Endocrine Abstracts

Within the basolateral membrane of thyroid follicular epithelial cells, two transporter proteins are important for thyroid hormone (TH) biosynthesis. Initially, sodium iodide symporter (NIS) delivers iodide from the bloodstream into the thyroid and, following biosynthesis, monocarboxylate transporter 8 (MCT8) mediates secretion of TH from the thyroid gland. NIS-mediated radioiodine uptake is also critical in the treatment of thyroid tumours and metastases. We have previously d...

Obesity is a global health concern and the proportion of overweight and obese people in the UK is rapidly increasing. Patients undergoing treatment for hyperthyroidism frequently express concerns regarding excessive weight gain, especially when offered treatment with I-131. We investigated 1047 patients with overt hyperthyroidism to determine the extent of weight changes and to identify risk factors for weight gain following treatment. Overall, 727 (69.4%) patients gained &#88...

Objective: To investigate the management of thyroid replacement during pregnancy in women who were prescribed thyroxine prior to pregnancy.Design: Record-linkage technology was used retrospectively to identify pregnant women who were prescribed thyroxine in the general population of Tayside, Scotland.Patients: All pregnant women who were 18 years and above and who delivered between 1st January 1993 and 31st March 2011 in Tayside we...

Introduction: Subclinical hypothyroidism (SCH) has been associated with increased risk of atherosclerosis and myocardial infarction in a number of cross-sectional and longitudinal studies. As the majority of cardiovascular (CV) events are thromboembolic, we evaluated blood thrombogenicity in patients a few days post acute myocardial infarction with relation to their thyroid status.Aim: To assess the relationship between thyroid function/status and thromb...

PBF is a proto-oncogene implicated in the aetiology of thyroid cancer. Recently, we have shown that PBF binds NIS, MCT8 and p53, but the full spectrum of its interactions and physiological role within the thyroid remain unknown. Previously, we reported a shortlist of potential binding partners elucidated from K1 and TPC1 papillary thyroid carcinoma cells using tandem mass spectrometry (MS/MS, n=4). Here we present validation and characterisation of 2 of these proteins; ...

Background: Anaplastic thyroid-carcinomas (ATC) and a subset of papillary (PTC) and follicular (FTC) thyroid carcinomas behave aggressively showing metastatic spread and radio-resistance. Both the PI3K and HIF pathways are associated with aggressiveness and metastasis in thyroid carcinoma.Aims: To assess if the PI3K/HIF pathways contribute to radio-resistance and assess the effect of PI3K/HIF inhibition on radio-sensitivity and metastatic behaviour of th...

The human pituitary tumor transforming gene is overexpressed in thyroid cancers; inducing genetic instability through its role as a securin and propagating growth through induction of growth factors. We have demonstrated reduced cellular proliferation following hPTTG overexpression in neuronal cells. We hypothesised targeted hPTTG overexpression in mouse thyroids will result in hyperplastic/neoplastic growth and that stimulation of thyroid cell growth through standard methods ...

Introduction: Thyroid eye disease (TED) is a visually disabling and cosmetically disfiguring condition. There is a paucity of research on the psychosocial impact of TED. One of the aims of this research is to improve understanding of the extent and type of psychosocial distress experienced by TED patients.Method: 77 patients with TED were recruited (53 female, 24 male; aged between 25 and 73 years, average age=47.6±11.6 yrs; 58% Caucasian). Particip...

Graves’ orbitopathy affects approximately 0.25 million people in the UK and is associated with a significant psychological and socioeconomic burden. Surveys have illustrated that Graves’ orbitopathy is often treated inadequately. The Amsterdam Declaration is a recent incentive supported by many national and international professional and patient-led organizations including the SfE, aiming to improve the outcomes of patients with Graves’ orbitopathy. This report ...

Lithium increases retention of Iodine-131 in the thyroid gland and inhibits thyroid hormone release following radioactive iodine (RAI) administration. However, outcomes of studies of the effects of lithium on the efficacy of RAI are conflicting. The aim of this study was to assess whether adjuvant lithium increases the efficacy of RAI treatment in hyperthyroidism. A retrospective cohort study was performed of 204 hyperthyroid patients (163 Graves’ disease, 26 toxic multin...

Background: Graves’ disease is widely treated with anti-thyroid medication. After an initial course of treatment, remission is achieved in around 50% of patients. Definitive treatment is generally offered in relapsed cases, based on the assumption that remission rates following a second course of anti-thyroid medication are significantly lower.Method: A database of patients with Graves’ disease has been kept from 2004. 150 patients were suitabl...

