Etiology and Biochemical Profile of Rickets in Tertiary Care Centres in Eastern India: A Retrospective Cross-sectional Study.

Introduction: We aimed to describe the clinical, biochemical and etiological profile of patients referred with a provisional diagnosis of rickets in tertiary care centres. In addition, we tried to propose a diagnostic algorithm for the evaluation of such patients. Methods: This was a retrospective cross-sectional study conducted in two tertiary care centres of West Bengal. Data of patients were retrieved between 2014 and 2021. Results: Out of 101 children, 22 had conditions simulating rickets. Renal tubular acidosis (RTA) was the most common (53.2%) etiology of rickets, followed by phosphopenic rickets (PR) (22.8%) and calcipenic rickets (CR) (17.7%). The prevalence of true nutritional rickets (NR) was only 8.9%. Children with RTA had a significantly higher prevalence of chronic ill health (69%) and polyuria (95.2%). Weight standard deviation score (SDS) and body mass index (BMI) SDS scores were significantly lower in the RTA group compared to others. Around 90.5% of children with RTA, and none in the other groups, had hypokalemia. Biochemically, hypophosphatemia and elevated alkaline phosphatase (ALP) were present in all patients with PR and CR. Compared to CR, median serum phosphate was significantly lower in the PR group. A significant difference in ALP values was noticed in patients with hypophosphatemia (815 ± 627 IU/L) compared to those without (279 ± 204 IU/L). Plasma parathyroid hormone (PTH) of 100 pg/ml seemed useful to differentiate CR from other forms. Conclusion: NR is uncommon in tertiary care centres. Children with rickets should be approached systematically with the estimation of ALP, phosphorus, creatinine, calcium, PTH and 25-hydroxy vitamin D to reach an etiological diagnosis.

Effect of morning versus night-time administration of proton pump inhibitor (pantoprazole) on thyroid function test in levothyroxine-treated primary hypothyroidism: a prospective cross-over study.

BACKGROUND: One of the common causes of suboptimal control of thyroid stimulating hormone (TSH) in levothyroxine-treated hypothyroidism is coadministration of proton pump inhibitors (PPIs). Morning administration of pantoprazole has been shown to suppress intragastric pH to a greater extent. We therefore aimed to determine the effect of pantoprazole at different time points of the day on thyroid function test (TFT) in levothyroxine-treated overt primary hypothyroidism. METHODS: In this single centre, hospital based, prospective, two arm cross-over study (AB, BA), participants were randomized into 2 groups based on morning (6:00 am - 7:00 am simultaneously with the scheduled levothyroxine tablet) (group M) and evening (30 min before dinner) intake of 40 mg pantoprazole tablet (group N). After the initial 6 weeks (period 1), a washout period of 1 week for pantoprazole was given, and then both the groups crossed over for another 6 weeks (period 2). Patients were instructed to continue the same brand of levothyroxine tablet at empty stomach 1-hour before breakfast. Serum TSH was measured at baseline, week 6, and week 13. RESULTS: Data from 30 patients, who completed the study with 100% compliance, were analysed. Mean TSH values of the study participants were significantly higher both at week 6 and week 13 compared to the baseline. Mean baseline serum TSH concentrations for groups M and N were 2.70 (± 1.36), and 2.20 (± 1.06) µlU/mL, respectively. Mean serum TSH concentrations at the end periods 1 and 2 for group M were 3.78 (± 4.29), and 3.76 (± 2.77) while the levels in group N were 3.30 (± 1.90), and 4.53 (± 4.590) µlU/mL, respectively. There was a significant rise in serum TSH concentration across periods 1 and 2 in both the groups (F2, 58 = 3.87, p = 0.03). Within group changes in TSH across periods 1 and 2 were not statistically significant. Similarly difference in TSH between the groups, either at 6 weeks or at 13 weeks, were also not statistically significant. CONCLUSIONS: Concomitant use of pantoprazole, even for 6 weeks, leads to significant elevation in serum TSH in levothyroxine-treated patients who are biochemically euthyroid, irrespective of timing of pantoprazole intake. Early morning and night-time administration of pantoprazole have similar effect on TFT in these patients.

Rickets in proximal renal tubular acidosis: a case series of six distinct etiologies.

OBJECTIVES: Proximal renal tubular acidosis (pRTA) is characterized by a defect in the ability of the proximal convoluted tubule to reabsorb bicarbonate. The biochemical hallmark of pRTA is hyperchloremic metabolic acidosis with a normal anion gap, accompanied by appropriate acidification of the urine (simultaneous urine pH <5.3). Isolated defects in bicarbonate transport are rare, and pRTA is more often associated with Fanconi syndrome (FS), which is characterized by urinary loss of phosphate, uric acid, glucose, amino acids, low-molecular-weight proteins, and bicarbonate. Children with pRTA may present with rickets, but pRTA is often overlooked as an underlying cause of this condition. CASE PRESENTATION: We report six children with rickets and short stature due to pRTA. One case was idiopathic, while the remaining five had a specific underlying condition: Fanconi-Bickel syndrome, Dent's disease, nephropathic cystinosis, type 1 tyrosinemia, and sodium-bicarbonate cotransporter 1-A (NBC1-A) defect. CONCLUSIONS: Five of these six children had features of FS, while the one with NBC1-A defect had isolated pRTA.

Desmopressin treatment in dipsogenic form of primary polydipsia: keep serum osmolality marginally below thirst threshold for symptomatic relief.

