is essential to ensure timely diagnosis of FRTS. The novel variants and phenotypic manifestations described here expand the disease spectrum of FRTS., (© 2024. The Japanese Society Bone and Mineral Research.)

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&#95;145+4delins) and two recurrent variants (p.Val370Met, and c.145+1&#95;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., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare disorder of phosphate homeostasis. We describe a single-center experience of genetically proven HHRH families and perform systematic review phenotype-genotype correlation in reported biallelic probands and their monoallelic relatives. Detailed clinical, biochemical, radiological, and genetic data were retrieved from our center and a systematic review of Pub-Med and Embase databases for patients and relatives who were genetically proven. Total of nine subjects (probands:5) carrying biallelic SLC34A3 mutations (novel:2) from our center had a spectrum from rickets/osteomalacia to normal BMD, with hypophosphatemia and hypercalciuria in all. We describe the first case of genetically proven HHRH with enthesopathy. Elevated FGF23 in another patient with hypophosphatemia, iron deficiency anemia, and noncirrhotic periportal fibrosis led to initial misdiagnosis as tumoral osteomalacia. On systematic review of 58 probands (with biallelic SLC34A3 mutations; 35 males), early-onset HHRH and renal calcification were present in ~ 70% and late-onset HHRH in 10%. c.575C > T p.(Ser192Leu) variant occurred in 53% of probands without skeletal involvement. Among 110 relatives harboring monoallelic SLC34A3 mutation at median age 38 years, renal calcification, hypophosphatemia, high 1,25(OH) 2 D, and hypercalciuria were observed in ~30%, 22.3%, 40%, and 38.8%, respectively. Renal calcifications correlated with age but were similar across truncating and non-truncating variants. Although most relatives were asymptomatic for bone involvement, 6/12(50%) had low bone mineral density. We describe the first monocentric HHRH case series from India with varied phenotypes. In a systematic review, frequent renal calcifications and low BMD in relatives with monoallelic variants (HHRH trait) merit identification., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Context: Data on the overnight 1 mg-dexamethasone suppression test (ONDST) in renal dysfunction are limited., Objective: We aim to determine the normative range of ONDST cortisol across chronic kidney disease (CKD) stages and reasons for its alteration., Methods: Prospectively, 180 CKD (30 each in G2-G5/5D) patients and 30 healthy controls underwent ONDST 8 Am serum cortisol (chemiluminescent immunoassay [CLIA]). In an exploratory cohort, 45 (15 each: G3b/G4, G5/G5D, and healthy controls) individuals' blood biochemistry for basal (8 Am) cortisol and adrenocorticotropin (ACTH), post-ONDST 8 Am dexamethasone, ACTH, cortisol (CLIA and liquid chromatography-tandem mass spectrometry), and 4 Pm cortisol was collected., Results: Post-ONDST cortisol (µg/dL) correlated inversely ( r  = 0.47; P < .005) with estimated glomerular filtration rate (eGFR) (mL/min/1.73 m 2 ), with 95th percentile being 1.2 in controls, 3.0 in G2, 3.2 in G3a, 4.3 in G3b, 4.7 in G4, 5.7 in G5, and 7.1 in G5D. In the exploratory cohort, basal 8 Am cortisol and ACTH, and post-ONDST dexamethasone were similar among controls and CKD subgroups. ONDST ACTH (for evaluating the hypothalamo-pituitary-adrenal axis) was slightly higher in G5/5D vs controls (8.9 vs 6.1 pg/mL), while it was similar in G3b/G4 vs controls. Median 8 Am ONDST cortisol was similar on CLIA and LC-MS/MS in controls and higher on CLIA in G3b/4 (1.7 vs 1.1 µg/dL; P  = .012) and G5/5D (2.4 vs 1.7 µg/dL; P  = .002) than LC-MS/MS. Post-ONDST serum cortisol drop from 8 Am to 4 Pm was significant in controls (0.5-<0.2 µg/dL) and G3b/4 (1.7-1.2 µg/dL), but not in G5/5D (2.4-2.2 µg/dL)., Conclusion: The normative data of ONDST serum cortisol with eGFR-based cutoffs are useful in evaluating Cushing syndrome in CKD. Prolonged cortisol half-life and immunoassay-related assay cross-reaction are likely contributors to higher ONDST cortisol., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Introduction: Cushing's disease (CD) due to macrocorticotropinoma (MC) in children and adolescents is a rare entity with limited information regarding its characteristics. The objective of the study is to describe the clinical, biochemical, imaging, management, outcome, and genetic characteristics of children and adolescents with CD due to MC and compare them with those of microcorticotropinoma (mc)., Methods: This retrospective study was conducted at a single tertiary care center. Thirty-two patients with CD and MC (maximum