Thyrotoxicosis in an Indigenous New Zealand Population - a Prospective Observational Study.

BACKGROUND: Reported international incidence rates of thyrotoxicosis vary markedly, ranging from 6 to 93 cases per 100 000 per annum. Along with population demographics, exposures, and study design factors, ethnicity is increasingly being recognized as a potential factor influencing incidence. This study aimed to document the epidemiology and clinical presentation of thyrotoxicosis for Maori, the indigenous population in New Zealand. METHODS: A prospective study of adult patients presenting with a first diagnosis of thyrotoxicosis between January 2013 and October 2014 to a single New Zealand center. Demographic data were collected, and detailed clinical assessment performed. RESULTS: With 375 patients, an incidence rate of thyrotoxicosis of 73.0 per 100 000 per annum was identified. Of these, 353 (94.1%) participated in the study. The median age of the cohort was 47 years, 81% were female, and 58% had Graves disease. The overall incidence of thyrotoxicosis for Maori, the indigenous people of New Zealand, was higher than non-Maori (123.9 vs 57.3 per 100 000 per annum). Rates of both Graves disease and toxic multinodular goiter were higher in Maori as compared to non-Maori (incidence rate ratios of 1.9 [1.4, 2.6] and 5.3 [3.4, 8.3], respectively), with this increase being maintained after controlling for age, deprivation, and smoking. CONCLUSIONS: Maori, the indigenous people of New Zealand, have an increased incidence of thyrotoxicosis compared to non-Maori and, in particular, toxic multinodular goiter. A greater understanding of the epidemiology of thyrotoxicosis in other indigenous and marginalized ethnic groups may help to optimize therapeutic pathways, equitable care and outcomes.

Inequitable Long-Term Outcomes for an Indigenous Population After Definitive Treatment of Patients With Graves Disease.

BACKGROUND: Maori, the indigenous people of Aotearoa/New Zealand, have an increased incidence of Graves disease and often require more than one radioiodine (RAI) dose, raising the question as to whether surgery may be preferable in this population. However, there is a lack of outcome data after definitive therapy in an indigenous population. AIM: To assess ethnic differences in thyroid status after definitive therapy for Graves disease. METHODS: Single-center retrospective review of patients treated by RAI or thyroidectomy from 1 December 2001 to 31 March 2013. TSH levels at 1, 2, 5, and 10 years after treatment were recorded. RESULTS: A total of 798 patients were included: 589 received RAI, and 209 underwent surgery. Overall, 48% of patients were euthyroid at 1 year after definitive treatment, and 63.5% were euthyroid by 10 years. Maori were less likely to be euthyroid when compared with Europeans at all time points (e.g., 29.7% vs 57.3% at 1 year and 52.2% vs 70.9% at 10 years, P < 0.0005). Maori were more likely to receive more than one dose of RAI compared with Europeans (30.2% vs 14.2%, P < 0.0005). Persistent thyrotoxicosis at 1 year after RAI was seen in 25.8% of Maori compared with 8.3% of Europeans (P < 0.0005). CONCLUSIONS: Maori have lower rates of optimal thyroid levels than their European counterparts at all time points studied. Early disparity was associated with a higher RAI failure rate. Late differences were due to higher rates of untreated hypothyroidism. Overall, euthyroid rates were low, indicating the need for improvement in care, particularly for indigenous peoples.

Regulation of murine skeletal muscle growth by STAT5B is age- and sex-specific.

