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BACKGROUND: Two main types of galenic formulation, immediate release and prolonged release, have been developed to optimize melatonin bioavailability. We recently described the kinetic profile of a prolonged-release form generating a peak of plasma melatonin 1 h (Tmax) after intake, followed by a prolonged decay over time. We have developed a new oral form of melatonin with the aim of producing a melatonin peak several hours after intake. OBJECTIVE: The objective is to investigate melatonin bioavailability after administration of this new delayed-release form (DR form). METHODS: In this single-centre open-label study, 12 healthy male volunteers received one tablet of the DR form containing 1.9 mg melatonin, 10 mg zinc and 200 mg lemon balm extract (Melissa officinalis L aerial parts). Blood samples were collected for 12 h, beginning at 8:00 am. Plasma concentrations of melatonin and 6-sulfatoxymelatonin (6-SMT), the main hepatic melatonin metabolite, were determined by radioimmunoassay. RESULTS: A progressive increase in plasma melatonin concentrations was observed from 20 min and a peak about 3 h after intake (Cmax 740 ± 824 pg/mL; Tmax 179 ± 60 min). Concentrations remained high between 140 and 220 min, the concentration remaining physiologically significant (over 100 pg/mL) up to 7 h after intake. The DR form was well tolerated. CONCLUSIONS: The melatonin release profile was consistent with what was anticipated for the DR form. The DR form generated a 2 h delayed Tmax compared with a prolonged-release form previously evaluated. This suggests that the DR form is suitable for the treatment of certain sleep disorders such as short sleep duration or early awakening. TRIAL REGISTRY: Registration number: NCT05419466.
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Background: Determining the cause of hypoglycemia partly relies on blood insulin and C-peptide assays. Although the pancreatic secretion of these peptides is equimolar, discrepancies in their concentrations may occur. Case presentation: We report the case of a 73-year-old woman with type 2 diabetes mellitus (T2DM) and a history of gastric bypass. The T2DM was initially treated with insulin analogs, which were interrupted due to transient hypoglycemia episodes three years before hospitalization in our endocrinology department. During this hospitalization, the most common etiologies of hypoglycemia were excluded. Fasting insulin level was high (190 mIU/L, reference values (RV): 5-25) on Architect i2000 (an assay recognizing insulin analogs) despite normal blood C-peptide (4.5 µg/L, RV: 0.8-5.2) and slight hypoglycemia (4.5 mmol/L, RV: 4.6-6.1). Insulin level using the Elecsys assay (an assay with low sensitivity to insulin analogs) was very high (>1000 mIU/L, RV: 2.6-24.9). This pattern was observed on several samples, including some taken during a fasting test. Insulin level was only slightly increased using the Mercodia iso-insulin ELISA kit (an assay recognizing insulin analogs). These results excluded an exogenous insulin intake and were suggestive of an interference on insulin assays. To explore the latter possibility, free anti-insulin antibodies were measured and found strongly positive. The presence of interfering insulin-antibody complexes was further investigated using gel filtration chromatography, polyethylene glycol precipitation, and dilution test. Based on these findings, an insulin autoimmune syndrome (IAS) was suspected to cause the hypoglycemic episodes observed. Conclusion: Although a discrepancy between blood insulin and C-peptide levels points to insulin analog intake, IAS should also be considered, particularly in a patient with transient hypoglycemia. IAS is characterized by the presence of insulin-antibody complexes, which can induce varying degrees of interference on insulin immunoassays and may lead to discordant insulin and C-peptide levels according to the insulin immunoassay used.