tumor dimension ≥10 mm on imaging) and 65 patients with mc (&lt;10 mm on imaging) aged ≤20 years at presentation were enrolled., Results: Nineteen girls and 13 boys with MC presented at a median (IQR) age of 14.5 (12.0-17.9) years. Patients with MC had higher body mass index-standard deviation score (BMI-SDS) (3.70 ± 2.60 vs. 2.59 ± 2.01, p = 0.04), more frequent neuro-ophthalmic symptoms (25% vs. 9% p = 0.04) and short stature (59% vs. 34%, p = 0.049) but less frequent livid striae (53% vs. 77%, p = 0.01), hypokalemia (12% vs. 36%, p = 0.04), and lower cortisol (nmol/L) to corticotropin (pmol/L) ratio (41.20 vs. 55.74, p = 0.04) than those with mc. The remission (59% vs. 64%, p = 1.0) and relapse (53% vs. 37%, p = 0.26) rates after first-line surgery and remission rate after radiotherapy (RT) were comparable between the two cohorts, whereas time to remission after RT (27 vs. 13 months, p = 0.05) was longer in the MC group. A patient with MC had a pathogenic germline variant in CDH23., Conclusion: In this large monocentric series of pediatric CD, frequent mass effect symptoms and short stature, higher BMI-SDS, less frequent livid striae, and hypokalemia with lower effective cortisol secretion characterize the MC cohort. The outcomes of surgery and RT were similar between the groups except for a longer time to remission after RT in the MC cohort. Germline variants are rare (4%) in pediatric MC., (© 2023 S. Karger AG, Basel.)

Purpose: Giant prolactinomas (GP) are rare tumors accounting for 4.3% of prolactinomas, with paucity of literature from India. We aim to describe clinical, biochemical, radiological, and treatment outcomes in a large series of Asian-Indian patients with GP., Methods: A single-center retrospective analysis of GPs (n=84), age-based (adults: 66 versus pediatric: 18) and gender-based (males: 64 versus females: 20) comparison was done., Results: The mean age at presentation was 34.1±13years, and 64 (76.2%) were males. Males were younger at presentation (32.1±12.2 versus 40.1±13.8years, P: 0.01). The majority presented with mass-effect-related manifestations (visual disturbances: 91.6%, headache: 84.5%) and/or hypogonadism (98.7%). At baseline, largest tumor dimension was 5.3±1.0cm, and serum prolactin was 8343 (3865.5-12,306) ng/mL; most (94.6%) had gonadal axis involvement. Dopamine-agonist (DA) as first-line therapy (45/67, 67.2%) achieved normoprolactinemia (maximum cabergoline dose: 2.0±1.2mg/week) in 36/45 (80%) and tumor response (≥50% reduction) in 36/37 (97.3%) patients at the last follow-up (median duration: 33 [14.5-53.5]months). Notably, gonadal axis recovery was poor (6/30, 20%) despite normoprolactinemia post-DA monotherapy. At latest follow-up, secondary hypothyroidism (32.5% versus 82.6%, P: 0.001) and central hypocortisolism (5.6% versus 42.9%, P: 0.007) were less frequent in DA monotherapy (n=43) than in multimodal therapy group (n=23). The proportion of males (94.4% versus 71.2%, P: 0.04) was higher in the pediatric age group, with DA-induced (first-line) normoprolactinemia observed in 66.7% of them., Conclusion: GP has male predominance, DA as first-line therapy normalized prolactin in four-fifths of patients with better preservation of HPT and HPA axes in patients with DA monotherapy., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Objective: Data regarding rare FPAs from India, a resource limited setting, are limited. We describe a case series of rare FPAs from a single center in western India., Materials and Methods: This was a retrospective case record review of patients diagnosed between January 2010 and July 2022. The diagnosis was based on biochemical(inappropriately elevated serum FSH/LH) and pathologic (positive immunostaining for FSH/LH) features in patients with FGA, and elevated serum thyroid hormones and normal/elevated TSH in patients with TSHomas., Results: We identified 11 patients with a total of six FGAs (median age 43.5 years, five men, one FGA cosecreting TSH, median largest dimension 40 mm, range 33-60 mm) and six TSHomas (median age 34.5 years, four women, two TSHomas cosecreting GH, median largest dimension 42.5 mm, range 13-60 mm). Symptoms of sellar mass effects led to pituitary imaging in most patients with FGA. Patients with TSHomas had symptoms of excess hormone secretion (GH/TSH) or sellar mass effects. The TSHomas that cosecreted GH/FSH were larger than those secreting only TSH. Transsphenoidal resection was the most common first-line therapy but significant residual disease was frequent (3 out of 6 FGAs and 4 out of 5 TSHomas)., Conclusion: This is the first and second case series of FGAs and TSHomas, respectively, from India. In this study, TSHomas presented at younger age, were larger andhad low surgical cure rates.