BACKGROUND: Sexually dimorphic growth has been attributed to the growth hormone (GH)/insulin-like growth factor 1 (IGF1) axis, particularly GH-induced activation of the intracellular signal transducer and activator of transcription 5B (STAT5B), because deletion of STAT5B reduces body mass and the mass of skeletal muscles in male mice to that in female mice. However, it remains unclear why these effects are sex- and species-specific, because the loss of STAT5B retards growth in girls, but not in male mice. Our objectives were to determine whether sexually dimorphic growth of skeletal muscle persisted in STAT5B-/- mice and investigate the mechanisms by which STAT5B regulates sexually dimorphic growth. METHODS: Blood and skeletal muscle were harvested from male and female STAT5B-/- mice and their wild-type littermates from the onset of puberty to adulthood. RESULTS: Growth of the skeleton and skeletal muscles was retarded in both sexes of STAT5B-/- mice, but more so in males. Although reduced, sexually dimorphic growth of skeletal muscle persisted in STAT5B-/- mice with an oxidative shift in the composition of myofibres in both sexes. Concentrations of IGF1 in blood and skeletal muscle were reduced in male STAT5B-/- mice at all ages, but only in female STAT5B-/- mice at the onset of puberty. Expression of androgen receptor (AR) and oestrogen receptor alpha (ERα) mRNA and protein was reduced in skeletal muscles of male and female STAT5B-/- mice, respectively. Loss of STAT5B abolished the sexually dimorphic expression of myostatin protein and Igf1, Ar, Erα, suppressor of cytokine signalling 2 (Socs2), and cytokine-inducible SH2-containing protein (Cis) mRNA in skeletal muscle. CONCLUSIONS: STAT5B appears to mediate GH signalling in skeletal muscles of male mice at all ages, but only until puberty in female mice. STAT5B also appears to mediate the actions of androgens and oestrogens in both male and female mice, but sexually dimorphic growth persists in STAT5B-/- mice.

Increased Admissions Due to Cardiac Complications of Thyrotoxicosis in Maori.

BACKGROUND: As thyrotoxicosis is a risk factor for atrial fibrillation, current guidelines recommend measuring a thyroid-stimulating hormone level in patients with this disorder. Hyperthyroidism may also be associated with other heart diseases including cardiac ischaemia and cardiac failure. Currently, the prevalence of thyrotoxicosis in cardiac admissions in the absence of a rhythm disorder is unknown. AIMS: The aims of this study were: 1) to calculate the prevalence of admissions for thyrotoxicosis-associated cardiac disease, 2) determine the type of cardiac disease i.e. dysrhythmic, ischaemic or cardiac failure, and 3) to assess whether Maori are over-represented amongst patients admitted to hospital with cardiac complications of thyrotoxicosis. METHODS: A retrospective review of admissions with both thyrotoxicosis and cardiac disease from 1 January 2005 to 31 December 2012 inclusive. RESULTS: Seventy-two patients were identified as being admitted for a cardiac complication of thyrotoxicosis, giving a mean of nine admissions per year. Dysrhythmia was the cause for admission in 32 patients, ischaemia in 12, cardiac failure in 11 and mixed cardiac disease in 17. Graves' disease and amiodarone-induced were the most common causes of the thyrotoxicosis (25 and 19 cases, respectively). Of the cohort 26 (36.1%) were Maori (compared to 16.8% of all cardiac admissions over the same period). Maori were more likely to present with cardiac failure than non-Maori (57.7% vs. 26.1%, p=0.008 respectively). CONCLUSIONS: Maori are over-represented amongst patients admitted with cardiac complications of thyrotoxicosis and more often present with cardiac failure than non-Maori. Measurement of thyroid function should be considered in patients presenting not only with atrial fibrillation but also in patients presenting with cardiac failure, particularly if they are Maori.

GH replacement titrated to serum IGF-1 does not reduce concentrations of myostatin in blood or skeletal muscle.

OBJECTIVE: Traditional weight-based regimens of GH replacement are more effective at reversing the loss of skeletal muscle in GH-deficient adults than currently recommended regimens, where the dose of GH is increased to restore serum concentrations of IGF-1. While weight-based regimens increase concentrations of IGF-1 and decrease concentrations of myostatin, it is not known whether the reduced effectiveness of individually titrated GH regimens is due to ongoing hypersecretion of myostatin. Consequently, the aims of this study were to determine whether concentrations of myostatin in blood and skeletal muscle are increased in GH-deficient adults, and whether these concentrations are decreased by GH replacement regimens titrated to restore serum IGF-1. DESIGN: Twenty-six GH deficient adults (18 men and 8 women) were treated with individualised regimens of recombinant human GH aiming to achieve serum concentrations of IGF-1 within one standard deviation of the age- and gender-adjusted mean. Plasma concentrations of myostatin were measured at baseline and after 6 months of treatment were compared to fifteen healthy controls (9 men and 6 women). Skeletal muscle biopsies were performed in 19 of these GH-deficient adults (15 men and 4 women) and 10 of the healthy controls (6 men and 4 women). Expression of IGF-1 and myostatin mRNA was determined by qPCR. RESULTS: Concentrations of IGF-1 in serum and mRNA in skeletal muscle were reduced, and concentrations of myostatin in plasma and mRNA in skeletal muscle were increased in GH-deficient adults at baseline (P < .05 versus healthy controls). Despite restoring concentrations of IGF-1, GH replacement did not reduce concentrations of myostatin in either blood or skeletal muscle. Concentrations of IGF-1 and myostatin in both blood and skeletal muscle were positively correlated in GH-deficient adults at baseline (P < .05), but not in GH-replete adults. CONCLUSIONS: Concentrations of myostatin in blood and skeletal muscle are increased in GH-deficient adults. Despite normalising concentrations of IGF-1, individualised regimens of GH replacement do not reduce concentrations of myostatin in blood or skeletal muscle. Ongoing hypersecretion of myostatin may explain why individually titrated GH replacement regimens are less effective than higher weight-based regimens in increasing skeletal muscle mass.

