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BACKGROUND: Primary aldosteronism (PA) is the most common secondary endocrine cause of hypertension with familial hyperaldosteronism type 1 (FH-1), a rare heritable subtype. Timely identification of FH-1 is important because of an increased risk of vascular events in affected individuals and because it provides the opportunity to guide appropriate treatment. Genetic testing is recommended if onset is at a young age (<20 years), there is a family history of PA or early cerebrovascular events occur. AIMS: To assess national rates of testing for FH-1, whether this varied over time and by region. METHODS: De-identified data were obtained on genetic testing performed for FH-1 from 1 April 2010 to 30 October 2023 (163 months) from the Canterbury Health Laboratories database, the sole national testing laboratory for FH-1. RESULTS: A total of 147 tests were performed, of which 19 (12.9%) were positive. Eleven of the positive tests were requested by one region. Testing rates varied from 0.00 to 0.63 per 100 000 people per annum. Most tests were requested by endocrinology services. Testing increased over time from an average of 4.6 tests per annum in the first 5 years of the period studied to 17.7 tests in the most recent 5 years. Limitations include lack of ethnicity data, information on testing indications and testing rates for other familial PA subtypes. CONCLUSIONS: Testing for FH-1 has increased over time but remains low. Testing for familial forms of PA should be considered in those in whom PA was diagnosed at a young age or with a suggestive family history.
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OBJECTIVE: Type B insulin resistance syndrome is a rare autoimmune disorder affecting glucose homeostasis, characterized by serum autoantibodies to the insulin receptor (AIRAbs). Patients typically present with severe insulin resistance. A mixed hyper- and hypoglycemia phenotype may also occur, as may isolated hypoglycemia. The classic biochemical pattern comprises elevated insulin levels despite hypoglycemia; however, a small proportion of cases demonstrate "isolated hypoglycemia with low insulin." The primary objectives of this systematic review were to identify the clinical characteristics and outcome of this subgroup. DESIGN: Systematic review of cases with hypoglycemia with suppressed insulin. Exclusions: hyperglycemia, elevated insulin, AIRAbs not confirmed. METHODS: PubMed, Medline, and Embase databases were searched up until February 2023 and complemented by manual citation search. The Joanna Briggs Institute critical appraisal checklist for case reports was used to assess bias. RESULTS: A total of 5342 articles were identified after duplicate removal. Eleven, all case reports, met all inclusion criteria and were included. Cases belonging to this subgroup were more diverse in sex, age, and ethnicity when compared with type B insulin resistance as a whole. Of the 11 cases, 3 developed lymphoma. High-dose corticosteroid therapy appeared to be effective therapy for the hypoglycemia, with often rapid response. CONCLUSIONS: Isolated hypoglycemia with low insulin forms a rare subgroup of type B insulin resistance. These patients lack the common characteristics of hyperinsulinemic hypoglycemia and hyperglycemia/insulin resistance. Furthermore, while coexisting autoimmune disease is commonly observed, there is potentially an association with aggressive lymphoma, the onset of which may be delayed.
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Enfermedades Autoinmunes , Hiperglucemia , Hiperinsulinismo , Hipoglucemia , Resistencia a la Insulina , Linfoma , Humanos , Insulina , Hiperinsulinismo/complicaciones , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/complicacionesRESUMEN
BACKGROUND: Familial hyperaldosteronism type 1 (FH1), previously known as glucocorticoid-remediable aldosteronism, was the first identified monogenic cause of primary aldosteronism. Patients classically develop hypertension at a young age and are at risk of premature vascular complications. A systematic review of FH1 was performed to determine long-term treatment outcomes. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted searches with a patient/population, intervention, comparison and outcomes (PICO) framework using Embase, Medline, PubMed, Scopus, and Web of Science databases to identify patients with FH1 prescribed either no treatment with a minimum 3 months follow-up or medical treatment of at least 3 months duration. RESULTS: A total of 99 FH1 cases were identified from 42 studies. Most had early-onset hypertension but variable hypokalemia, hyperaldosteronism, and hyporeninemia. Of the 62 cases with a reported age of FH1 diagnosis, median age was 18 ± 17.6 years old. Of those treated, 72% received a glucocorticoid for long-term treatment compared with 22% receiving a potassium-sparing diuretic. Data on long-term treatment and disease side effects, complications, and outcomes were seldom reported. However, of 20 patients with reported complications, premature vascular complications were evident with the median age of diagnosis for left ventricular hypertrophy and hypertensive retinopathy 15 and 16.5 years old respectively, the youngest age of aortic dissection age 10 years, and those with reported cerebrovascular history had strokes or transient ischemic attacks before age 40 years. CONCLUSIONS: Major gaps in the literature around FH1 patients' long-term treatment and disease outcomes still exist. Long-term outcome data are required to help inform clinicians of the best long-term treatment for FH1.
