RESUMEN
CONTEXT: The recent WHO 2022 Classification of pituitary tumours identified a novel group of 'plurihormonal tumours without distinct lineage differentiation (WDLD)'. By definition, these express multiple combinations of lineage commitment transcription factors, in a monomorphous population of cells. OBJECTIVES: To determine the expression of stem cell markers (SOX2, Nestin, CD133) within tumours WDLD, immature PIT-1 lineage and acidophil stem cell tumours, compared with committed cell lineage tumours. METHODS: Retrospective evaluation of surgically resected pituitary tumours from St Vincent's Hospital, Sydney. Patients were selected to cover a range of tumour types, based on transcription factor and hormone immunohistochemistry. Clinical data was collected from patient files. Radiology reports were reviewed for size and invasion. Samples were analysed by immunohistochemistry and RT-qPCR for SF-1, PIT-1, T-PIT, SOX2, Nestin and CD133. Stem cell markers were compared between tumours WDLD and those with classically "mature" types. RESULTS: On immunohistochemistry, SOX2 was positive in a higher proportion of tumours WDLD compared with those meeting WHO lineage criteria, 7/10 v 10/42 (70 v 23.4%, p = 0.005). CD133 was positive in 2/10 tumours WDLD but 0/41 meeting lineage criteria, P = 0.003. On RT-qPCR, there was no significant difference in relative expression of stem cell markers (SOX2, CD133, Nestin) between tumours with and WDLD. CONCLUSIONS: Our study is the first to biologically characterise pituitary tumours WDLD. We demonstrate that these tumours exhibit a higher expression of the stem cell marker SOX2 compared with other lineage-differentiated tumours, suggesting possible involvement of stem cells in their development.
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Diferenciación Celular , Linaje de la Célula , Nestina , Neoplasias Hipofisarias , Factores de Transcripción SOXB1 , Humanos , Factores de Transcripción SOXB1/metabolismo , Neoplasias Hipofisarias/metabolismo , Neoplasias Hipofisarias/patología , Estudios Retrospectivos , Diferenciación Celular/fisiología , Femenino , Nestina/metabolismo , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Adulto , Antígeno AC133/metabolismo , Biomarcadores de Tumor/metabolismo , Anciano , Células Madre/metabolismo , Células Madre/patologíaRESUMEN
OBJECTIVES: To (1) identify the frequency of IGF-1 elevation in a cohort of patients without clinically suspected GH excess, in a state-based reference laboratory over a 24-month period, and (2) to examine potential differences in comorbidities and relevant medications between people with an elevated IGF-1 compared to a matched control group. DESIGN: All IGF-1 measurements at Pathology Queensland between 1/12/2018-1/12/2020 were identified. The medical records of those with IGF-1 ≥1.1x the upper limit of the reference range were appraised to determine: (1) documentation of acromegalic features, (2) relevant comorbidities and medication use, and (3) further investigations to exclude pathological GH excess. PATIENTS AND MEASUREMENTS: There were 2759 IGF-1 samples measured in 1963 people ≥18 years, over the specified period. Of these, 204 had IGF-1 ≥1.1x the upper limit of the age-matched reference range; 102 cases (61M, 41F) met inclusion criteria, and were matched to 102 controls with a normal IGF-1 based on age, sex, gonadal status and pituitary anatomy on MRI. RESULTS: There were significant differences in the frequency of dopamine agonist use (19/102 cases vs. 6/102 controls, OR = 3.66, 95% confidence interval [CI]: 1.45-9.29, p = .009) and chronic kidney disease (CKD) (14/102 cases vs. 4/102 controls, OR = 3.90, 95% CI: 1.28-11.14, p = .024). CONCLUSIONS: Out of 1963 patients having IGF-1 measured, 102 (5.2%) had an elevated IGF-1 where there was no known acromegaly, GH replacement or endogenous glucocorticoid excess. Intraindividual biological variability, assay imprecision and physiological factors are known contributors to falsely elevated IGF-1, dopamine agonist therapy and CKD should also be considered.
