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To describe the differences in presentation, biochemistry, and radiological evaluation of various etiologies of adrenal Cushing's syndrome (CS) from a single center. To emphasize caution for interpretation of plasma adrenocorticotropic hormone (ACTH), as a spuriously unsuppressed ACTH level by immunometric assay may lead to therapeutic misadventures in adrenal CS. Design: Retrospective, single-center, observational study. Methods: Fifty-eight adrenal CS patients [Adrenocortical carcinoma (ACC), n=30; Adenoma (ACA), n=15; Primary pigmented nodular adrenocortical disease (PPNAD), n=10; ACTH independent macronodular adrenal hyperplasia (AIMAH), n=3) evaluated at a tertiary care center in western India between January 2006 to March 2020 were included. Data on demography, clinical evaluation, biochemistry, imaging, management, histopathology, and outcome were recorded in a standard format and analyzed. Results: Cortisol secreting ACC presented at 38(1–50) years with abdominal mass in 26/30 (86.7%) and 16/30 (53.3%) had metastases at presentation. ACA with autonomous cortisol excess presented at 25(4.9–40) years with discriminating features of CS in 14/15 (93.3%), sex steroid production in 2/15, unenhanced HU <10 in only one, and relative washout >40% in 8/11 (72.7%). One ACA and eight ACC patients had plasma ACTH (by Siemens Immulite assay) > 20 pg/ml, despite hypercortisolemic state. Conclusions: Cortisol-secreting ACC and ACA most often present with mass effects and florid CS, respectively. Baseline HU has low sensitivity to differentiate cortisol-secreting ACA from ACC. Plasma ACTH measured by Seimens Immulite is often unsuppressed, especially in ACC patients, which can be addressed by measuring ACTH by more accurate assays. [ABSTRACT FROM AUTHOR]

Context: As synacthen use is not licensed in India and there are concerns about the safety of the insulin tolerance test (ITT), an alternative dynamic test to diagnose adrenal insufficiency (AI) is required. Objective: The study aimed to evaluate the diagnostic performance of the Acton Prolongatum stimulation test (APST) with a standard ITT for the diagnosis of AI. Design: Prospective study comparing two diagnostic tests. Participants: Six healthy volunteers and 53 suspected or known AI patients. Measurements: Serum cortisol response to ITT and APST. Results: The median (95% confidence interval [CI]) peak cortisol levels among healthy volunteers in ITT and APST were 17 (14.58–19.08) and 30.5 (22.57–34.5) μg/dL. Of the 53 patients (age: 39.6 ± 9.38 years; females: 38 [71.1%]), 34 had AI (peak ITT serum cortisol < 14.5 μg/dL) whereas 19 had a normal hypothalamic-pituitary-adrenocortical (HPA) axis. In the receiver operator characteristic curve analysis, 60-min APST cortisol had an area under the curve of 0.984 (95% CI: 0.904–1.00, P < 0.0001). The best accuracy was obtained at a cut-off of 16.42 μg/dL (sensitivity: 97.7% [95% CI: 87.7–99.9%]; specificity: 100% [69.2-100%]). Forty-three of the 53 patients with suspected AI had hypoglycemic symptoms during ITT and two of them required intravenous dextrose, whereas, none had adverse events during APST. The ITT was incomplete in two patients whereas all completed APST. Conclusions: APST is a simple, safe, and reliable alternative to ITT for the diagnosis of AI; 60-min serum cortisol of 16.42 μg/dL in APST best distinguishes the AI patients from those with adequate cortisol response. [ABSTRACT FROM AUTHOR]

