Endocrine Abstracts

Introduction: Levothyroxin (T4) is commonly employed to correct thyroid hormone deficiency from various causes, and as total thyroidectomy is increasingly used to treat benign thyroid conditions, lifelong treatment with optimal dose of thyroxin (T4) is required which is difficult to predict. This study investigated factors that might predict the ideal T4 dose, with the aim of reducing delays in achieving normal thyroid function after surgery.</...

Introduction: Recent reports suggest that thyroid hormones are independently associated with components of metabolic syndrome. We studied the association between thyroid hormones, insulin resistance and components of metabolic syndrome in euthyroid overweight or obese individuals.Methods: A total of 45 overweight or obese women with no past history of thyroid disease or diabetes mellitus were studied. Body fat was estimated by bio-impedance method and wa...

Introduction: Obesity effects pituitary–thyroid axis resulting in elevated thyroid stimulating hormone (TSH) level. We studied the relation between body mass index (BMI) and TSH in euthyroid and subclinical hypothyroid obese children and compared serum TSH level among obese and overweight children.Methods: Fifty consecutive children (aged 2–18 years) presenting for obesity were studied. All cases with TSH >10, low T3/T4</sub...

Introduction: In the management of patients with differentiated thyroid carcinoma, serum thyroglobulin levels are often well correlated with whole-body radioiodine scanning (WBS) results. However, occasionally, a mismatched result – increased thyroglobulin with negative WBS – is observed. Radioiodine therapy has been suggested as a therapeutic choice with controversial results.Method: We studied 32 differentiated thyroid carcinoma patients with...

Case: A fit strong 26-year-old Caucasian male presented with recurrent falls. He attended the accident and emergency department with a three-month history of episodic weakness of the lower limbs. There was no previous history of medical problems and he was not on medication. On admission a full neurological examination was normal except for reduced power in the lower limbs. He had a raised creatinine kinase 472 U/l (0–170). Potassium was 3.8 mmol/l (3.5–5.3). He was ...

Rationale for change: Two years ago the Endocrine department instigated an audit of patients who had received radioiodine treatment (RAI) for hyperthyroidism. This highlighted there was a variation in timeliness of follow-up appointments and at least a third of patients were rendered symptomatic as a result of the treatment, prior to review taking place.Innovation: As a result of the initial audit a nurse-led clinic was established to monitor patients fo...

Case: In April 2008, a 68-year-old male was referred to the endocrine clinic with symptoms of hyperthyroidism and was prescribed carbimazole 20 mg daily. A week later, he developed sudden onset dizziness, together with reduced hearing in his left ear and associated tinnitus. Similar symptoms developed in his right ear shortly thereafter. Seven weeks after starting carbimazole, he attended the ENT outpatient clinic with severe vertigo, tinnitus and bilateral hearing loss. Otosc...

Background: Thyroid hormone replacement is one of the most commonly prescribed and cheapest treatments for a chronic disease. There have been recent changes in community prescribing policies in many areas of the UK that have changed patient access to necessary medications.Aim: To provide a picture of thyroid hormone usage in the UK and to survey patient opinion about current community prescribing policies for levothyroxine.Methods:...

A 62-year-old woman was referred to the endocrine clinic with new onset thyrotoxicosis. She had previously had two other conditions affecting her thyroid gland. In 1977, she underwent a right thyroid lobectomy for a non-functioning thyroid adenoma. In 2002, she presented with a rapidly enlarging left sided goitre, which proved to be thyroid B-cell lymphoma on core biopsy. She was treated with chemotherapy alone and remains under regular haematology follow up. Serial thyroid fu...

Case report: A 76-year-old lady was referred to our Endocrinology department due to general malaise and abnormal thyroid function tests: TSH 1.1 (0.3–4.2) mU/l, fT4 30.6 (12.0–23.0) pmol/l, fT3 8.3 (4.0–7.8) pmol/l. She had received 131I twice, 16 and 36 years previously, at different hospitals for presumed thyrotoxicosis. She was clinically euthyroid and had a small diffuse goitre.Repeat thyroid function t...