Colorectal (CRC) and anal (AC) cancer, both lower gastrointestinal (GI) cancers vary in their presentation and treatment. Overall, the incidence of CRC has decreased. However, the incidence of CRCs in younger adults has increased over the last 5 years. The incidence of ACs has increased, too. Women are disproportionally impacted by AC which is frequently associated with human papilloma virus (HPV). Patients diagnosed with both cancers often experience multiple symptoms including pain, constipation, nausea, and vomiting. Psychosocial distress including embarrassment and shame often results from both the cancers itself as well as surgical procedures such as creation of ostomy. Palliative care (PC) is an emerging specialty that focuses on maximizing the quality of life (QOL) for patients through expert symptom assessment and management, psychosocial support, and improved communication around illness. The evidence to support earlier integration of PC has steadily increased over the last ten years. The literature shows that early involvement of PC for these populations can result in improved QOL, improved symptom control and decreased intensity of care at the end of life. This article will review the palliative needs of patients diagnosed with CRC and discuss how PC as a specialty is well poised to support these needs.

Objective: The data on clinical, biochemical, radiological characteristics, and outcomes in paediatric ectopic adrenocorticotropic hormone syndrome (EAS) are limited owing to rarity of the condition. We report three new cases and perform a systematic review of paediatric EAS., Design and Method: Case records of paediatric and adolescent EAS patient's ≤20 years presenting at our centre between 1997 and 2021 were retrospectively reviewed, and a systematic review of the literature published between January 1970 and December 2022 was performed., Results: A total of 161 patients including 3 new patients from our centre were identified. Bronchial neuroendocrine tumours (NET) (28.5%), thymic NET (22.9%), primitive cell-derived tumours (18.6%), and gastro-entero-pancreatic-NET (13.7%) were the common causes. Primitive cell-derived tumours were the most common in the first decade (24/45, 53.4%) and were the largest (82 [60-100] mm), whereas bronchial NETs predominated during the second decade (42/116, 36.2%) and were the smallest (15 [10-25] mm). Computed tomography localized 92.9% (118/127) of paediatric EAS patients. Immediate postoperative remission was attained in 77.9% (88/113) patients, whereas 30.4% (24/79) relapsed over a median (IQR) period of 13 (8-36) months. Over a median (IQR) follow-up of 2 (0.6-4.6) years, 31.4% of patients died. The median survival was higher in bronchial NET than in other tumour groups. Distant metastasis and tumour size were independent negative predictors of survival., Conclusions: Aetiological profile of paediatric and adolescent EAS is distinct from that of adults. Bronchial NETs have the best long-term survival, whereas distant metastasis and tumour size predict poor survival., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Childhood and adolescent primary hyperparathyroidism (PHPT) is a rare disease caused by single adenomas in 65-94% of patients. In this patient group, there is no data on computed tomography (CT) for pre-operative parathyroid localization that may facilitate focused parathyroidectomy., Methods: Two radiologists reviewed dual-phase (nonenhanced and arterial) CT images of twenty-three operated children and adolescents [20:single-gland disease(SGD), 3:multi-glandular disease(MGD)] with proven histopathological PHPT. Percentage arterial enhancement (PAE) was calculated as [100*{arterial-phase Hounsfield unit (HU)-nonenhanced phase HU}/nonenhanced HU] of the parathyroid lesion(s), thyroid, and lymph node., Results: Dual-phase CT lateralized 100%, localized to the correct quadrant/site 85% SGD (including 3/3 ectopic), and identified 1/3 MGD. PAE (cutoff ≥ 112.3%) was sensitive (91.3%) and specific (99.5%) in distinguishing parathyroid lesions from local mimics (P<0.001). The average effective dose was 3.16±1.01mSv, comparable to the planar/single photon emission CT (SPECT) Technetium 99m(Tc)-sestamibi and choline positron emission tomography (PET)/CT scans. Solid-cystic morphology identified in 4 patients