Treatment choice, satisfaction and quality of life in patients with Graves' disease.

BACKGROUND: Thyrotoxicosis, most often caused by Graves' disease (GD), when treated inadequately may result in premature mortality. There is little consensus as to which of the 3 treatment options available - antithyroid drugs (ATD), radioactive iodine (RAI) and surgery, is better. AIMS: (i) To assess factors involved in treatment choice and treatment satisfaction in patients treated for Graves' disease; (ii) To assess quality of life (QoL) following treatment of Graves' disease. METHOD: Participants were selected from a prospective study cohort assessing thyrotoxicosis incidence and severity. Of the 172 eligible patients with Graves' disease, 123 treated patients participated (64% had received ATD only, 11% RAI and 25% total thyroidectomy, the latter 2 usually after a period of ATD), along with 18 untreated patients with newly diagnosed Graves' disease (overall participation rate, 73%). Consented patients completed a questionnaire detailing factors involved in treatment choice, QoL and satisfaction with treatment. RESULTS: Participants reported that the most important factors in choosing a treatment were the following: the effects on activities of daily living, concern about use of radioiodine, possibility of depression or anxiety, and doctor's recommendations. Satisfaction levels were high across all 3 treatment types. QoL 1-year following treatment was higher than in untreated patients, and comparable with other international studies. CONCLUSIONS: Patient satisfaction with therapy and QoL does not differ by treatment type. Therefore, clinical and social factors, in combination with patient choice and resource availability, should determine which treatment modality patients with Graves' disease should receive.

Rates of unsuspected thyroid cancer in multinodular thyroid disease.

BACKGROUND: Previously the risk of concomitant thyroid cancer in multinodular goitre (MNG) has been reported as approximately 4%. Cancer risk in toxic MNG was often considered lower than for non-toxic MNG, due to a possible protective effect of TSH suppression. However, recent American data suggest an approximately 18% risk of occult malignancy in both toxic and non-toxic MNG. AIMS: To assess malignancy risk in a New Zealand population undergoing thyroidectomy for MNG. METHODS: Single-centre study of patients undergoing thyroidectomy for MNG from 1 December 2006 to 30 November 2016. RESULTS: Six hundred and two patients underwent surgery for MNG (448 non-toxic and 154 toxic). Of these, 95/602 (16%) had thyroid cancer. After excluding patients operated for preoperative suspicion for cancer, 30/401 (8%) patients with non-toxic MNG and 15/151 (10%) with toxic MNG had unsuspected or occult thyroid cancer (p=0.358). Patients with toxic MNG were less likely to undergo preoperative fine needle aspiration than those with non-toxic MNG (34% vs 52%, respectively p=0.0001). Two-thirds of unsuspected thyroid cancers were incidental micropapillary carcinomas and unlikely to alter survival irrespective of therapy. CONCLUSION: Malignancy rates in MNG are higher than historically reported, although most unsuspected cancers are unlikely to alter mortality even if diagnosis is delayed.

Absence of Myostatin Improves Cardiac Function Following Myocardial Infarction.