Dipsogenic polydipsia (DP), a distinct variety of primary polydipsia, is characterised by selective diminution of osmotic threshold for thirst leading to polydipsia and subsequent hypotonic polyuria. Seen in patients without underlying psychiatric illness, DP closely mimics central diabetes insipidus (CDI), making it difficult for clinicians to discriminate these two conditions from each other. Carefully performed osmotic stimulation study, incorporating objective assessment of threshold for thirst and arginine vasopressin (AVP) release is the key to differentiate DP from CDI or psychogenic polydipsia, also termed compulsive water drinking (CWD). Low thirst threshold and high AVP release threshold separate DP from CDI and CWD, respectively. Unlike CWD, desmopressin may be successfully used in DP without concomitant risk of hyponatremia. We describe a child, in whom an initial diagnosis of partial CDI was subsequently revised to DP based on osmotic stimulation test. The child was treated successfully with desmopressin therapy with a target to keep serum osmolality close to thirst threshold.

Secondary distal renal tubular acidosis and sclerotic metabolic bone disease in seronegative spondyloarthropathy.

Adults with distal renal tubular acidosis (dRTA) commonly present with hypokalaemia (with/without paralysis), nephrolithiasis/nephrocalcinosis and vague musculoskeletal symptoms. All adults with dRTA should be thoroughly evaluated for systemic diseases, certain medications and toxins. The leading cause of acquired or secondary dRTA in adults is primary Sjögren syndrome (SS); however, other collagen vascular diseases (CVDs) including seronegative spondyloarthropathy (SSpA) may at times give rise to secondary dRTA. Metabolic bone disease is often encountered in adults with dRTA, and the list includes osteomalacia and secondary osteoporosis; sclerotic metabolic bone disease is an extremely rare manifestation of dRTA. Coexistence of dRTA and sclerotic bone disease is seen in primary dRTA due to mutation in CA2 gene and acquired dRTA secondary to systemic fluorosis. Primary SS and SSpA, rarely if ever, may also lead to both secondary dRTA and osteosclerosis. Circulating autoantibodies against carbonic anhydrase II and possibly calcium sensing receptor may explain both these features in patients with CVD.

Hypoplastic amelogenesis imperfecta, bilateral nephrolithiasis and FGF-23-mediated hypophosphataemia: a triad of FAM20A-related enamel renal syndrome.

Enamel renal syndrome (ERS) due to loss of function (LOF) mutation of FAM20A gene typically consists of hypoplastic amelogenesis imperfecta (AI) and bilateral nephrolithiasis/nephrocalcinosis. Recent evidence suggests that FAM20A interacts with FAM20C and increases its activity; thus LOF mutation of FAM20A leads to impaired FAM20C action. FAM20C, a golgi casein kinase, phosphorylates fibroblast growth factor (FGF)-23, prevents its glycosylation and makes it more susceptible to degradation by furine proteases. Consequently, inactivating mutations of FAM20C lead to increased concentration of bioactive and intact FGF-23 in circulation and resultant hypophosphataemia. LOF mutation of FAM20A, thus, might also be associated with FGF-23-mediated hypophosphataemia; however, such an association has never been reported in the literature. We describe, for the first time, a triad of AI, bilateral nephrolithiasis and FGF-23-mediated hypophosphataemia in LOF mutation of FAM20A. We suggest that serum phosphate should be measured in all patients with ERS to avoid metabolic and skeletal complications of undiagnosed, hence untreated hypophosphataemia.

Continuous and progressive 'wash-in' without 'wash-out' of contrast in adrenal mass: a useful feature of ganglioneuroma.

Computed tomography (CT) scan is a useful and widely performed diagnostic modality to evaluate adrenal masses. Nature of the mass determines the degree of attenuation both in unenhanced and in different phases of contrast enhancement. Benign neurogenic tumours like ganglioneuroma mimicks pheochromocytoma and adrenocortical carcinoma in non-contrast CT scan. The 'adrenal protocol' routinely calculates the wash-out pattern at delayed venous phase (DVP) (15 min) following contrast administration to differentiate majority of benign masses from the malignant ones. Ganglioneuromas typically exhibit continuous wash-in of contrast where enhancement gradually increases to attain its peak in DVP. Such wash-in pattern is different from the wash-out pattern observed in pheochromocytomas or adrenocortical adenomas or carcinomas. Presence of this wash-in pattern provides a useful clue to the clinician for underlying ganglioneuroma in hormonally inactive adrenal masses with suspicious morphological appearances. This wash-in pattern also effectively rules out any malignant potential of ganglioneuroma, and thus helps in preoperative decision-making.

False elevation of serum cortisol in chemiluminescence immunoassay by Siemens Advia Centaur XP system in 21-hydroxylase deficiency: an 'endocrine laboma'.

Liquid chromatography-mass spectrometry, the gold standard method for cortisol measurement, is expensive and not widely available in the developing countries. Chemiluminescent immunoassay, commonly used for cortisol measurement is prone to clinically meaningful inter-assay variability in some analysers. This occurs due to non-specific nature of anticortisol antibodies used in different platforms, having cross reactivity with structurally similar cortisol precursors like 17α-hydroxyprogesterone (17OHP), 11-deoxycortisol and 21-deoxycortisol. In patients with 21-hydroxylase deficiency, where 17OHP and 21-deoxycortisol are significantly elevated, older generation machines like Siemens Advia Centaur XP provide spuriously high cortisol concentration compared with values measured by Roche Cobas e 411 or Siemens Immulite 1000. Diagnosis of potentially life-threatening salt-wasting 21-hydroxylase deficiency may be missed and treatment may be delayed due to such interference. Two children with classic 21-hydroxylase deficiency are being reported here, in whom high cortisol values were observed in Siemens Advia Centaur XP system.