Objective: COVID-19 has emerged as a multi-system disease with the potential for endocrine dysfunction. We aimed to study the hormonal profile of hospitalized patients with COVID-19 at a tertiary care referral hospital at Jodhpur, India. Design: A hospital-based clinical study of endocrine profile of COVID-19 patients conducted from 15th May to 30th June 2020 after ethical approval. Measurements: Fasting blood samples for free thyroxine (T4), free tri-iodothyronine (T3), thyroid stimulating Hormone (TSH), serum prolactin; basal and 1 h post-intramuscular adrenocorticotropic hormone (ACTH) stimulated cortisol, interleukin-6 (IL-6), and high sensitivity C-reactive protein (hsCRP) were collected within 24 h of admission after written informed consent. All hormones and IL-6 were analyzed by chemiluminescent immunoassay. hsCRP was measured by immune-turbidimetric assay. Results: Of 235 patients studied, 14% had severe disease and 5.5% died. Adrenal insufficiency was present in 14%, most of whom had mild disease. A robust adrenal response was observed in those with severe disease. Basal and post-ACTH serum cortisol were significantly increased in severe disease or those who died compared to those who were mild or asymptomatic. Basal and post-ACTH serum cortisol showed a significant positive correlation with hsCRP but not with IL-6. Low T3 and low T4 syndrome were documented in 25% and 5%, respectively. Serum TSH and FT3 levels declined significantly from asymptomatic to severe category. Hyperprolactinemia was found in 21 patients. hsCRP showed a rising trend with disease severity while IL-6 did not. Conclusions: Endocrine dysfunction in the form of adrenal insufficiency, low T3, and low TSH syndrome and hyperprolactinemia were common COVID-19 hospitalized patients. [ABSTRACT FROM AUTHOR]

Syndromic congenital ichthyoses (CI) are genetically determined disorders of cornification that are characterized by generalized scaling along with systemic symptoms. Data on congenital syndromic ichthyosis from developing countries are scarce. We aimed to assess the prevalence, phenotype‐genotype correlation, and management of syndromic CI patients presenting to our outpatient during the specified period this was a retrospective study of congenital syndromic ichthyosis patients attending a dermatology clinic in a tertiary care center from 2105‐2018. We reviewed epidemiological and comorbidities data, phenotype‐genotype correlations, and treatments of syndromic congenital ichthyosis patients. Six patients of Syndromic CI were diagnosedamongst 86 patients of CI (8.1%). Amongst these, three patients of Sjogren‐Larrson syndrome (SLS), two patients of Netherton syndrome (NS), and one of Chanarin‐Dorfman disease (CDD) were reported. Next‐generation sequencing (NGS) was performed with novel variants reported in one patient each of SLS, NS, and CDD. An atypical phenotype was observed in a patient with NS with associated growth hormone and adrenocorticotropic hormone deficiency but with favorable clinical response to intravenous immunoglobulin. Our reports point towards the unreported pool of genetic mutations in CI from India. Novel mutations were associated with variable cutaneous and systemic involvement. [ABSTRACT FROM AUTHOR]

Objective: Efficacy of bilateral inferior petrosal sinus sampling (BIPSS) in corticotropin-dependent Cushing's syndrome (CS) for localization and lateralization of excess adrenocorticotropic hormone (ACTH) source, as compared to high-dose dexamethasone suppression test (HDDST) and magnetic resonance imaging (MRI) pituitary, respectively. Methodology: Thirteen patients with clinically and biochemically confirmed CS underwent HDDST, MRI pituitary, and BIPSS by an experienced team of intervention neurologist, neurosurgeon, and endocrinologist using percutaneous femoral vein approach. Results: Of 13 patients (11 adults and two children) who underwent BIPSS, raised central to peripheral ACTH ratio was achieved in 12 cases, remaining one case being ectopic ACTH secretion (EAS). However, inter IPS gradient >1.4 was achieved in 11 (91.6%) of 12 Cushing's disease (CD) cases before vasopressin stimulation; and in 9 (75%) of 12 CD cases after vasopressin stimulation (P-value 0.583). HDDST suppression of more than 50% was present in only ten cases with CD, falsely negating CD in two cases (16.6%), sensitivity 83.3% and specificity 100%. MRI sella demonstrated pituitary microadenoma in 12 cases and macroadenoma in one case. Lateralization by BIPSS and MRI was concordant in 7 (58.3%) out of 12 cases with CD, with rate of remission after transsphenoidal surgery being higher in patients with concordant lateralization by BIPSS and MRI. Conclusions: BIPSS is an important investigation to distinguish CD and EAS. BIPSS was superior to HDDST for confirming the source of excess ACTH. Our findings favor the use of BIPSS for localization and pituitary MRI for lateralization of microadenoma. [ABSTRACT FROM AUTHOR]

