Co-existence of type 1 diabetes and other autoimmune ailments in subjects with autoimmune thyroid disorders.

BACKGROUND AND AIMS: Autoimmune thyroid dysfunction (AITD) is a significant autoimmune disorder affecting the population across age groups. The clustering of autoimmune diseases tends to occur within the same patients and families. Thus, this study aimed to determine the association of Type 1 diabetes and other autoimmune ailments in patients with autoimmune thyroid disorders. METHODS: We performed a cross-sectional study, evaluating 500 subjects with a diagnosis of AITD (130 with Graves' disease; 370 with Hashimoto's thyroiditis) on presentation to our tertiary care centre to ascertain the prevalence of associated autoimmune disorders. RESULTS: The frequency of Type 1 diabetes and other autoimmune disorders was 18.5% in Graves' disease and 27.8% in Hashimoto's thyroiditis patients. Coeliac disease (8.8%) (found in 6.9% of Graves' disease and 9.5% of Hashimoto's thyroiditis patients) and type 1 diabetes (7.8%) (found in 3.1% of Graves' disease and 9.5% of Hashimoto's thyroiditis patients) were the most common coexisting autoimmune disorders. Rheumatoid arthritis was the most common non-endocrine autoimmunity (2.8%). Female sex and duration of AITD more than five years were associated with increased odds of associated autoimmune disorders. CONCLUSION: A high prevalence of associated autoimmune disorders was observed in subjects with autoimmune thyroid dysfunction. We suggest the patients who remain symptomatic and those who develop other symptoms even with appropriate treatment undergo screening for associated autoimmune disorders, thus preventing a delay in diagnosis.

Adrenal histoplasmosis in immunocompetent individuals a case series from the North-Western part of India, Rajasthan province: An emerging endemic focus.

Histoplasmosis is a fungal infection caused by Histoplasma capsulatum and very few cases reported from North-West India. Adrenal histoplasmosis is an even more uncommon mycotic disease. We describe five immunocompetent men with adrenal histoplasmosis presenting with constitutional symptoms. Four patients had bilateral adrenal involvement, whereas one had unilateral adrenal mass. Three patients had adrenal insufficiency at presentation and the other two developed adrenal insufficiencies during follow-up. All the patients received amphotericin B and itraconazole treatment which led to symptomatic improvement but adrenal insufficiency persisted in all patients at the end of the follow-up.

Bilateral Inferior Petrosal Sinus Sampling in Corticotropin-Dependent Cushing's Syndrome: A Single Center Experience from Western India.

OBJECTIVE: Efficacy of bilateral inferior petrosal sinus sampling (BIPSS) in corticotropin-dependent Cushing's syndrome (CS) for localization and lateralization of excess adrenocorticotropic hormone (ACTH) source, as compared to high-dose dexamethasone suppression test (HDDST) and magnetic resonance imaging (MRI) pituitary, respectively. METHODOLOGY: Thirteen patients with clinically and biochemically confirmed CS underwent HDDST, MRI pituitary, and BIPSS by an experienced team of intervention neurologist, neurosurgeon, and endocrinologist using percutaneous femoral vein approach. RESULTS: Of 13 patients (11 adults and two children) who underwent BIPSS, raised central to peripheral ACTH ratio was achieved in 12 cases, remaining one case being ectopic ACTH secretion (EAS). However, inter IPS gradient >1.4 was achieved in 11 (91.6%) of 12 Cushing's disease (CD) cases before vasopressin stimulation; and in 9 (75%) of 12 CD cases after vasopressin stimulation (P-value 0.583). HDDST suppression of more than 50% was present in only ten cases with CD, falsely negating CD in two cases (16.6%), sensitivity 83.3% and specificity 100%. MRI sella demonstrated pituitary microadenoma in 12 cases and macroadenoma in one case. Lateralization by BIPSS and MRI was concordant in 7 (58.3%) out of 12 cases with CD, with rate of remission after transsphenoidal surgery being higher in patients with concordant lateralization by BIPSS and MRI. CONCLUSIONS: BIPSS is an important investigation to distinguish CD and EAS. BIPSS was superior to HDDST for confirming the source of excess ACTH. Our findings favor the use of BIPSS for localization and pituitary MRI for lateralization of microadenoma.