Hyperthyroidism per se can cause mild elevation in liver enzymes which normalizes with treatment. Thyrostatic medications (carbimazole or propylthiouracil) as first line therapy to treat hyperthyroidism can rarely cause potentially fatal hepatotoxicity.We report a patient who developed cholestatic jaundice after carbimazole therapy.Case report: A 32-year-old woman presented with weight loss, heat intolerance, palpitations an...

Radioiodine is the treatment of choice for relapsed hyperthyroidism although the optimum protocol is uncertain. We assessed the outcome of therapy with 131I in relapsed hyperthyroidism using a fixed dose regimen.We retrospectively studied 449 patients (M: F 82: 367; age range 13–89 y, median 42 y) treated between 2003 and 2007 with a fixed dose of 550 MBq 131I for relapsed hyperthyroidism. Patients were classified as either Gra...

Background: Hypothyroidism occurs in 2.5% of pregnancies. We are using a database follow up system for pregnant women with hypothyroidism in our hospital. All the women with hypothyroidism are added on a database system at their first visit to the antenatal clinic. Any adjustment to thyroxine was made on the first visit after checking TFT and repeat TFTs were done at 20 and 30-weeks gestation. Any adjustments to thyroxine were communicated to them via letter. The aim of this s...

Generalised resistance to thyroid hormone (GRTH), a subset of the syndrome of resistance to thyroid hormone (RTH), is characterised by variable reduced target tissue responsiveness to circulating thyroid hormones. Plasma thyroid hormone levels are raised and TSH levels inappropriately non-suppressed. We describe a 54-year-old female with GRTH diagnosed from the finding of raised fT4 and fT3 levels coincidental with non-suppressed TSH levels. A thyrotropin (TRH) test resulted i...

Radioiodine is used for the treatment of hyperthyroidism and has been proven to be safe, efficacious and inexpensive. Despite the widespread use, there is a lack of consensus on many aspects of the treatment including aim, radioiodine dose, timing of the second dose and the role of antithyroid medication.This was a retrospective study to investigate the outcome of radioiodine therapy in thyrotoxic patients. The aim was to determine the overall rate of su...

Interferon alpha (IFNα) and Ribavirin combination therapy effectively eradicates Hepatitis C Virus (HCV) in up to 80% of patients. Transient thyroid dysfunction (TD) (>80% hypothyroidism) usually due to a destructive thyroiditis has been recognised to occur in up to 25% of patients treated in Italy, Japan and Australia. However, data are lacking in a UK cohort and no standardised protocol for testing of thyroid function testing exists. The aim of this study was to det...

Full replacement dose of thyroxine should not be administered initially to elderly hypothyroid patients, those with a history of coronary artery disease and to patients with long-standing severe hypothyroidism. Here, we present a 27-year-old lady with profound longstanding hypothyroidism, who developed cardiac failure on a small dose of thyroxine.She presented to her General Practitioner with longstanding symptoms of lethargy, poor concentration, constip...

Introduction: The treatment of hyperthyroidism is complex. Radio-iodine administration remains the definitive option despite debate regarding optimum dosage and strategy.Method: Thyroid status in all patients receiving first dose radio-iodine over a 5 year period was reviewed at 3, 6, 12 and (most at) 24 months. Radio-iodine doses were individualised depending on thyroid gland size, co-morbidities and patient choice. The objective was euthyroidism with h...

Background: Absorption of levothyroxine is significantly reduced in the presence of oral iron if these two medications are ingested simultaneously, possible as a result of the formation of an insoluble complex with these 2 medications. Ideally all hypothyroid pregnant women on thyroid replacement therapy should be advised to avoid simultaneous ingestion of levothyroxine and iron containing medicines.Patients and methods: We conducted a retrospective obse...

Introduction: There remains considerable debate over combination T4/T3 therapy for thyroid hormone replacement. Whilst large randomised-controlled studies have failed to show benefit over T4 only, there remain patients who feel better on the combination. Animal studies suggest that up to 80% of intracellular T3 in the brain is derived from circulating T4 by local deiodination. We hypothesized that in patients on thyroxine ...