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Acromegalia , Hormona de Crecimiento Humana , Humanos , Acromegalia/terapia , Factor I del Crecimiento Similar a la Insulina/metabolismo , Agonistas de Dopamina , Hipófisis/metabolismoRESUMEN
Prolactinomas are the commonest form of pituitary neuroendocrine tumor (PitNET), representing approximately half of such tumors. Dopamine agonists (DAs) have traditionally been the primary treatment for the majority of prolactinomas, with surgery considered the second line. The aim of this review is to examine the historical and modern management of prolactinomas, including medical therapy with DAs, transsphenoidal surgery, and multimodality therapy for the treatment of aggressive prolactinomas and metastatic PitNETs, with an emphasis on the efficacy, safety, and future directions of current therapeutic modalities. DAs have been the mainstay of prolactinoma management since the 1970s, initially with bromocriptine and more recently with cabergoline. Cabergoline normalizes prolactin in up to 85% of patients and causes tumor shrinkage in up to 80%. Primary surgical resection of microprolactinomas and enclosed macroprolactinomas performed by experienced pituitary neurosurgeons have similar remission rates to cabergoline. Aggressive prolactinomas and metastatic PitNETS should receive multimodality therapy including high dose cabergoline, surgery, radiation therapy (preferably using stereotactic radiosurgery where suitable), and temozolomide. DAs remain a reliable mode of therapy for most prolactinomas but results from transsphenoidal surgery in expert hands have improved considerably over the last one to two decades. Surgery should be strongly considered as primary therapy, particularly in the setting of microprolactinomas, non-invasive macroprolactinomas, or prior to attempting pregnancy, and has an important role in the management of DA resistant and aggressive prolactinomas.
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Neoplasias Hipofisarias , Prolactinoma , Bromocriptina/uso terapéutico , Cabergolina/uso terapéutico , Agonistas de Dopamina/uso terapéutico , Femenino , Humanos , Neoplasias Hipofisarias/tratamiento farmacológico , Embarazo , Prolactinoma/tratamiento farmacológico , Prolactinoma/patología , Resultado del TratamientoRESUMEN
OBJECTIVE: Clinically non-functioning pituitary tumours (NFPT) are a heterogenous group of neoplasms with diverse outcomes. The purpose of this narrative review was to summarize available data on predictive factors, both in routine practice and research settings. DESIGN: A literature review was conducted for papers published in peer-reviewed journals, investigating clinical, radiological, pathological and genetic predictive factors in NFPT. RESULTS: Several clinical and radiological factors have been associated with NFPT recurrence and/or aggressiveness, including larger size and pre-/post-operative growth rates. Application of transcription factor immunohistochemistry has given rise to improved subtype identification, including 'higher-risk' subtypes, in routine clinical practice. Numerous other pathological and genetic biomarkers have demonstrated promise for prognostication in the research setting. CONCLUSION: NFPT are a heterogenous group of tumours, characterized by diverse presentation, pathogenesis and outcomes. Ongoing refinements in understanding of tumour biology are likely to pave the way to improved integrative prognostication and precision medicine for NFPT.
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Neoplasias Hipofisarias , Humanos , Inmunohistoquímica , Recurrencia Local de Neoplasia , Neoplasias Hipofisarias/genética , Medicina de Precisión , Factores de TranscripciónRESUMEN
OBJECTIVE: To determine whether early (4-8h) post-operative ACTH after trans-sphenoidal surgery (TSS) predicts long-term hypothalamic-pituitary-adrenal (HPA) axis function and to investigate early morning day 1 ACTH/cortisol variability using rapid sampling. DESIGN: Prospective observational study. METHODS: Participants undergoing TSS were included; those treated with glucocorticoids pre-operatively received 100 mg intravenous hydrocortisone on anaesthetic induction. ACTH and cortisol were measured post-operatively at + 4h and + 8h after induction and on day 1 every 10 minutes between 0700h and 0900h. PRIMARY OUTCOME: glucocorticoid requirement at 6 months. RESULTS: Nineteen participants (10F, 9M): 6/19 (32%) were treated with replacement glucocorticoids pre-operatively; 4 had ceased by 6 weeks post-operatively. One patient developed new hypopituitarism post-operatively meaning 3/19 (16%) required glucocorticoids at 6 months. Post-operative + 4h ACTH < 14.3 pmol/L (65 ng/L) predicted secondary adrenal insufficiency (SAI) (sensitivity 100%, specificity 75%), whilst no participant with a post-operative + 4h ACTH ≥ 14.3 pmol/L (65 ng/L) required glucocorticoids at 6 months. Day 1 ACTH and cortisol showed a significant circadian fall between 0700h-0900h; ACTH 4.2 pmol/L (IQR 2.9-5.9) to 3.7 pmol/L (IQR 2.9-5.1) P = .006 and cortisol 549 nmol/L (IQR 337-618) to 439 nmol/L (IQR 315-606) P < .001, with clinically insignificant ultradian secretory pulses. CONCLUSIONS: No participant with a post-operative + 4h ACTH ≥ 14.3 pmol/L (65 ng/L) required glucocorticoids at 6 months; however, given only 3/19 participants had the primary outcome of interest, this must be confirmed in a larger cohort. The timing of a day 1 morning cortisol between 0700h and 0900h influences the accuracy of a single cut-off to diagnose SAI after pituitary surgery.
