Dinesh Kumar Dhanwal

Epidemiology of hip fracture: Worldwide geographic variation

Osteoporosis is a major health problem, especially in elderly populations, and is associated with fragility fractures at the hip, spine, and wrist. Hip fracture contributes to both morbidity and mortality in the elderly. The demographics of world populations are set to change, with more elderly living in developing countries, and it has been estimated that by 2050 half of hip fractures will occur in Asia. This review conducted using the PubMed database describes the incidence of hip fracture in different regions of the world and discusses the possible causes of this wide geographic variation. The analysis of data from different studies show a wide geographic variation across the world, with higher hip fracture incidence reported from industrialized countries as compared to developing countries. The highest hip fracture rates are seen in North Europe and the US and lowest in Latin America and Africa. Asian countries such as Kuwait, Iran, China, and Hong Kong show intermediate hip fracture rates. There is also a north–south gradient seen in European studies, and more fractures are seen in the north of the US than in the south. The factors responsible of this variation are population demographics (with more elderly living in countries with higher incidence rates) and the influence of ethnicity, latitude, and environmental factors. The understanding of this changing geographic variation will help policy makers to develop strategies to reduce the burden of hip fractures in developing countries such as India, which will face the brunt of this problem over the coming decades.

Thyroid disorders and bone mineral metabolism.

Thyroid diseases have widespread systemic manifestations including their effect on bone metabolism. On one hand, the effects of thyrotoxicosis including subclinical disease have received wide attention from researchers over the last century as it an important cause of secondary osteoporosis. On the other hand, hypothyroidism has received lesser attention as its effect on bone mineral metabolism is minimal. Therefore, this review will primarily focus on thyrotoxicosis and its impact on bone mineral metabolism.

High prevalence of subclinical hypothyroidism during first trimester of pregnancy in North India.

Background: Thyroid dysfunction is a common occurrence in pregnancy and affects both maternal and fetal outcomes. There are limited data on prevalence of hypothyroidism during pregnancy from India. Therefore, this study was designed to evaluate the prevalence of thyroid dysfunction especially hypothyroidism during first trimester in a large public hospital in North India. Materials and Methods: All the consecutive first trimester pregnant women attending Lok Nayak and Kasturba Hospitals were enrolled in the study after institutional ethics approval and consent from the study subjects. The pregnant women with diagnosed thyroid disease and on thyroid medications were excluded from the study. Morning samples of study participants were analyzed for thyroid hormone profile which included free T3, free T4, TSH, and TPO Ab. In addition, all study participants were tested for CBC, LFT, KFT, and lipid profile. Results: A total of 1000 women were enrolled for this prospective observational study. The mean (SD) age of study subjects was 25.6 (11.1) years, and mean (SD) gestational age was 10.3 (3.4) weeks. One hundred and forty-three (14.3%) subjects had TSH values more than 4.5 mIU/L above the cutoff used for definition of hypothyroidism. Out of these, 135 had normal free T4 and therefore labeled as subclinical hypothyroidism and 7 had low free T4 suggestive of overt hypothyroidism. TPO Ab was positive in 68 (6.82%) of total, 25 (18.5%) of subclinical and 5 (71%) of overt hypothyroid patients. Conclusion: Hypothyroidism, especially subclinical, is common in North Indian women during first trimester. Further countrywide studies are needed to evaluate the prevalence and etiology of hypothyroidism to prevent maternal and fetal adverse effects of hypothyroidism in India.

Hypovitaminosis D and Bone Mineral Metabolism and Bone Density in Hyperthyroidism

