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.

Cabergoline may act as a radioprotective agent in Cushing's disease.

CONTEXT: Conventional fractionated radiotherapy (CRT) achieves control of pathological hypercortisolism in 75%-80% of patients with persistent or recurrent Cushing's disease (CD), over a mean period of 18-24 months. Medical therapy is recommended as bridge therapy while awaiting RT effect. OBJECTIVE: To determine long-term outcome of CRT and its predictors in CD patients. DESIGN, SETTING AND PATIENTS: This is a retrospective case record analysis of 42 patients with CD who received CRT as a treatment modality and had at least 12 months post-RT follow-up. The dose delivered was 45 Gy in 25 fractions over 5 weeks. Demographic details, hormonal evaluation and radiological data were extracted from case records. Dexamethasone suppressed cortisol at cut-off of 1.8 µg/dL was used to define remission or recurrence. Possible predictors for remission and recurrence were analysed. RESULTS: The mean age at the time of CRT administration was 23.7 ± 10.7 (range: 12-48) years. A total of 29 (69%) patients achieved remission 26.5 ± 28.5 (median: 18, range: 3-120) months after RT, while 13 (31%) patients had persistent disease at last follow-up. There were no significant predictors of disease remission after CRT. Six (20.7%) patients had recurrence after a documented initial remission. Recurrence occurred 66.6 ± 25.9 (median: 74; range: 18 to 90) months after documented remission. Recurrence of the disease was exclusively seen in patients who received peri-RT cabergoline. Peri-CRT use of cabergoline was significantly associated with increased recurrence rates (P = .016). CONCLUSION: Use of cabergoline in the peri-CRT period did not affect initial remission after CRT but was associated with increased recurrence after initial remission in CD.

Genetic spectrum and predictors of mutations in four known genes in Asian Indian patients with growth hormone deficiency and orthotopic posterior pituitary: an emphasis on regional genetic diversity.

CONTEXT: Regional variation in prevalence of genetic mutations in growth hormone deficiency (GHD) is known. AIM: Study phenotype and prevalence of mutations in GH1, GHRHR, POU1F1, PROP1 genes in GHD cohort. METHODS: One hundred and two patients {Isolated GHD (IGHD): 79; combined pituitary hormone deficiency (CPHD): 23} with orthotopic posterior pituitary were included. Auxologic, hormonal and radiological details were studied. All four genes were analysed in IGHD patients. POU1F1 and PROP1 were studied in CPHD patients. RESULTS: Of 102, 19.6% were familial cases. Height SDS, mean (SD) was - 5.14 (1.63). Peak GH, median (range) was 0.47 ng/ml (0-6.59), 72.5% patients had anterior pituitary hypoplasia (APH). Twenty mutations (novel: 11) were found in 43.1% patients (n = 44, IGHD-36, CPHD-8). GHRHR mutations (n = 32, p.Glu72* = 24) were more common than GH1 mutations (n = 4) in IGHD cohort. POU1F1 mutations (n = 6) were more common than PROP1 mutations (n = 2) in CPHD cohort. With few exceptions, this prevalence pattern is contrary to most studies in world-literature. No patients with peak GH > 4 ng/ml had mutations, signifying it as negative predictor. While many parameters were significant on univariate analysis, only positive family history and lower median peak GH levels were significant predictors of mutations on multivariate analysis in IGHD patients. CONCLUSION: At variance with world literature, we found reverse predominance of GHRHR over GH1 mutations, POU1F1 over PROP1 mutations and predominance of GHRHR p.Glu72* mutations thus re-affirming the regional diversity in GHD genetics. We report positive and negative predictors of mutations in GHD.

SYMPATHETIC PARAGANGLIOMA: A SINGLE-CENTER EXPERIENCE FROM WESTERN INDIA.

