Russell-Silver Syndrome With Growth Hormone Deficiency.

Russell-Silver syndrome (RSS) is a rare genetic disorder characterized by intrauterine growth restriction (IUGR), postnatal growth failure, and distinctive dysmorphic features. We present a case of a four-year-old male presenting with a slow growth velocity with a history of IUGR and surgical interventions, exhibiting classic RSS features. Laboratory investigations revealed low insulin-like growth factor 1 (IGF-1) and low growth hormone (GH) levels on stimulation tests. Clinical exome sequencing revealed a de novo mutation in the insulin-like growth factor 2 (IGF2) gene. Additionally, a variant of uncertain significance in the DHX37 gene was noted in the patient and the asymptomatic father. After genetic counseling, recombinant GH therapy was initiated. This case underscores the genetic complexity of RSS and highlights the importance of early diagnosis, genetic testing, and multidisciplinary management in optimizing outcomes for patients with RSS.

Impending myocardial ischaemia during thyroid storm diagnosed through Wellens' syndrome.

We present a case of thyroid storm precipitated by discontinuation of antithyroid drugs. The patient developed a concurrent acute coronary event during the resolution period of the thyroid storm. After 48 hours of prudent management of thyroid storm, the patient's sensorium and haemodynamics were stabilised but he had persistent mild chest discomfort and developed new-onset jaw pain. On admission, ECG showed sinus tachycardia. In consideration of persistent mild chest discomfort and new-onset jaw pain, serial ECGs were performed which revealed biphasic T waves in V2-V3 suggestive of Wellens' syndrome type A. This indicated a critical stenosis of the left anterior descending (LAD) coronary artery and impending myocardial ischaemia. The patient underwent urgent coronary catheterisation, which revealed 80% stenosis of proximal LAD and was subsequently revascularised resolving his symptoms. This case underscores the significance of serial ECG monitoring even after the acute phase of thyroid crisis, which helped in timely identification of Wellens' syndrome.

Gout in Primary Hyperparathyroidism, Connecting Crystals to the Minerals.

Musculoskeletal manifestations in primary hyperparathyroidism (PHPT) range from 13% to 93% encompassing pseudogout, vertebral fracture, myopathy, and cord compression. Though pseudogout has been the most prevalent musculoskeletal condition in PHPT, rarely reports of acute gouty attacks in large joints including the knee have been reported in the literature. Here we detail a unique case of PHPT presenting with acute severe bilateral knee joint inflammatory arthritis accompanied by occasional abdominal pain. Joint aspiration fluid study revealed extracellular monosodium urate crystals exhibiting strong negative birefringence on polarized light microscopy suggestive of acute gouty arthritis. Hypercalcemia and hypophosphatemia with high intact parathyroid hormone (iPTH) confirmed the diagnosis of PHPT and a right inferior parathyroid adenoma was localized. Parathyroidectomy resulted in statistically significant clinical improvement of the debilitating joint manifestations, and the patient was able to walk again without support. Although the incidence of gout is increasing because of an overall increase in metabolic syndrome prevalence, a higher prevalence than in the general population is reported in PHPT. Serum uric acid levels positively correlate with serum iPTH levels in PHPT, and parathyroidectomy leads to a reduction in levels. Acute inflammatory joint pain due to urate crystal deposition in a large joint like the knee is an uncommonly reported condition in PHPT. Identifying the correct etiology in such a case can result in marked clinical improvement in the joint manifestations following surgical cure of hyperparathyroidism.

Clinical and Biochemical Characteristics of Patients with Renal Tubular Acidosis in Southern Part of West Bengal, India: A Retrospective Study.

PURPOSE OF THE STUDY: Reversible proximal tubular dysfunction associated with distal renal tubular acidosis (dRTA) mimics type 3 RTA, a condition classically associated with features of both proximal RTA (pRTA) and dRTA. Proximal tubulopathy has been reported in children with primary dRTA, but the data in adults are lacking. STUDY DESIGN: In this hospital record-based retrospective study, data from 66 consecutive cases of RTA, between January 2016 to December 2018, were retrieved and analyzed. RESULTS: Mean age of the study population was 25.3 years (range: 3 months to 73 years). Six (9.1%) of them had pRTA, 58 (87.9%) had dRTA, 1 (1.5%) had type 3 RTA, and the remaining 1 (1.5%) had type 4 RTA. Ten patients (17.2%) with dRTA and 3 patients of pRTA (50%) had underlying secondary etiologies. Data on proximal tubular dysfunction were available for 30 patients with dRTA, of whom 1 had isolated dRTA, and the rest 29 patients had accompanying completely reversible proximal tubular dysfunction. Among the 10 cases of secondary dRTA, 6 were not evaluated for proximal tubular dysfunction. Of the remaining 4, 3 had reversible form of proximal tubular abnormality. Fifty-two patients with dRTA came from a population, indigenous to the "Rarh" region of India. CONCLUSIONS: Proximal tubular dysfunction often accompanies dRTA; 75% of the children with primary dRTA, at least 29% of adults with primary dRTA, and at least 30% of adults with secondary dRTA manifest such completely reversible form of proximal tubulopathy. "Rarh' region of India probably is a hotspot for endemic dRTA.

