Unravelling a hidden pathology of a vertebral fracture in a teenage girl.

BACKGROUND: Although the skeleton remains a common target of primary hyperparathyroidism, the classic bone disease "osteitis fibrosa cystica" is currently rare due to early diagnosis. This case represents severe classic bone manifestations of primary hyperparathyroidism due to delayed diagnosis and delayed medical attention. CASE PRESENTATION: A 19-year-old young female was symptomatically managed for chronic back pain and nonspecific bone pain in the small joints of both hands over 2 months by a general practitioner. The patient had delayed seeking for treatment for 3 months. Later, she was evaluated for tuberculosis, hematological malignancies and rheumatic disorders following a fractured T12 vertebra and underwent pedicle screw fixation. However, clinical examination and investigations, including biochemistry, imaging and histology, ruled out the above conditions. Unfortunately, serum calcium level was not performed at the initial presentation. Later, primary hyperparathyroidism was diagnosed on the basis of moderate hypercalcaemia and elevated intact PTH levels (2064 pg/ml). She had sufficient vitamin D levels and normal kidney function. Her DXA scan revealed severe secondary osteoporosis with the lowest Z score of -8 at the total lumbar spine. Ultrasonography of the thyroid revealed a hypo echoic mass in the left lower neck, and localization studies with technetium-99 m sestamibi and 4D-CT revealed a left inferior parathyroid adenoma (1.6 × 1.5 × 1.6 cm). CT scan also revealed brown tumors in the mandible and vertebrae and diffuse bony changes in the skull, sternum, humerus and vertebrae. Her radiographs revealed subperiosteal bone resorption on the radial aspects of the middle and distal phalanges and brown tumors in both the ulna and fibula. We excluded MEN and other hereditary syndromes in our patient with a personal and family history and with a normal pituitary hormone profile because of poor resources for genetic testing. She underwent parathyroid adenoma excision, and the postoperative period was complicated with hungry bone syndrome, requiring high doses of calcium and active vitamin D supplements. These supplements were gradually weaned off over 6 months, and she recovered with normal biochemical investigations. Histology revealed parathyroid adenoma without malignant features. CONCLUSION: In developing countries where routine calcium screening is not available, clinicians should be aware of various manifestations of primary hyperparathyroidism to allow diagnosis as soon as possible without delay to prevent further progression, as it is a treatable condition.

A case report of subacute thyroiditis after inactivated SARS-CoV-2 vaccine.

Subacute thyroiditis is an inflammatory thyroid disorder. It is often triggered following viral infections. Amid the current COVID-19 pandemic, several cases of subacute thyroiditis were reported worldwide related to SARS-CoV-2 infection and vaccines. We report a rare case of subacute thyroiditis possibly related to immunization with inactivated SARS-CoV-2 vaccine Sinopharm BIBP. A 29-year-old previously healthy Sri Lankan woman presented with anterior neck pain, low-grade fever and fatigue appearing 7 days after immunization with the second dose of inactivated SARS-CoV-2 vaccine Sinopharm BIBP. She apparently reported similar symptoms which subsided spontaneously within a few days, following immunization with first dose of vaccine. On examination, she had tenderness over the anterior neck. She was afebrile, not tachycardic and clinically euthyroid. Her inflammatory markers were elevated. An ultrasound scan of the neck demonstrated two low echogenic micronodules of 6 x 3 mm2 and 5 x 3 mm2 and low background thyroid vascularity. Technetium 99 m pertechnetate (Tc - 99 m) thyroidal uptake scan shows reduced thyroidal uptake suggestive of subacute thyroiditis. Thyroid function tests were normal at the time of the assessment. The patient was treated symptomatically with non-steroidal anti-inflammatory drugs. Her neck pain and tenderness resolved gradually. Serial measurements of thyroid functions during follow-up were within normal limits. Inflammatory markers normalized over the course of follow-up. Subacute thyroiditis following COVID-19 vaccination is a rare occurrence. However, due to its mild clinical course, it could very well be underreported. It is a mild and self-limiting illness with transient thyroid dysfunction; thus, it should be emphasized that the benefits of COVID-19 vaccination outweigh any rare and mild side effects reported.

Individualizing Time-in-Range Goals in Management of Diabetes Mellitus and Role of Insulin: Clinical Insights From a Multinational Panel.