OBJECTIVE: Most of the Indian studies on pheochromocytoma/paraganglioma (PCC/PGL) have focused on PCC, and there is a paucity of information regarding sympathetic paraganglioma (sPGL). Here, we describe the clinical, biochemical, and imaging features of sPGL compared with PCC. METHODS: This retrospective study included 75 patients with sPGL and 150 patients with PCC. Diagnosis of PCC/PGL was based on surgical histopathology, and if histopathology was not available, on biochemistry and/or radiology. RESULTS: sPGL was more frequently detected incidentally ( P = .03), normetanephrine-secreting ( P<.01), and metastatic compared with PCC ( P≤.01). sPGL was most commonly located in the organ of Zuckerkandl (OOZ) (49%) and infradiaphragmatic area above the OOZ (27%). Patients with mediastinal sPGL were significantly older than those with sPGL in the OOZ ( P = .03). Primary tumors of metastatic sPGL were significantly larger than those without metastasis (7.8 ± 4 cm vs. 5.6 ± 3.2 cm; P = .004). Percentage arterial enhancement (PAE) >100% was seen in 98% of sPGLs. CONCLUSION: Incidental presentation, normetanephrine-secreting phenotype, and metastatic disease were more frequent in patients with sPGL than those with PCC. sPGL arose most commonly in the OOZ. Tumor size is an independent predictor of malignancy among sPGL patients. PAE >100% is almost a universal finding in sPGL, and its absence is a sensitive parameter to differentiate sPGL from other abdominal masses. ABBREVIATIONS: AP = arterial phase; CECT = contrast-enhanced computed tomography; CT = computed tomography; DP = delayed phase; EVP = early venous phase; FDG = fluorodeoxyglucose; fPFMN = fractionated plasma free metanephrine; HU = Hounsfield units; MIBG = metaiodobenzylguanidine; MRI = magnetic resonance imaging; OOZ = organ of Zuckerkandl; PAE = percentage arterial enhancement; PCC = pheochromocytoma; PET = positron emission tomography; PFNMN = plasma free normetanephrine; PGL = paraganglioma; PRRT = peptide receptor radionuclide therapy; PVE = percentage venous enhancement; sPGL = sympathetic paraganglioma; UP = unenhanced phase; VMA = vanillyl mandelic acid.

Hashimoto's thyroiditis: relative recurrence risk ratio and implications for screening of first-degree relatives.

CONTEXT: The relative recurrence risk ratio (λR ) for Hashimoto's thyroiditis (HT) has not been widely studied. The age at which thyroid function evaluation should be initiated for relatives of HT patients remains unclear. OBJECTIVE: To study λR and age-related prevalence of HT in first-degree relatives of HT patients. METHODS: First-degree relatives (n = 861) of 264 HT patients were evaluated for goitre, thyroid function tests, thyroid antibodies (TAb) and urinary iodide concentration (UIC). HT was defined as TAb positivity and hypothyroidism (subclinical/overt). λR was calculated as {number of index patients whose relatives (of particular subtype) had HT/number of index patients having relatives of same subtype}÷ population prevalence of HT (5·1%). The age-related prevalence of HT was studied using Kaplan-Meier method. RESULTS: A total of 861 relatives (205 parents, 336 siblings and 320 offspring) participated in the study. About 38·3% were TAb positive. The prevalence of HT was 16·7% (22·9% in parents, 19·6% in siblings and 9·6% in offspring). TAb positivity (48·3% vs 33·1%) and HT (23·5% vs 13·6%) were significantly more common in the goitrous group (n = 267) vs nongoitrous group. The median UIC for the study population was 182·5 µg/l. Computed λR was 9·1 for any one relative being affected, 5·9 for parents, 6·3 for siblings and 3·1 for offspring. The prevalence of HT increased with age and exceeded the adult population prevalence of 5·1% at 20 years in females and 27 years in males. CONCLUSIONS: Relatives of HT patients have a ninefold increased risk for developing HT as compared to the general population. The risk of developing HT exceeds that of the general population at 20 years in females and 27 years in males.

Percentage arterial enhancement: An objective index for accurate identification of parathyroid adenoma/hyperplasia in primary hyperparathyroidism.