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Hiperaldosteronismo , Hipertensión , Hipopotasemia , Humanos , Lactante , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/tratamiento farmacológico , Hiperaldosteronismo/genética , Glucocorticoides/uso terapéutico , Hipertensión/complicaciones , Hipopotasemia/complicacionesRESUMEN
BACKGROUND: Maori have an increased incidence of thyrotoxicosis when compvared to non-Maori, however there are limited data on benign non-toxic nodular thyroid disease. AIMS: The aims of this study were to determine the rates of non-toxic multinodular goitre (NTMNG) surgery for Maori and non-Maori and to determine if there were differences in thyroid size between Maori and non-Maori undergoing total thyroidectomy for NTMNG. METHODS: Single centre study of patients undergoing thyroidectomy for NTMNG from 1 December 2006 to 30 November 2016. RESULTS: Maori were overrepresented amongst the 427 patients who underwent surgery for NTMNG at 34% compared to the expected ~17% of the background Maori adult population in the region. At the time of surgery, Maori were younger (P = 0.004) and had a larger thyroid gland (P < 0.001) when compared to non-Maori also undergoing total/near total thyroidectomy. Complication rates were low across all ethnic groups. CONCLUSION: Maori have increased rates of surgery for NTMNG compared to non-Maori and thyroid size is larger at the time of surgery. The reasons for this are currently unknown and more research is required.
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Bocio , Enfermedades de la Tiroides , Adulto , Humanos , Tiroidectomía/efectos adversos , Bocio/cirugía , Enfermedades de la Tiroides/cirugía , IncidenciaRESUMEN
Context: Pheochromocytomas and paragangliomas (PPGLs) are known to be rare. However, there is scant literature reporting their epidemiology, particularly whether the diagnosis of PPGL has increased with advances in medical imaging and biochemical and genetic testing. Objective: The primary objective of this systematic review was to determine the annual incidence of PPGLs and change over time. Design: A systematic review was performed. Medline, Embase, PubMed, and Web of Science Core Collection databases were searched to identify studies reporting PPGL incidence. Studies were eligible for inclusion from the database's inception until August 30, 2021. Results: A total of 6109 manuscripts were identified; 2282 duplicates were excluded, and a further 3815 papers were excluded after abstract and/or full text review. Twelve studies were included in the final review. The incidence of PPGL ranged from 0.04 to 0.95 cases per 100â 000 per year. Incidence increased over time, from approximately 0.2/100,000 individuals in studies performed before 2000, to approximately 0.6/100,000 in studies undertaken after 2010. The mode of diagnosis changed over the same time period, with more patients diagnosed from incidental imaging findings, and fewer at autopsy or from symptoms. Conclusion: The annual incidence of PPGL has increased over time. Much of this increase is likely from incidental identification of tumors on imaging. However, the epidemiology of PPGL remains understudied, in particular, in associations with altitude, ethnicity, and genetics. To improve early detection and management guidelines, these gaps should be addressed.
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Autosomal dominant hypocalcemia type 1 (ADH1) is a disorder of extracellular calcium homeostasis caused by germline gain-of-function mutations of the calcium-sensing receptor (CaSR). More than 35% of ADH1 patients have intracerebral calcifications predominantly affecting the basal ganglia. The clinical consequences of such calcifications remain to be fully characterized, although the majority of patients with these calcifications are considered to be asymptomatic. We report a 20-year-old female proband with a severe form of ADH1 associated with recurrent hypocalcemic and hypercalcemic episodes, persistent childhood hyperphosphatemia, and a low calcium/phosphate ratio. From the age of 18 years, she had experienced recurrent myoclonic jerks affecting the upper limbs that were not associated with epileptic seizures, extra-pyramidal features, cognitive impairment, or alterations in serum calcium concentrations. Computed tomography (CT) scans revealed calcifications of the globus pallidus regions of the basal ganglia bilaterally, and also the frontal lobes at the gray-white matter junction, and posterior horn choroid plexuses. The patient's myoclonus resolved following treatment with levetiracetam. CASR mutational analysis identified a reported germline gain-of-function heterozygous missense mutation, c.2363T>G; p.(Phe788Cys), which affects an evolutionarily conserved phenylalanine residue located in transmembrane domain helix 5 of the CaSR protein. Analysis of the cryo-electron microscopy CaSR structure predicted the wild-type Phe788 residue to form interactions with neighboring phenylalanine residues, which likely maintain the CaSR in an inactive state. The p.(Phe788Cys) mutation was predicted to disrupt these interactions, thereby leading to CaSR activation. These findings reveal myoclonus as a novel finding in an ADH1 patient with intracerebral calcifications.