BACKGROUND: Myostatin inhibits the development of skeletal muscle and regulates the proliferation of skeletal muscle fibroblasts. However, the role of myostatin in regulating cardiac muscle or myofibroblasts, specifically in acute myocardial infarction (MI), is less clear. This study sought to determine whether absence of myostatin altered left ventricular function post-MI. METHODS: Myostatin-null mice (Mstn-/-) and wild-type (WT) mice underwent ligation of the left anterior descending artery to induce MI. Left ventricular function was measured at baseline, days 1 and 28 post-MI. Immunohistochemistry and immunofluorescence were obtained at day 28 for cellular proliferation, collagen deposition, and myofibroblastic activity. RESULTS: Whilst left ventricular function at baseline and size of infarct were similar, significant differences in favour of Mstn-/- compared to WT mice post-MI include a greater recovery of ejection fraction (61.8±1.1% vs 57.1±2.3%, p<0.01), less collagen deposition (41.9±2.8% vs 54.7±3.4%, p<0.05), and lower mortality (0 vs. 20%, p<0.05). There was no difference in the number of BrdU positive cells, percentage of apoptotic cardiomyocytes, or size of cardiomyocytes post-MI between WT and Mstn-/- mice. CONCLUSIONS: Absence of myostatin potentially protects the function of the heart post-MI with improved survival, possibly by limiting extent of fibrosis.

A Duodenal SDH-Deficient Gastrointestinal Stromal Tumor in a Patient With a Germline SDHB Mutation.

Context: Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract arising from the interstitial cells of Cajal. Succinate dehydrogenase (SDH)-deficient GISTs are a unique class of GIST defined by loss of immunohistochemical expression of SDHB, indicating dysfunction of the mitochondrial complex 2; lack of driver mutations in KIT and PDGFRA; and distinctive morphologic features and natural history. To date, all reported SDH-deficient GISTs have arisen in the stomach. We report an SDH-deficient GIST arising in the gastrointestinal tract outside the stomach. Case description: A 29-year-old man with a germline SDHB mutation (p.Arg90*) presented with acute upper gastrointestinal hemorrhage. Endoscopy identified a lesion in the second part of the duodenum, close to the distal common bile duct, consistent with a GIST. Endoscopic ultrasonography and magnetic resonance imaging did not demonstrate metastatic or nodal disease. Open transduodenal excision was performed to remove the tumor. Histologic evaluation confirmed the clinical diagnosis of a GIST, with positive staining for DOG1 and KIT. The mitotic count was low (1 per 50 high-power fields). Immunohistochemistry for SDHB was negative in the presence of an internal control. SDHA expression was retained. No somatic mutations were identified in KIT (exons 9, 11, 13, and 17) or PDGFRA (exons 12, 14, and 18). The germline SDHB mutation and loss of heterozygosity were confirmed on molecular testing of the tumor. Conclusion: We describe an SDH-deficient GIST occurring outside of the stomach. This case indicates that SDH-deficient GISTs may also arise in the small intestine.

Quality of Life and Sexual Distress in Women With Erosive Vulvovaginal Lichen Planus.

OBJECTIVES: Erosive vulvovaginal lichen planus (EVLP) is a chronic and painful genital dermatosis. Little is published about its impact on quality of life. This study aimed to evaluate quality of life and sexual function in women with EVLP. MATERIALS AND METHODS: Women with genital dermatoses were surveyed using the Dermatology Life Quality Index (DLQI) and Hospital Depression and Anxiety Scales. A subgroup completed the Female Sexual Distress Scale and Female Sexual Function Index subscales. Patient characteristics including age, diagnosis, and current treatment were recorded. Results from women with EVLP were compared with other diagnoses. RESULTS: Data from 77 women who participated between March 2013 and March 2014 were analyzed. Of these, 17 had EVLP. Comparator groups included women with vulval lichen sclerosus (n = 48) and vulval dermatitis (n = 12). In women with EVLP, 59% reported at least moderate impact on quality of life; mean DLQI scores: EVLP, 7.18; lichen sclerosus, 3.79; dermatitis, 8.67; p = .008. Overall, scores suggested depression in 14% and anxiety in 16% of participants. Sexual distress scores 11 or higher were recorded by 69% of women with EVLP, 63% of women with lichen sclerosus, and 56% of women with dermatitis. In those completing all sections of the survey (n = 40), DLQI was significantly correlated with depression (p = .004), sexual distress (p = .001), and sexual satisfaction (p = .01). CONCLUSIONS: Sixty-nine percent of women with EVLP reported sexual distress. Women with EVLP reported lesser quality of life than those with lichen sclerosus. Quality of life, anxiety and depression, sexual distress, and sexual function were all related in these participants.

Symptoms and signs of acromegaly: an ongoing need to raise awareness among healthcare practitioners.