Little is known about the impact of concomitant vitamin D deficiency on bone mineral density in hyperthyroidism. Therefore, we evaluated bone mineral measures in vitamin D-deficient and sufficient patients with hyperthyroidism. Thirty newly diagnosed consecutive patients with hyperthyroidism were included. Blood samples were used for measurement of calcium, phosphate, alkaline phosphatase, 25-hydroxy vitamin D [25(OH) D], and parathyroid hormone (PTH). Bone mineral density (BMD) was measured at the hip, spine, and forearm. The patients were divided into vitamin D-deficient (< 25 nmol/L) and vitamin D-sufficient groups (≥ 25 nmol/L). Eight (26.6%) patients had 25(OH) D levels less than 25 nmol/L, with mean ± standard deviation (SD) level of 16.5 ± 3.2 (vitamin D-deficient group 1), and the remainder had a mean ± SD of 46.0 ± 13.5 nmol/L (vitamin D-sufficient group 2). Serum-intact PTH levels were significantly higher in group 1 compared with those in group 2 (31.2 ± 16.3 vs 18.0 ± 13.1 pg/mL; p=0.041). In the vitamin D-deficient group, the mean BMD T-scores were in the osteoporotic range at hip and forearm (-2.65 ± 1.13 and -3.04 ± 1.3) and in the osteopenia range at lumbar spine (-1.83 ± 1.71). However, in vitamin D-sufficient group, the mean BMD T-scores were in the osteopenia range (-1.64 ± 1.0, -1.27 ± 1.6, and -1.60 ± 0.7) at hip, forearm, and lumbar spine, respectively. The mean BMD Z-scores were also significantly lower in vitamin D-deficient group compared with those in vitamin D-sufficient group. Finally, BMD values (gm/cm(2)) at the hip and forearm were significantly lower in the vitamin D-deficient group compared with those in the vitamin D-sufficient group. In conclusion, hyperthyroid patients with concomitant vitamin D deficiency had lower BMD compared with vitamin D-sufficient patients.

Hypothalamic pituitary abnormalities in tubercular meningitis at the time of diagnosis

Tubercular meningitis (TBM) is the most dreaded form of extra pulmonary tuberculosis associated with high morbidity and mortality. Various hypothalamic pituitary hormonal abnormalities have been reported to occur years after recovery from disease but there are no systematic studies in the literature to evaluate the pituitary hypothalamic dysfunction in patients with TBM at the time of presentation. Therefore, the present study was designed to evaluate hypothalamic pituitary abnormalities in newly diagnosed patients with TBM. Patient case series. This prospective study included 75 untreated adult patients with TBM diagnosed as “definite”, “highly probable” and “probable” TBM by Ahuja’s criteria and in clinical stage 1, 2 or 3 at the time of presentation to hospital. Basal hormonal profile was measured by electrochemilumniscence technique for serum cortisol, luetinizing hormone (LH), follicular stimulating hormone (FSH), prolactin (PRL), thyrotropin (TSH), free tri-iodothyronine (fT3), and free thyroxine (fT4). All patients were subjected to MRI to image brain and hypothalamic pituitary axis and CT for adrenal glands. Thirty-two (42.7%) cases showed relative or absolute cortisol insufficiency. Twenty-three (30.7%) cases showed central hypothyroidism and 37 (49.3%) cases had hyperprolactinemia. No patient had evidence of diabetes insipidus. Multiple hormone deficiency was seen in 22 (29.3%) cases. MRI of hypothalamic pituitary axis using dynamic scanning and thin cuts revealed abnormalities in 10 (13.3%) of the cases. CT adrenal gland was normal in all the patients. Tubercular meningitis is associated with both hormonal and structural abnormalities in the hypothalamic pituitary axis at the time of diagnosis.

A Randomized Controlled Trial on Safety and Efficacy of Single Intramuscular versus Staggered Oral Dose of 600 000IU Vitamin D in Treatment of Nutritional Rickets

OBJECTIVE Comparison of efficacy and safety of two different regimens of vitamin D-600 000 IU as a single intramuscular dose, and 60 000IU orally once a week for 10 weeks-in treatment of nutritional rickets. METHODS Children with nutritional rickets (age: 0.5-5 years, n = 61) were randomized to receive either 60 000IU vitamin D orally once a week for 10 weeks or 600 000IU single intramuscular injection. Serum calcium, phosphate, alkaline phosphatase, urinary calcium/creatinine ratio, serum 25 hydroxy vitamin D and radiological score were compared at 12-week follow-up. RESULTS No difference was found in efficacy of the two regimens on comparing biochemical and radiological parameters. Serum 25 hydroxy vitamin D >100 ng/ml was found in two children in the oral group and one child in the intramuscular group. No child developed hypercalcemia or hypercalciuria after starting treatment. CONCLUSION Staggered oral and one-time intramuscular administrations of 600 000IU vitamin D are equally effective and safe in treatment of nutritional rickets.