Diabetes mellitus is a global health concern associated with significant morbidity and mortality. Inadequate control of diabetes leads to chronic complications and higher mortality rates, which emphasizes the importance of achieving glycemic targets. Although glycated hemoglobin (HbA1c) is the gold standard for measuring glycemic control, it has several limitations. Therefore, in recent years, along with the emergence of continuous glucose monitoring (CGM) technology, glycemic control modalities have moved beyond HbA1c. They encompass modern glucometrics, such as glycemic variability (GV) and time-in-range (TIR). The key advantage of these newer metrics over HbA1c is that they allow personalized diabetes management with person-centric glycemic control. Basal insulin analogues, especially second-generation basal insulins with properties such as longer duration of action and low risk of hypoglycemia, have demonstrated clinical benefits by reducing GV and improving TIR. Therefore, for more effective and accurate diabetes management, the development of an integrated approach with second-generation basal insulin and glucometrics involving GV and TIR is the need of the hour. With this objective, a multinational group of endocrinologists and diabetologists reviewed the existing recommendations on TIR, provided their clinical insights into the individualization of TIR targets, and elucidated on the role of the second-generation basal insulin analogues in addressing TIR.

Tolerability and effectiveness of every-other-day atorvastatin compared to daily atorvastatin in patients with muscle symptoms: A randomized controlled clinical trial.

Despite limited evidence, non-daily dosing of statins is recommended for managing muscle symptoms associated with statin therapy. We assessed the tolerability and effectiveness of every-other-day atorvastatin compared to daily atorvastatin in patients having muscle symptoms associated with atorvastatin therapy. A parallel-group, outcome-assessment-blinded, randomized controlled clinical trial was conducted at Colombo South Teaching Hospital, Sri Lanka. Patients with muscle pain, tenderness or cramps alone or in combination for ≥2 weeks while on daily atorvastatin for ≥1 month, with no alternative cause, were recruited. Patient's regular atorvastatin dose was given every-other-day to those in intervention group (IG) and daily to those in control group (CG). Primary outcomes were assessed at 24 weeks and included composite of myalgia and myositis, LDL-cholesterol level and percentage reduction of LDL-cholesterol from baseline. Number recruited was 49 to IG (women:79.6%; mean-age:60.6 ± 8.7years) and 52 to CG (women:73.1%; mean-age:61.7 ± 9.8years). Mean atorvastatin dose per day was 8.6 mg (SD = 4 mg) and 17.6 mg (SD = 8.4 mg) in IG and CG, respectively. Composite of myalgia and myositis at 24 weeks was 79.6% in IG and 69.2% in CG (OR = 1.7, 95% CI 0.7-4.3; p = 0.234). IG failed to show noninferiority for mean LDL-cholesterol (difference:0.31 mmol/L; upper limit 97.5% CI:0.61 mmol/L; p for noninferiority = 0.989) and for mean percentage reduction of LDL-cholesterol from baseline (difference:3.13%; upper limit 97.5% CI:15.5%; p for noninferiority = 0.718). At 24 weeks, mean creatine kinase and discomfort due to muscle symptoms (assessed with Visual Analogue Scale) were not different between the two groups. Findings of this study do not favor every-other-day atorvastatin as an option for managing patients with muscle symptoms associated with atorvastatin therapy.

A Practitioner's Toolkit for Insulin Motivation in Adults with Type 1 and Type 2 Diabetes Mellitus: Evidence-Based Recommendations from an International Expert Panel.

AIM: To develop an evidence-based expert group opinion on the role of insulin motivation to overcome insulin distress during different stages of insulin therapy and to propose a practitioner's toolkit for insulin motivation in the management of diabetes mellitus (DM). BACKGROUND: Insulin distress, an emotional response of the patient to the suggested use of insulin, acts as a major barrier to insulin therapy in the management of DM. Addressing patient-, physician- and drug-related factors is important to overcome insulin distress. Strengthening of communication between physicians and patients with diabetes and enhancing the patients' coping skills are prerequisites to create a sense of comfort with the use of insulin. Insulin motivation is key to achieving targeted goals in diabetes care. A group of endocrinologists came together at an international meeting held in India to develop tool kits that would aid a practitioner in implementing insulin motivation strategies at different stages of the journey through insulin therapy, including pre-initiation, initiation, titration and intensification. During the meeting, emphasis was placed on the challenges and limitations faced by both physicians and patients with diabetes during each stage of the journey through insulinization. REVIEW RESULTS: After review of evidence and discussions, the expert group provided recommendations on strategies for improved insulin acceptance, empowering behavior change in patients with DM, approaches for motivating patients to initiate and maintain insulin therapy and best practices for insulin motivation at the pre-initiation, initiation, titration and intensification stages of insulin therapy. CONCLUSIONS: In the management of DM, bringing in positive behavioral change by motivating the patient to improve treatment adherence helps overcome insulin distress and achieve treatment goals.