harboring pathogenic germline variants (3:CDC73, 1:CASR) may serve as a radiological clue to molecular diagnosis. Nineteen out of 20 (95%) patients with SGD who had undergone single gland resection based on pre-operative CT findings were in remission over a median follow-up of 18 months., Conclusion: As most children/adolescents with PHPT have SGD, dual-phase CT protocols which reduce the effective radiation dose with high localization sensitivity for single parathyroid lesions may be a sustainable pre-operative imaging modality in this patient group., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Importance: Specialist palliative care benefits patients undergoing medical treatment of cancer; however, data are lacking on whether patients undergoing surgery for cancer similarly benefit from specialist palliative care., Objective: To determine the effect of a specialist palliative care intervention on patients undergoing surgery for cure or durable control of cancer., Design, Setting, and Participants: This was a single-center randomized clinical trial conducted from March 1, 2018, to October 28, 2021. Patients scheduled for specified intra-abdominal cancer operations were recruited from an academic urban referral center in the Southeastern US., Intervention: Preoperative consultation with palliative care specialists and postoperative inpatient and outpatient palliative care follow-up for 90 days., Main Outcomes and Measures: The prespecified primary end point was physical and functional quality of life (QoL) at postoperative day (POD) 90, measured by the Functional Assessment of Cancer Therapy-General (FACT-G) Trial Outcome Index (TOI), which is scored on a range of 0 to 56 with higher scores representing higher physical and functional QoL. Prespecified secondary end points included overall QoL at POD 90 measured by FACT-G, days alive at home until POD 90, and 1-year overall survival. Multivariable proportional odds logistic regression and Cox proportional hazards regression models were used to test the hypothesis that the intervention improved each of these end points relative to usual care in an intention-to-treat analysis., Results: A total of 235 eligible patients (median [IQR] age, 65.0 [56.8-71.1] years; 141 male [60.0%]) were randomly assigned to the intervention or usual care group in a 1:1 ratio. Specialist palliative care was received by 114 patients (97%) in the intervention group and 1 patient (1%) in the usual care group. Adjusted median scores on the FACT-G TOI measure of physical and functional QoL did not differ between groups (intervention score, 46.77; 95% CI, 44.18-49.04; usual care score, 46.23; 95% CI, 43.08-48.14; P = .46). Intervention vs usual care group odds ratio (OR) was 1.17 (95% CI, 0.77-1.80). Palliative care did not improve overall QoL measured by the FACT-G score (intervention vs usual care OR, 1.09; 95% CI, 0.75-1.58), days alive at home (OR, 0.87; 95% CI, 0.69-1.11), or 1-year overall survival (hazard ratio, 0.97; 95% CI, 0.50-1.88)., Conclusions and Relevance: This randomized clinical trial showed no evidence that early specialist palliative care improves the QoL of patients undergoing nonpalliative cancer operations., Trial Registration: ClinicalTrials.gov Identifier: NCT03436290.

Objective: To describe the characteristics of gonadotropin-dependent precocious puberty (GDPP) in Indian children., Methods: Clinical profiles of GDPP (n=78, 61 females) and premature thelarche (n=12) from a single center in Western India were retrospectively studied., Results: Pubertal onset was earlier in boys than girls (29 vs 75 months, respec-tively; P=0.008). The basal luteinizing hormone (LH) was ≥0.3 mIU/mL, except 18% of GDPP girls. At 60 minutes after GnRHa-stimulation, all patients (except one girl) had LH ≥5 mIU/mL. The GnRHa-stimulated LH/FSH ratio was ≥0.34 at 60 minutes in girls with GDPP unlike premature thelarche. Only one girl had an allergic reaction to long-acting GnRH agonist. Among GnRH agonist-treated girls (n=24), the predicted final adult height was -1.67±1.5 SDS, whereas the attained final height was -0.25±1.48 SDS., Conclusion: We establish the safety and efficacy of long acting GnRH agonist therapy in Indian children with GDPP. The 60-minute stimulated serum LH/FSH of ≥0.34 differentiated GDPP from premature thelarche.