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Craniopharyngiomas are rare hypothalamic-pituitary tumors found in young children, adolescents and adults, and their multidisciplinary management required, calls for consistent practices for practicioners, patients and families. The French Endocrine Society and French Society for Pediatric Endocrinology & Diabetes enlisted and coordinated adult and paediatric endocrinologists, neurosurgeons, pathologists, radiotherapists as well as psychologists, dieticians and a patient association, to draft a reference document on this severe disease. The management of craniopharyngiomas remains complex due to their aggressive nature, invasive behavior, and propensity for recurrence, requiring a sequential and measured therapeutic approach and follow-up in expert centers. Although patient survival rates are high, the consequences of both the tumor and its treatment can lead to serious comorbidities and impaired quality of life, particularly in those patients with lesional hypothalamic syndrome. Recent advances have allowed the two described tumor types - papillary and adamantinomatous - to be associated with distinct molecular signatures, specific pathophysiological mechanisms and ipso facto, distinct therapeutic approaches, including innovative medications for hyperphagia, that will continue to evolve. This consensus statement covers all stages in the management of patients with craniopharyngioma, from diagnosis to therapeutic strategies including the long-term follow-up.
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MacroTSH still interferes with TSH assays. We present here a case report illustrating the difficulties that can arise in such conditions and attempt to discuss the steps involved in diagnosis.
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Tirotropina , Humanos , Tirotropina/sangreRESUMEN
X-linked acrogigantism (X-LAG) is a rare form of pituitary gigantism that is associated with growth hormone (GH) and prolactin-secreting pituitary adenomas/pituitary neuroendocrine tumors (PitNETs) that develop in infancy. It is caused by a duplication on chromosome Xq26.3 that leads to the misexpression of the gene GPR101, a constitutively active stimulator of pituitary GH and prolactin secretion. GPR101 normally exists within its own topologically associating domain (TAD) and is insulated from surrounding regulatory elements. X-LAG is a TADopathy in which the duplication disrupts a conserved TAD border, leading to a neo-TAD in which ectopic enhancers drive GPR101 over-expression, thus causing gigantism. Here we trace the full diagnostic and therapeutic pathway of a female patient with X-LAG from 4C-seq studies demonstrating the neo-TAD through medical and surgical interventions and detailed tumor histopathology. The complex nature of treating young children with X-LAG is illustrated, including the achievement of hormonal control using a combination of neurosurgery and adult doses of first-generation somatostatin analogs.
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Acromegalia , Enfermedades Genéticas Ligadas al Cromosoma X , Gigantismo , Hormona de Crecimiento Humana , Neoplasias Hipofisarias , Adulto , Humanos , Niño , Femenino , Preescolar , Gigantismo/genética , Gigantismo/terapia , Gigantismo/metabolismo , Acromegalia/patología , Hormona del Crecimiento/metabolismo , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/terapia , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/patologíaRESUMEN
STUDY QUESTION: Is the 24-h urinary gonadotropin assay an effective diagnostic tool in central precocious puberty (CPP) in girls? SUMMARY ANSWER: This study is the first to provide 24-h urinary gonadotropin assay data, using an electrochemiluminescent immunoassay (CMIA), and to report its usefulness as a tool for the diagnosis of CPP. WHAT IS KNOWN ALREADY: Data about the GnRH test in the diagnosis of CPP are variable and there is no consensus regarding its interpretation. The measurement of FSH and LH in urines was previously reported to be an alternative biological tool. STUDY DESIGN, SIZE, DURATION: This is a retrospective two-cohort study, involving a setting and a validation cohort. A total of 516 girls, included between October 2012 and July 2015, and 632 urinary collections were