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Hormona Adrenocorticotrópica , Hidrocortisona , Hipófisis , Ritmo Ultradiano , Glucocorticoides , Humanos , Sistema Hipotálamo-Hipofisario , Procedimientos Neuroquirúrgicos , Hipófisis/cirugía , Sistema Hipófiso-SuprarrenalRESUMEN
A biochemical diagnosis of subclinical hypothyroidism (SCH) is defined by an elevated serum thyroid-stimulating hormone (TSH) with a normal serum free thyroxine (FT4). This paper discusses SCH in the Australian population, the impact of SCH on health-related quality of life (HRQoL), and the evidence for thyroid hormone therapy as well as exercise therapy to improve HRQoL in SCH. The prevalence of SCH in Australia is approximately 4-5% and is higher in females and the elderly. Current evidence suggests thyroid hormone therapy is not associated with an improvement in HRQoL. However, there does appear to be a subgroup of those with SCH that experience an impairment in HRQoL who may potentially benefit from treatment. Because the majority of research to date has been done in elderly, largely asymptomatic individuals, this may not be representative of the entire SCH population. In addition, alternative treatments, such as exercise therapy, have not been well explored in the literature, despite exercise therapy's effects on HRQoL in other populations. Further research is required to define clearly which individuals with SCH are likely to experience an impaired HRQoL, as well as explore the effects of thyroid hormone therapy and exercise therapy in these individuals.
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Hipotiroidismo , Calidad de Vida , Anciano , Australia/epidemiología , Femenino , Humanos , Hipotiroidismo/diagnóstico , Hipotiroidismo/epidemiología , Hipotiroidismo/terapia , PrevalenciaRESUMEN
OBJECTIVE: To determine if patients with untreated Cushing's disease have higher serum insulin-like growth factor-1 (IGF-1) compared to matched controls, and if IGF-1 decreases following remission of Cushing's disease. DESIGN: Retrospective case-control study matching Cushing's disease cases to control patients for adenoma size, age, sex, diabetic and gonadal status, body mass index and serum IGF-1 measured within one year. Paired analysis of pre-operative (untreated) and >3 months post-operative (remission) serum IGF-1 for cases. PATIENTS AND MEASUREMENTS: All patients were investigated at the Princess Alexandra Hospital Endocrine Unit between 2005 and 2017. Serum IGF-1 was measured in 25 cases and 49 controls, 23 case-control pairs and 13 cases pre- and post-operatively. RESULTS: Mean serum IGF-1 in cases was significantly higher compared to controls-32 ± 12 nmol/L compared to 25 ± 8 nmol/L, (P = 0.005). The proportion of cases with elevated serum IGF-1 above an age-adjusted reference range was higher compared to 1:1 matched controls (8/23 (35%) vs 1/23 (4%), P = 0.02). In 13 cases in remission post-operatively, serum IGF-1 decreased significantly from 31 (IQR 29-40.5) nmol/L to 23 (IQR 15-28.5) nmol/L, (P < 0.001), despite no difference in the prevalence of pre- vs post-operative pituitary hormone dysfunction (P = 0.47). CONCLUSION: Patients with untreated Cushing's disease may have elevated IGF-1, which decreases following remission. Mildly elevated IGF-1 in Cushing's disease does not imply pathological growth hormone (GH) excess.
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Factor I del Crecimiento Similar a la Insulina/metabolismo , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/sangre , Hormona Adrenocorticotrópica/sangre , Adulto , Índice de Masa Corporal , Estudios de Casos y Controles , Femenino , Hormona del Crecimiento/sangre , Humanos , Masculino , Persona de Mediana Edad , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/cirugía , Hormonas Hipofisarias/sangre , Estudios RetrospectivosRESUMEN
OBJECTIVE: Hyponatraemia in hospitalized patients is common and associated with increased mortality. International guidelines give conflicting advice regarding the role of urea in the treatment of SIADH. We hypothesized that urea is a safe, effective treatment for fluid restriction-refractory hyponatraemia. DESIGN: Review of urea for the treatment of hyponatraemia in patients admitted to a tertiary hospital during 2016-2017. Primary end-point: proportion of patients achieving a serum sodium ≥130 mmol/L at 72 hours. PATIENTS: Urea was used on 78 occasions in 69 patients. The median age was 67 (IQR 52-76), 41% were female. Seventy (89.7%) had hyponatraemia due to SIADH-CNS pathology (64.3%) was the most common cause. The duration was acute in 32 (41%), chronic in 35 (44.9%) and unknown in the rest. RESULTS: The median nadir serum sodium was 122 mmol/L (IQR 118-126). Fluid restriction was first-line treatment in 65.4%. Urea was used first line in 21.8% and second line in 78.2%. Fifty treatment episodes (64.1%) resulted in serum sodium ≥130 mmol/L at 72 hours. In 56 patients who received other prior treatment, the mean sodium change at 72 hours (6.9 ± 4.8 mmol/L) was greater than with the preceding treatments (-1.0 ± 4.7 mmol/L; P < 0.001). Seventeen patients (22.7%) had side effects (principally distaste), none were severe. No patients developed hypernatraemia, overcorrection (>10 mmol/L in 24 hours or >18 mmol/L in 48 hours), or died. CONCLUSIONS: Urea is safe and effective in fluid restriction-refractory hyponatraemia. We recommend urea with a starting dose of ≥30 g/d, in patients with SIADH and moderate to profound hyponatraemia who are unable to undergo, or have failed fluid restriction.