BACKGROUND: Radiation exposure to neck by four-dimensional computerized tomography (4DCT) is relatively high and limits its use as a first-line investigation in evaluation of primary hyperparathyroidism (PHPT). Radiation exposure can be reduced by restricting the number of CT phases. Our aim was to study the performance of 4DCT in cohort of surgery-naïve PHPT patients, and to evaluate percentage enhancement as an objective radiological index to discriminate parathyroid lesions (adenoma/hyperplasia) from thyroid tissue and lymph nodes. MATERIALS AND METHOD: Retrospective study of 49 PHPT patients {(44 single-gland diseases (SGD) and five multiple-gland disease (MGD)} who underwent 4DCT (unenhanced, early arterial, early venous and delayed venous phase) pre-operatively. Two radiologists who were blinded to surgical location of parathyroid lesions examined the scans. Attenuation values were recorded for parathyroid lesions (n=50), thyroid gland (n=50) and lymph nodes (n=12) in different phases. Percentage enhancement for different phases was calculated as "(HU in a specific enhanced phase-HU in unenhanced phase)/HU in unenhanced phase" ×100. RESULTS: Inter-rater reliability between the two radiologists was 0.83 (Cohen's kappa). In SGD, sensitivity and PPV were 93.18% and 98.8% for lateralization, and 89.77% and 95.18% for quadrant localization, respectively. In MGD, 4DCT showed 50% sensitivity and 100% PPV. Percentage arterial enhancement showed highest area under curve (AUC=0.992) for differentiation of parathyroid lesions from thyroid tissue and lymph nodes. A cut-off value of 128.9% showed 95.8% sensitivity and 100% specificity for the identification of parathyroid lesions. CONCLUSIONS: We propose that percentage arterial enhancement can be used as an objective radiological index for accurate identification of parathyroid adenoma/hyperplasia.

PRIMARY ADRENAL LYMPHOMA: A SINGLE-CENTER EXPERIENCE.

OBJECTIVE: To describe the clinical presentation, biochemistry, imaging features, and treatment outcome of patients with primary adrenal lymphoma (PAL) presenting to a single tertiary care center. METHODS: We performed a retrospective analysis of case records of 7 patients diagnosed with PAL between January 2011 and May 2014 at our institution in Mumbai, India. RESULTS: Median age of presentation in our series was 48 years (range, 41 to 60 years), with a male to female ratio of 6:1. Bilateral adrenal involvement was seen in 4 of 7 patients (58%). Adrenal insufficiency (AI) was seen in 3 of the 4 patients with bilateral involvement (75%). Computed tomography showed slight to moderate contrast enhancement of adrenal masses in 4 of 5 patients (80%). Diffuse, large, B-cell lymphoma (DLBCL) was the most common immunophenotype (85%). One patient died due to rapid disease progression even before starting chemotherapy. Six patients were treated with chemotherapy and/or external beam radiotherapy. After 1 year, 2 more patients had died, whereas 4 patients were in remission. CONCLUSION: PAL should always be considered in differential diagnosis of bilateral adrenal mass with AI. DLBCL is the most common histologic subtype of PAL. Despite treatment, long-term prognosis of PAL remains poor.

Plasma cell leukaemia a rare cause of disproportionate anaemia in a patient presenting as CKD.

The anaemia in patient of chronic kidney disease is commonly related to secondary erythropoietin deficiency. When the severity of anaemia is disproportionate and associated with other haematological abnormalities like thrombocytopenia, then primary haematological disorder and secondary renal involvement must be considered. Renal involvement is common in haematologic disorder like Multiple Myeloma. The diagnosis of haematological disorder may be missed. This is a case of chronic kidney disease with disproportionate severe anaemia with bleeding diasthesis which ultimately turned out to be plasma cell leukaemia.

Spectrum of renal dysfunction after curative parathyroidectomy in symptomatic primary hyperparathyroidism.