INTRODUCTION Chronic excess growth hormone production results in acromegaly, a condition associated with widespread physical changes, including soft tissue and bony overgrowth. When untreated, acromegaly reduces life expectancy. Patients usually remain undiagnosed for years after the onset of symptoms, by which stage irreversible physical changes have often occurred. METHOD A cross-sectional questionnaire study involving patients with acromegaly from the Waikato Endocrine Unit and the New Zealand Acromegaly Society evaluated features of acromegaly that were present before diagnosis. The aim of this study was to identify acromegaly features that were most prevalent to promote increased awareness about the disease by healthcare providers. RESULTS 81 participants were included. The main pre-diagnosis physical changes participants reported were acral changes, alterations in facial features and oral symptoms. For some, these features were present for more than 10 years before the acromegaly diagnosis. Multiple co-morbidities associated with acromegaly were reported. Two-thirds of the participants felt that an earlier diagnosis was possible. Most participants were in contact with General Practitioners (GPs) and/or dentists before diagnosis. Endocrinologists had the highest diagnosis rate, followed by GPs. Dentists had a low diagnosis rate despite a high prevalence of oral symptoms among study participants. CONCLUSION Increased awareness of acromegaly among primary care clinicians is important as they are the first-point-of-contact with the healthcare system for most patients. Health professionals' early recognition of symptoms and signs of acromegaly would reduce delays in time-to-diagnosis, enable earlier treatment and may improve outcomes for patients with acromegaly. MESH KEYWORDS Acromegaly; symptoms; delayed diagnosis; clinicians; primary healthcare.

Factitious Graves' Disease Due to Biotin Immunoassay Interference-A Case and Review of the Literature.

CONTEXT: Biotin (vitamin B7) is an essential co-factor for four carboxylases involved in fatty acid metabolism, leucine degradation, and gluconeogenesis. The recommended daily intake (RDI) of biotin is approximately 30 µg per day. Low-moderate dose biotin is a common component of multivitamin preparations, and high-dose biotin (10 000 times RDI) has been reported to improve clinical outcomes and quality of life in patients with progressive multiple sclerosis. Biotin is also a component of immunoassays, and supplementation may cause interference in both thyroid and non-thyroid immunoassays. OBJECTIVE: To assess whether biotin ingestion caused abnormal thyroid function tests (TFTs) in a patient through assay interference. DESIGN: We report a patient with biotin-associated abnormal TFTs and a systematic review of the literature. SETTING: A tertiary endocrine service in Hamilton, New Zealand. RESULTS: The patient had markedly abnormal TFTs that did not match the clinical context. After biotin cessation, TFTs normalized far more rapidly than possible given the half-life of T4, consistent with assay interference by biotin. Multiple other analytes also tested abnormal in the presence of biotin. CONCLUSION: Biotin ingested in moderate to high doses can cause immunoassay interference. Depending on the assay format, biotin interference can result in either falsely high or low values. Interference is not limited to thyroid tests and has the potential to affect a wide range of analytes. It is important for clinicians to be aware of this interaction to prevent misdiagnosis and inappropriate treatment.

Response to Radioiodine Therapy for Thyrotoxicosis: Disparate Outcomes for an Indigenous Population.

Despite 70 years of experience treating thyrotoxic patients with radioiodine not all patients are successfully treated by a single dose. Multiple factors predicting radioiodine efficacy have been reported. The aim of this study was to assess whether ethnicity was associated with radioiodine response. A retrospective review was performed of patients who received radioiodine therapy for thyrotoxicosis from 1 January 2008 to 31 December 2010 and had follow-up available of a minimum of 12 months. 224 patients were included, 82.4% female, and 63.7% had Graves's disease. Radioiodine failed in 21.5% of patients overall, with a higher failure rate in the indigenous population (35.2%). When controlling for other influencing factors by logistic regression, there continued to be an increased risk for the indigenous group (OR 2.82) and those treated with antithyroid drugs following radioiodine (OR 2.04). Younger age was also associated with an increased risk of failing radioiodine therapy (OR 0.97 for each year of age). Cure rates following radioiodine were lower for indigenes independent of factors known to affect radioiodine outcome. This is the first report demonstrating ethnicity as a possible independent variable for radioiodine efficacy. Further work is needed to investigate the cause of this difference.

The management of Graves' disease in New Zealand 2014.