Background: Adrenal vein sampling (AVS) is the recommended standard test to distinguish between unilateral and bilateral disease in patients with primary hyperaldosteronism. Use of co syntropin stimulation during AVS has been advocated. However, co syntropin is not widely available in India. Synthetic porcine sequence corticotrophin is freely available as Acton Prolongatum. Here we report 2 cases, where Acton Prolongatum stimulated AVS was used for subtyping primary aldosteronism. Methods: Two patients with hypertension and hypokalemia were detected to have hyperaldosteronism. Their clinical and laboratory parameters are shown in [Table 1]. AVS was done to subtype the disease. Two doses of Inj. Acton Prolongatum, 0.5 ml, were given, intra muscularly, 1 hour apart (2nd dose given 30 minutes before procedure). Peripheral blood samples for ACTH were taken 1 hour and 2 hours afterthe 2nd injection. The right and left adrenal veins were sequentially cannulated, via the right femoral vein and samples were collected from each side and from the right femoral vein. The samples were assayed for aldosterone and cortisol.{Table 1} Results: The results of AVS are shown in [Table 2]. The peripheral blood samples collected after intra muscular injection of Acton Prolongatum showed high levels of ACTH (at 1 hour and 2 hour) suggesting adequate stimulation. The first patient had no lateralisation and the second patient had lateralisation to the right side. Accordingly, the first patient was managed with spironolactone and the second patient underwent robotic right adrenalectomy.{Table 2} Conclusion: In instances where Co syntropin is not available for AVS, Acton prolongatum may be successfully used as an alternative. [ABSTRACT FROM AUTHOR]

While the ACTH1-24 test has some well-documented shortcomings, it is the most wid ely used test to diagnose primary and secondary adrenal insufficiency. However, this synthetic ACTH preparation is not readily available in some countries. Research from India has demonstrated that using a lo ng-acting porcine sequence ACTH has similar diagnostic performance to ACTH1-24 at around 25% of the cost. This may allow access to a robust t est for adrenal insufficiency to developing countries and potentially all ow thousands of patients to be identified and appropriately treated. [ABSTRACT FROM AUTHOR]

Background & objectives: Adrenal insufficiency (AI) is rarely diagnosed in patients with HIV infection, in spite of autopsy studies showing very high rates of adrenal involvement. This study was aimed to determine the presence, patterns and predictors of AI in patients with HIV infection. Methods: Consecutive HIV patients, 18-70 yr age, without any severe co-morbid state, having at least one-year follow up at the antiretroviral therapy clinic, underwent clinical assessment and hormone assays. Results: From initially screened 527 patients, 359 patients having good immune function were analyzed. Basal morning cortisol <6 μg/dl (<165 nmol/l; Group 1), 6-11 μg/dl (165-300 nmol/l; Group 2), 11-18 μg/dl (300-500 nmol/l; Group 3) and ≥18 μg/dl (500 nmol/l; Group 4) were observed in 13, 71, 199 and 76 patients, respectively. Adrenocorticotropic hormone (ACTH) stimulation test revealed 87 patients (24.23%) to have AI. AI in groups 1-4 was 100, 56.34, 17.09 and 0 per cent, respectively. AI patients were more likely to be females (P< 0.05), having longer disease duration (P< 0.05), immune reconstitution inflammatory syndrome, hyperkalaemia (P< 0.01), lower fasting glucose (P< 0.01), dehydroepiandrosterone sulphate (DHEAS) and vitamin D. Regression analysis revealed morning cortisol and DHEAS to be best predictors of AI (P=0.004 and 0.028, respectively). Interpretation & conclusions: AI is a significant problem in HIV-infected individuals, observed in nearly a quarter of patients. Diagnosis warrants high index of suspicion and low threshold for screening, especially in those having low DHEAS and hyperkalaemia. Morning cortisol is a reasonable screening test, with ACTH stimulation warranted to confirm diagnosis, especially in patients with morning cortisol <11 μg/dl (300 nmol/l). [ABSTRACT FROM AUTHOR]