Coexistence of Autoimmune Disorders and Type 1 Diabetes Mellitus in Children: An Observation from Western Part of India.

INTRODUCTION: Type 1 diabetes mellitus (T1DM) is associated with various autoimmune disorders like celiac disease, thyroid disorder, adrenal failure, etc. However, how common is this association in Indian children is not clearly known. OBJECTIVE: To assess the prevalence of other coexisting autoimmune disorders in children with T1DM. MATERIALS AND METHODS: In this cross-sectional study, patients requiring insulin and ketosis-prone diabetic and with history of diabetic ketoacidosis/undetectable fasting C-peptide levels were included. Beside demographic and clinical data, detailed biochemistry evaluations were performed. Celiac disease was diagnosed as per the ESPGHAN diagnostic criteria. ACTH stimulation test was done to confirm the adrenal insufficiency in patients with basal serum cortisol <5 µg/dL. Thyroid function test (TSH) and anti-TPO antibody were assessed in all patients. Screening for other autoimmune disorders was done only when clinically indicated or symptoms or family history was suggestive of presence of such disorder. RESULTS: Among 150 patients enrolled, 64.66% were males and mean age was 13.48 ± 3.29 years (range 3-18 years). Mean age at diagnosis of T1DM was 10.0 ± 3.63 years and duration of diabetes was 3.46 ± 3.18 years. The prevalence of antibodies positive against autoimmune diseases was anti-tTG IgA (20.7%), anti-TPO (33.7%), anti-CCP ab (1.3%), and ANA (0.7%). Significantly higher proportion of females had raised anti-TPO antibodies than males (47.2% vs. 25.8%, P = 0.006). Celiac disease was most common association (24.8%) followed by hypothyroidism (14.1%) and Grave's disease (3.3%). Significantly higher proportion of females had hypothyroidism than males (25.0% vs. 8.2%, respectively, P = 0.005). Prevalence of raised anti-tTG and anti-TPO did not differ significantly by the age (P = 0.841 and P = 0.067) or duration of T1DM (P = 0.493 and P = 0.399). CONCLUSION: In this part of country, celiac disease, hypothyroidism, and Graves's disease are common associations in children with T1DM.

Correlation of Olfactory Phenotype by Indian Smell Identification Test and Quantitative MRI of Olfactory Apparatus in Idiopathic Hypogonadotropic Hypogonadism.

OBJECTIVES: Idiopathic hypogonadotropic hypogonadism (IHH) can be associated with anosmia/hyposmia. The objective of this study is to evaluate olfaction by Indian smell identification test (INSIT) and measure olfactory bulbs (OBs) and sulci using dedicated magnetic resonance imaging (MRI) in patients with IHH and correlate MRI findings with INSIT. METHODS: Forty patients with IHH underwent (a) brief smell identification test (INSIT) and (b) MRI of the olfactory apparatus. The size of olfactory sulcus and bulb was quantified and compared with the normative data obtained in 22 controls. The agreement between INSIT and MRI was assessed using Kappa index. RESULTS: Of the 40 patients, 8 patients who reported abnormal smell sensation and 12 of the remaining 32 patients who reported normal smell sensation historically had a low score on INSIT. Thus, there were 20 patients with Kallmann syndrome (KS) and the rest 20 were normosmic IHH (nIHH). Of 40 patients with IHH, MRI finding was suggestive of normal (n = 16), hypoplastic (n = 12), and aplastic (n = 12) olfactory apparatus. All 20 patients with KS have olfactory abnormalities (n = 12 aplastic, n = 8 hypoplastic), and 4 of 20 nIHH have olfactory abnormalities (hypoplastic only) on MRI. There is (a) significant positive correlation (r = 0.54, P = 0.013) between the OB volume (MRI) and smell test scores and (b) moderate agreement (Kappa index: 0.49) between smell defect (INSIT score ≤ 4) and aplastic olfactory apparatus. CONCLUSION: Self-reporting of smell significantly underestimates olfactory phenotype, and hence we recommend an objective smell test to differentiate KS from nIHH. Olfactory phenotype significantly correlates with MRI quantification of olfactory apparatus in IHH.

Osteoporosis in Otherwise Healthy Patients with Type 2 Diabetes: A Prospective Gender Based Comparative Study.