OBJECTIVE: The long-term renal consequences of curative parathyroidectomy (PTX) in symptomatic primary hyperparathyroidism (sPHPT) are not well characterized. We aimed to assess renal glomerular and tubular functions in an sPHPT cohort at ≥1 year's follow-up. DESIGN: Retrospective-prospective study. METHODS: sPHPT patients with preoperative eGFR ≥60mL/min/1.73m2 and in remission (normocalcemic) for ≥1 year after PTX underwent clinical and biochemical assessment (calcium profile, renal parameters). Ammonium chloride and bicarbonate loading tests were performed in patients with renal tubular dysfunction (RTD). RESULTS: Forty-eight patients (31 females) with median plasma PTH 1,029 (338-1604) pg/mL and mean eGFR 109.2±26.0mL/min/1.73m2 at diagnosis were evaluated at 5.62±3.66 years after curative PTX. At follow-up, eGFR was <60mL/min/m2 in 5 patients (10.4%). Patients with >10% drop in eGFR (n=31) had significantly higher pre-PTX plasma PTH (1,137 vs. 687pg/mL), and longer time to post-PTX evaluation (6.8 vs. 3.4 years). RTD was seen in 11 patients (22.9%): urinary low molecular weight proteinuria (14.6%), distal renal tubular acidosis (12.5%), hypophosphatemia (8.3%), and hypokalemia (8.3%); RTD was associated with significantly lower post-PTX eGFR (72.7 vs. 95.4mL/min/m2). Five of the 7 RTD patients undergoing loading test had impaired urinary acidification, whereas none had impaired bicarbonate resorption. CONCLUSIONS: Reduction in eGFR and subclinical RTD were prevalent at long-term follow-up in the present Asian-Indian cohort with cured sPHPT. Further studies are warranted to understand the clinical implications of these various renal abnormalities.

Percentage arterial enhancement on 2D CT in the diagnosis of primary hyperparathyroidism: A prospective validation study and potential pitfalls.

BACKGROUND: Parathyroid lesions are identified by subjective enhancement and washout patterns on computed tomography (CT). We have previously proposed "percentage arterial enhancement" (PAE) as an objective index and now aim to validate its performance prospectively. METHODS: Dual-phase CT was performed in 40 consecutive primary hyperparathyroidism patients. PAE was calculated as [{arterial phase Hounsfield unit (HU)-unenhanced phase HU}/unenhanced phase HU] × 100. PAE > 128.9% was considered parathyroid. RESULTS: PAE had 94.2% sensitivity, 100% positive predictive value (PPV) in lateralization, and sensitivity and PPV of 93.9% in quadrant localization of single-gland disease. PAE failed to identify two lesions: an intrathyroidal parathyroid carcinoma in the background of multinodular goiter and another lower enhancing cystic parathyroid adenoma. PAE had 60% sensitivity, and 100% PPV to identify multigland disease. The mean effective dose was 2.74 mSV. CONCLUSIONS: PAE is a specific CT index for parathyroid lesions with less radiation exposure. Areas of caution include intrathyroidal and cystic lesions.

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.

Comparison of 68Ga-DOTA-NaI3-Octreotide/tyr3-octreotate positron emission tomography/computed tomography and contrast-enhanced computed tomography in localization of tumors in multiple endocrine neoplasia 1 syndrome.

The optimum imaging modality for the screening of multiple endocrine neoplasia type 1 (MEN1)-associated tumors is not well established. Here, we compare the performance of contrast-enhanced CT (CECT) versus 68Ga DOTA-NOC/TATE PET/CT in MEN1 patients. The retrospective case record study is conducted at a tertiary health-care center. Thirty-four patients, who have undergone both CECT and 68Ga DOTA-NOC/ TATE PET, were included in the analysis. CECT had higher per-lesion sensitivity than 68Ga DOTA-NOC/TATE PET/CT for the detection of parathyroid lesions, (82.6% vs. 24.6%, P < 0.001). 68Ga DOTA-NOC/TATE PET/CT had higher per-lesion sensitivity than CECT for the detection of metastases (85% vs. 47.5%, P < 0.001) and gastrinomas (90% vs. 10%, P = 0.003). When combined use of the two imaging modalities is compared to CECT alone (63.7% vs. 93.1%, P = 0.00012) and 68Ga-DOTA-NOC/TATE PET/CT alone (74.1% vs. 93.1%, P = 0.0057), it provided significantly higher per-lesion sensitivity for the detection of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). 68Ga-DOTA-NOC/ TATE PET was more sensitive for the detection of gastrinomas and metastases than CECT, whereas it was less sensitive for the detection of parathyroid lesions than CECT. The combined use of both the imaging modalities significantly increases the sensitivity for detection of GEP-NETs.