analyzed in the setting cohort. In the validation cohort, 39 girls were included between January 2021 and May 2023, and 49 urinary collections were analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study included girls who consulted for an investigation of disturbed growth rate or a clinical suspicion of puberty onset in different medical centres across France (setting cohort). Girls with a suspicion of precocious puberty onset were addressed at the expert centre of paediatric endocrinology of the Groupement Hospitalier Lyon Est (validation cohort). Pelvic ultrasonography was performed and enabled their classification according to clinical and morphologic changes criteria (prepubertal or pubertal groups). The parents collected 24-h urine samples (u24) according to standardized instructions. FSH and LH (urinary or plasmatic) were measured using a current and automated CMIA. MAIN RESULTS AND THE ROLE OF CHANCE: The area under the ROC curves for CPP prediction was 0.709 for u24FSH (P < 0.001), 0.767 for u24LH (P < 0.001), and 0.753 for the u24LH/u24FSH ratio (P < 0.001). We retained all possible combinations of the four thresholds in the validation cohort (u24FSH = 1.1 or 2.0 IU/24 h; u24LH = 0.035 or 0.08 IU/24 h). The combination of u24FSH > 1.1 IU/24 h and u24LH > 0.08 IU/24 h had a positive PV of 85.7% and a negative PV of 94.3%, a sensitivity of 85.7% and a specificity of 94.3%, for classifying prepubertal and pubertal girls in this cohort. LIMITATIONS, REASONS FOR CAUTION: This is a retrospective study, in which a margin of error remains due to the inherent uncertainty regarding the clinical assessment of pubertal onset. It must be considered that the thresholds can only apply to the used reagents; measurements without extractions using other reagents are likely to show important heterogeneity. WIDER IMPLICATIONS OF THE FINDINGS: The assay performed herein is a simple, non-invasive, and analytically robust technique meeting the criteria for an alternative to the GnRH test which could be used to supplement its lack of sensitivity. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was used. All authors declared no conflict of interest. TRIAL REGISTRATION NUMBER: In-house #23-5214 registered study.
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Hormona Folículo Estimulante , Hormona Luteinizante , Pubertad Precoz , Humanos , Femenino , Pubertad Precoz/orina , Pubertad Precoz/diagnóstico , Pubertad Precoz/sangre , Estudios Retrospectivos , Niño , Hormona Luteinizante/sangre , Hormona Luteinizante/orina , Hormona Folículo Estimulante/sangre , Hormona Folículo Estimulante/orina , Inmunoensayo/métodos , Valor Predictivo de las PruebasRESUMEN
STUDY DESIGN: Prospective observational study. OBJECTIVES: To evaluate melatonin secretion, daytime sleepiness and sleep disorders in patients with spinal cord injuries (SCI), and their association with lesion level. SETTING: Specialized neuro rehabilitation hospital in France METHODS: Prospective observational study of patients aged over 18 hospitalized in for spinal cord injury. Sleep quality was measured with the Pittsburgh Sleep Quality Index (PQSI), daytime sleepiness with the Epworth Sleepiness scale (ESS), and melatonin secretion by 24 h urinary dosage of 6-sulphatoxy-melatonin. RESULTS: 213 patients were screened, 21 patients were included: 17 complete (AIS A) and 4 lesions (AIS B), 76% of traumatic origin with 12 tetraplegic and 9 paraplegic, mean 10 (range 0.5-40) years after injury. Mean age was 46.8 ± 14.7 years, mean BMI 23.56 ± 4.1 and men outnumbered women (15 vs 6). Melatonin secretion was analyzed by 24 h secretion and by secretion profile. Comparing retained vs abolished secretion, only 23% (4/17) of patients with a lesion above T8 retained melatonin secretion, compared to 80% (4/5) with a lesion below T8 (p = 0.022). Non significant differences were found in secretion profile in patients who retained secretion: no patient with a lesion above T8 had a normal secretion profile compared to 50% with a lesion below T8 and in the impact of partial vs total lesions above T8 in whom 17% (2/12) of complete ASIA-A lesions and 50% (2/4) of incomplete lesions retained secretion. CONCLUSION: Lesions of the spinal cord above T8 are strongly associated with abolition of melatonin secretion.