Type 2 diabetes mellitus and oral Candida colonization: Analysis of risk factors in a Sri Lankan cohort.

Aims: Oral candidiasis is a major oral manifestation of uncontrolled diabetes mellitus, and a number of cofactors are associated with the pathogenesis of this infection. Here, we describe the prevalence of oral Candida in a Sri Lankan cohort of type 2 diabetes mellitus and risk factors that predispose them to this common fungal infection. Methods: A case-control study was conducted in 250 diabetics with type 2 diabetes and 81 nondiabetic controls. Clinical and demographic data were collected using an interviewer administered questionnaire, and patient records. Oral rinse samples were collected to determine the candidal carriage, and the resultant yeast growth was quantified and speciated using multiplex-PCR and phenotypic analyses. Chi-square test (χ2 test) and Fisher exact test were used for the determination of the significant relationships between risk factors and oral candidiasis. Results: The oral prevalence of Candida species among both groups was similar (81%) although a significantly higher proportion of diabetics (32.8%) yielded >2000 CFU/mL of yeasts compared with only 12.3% of the healthy controls (p < .05). Significant associations were noted between oral candidal carriage amongst diabetics, and (i) denture wearing, (ii) female gender and (iii) cigarette smoking (all, p < .05). Amongst both groups, C.albicans was the most common Candida species isolated followed by C. parapsilosis, C. tropicalis and C. glabrata. Conclusions: The oral infestation of Candida in our Sri Lankan cohort of diabetics is significantly higher than their healthy counterparts, and co-carriage of multiple yeast species is a common finding in the study population. As there are no previous such reports of the latter phenomenon particularly from the Asian region it is noteworthy, mainly in view of the recent data on the emergence of drug-resistant yeast species the world over.

Successful Management of Pheochromocytoma Detected in Pregnancy by Interval Adrenalectomy in a VHL Patient.

A 34-year-old mother with diabetes mellitus for 6 years presented in the late second trimester of her third pregnancy with new onset hypertension and characteristic hyperadrenergic spells. Clinical examination was unremarkable except a blood pressure of 170/110 mmhg. She had an elevated 24 hour urinary normetanephrine level with ultrasonic evidence of a hyperechoic hypervascular well-defined right supra renal mass of 6 x 5 cm in size which was very suggestive of a pheochromocytoma. Her management decisions were made by a multidisciplinary team which decided to deliver the baby by lower segment cesarean section (LSCS) as the pregnancy was advanced and to proceed with interval adrenalectomy after contrast enhanced computer tomography (CECT) of the abdomen with adrenal protocol. As a result a healthy baby was delivered by an uncomplicated elective LSCS at 36 weeks of POA. CECT abdomen with adrenal protocol confirmed a right-sided pheochromocytoma without any evidence of metastasis. Uncomplicated laparoscopic right adrenalectomy led to a clinical and biochemical recovery of the patient while histology confirmed the pheochromocytoma without any evidence of invasion. Subsequent follow up revealed cerebellar hemangioblastomas and retinal angioma in the right eye which led to a clinical diagnosis of Von Hippel Lindau disease (VHL). Even though clinical criteria for Von Hippel Lindau disease were fulfilled, her VHL genetic test was negative. At present she and her family are under surveillance of the endocrine team.

Comparison of duplex PCR and phenotypic analysis in differentiating Candida dubliniensis from Candida albicans from oral samples.

