Endocrine disorders in patients with Fabry disease: insights from a reference centre prospective study

Context Fabry Disease (FD) is a rare X-linked storage disease characterised by a-galactosidase A deficiency and diffuse organ accumulation of glycosphingolipids. Enzyme replacement and chaperone therapies are only partially effective. It remains unclear if FD-related endocrine disorders contribute to the observed morbidity. Objective To investigate the function of the endocrine system in patients with FD. Design We conducted an observational prospective study from 2017 to 2020. Setting and patients We included 77 patients with genetically confirmed FD (27 men, 20/27 Classic, 7/26 Late Onset phenotype, 50 women, 41/50 and 9/50 respectively), who are systematically followed by our reference centre. Results 36/77 (46.8%) patients had VitD deficiency (25(0H)VitD <20 μg/L) despite the fact that 19/36 (52.8%) were substituted with cholecalciferol. Only 21/77 (27.3%) patients had normal VitD levels without VitD substitution. 11/77 (14.3%) had significant hypophosphatemia (p < 0.80 mmol/L). Three new cases (3.9%) of subclinical, two (2.6%) of overt and six (7.8%) of known hypothyroidism were identified. Of note, men had significantly higher renin levels than women [61.4 (26.1–219.6) vs.25.4 (10.9–48.0) mU/L, p = 0.003]. There were no major abnormalities in adrenal, growth and sex-hormone axes. Patients of Classic phenotype had significantly higher High-Density Lipoprotein Cholesterol (HDL-C) levels (p = 0.002) and in men those levels were positively correlated with globotriaosylsphingosin (Lyso-Gb3) values. 10/77 (13%) of the patients were underweight. Conclusions VitD supplementation should be considered for all patients with FD. Thyroid screening should be routinely performed. Malnutrition should be prevented or treated, particularly in Classic phenotype patients. Overall, our data suggest that FD specialists should actively seek and diagnose endocrine disorders in their patients.

Cost-Effectiveness Analysis of Ultrasound Screening for Thyroid Cancer in Asymptomatic Adults

Objectives: This study evaluated the long-term cost-effectiveness of ultrasound screening for thyroid cancer compared with non-screening in asymptomatic adults.Methods: Applying a Markov decision-tree model with effectiveness and cost data from literature, we compared the long-term cost-effectiveness of the two strategies: ultrasound screening and non-screening for thyroid cancer. A one-way sensitivity analysis and a probabilistic sensitivity analysis were performed to verify the stability of model results.Results: The cumulative cost of screening for thyroid cancer was $18,819.24, with 18.74 quality-adjusted life years (QALYs), whereas the cumulative cost of non-screening was $15,864.28, with 18.71 QALYs. The incremental cost-effectiveness ratio of $106,947.50/QALY greatly exceeded the threshold of $50,000. The result of the one-way sensitivity analysis showed that the utility values of benign nodules and utility of health after thyroid cancer surgery would affect the results.Conclusions: Ultrasound screening for thyroid cancer has no obvious advantage in terms of cost-effectiveness compared with non-screening. The optimized thyroid screening strategy for a specific population is essential.

Risk of Benign and Malignant Thyroid Disorders in Subjects Treated for Paediatric/Adolescent Neoplasia: Role of Morphological and Functional Screening

Background: Patients treated for paediatric/adolescent (P/A) neoplasia have a high incidence of both benign and malignant thyroid diseases. Given the high incidence of sequelae, literature data show a clinical benefit of morpho-functional thyroid screening in paediatric/adolescent cancer survivors and a careful lifetime follow-up. Patients and methods: The incidence of thyroid alterations was evaluated in a consecutive series of 343 patients treated with chemotherapy (CHE) and radiotherapy (RTE) or only with CHE for P/A tumours between 1976 and 2018 (mean age at time of primary paediatric malignancy 7.8 ± 4.7 years). All patients underwent thyroidal morpho-functional evaluation between 2000 and 2019. Results: 178 patients (51.9%) were treated only with CHE and 165 (48.1%) with CHE+RTE. A functional and/or structural thyroid disease was diagnosed in 147 (42.5%; 24.2% in CHE and 62.4% in CHE+RTE group; p = 0.0001). Of note, 71 (20.7%) patients with no evidence of disease at first evaluation developed a thyroid alteration during the follow-up. Primitive hypothyroidism was diagnosed in 54 patients (15.7%; 11.2% in CHE vs. 20.6% in CHE+RTE group; p = 0.01) and hyperthyroidism in 4. Sixty-three patients developed thyroid nodules (18.4%; 4.0% in CHE and 14.1% in CHE+RTE group; p < 0.001); thyroid cancer was diagnosed in 30 patients (8.7%; 4.5% in CHE and 12.4% in CHE + RTE group; p = 0.007). Conclusions: In patients treated with CHE+RTE, the prevalence of hypothyroidism and nodular pathology, both malignant and benign, were significantly greater than in patients treated with CHE. However, also in the CHE group, the frequency of thyroid disease is not negligible and the pathogenetic mechanisms remain to be clarified. Our data suggest the clinical benefit of morpho-functional thyroid screening in P/A cancer survivors.