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Trastornos de Somnolencia Excesiva , Melatonina , Trastornos del Sueño-Vigilia , Traumatismos de la Médula Espinal , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sueño , Trastornos del Sueño-Vigilia/etiología , Traumatismos de la Médula Espinal/complicacionesRESUMEN
Fluctuations of consciousness and their rhythmicities have been rarely studied in patients with a disorder of consciousness after acute brain injuries. 24-h assessment of brain (EEG), behaviour (eye-opening), and circadian (clock-controlled hormones secretion from urine) functions was performed in acute brain-injured patients. The distribution, long-term predictability, and rhythmicity (circadian/ultradian) of various EEG features were compared with the initial clinical status, the functional outcome, and the circadian rhythmicities of behaviour and clock-controlled hormones. Here we show that more physiological and favourable patterns of fluctuations are associated with a higher 24 h predictability and sharp up-and-down shape of EEG switches, reminiscent of the Flip-Flop model of sleep. Multimodal rhythmic analysis shows that patients with simultaneous circadian rhythmicity for brain, behaviour, and hormones had a favourable outcome. Finally, both re-emerging EEG fluctuations and homogeneous 24-h cycles for EEG, eye-opening, and hormones appeared as surrogates for preserved functionality in brainstem and basal forebrain, which are key prognostic factors for later improvement. While the recovery of consciousness has previously been related to a high short-term complexity, we suggest in this exploratory study the importance of the high predictability of the 24 h long-term generation of brain rhythms and highlight the importance of circadian body-brain rhythms in awakening.
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Trastornos de la Conciencia , Estado de Conciencia , Humanos , Estado de Conciencia/fisiología , Ritmo Circadiano/fisiología , Sueño/fisiología , HormonasRESUMEN
BACKGROUND: Insulin is essential for glycemic regulation but diseases can cause a default or an excess of insulin secretion leading to dysregulated glycemia. Hence, measurement of insulinemia is useful to investigate hypoglycemia, determine the pathogenesis of diabetes and evaluate ß-cell function. Thus, diabetic patients need supplementation with recombinant human insulin and/or insulin analogues. Analogues have primary sequences different from native human insulin and may not be detected by some immunoassays. The objective of our study was to evaluate new insulin immunoassays by determining their ability to detect different types of human insulin or analogues. METHODS: This study compared the reactivity of two new insulin immunoassays with five well-established immunoassays on ten commercial insulins. We also measured insulin in blood samples from diabetic or pancreas transplant patients with known treatment. RESULTS: Contrary to recombinant human insulin, there were differences in the specificity to insulin analogues. We distinguished three immunoassay categories: those recognizing all types of insulin such as the non-specific BI-INS-IRMA®, Architect® and Access® immunoassays; those recognizing human insulin only (Cobas®); and those recognizing human insulin and analogues in variable proportions (Liaison XL®, iFlash® and Maglumi®). CONCLUSION: An accurate biological interpretation of insulinemia relies on knowledge of the specificity of the immunoassay used.
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Secreción de Insulina , Insulina , Humanos , Hipoglucemia/sangre , Inmunoensayo , Insulina/sangre , Células Secretoras de InsulinaRESUMEN
BACKGROUND: The benefit of exogenous melatonin is based on its bioavailability, which depends on the galenic form, the route of administration, the dosage, and the individual absorption and rate of hepatic metabolism. OBJECTIVE: The objective of this study is to investigate the bioavailability of melatonin after administration of an oral prolonged-release tablet (PR form) and an immediate-release sublingual spray (IR form). The main metabolite of melatonin, 6-sulfatoxymelatonin (6-SMT), was also measured, which has not been done in previous studies. Its determination is important as an index of the hepatic transformation of melatonin. METHODS: In this single-center, open-label, randomized, crossover study, 14 healthy male volunteers received one tablet of the PR form (1.9 mg melatonin) or two sprays of the IR form (1 mg melatonin) during two visits separated by a washout period. Blood samples were collected over 7 and 9 h for the IR and PR form, respectively, to determine the main pharmacokinetic parameters. RESULTS: The observed kinetics were consistent with those expected for immediate and prolonged-release forms. Pulverization of the spray resulted in an early, high plasma melatonin peak (Cmax: 2332 ± 950 pg/mL; Tmax: 23.3 ± 6.5 min), whereas tablet intake produced a lower peak (Cmax: 1151 ± 565 pg/mL; Tmax: 64.2 ± 44.2 min; p < 0.001 for comparison of Cmax and Tmax) followed by a plasma melatonin plateau and a more prolonged decay over time. Plasma melatonin/6-SMT AUC0-540/420 ratio was 0.09 for the PR form and 0.16 for the IR form. Both galenic forms were well tolerated. CONCLUSIONS: The results suggest that the galenic forms containing melatonin assessed in this study are suitable for the treatment of certain sleep disorders such as sleep onset delay and transient nocturnal awakenings for the IR form and insomnia for the PR form. TRIAL REGISTRY: Registration number: NCT04574141.