Pulse methyl prednisolone followed by oral prednisolone and abrupt switch to chlorambucil/cyclophosphamide (Ponticelli/modified Ponticelli regimen) is used in patients with idiopathic membranous nephropathy. This therapy where steroids are stopped abruptly is unphysiologic and expected to have hypothalamic pituitary adrenal (HPA) axis suppression; however, this has not been evaluated. A total of 13 consecutive adult patients with idiopathic membranous nephropathy who had completed modified Ponticelli regimen were studied. The regimen included administration of pulse methylprednisolone 1 g for 3 days followed by oral prednisolone 0.5 mg/kg/day for 27 days followed by oral cyclophosphamide at a dose of 2 mg/kg/day for the next month. This was repeated for three courses. Patients who had received corticosteroids prior to therapy were excluded. The HPA axis was evaluated after 1 month of completing the last course of steroid therapy. The evaluation was done using a low‑dose adrenocorticotropic hormone stimulation test. A single intravenous bolus dose of synacthen (1 g) was given at 9.00 am and the serum cortisol levels were estimated by radioimmunoassay at 0, 30, and 60 min. A peak cortisol level of 550 nmol/L or higher was considered as normal. Mean baseline cortisol levels was 662.3 ± 294.6 nmol/L and peak cortisol level was 767 ± 304.4 nmol/L. A total of 6 patients (46.2%) had low basal cortisol levels, only 3 (23%) had both basal and peak cortisol levels < 550 nmol/L suggestive of HPA axis suppression. To conclude, 23% of patients had suppression of HPA axis after modified Ponticelli regimen. [ABSTRACT FROM AUTHOR]

Context: Use of steroids in septic shock is an issue of contention, more so with two major trials reporting conflicting results. Aims: To assess the current knowledge, attitudes and practices (KAP) related to the role of steroids in septic shock among intensivists practising in Hyderabad. Setting, Design, Materials and Methods: Questionnaires containing 10 questions pertaining to the role of steroids in septic shock, were distributed to 76 intensivists during the monthly critical care meeting. Results: A great majority of intensivists (82%) agreed that the role of steroids is restricted to septic shock not responding to vasopressors. There was no clear consensus regarding the role of corticotropin stimulation test or the timing of total cortisol level testing, if it has to be performed. Hydrocortisone was clearly the choice of steroid for most intensivists and intravenous bolus injection being the preferred route of administration. There was no agreement regarding the dose of steroids, the role of fludrocortisone and whether steroids should be tapered. Most of the respondents did not extend the steroid therapy beyond seven days and the most common side effect reported was hyperglycemia. Conclusion: There is a lot of ambiguity in the knowledge, attitudes or practices regarding role of steroids in septic shock among intensivists in Hyderabad. Uniform policies and protocols need to be devised at institutional level, with multispecialty inputs, and doctors need to be familiarized accordingly. [ABSTRACT FROM AUTHOR]

The author comments on a study by A. Bhansali et al on the role of ectopic secretion of adrenocorticotropic hormone (ACTH) in Cushing's disease (CD) in tertiary care patients in India published in the same issue. He notes that the prevalence of weight loss in patients contradicts with weight gain observed in British and U.S. studies. He adds that no patients developed small lung cancer compared to 50% of cases in previous studies due to hypercortisolaemia. He says that the various tests used by researchers depict the difficulty in CD diagnosis.

An editorial is presented on psychiatry and psychology of the human mind. Topics discussed include advancement of research in biological psychiatry, the development of systems biology of neuron is vital; biologically homogenous subtypes may traverse different phenotypic presentations of the illness; and inflammatory cytokines access the brain through leaky areas in blood brain barrier.