Background: Thyroid hormone is essential in foetal neurological development and thyroid hormone deficiency in pregnant women has been linked to lower intelligence quotient and underperformance in their children later in life. Thyroid hormone requirement increases during pregnancy by approximately 50% in the first trimester. We audited our practice of increasing thyroid hormone dose at booking and thereafter in pregnant women attending our combined obstetric medical clinic....

Objective: An audit comparing how the treatment of hypothyroidism has changed since the introduction of the Quality Outcome Framework (QOF) in April 2004 according to UK guidelines published by the Association of Clinical Biochemists and the British Thyroid Association (BTA) in 2005.Method: Data were collected from all patients with primary hypothyroidism in a fully computerized practice of 9830 patients under the care of 9 general practitioners. The mos...

We report the management of 16 predominately elderly patients (12 female: 2 male; mean age at presentation 73.8 years, range 48 to 85 years) presenting with massive goitres. Seventy-five percent had significant co-morbidities. Fifteen had multinodular goitres and 1 Reidel’s thyroiditis. Four goitres were confined to the neck; 6 were intra-thoracic and 6 had both neck and intra-thoracic goitres. Five had symptoms of compression; 9 were thyrotoxic and 2 hypothyroid. Mean fo...

Background: Recent evidence suggests that detection of fetal goitre (defined as fetal thyroid circumference >95th percentile) may be a useful way of detecting over and under activity of the fetal thyroid in maternal Graves’ disease. Clinical translation is made difficult by the large differences in normative data from different populations. We examined fetal thyroid circumference in our population against normative data based on at least 150 examinations. Normative da...

History and examination: A 46-year-old gentleman presented with right sided goitre which had increased in size over one month. He previously had a left thyroidectomy for non-toxic goitre.As a child he had several lipomas removed. On examination he has mucosal neuromas, an AV malformation on his left wrist, white papules on his hands and trichilemmonas on his legs. He has macroencephalopathy, 64.4 cm round. The right lobe of the thyroid was enlarged and h...

Thyroid function changes with advancing age, however there is little good quality data available that characterises the extent of thyroid disease in the elderly, or the parameters of normal thyroid function in the ‘oldest old’. Reference ranges for serum TSH and free thyroid hormones based on unselected younger adults are currently applied uniformly to older individuals.The Newcastle 85+ study has collected health and lifestyle information from...

Introduction: Thyroid eye disease (TED) is a chronic disorder with a potential to cause facial disfigurement and visual impairment. Recent surveys of clinicians have shown variability and deficits in the management of TED. The European Group on Graves’ Orbitopathy (EUGOGO) recently published guidelines on the management of TED, recommending that all patients with TED should be referred to specialist multi-disciplinary TED clinics. We aimed to study the patients’ expe...

Context: Respiratory failure as a component of severe hypothyroidism has high mortality and a number of pathological mechanisms have been proposed. These range from cerebral causes to neuromuscualr and pulmonary factors. Changes due to mucopolysacharide deposition in the lungs is another postulated mechanism, but radiological changes are hitherto not clinically demonstrated.Objective: A case of hypothyroidism with hypoxia associated with CT features sugg...

Since the observation in 1961, that phenytoin treatment caused a reduction in protein bound iodine, the effect of various anticonvulsants on the thyroid hormones and in causing sub clinical and overt hypothyroidism has been a matter of debate. There are no reports linking newer antiepileptics like lamotrignine to thyroid hormone abnormalities. We report three patients who developed overt hypothyroidism while on treatment with Primidone, Lamotrignine and Carbamazepine respectiv...

Introduction: Autoimmune thyroiditis can occasionally be associated with a transient hyperthyroid phase which is followed by a hypothyroid state. Thyrotoxicosis is thought to be caused by thyroid cell destruction with release of preformed thyroid hormones into the circulation.Case: An 18-year-old Asian male was admitted to hospital 7with a four week history of lethargy, weight loss, palpitations and excessive sweating. He had tachycardia, sweating, tremo...