To determine the impact of a letter-based advance care planning (ACP) healthcare improvement (HI) initiative on rates of ACP conversations and documentation among gynecologic oncology (GO) inpatients. An HI initiative was implemented from January to December 2020 to improve ACP documentation among GO inpatients. Patients admitted to the GO service were given ACP packets with a letter-based ACP worksheet. GO inpatients who were interested in learning more about ACP were visited by medical students trained to lead ACP conversations. ACP documentation rates in the EMR (electronic medical record) pre- and post-intervention were evaluated. Descriptive statistics were calculated. Associations between sociodemographic characteristics and ACP documentation were analyzed using logistic regression. There were 172 patients admitted in 2019 (pre-implementation cohort). Of these, 45/172 patients (26%) had an advance directive (AD) documented in their electronic medical record (EMR). Following the implementation of the ACP HI in 2020, 55/168 patients (33%) had an AD documented in their EMR. This was a 7% absolute increase and 27% relative increase from pre-intervention AD documentation rates. Increasing age was associated with an increased likelihood of having an AD in the chart (p = 0.004). Married women were less likely to have an AD in their chart (p = 0.05). An HI utilizing a letter-based ACP packet given to GO inpatients improved AD documentation in the EMR. This HI offers a unique method for introducing ACP to patients. More work is needed to improve the occurrence and documentation of ACP conversations., (© 2022. The Author(s) under exclusive licence to American Association for Cancer Education.)

Alopecia in hereditary vitamin D resistant rickets (HVDRR) has some correlation with severe rickets and poor overall response. However, these observations are based on small series. Hence, we aim to assess the genotypic spectrum of HVDRR and its correlation with alopecia and clinical response. Seven genetically-proven HVDDR patients from five unrelated families and 119 probands from systematic review were analysed retrospectively for phenotypic and genotypic data and overall response to therapy. In our cohort mean age at rickets onset was 12 (± 3.4) months. Alopecia was present in all patients but one. All patients had poor overall response to oral high-dose calcium and calcitriol and most required intravenous calcium. Genetic analyses revealed four novel variants. On systematic review, alopecia was present in majority (81.5%) and preceded the onset of rickets. Patients with alopecia had higher serum calcium (7.6 vs.6.9 mg/dl, p = 0.008), lower 1, 25(OH) 2 D (200 vs.320 pg/ml, p = 0.03) and similar overall response to oral therapy (28.7% vs. 35.3%, p = 0.56). Alopecia was present in 51.4% of non-truncating (NT) ligand-binding domain (LBD) variants, whereas it was universal in truncating LBD and all DNA binding-domain (DBD) variants. Overall response to oral therapy was highest in LBD-NT (46.4%) as compared to 7.6% in LBD-truncating and 19% in DBD-NT variants. Among LBD-NT variants, those affecting RXR heterodimerization, but not those affecting ligand affinity, were associated with alopecia. Both alopecia and overall response have genotypic correlation. Age at diagnosis and overall response to oral therapy were similar between patients with and without alopecia in genetically proven HVDRR., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To study phenotype-genotype data of Asian-Indian Kallmann syndrome (KS) from our center and systematically review the studies analyzing multiple congenital hypogonadotropic hypogonadism (CHH) genes in KS cohorts using next-generation sequencing., Design, Patients, Measurement: Five hundred twenty-two KS probands (our center n = 78, published studies n = 444) were included in this systematic review. Molecular diagnosis was considered if the likely pathogenic/pathogenic variant in known CHH gene/s was reported in the appropriate allelic state. Varsome prediction tool (following American College of Medical Genetics standards) was used to analyze the variants., Result: For our center, the molecular diagnosis was seen in 20.5% of probands and was seen more often with severe than partial reproductive phenotype (28.3% vs. 4%, p = .0013). Our center data adds eight novel variants. The molecular diagnosis was seen in 31% as per the systematic review and analysis. It ranged from 16.6% to 72.2% at different centers. The affected genes were FGFR1 (9.8%), ANOS1 (7.5%), PROKR2 (6.1%), CHD7 (5.4%), oligogenic (2.1%), and others &lt;1% each (FGF8, SOX10, PROK2, SEMA3A, IL17RD, and GNRHR). FGFR1 and ANOS1 were the commonly affected genes globally, whereas PROKR2 was commonest in studies from China and CHD7 from Japan, South Korea and Poland., Conclusion(s): This systematic review highlights that the genetic yield is 31% in KS probands, with distinct regional variations. The association of severe reproductive phenotype with the higher genetic yield needs further validation., (© 2022 John Wiley & Sons Ltd.)