Background: The quoted risk of morbidity after thyroidectomy is based on published data from large series but patients’ perception remains insufficiently explored.Methods: A standardized questionnaire was mailed to 312 patients who underwent thyroid surgery in a large university hospital between Jan2008–Dec2010.Results: Replies were received from 202(64%) patients (56M:166F, age 55±16 yrs) at median 23 months after l...

Measurement of anti-thyroglobulin (TgAb) predicts interference in thyroblobulin (Tg) assays and is a tumour marker for differentiated thyroid cancer (dtc). However, there is poor concordance between methods. This is attributed to the nature of TgAb, the method and cut-off used. We have assessed concordance between three TgAb assays and investigated the cause of discordant results. TgAb was measured in sera from 606 different patients being treated for dtc using the Abbott Arch...

Heterophilic antibody interference in serum TSH immunoassays can result in misdiagnosis of patients with suspected thyroid disease. Rheumatoid factor (RhF) is an immunoglobulin with reactivity to the Fc portion of human IgG. Some RhF species also cross-react with animal immunoglobulins so have the potential to act as heterophile antibodies. As part of the Cambridge Supra-Regional Assay service for thyroid function testing five serum samples with strongly positive RhF and posit...

Background: Radioiodine is a safe and effective treatment for Graves’ disease. Iatrogenic hypothyroidism is very common after treatment, but its onset is unpredictable. Even a short episode of hypothyroidism can result in significant morbidity and ideally should be avoided. In our centre a standard dose of radioiodine (400 MBq) is used, but for historical reasons two different protocols are used after radioiodine: Regimen A: regular clinical and biochemical monitoring and...

Background: The Royal College advises 500–800 MBq of Radioiodine(RAI) for toxic multinodular goitres (MNG), and 400–800 MBq RAI for euthyroid MNG. In our institution, a standard low dose of 370 MBq has traditionally been given to all patients with benign thyroid disease. This audit examined whether outcomes are optimal with low dose therapy, and whether a variable dose protocol should be adopted.Patients and Methods: We analysed 49 patients at ...

Discordant thyroid function is common; differential diagnosis includes assay interference, familial dysalbuminaemic hyperthyroxinaemia, thyroid hormone resistance (RTH) and TSHoma. We present four TSHomas, demonstrating the diversity of clinical course. All had assay interference and RTH excluded. Case 1: A 64-year-old lady with thyrotoxic symptoms and no family history. TSH 6.36 mU/l, with fT4 32.6 pmol/l and raised SHBG. Pituitary MRI showed a 7 mM lesion. She was unresponsi...

Background: Graves’ hyperthyroidism is treated with anti-thyroid drugs (ATD) for 12–18 months, after which ~50% of patients remain euthyroid. Risk factors predicting relapse are: male gender, younger age, orbitopathy, large goitres, severe hyperthyroidism at diagnosis and smoking. Recent reports suggest measurement of TBII at ATD cessation is useful in predicting risk of relapse. Aim: To prospectively investigate whether TBII levels at cessation of ATD therapy are us...

Introduction and Objectives: Guidelines are available for the investigation of thyroid nodules. These include a general agreement that patients with abnormal thyroid function tests (TFTs) do not need routine ultrasound (US) assessment. Thyroid US is a common imaging request made by General Practitioners (GPs). This audit was devised to determine the range of clinical indications for GP thyroid US and the frequency with which TFTs are assessed by the GP prior to requesting the ...

Introduction: In our institution the post high-dose RAI whole body scan (WBS) report includes a measurement of quantitative percentage uptake of the dose of RAI administered although this may not be standard practice elsewhere. We aimed to ascertain whether this was associated with the extent of unresected thyroid tissue or residual thyroid cancer following total thyroidectomy and neck dissection represented by the post-surgery TSH-stimulated thyroglobulin concentrations. Meth...

Background: Early diagnosis of thyroid cancer has a significant impact on outcome. However, the identification of incidental microcarcinomas potentially leads to raised anxiety and overtreatment in some cases. Ultrasound (US) guided FNA is therefore the initial investigation of choice, and NICE recommends that patients presenting clinically with a thyroid lump or swelling should be seen by a specialist within two weeks of the referral. We launched a multidisciplinary thyroid l...