The RCP clinical guideline on Radioiodine in the management of benign thyroid disease was published in 2007. An audit was undertaken in patients receiving this treatment between April 2006 and April 2007. The audit was performed to assess compliance with the guidelines and provide patients receiving radioiodine data regarding the efficacy of the treatment and its complications.Sixty-two patients received radioiodine and 59 patients entered into the audit...

Context: Autoimmune polyendocrine syndrome type 1 (APS1) is an autosomal recessive disorder caused by mutations in the autoimmune regulator gene. Hypoparathyroidism occurs in 80% of patients with APS1 and has been suggested to result from an autoimmune reaction against the calcium-sensing receptor (CaSR) on parathyroid cells. Previously, we have detected CaSR-binding antibodies in patients with APS1 using immunoprecipitation and flow cytometry assays.Obj...

Thyroid hormones (TH) are important for the development of the fetus and placenta. Monocarboxylate transporter 8 (MCT8) is a potent plasma membrane TH transporter, present in the human placenta from 6 weeks of gestation. Its expression increases significantly with advancing gestational age. We postulate that MCT8 plays an important role in human placental development.Objective: To assess the effects of altered MCT8 expression on the survival, syncytialis...

PTTG binding factor (PBF) is a poorly characterised 22 kDa protein that is implicated in the aetiology of pituitary and thyroid tumours. Our recent investigations have attempted to discern the function of PBF in vitro. In particular, we reported that PBF can inhibit the activity of the sodium iodide symporter (NIS), which is responsible for iodide uptake into thyroid cells. However, little is known about the precise role of PBF in vivo. We have now generated a mu...

Genome wide association (GWA) studies have revolutionised the search for new susceptibility loci for complex diseases such as Graves’ disease (GD), by confirming association of known genes and identifying several novel susceptibility loci. The high density lipoprotein binding protein (HDLBP) on chromosome 2q37 is one such novel locus recently identified by the WTCCC as part of a 14 500 nonsynonymous single nucleotide polymorphisms (SNP) screen performed in 900 UK C...

Autoimmune diseases (AIDs) have been shown to share a series of genetic susceptibility loci, including the HLA class II region, CTLA-4 and PTPN22, indicating the sharing of key pathways between diseases. Recently, the rs1801274 single nucleotide polymorphism (SNP) within the Fc gamma receptor 2a gene (FcGR2a) has been shown to be associated with several common AIDs including type 1 diabetes, rheumatoid arthritis and coeliac disease. FcGR2a is an immune mod...

There is a paucity of information regarding the genetic and somatic mutation events that lead to the production of pathogenic thyroid stimulating antibodies (TSAbs) in Graves’ disease. We have previously isolated two murine monoclonal antibodies (KSAb1 and KSAb2) with potent TSAb activity that demonstrate subtle differences in their interaction with the thyrotropin receptor (TSHR). Analyses of the variable region genes of the heavy and light chains of these TSAbs were per...

Identifying the pathogenic pathways involved in complex diseases such as Graves’ disease (GD) has proved challenging. Although several genetic risk factors, including the HLA class II region, CTLA4, PTPN22 and CD25, encode molecules playing key roles in antigen presentation and controlling T cell recognition/signalling, the identification of novel susceptibility loci has the potential to provide further insights into disease pathogenesis. Recently gen...

We would like to present this fascinating case in the forthcoming BES meeting as an oral or poster presentation.A 65-year-old retired teacher was found on routine check up by her GP to be severely hypothyroid biochemically (TSH 70.89 mU/l (0.4–5.0) and fT4 7.5 pmol/l (12.0–23.0)).There were no symptoms suggestive of hypothyroidism whatsoever. She was full of energy, not gaining weight, not cold intolerant, not constipated...

Background: In the first trimester, the foetus is dependent on circulating maternal thyroid hormones for normal brain development. Maintenance of euthyroidism is important throughout pregnancy and maternal hypothyroidism is associated with adverse foetal outcomes.Aim: To audit the management of pregnancies complicated by hypothyroidism in a joint antenatal endocrine clinic in comparison with the UK guidelines from the British Thyroid Association (2006).<...