Purpose: Giant prolactinoma (GP) in childhood and adolescence is a rare entity with scarce literature. We aimed to describe clinical features, biochemistry, radiology, genetics, management, and outcome in pediatric (≤ 20 years) GP., Methods: Retrospective record review of 18 pediatric GP patients from our center and systematic review including these and 77 from the literature (total cohort: 95)., Results: GP constituted 20% of our pediatric prolactinoma cohort. In the total cohort (age: 15.4 ± 3.5 years), the majority (77, 82.8%) were males. Mass effect symptoms (88.6%), and pubertal delay/arrest in males (82.1%) were frequent. Median basal prolactin was 8649 (3246-17,532) ng/ml and the maximum tumor dimension was 5.5 ± 1.5 cm. MEN1 and AIP mutations were noted in 7 (21.9%) and 6 (18.8%) patients, respectively. Males with central hypogonadism had baseline bi-testicular volume of 20.2 ± 8.4 cc, lower LH than FSH (-2.04 ± 0.9 vs. -0.7 ± 1.6 SDS, p = 0.0075), and mostly, normal inhibin B. Majority (49/76, 64.5%) received dopamine agonist (DA) as first-line treatment with additional therapy in 35% (17/49). DA monotherapy arm had less frequent central hypothyroidism (42.9% vs 87.1%, p = 0.002) and central adrenal insufficiency (7.1% vs 66.7%, p = 0.0003) than multimodal therapy. A smaller tumor dimension (4.7 vs. 5.7 cm, p = 0.04) was associated with normoprolactinemia on DA monotherapy and AIP mutations (33.3% vs. nil, p = 0.02) with multimodal therapy., Conclusion: GP is characterized by male predominance with frequent delay/arrest of puberty (82%), but relative sparing of the FSH-inhibin B axis in boys. DA monotherapy may be preferred as the first-line therapy in pediatric GP., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The COVID-19 pandemic created surges of rapidly deteriorating patients straining health care necessitating the evaluation of novel models of palliative care (PC) integration to reduce patient suffering and hospital strain. Objective: To evaluate an integrated PC model's effect on code status change. Design: This is an observational retrospective study. Setting: Urban quaternary referral center in the southeastern United States from April 6th to August 20th, 2020. Patients: All patients admitted to our medical intensive care unit and stepdown unit were diagnosed with COVID-19. Measurements: Code status change, multivariate regression on patient characteristics. Results: In total, 79.7% (98/123) patients were full code at admission. After PC consultation, 33.3% (41/123) patients remained full code, 13.0% (16/123) were do not resuscitate (DNR), and 53.6% (66/123) changed to DNR/do not intubate (DNI). An ordinal logistic model determined that consultation location (odds ratio [OR] 3.35, p  = 0.017) and patient age (OR 1.09, p  < 0.001) were predictive of code status change to DNR/DNI. Conclusion: Within an integrated PC model, PC consultation was associated with code status change. The effect of an integrated PC model warrants further study in comparison with a traditional PC model in a similar patient cohort.

Childhood and adolescent primary hyperparathyroidism (PHPT) is a very rare disease. Data on its molecular genetics are scarce. We performed a retrospective analysis (January 2000-January 2021) to determine the deleterious germline variants and genotype-phenotype correlations in children and adolescents < 20 years diagnosed with PHPT from a single referral center. Clinical features, biochemistry, imaging, management, and genetics (clinical exome analyzed for 11 PHPT and 7 pancreatitis-associated genes, MLPA for CDC73) were recorded. Thirty-six patients (20 males; median age 17 years) were classified into those with familial and/or syndromic (F/S) or apparently sporadic (AS) presentation. Sixteen (44.4%) harbored pathogenic/likely pathogenic germline variants in PHPT-associated genes. The genetic yield in F/S group was 90% (MEN1:8/10; CDC73:1/10), and AS group was 26.9% (CDC73:4/26; CASR:3/26). F/S group had frequent asymptomatic presentation (60% vs none; P < 0.001), lower serum PTH (237.5 vs 1369.1 pg/mL; P = 0.001), and maximum parathyroid dimension (0.9 vs 2.2 cm; P = 0.01) than AS group. Among the AS group, renal involvement was higher in those with molecular diagnoses (71.4% vs 10.5%; P = 0.01). All those with novel CASR variants (including one homozygous) had hypercalciuria and histology-proven parathyroid adenoma/carcinoma. A missense CTRC VUS occurred in one patient with chronic pancreatitis. In summary, Asian Indian children and adolescents with PHPT have high genetic yield, even with apparently sporadic presentation. The phenotypic spectrum of CASR variants is expanded to include childhood/adolescent PHPT with hypercalciuria and single gland neoplasia. The proposed roles for renal involvement to predict molecular diagnosis among those with apparently sporadic presentation require further elucidation., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: There is limited data regarding Pituitary Stalk Interruption