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Melatonina , Humanos , Masculino , Disponibilidad Biológica , Estudios Cruzados , Comprimidos , Voluntarios , Administración Oral , Área Bajo la CurvaRESUMEN
According to the International Classification of Sleep Disorders, third edition guidelines, the diagnosis of narcolepsy type 1 is based on the association of excessive daytime sleepiness plus either cataplexy and electrophysiological criteria, or a cerebrospinal fluid hypocretin-1 concentration below 110 pg/mL. This threshold remains debated, and recent works have proposed alternative values in the intermediate (110 to 200 pg/mL) zone. We report the case of a patient who presented with typical clinical symptoms of narcolepsy type 1 developing over six years but in whom initial polysomnography and multiple sleep latency test were negative and cerebrospinal fluid hypocretin-1 was intermediate (132 pg/mL). Cerebrospinal fluid hypocretin-1 reassessment four years later found a dramatic decrease, < 50 pg/mL, and the multiple sleep latency test proved to be abnormal, eventually allowing to confirm the diagnosis. This case highlights the importance of reassessing patients with intermediate hypocretin-1 values and contributes to the debate on the determination of alternative cerebrospinal fluid hypocretin1 thresholds for narcolepsy type 1 diagnosis. CITATION: Ricordeau F, Bridoux A, Raverot V, Peter-Derex L. Progressive narcolepsy: how to deal with intermediate hypocretin-1 values? J Clin Sleep Med. 2023;19(7):1375-1378.
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Cataplejía , Trastornos de Somnolencia Excesiva , Narcolepsia , Neuropéptidos , Humanos , Orexinas , Neuropéptidos/líquido cefalorraquídeo , Péptidos y Proteínas de Señalización Intracelular , Narcolepsia/complicaciones , Narcolepsia/diagnóstico , Trastornos de Somnolencia Excesiva/diagnóstico , Cataplejía/complicaciones , Cataplejía/diagnósticoRESUMEN
OBJECTIVES: Elevated free T3 (FT3) is an important feature for the early diagnosis of several diseases among which Grave's disease or Allan-Hernon-Dudley syndrome. However, there is a lack of age-adapted reference intervals for plasma thyroid hormones in children. We conducted a study to define reference values of peripheral FT3 in children using a commonly used automated immunoassay. METHODS: All thyroid function test (TFT) results from our lab collected during 9 months were extracted anonymously, and reference intervals establishment followed recommendations validated by International Federation of Clinical Chemistry (IFCC). RESULTS: We defined five reference intervals covering the whole pediatric period. Overall, 26.1% of peripheral FT3 measured in children with normal TSH are out of the adult reference range, and 22.2% are upper it leading to misinterpretation. In a 9-month old patient with severe neurodevelopmental disorders, a pathological elevated FT3 has been securely interpreted using the newly established interval. CONCLUSIONS: The study highlights the poor relevance of adult intervals in pediatric cares, as it confirms that plasmatic FT3 is higher during the whole pediatric period. This work reports useful age-adapted reference intervals for free T3 in pediatrics using a widely used electrochemiluminescent Immunoassay (ECLIA) kit.