Radiological differentiation of phaeochromocytoma from other malignant adrenal masses: importance of wash-in characteristics on multiphase CECT.

Rationale and introduction: To evaluate the computerised tomography (CT) characteristics of phaeochromocytoma (PCC) that differentiate them from other non-benign adrenal masses such as adrenocortical carcinoma (ACC), primary adrenal lymphoma (PAL) and adrenal metastases (AM). Methods: This retrospective study was conducted at a tertiary health care institute from Western India. Patients presented between January 2013 and August 2016 with histological diagnosis of PCC or other non-benign adrenal mass having adequate reviewable imaging data comprising all four CECT phases were included. Results: The study cohort consisted of 72 adrenal masses from 66 patients (33 PCC, 22 ACC, 4 PAL, 13 AM). Unlike other masses, majority of PCC (25/33) showed peak enhancement in early arterial phase (EAP). PCC had significantly higher attenuation in EAP and early venous phase (EVP), and higher calculated percentage arterial enhancement (PAE) and percentage venous enhancement (PVE) than other adrenal masses (P < 0.001). For diagnosis of PCC with 100% specificity, PAE value ≥100% and EAP attenuation ≥100 HU had 78.8 and 63.6% sensitivity respectively. ACC were significantly larger in size as compared to PCC and metastasis. The adreniform shape was exclusively found in PAL (two out of four) and AM (4 out of 13). None of the enhancement, wash-in or washout characteristics were discriminatory among ACC, PAL and AM. Conclusion: Peak enhancement in EAP, PAE value ≥100% and EAP attenuation ≥100 HU differentiate PCC from other malignant adrenal masses with high specificity.

Alveolar Soft Part Sarcoma Presenting as Hypervascular Adrenal Metastasis.

Hypervascular adrenal masses include pheochromocytoma, metastases caused by clear renal cell carcinoma/hepatocellular carcinoma. Alveolar soft part sarcoma (ASPS) causing hypervascular metastases is not described in the literature. Here, we describe the first case of ASPS presenting as hypervascular metastasis. Our case was a 23-year-old male incidentally detected right adrenal mass during the evaluation of pain in the abdomen. On computed tomography (CT), adrenal mass showed bright enhancement in early arterial phase (unenhanced Hounsfield unit [HU]-45.3; arterial phase HU-158.2). 18- flurodeoxyglucose positron emission tomography/CT showed multiple lesions and was confirmed histologically to be due to ASPS.

Genotype phenotype correlation in Asian Indian von Hippel-Lindau (VHL) syndrome patients with pheochromocytoma/paraganglioma.

The data in genotype-phenotype correlation in Indian von Hippel-Lindau (VHL) patients is limited. We have retrospectively studied 31 genetically proven VHL patients with pheochromocytoma/paraganglioma (PCC/PGL) from families and have reviewed the World literature on PCC/PGL in patients with large VHL deletions. Three patients had large deletions and 28 patients had other mutations [missense mutations in 25, 3 bp deletion in 2 and single bp duplication in one]. Unilateral PCC were significantly more common in patients with large VHL deletions whereas multiple PCC (bilateral PCC or PCC + sympathetic PGL) were significantly more common in those with other mutations. World literature review confirmed the rarity of PCC/PGL in patients with large deletions and we report the first definitive case of PCC associated with complete VHL deletion. Pancreatic neuroendocrine tumours were more common, often metastatic and the most common cause of death in our cohort. Our study had eight parent off-spring pairs from five families. The off-springs were significantly younger at presentation and had significantly higher number of PCC/PGL. In conclusion, PCC/PGL are rare in patients with large VHL deletions and if occur are most likely to be solitary. Patients with bilateral PCC or multifocal PCC/PGL are least likely to have large VHL deletions. Our study also provides additional evidence for existence of the phenomenon of anticipation in VHL syndrome.