BACKGROUND: Treatment options for Graves' disease (GD), namely anti-thyroid drugs (ATD), surgery or radioiodine (RAI), have not changed over the past two decades. There is no 'gold-standard' treatment for GD. AIMS: To assess whether the management of GD in New Zealand has changed since the previous 1991 New Zealand survey and compare current management with that of contemporary international studies. METHODS: We conducted an online survey of New Zealand physicians currently practising internal medicine, diabetes and/or endocrinology, using the cases and questions from the original European and 1991 New Zealand studies. RESULTS: The first-line use of RAI was 5.5%, compared to 41% in the 1991 New Zealand survey. This corresponded to an increase in ATD use, while the rates of surgery as a first-line treatment have remained static over time. New Zealand physicians use technetium scanning for diagnosis, whereas ultrasound and radioiodine uptake were the most commonly selected investigations by European and North American physicians, respectively. The pattern of ATD use in pregnancy was similar to international practice. CONCLUSION: Treatment of GD in New Zealand has shifted away from the use of RAI as first line treatment. There are significant differences in the investigation and treatment of Grave's disease between New Zealand, Europe and North America.

Adherence to adrenal incidentaloma guidelines is influenced by radiology report recommendations.

INTRODUCTION: Approximately 5% of all abdominal computed tomography (CT) and magnetic resonance imaging (MRI) scans reveal an adrenal incidentaloma. Although most adrenal incidentalomas are benign non-functioning adenomas, lesions may be hormonally active and/or malignant. The aim of this study was to determine adherence to recommended international guidelines and potential influencing factors when an adrenal incidentaloma is identified in routine clinical practice. METHODS: A retrospective study was performed of all CT and MRI reports from December 2009 to December 2011 using a key phrase search to identify patients with an incidental adrenal lesion. RESULTS: A total of 125 patients with incidental adrenal lesions were identified, of which 74 patients were considered appropriate for further endocrine/radiological workup. Of the 74 patients, only 19 (26%) were initially referred to the endocrine service for investigation; 21/74 (28%) had complete biochemical workup and 24/74 (32%) had imaging follow-up arranged. The reporting radiologist provided advice for follow-up in 31/74 (42%), and action was more likely to be taken when this recommendation was given. Follow-up of the patients who had not received investigation was attempted resulting in assessment of a further 23 patients. Of the 44 patients who have undergone full assessment, four patients were found to have clinically significant lesions (one each of: Cushing's syndrome, phaeochromocytoma, Conn's syndrome and plasmacytoma). CONCLUSION: This study suggests that the majority of adrenal incidentalomas may not be investigated according to current international guidelines. The recommendations by the reporting radiologist appear to influence whether a patient is referred for further investigation.

A low incidence of iodine-induced hyperthyroidism following administration of iodinated contrast in an iodine-deficient region.

OBJECTIVE: There are limited data on the incidence of iodinated contrast-induced thyrotoxicosis, particularly in iodine-deficient regions. The aim of this study was to determine the incidence of iodinated contrast-induced thyrotoxicosis and to determine whether thyrotoxicosis was more common in patients ≥70 years compared to those <70 years of age. DESIGN: A prospective study of adult patients undergoing an outpatient CT with iodinated contrast was performed. MEASUREMENTS: Thyroid function tests (TFTs) and urine iodine measurements were performed prior to the scan. TFTs were repeated at 4- and 8-weeks postscan. Changes in TFTs from baseline were analysed. RESULTS: A total of 102 patients were included in the final analysis. Overall, TSH levels dropped (P = 0·0002), and free T3 (FT3 ) levels increased (P = 0·04) between baseline and week 4 with normalization by week 8; however, these changes were not considered clinically significant. No significant differences in free T4 (FT4 ) occurred in the overall group (P = 0·82). There were no differences in TFTs between baseline and 4 or 8 weeks for those patients aged <70 compared to ≥70 years. Two patients developed new subnormal TSH values. Of these, one had a 90-mm follicular variant papillary thyroid carcinoma diagnosed while the other had a normal thyroid assessment and TSH spontaneously normalized by 12 weeks. CONCLUSIONS: Only 2% of patients developed subclinical hyperthyroidism following a standard dose of iodinated contrast for CT investigations. Given the low incidence of iodine-induced thyrotoxicosis, there is no indication for routine pre- and post-CT thyroid function testing in our region.

Early Onset Primary Hyperparathyroidism Associated with a Novel Germline Mutation in CDKN1B.