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Pruebas de Función de la Tiroides , Triyodotironina , Adulto , Humanos , Niño , Lactante , Pruebas de Función de la Tiroides/métodos , Tiroxina , Tirotropina , Hormonas Tiroideas , Valores de ReferenciaRESUMEN
OBJECTIVE: To assess the impact of 3 different ovarian stimulation protocols on surrogate biomarkers of coagulation. DESIGN: Observational multicenter cohort study. SETTING: The study was conducted in assisted reproductive technology (ART) units. PATIENTS: Infertile women undergoing ART in 2017-2019 were included. INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Our primary outcome was the endogenous thrombin potential (ETP) assessed by the calibrated automated thrombogram. The ETP was measured at baseline (T1), on the day of ovulation triggering (T2), and 7 days after triggering (T3). Three protocols were prescribed according to the standards used and without hormonal before treatment: agonist protocol with human chorionic gonadotropin (hCG) trigger (ag-hCG), antagonist protocol with hCG trigger (atg-hCG), or GnRH agonist trigger. The evolution of ETP was compared among groups using a mixed-effects linear regression model. RESULT(S): Sixty-four women with a mean age of 37.8 years participated in the study: of which 24, 16, 24 received ag-hCG, atg-hCG, and GnRH agonist triggers, respectively. As expected, the mean serum estradiol levels in GnRH agonist trigger were statistically higher at T2 and lower at T3 than that for both ag-hCG and atg-hCG. Overall, the ETP evolution over time was statistically different between the groups. Values were similar between groups at T1 and increased at T2 in each group. The greatest difference occurred between T2 and T3 in each group. The ETP continued to increase at T3 in ag-hCG (+110 nM/L × min) and atg-hCG (+171 nM/L × min), but it remained stable in GnRH agonist trigger (-2 nM/L × min). Sex hormone-binding globulin showed persistent increase at T3 despite the fall in estradiol levels, particularly in the GnRH agonist trigger group. CONCLUSION(S): The ag-hCG and atg-hCG groups were associated with a higher hypercoagulable state at T3 than the GnRH agonist trigger group. However, our results show the persistence of a hypercoagulable state after the GnRH agonist triggering despite a sharp drop in estradiol levels. These findings may support the use of GnRH agonist trigger protocol in patients with high thrombotic risk and gives new insight into the fact that coagulation parameters could be disturbed for long time periods. CLINICAL TRIAL REGISTRATION NUMBER: NCT04188444.
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Infertilidad Femenina , Síndrome de Hiperestimulación Ovárica , Embarazo , Humanos , Femenino , Adulto , Síndrome de Hiperestimulación Ovárica/etiología , Síndrome de Hiperestimulación Ovárica/inducido químicamente , Fertilización In Vitro , Infertilidad Femenina/diagnóstico , Infertilidad Femenina/terapia , Infertilidad Femenina/inducido químicamente , Índice de Embarazo , Hormona Liberadora de Gonadotropina , Estudios de Cohortes , Inducción de la Ovulación/métodos , Gonadotropina Coriónica/efectos adversos , EstradiolRESUMEN
OBJECTIVES: Assay of sex hormone binding globulin (SHBG), the main carrier protein for sexual steroids, is prescribed mainly by endocrinologists and performed in specialized laboratories. This study aimed to evaluate the analytic performance of an automated immunochemiluminescent assay (ImmunoDiagnostic Systems (IDS), Boldon, United Kingdom) compared to a manual radioimmunoassay (Cisbio Bioassays, Codolet, France). It further aimed to assess the suitability of the reference values proposed by IDS. MATERIALS AND METHODS: One hundred and forty sera were used to assess the analytic performance of the IDS kit. The coefficients of variation (CV%) for within- and between-run precision were calculated. The reference values provided by IDS were recalculated based on the regression curve equation obtained by comparing the IDS and Cisbio values on Passing-Bablok regression. The new sex-based reference values were then established and their concordance with clinical status was evaluated on Kappa coefficient. RESULTS: The new kit correlated strongly with the reference technique (R2=0.96). Based on the regression line equation, the new reference values for IDS were [20.9-50.6] nmol/L for men and [33.8-71.1] nmol/L for women. Agreement with the reference values we established was 0.933 for men and 0.825 for women, compared with 0.606 and 0.286 for the supplier's values. CONCLUSION: The performance of the IDS kit met the current recommendations and correlated strongly with the Cisbio method. The calculation of new sex-based reference values was needed to correctly classify patients according to androgen status, underlining the importance of systematically checking the reference values provided by suppliers.