We present a case of a 52 year old man with a past medical history of primary hypothyroidism on treatment, presenting with elevated TSH levels, suggesting inadequate thyroxine replacement. The patient was managed with 200 mcg of thyroxine for 14 years with no compliance issues. TSH levels failed to normalise despite increasing the dose of thyroxine. In addition to elevated TSH levels the patient noted progressive leg swelling and associated shortness of breath over the precedi...

Little has been published on the long-term management of thyrotoxicosis with antithyroid drugs (ATDs). We analysed 376 thyrotoxic subjects on the Morriston database since 2002. 170 had Graves’ disease, 181 toxic multinodular goitre (TMNG); in 25 the diagnosis was not recorded. When euthyroid subjects were requested to have annual thyroid function testing 42 (11%) had died. 111(30%) did not have TFT’s done in last two years. 135 graves’s cases were given ATDs whi...

Background: Autoimmune Graves’ disease is the most common cause of hyperthyroidism. Medical management of Graves’ thyrotoxicosis with thionamides is complicated by a reported relapse rate of about 60%.Aims: The aims of this study were to determine the relapse rate of patients treated with drugs as first line treatment for Graves’ disease and to assess the impact of patient demographics, serum free T4(fT4) and clinical characteristics on re...

Background: Thyroid fine needle aspiration cytology (FNAC) is an essential component of investigating discrete thyroid nodules. Grade THY3 Cytology implies a follicular lesion and usually requires diagnostic Hemithyroidectomy. Published data from UK suggests an incidence of malignancy in the range of 25 to 28% following Thy3 cytology. Nodular size of > 40 mm is shown to be significantly associated with increased incidence of thyroid malignancy. Aim: To assess the biochemic...

Introduction: Hypothyroidism is usually easily treated with levothyroxine tablets. Patients who show poor response to oral therapy are usually found to have inadequate absorption of levothyroxine, or non-compliance. We report a case where intramuscular thyroxine was used successfully in treating a case of resistant hypothyroidism due to possible malabsorption. Case report: A 47 year old lady with primary hypothyroidism, diagnosed aged 34 years, was referred to the endocrine cl...

Background: Male sex, cigarette smoking, young age, severe thyrotoxicosis, large goitre and marked or persistent elevation of TRABs are consistently reported as predictors of relapse following withdrawal of thionamides in Graves’ disease. Early recurrence rates are commonly quoted at 50% but the definition of early recurrence varies widely across the literature. AIM We sought to determine the best clinical predictors of recurrent thyrotoxicosis and whether these would per...

Macroprolactin is formed by prolactin-immunoglobulin complexes and may cause elevation of prolactin (Prl) concentrations, potentially leading to unnecessary investigations and/or treatment. We have endeavoured to assess the prevalence of macroprolactinaemia in euthyroid women with non-toxic goitre and to assess whether autoimmune thyroid disease may result in an increased prevalence of macroprolactinaemia.Material & Methods: We measured serum Prl in ...

Introduction: In this presentation, data on 67 hyperthyroid patients , aged 5 to 18 years, (53 female) who presented to an endocrine referral centre in Calcutta, India, between 1996 and 2010 are analysed.Material & Methods: All patients had a full clinical examination. Free T3, Free T4 and TSH were measured by a chemiluminescence assay and thyroiditis was excluded. Only 21 patients (32 %) were 12 years or younger. Estimated goitre size was 20 g or mo...

Background: Papillary thyroid cancer (PTC) metastasizes to central compartment lymph nodes (CCLN) in majority of patients. Such metastases are associated with high risk of locoregional recurrence and distant metastasis. Only one study has investigated the relation between the number of metastatic CCLN and prognosis (Soon Lee et al. 2010 WJS). This study evaluated the clinical implication of the number of metastatic CCLN in PTC.Methods: Between Jan...

Acute deterioration in Graves Opthalmopathy (GO) has infrequently been described following total thyroidectomy. A 56 year old female smoker presented in January 2010. Thyroid function tests: TSH<0.01, free T4 (fT4) 47. Thyroid receptor antibody (TRAb) was raised at 31 (<1.5). She was commenced on carbimazole treatment. She had no GO at time of diagnosis. She discontinued carbimazole due to rash. She represented in December 2010 with symptoms of thyrotoxicosis. TSH<...

Introduction: Central hypothyroidism is frequently seen after pituitary surgery, radiation therapy or head injury. We present a case of silent thyroiditis in a patient with secondary hypothyroidism. Case Description A 24 year old woman complained of tiredness during her periodic review in the endocrine clinic. Her endocrine history included surgery for craniopharyngioma at the age of 3 years and subsequent hypopituitarism with growth hormone, ACTH deficiency, diabetes insipidu...