Syndrome (PSIS) from India. Moreover, the pathophysiological link between perinatal events and PSIS is unclear. We aim to elucidate the predictors of PSIS among patients with growth hormone deficiency (GHD) and perinatal events in PSIS by comparing cohorts of PSIS and genetically proven GHD without PSIS., Methods: Among 179 GHD patients, 56 PSIS and 70 genetically positive GHD (52-GHRHR, 15-POU1F1, and 3-PROP1) patients were included. Perinatal events, clinical anomalies, pituitary hormone deficiency, and imaging findings were recorded. We compared PSIS-isolated GHD (PSIS-IGHD) subgroup with GHRHR-IGHD and PSIS-combined pituitary hormone deficiency (PSIS-CPHD) subgroup with POU1F1/PROP1-CPHD., Results: PSIS patients (45 males, median age: 12.5 years) most commonly presented with short stature. At last follow-up (median age: 17.35 years), gonadal (during pubertal-age), thyroid and cortisol axes were affected in 81.6%, 62.5%, and 62.5%. 10/13 (77%) of PSIS children with initial IGHD diagnosis manifested hypogonadism during pubertal age. Male predominance, sporadic presentation, and clinical anomalies were significantly higher in both PSIS subgroups than in the respective genetic subgroups. Breech presentation was higher in PSIS-CPHD than POU1F1/PROP1-CPHD (44.4% vs 5.5%, p = 0.004). Neonatal hypoglycemia (22% vs. 0%, p = 0.05) and jaundice (42 vs. 5%, p = 0.004) were higher in PSIS-CPHD than PSIS-IGHD., Conclusion: Later age at presentation and frequent hypogonadism were observed in our PSIS cohort. Male sex, sporadic presentation, clinical anomalies, and breech presentation predicted PSIS at presentation. Breech presentation in PSIS is likely due to stalk interruption rather than hormonal deficiency., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Advance care planning (ACP) is a fluid discussion between patients and providers to define preferences for future medical care. In the acute care setting, ACP is limited due to lack of structured process for identifying persons who may benefit from ACP. This quality improvement (QI) project aimed to increase the frequency of ACP discussions and documentation of preferences by targeting geriatric patients with an episodic disease trajectory for ACP., Methods: This project used an intervention and comparison group design to target English-speaking, geriatric adults at a large academic medical center with a diagnosis of NYHA class III/IV HF and/or GOLD criteria III/IV COPD for ACP discussions. The intervention group was compared to a group with a range of diagnoses who were approached in a non-systematic way., Results: Thirteen (n = 13) participants completed all aspects of the QI project. Results showed a non-significant increase in the number of patients with a diagnosis of HF and/or COPD who participated in an ACP discussion when compared to the comparison group (n = 20, p = 0.131), as well as a non-significant increase in the number of ACP tools documented in the HER (53.8% compared to 30%) (x = 1.877, p = 0.171)., Conclusion: While this project demonstrated non-significant statistical results in the incidence and documentation of an ACP tool, this project increased the number of ACP discussions had, which is clinically significant.

Competing Interests: The authors report no conflicts of interest.

Introduction: Advance care planning (ACP) discussions help guide future medical care consistent with patient wishes. These discussions should be a part of routine care and should be readdressed frequently as a patient's medical condition changes. Limited literature exists supporting structured processes for identifying persons who may benefit from these conversations. The purpose of this integrative review was to understand whether targeting patients with episodic disease trajectories in the acute care setting will increase their willingness to participate in ACP discussions., Methods: Using the Johns Hopkins Nursing Evidence-Based Practice Model as a guideline, this integrative review focused on the research query "In the acute care setting, does targeting patients with heart failure or chronic obstructive pulmonary disease for ACP lead to increased willingness to participate in these discussions." Articles from 2009 to September 2019 were considered for review., Results: Six articles met inclusion criteria for final analysis. Articles outside of the United States were excluded. Four themes emerged from the literature: (1) improved patient attitudes toward ACP, (2) effective communication surrounding care preferences, (3) strengthened connection between preferred and delivered care, and (4) increased patient involvement in ACP., Conclusion: Chronic diseases such as heart failure and COPD have a high symptom burden punctuated by exacerbations, making it difficult to know when introduction of ACP discussions would be most beneficial. Future research should focus on a deeper evaluation of when to introduce ACP conversations in this population and which ACP interventions are effective to facilitate these discussions.