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Hiponatremia/sangre , Hiponatremia/tratamiento farmacológico , Sodio/sangre , Urea/uso terapéutico , Anciano , Femenino , Humanos , Hiponatremia/mortalidad , Masculino , Persona de Mediana Edad , Centros de Atención Terciaria/estadística & datos numéricos , Resultado del TratamientoRESUMEN
OBJECTIVE: Thrombospondin-1 (TSP1), a matricellular protein, and Osteocalcin (OCN), a noncollagenous protein secreted by osteoblasts, are known to be up- and down-regulated, respectively, by glucocorticoids. The aim of this study was to determine whether a ratio between TSP1:OCN was altered by changes in glucocorticoid activity in humans. DESIGN: Prospective observational study. SETTING: Tertiary university hospital in Queensland, Australia. PATIENTS AND MEASUREMENTS: Patients with Cushing's syndrome (CS, n = 19), asthma or giant cell arteritis on chronic prednisolone treatment (PRED, n = 13), adrenal insufficiency (AI, n = 16) and healthy volunteers (HV, n = 20). Plasma TSP1 and serum total OCN were measured by immunoassay at 0800h, 1200h and 1600h in patients with CS, patients with AI taking replacement glucocorticoids, HV before and after 4 mg dexamethasone and PRED patients predose at 800 and 4 hours post-dose at 1200 hours. RESULTS: Plasma TSP1 in CS was higher (P < .0001), and serum OCN was lower (P < .0001) than HV. The TSP1:OCN ratio in HV increased significantly after 4 mg dexamethasone (P < .0001) and in AI after taking their hydrocortisone replacement therapy (P < .001). PRED patients had a higher TSP1:OCN ratio compared with HV at both 800 and 1200 hours (both P < .001), but no significant change occurred from pre- to post-dose. A TSP1:OCN ratio of >73 at 800 hours differentiated CS from HV with a sensitivity of 95% and a specificity of 100%. CONCLUSIONS: The TSP1:OCN ratio is elevated in patients on prednisolone and in patients with CS compared with healthy volunteers. It may be a useful biomarker of total body glucocorticoid activity in humans.
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Glucocorticoides/uso terapéutico , Osteocalcina/sangre , Trombospondina 1/sangre , Insuficiencia Suprarrenal/sangre , Insuficiencia Suprarrenal/tratamiento farmacológico , Adulto , Anciano , Asma/sangre , Asma/tratamiento farmacológico , Síndrome de Cushing/sangre , Síndrome de Cushing/tratamiento farmacológico , Femenino , Voluntarios Sanos , Humanos , Hidrocortisona/sangre , Masculino , Persona de Mediana Edad , Prednisolona/uso terapéutico , Estudios Prospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND/AIMS: Participant recruitment to diabetes prevention randomised controlled trials is challenging and expensive. The T4DM study, a multicentre, Australia-based, Phase IIIb randomised controlled trial of testosterone to prevent Type 2 diabetes in men aged 50-74 years, faced the challenge of screening a large number of prospective participants at a small number of sites, with few staff, and a limited budget for screening activities. This article evaluates a high-volume, low-cost, semi-automated approach to screen and enrol T4DM study participants. METHODS: We developed a sequential multi-step screening process: (1) web-based pre-screening, (2) laboratory screening through a network of third-party pathology centres, and (3) final on-site screening, using online data collection, computer-driven eligibility checking, and automated, email-based communication with prospective participants. Phone- and mail-based data collection and communication options were available to participants at their request. The screening process was administered by the central coordinating centre through a central data management system. RESULTS: Screening activities required staffing of approximately 1.6 full-time equivalents over 4 years. Of 19,022 participants pre-screened, 13,108 attended a third-party pathology collection centre for laboratory screening, 1217 received final, on-site screening, and 1007 were randomised. In total, 95% of the participants opted for online pre-screening over phone-based pre-screening. Screening costs, including both direct and staffing costs, totalled AUD1,420,909 (AUD75 per subject screened and AUD1411 per randomised participant). CONCLUSION: A multi-step, semi-automated screening process with web-based pre-screening facilitated low-cost, high-volume participant enrolment to this large, multicentre randomised controlled trial. Centralisation and automation of screening activities resulted in substantial savings compared to previous, similar studies. Our screening approach could be adapted to other randomised controlled trial settings to minimise the cost of screening large numbers of participants.