Introduction: Dilated cardiomyopathy is an uncommon, but well recognized, manifestation of thyrotoxicosis. However, hyperthyroidism presenting with dilated cardiomyopathy is very rare. We describe an unusual case of dilated cardiomyopathy as the initial manifestation of Graves’ hyperthyroidism.Case: A 61-year-old man of Malaysian origin, with no significant past medical history, was admitted with two month history of worsening shortness of breath, o...

Background: Thyroid cancer commonly presents as a new palpable thyroid nodule or increase in size of a pre-existing nodule. A multidisciplinary thyroid lump clinic was established in September 2008 enabling patients to have one-stop clinical, biochemical, radiological and cytological assessment for evaluation of thyroid nodules. This audit predates this period, aiming to provide background information for future audit.Aim: To evaluate the requests for th...

Survival following treatment for childhood malignancy has improved considerably over the last 40 years. Complications of treatment are frequent and although the long-term follow-up of patients is recommended, only 35% of patients are seen regularly. Endocrine complications of cancer therapy, including thyroid dysfunction, are well recognised. The aim of this study is to determine the frequency of hypothyroidism amongst the patients within the Bristish Childhood Cancer Survivor...

This is an unusual case of sleep apnoea treated with C-PAP as a result of multinodular goitre (MNG) which was overlooked.This is a case of a 69-year-old gentleman who was referred to the endocrine clinic for assessment of his diabetes. Sleep apnoea was diagnosed around four years ago and he has been using C-PAP every night. Enlargement of multinodular goitre coincided with the diagnosis of sleep apnoea. He has previously been seen by another endocrinolog...

Aim: Thyroidectomy is a common surgical procedure done in adults. However, thyroid surgery in children is infrequently undertaken. But due to genetic screening of families with multiple endocrine neoplasia (MEN) syndromes, more paediatric thyroidectomies are being performed. It is suggested that general and endocrine specific complications in children after thyroid surgery are higher than in adults. In this study we explored the indications for thyroidectomy and the post opera...

Background: Hashimoto’s thyroiditis is an autoimmune thyroid disorder. Being a chronic inflammatory process, thyroidits has been recognised as a risk factor for thyroid lymphoma. We present a case of a female with Hashimoto’s thyroiditis, who suffered an out of hospital cardiac arrest and later on died in hospital.Case report: A 30-year-old lady with a background history of Down’s syndrome was referred to endocrinology clinic in 2003 with ...

Interferon therapy for chronic hepatitis C infection has been associated with thyroid abnormalities. We sought to characterise the incidence of this in a cohort of treated hepatitis C patients receiving weekly pegylated interferon therapy in a tertiary Hepatology unit. Patients were scheduled to receive 24 or 48 weeks treatment with monthly thyroid function tests (TFTs). Data was collected from electronic treatment records of 154 consecutive patients and analysed by a single i...

Aim: Audit the management of patients with thyrotoxicosis in the thyroid clinic at a District General Hospital, focusing on treatment methods and long term follow up.Method: Prospective data collected from randomly selected 50 case notes and laboratory results over 4 months. Titration dose with Carbimazole or Propylthiouracil with close monitoring of thyroid function test is the treatment method followed.Results: Eighty-six percent...

We present two cases with biochemistry results suggesting thyrotoxicosis, caused by laboratory artefacts.Case 1: A 68-year-old male with type 2 diabetes was referred with weight loss. Results showed fT4 of 30.5 and TSH of 1.07, confirmed on repeat. He had no symptoms of hyperthyroidism.Blood was sent for treatment with antibody-blocking reagents:...

PTPN22, encodes lymphoid tyrosine phosphatise (LYP), an important inhibitor of T lymphocyte activation and has been associated with numerous autoimmune diseases including type 1 diabetes, rheumatoid arthritis, and Graves’ disease (GD). Consistent association has been reported between disease and a non-synonymous SNP +1858 C>T (rs2476601) encoding an Arginine to Tryptophan substitution at amino acid 620 of LYP. Our group was the first to show strong evidence of ...

