Sahana Shetty

Bone turnover markers: Emerging tool in the management of osteoporosis

Bone is a dynamic tissue which undergoes constant remodeling throughout the life span. Bone turnover is balanced with coupling of bone formation and resorption at various rates leading to continuous remodeling of bone. A study of bone turnover markers (BTMs) provides an insight of the dynamics of bone turnover in many metabolic bone disorders. An increase in bone turnover seen with aging and pathological states such as osteoporosis leads to deterioration of bone microarchitecture and thus contributes to an increase in the risk of fracture independent of low bone mineral density (BMD). These microarchitectural alterations affecting the bone quality can be assessed by BTMs and thus may serve as a complementary tool to BMD in the assessment of fracture risk. A systematic search of literature regarding BTMs was carried out using the PubMed database for the purpose of this review. Various reliable, rapid, and cost-effective automated assays of BTMs with good sensitivity are available for the management of osteoporosis. However, BTMs are subjected to various preanalytical and analytical variations necessitating strict sample collection and assays methods along with utilizing ethnicity-based reference standards for different populations. Estimation of fracture risk and monitoring the adherence and response to therapy, which is a challenge in a chronic, asymptomatic disease such as osteoporosis, are the most important applications of measuring BTMs. This review describes the physiology of bone remodeling, various conventional and novel BTMs, and BTM assays and their role in the assessment of fracture risk and monitoring response to treatment with antiresorptive or anabolic agents.

Osteoporosis in Healthy South Indian Males and the Influence of Life Style Factors and Vitamin D Status on Bone Mineral Density

Objective. To study the prevalence of osteoporosis and vitamin D deficiency in healthy men and to explore the influence of various life style factors on bone mineral density (BMD) and also to look at number of subjects warranting treatment. Methods. Ambulatory south Indian men aged above 50 were recruited by cluster random sampling. The physical activity, risk factors in the FRAX tool, BMD, vitamin D, and PTH were assessed. The number of people needing treatment was calculated, which included subjects with osteoporosis and osteopenia with 10-year probability of major osteoporotic fracture >20 percent and hip fracture >3 percent in FRAX India. Results. A total of 252 men with a mean age of 58 years were studied. The prevalence of osteoporosis and osteopenia at any one site was 20% (50/252) and 58%, respectively. Vitamin D deficiency (<20 ng/dL) was seen in 53%. On multiple logistic regression, BMI (OR 0.3; P value = 0.04) and physical activity (OR 0.4; P value < 0.001) had protective effect on BMD. Twenty-five percent warranted treatment. Conclusions. A significantly large proportion of south Indian men had osteoporosis and vitamin D deficiency. Further interventional studies are needed to look at reduction in end points like fractures in these subjects.

Wilson's disease: An endocrine revelation

Wilsons disease is an inherited disorder of copper metabolism. The affected patients, who otherwise have a near normal life span, may often suffer from some potentially treatable and under recognized endocrine disorders that may hinder their quality of life. We explored previously published literature on the various endocrine aspects of this disease with their probable underlying mechanisms, highlighting the universal need of research in this area.

Olfactory Agenesis in Kallmann Syndrome (KS).

Kallmann syndrome (KS) is a heterogeneous genetic disorder characterised by isolated gonadotrophic deficiency and anosmia. Defective migration of GnRH neurons along with olfactory neurons results in hypoplasia or agenesis of olfactory bulb and or sulci and gonadotrophin deficiency. We hereby report a young female who presented with features of hypogonadism and anosmia. A 17-year-old female presented to our endocrine clinic with primary amenorrhea. She was born of non-consanguineous marriage and her birth history was unremarkable and developmental mile stones were normal. On questioning, she admitted to the fact that she was not very appreciative of smell from the childhood when compared to other family members. Her stature was at par with her peers and there was neither a history of any chronic illness nor any medication. She had one male elder sibling whose growth and pubertal development were normal according to age. On examination, her height was 162 cm with a mid-parental height of 159 cm. There was no pallor or oedema or thyromegaly. There were no dysmorphic features. Her Tanner staging for breasts was prepubertal (Tanner 1) and pubic hair was also Tanner stage 1. Cardiovascular, respiratory and neurological examinations were within normal limits. Her blood investigations were as follows: TSH – 2 uIU/ml (Normal: 0.8-4), FT4-1.1 ng/dl (Normal: 0.8-1.8), FSH-0.2mIU/ml, LH-0.2mIU/ml, Prolactin-12 ng/ml (Normal<20), morning cortisol -16 μg/dl (Normal: 12-15), Hemoglobin- 13.2 gm/dl, Creatinine- 1.1 mg/dl (Normal: 0.8-1.3). She underwent MRI scanning of the brain [Table/Fig-1] which revealed the absence of olfactory bulb and olfactory sulci [Table/Fig-1]. The MRI brain of a normal subject is shown in [Table/Fig-2] for comparison. Her low gonadotropin levels in the absence of normal pubertal development and imaging features were suggestive of KS, a form of hypogonadotropic hypogonadism. There were no skeletal or renal abnormalities. She was initiated on cyclical oestrogen – progesterone pills with which she developed secondary sexual characters along with menstrual bleeding at one year follow up. [Table/Fig-1]: MRI brain of the patient showing absence of olfactory sulci and bulb [Table/Fig-2]: MRI brain of a normal subject displaying olfactory sulci and bulb KS is a heterogeneous genetic disorder which include hypogonadism and anosmia due to hypoplasia or agenesis of olfactory bulb and sulci along with GnRH deficiency [1]. It is a genetically heterogenous condition, with X-linked, autosomal dominant and recessive modes of inheritance due to mutataions in KAL 1, FGF 8/ FGFR1 and PROK2/PROK2R respectively [2]. The X linked forms may be associated with other phenotypic features. The autosomal forms of KS (A-KS) exhibit no consistent phenotype apart from gonadotropin deficiency and anosmia, although a heterogeneous collection of defects are seen in a minority of cases. The associated defects include cleft palate or other craniofacial and dental defects, unilateral renal agenesis or aplasia; cryptorchidism, micropenis, neural hearing defects and synkinesis or mirror movements of hand [3]. Since GnrH pulsation studies may not be possible at all centres, MRI with 1 mm cut is an important diagnostic tool for diagnosis of KS. Management of these subjects include screening for associated anomalies and monitoring for progressive worsening secondary to organ defects. The goal of the treatment is two folds. First, hormone replacement therapy is needed to induce puberty and to maintain gonadal hormones at near normal physiological levels till fifth decade of life. Secondly, fertility treatment involves administering gonadotrophins to induce ovulation.