Background: Patient-centered care for older adults with CKD requires communication about patient's values, goals of care, and treatment preferences. Eliciting this information requires tools that patients understand and that enable effective communication about their care preferences., Methods: Nephrology clinic patients age ≥60 years with stage 4 or 5 nondialysis-dependent CKD selected one of four responses to the question, "If you had a serious illness, what would be important to you?" Condensed versions of the options were, "Live as long as possible;" "Try treatments, but do not suffer;" "Focus on comfort;" or "Unsure." Patients also completed a validated health outcome prioritization tool and an instrument determining the acceptability of end-of-life scenarios. Patient responses to the three tools were compared., Results: Of the 382 participants, 35% ( n =134) selected "Try treatments, but do not suffer;" 33% ( n =126) chose "Focus on comfort;" 20% ( n =75) opted for "Live as long as possible;" and 12% ( n =47) selected "Unsure." Answers were associated with patients' first health outcome priority and acceptability of end-of-life scenarios. One third of patients with a preference to "Focus on comfort" reported that a life on dialysis would not be worth living compared with 5% of those who chose "Live as long as possible" ( P <0.001). About 90% of patients agreed to share their preferences with their providers., Conclusions: Older adults with advanced CKD have diverse treatment preferences and want to share them. A single treatment preference question correlated well with longer, validated health preference tools and may provide a point of entry for discussions about patient's treatment goals., (Copyright © 2019 by the American Society of Nephrology.)

Context: Palliative care interventions have shown promise in improving quality of life and reducing health-care utilization among patients with chronic organ failure., Objectives: To evaluate the effect of a palliative care intervention for adults with end-stage liver disease., Methods: A randomized controlled trial of patients with end-stage liver disease admitted to the hepatology service at a tertiary referral center whose attending hepatologist indicated they would not be surprised if the patient died in the following year on a standardized questionnaire was performed. Control group patients received usual care. Intervention group patients received inpatient specialist palliative care consultations and outpatient phone follow-up by a palliative care nurse. The primary outcome was time until first readmission. Secondary outcomes included days alive outside the hospital, referral to hospice care, death, readmissions, patient quality of life, depression, anxiety, and quality of end-of-life care over 6 months., Results: The trial stopped early because of difficulties in accruing patients. Of 293 eligible patients, only 63 patients were enrolled, 31 in the intervention group and 32 in the control group. This pace of enrollment was only 25% of what the study had planned, and so it was deemed infeasible to complete. Despite stopping early, intervention group patients had a lower hazard of readmission (hazard ratio: 0.36, 95% confidence interval: 0.16-0.83, P = 0.017) and greater odds of having more days alive outside the hospital than control group patients (odds ratio: 3.97, 95% confidence interval: 1.14-13.84, P = 0.030). No other statistically significant differences were observed., Conclusion: Logistical obstacles hindered completion of the trial as originally designed. Nevertheless, a preemptive palliative care intervention resulted in increased time to first readmission and more days alive outside the hospital in the first six months after study entry., (Copyright © 2019 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To identify common themes and topics that patients nearing the end of life want to discuss when sharing their life stories., Methods: Twenty audio-recorded transcripts of open-ended interviews of patients cared for by a palliative care team when approaching the end of life were analyzed using a qualitative analysis., Results: Qualitative analysis revealed that the primary contextual factors that patients drew upon to generate his or her life story are life events (including upbringing, job, education, travel, trauma, hardships, special events, military history, and hobbies), family and support system, and values and beliefs. Participants used their current medical condition, which included mortality, morbidity, and prognosis, to frame their life story., Conclusion: Patients facing serious illness incorporate four major themes when reflecting upon their lives to create their personal life story: life events, family and support system, values and beliefs, and current medical condition.

Interest and appreciation for palliative care (PC) has resulted in increased demand for both PC services and education. The PC rotation has been shown to improve PC knowledge in medical students (MS) and internal medicine (IM) residents, and PC specialists stand poised to direct the primary PC education of learners at different levels of training. To concurrently teach learners of different levels of training on a busy PC service, we created an educational system that emphasizes management of learner schedules, organization of teaching activities, faculty development to improve teaching skills, and learner self-evaluation. Both MS and IM residents showed an improvement in self-assessed competence as well as increased comfort level with seriously ill patients after PC rotation. Careful adjustment of learner schedules has accommodated an increasing number of learners, while maintaining a low learner to faculty ratio. The PC educators face an exciting and daunting challenge as the number of patients with PC needs and the number of learners requesting PC experience grow. We continue to improve milestone-based PC assessment tools, to invest in faculty development, and to explore innovative ways to support PC educators as they strive to provide consistent PC education that is both useful for learners and can be incorporated into busy PC clinical practice.