Background: Intratumoural hypoxia is associated with an aggressive and metastatic phenotype and poor prognosis. The transcription factor Hypoxia-inducible Factor-1α (HIF-1α) is a key regulator of hypoxia, inducing the expression of genes which promote tumour cell survival, such as carbonic-anhydrase IX (CA-IX) playing a role in cell adhesion, pH regulation and dedifferentiation of the tumours. Here we investigated whether there is cross talk between the HIF-1 and Wnt...

Background: In clinical practice, occasional hypothyroid patients require more than the expected dose of levothyroxine. This could be due to compliance issues, excess body weight, drug interference or malabsorption. The Grampian Automated Follow-Up Register (GAFUR) currently monitors around 17 500 hypothyroid patients on levothyroxine; 36 (0.6%) patients take more than 250 μg of levothyroxine daily.Methods: A questionnaire was sent to these patients...

Introduction: Fine needle aspiration (FNA) is used, in conjunction with clinical assessment and imaging, to assess thyroid nodules for suspected malignancy. Cytological assessment of FNA samples involves both a text report and classification into a diagnostic category Thy1–Thy 5. The cytological category Thy 2 describes a FNA sample assessed to be non-neoplastic. Current BTA guidelines recommend two FNA samples, 3–6 months apart, are obtained to exclude neoplasia.</p...

Background: Patients with uncomplicated hyperthyroidism referred by their GP to our Department had a waiting time of 3–4 months before been seen by a Consultant. As a result of this, funding was provided for setting-up a Thyroid Nurse-Led Clinic (TNLC) aiming to resolve the problem. The clinic started running in May 2005.Aim: To assess the benefits of the TNLC for the NHS.Patients and methods: The data of visits of patients se...

Background: A Thyroid Nurse-Led Clinic (TNLC) was set up within the Department of Endocrinology in Oxford aiming primarily to reduce waiting times of patients with uncomplicated thyrotoxicosis from 3 to 4 months to 2 to 4 weeks. It proved to be a cost effective measure.Aims: To explore the patients’ perspective on the provision of care and on the service delivery of the TNLC.Patients and methods: A structured questionnaire wit...

Sunitinib and sorafenib are orally active tyrosine kinase inhibitors which have recently been developed as therapy for renal cell cancer and gastro-intestinal stromal tumours. Changes in thyroid function are frequently found during sunitinib therapy, typically occurring 7–24 months into therapy; the mechanism is not clear, though inhibition of iodine uptake, thyroid follicular cell apoptosis and thyroiditis have all been proposed. In contrast, thyroid dysfunction is repor...

Radio-iodine is a safe and effective treatment of thyrotoxicosis, but carries a risk of the late development of hypothyroidism several years after therapy. Patients treated with radio-iodine require long-term follow-up to ensure that late hypothyroidism is detected and treated. Current changes in health care commissioning propose an increasing reliance on primary care for the long term follow-up of patients with thyroid disease. We report a study of the 8 year follow-up of 100...

Thyroid nodules are common in the general population. In 2006, we audited and discovered that primary care direct access to thyroid ultrasound (TUS) has limited value in detecting sinister thyroid pathology. To improve quality of thyroid nodule management, in May 2007, we introduced four changes (1) appointed a thyroid MDT coordinator, (2) produced a thyroid nodule proforma to guide primary care referrals, (3) established the rapid access one-stop thyroid ultrasound FNA clinic...

The Royal College of Physicians guidelines (2007) on follow-up post radioiodine therapy for hyperthyroidism recommend thyroid function monitoring around weeks 6, 12, 26, 39, 52 and yearly thereafter in stable patients. We retrospectively analyzed data from 91 patients given radioiodine in 2005 who were followed-up locally comparing our practice with these standards. Fifteen percent of patients were lost to follow-up before year one with 40% of these not having their thyroid fu...