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Diabetes Mellitus Tipo 2/prevención & control , Selección de Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Anciano , Australia , Ensayos Clínicos Fase III como Asunto , Análisis Costo-Beneficio , Correo Electrónico , Humanos , Internet , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto/economía , Proyectos de InvestigaciónRESUMEN
Both hip fractures and vitamin D (25-hydroxyvitamin D (25-OHD)) deficiency are more common in winter in regions with temperate climates, but few data exist for a sub-tropical climate. In a South East Queensland tertiary hospital over a 7-year period, there were significantly more hip fractures in winter than the other three seasons (analysis of variance P = 0.003), with associated higher frequency of 25-OHD deficiency - 42.5% in winter compared to 28.5% in summer, odds ratio 1.86 (95% confidence interval 1.35-2.56), P = 0.0001. Seasonality of hip fracture and 25-OHD deficiency occurs even in a sub-tropical climate.
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Fracturas de Cadera/epidemiología , Estaciones del Año , Clima Tropical , Deficiencia de Vitamina D/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Fracturas de Cadera/sangre , Humanos , Masculino , Persona de Mediana Edad , Queensland/epidemiología , Factores de Riesgo , Centros de Atención Terciaria , Vitamina D/análogos & derivados , Vitamina D/sangre , Deficiencia de Vitamina D/sangre , Adulto JovenRESUMEN
BACKGROUND: Radioactive iodine (I131) is a common definitive treatment for Graves' Disease. Potential complications include worsening, or new development of Graves' eye disease and development of a radiation thyroiditis. The purpose of the present study was to assess outcomes of patients treated with I131 in an Australian tertiary centre over 10 years. METHODS: Data from 101 consecutive patients treated with I131 for a diagnosis of Graves' disease between 2005 to 2015 was collected and reviewed retrospectively. Baseline TSH receptor antibody titre, pre-treatment free thyroxine (FT4), technetium scan uptake, initial treatment, duration of treatment, reason for definitive therapy, complications, and time to remission (defined as euthyroidism or hypothyroidism after 12 months) were recorded. RESULTS: Of the 92 patients with adequate outcome data, 73 (79.3%) patients achieved remission with a single dose of I131. Of the remaining 19 patients, 12 had a second dose and became hypothyroid. TSH receptor antibody titre at diagnosis was significantly lower in the group that achieved remission with the first dose compared with those who did not (P = 0.0071). There was no difference in technetium uptake, I131 dose, duration of therapy or pre-treatment free thyroxine (FT4). I131 was complicated by development of eye disease in 3 patients and 1 (of 11 with pre-existing eye disease) had worsening eye disease. A clinically apparent flare of hyperthyroidism following I131 was evident in 8 patients (8.6%). CONCLUSION: Radioiodine is an effective therapy for Graves' Disease with few complications. The majority of patients achieve remission with a single dose. Those who require a second dose are more likely to have higher TSH receptor antibody titres at diagnosis. To the best of our knowledge, this is the first study to report outcomes from radioiodine treatment for Graves' disease in an Australian population.
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Enfermedad de Graves/diagnóstico , Enfermedad de Graves/tratamiento farmacológico , Radioisótopos de Yodo/administración & dosificación , Australia/epidemiología , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Enfermedad de Graves/epidemiología , Humanos , Masculino , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Hyponatraemia is the most common electrolyte disturbance amongst hospitalised patients. Both American and European guidelines recommend fluid restriction as first line treatment for SIADH, however differ on second line recommendations. The objective of this study was to examine investigation and management of hyponatraemia in hospitalised patients in an Australian tertiary hospital. METHODS: A retrospective audit was conducted of electronic medical records and laboratory data of inpatients with serum sodium (Na) ≤125 mmol/L, admitted over a 3 month period to the Princess Alexandra Hospital, Brisbane, Australia. The main outcomes measured included: demographic characteristics, investigations, accuracy of diagnosis, management strategy, change in Na and patient outcomes. RESULTS: The working clinical diagnosis was considered accurate in only 37.5% of cases. Urine Na and osmolality were requested in 72 of 152 patients (47.4%) and in 43 of 70 euvolaemic patients (61.4%). Thyroid function tests (67.1%) and morning cortisol (45.7%) were underutilized in the euvolaemic group. In the SIADH cohort, fluid restriction resulted in a median (IQR) 7.5 mmol/L (4-10.5) increase in Na after 3 days; no treatment resulted in a median 0 mmol/L (- 0.5-1.5) change. Oral urea was utilized in 5 SIADH patients where Na failed to increase with fluid restriction alone. This resulted in a median 10.5 mmol/L (3.5-13) increase in Na from baseline to day 3. There were no cases of osmotic demyelination. The median length of stay was 8 days (4-18.5). Mortality was 11.2% (17 patients). There was a weak but significant correlation between nadir serum Na and mortality (R = 0.18, P = 0.031). CONCLUSION: Inpatient hyponatraemia is often inadequately investigated, causing errors in diagnosis. Treatment is heterogeneous and often incorrect. In cases with hyponatraemia refractory to fluid restriction, oral urea presents an effective alternative treatment.