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Peptide receptor radionuclide therapy (PRRT) is an increasingly used treatment for unresectable neuroendocrine tumours (NETs) that express somatostatin receptors. Normal pituitary tissue expresses somatostatin receptors so patients receiving PRRT may be at risk of developing hypopituitarism. The aim was to assess the prevalence of clinically significant hypopituitarism a minimum of 2 years following radioisotope therapy for metastatic NET. This was a multicentre study (Australia and New Zealand). Sixty-six patients with unresectable NETs were included-34 had received PRRT and 32 comparison patients. Median follow-up after PRRT was 68 months. Male hypogonadism was the most common hormonal abnormality (16 of 38 men [42%]) from the total cohort. Of these, seven men had primary hypogonadism (five from PRRT group) and nine had secondary hypogonadism (six in PRRT group). There was no difference in either male hypogonadism or other hormonal dysfunction between patients who had received PRRT and those that had not. Patients who have received PRRT out to 68 months following treatment do not show concerning hypopituitarism although there may be the suggestion of growth hormone deficiency developing. However, hypogonadism is common in men with NETs so the gonadal axis should be assessed in men with suggestive symptoms as the treatment of testosterone deficiency may improve the quality of life.
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Hipopituitarismo/etiología , Tumores Neuroendocrinos/radioterapia , Anciano , Australia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/metabolismo , Tumores Neuroendocrinos/patología , Nueva Zelanda , Pruebas de Función Hipofisaria , Calidad de Vida , Dosificación Radioterapéutica , Receptores de Péptidos/metabolismoRESUMEN
BACKGROUND: Reported international incidence rates of thyrotoxicosis vary markedly, ranging from 6 to 93 cases per 100â 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 100â 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 100â 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.
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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.
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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.
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Desarrollo de Músculos/fisiología , Músculo Esquelético/crecimiento & desarrollo , Músculo Esquelético/metabolismo , Factor de Transcripción STAT5/metabolismo , Factores de Edad , Animales , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Femenino , Hormona del Crecimiento/metabolismo , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Desarrollo de Músculos/genética , Miostatina/genética , Miostatina/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Factor de Transcripción STAT5/deficiencia , Factor de Transcripción STAT5/genética , Caracteres Sexuales , Transducción de Señal , Proteínas Supresoras de la Señalización de Citocinas/genética , Proteínas Supresoras de la Señalización de Citocinas/metabolismoRESUMEN
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.
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Cardiopatías/epidemiología , Admisión del Paciente/tendencias , Medición de Riesgo , Tirotoxicosis/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Cardiopatías/etiología , Cardiopatías/terapia , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Nueva Zelanda/epidemiología , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Tirotoxicosis/epidemiología , Adulto JovenRESUMEN
The gene CDC73 (previously known as HRPT2) encodes the protein parafibromin. Biallelic mutation of CDC73 is strongly associated with malignancy in parathyroid tumors. Heterozygous germline mutations cause hyperparathyroidism jaw tumor syndrome,which is associated with a high life-time risk of parathyroid carcinoma. Therefore loss of parafibromin expression by immunohistochemistry may triage genetic testing for hyperparathyroidism jaw tumor syndrome and be associated with malignant behavior in atypical parathyroid tumors. We share our experience that parafibromin-negative parathyroid tumors show distinctive morphology. We searched our institutional database for parathyroid tumors demonstrating complete loss of nuclear expression of parafibromin with internal positive controls. Forty-three parafibromin-negative tumors from 40 (5.1%) of 789 patients undergoing immunohistochemistry were identified. Thirty-three (77%) were external consultation cases; the estimated incidence in unselected tumors was 0.19%. Sixteen (37.2%) fulfilled World Health Organization 2017 criteria for parathyroid carcinoma and 63% had serum calcium greater than 3mmol/L. One of 27 (3.7%) noninvasive but parafibromin-negative tumors subsequently metastasized. Parafibromin-negative patients were younger (mean, 36 vs. 63 y; P<0.001) and had larger tumors (mean, 3.04 vs. 0.62 g; P<0.001). Not all patients had full testing, but 26 patients had pathogenic CDC73 mutation/deletions confirmed in tumor (n=23) and/or germline (n=16). Parafibromin-negative tumors demonstrated distinctive morphology including extensive sheet-like rather than acinar growth, eosinophilic cytoplasm, nuclear enlargement with distinctive coarse chromatin, perinuclear cytoplasmic clearing, a prominent arborizing vasculature, and, frequently, a thick capsule. Microcystic change was found in 21 (48.8%). In conclusion, there are previously unrecognized morphologic clues to parafibromin loss/CDC73 mutation in parathyroid tumors which, given the association with malignancy and syndromic disease, are important to recognize.