The impact of the Hologic vs the ICMR database in diagnosis of osteoporosis among South Indian subjects.

Recently, the Indian Council of Medical Research (ICMR) has published normative data for bone mineral density (BMD) measured by dual‐energy X‐ray absorptiometry (DXA) scanning. However, the impact this has had on the diagnosis of osteoporosis when compared to currently used Caucasian databases has not been analysed. Hence, this study was undertaken to look at agreement between the Hologic Database (HD) based on BMD normative data in Caucasians and the ICMR database (ICMRD) in defining osteoporosis in subjects with or without hip fracture.

Metastatic parathyroid carcinoma treated with radiofrequency ablation: A novel therapeutic modality.

Parathyroid carcinoma (PCA), accounting for less than one per cent of all endocrine malignancies, is a rare cause of primary hyperparathyroidism. A diagnosis of parathyroid carcinoma may be challenging in the presence of localised disease and involves a histological diagnosis based on capsular, vascular, or perineural invasion or the presence of metastasis. Distant metastasis remains a rare presentation, with the lung being the most common site. Surgery remains the treatment of choice as radiotherapy and chemotherapy have proved to be of limited benefit in metastatic disease. This case reports suggests that radiofrequency ablation has the potential to be a novel and effective treatment option in these patients.

The H Syndrome: Molecular Diagnosis Using Next-Generation Sequencing

ABSTRACT Objective: H syndrome is a monogenic systemic inherited form of histiocytosis, with characteristic cutaneous findings accompanying systemic manifestations. The major common endocrine manifestations include hypogonadism, short stature, and diabetes mellitus with characteristic genodermatosis and lead to the diagnosis. Here, we report a rare case of H-syndrome, an autosomal recessive non-autoimmune disorder in a 19-year-old woman who presented with short stature, diabetes mellitus, and hypogonadism associated with characteristic hyperpigmentation and hypertrichosis. The molecular diagnosis was established utilizing next-generation sequencing (NGS) technology. Methods: We describe the clinical spectrum of H syndrome with endocrine and non endocrine multisystem involvement. The solute carrier family 29 (nucleoside transporters), member 3 (SLC29A3) gene was screened for molecular diagnosis utilizing NGS based mutational analysis. Results: H syndrome is caused by a mutation in the SLC29A3 gene, which e...

An Unusual Presentation of a Patient with Multiple Endocrine Neoplasia- 1

Prolonged under-recognized hypoglycaemia may later manifest with wide range of neurological symptoms and signs including recurrent seizures, cognitive decline, ataxia secondary to cerebellar atrophy, small muscle wasting and peripheral neuropathy. We hereby report a young man who presented with recurrent episodes of seizures and intention tremor.

Toxic Thyroid Adenoma in McCune-Albright Syndrome

Case A 17-year-old lady presented with history of palpitations, tremors, heat intolerance and weight loss, all of two months duration. She also had a history of fractures, following a trivial trauma. The first fracture was in left forearm at the age of 10 years, which was managed conservatively and the second was in neck of left femur two months ago, for which she had undergone closed reduction and internal fixation [Table/Fig-1]. She also had noticed a left facial swelling since childhood, which had been gradually progressive and was operated two years back. Her age of menarche was 13 years and she had regular menstrual cycles.

Images in Medicine - Bisphosphonate Induced Atypical Fracture

Bisphosphonates are the first line therapy for treating post menopausal osteoporosis. Usually,they are well tolerated and have good efficacy in decreasing fracture risk with few adverse effects. The common side effect is upper gastrointestinal tract irritation like oesophagitis especially seen with oral bisphosphonates. One of the less commonly encountered adverse effect is atypical fracture of femoral shafts. Physicians who are prescribing bisphosphonates should be aware of this rare adverse effect. We report a case who presented to us with an atypical fracture.