Raynaud's Phenomenon: Revisiting a Rare Sign of Pheochromocytoma and Paraganglioma.

Paraganglioma (PGL) are rare tumors arising from extra-adrenal chromaffin cells and occasionally secret catecholamines. The patient commonly presents with headache, palpitation, anxiety, diaphoresis, and episodic or sustained hypertension. Rarely patient can present with Raynaud's phenomenon. We present a case of adolescent girl who presented with isolated Raynaud's phenomenon as only manifestation of metastasis of PGL 3 years after undergoing surgical excision of normetanephrine secreting abdominal PGL.

Duration of post-operative hypocortisolism predicts sustained remission after pituitary surgery for Cushing's disease.

PURPOSE: Transsphenoidal surgery (TSS) is the primary treatment modality for Cushing's disease (CD). However, the predictors of post-operative remission and recurrence remain debatable. Thus, we studied the post-operative remission and long-term recurrence rates, as well as their respective predictive factors. METHODS: A retrospective analysis of case records of 230 CD patients who underwent primary microscopic TSS at our tertiary care referral centre between 1987 and 2015 was undertaken. Demographic features, pre- and post-operative hormonal values, MRI findings, histopathological features and follow-up data were recorded. Remission and recurrence rates as well as their respective predictive factors were studied. RESULTS: Overall, the post-operative remission rate was 65.6% (early remission 46%; delayed remission 19.6%), while the recurrence rate was 41% at mean follow-up of 74 ± 61.1 months (12-270 months). Significantly higher early remission rates were observed in patients with microadenoma vs macroadenoma (51.7% vs 30.6%, P = 0.005) and those with unequivocal vs equivocal MRI for microadenoma (55.8% vs 38.5%, P = 0.007). Patients with invasive macroadenoma had poorer (4.5% vs 45%, P = 0.001) remission rates. Recurrence rates were higher in patients with delayed remission than those with early remission (61.5% vs 30.8%, P = 0.001). Duration of post-operative hypocortisolemia ≥13 months predicted sustained remission with 100% specificity and 46.4% sensitivity. Recurrence could be detected significantly earlier (27.7 vs 69.2 months, P < 0.001) in patients with available serial follow-up biochemistry as compared to those with infrequent follow-up after remission. CONCLUSION: In our study, remission and recurrence rates were similar to that of reported literature, but proportion of delayed remission was relatively higher. Negative/equivocal MRI findings and presence of macroadenoma, especially those with cavernous sinus invasion were predictors of poor remission rates. In addition to early remission, longer duration of post-operative hypocortisolism is an important predictor of sustained remission. Regular biochemical surveillance may help in identifying recurrence early.

Genotype-phenotype correlation in paediatric pheochromocytoma and paraganglioma: a single centre experience from India.

BACKGROUND: Data on genotype-phenotype correlation in children is limited. Hence, we studied the prevalence of germline mutations and genotype-phenotype correlation in children with pheochromocytoma (PCC)/paraganglioma (PGL) and compared it with adult PCC/PGL cohort. METHODS: A total of 121 consecutive, unrelated, index PCC/PGL patients underwent genetic testing for five PCC/PGL susceptibility genes (RET, VHL, SDHB, SDHD and SDHC) and were evaluated for clinical diagnosis of neurofibromatosis type1 (NF1). RESULTS: Thirty patients (12 boys, 18 girls) presented at ≤20 years of age (mean age of 15.9±3.8 years). Children were more frequently symptomatic and more frequently had bilateral PCC than adults. Fourteen (46.7%) PCC/PGL children had germline mutations (VHL 10 [33.3%], SDHB 2 [6.6%], and SDHD 2 [6.6%]). Overall germline mutations (46.7% vs. 26.4%, p=0.04) and VHL mutations (33.3% vs. 10.9%, p=0.026) were significantly more common in children than in adults. In children with VHL mutations, bilateral PCC were more frequent than in adults with VHL mutations. Within the paediatric cohort, bilateral PCC (60% vs. 5%, p=0.002), PCC+sPGL (30% vs. 0%, p=0.03) and occurrence of a second PCC/PGL (30% vs. 0%, p=0.03) were significantly more frequent among children with VHL mutations than others. CONCLUSIONS: All PCC/PGL children should be screened for germline mutations with first priority for VHL gene testing. Paediatric PCC/PGL patients with VHL mutations should be thoroughly evaluated for bilateral PCC and PCC+sPGL at initial presentation and closely followed up for occurrence of a second PCC/PGL.