Candida dubliniensis shares a wide range of phenotypic characteristics with Candida albicans including a common trait called germ tube positivity. Hence, laboratory differentiation of these two species is cumbersome. Duplex PCR analyses for C. albicans and C. dubliniensis was performed directly on DNA extracted from a total of 122 germ tube positive isolates derived from 100 concentrated oral rinse samples from a random cohort of diabetics attending a clinic in Sri Lanka. These results were confirmed by DNA sequencing of internal transcribed spacer (ITS) region of rDNA of the yeasts. Performance efficacy of duplex PCR was then compared with phenotypic identification using a standard battery of phenotypic tests. Of the 122 germ tube positive isolates three were identified by duplex PCR as C. dubliniensis and the remainder as C. albicans. On the contrary, when the standard phenotypic tests, sugar assimilation and chlamydospore formation, were used to differentiate the two species 13 germ tube positive isolates were erroneously identified as C. dubliniensis. Duplex PCR was found to be rapid, sensitive and more specific than phenotypic identification methods in discriminating C. dubliniensis from C. albicans. This is also the first report on the oral carriage of C. dubliniensis in a Sri Lankan population.

Myxedema Crisis Presenting with Seizures: A Rare Life-Threatening Presentation-A Case Report and Review of the Literature.

Myxedema crisis is a life-threatening extreme form of hypothyroidism with a high mortality rate if left untreated. Myxedema crisis is commonly seen in older patients, especially in women, and is associated with signs of hypothyroidism, hypothermia, hyponatraemia, hypercarbia, and hypoxemia. Patients might present with different organ specific symptoms. Seizures are a recognized but rare manifestation of myxedema with a very high mortality rate. Prompt diagnosis and appropriate management may improve the prognosis. Many contributory factors may involve development of seizures in a patient with myxedema. Hyponatraemia is one such cause, which is seen in moderate-severe form in the background of myxedema. We report an elderly male who presented with generalized tonic clonic seizure preceded by memory impairment and drowsiness. He had moderate hyponatraemia and very high thyroid stimulatory hormone levels in association with low free thyroxin levels. Diagnosis of myxedema crisis was made and patient was successfully treated with sodium correction and thyroid hormone replacement.

Novel mutation in the SLC12A3 gene in a Sri Lankan family with Gitelman syndrome & coexistent diabetes: a case report.

BACKGROUND: Gitelman syndrome (GS) is a rare autosomal recessively inherited salt-wasting tubulopathy associated with mutations in the SLC12A3 gene, which encodes for NaCl cotransporter (NCC) in the kidney. CASE PRESENTATION: In this report, we describe two siblings from a Sri Lankan non-consanguineous family presenting with hypokalaemia associated with renal potassium wasting, hypomagnesemia, hypocalciuria and hypereninemic hyperaldosteronism with normal blood pressure. Genetic testing showed that both were homozygotes for a novel missense mutation in exon 10 of the SLC12A3 gene [NM_000339.2, c.1276A > T; p.N426Y], which has not previously been reported in the literature in association with GS. Their mother was a heterozygous carrier for the same mutation. The father was not alive at the time of testing. This novel mutation extends the spectrum of known SLC12A3 gene mutations and further supports the allelic heterogeneity of GS. Interestingly both siblings had young onset Diabetes with strong family history. CONCLUSION: These findings have implications in providing appropriate genetic counseling to the family with regard to the risk associated with inbreeding, the detection of carrier/presymptomatic relatives. It further expands the known spectrum of genotypic and phenotypic characteristics of Gitelman syndrome.

Safe and pragmatic use of sodium-glucose co-transporter 2 inhibitors in type 2 diabetes mellitus: South Asian Federation of Endocrine Societies consensus statement.

Diabetes prevalence shows a continuous increasing trend in South Asia. Although well-established treatment modalities exist for type 2 diabetes mellitus (T2DM) management, they are limited by their side effect profile. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) with their novel insulin-independent renal action provide improved glycemic control, supplemented by reduction in weight and blood pressure, and cardiovascular safety. Based on the clinical outcomes with SGLT2i in patients with T2DM, treatment strategies that make a "good clinical sense" are desirable. Considering the peculiar lifestyle, body types, dietary patterns (long duration religious fasts), and the hot climate of the South Asian population, a unanimous decision was taken to design specific, customized guidelines for T2DM treatment strategies in these regions. The panel met for a discussion three times so as to get a consensus for the guidelines, and only unanimous consensus was included. After careful consideration of the quality and strength of the available evidence, the executive summary of this consensus statement was developed based on the American Association of Clinical Endocrinologists/American College of Endocrinology protocol.