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Biomarcadores de Tumor/análisis , Neoplasias de las Paratiroides/patología , Proteínas Supresoras de Tumor/biosíntesis , Adenoma/complicaciones , Adenoma/diagnóstico , Adolescente , Adulto , Anciano , Femenino , Fibroma/complicaciones , Fibroma/diagnóstico , Humanos , Hiperparatiroidismo/complicaciones , Hiperparatiroidismo/diagnóstico , Neoplasias Maxilomandibulares/complicaciones , Neoplasias Maxilomandibulares/diagnóstico , Masculino , Persona de Mediana Edad , Mutación , Neoplasias de las Paratiroides/diagnóstico , Neoplasias de las Paratiroides/genética , Proteínas Supresoras de Tumor/análisis , Proteínas Supresoras de Tumor/genética , Adulto JovenRESUMEN
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 6â¯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 (Pâ¯<â¯.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 (Pâ¯<â¯.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.
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Trastornos del Crecimiento/tratamiento farmacológico , Hormona de Crecimiento Humana/administración & dosificación , Factor I del Crecimiento Similar a la Insulina/análisis , Músculo Esquelético/metabolismo , Miostatina/metabolismo , Adulto , Estudios de Casos y Controles , Femenino , Trastornos del Crecimiento/sangre , Hormona de Crecimiento Humana/sangre , Humanos , Masculino , Persona de Mediana EdadRESUMEN
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.
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Antitiroideos/uso terapéutico , Enfermedad de Graves/fisiopatología , Actividades Cotidianas , Adulto , Anciano , Femenino , Enfermedad de Graves/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Encuestas y Cuestionarios , Tiroidectomía , Tirotoxicosis/tratamiento farmacológico , Tirotoxicosis/cirugíaRESUMEN
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.
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Bocio Nodular/complicaciones , Glándula Tiroides/patología , Neoplasias de la Tiroides/epidemiología , Adulto , Biopsia con Aguja Fina , Femenino , Bocio Nodular/cirugía , Humanos , Masculino , Persona de Mediana Edad , Nueva Zelanda/epidemiología , Estudios Retrospectivos , Riesgo , Medición de Riesgo , Neoplasias de la Tiroides/etiología , Neoplasias de la Tiroides/patología , TiroidectomíaRESUMEN
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.
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Ventrículos Cardíacos/fisiopatología , Infarto del Miocardio/fisiopatología , Miocardio/patología , Miocitos Cardíacos/metabolismo , Miostatina/deficiencia , Función Ventricular Izquierda/fisiología , Remodelación Ventricular , Animales , Apoptosis , Vasos Coronarios/metabolismo , Vasos Coronarios/patología , Vasos Coronarios/fisiopatología , Modelos Animales de Enfermedad , Ecocardiografía , Fibroblastos/metabolismo , Fibroblastos/patología , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/patología , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Miocardio/metabolismo , Miocitos Cardíacos/patología , Miostatina/metabolismoRESUMEN
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.
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Neoplasias Duodenales/genética , Tumores del Estroma Gastrointestinal/genética , Succinato Deshidrogenasa/genética , Adulto , Anoctamina-1 , Canales de Cloruro/metabolismo , Enfermedades Duodenales/etiología , Neoplasias Duodenales/complicaciones , Neoplasias Duodenales/metabolismo , Neoplasias Duodenales/cirugía , Hemorragia Gastrointestinal/etiología , Tumores del Estroma Gastrointestinal/complicaciones , Tumores del Estroma Gastrointestinal/metabolismo , Tumores del Estroma Gastrointestinal/cirugía , Mutación de Línea Germinal , Humanos , Inmunohistoquímica , Pérdida de Heterocigocidad , Masculino , Proteínas de Neoplasias/metabolismo , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/metabolismo , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Succinato Deshidrogenasa/metabolismoRESUMEN
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.
Asunto(s)
Acromegalia/diagnóstico , Acromegalia/fisiopatología , Medicina General , Acromegalia/epidemiología , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Comorbilidad , Estudios Transversales , Diagnóstico Tardío , Etnicidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nueva Zelanda/epidemiología , PrevalenciaRESUMEN
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.
RESUMEN
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.