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Andrógenos , Globulina de Unión a Hormona Sexual , Masculino , Humanos , Femenino , Globulina de Unión a Hormona Sexual/metabolismo , Valores de Referencia , Reino Unido , FranciaRESUMEN
The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid, with benign non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians and surgeons, but also involves other specialists. Therefore, this consensus statement was established jointly by 3 societies: the French Society of Endocrinology (SFE), French Association of Endocrine Surgery (AFCE) and French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This section deals with the initial work-up for thyroid nodules in adult patients, including clinical and biological evaluation, standardized ultrasound characterization and EU-TIRADS-based nodule selection for fine-needle aspiration biopsy. Indications for thyroid core-biopsies or open surgical biopsies and for cross-sectional imaging of the neck and upper chest are also mentioned.
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Endocrinología , Medicina Nuclear , Neoplasias de la Tiroides , Nódulo Tiroideo , Adulto , Humanos , Nódulo Tiroideo/diagnóstico , Nódulo Tiroideo/terapia , Biopsia con Aguja Fina/métodos , Cintigrafía , Ultrasonografía/métodos , Neoplasias de la Tiroides/terapia , Neoplasias de la Tiroides/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
Pain intensity has been reported to fluctuate during the day in some experimental and clinical conditions, but the mechanisms underlying these fluctuations are unknown. Although the circadian timing system is known to regulate a wide range of physiological functions, its implication in pain regulation is largely unknown. Using highly controlled laboratory constant-routine conditions, we show that pain sensitivity is rhythmic over the 24â h and strongly controlled by the endogenous circadian timing system. We found that the circadian component of pain sensitivity can be modelled with a sinusoidal function, with a maximum in the middle of the night and a minimum in the afternoon. We also found a weak homeostatic control of pain sensitivity, with a linear increase over the 34â h of prolonged wakefulness, which slowly builds up with sleep pressure. Using mathematical modelling, we describe that the circadian system accounts for â¼80% of the full magnitude of pain sensitivity over the 24â h, and that sleep-related processes account for only â¼20%. Overall, our data reveal the neurobiological mechanisms involved in driving the rhythmicity of pain perception in humans. We show that pain sensitivity is controlled by two superimposed processes: a strong circadian component and a modest homeostatic sleep-related component. Our findings highlight the need to consider time of day in pain assessment, and indicate that personalized circadian medicine may be a promising approach to pain management.