Methods: We retrospectively reviewed the medical notes of 39 patients who received radioiodine treatment (RAI) for thyrotoxicosis from 2004 until February 2010. Only 5.1% of patients had history of partial thyroidectomy; patients with previous history of RAI for thyrotoxicosis were excluded. All patients received written information leaflet for RAI.Results: Thirty (76.9%) patients were females and the median age of diagnosis was 59.5 years. 97.4% were Ca...

Background: Antithyroid drugs include thioimidazoles (carbimazole, methimazole) and propylthiouracil. Carbimazole is most commonly used in the UK. A fixed drug eruption is the drug-induced cutaneous reaction which occurs at the same site after each exposure to that agent. It is uncommon with anti-thyroid medications. Here we report this rare presentation. A 40-year-old Chinese lady who was diagnosed with Graves’ disease was initially treated with carbimazole, and then wit...

Introduction: Maternal hypothyroidism is associated with an increased risk of complications both to the pregnant mother and the developing fetus. The 2007 American Endocrine Society Guidelines recommend a rapid titration of thyroxine dose to attain a target TSH concentration of ≤2.5 µU/mL in the 1st trimester (≤3 µU/mL in the 2nd and 3rd trimesters). Objectives Our aims were to assess the adequacy of thyroxine replacement in pregnant women with hypothyroi...

Inappropriately raised TSH levels in patients on thyroxine replacement therapy are frequently encountered in clinical practice. Following discussing patient compliance with medication, causes of thyroxine malabsorption including drug interactions, coeliac disease or autoimmune gastritis should be considered. We describe the investigation of a patient with persistently elevated TSH levels in spite of apparently taking adequate thyroxine replacement.Case H...

A 77 year old man with a background of Crohns disease requiring ileostomy, pernicious anaemia and hypertension, presented with a 4month history of dysphagia to solids, hoarseness of voice, anorexia and marked weight loss of 30 kg. He was initially referred to gastroenterology, who performed an endoscopy which was normal. Subsequently he was referred to the ENT and speech and language therapy departments. A video fluoroscopy confirmed severe oropharyngeal dysphagia with effortf...

Introduction: Hypothyroidism including its subclinical form affects about 3% of pregnant women. It has adverse effects on pregnancy and the fetus with evidence of impaired intellectual development. The fetal thyroid gland reaches maturity by 12 weeks of gestation. Hence in the first trimester of pregnancy the fetus is dependant on the mother and optimising serum levels of thyroxine is important.Methods: we conducted a retrospective audit of the managemen...

A 27 year old lady with a background of Langerhans cell histiocytosis (LCH) presented to endocrinology clinic for investigation of thyrotoxicosis. At the age of three years old, she presented with a rash on her forehead, which on biopsy revealed Langerhans cell histiocytosis. She was also noted to have symptoms consistent with diabetes insipidus, for which she remains on desmopressin therapy. At the age of six she received pituitary radiotherapy and 6 years ago developed secon...

An 18 year old male presented with dyspnoea, haemoptysis, weight loss and a large right testicular swelling. On examination he appeared cachectic, diaphoretic and tachycardic. A large firm non-fluctuant right-sided scrotal swelling was present. There were no signs of goitre or dysthyroid eye disease. Thyroid function tests revealed biochemical hyperthyroidism: [fT4 38.6 pmol/L (NR: 9.4–18.6), TSH <0.01 mu/L (NR: 0.3–4.4)]. CT chest demonstrated multiple large pul...

A 42-year-old gentleman of Ghanaian origin presented with a one month history of worsening severe proximal myopathy. On presentation his symptoms had progressed to the extent that he was unable to mobilise from his bed. Prior to this illness he had been fit and well. Examination revealed severe proximal myopathy and a uniformly enlarged, smooth thyroid gland. There was no clinical evidence of hyperthyroidism. Blood tests on admission showed a serum potassium level of 2.1 mmol/...

A 54 year old woman was admitted by her GP to our Medical Admissions Unit earlier this year with a suspected diagnosis of malignancy due to her history of weight loss, lethargy and breathlessness. She was found to be hypercalcaemic with calcium of 3.35 mmol/l. Unfortunately, our acute physicians treated her with pamidronate before her hypercalcaemia was fully investigated which resulted in transient but symptomatic hypocalcaemia (with a nadir calcium of 1.72 mmol/l). A resti...