Introduction: Cushing syndrome due to pituitary macroadenoma is less common compared to microadenoma. Behavior of the tumor in terms of clinical profile and response to various modalities of treatment is different from microadenoma. We share our 20 years of experience of Cushing macroadenoma with the clinical profile and treatment outcome. Aim and Objective: To study clinical profile and treatment outcome of a patient of Cushing disease with macroadenoma to a single tertiary care center in India. Patients and Methods: Medical record of 40 patients diagnosed with Cushing syndrome with macroadenoma from the year 1993-2012 were reviewed and analyzed. Results: Out of 40 patients, 16 (40%) were male and 24 (60%) were female. Mean age of presentation was 27.6 ± 10.67 years. Median duration between the onset of symptoms and diagnosis was 24 months. Median adrenocorticotrophic hormone (ACTH) value was 97.1 pg/ml. 50% or more supressibility for low dose dexamethasone suppression (LDDS) was found in 10/38 patients. Visual field defects and mass effects were found in 15 patients. Mean maximum dimension of tumor was 20.7 ± 9.8 mm. All 40 patients underwent TSS. Five patients underwent early remission defined as day 5 cortisol <1.8 μg/dl (though five patients showed relapse) and 10 patients showed delayed remission defined as 6-12 weeks LDDS <1.8 μg/d (no relapses). Between 25 uncured patients and two relapses, nine lost follow-up. Among two relapsed patients, one patient underwent 2nd TSS, remined uncured and cured by radiotherapy and the second patient is on medical management. Between 18 uncured patients, two expired and two preferred medical management. Fourteen patients underwent definitive management in the form of TSS or radiotherapy, 2nd TSS was done in four patients, and three patients who remained uncured were subjected to RT and got cured. Ten patients underwent radiotherapy as 2nd line of treatment of which six patients were cured, two remained uncured and two patients lost follow-up. Between two uncured patients after radiotherapy, one patient managed with medical therapy and the other underwent 2nd and 3rd TSS, still uncured and on medical management. Conclusion: Out of 40, 15 (37.5%) patients were cured after 1st TSS. 2nd TSS was done in six patients, but only 1 (17.5%) got cured. Radiotherapy was done in 14 patients, out of which 10 (71.5%) were cured, proving as effective modality of treatment for Cushing macroadenomas. [ABSTRACT FROM AUTHOR]

Objective: To study clinical profile and treatment outcome of patient of Cushing disease with macroadenoma to a single tertiary care center in India. Patients and Methods: Medical records of 42 patients diagnosed with Cushing macroadenoma from 1993 to 2012 were reviewed. Results: Out of 42 patients, 16 were male and 24 were female. Mean age of presentation was 27.6 ± 10.67 years. Median duration between onset of symptoms and diagnosis was 24 months. Median ACTH value was 97.1 pg/mL. Visual field defects and mass effect were found in 15 patients. Mean maximum dimension of tumor was 20.7 ± 9.8 mm. All 42 patients underwent TSS . Six patients underwent early remission and eleven patients showed (first TSS: cure rate: 37%) delayed remission. Among 25 uncured patients and 4 relapses, 8 lost to follow-up and 2 died. Nineteen underwent second line of management-seven: second TSS, two: medical management and ten: radiotherapy. Cure rate of second TSS was 12.5% and radiotherapy was 71%. Conclusion: Largest series of Cushing macroadenoma. Compared to literature, we have large proportion of macroadenoma, young macros (<30 years: 60%), and larger tumor size. The peculiar feature is delayed cure 65% of cured patients. Results of second TSS were poor and radiotherapy is very effective mode of therapy. [ABSTRACT FROM AUTHOR]

Objective: To study clinical profile of patient presented with EAS presented to a single tertiary care center in India. Materials and Methods: Medical record of 16 patients diagnosed with EAS from 1993 to 2012 were reviewed and analyzed. Results: Out of 250 patients with endogenous hypercortisolism, 16 patients had EAS. Of 16 patients, 10 were male and 06 were female. Median age of onset of symptom was 31.5 years. Median ACTH was 141 pg/ml with the range of 53.5 to 491 pg/ml. Eight patients had bronchial carcinoid, 6 had thymic and 2 had MTC. Median lag period between consultation and diagnosis was 6 months. Patients of bronchial carcinoid had more lag period than thymic carcinoid and MTC. MRI had false positivity in 5 patients and all of them underwent TSS. IPSS was done in 7 patients, all have shown peripheral cause. Even though initial imaging was negative in 3 cases, CT scan localized lesion in all patients. Five out of 7 patients of bronchial carcinoid were cured while 2 with metastatic lesion remained uncured. Out of 6, only 2 patients with thymic carcinoid underwent surgery and both remained uncured. Two patients had MTC, out of which 1 was cured. Conclusion: Bronchial carcinoids are more indolent, difficult to localize, but amiable for surgery with less metastatic potential. Thymic carcinoids and MTC even though diagnosed easily show aggressive course. CT scan remains most useful modality for localization. MRI pituitary gives false positivity in some cases. Due to false positivity on MRI, some patient may undergo TSS. IPSS most useful investigation for localization of central verses peripheral cause. [ABSTRACT FROM AUTHOR]