BACKGROUND AND OBJECTIVE: Type 2 diabetes mellitus (T2DM) may affect bone loss differentially in adult males and postmenopausal females. We evaluated the prevalence of osteoporosis in otherwise healthy adults with T2DM. MATERIALS AND METHODS: In a cross-sectional study, adults with T2DM, aged 50 years and above, were evaluated for bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA) scan at spine and hip. T-score of ≤-2.5 was defined as osteoporosis and score -2.49 to -1.0 as osteopenia at either site. Correlation of low BMD with demographic, clinical, and laboratory parameters including serum Vitamin D and serum testosterone (in males) was evaluated. RESULTS: In 200 patients, mean age was 64.5 ± 7.0 years and age differed significantly in males and females (P < 0.0001). Osteoporosis was present in 35.5% adults with T2DM. Significantly greater proportion of females had osteoporosis (49.5% vs. 22.3%, P < 0.0001). Frequency of osteoporosis at spine (33.5%) was higher than the same at hip (13.5%). Compared to males, significantly greater proportion of females had osteoporosis and osteopenia at both spine (P < 0.0001) and hip (P < 0.0001). Among all parameters assessed, a significant positive correlation of T-score at spine and hip was seen with body mass index in both males (r = 0.287, P = 0.003 at spine and r = 0.421, P < 0.0001 at hip) and females (r = 0.291, P = 0.004 at spine and r = 0.280, P = 0.010 at hip). There was no association of Vitamin D deficiency (45.5% patients) with either T-score and presence of osteoporosis either at spine (P = 0.388 and P = 0.177) or hip (P = 0.431 and P = 0.593). CONCLUSION: Prevalence of osteoporosis in otherwise healthy T2DM was 35.5% with greater prevalence in females than males. Body mass but not Vitamin D or testosterone has an important role in the determination of bone loss in T2DM.

Effect of hypothyroidism on female reproductive hormones.

OBJECTIVE: Objective was to evaluate reproductive hormones levels in hypothyroid women and impact of treatment on their levels. MATERIALS AND METHODS: A total of 59 women with untreated primary hypothyroidism were included in this prospective study. Venous blood was taken at baseline and after euthyroidism was achieved for measuring serum free thyroxine, free triiodothyronine (FT3), thyroid stimulating hormone (TSH), prolactin (PRL), follicular stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T), and thyroid peroxidase antibody. Thirty-nine healthy women with regular menstrual cycles without any hormonal disturbances served as controls. The statistical analysis was performed using the Statistical Package for the Social Sciences Version 20 ([SPSS] IBM Corporation, Armonk, NY, USA). P < 0.05 was considered statistically significant. RESULTS: On an average at diagnosis cases have more serum TSH (mean [M] = 77.85; standard error [SE] = 11.72), PRL (M = 39.65; SE = 4.13) and less serum E2 (M = 50.00; SE = 2.25) and T (M = 35.40; SE = 2.31) than after achieving euthyroidism (M = 1.74; SE = 0.73), (M = 16.04; SE = 0.84), (M = 76.25; SE = 2.60), and (M = 40.29; SE = 2.27), respectively. This difference was statistically significant t (58) = 6.48, P <0.05; t (58) = 6.49, P < 0.05; t (58) = 12.47; P < 0.05; and t (58) = 2.04, P < 0.05; respectively. Although average serum FSH (M = 12.14; SE = 0.40) and LH (M = 5.89; SE = 0.27) were lower in cases at diagnosis than after achieving euthyroidism (M = 12.70; SE = 0.40), (M = 6.22; SE = 0.25), respectively, but these differences were statistically insignificant t (58) = 1.61, P = 0.11; t (58) = 1.11, P = 0.27, respectively. CONCLUSION: The study has demonstrated low E2 and T levels in hypothyroid women which were increased after achieving euthyroidism. Although average serum FSH and LH were increased in hypothyroid women after achieving euthyroidism but this difference was statistically insignificant.

Congenital hypothyroidism.