Evaluation of autonomic functions in subclinical hypothyroid and hypothyroid patients

Background: Autonomic dysfunction may contribute to cardiovascular morbidity in subclinical hypothyroid patients. It is controversial whether the abnormality exists in sympathetic or the parasympathetic function. It is also not known whether the severity of autonomic dysfunction is related to the degree of thyroid deficiency. Design of Study: Prospective case control. Materials and Methods: Autonomic functions based on heart rate (HR) and blood pressure (BP) responses to various maneuvers were evaluated and scored in twenty two subclinical hypothyroid patients, 30-50 years and compared with twenty hypothyroid patients. Biochemical estimation of TSH, fT3, fT4, TPO antibody was done. Result: Sympathetic function abnormalities were seen in 82% subclinical hypothyroid patients and 85%hypothyroid patients when one test was abnormal. Parasympathetic dysfunction was also recorded in eight patients in both groups. When two abnormal tests were used as the selection criteria sympathetic function abnormality was observed in about 41% subclinical hypothyroid and 65% hypothyroid patients. There were no intergroup differences in autonomic functions, score and TPO levels. The TSH levels were not related to type or degree of autonomic dysfunction. Systolic BP in both groups and diastolic BP in hypothyroid patients were higher with lower thyroxine levels but the patients were normotensive. Conclusion: Autonomic dysfunction of comparable degree was seen in subclinical hypothyroid and hypothyroid patients. Sympathetic function abnormality was more common although decreased parasympathetic function reactivity was also present. These abnormalities were unrelated to TSH levels.

Recurrent symptomatic hypoglycaemia with pancytopenia as a delayed presentation of Sheehan's syndrome with complete recovery after hormone replacement

A 38-year-old woman presented to our hospital emergency section in altered sensorium and with blood pressure of 80/60 mm Hg. She gave a history of recurrent episodes of loss of consciousness for 15–20 days, generalised body swelling and generalised weakness for the past 5–6 years. On further evaluation she was found to have severe hypoglycaemic episodes. In view of history of pregnancy and significant blood loss during surgery and long history of lethargy, asthaenia and generalised anasarca, the patient was evaluated for Sheehans syndrome. Her serum cortisol levels were very low and she was found to have central hypothyroidism. MRI of the brain also revealed small sella turcica and small pituitary gland suggestive of hypopituitarism. The patient was started on high-concentration dextrose drips, steroids and thyroid hormone replacement. The patient showed a marked improvement within 1 week of treatment. And she was discharged with an advice to follow-up at our outpatient department.

Hormonal profile in children with isolated hypospadias associates better with comprehensive score of local anatomical factors as compared to meatal location or degree of chordee.

Background: To evaluate if hormonal profile of children with isolated hypospadias (IH) associates better with comprehensive local anatomical factor score (LAFS) than with clinically adjudged urethral meatus location or severity of chordee/k.j. Material and Methods: Ninety-nine children with IH were enrolled, as per inclusion criteria. Meatal location was recorded at first clinical examination in OPD; while LAFS was computed per-operatively using indigenously devised scale, except for neonates. Hypospadiacs were first classified into three standard meatal based groups and subsequently into LAFS based two groups (≤19, >19). For all participants, pre HCG and post HCG (96 hour post- injection) estimation of serum gonadotropins, DHEA-S, estrogen (E), progesterone (P), testosterone (T) and Dihydrotestosterone (DHT) was done. Statistical tests were applied to assess significance of hormonal levels with respect to meatal location, chordee and LAFS. Results: Only FSH levels differed significantly among meatal based groups; while among LAFS groups, multiple hormonal differences were noted; with poor LAFS associated significantly with higher FSH, LH and lower E, T/DHT. Children with severe degree of chordee had poorer T output and a significantly lower LAFS as compared to those with moderate/mild chordee. Conclusion: Serotoli cell dysfunction, indirectly indicated by high FSH was found among midpenile hypospadiacs and those with poorer LAFS. Since groups based on LAFS revealed multiple intergroup hormonal differences than what was seen for meatal/chordee based groups; LAFS should be considered a better guide for prognostication and for deciding about hormonal supplementation. Lower androgenic output was particularly noted in children with severe chordee.

Acute psychosis as a presentation of hypopituitarism.

Acute onset neuropsychiatric manifestations in hypopituitarism are uncommon. We report a case of a 60-year-old man who was a follow-up case of macroprolactinoma with hypopituitarism for the last 9 years. He was on medical treatment with cabergoline, thyroxine and depot testosterone. During the last 2 years he was non-adherent to medications especially cabergoline. He was hospitalised for 2 days through emergency services following acute onset psychosis. His pituitary hormone profile was suggestive of adrenal insufficiency, secondary hypothyroidism and hypogonadism. MRI of the hypothalamic pituitary region revealed a pituitary macroadenoma which was larger in size compared to the previous scan. Further, this lesion was compressing on the adjoining structures including optic chiasma. The patient was treated with intravenous fluids, hydrocortisone and thyroxine replacement therapy. With this treatment he completely recovered from psychosis within 48 h.