Introduction: FNA cytology are done for solitary nodule or a dominant nodule in MNG.FNA classified in 5 groups (THY1 to THY5). FNA labelled as THY1 and THY2 should have repeat FNA. We have studied the FNA cytology over the period of 5 years. They are done in clinical settings by physician, surgeon or radiologist. Aim: To assess the trust practice of FNA cytology in Thyroid swelling and compare them with standards.Methods: Data were collected from patholo...

Introduction: Radioiodine is used for the treatment of Thyrotoxicosis when medical treatment (anti-thyroid drugs) has failed or cannot be tolerated and surgical treatment is not an option. We aimed to assess our compliance with the Royal College of Physicians (RCP) guidelines for Radioiodine treatment, and assess patient satisfaction with our Radioiodine service.Methods: Notes for patients who received Radioiodine treatment between January 2010 and April...

Introduction: Symptoms of hypothyroidism are very variable and are frequently present in the healthy population. The diagnosis can easily be missed if considered only in patients with classical symptoms. Aim: To describe the range of presentations in patients diagnosed with hypothyroidism in primary care.Method: Patients were recruited via the British Thyroid Foundation and from a local GP surgery. Respondents were asked to complete a questionnaire for t...

A 42 year old female presented with classical symptoms of hypothyroidism. Thyroid function tests confirmed hypothyroidism: TSH >100 mu/L and free T4 7 pmol/L. Thyroid peroxidase antibodies were significantly elevated at >3340 iu/ml. She was started on thyroxine 150 mcg but 3 months later the TSH remained elevated at 45 mu/L. Further review indicated no significant symptomatic improvement and TSH remained high at 61 mu/L. Her thyroxine dose was increased to 200 mcg but ...

Methods: We retrospectively reviewed the medical notes of 39 patients who received radioiodine treatment (RAI) for thyrotoxicosis from 2004 until February 2010.Results: Thirty (76.9%) patients were females and the median age of diagnosis was 59.5 years. 17.9% had positive family history of thyrotoxicosis; current smokers (31%), ex-smokers (18%); Graves’ disease (56.4%), Multinodular goitre (41%), and unspecified diagnosis (2.6%). 18% of patients had...

A 60year old gentleman was referred to endocrine team with new onset hyperthyroidism. He had developed tubulointerstitial nephritis secondary to carbamazepine resulting in ESRF 3 years previously. Four months prior to presentation he received a live-unrelated renal transplant including a single dose of Alemtuzamab post-operatively for induction of immunosuppression. Thereafter his immunosuppression was maintained with tacrolimus. Other medical history included bipolar disorder...

Heterophilic antibodies are human immunoglobulins with antigenic determinants directed against non-human species. These antibodies can interfere with the measurement of analytes in routine clinical laboratories, in particular in 2-site immunoassays. Skybio heterophilic blocking tubes-50 (HBT-50) are one way of overcoming this interference but, it has been reported (Sturgeon and Viljoen, Annals Clin Biochem, 2011, 48, 418), some samples may require two treatments to completely ...

An 85 year old lady was admitted with painless jaundice and cholestatic liver functions (LFTs). Investigations organised by gastroenterologists were fine including hepatitis viral screen, copper and ceruloplasmin levels, alpha -one antitrypsin, alpha -fetoprotein, immunoglobulins, auto-immune screen and ultrasound scan of the liver. In view of palpitations and weight loss, thyroid functions (TFTs) were done and showed biochemical hyperthyroidism: FT4 of 36.8 pmol/L (12–22...

Introduction: Palpable thyroid nodules have a prevalence of 4–7%, which increases with imaging. About 5% are malignant. Efficient management is essential. USG and FNAC are valuable in assessing and preventing unnecessary thyroidectomies. Objective To compare our practice with local and Royal College of Pathologists guidelines. Methods All thyroid nodule patients seen in clinic between April to September 2010 were included. Data collected included age, gender, TFT, thyroid...

Background: It is well documented that some patients with hypothyroidism continue to be symptomatic despite normalisation of TSH levels with T4 mono-therapy. The Royal College of Physicians 2008 statement recommends that T4 alone should be used for the treatment of hypothyroidism with no recommendation for additional T3 therapy. However, the Internet has many reports of symptomatic benefit on combination therapy and patients may present to the outpatient clinic requesting T3 t...