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Ritmo Circadiano , Sueño , Ritmo Circadiano/fisiología , Homeostasis , Humanos , Dolor , Sueño/fisiología , Vigilia/fisiologíaRESUMEN
PURPOSE: Measurement of prolactin in clinical laboratories is an important component in the management of patients with pituitary adenoma. Prolactin measurement is known to be sensitive to the high-dose hook effect, in the presence of extremely high prolactin concentrations. This interference is referred to in most recent articles discussing prolactin assays and the management of prolactin-secreting pituitary adenomas. The objective of our study was to evaluate if the high-dose hook effect remains relevant in current practice, when using currently available assays. METHODS: Serum from a patient with a giant macroprolactinoma was assayed using all of the available prolactin assays in France in 2020, using native serum and after dilution. Technical inserts from assays were reviewed to assess the information on analytical principles, numbers of steps, and any reference to high dose hook effect. RESULTS: Fourteen assay kits were studied by 16 laboratories; all were two-site immunometric assays, mostly using one step (11/14). Results obtained after dilution varied from 17,900 µg/L to 86,900 µg/L depending on the assay used. One tested assay was sensitive to the high-dose hook effect leading to a falsely lower prolactin concentration when measuring native serum (150 µg/L compared to 17,900 µg/L after dilution). CONCLUSION: The high-dose hook effect still exists in a very small minority of prolactin assays. The evolution of assay methods may lead to new assays that remain sensitive to this effect in the future. We therefore advise that the hook effect should still be mentioned in prolactin assay recommendations.
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Adenoma , Neoplasias Hipofisarias , Prolactinoma , Humanos , Inmunoensayo , ProlactinaRESUMEN
CONTEXT: Ectopic acromegaly is a consequence of rare neuroendocrine tumors (NETs) that secrete GHRH. This abnormal GHRH secretion drives GH and IGF-1 excess, with a clinical presentation similar to classical pituitary acromegaly. Identifying the underlying cause for the GH hypersecretion in the setting of ectopic GHRH excess is, however, essential for proper management both of acromegaly and the NET. Owing to the rarity of NETs, the imaging characteristics of the pituitary in ectopic acromegaly have not been analyzed in depth in a large series. OBJECTIVE: Characterize pituitary magnetic resonance imaging (MRI) features at baseline and after NET treatment in patients with ectopic acromegaly. DESIGN: Multicenter, international, retrospective. SETTING: Tertiary referral pituitary centers. PATIENTS: Thirty ectopic acromegaly patients having GHRH hypersecretion. INTERVENTION: None. MAIN OUTCOME MEASURE: MRI characteristics of pituitary gland, particularly T2-weighted signal. RESULTS: In 30 patients with ectopic GHRH-induced acromegaly, we found that most patients had hyperplastic pituitaries. Hyperplasia was usually moderate but was occasionally subtle, with only small volume increases compared with normal ranges for age and sex. T2-weighted signal was hypointense in most patients, especially in those with hyperplastic pituitaries. After treatment of the NET, pituitary size diminished and T2-weighted signal tended to normalize. CONCLUSIONS: This comprehensive study of pituitary MRI characteristics in ectopic acromegaly underlines the utility of performing T2-weighted sequences in the MRI evaluation of patients with acromegaly as an additional tool that can help to establish the correct diagnosis.
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Acromegalia , Tumores Neuroendocrinos , Acromegalia/complicaciones , Acromegalia/diagnóstico por imagen , Hormona Liberadora de Hormona del Crecimiento , Humanos , Imagen por Resonancia Magnética , Tumores Neuroendocrinos/complicaciones , Tumores Neuroendocrinos/diagnóstico por imagen , Hipófisis/patología , Estudios RetrospectivosRESUMEN
Cushing's syndrome is defined by prolonged exposure to glucocorticoids, leading to excess morbidity and mortality. Diagnosis of this rare pathology is difficult due to the low specificity of the clinical signs, the variable severity of the clinical presentation, and the difficulties of interpretation associated with the diagnostic methods. The present consensus paper by 38 experts of the French Society of Endocrinology and the French Society of Pediatric Endocrinology and Diabetology aimed firstly to detail the circumstances suggesting diagnosis and the biologic diagnosis tools and their interpretation for positive diagnosis and for etiologic diagnosis according to ACTH-independent and -dependent mechanisms. Secondly, situations making diagnosis complex (pregnancy, intense hypercortisolism, fluctuating Cushing's syndrome, pediatric forms and genetically determined forms) were detailed. Lastly, methods of surveillance and diagnosis of recurrence were dealt with in the final section.