A sensitive and a rapid multiplex polymerase chain reaction for the identification of Candida species in concentrated oral rinse specimens in patients with diabetes.

OBJECTIVES: Oral candidiasis is being frequently recognized in patients with diabetes, and is associated with multiple pathogens including Candida albicans, Candida parapsilosis, Candida glabrata and Candida tropicalis. The aim of this study was to evaluate a usefulness of a Multiplex Polymerase Chain Reaction as a rapid diagnostic tool for identification of four oral Candida pathogens in patients with diabetes. MATERIALS AND METHODS: A multiplex PCR was optimized to identify four Candida species in concentrated oral rinse samples. Common reverse primer, ITS4 and four species-specific forward primers targeting ITS1 and ITS2 regions of yeast genome were used. Species-specific single amplicon were detected by agarose gel electrophoresis. Performance efficacy of multiplex PCR was compared with phenotypic identification. RESULTS: Out of 100 oral rinse samples, 72 were culture positive and of these 43 were at risk of oral Candida infection (>600cfu/ml). Multiple Candida species including C. albicans, C. parapsilosis and C. tropicalis were identified in 22 samples which had risk of oral Candida infection. In total, 85 patients were positive for Candida by multiplex PCR and of them 49 had multiple Candida species. All 43 colonized specimens were also positive by multiplex PCR. C. albicans was the most predominant organism (75/85) followed by C. parapsilosis (47/85), C. tropicalis (17/85) and C. glabrata (6/85). In specimens with multiple species, the two most common organisms were C. albicans and C. parapsilosis. Multiplex PCR yielded a sensitivity of 10 Candida cells/ml of oral rinse sample. CONCLUSIONS: Multiplex PCR is found to be rapid, sensitive and specific than phenotypic identification methods in discriminating multiple Candida species in oral rinse specimens.

Rhabdomyolysis: A rare presentation of aldosterone-producing adenoma.

Rhabdomyolysis results from acute damage of the skeletal muscle brought on by various conditions of which hypokalemia is a recognized, but less common condition. Although primary aldosteronism may cause severe hypokalemia leading to rhabdomyolysis, the patients may have potassium levels within the normal range on routine biochemistry. In addition, hypokalemia may be triggered by initiation of diuretic therapy for control of hypertension. Here, we describe a patient with an aldosterone secreting adrenal adenoma, who presented with acute rhabdomyolysis secondary to severe hypokalemia triggered by initiation of diuretic therapy.

Steroid cell tumor not otherwise specified of bilateral ovaries: A rare cause of post menopausal virilization.

Steroid cell tumors of the ovaries are rare sex-hormone secreting tumors which are usually benign and unilateral. One previous study has estimated the tumors to be bilateral in 6% of patients. We report a case of post menopausal virilization where tumor histology revealed steroid cell tumor not otherwise specified with benign charactsristics. The presence of tumor in bilateral ovaries made this case unique.

The clinical impact of identifying metabolic syndrome in patients with diabetes: a cross-sectional study.

The objectives of the study were to determine whether identifying patients with metabolic syndrome (MetS) (as defined by International Diabetes Federation [IDF] criteria) among patients with diabetes would affect the decision to prescribe statin for primary prevention of cardiovascular disease (CVD), based on currently available public health guidelines. We analysed the most recent recorded CVD risk profiles obtained from electronic patient files from 304 general practices in England and Wales. Of 60,258 patients with diabetes, 11,005 men and women aged 30-74 years fulfilled criteria for primary CVD prevention and were not on lipid-lowering drugs. Outcome data were extrapolated to an estimated national diabetes prevalence of 3.6%. Identifying MetS in this group of patients would produce an additional 29,536 (8.4%; 95% CI: 7.7, 9.0), 104,288 (29.6%; 95% CI: 28.5, 30.7) and 147, 328 (41.9%; 95% CI: 40.8, 43.0) patients nationally who would not have been eligible otherwise for primary CVD prevention strategies with statins, based on the Joint British Societies', the National Institute for Health and Clinical Excellence and the General Medical Services contract guidelines, respectively. The sensitivity and positive predictive value of these different strategies to detect metabolic syndrome were 87.5% and 69.1%; 57.3% and 76.8%; and 37.8% and 70.2%, respectively. In conclusion, among individuals with diabetes, identifying patients with MetS may further increase the use of statin therapy for primary CVD prevention.