Congenital hypothyroidism (CH) is the one of the most common preventable cause of mental retardation. In the majority of patients, CH is caused by an abnormal development of the thyroid gland (thyroid dysgenesis) that is a sporadic disorder and accounts for 85% of cases and the remaining 15% of cases are caused by dyshormonogenesis. The clinical features of congenital hypothyroidism are so subtle that many newborn infants remain undiagnosed at birth and delayed diagnosis leads to the most severe outcome of CH, mental retardation, emphasizing the importance of neonatal screening. Dried capillary blood is used for screening and it is taken from heel prick optimally between 2 and 5 days of age. Blood spot TSH or thyroxine (T4) or both are being used for CH screening in different programs around the world. Neonates with abnormal thyroid screening tests should be recalled immediately for examination and a venipuncture blood sample should be drawn for confirmatory serum testing. Confirmatory serum should be tested for TSH and free T4, or total T4. Serum TSH and T4 undergo dynamic changes in the first weeks of life; it is important to compare serum results with age-normal reference ranges. Treatment should be started promptly and infant should be rendered euthyroid as early as possible, as there is an inverse relationship between intelligence quotient (IQ) and the age at diagnosis. Levothyroxine (l-thyroxine) is the treatment of choice and American academy of pediatrics and European society of pediatric endocrinology recommend 10-15µgm/kg/day as initial dose. The immediate goal of therapy is to normalize T4 within 2 weeks and TSH within one month. The overall goal of treatment is to ensure growth and neurodevelopmental outcomes as close as possible to their genetic potential.

An unusual presentation of Hashimoto's encephalopathy.

Hashimoto's encephalopathy (HE) is a rare steroid-responsive encephalopathy syndrome, which can have highly variable neuropsychiatric manifestations and can go unrecognized for a long time. HE is a diagnosis of exclusion and should be kept in mind when evaluating a patient with a cognitive dysfunction and high titers of anti-thyroid antibodies as it responds dramatically to steroids. Steroid responsive myoclonus can be a presentation of HE.

Pituitary stalk interruption syndrome: Case report of three cases with review of literature.

Pickardt syndrome (Pickardt-Fahlbusch syndrome) is a rare congenital syndrome characterized by tertiary hypothyroidism caused by the interruption of the portal veins between hypothalamus and adenohypophysis. Typical features of this syndrome are tertiary hypothyroidism with low thyroid stimulating hormone, hyperprolactinemia and other pituitary hormone deficiencies. Pituitary stalk interruption syndrome is characterized by a triad of thin or interrupted pituitary stalk, aplasia or hypoplasia of the anterior pituitary and absent or ectopic posterior pituitary (EPP) seen on magnetic resonance imaging (MRI). It is a congenital anomaly of pituitary whose exact prevalence is unknown. In some cases, it is restricted to EPP or pituitary stalk interruption. We are presenting the case history along with MRI finding of three children's who presented with short stature and delayed puberty.

Pulse dexamethasone therapy versus pulse methylprednisolone therapy for treatment of Graves's ophthalmopathy.

Pulse methylprednisolone therapy is the recommended therapy for moderate to severe and active ophthalmopathy, but high dose pulse methylprednisolone therapy is marred by the chances of fulminant hepatic failure and the high cost of therapy. Dexamethasone pulse therapy can be considered as an alternative to pulse methylprednisolone therapy. A prospective randomized control trial was carried out in 21 patients comparing pulse dexamethasone therapy versus pulse methyprednisolone therapy in Graves's ophthalmopathy. This study proved that pulse dexamethasone therapy is a cheaper and equally effective therapy for Graves's ophthalmopathy and the cost of therapy is reduced to at least 1/8(th) s. Furthermore, dexa had a better effect on reduction of exophthalmos. The dreaded complication of fulminant hepatic failure, associated with high dose of methylprednisolone, is not seen with dexa therapy.

Skeletal manifestations of juvenile hypothyroidism and the impact of treatment on skeletal system.