Viper bite and its complications at a tertiary care centre in southern part of West Bengal: A prospective, clinical, socioeconomic and epidemiological study.

Background: Viper snake bite is a threat to the Indian health system with 83 000 deaths annually. There is a paucity of literature regarding independent risk factors for renal damage due to viper bite. We present the scenario in a rural part of West Bengal and highlight some vital factors to prevent the complications. Methods: We screened all patients with snake bite from January 2012 to December 2015 in Midnapore Medical College and chose definite viper bites according to our inclusion criteria, treated them as per the Indian government protocol, followed them for any acute kidney injury, managed them with haemodialysis (HD) if needed and compared some socioeconomic and clinical factors between HD and non-HD groups to predict the outcome. Results: A total of 1220 snake bites were screened, 660 were viper bites, and 1 80 needed HD at least once. The HD group mostly consists of tribal population (75% v. 45% in non-HD group) who used unscientific first-aid measures. Bite timing was characteristically between 4 a.m. and 8 a.m., especially during defecation in fields, without any considerable seasonal variation. The average bite-to-needle time was 24.6 hours in the HD group and 5.1 hours in the non-HD group, with the average economic burden of ₹3345 in the HD group and ₹730 in the non-HD group. Conclusions: Along with formal education, there is a need to create awareness among the relatively poor tribal population about snake bite to reduce the bite-to-needle time.

Promising approaches of small interfering RNAs (siRNAs) mediated cancer gene therapy.

RNA interference (RNAi) has extensive potential to revolutionize every aspect of clinical application in biomedical research. One of the promising tools is the Small interfering RNA (siRNA) molecules within a cellular component. Principally, siRNA mediated innovative advances are increasing rapidly in support of cancer diagnosis and therapeutic purposes. Conversely, it has some delivery challenges to the site of action within the cells of a target organ, due to the progress of nucleic acids engineering and advance material science research contributing to the exceptional organ-specific targeted therapy. This siRNA based therapeutic technique definitely favors a unique and effective prospect to cancer patients. Herein, the significant drive also takes to review and summarize the major organ specific targets of diverse siRNAs based gene silencing mechanism. This machinery promisingly served as the inhibitor components for cancer development in the human model. Furthermore, the focus is also given to current applications on siRNA based quantifiable therapy leading to the silencing of cancer related gene expression in a sequence dependent and selective manner for cancer treatment. That might be a potent tool against the traditional chemotherapy techniques. Therefore, the siRNA mediated cancer gene therapy definitely require sharp attention like future weapons in opposition to cancer by the method of non-invasive siRNA delivery and effective gene silencing approaches.

Etiological Search and Epidemiological Profile in Patients Presenting with Hypokalemic Paresis: An Observational Study.

INTRODUCTION: Hypokalemia is associated with increased morbidity and at times mortality. "Hypokalemic paralysis", particularly if recurrent, has often been considered synonymous with "hypokalemic periodic paralysis (HPP)"; however, diseases such as Gitelman syndrome (GS), Bartter syndrome (BS), and renal tubular acidosis (RTA) can have identical presentation. We have tried to explore the etiological spectrum along with epidemiological and certain clinical, biochemical, and electrophysiological features in patients with hypokalemic paralysis. MATERIALS AND METHODS: In this observational study, 200 appropriate patients with hypokalemic paralysis (serum K+ <3.5 mmol/L) were evaluated for transcellular shift, extra-renal or renal loss of K+ as the underlying etiology of hypokalemia. We took urinary potassium >25 mmol/day as the cutoff for inappropriate renal loss of potassium in presence of hypokalemia. Serum and urinary osmolality along with arterial blood gas analysis were performed in all patients with renal loss of potassium. Serum and urinary sodium, potassium, calcium, magnesium, chloride, and creatinine were measured in normotensive patients with metabolic alkalosis. Hypertensive patients were evaluated with plasma aldosterone and renin activity. RESULTS: Probable GS topped the list involving 28% individuals of the entire cohort while probable BS, distal RTA, and HPP were diagnosed in 20%, 22%, and 19% cases, respectively. Rural tribal population (61%) and age group of 30-40 years suffered the most (48%) with concentration of cases in hot and humid summer months. CONCLUSIONS: We suggest that patients with hypokalemic paresis should be evaluated thoroughly to unmask the underlying etiology that may have a different therapeutic and prognostic connotations and not to use the term "periodic" in cases of recurrent hypokalemic paralysis.

Primary male factor infertility due to asthenospermia in maturity-onset diabetes of the young type 5 (MODY 5): uncommon presentation of an uncommon disease.