Individuals presenting with primary hyperparathyroidism (PHPT) at a young age commonly have an underlying germline gene mutation in one of the following genes: MEN1, CASR, or CDC73. A small number of families with primary hyperparathyroidism have been identified with germline mutations in CDKN1B and those patients with primary hyperparathyroidism have almost exclusively been women who present in middle age suggesting that the age of onset of PHPT in MEN4 may be later than that of MEN1. We present a case of apparently sporadic PHPT presenting in adolescence with single gland disease associated with a novel CDKN1B germline mutation (heterozygote for a missense mutation in exon 1 of the CDKN1B gene (c.378G>C) (p.E126D)). The implication from this case is that CDKN1B germline mutations may be associated with PHPT at an earlier age than previously thought.

Body Image Disturbance in Acromegaly Patients Compared to Nonfunctioning Pituitary Adenoma Patients and Controls.

Purpose. Excess growth hormone secretion in adults results in acromegaly, a condition in which multiple physical changes occur including bony and soft tissue overgrowth. Over time these changes can markedly alter a person's appearance. The aim of this study was to compare body image disturbance in patients with acromegaly to those with nonfunctioning pituitary adenomas (NFAs) and controls and assess the impact of obesity in these groups. Methods. A cross-sectional survey including quality of life, body image disturbance, anxiety and depression measures, growth hormone, and BMI measurement was carried out. Results. The groups did not differ with respect to body image disturbance. However separate analysis of obese participants demonstrated relationships between mood scales, body image disturbance, and pain issues, particularly for acromegaly patients. Conclusions. While the primary hypothesis that acromegaly might be associated with body image disturbance was not borne out, we have shown that obesity together with acromegaly and NFA can be associated with body image issues, suggesting that BMI rather than primary diagnosis might better indicate whether patients might experience body image disturbance problems.

Paraganglioma in Pregnancy: A Case Series and Review of the Literature.

CONTEXT: Pregnancies complicated by a pheochromocytoma or paraganglioma are very rare, being estimated to occur in 0.007% of all pregnancies. Both the well-being of the mother and fetus need to be considered, and management can be challenging. The optimal management of women with a pheochromocytoma or paraganglioma in pregnancy is not well established. OBJECTIVE: The objective of the study was to assess whether there is a difference in fetal or maternal mortality between pheochromocytomas and paragangliomas in pregnancy. DESIGN: We present an experience of eight pregnancies in four SDHB germline mutation-positive women with sympathetic paragangliomas, followed by a systematic review of the literature to compare the outcome of paragangliomas with that of pheochromocytomas occurring in pregnancy. RESULTS: In our case series, favorable fetal and maternal outcomes were seen in all eight pregnancies. From the systematic review, maternal and fetal mortality were lower in women with paragangliomas, at 3.6% and 12% respectively, compared with 9.8% and 16% in women with pheochromocytomas. CONCLUSION: Pregnant women with paragangliomas may be at a lower risk of adverse outcome than those with pheochromocytomas, but both maternal and fetal mortality rates are still higher than that of the general obstetric population.

Case report: clues to the diagnosis of an unsuspected massive levothyroxine overdose.

There is currently little literature pertaining to levothyroxine overdose apart from minor or accidental overdoses in the pediatric population. In particular, there is little information available on how to confidently differentiate levothyroxine overdose from endogenous causes of thyrotoxicosis when there is no history available at the time of assessment. We report a levothyroxine (15,800 mcg) and citalopram (2,460 mg) overdose in a 55-year-old woman presenting with seizure and tachycardia in which the diagnosis was not initially suspected. Clinical data, including a long history of treated hypothyroidism and lack of a goiter; and biochemical findings, such as an incompletely suppressed thyroid-stimulating hormone (TSH) level, despite a markedly elevated free thyroxine level (FT4), a normal sex hormone-binding globulin level at baseline, and an undetectable thyroglobulin, supported the diagnosis of thyrotoxicosis due to a massive exogenous thyroid hormone overdose. Treatment was given to decrease free triiodothyronine (FT3) conversion and increase thyroid hormone clearance with dexamethasone and cholestyramine. The patient made a full recovery. Levothyroxine overdose can result in subtle symptoms and signs clinically, even when in massive quantities. This can make diagnosis challenging. Biochemical features, such as the pattern of thyroid hormone elevation and thyroglobulin levels, help differentiate exogenous thyroid hormone overdose from endogenous causes of thyrotoxicosis.