Thyroid hormone mediates growth and development of the skeleton through its direct effects and through its permissive effects on growth hormone. The effect of hypothyroidism on bone is well described in congenital hypothyroidism, but the impact of thyroid hormone deficiency on a growing skeleton, as it happens with juvenile hypothyroidism, is less defined. In addition, the extent to which the skeletal defects of juvenile hypothyroidism revert on the replacement of thyroid hormone is not known. A study was undertaken in 29 juvenile autoimmune hypothyroid patients to study the skeletal manifestations of juvenile hypothyroidism and the impact of treatment of hypothyroidism on the skeletal system of juvenile patients. Hypothyroidism has a profound impact on the skeletal system and delayed bone age, dwarfism, and thickened bands at the metaphyseal ends being the most common findings. Post treatment, skeletal findings like delayed bone age and dwarfism improved significantly, but there were no significant changes in enlargement of sella, presence of wormian bones, epihyseal dysgenesis, vertebral changes and thickened band at the metaphyseal ends. With the treatment of hypothyroidism, there is an exuberant advancement of bone age, the catch up of bone age being approximately double of the chronological age advancement.

Re-emergence of a rare syndrome: A case of mauriac syndrome.

Mauriac syndrome is a rare syndrome associated with type 1 diabetes (T1DM) in children presenting with growth retardation, hepatomegaly, and cushingoid features. Recently, there has been re-emergence of this syndrome, especially with the use of premix insulin. A 15-year old type 1 diabetic boy, who was on premix insulin with erratic blood glucose, was referred to us for evaluation of short stature. He had significant short stature, hepatomegaly, and cushingoid features. His growth hormone (GH) stimulation was normal, and so was the overnight dexamethasone suppression test, based on which the diagnosis of Mauriac syndrome was reported. He was made to switch over to basal bolus regime, and was advised to follow-up for 6 months. He had reduction in hepatomegaly and a height gain of 3 cms.

Association of serum lipids with diabetic retinopathy in type 2 diabetes.

A total number of 140 type 2 diabetic patients with diabetic retinopathy (DR) were enrolled in the study from diabetic clinic during May 2011 till June 2012 to determine correlation between severity of DR with serum lipid and other modifiable risk factors in type 2 diabetic patients. Information including age, sex, height, body weight, body mass index (BMI), waist-hip ratio (WHR), and systolic and diastolic blood pressure was collected from each patient. Fasting plasma sugar, low density lipoprotein (LDL), triglyceride level (TG), high density lipoprotein (HDL), glycated hemoglobin (HbA1C), creatinine, and 24 h urinary albumin excretion was done for each patient. Estimated glomerular filtration rate (eGFR) was measured by modification of diet in renal disease (MDRD) equation. Patients were divided in five groups according to retinopathy status based on early treatment DR study (ETDRS) disease severity level. Statistical analysis was performed with Statistical Packages for Social Sciences (SPSS) statistical software (version 17.0 for Windows). The alpha level was set at P = 0.05 for all tests. Statistically significant positive correlation between severity of DR with systolic blood pressure P = 0.005 (r = 0.974), diastolic blood pressure P = 0.001(r = 0.994), LDL P = 0.005 (r = 0.976), TG P = 0.001 (r = 0.990), and 24 h urinary albumin P = 0.004 (r = 0.977) was documented. DR was also strongly positively correlated with smoking P = 0.017 (r = 0.941) and duration of diabetes P = 0.003 (r = 0.981). There was strong inverse correlation of DR with HDL P = 0.001 (r = -0.994) and eGFR P = 0.002 (r = -0.987). Serum lipids were significantly correlated with severity of DR.

Correlation between liver fat content with dyslipidemia and Insulin resistance.

Total 33 obese patients were studied to determine correlation in between liver fat content with dyslipidemia and insulin resistance. Liver and spleen attenuation measurements were taken with three regions of interests (ROIs) from the liver and two ROIs from the spleen. Hepatic attenuation indices were measured as follows: (1) Hepatic parenchymal attenuation (CTLP); (2) liver to spleen attenuation ratio (LSratio); and (3) difference between hepatic and splenic attenuation (LSdif). Bivariate correlation analysis showed moderate but statistically significant negative correlation between CTLP, LSratio, and LSdif with body mass index, triglyceride, fasting plasma sugar, fasting plasma insulin, homeostasis model assessment-insulin resistance (HOMA IR), 2 h oral glucose tolerance test (OGTT), and statistically significant positive correlation with high density lipoprotein. Nonalcoholic fatty liver disease (NAFLD) is closely associated with features of the metabolic syndrome. The amount of intrahepatic fat closely correlates with the number of metabolic syndrome features. The values of CTLP, LSratio, and LSdif demonstrate strong inverse correlations with degree of steatosis.