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Manejo de la Enfermedad , Hospitalización/tendencias , Hiponatremia/diagnóstico , Hiponatremia/terapia , Índice de Severidad de la Enfermedad , Centros de Atención Terciaria/tendencias , Anciano , Estudios de Cohortes , Femenino , Fluidoterapia/tendencias , Humanos , Hiponatremia/metabolismo , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Solución Salina Hipertónica/uso terapéutico , Urea/uso terapéuticoRESUMEN
The main determinants for the maintenance of water homeostasis are the hormone arginine vasopressin (AVP) and thirst. Disturbances in these regulatory mechanisms can lead to polyuria-polydipsia syndrome, which comprises of three different conditions: central diabetes insipidus (DI) due to insufficient secretion of AVP, nephrogenic DI caused by renal insensitivity to AVP action and primary polydipsia due to excessive fluid intake and consequent physiological suppression of AVP. It is crucial to determine the exact diagnosis because treatment strategies vary substantially. To differentiate between the causes of the polyuria-polydipsia syndrome, a water deprivation test combined with desmopressin administration is the diagnostic 'gold standard'. Thereby, AVP activity is indirectly evaluated through the measurement of urine osmolality after prolonged dehydration. However, this test has several limitations and may fail to distinguish precisely between patients with primary polydipsia and mild forms of central and nephrogenic DI. The direct measurement of AVP during the water deprivation test, which was reported in the 1980s, has not been widely adopted due to availability, assay issues and diagnostic performance. Recently, copeptin, the c-terminal portion of the larger precursor peptide of AVP, has been evaluated in the setting of polyuria-polydipsia syndrome and appears to be a useful candidate biomarker for the differential diagnosis. A standardised method for the water deprivation test is presented as part of a joint initiative of the Endocrine Society of Australia, the Australasian Association of Clinical Biochemists and the Royal College of Pathologists of Australasia to harmonise dynamic endocrine tests across Australia.
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Homeostasis/fisiología , Polidipsia/diagnóstico , Poliuria/diagnóstico , Arginina Vasopresina/orina , Diagnóstico Diferencial , Humanos , Polidipsia/fisiopatología , Polidipsia/orina , Poliuria/fisiopatología , Poliuria/orina , SíndromeRESUMEN
Growth hormone (GH) replacement therapy was recently recommended by the Pharmaceutical Benefits Advisory Committee (PBAC) for listing on the Pharmaceutical Benefits Scheme for adults with severe GH deficiency and impaired quality of life. This approval was significant for two reasons. First, the application was initiated and coordinated by a health professional working group, who prepared a 'public interest' submission to PBAC. Second, it resulted in a recommendation to subsidise therapy for a rare disease after two prior rejections on the basis of uncertainty about efficacy and cost effectiveness. There are important lessons to learn about the power of professional groups to drive health policy and attain funding for rare diseases.