An Ayurvedic Management of Depression in Hypothyroidism - A Case Report

Background: Hypothyroidism is one of the most common endocrinal disorders which are mainly diagnosed basing on the laboratory investigations. In hypothyroidism, most of the patients present with non-specific symptoms. Depression is one of the common non specific symptoms of hypothyroidism. Grading and management of depression along with the management of hypothyroidism is essential to prevent the risk of harm and provide potential benefit to the patient. Method: A 35 year old woman presented with a depressive disorder for the past one year. On thyroid screening she was found to have subclinical hypothyroidism. Depression was graded according to Montgomery and Asberg Depression Rating Scale (MADRS). Patient was managed with Ayurvedic drugs Kanchanara Gutika and Manasamitra vatakam on OPD basis. Result: She had a very good clinical improvement following the therapy. Thyroid screening assured the maintenance of Thyroid hormone levels and TSH in the normal range. MADR Scale showed marked improvement. Conclusion: We conclude that it is better to have a special focus on the management of depression along with thyroid screening when patients present with non specific symptoms as depression. Ayurvedic management showed good results on MADRS as well as thyroid hormone levels.

An Identification and Classification of Thyroid Diseases Using Deep Learning Methodology

The thyroid is one of the most important parts of our body. As part of the endocrine system, this tiny gland in our neck releases thyroid hormone, which is responsible for directing all your metabolic functions which means controlling everything from digestion to conversion to energy. When thyroid dysfunction, it can affect all aspects of our health. Both researchers and doctors face challenges in fighting thyroid disease. In that thyroid disease is a major cause of the emergence of medical diagnostics and prognosis, the beginning of which is a difficult confirmation in medical research. Thyroid hormones are suspected to regulate metabolism. Hyperthyroidism and hypothyroidism are one of the two most common thyroid diseases that release thyroid hormones to regulate the rate of digestion. Early detection of thyroid disease is a major factor in saving many lives. Frequently, visual tests and hand techniques are used for these types of diagnostic thyroid diseases. This manual interpretation of medical images requires the use of time and is highly affected by errors. This work is developed to successfully diagnose and detect the presence of five different thyroid diseases such as Hyperthyroidism, Hypothyroidism, Thyroid cancer, thyroid gland, Thyroiditis and general thyroid screening without the need for several consultations. This leads to predictable disease progression and allows us to take immediate steps to avoid further consequences in an effective and cost-effective way to avoid the human error rate. A web application will also be developed where a scanned image of the inclusion will provide the removal of the most time-consuming thyroid type and patient investment.

The Clinical Spectrum of PTEN Hamartoma Tumor Syndrome: Exploring the Value of Thyroid Surveillance

<b><i>Introduction:</i></b> Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) comprises a collection of clinical features characterized by constitutional variants in <i>PTEN</i>. Several guidelines recommend thyroid screening, beginning at the pediatric age at the time of PHTS diagnosis; however, the benefits of early surveillance has not been well defined. <b><i>Methods:</i></b> We conducted a retrospective investigation of patients followed up at the Children’s Hospital of Philadelphia with a diagnosis of PHTS between January 2003 and June 2019. In total, 81 patients younger than 19 years were identified. <b><i>Results:</i></b> The most common clinical feature at presentation was macrocephaly (85.1%), followed by impaired development (42.0%), skin/oral lesions (30.9%), and autism spectrum disorder (27.2%). A total of 58 of 81 patients underwent thyroid surveillance, with 30 patients (51.7%) found to have a nodule(s). Ultimately, 16 patients underwent thyroidectomy, with 7.4% (6/81) diagnosed with thyroid cancer. All thyroid cancer patients were older than 10 years at diagnosis, and all displayed low-invasive behavior. Of the patients younger than 10 years at the time of thyroid ultrasound (US) surveillance, 71.4% (15/21) had a normal US. The remaining 6 patients had thyroid nodules, including 4 undergoing thyroid surgery with benign histology. <b><i>Discussion/Conclusion:</i></b> Patients with macrocephaly, impaired cognitive development and thyroid nodules, and/or early-onset gastrointestinal polyps should undergo constitutional testing for PHTS. There does not appear to be a clinical advantage to initiating thyroid US surveillance before 10 years of age. In PHTS patients with a normal physical examination, thyroid US surveillance can be delayed until 10 years of age.