Phenotype-genotype spectrum of AAA syndrome from Western India and systematic review of literature.

OBJECTIVE: To study genotype-phenotype spectrum of triple A syndrome (TAS). METHODS: Retrospective chart analysis of Indian TAS patients (cohort 1, n = 8) and review of genotyped TAS cases reported in world literature (cohort 2, n = 133, 68 publications). RESULTS: Median age at presentation was 4.75 years (range: 4-10) and 5 years (range: 1-42) for cohorts 1 and 2, respectively. Alacrima, adrenal insufficiency (AI), achalasia and neurological dysfunction (ND) were seen in 8/8, 8/8, 7/8 and 4/8 patients in cohort 1, and in 99, 91, 93 and 79% patients in cohort 2, respectively. In both cohorts, alacrima was present since birth while AI and achalasia manifested before ND. Mineralocorticoid deficiency (MC) was uncommon (absent in cohort 1, 12.5% in cohort 2). In cohort 1, splice-site mutation in exon 1 (p.G14Vfs*45) was commonest, followed by a deletion in exon 8 (p.S255Vfs*36). Out of 65 mutations in cohort 2, 14 were recurrent and five exhibited regional clustering. AI was more prevalent, more often a presenting feature, and was diagnosed at younger age in T group (those with truncating mutations) as compared to NT (non-truncating mutations) group. ND was more prevalent, more common a presenting feature, with later age at onset in NT as compared to T group. CONCLUSION: Clinical profile of our patients is similar to that of patients worldwide. Alacrima is the earliest and most consistent finding. MC deficiency is uncommon. Some recurrent mutations show regional clustering. p.G14Vfs*45 and p.S255Vfs*36 account for majority of AAAS mutations in our cohort. Phenotype of T group differs from that of NT group and merits future research.

Myocardial Performance Index (Tei Index): A simple tool to identify cardiac dysfunction in patients with diabetes mellitus.

BACKGROUND: Cardiac dysfunction is the major cause of morbidity and mortality in diabetes. Myocardial Performance Index (MPI/Tei Index) includes both systolic and diastolic time intervals to assess the global cardiac dysfunction. Our aim was to assess the MPI in patients with type 2 diabetes. MATERIAL AND METHODS: This hospital-based analytic observational study was performed in the tertiary care center. The conventional Doppler parameters, tissue Doppler-derived E/E' and MPI, were measured in all patients. RESULTS: 100 patients with type 2 diabetes were included in the study. 65 patients showed diastolic dysfunction, 33 with Grade I diastolic dysfunction, 23 with Grade II diastolic dysfunction, and 14 patients with Grade III diastolic dysfunction. The conventional Doppler showed abnormality in 44% of patients (33 patients with Grade I and 14 patient with Grade III). 23 patients were in Grade II diastolic dysfunction (12 patients showed reversal E/A on valsalva maneuver and 11 patients showed abnormality in tissue Doppler-derived E/E', E/E'>15). MPI with cut-off 0.36 was found to have 94% sensitivity, 100 specificity, and 94% PPV for the detection of cardiac dysfunction. MPI negatively correlated with systolic dysfunction (rho=0.455, p<0.001) and positively correlated with grade of diastolic dysfunction (rho=0.832, p<0.001) and NYHA grading of dyspnea (rho=0.872, p<0.001) CONCLUSIONS: MPI as a single parameter can be used for assessment in diabetic cardiac dysfunction.