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Análisis Costo-Beneficio/economía , Terapia de Reemplazo de Hormonas/economía , Hormona de Crecimiento Humana/deficiencia , Seguro de Servicios Farmacéuticos/economía , Enfermedades Raras/tratamiento farmacológico , Enfermedades Raras/economía , Adulto , Análisis Costo-Beneficio/tendencias , Enanismo Hipofisario/tratamiento farmacológico , Enanismo Hipofisario/economía , Terapia de Reemplazo de Hormonas/tendencias , Humanos , Seguro de Servicios Farmacéuticos/tendencias , Enfermedades Raras/epidemiologíaRESUMEN
OBJECTIVE: Factors determining recurrence of nonfunctioning pituitary adenomas (NFAs) that require further therapy are unclear as are postoperative follow-up imaging guidelines. We aimed to identify predictors for secondary therapy after surgical resection of NFAs and use this knowledge to inform postoperative management. DESIGN AND PATIENTS: A single-centre retrospective study of surgically resected NFAs in 108 patients followed for up to 15 years. Serial tumour images were analysed for size, location and growth rate (GR) and tissue analysed for hormone cell type and proliferation indices with secondary treatment as outcome measure. RESULTS: Twenty-four of 66 (36%) patients harbouring a postoperative remnant required secondary treatment, all occurring within 10 years. No secondary treatment was required in any of 42 patients with complete tumour resection. Age, gender, remnant volume and tumour histology were not different between patients requiring and not requiring secondary therapy. Remnant GRs in those requiring secondary therapy were more than 10-fold higher (P<.01). Tumours with a GR ≥80 mm3 /y (Hazard Ratio[HR]: 8.1, Confidence Interval [CI]: 2.4-27.3,P<.01) and those located in the suprasellar region (HR: 6.1, CI: 1.1-32, P=.03) had a higher risk for secondary therapy. Tumour GR in the first three postoperative years correlated significantly (r2 =.6, P<.01) with GR during the period of follow-up. CONCLUSION: In surgically resected NFAs further treatment is dependent on the presence of residual tumour, growth rate and location but not tumour histology. Postoperative growth rate of NFAs in the first 3 years of imaging can be used to tailor long-term follow-up to optimize use of health resources.
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Adenoma/cirugía , Neoplasias Hipofisarias/cirugía , Intervalos de Confianza , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
OBJECTIVE: To determine whether an overnight metyrapone test (OMT) within the first week postpituitary surgery can definitively assess the hypothalamic-pituitary-adrenal (HPA) axis, compared with subsequent dynamic tests and glucocorticoid requirement at 6 months. DESIGN: Prospective study measuring morning cortisol levels on days 3 and 4 post-operatively, OMT day 5-7 and week 6, week 6 250 µg short Synacthen test (SST) and week 7 insulin tolerance test (ITT). PATIENTS AND MEASUREMENTS: Forty participants who underwent pituitary surgery at a single centre (Cushing's disease excluded) were followed for at least 6 months. 46% had pre-operative adrenal insufficiency. PRIMARY OUTCOME: week 1 OMT compared to glucocorticoid requirement at 6 months. SECONDARY OUTCOMES: the performance of ITT as a "definitive" test and all tests compared to glucocorticoid requirement at 6 months. RESULTS: Week 1 OMT showed concordance with ITT at week 7 of 78% and glucocorticoid requirement at 6 months of 81% respectively which was not significantly different from post-operative morning cortisol levels; 37% of participants with an abnormal OMT on day 6 had a normal OMT at week 6. All HPA axis tests showed similar concordance with glucocorticoid requirement at 6 months of 80%-85%. CONCLUSIONS: Overnight metyrapone test within the first week after pituitary surgery was no better than an early morning cortisol level at predicting glucocorticoid requirement at 6 months. OMT at week 6 demonstrated recovery of HPA axis in a substantial proportion of participants who failed earlier assessments; thus, definitive testing should be delayed until 6 weeks post-operatively.
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Sistema Hipotálamo-Hipofisario/fisiología , Metirapona/farmacología , Hipófisis/cirugía , Sistema Hipófiso-Suprarrenal/fisiología , Recuperación de la Función/fisiología , Insuficiencia Suprarrenal/cirugía , Adulto , Femenino , Glucocorticoides/uso terapéutico , Humanos , Hidrocortisona/sangre , Masculino , Metirapona/administración & dosificación , Persona de Mediana Edad , Periodo Posoperatorio , Valor Predictivo de las Pruebas , Estudios Prospectivos , Esteroide 11-beta-Hidroxilasa/antagonistas & inhibidores , Factores de TiempoRESUMEN
OBJECTIVE: The natural history of nonfunctioning pituitary macroadenomas (NFPMA) after surgical resection is variable, with guidelines unable to define the duration of radiological follow-up. In this first Australian series, we identify risk factors for regrowth/recurrence of NFPMA to assist with guiding recommendations for long-term follow-up. DESIGN: Retrospective analysis of all radiotherapy-naïve cases with NFPMA resected between 1995 and 2013. PATIENTS: One hundred and twenty-three cases had both ≥2 postoperative scans and ≥12-month follow-up. MEASUREMENTS: Regrowth was defined as any sustained increase in diameter of residual adenoma or recurrence as any new adenoma occurring post complete resection on serial pituitary MRI. RESULTS: Median follow-up time was 48 months (interquartile range [IQR]: 31-86). Overall regrowth/recurrence occurred in 29% (36/123). Regrowth occurred in 40% (30/76) at a median time of 44.5 months (IQR 22-80) compared to recurrence of 12.5% (6/48; P=.003), occurring at a median time of 48 months (IQR 12-96; P=.7). Further treatment was required in 66.7% and 56.7%, respectively (=1.0). Risk factors for regrowth/recurrence by multivariate analysis were presence of residual disease and younger age at presentation. The longest time for regrowth was 168 months (14 years) and recurrence 156 months (13 years). CONCLUSIONS: Presence of postoperative residual adenoma and younger age at presentation are the main predictors of regrowth/recurrence in NFPMA. Long-term serial imaging is required to detect regrowth and recurrence in younger patients and those with residual disease. Most regrowth/recurrences will occur within 10 years of follow-up.