Thyroid Disorders in Pregnancy: Role of Routine Antenatal Thyroid Screening

Background & objective:Thyroid disorders are among the common endocrine problems during pregnancy with well-known adverse effects on both mother and fetus. Many of these adverse effects could be prevented or ameliorated by early detection and appropriate treatment of conditions, provided routine antenatal thyroid screening is done. Considering this view, the present study was aimed to find the prevalence of thyroid disorders and their spectrum in pregnancy in order to justify the necessity of routine antenatal thyroid screening. Methods: This cross-sectional study was conducted in the Department of Obstetrics & Gynaecology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka over a period 1 year from July 2012 to June 2013 on pregnant women to screen for the thyroid disorders in pregnancy. Based on predefined eligibility criteria, a total of 246 pregnant women up to 36 weeks of gestation were consecutively included in the study. A short history with brief physical examination was done followed by collection of blood samples. Thyroid function was assessed by measuring serum levels of thyroid stimulating hormone (TSH). Serum free thyroxin (FT4) level was estimated in 71 cases, where TSH value was deranged. Trimester specific reference range of serum TSH was used to define hypothyroid, euthyroid and hyperthyroid cases. The suspected risk factors were then compared between abnormal and euthyroid groups to find their association with thyroid disorders. Result: The results of the study showed that the overall prevalence of abnormal thyroid function status was 30.9% (hypothyroidism 29.7% and hyperthyroidism 1.2%) based on normal range of serum TSH in different trimesters of pregnancy. Pregnant women with thyroid disorders were generally older than their euthyroid counterparts (p = 0.039). Hypothyroid state was fairly common with advancing gestation (21.3%, 30.3% and 34% in the 1st, 2nd, and 3rd, trimesters respectively). Pregnant women with personal or family history of thyroid disease in the past exhibited a higher prevalence of abnormal thyroid function than those who did not have such history (p = 0.041 and p = 0.044 respectively). Past menstrual irregularity, past history of subfertility or abortion were significantly associated with thyroid disorders (p = 0.042, p = 0.004 and p < 0.001 respectively). Presence of goitre (21.1%) in current pregnancy also showed significant association with thyroid dysfunction (p = 0.001). The risk of developing abnormal thyroid function was observed to be 3.6(95% CI = 1.9 – 6.4) times higher in those who had at least one risk factor than those who did not have any risk factors (p < 0.001). However, a sizable portion (27.6%) of pregnant women without any risk factors developed abnormal thyroid function. Conclusion: The study concluded that one in every three women may have thyroid disorder during pregnancy, primarily hypothyroidism. Adopting risk factor-based screening for thyroid disorders in pregnancy, there is every chance that a substantial number of cases with thyroid dysfunction may be missed. Therefore, routine antenatal thyroid screening is recommended. Ibrahim Card Med J 2020; 10 (1&2): 74-83

Neonatal thyroid screening a tertiary care experience at VSS Medical College and Hospital, Burla

Background: Congenital hypothyroidism is one of the most common preventable etiologies of mental retardation. The worldwide incidence of CH ranges from 1 in 3000 to 1 in 4000 live newborn. Objective of the study was to know the incidence of congenital hypothyroidism in this part of the country, which is necessary to understand the burden of congenital hypothyroidism to the society.Methods: Primary serum TSH measurement in screening neonates with backup thyroxine (T4) determination in infants with high TSH levels (>20 mIU/l). TSH and FT4 were estimated by chemi luminescence immunoassay (CLIA) method using reagent monobind, INC.Results: Serum TSH of screened neonates ranged between 0.16 mIU/l and 80.32 mIU/l, Mean±SD of sTSH being 5.80±3.96 mIU/l. Out of 2212 screened newborns, 9 newborns had sTSH value >20 mIU/l, who were recalled for confirmatory test, giving a recall rate of 0.4%. Out of 9 recalled newborns, 3 had persistently elevated sTSH >20 mIU/l making incidence of congenital hypothyroidism of 1:737 in our study.Conclusions: We found a higher incidence of 1:737 neonatal hypothyroidism in this region as compared to estimated national incidence. CH being preventable cause of mental retardation and other harmful effects on a growing newborn, neonatal screening programme for congenital hypothyroidism is highly recommended.