Mutations in hepatocyte nuclear factor-1ß gene result in a multisystemic syndrome where a monogenic form of diabetes (maturity-onset diabetes of young type 5; MODY 5) and renal anomalies, usually bilateral multiple cysts are the most characteristic findings. Many of them have pancreatic structural abnormalities as well. A plethora of extrapancreatic manifestations like altered liver function tests, hypomagnesaemia, hyperuricaemia with/without gout and urogenital malformations, particularly in females are also components of the syndrome. Structural malformation of male urogenital tract is rare in MODY 5, even rarer is asthenospermia. We encountered a young non-obese individual having insulin-requiring diabetes following secondary oral agent failure with primary male factor infertility secondary to asthenospermia. A suggestive family history, lack of acanthosis, negative pancreatic autoimmunity, hypomagnesaemia, bilateral renal and epididymal cysts, and absence of body and tail of pancreas pointed towards underlying MODY 5.

Hypersomatotropism induced secondary polycythaemia leading to spontaneous pituitary apoplexy resulting in cure of acromegaly and remission of polycythaemia: 'The virtuous circle'.

A young man with subtle clinical features suggestive of hypersomatotropism presented with acute-onset severe headache. Relevant investigations confirmed polycythaemia and growth hormone (GH)-secreting pituitary macroadenoma with apoplexy. Secondary polycythaemia and myeloproliferative disorders were ruled out. At follow-up after 3 months, resolution of polycythaemia and acromegaly was observed, evident on normal haemoglobin levels, a normocellular marrow, and normal insulin-like growth factor-1 (IGF-1) with glucose-suppressed GH levels. Direct mitogenic properties of GH-IGF-1 axis on bone marrow progenitor cells may very rarely lead to erythroid hyperplasia and subsequent polycythaemia, reversible with successful therapy of acromegaly. In this case, polycythaemia secondary to hypersomatotropism likely resulted in pituitary apoplexy with subsequent remission of both acromegaly and resultant polycythaemia.

Mucopolysaccharidosis type IVA (Morquio A): a close differential diagnosis of spondylo-epiphyseal dysplasia.

Patients with mucopolysaccharidoses (MPS) have a plethora of multisystemic manifestations depending on the particular type, and atypical presentations are not uncommon. MPS type IVA (Morquio A syndrome) has predominant musculoskeletal system involvement and corneal clouding with normal intelligence and can be misdiagnosed as primary skeletal disorders in clinical practice. The absence of corneal clouding with normal urinary glycosaminoglycans (GAGs) level in a proportion of patients with MPS IVA makes the correct diagnosis even more challenging for physicians. Healthcare providers across specialties should have a high degree of suspicion for MPS IVA in all patients with suspected spondylo-epiphyseal dysplasia as early diagnosis and early treatment significantly improve the clinical outcome and activity of daily living.

Adrenal myelolipoma(s) as presenting manifestation of subclinical Cushing's disease (eutopic ACTH-dependent Cushing's syndrome).

Primary adrenal myelolipomas, relatively rare benign tumours of the adrenal cortex are typically unilateral, hormonally inactive and asymptomatic, hence often diagnosed as 'adrenal incidentaloma'. Bilateral adrenal myelolipomas, in particular, may be associated with underlying endocrinopathies associated with elevated circulating adrenocorticotropic hormone (ACTH) concentration. Subclinical cortisol hypersecretion, irrespective of its ACTH dependency, does not manifest typical clinical phenotype of hypercortisolemia, and thus termed subclinical Cushing's syndrome. In this article, hormonal evaluation in a middle-aged woman with diabetes, hypertension and incidentally discovered unilateral adrenal myelolipoma revealed underlying subclinical Cushing's disease. Abdominal CT revealed another tiny focus in the contralateral adrenal gland, probably representing incipient myelolipoma.

Erroneously elevated glucose values due to maltose interference in mutant glucose dehydrogenase pyrroloquinolinequinone (mutant GDH-PQQ) based glucometer.

Currently available glucose test strip enzymes include glucose oxidase (GOD) and glucose dehydrogenase (GDH). In GDH-based glucometers, glucose oxidation can be catalysed by different cofactors: nicotinamide adenine dinucleotide (GDH-NAD), flavin adenine dinucleotide (GDH-FAD), pyrroloquinolinequinone (GDH-PQQ) and mutant GDH-PQQ. GOD-based and GDH-NAD-based glucometers are substrate-specific and do not react with sugars other than glucose. GDH-FAD reacts with xylose only in addition to glucose. GDH-PQQ is not glucose-specific; in addition to glucose, it reacts with different other sugars and produces falsely high values of capillary glucose in the presence of such substances. There are reports of several deaths associated with usage of GDH-PQQ-based test strips. A modified form of GDH-PQQ, the so-called mutant GDH-PQQ, is supposedly free from such interferences. In this article spuriously high glucose values due to maltose interference in a glucometer using the mutant GDH-PQQ chemistry are being reported.