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Adenoma/patología , Neoplasias Hipofisarias/patología , Adenoma/cirugía , Factores de Edad , Anciano , Australia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/cirugía , Recurrencia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Graves' hyperthyroidism commonly causes tachycardia and may result in pulmonary hypertension and high output cardiac failure. There is limited information regarding the effect of treatment on cardiac function measured using modern echocardiographic techniques. METHODS: Eight individuals with Graves' hyperthyroidism, aged 22-64 years, underwent comprehensive transthoracic echocardiography at three time points: before treatment, two weeks after commencement of carbimazole, and at six months or more when euthyroid. Exercise capacity was assessed using the 6-minute-walk-distance (6MWT), and quality of life was assessed by Medical Outcome Study 36-item Short-Form Health Status Survey. RESULTS: All individuals were rendered euthyroid by final assessment. At presentation, there was evidence of hyperdynamic right ventricular function as measured by peak systolic velocity of the free wall of the tricuspid annulus, tricuspid annular plane systolic excursion and right ventricular ejection fraction, which normalised after resolution of thyrotoxicosis. Baseline heart rate correlated significantly with severity of the thyrotoxicosis for either free T4 (r = 0.91, p=0.01) or free T3 (r=0.94, p=0.001). No individual had measurable pulmonary hypertension. Cardiac output was significantly lower in the euthyroid compared to the thyrotoxic state (p=0.03). A higher baseline TSH-receptor antibody titre corresponded to a greater improvement in exercise capacity (r=0.76, p<0.05) and physical quality of life (r=0.73, p<0.05) on resolution of the hyperthyroidism. CONCLUSION: Graves' hyperthyroidism causes increased cardiac output and a hyperdynamic right ventricle which normalise on restoration of the euthyroid state.
Asunto(s)
Ecocardiografía , Enfermedad de Graves , Función Ventricular Derecha , Adolescente , Adulto , Anciano , Velocidad del Flujo Sanguíneo , Prueba de Esfuerzo , Femenino , Enfermedad de Graves/diagnóstico por imagen , Enfermedad de Graves/fisiopatología , Enfermedad de Graves/terapia , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Volumen SistólicoRESUMEN
CONTEXT: The optimal management of nonfunctioning pituitary adenomas presenting without symptomatic mass effect remains uncertain. The objective of this study was to elucidate the natural history of nonfunctioning pituitary adenomas managed conservatively. DESIGN: Volumetric evaluation of tumour growth in serial pituitary MRI scans by a single observer and retrospective review of changes in pituitary function. PATIENTS: Patients with nonfunctioning pituitary adenomas who underwent at least 2 serial pituitary MRI scans over ≥6 months between 2003 and 2013 prior to any intervention. MEASUREMENTS: Primary end-point was a ≥20% increase in volume or surgery. Secondary end-points were rate of pituitary dysfunction and pituitary apoplexy. RESULTS: Fifty nonfunctioning pituitary adenomas (23 macroadenomas and 27 microadenomas, mean age 49, range 17-85 years) were identified. Mean follow-up was 36 months (range 6-79). An increase in volume occurred in macroadenomas (P < 0·01) but not in microadenomas (P = 0·44). A ≥20% increase in volume occurred in nine of 23 macroadenomas compared with two of 27 microadenomas (P < 0·05). Five macroadenomas (one with new visual field defect) and one microadenoma proceeded to surgery (P = 0·08). Hormone deficiency was present in four of 24 macroadenomas vs 0 of 27 microadenomas (P < 0·05) at baseline, while new hormone deficiency developed in only two macroadenomas during follow-up. Pituitary apoplexy occurred in one microadenoma. A growth rate of >10 mm3 /month assessed at approximately 2 years of follow-up among the macroadenoma group was highly predictive (sensitivity and specificity of 90%) of a ≥20% increase in volume or surgery. CONCLUSIONS: Nonfunctioning pituitary macroadenomas have a greater tendency to grow and require surgical intervention while microadenomas rarely progress.