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1.
Endocr Pract ; 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576041

RESUMO

OBJECTIVE: Opioid-induced adrenal insufficiency (OIAI) may develop in patients treated with chronic opioids due suppression of the hypothalamic-pituitary-adrenal axis. Our objective was to describe clinical manifestations, biochemical presentation and clinical course of OIAI. METHODS: A retrospective study of adults diagnosed with OIAI between 2006 and 2018 at an academic center. Opioid daily dose was converted into morphine mg equivalent (MME). RESULTS: Forty patients (n=29, 73% women) taking chronic opioids at a daily median MME dose of 105 (60-200) mg and median duration of 60 (3-360) months were diagnosed with OIAI. Patients reported fatigue (n=29, 73%), musculoskeletal pain (n=21, 53%), and weight loss (n=17, 53%) for a median of 12 (1-132) months prior to diagnosis and only 7.5% (n=3) patients were identified with OIAI through case detection. Biochemical diagnosis of OIAI was based on 1) low morning cortisol, baseline ACTH and/or DHEAS in 59% (n=26) patients or 2) abnormal cosyntropin stimulation test (CST) in 41% (n=14) patients. With glucocorticoid replacement, 16/23 (70%) patients with available follow up experienced improvement in symptoms. Opioids were tapered or discontinued in 15 patients, of whom 10 were followed for adrenal function of which 7 (70%) recovered from OIAI. CONCLUSION: Minimum daily MME in patients diagnosed with OIAI was 60 mg/day. OIAI causes significant morbidity and recognition requires a high level of clinical suspicion. Appropriate glucocorticoid treatment led to improvement of symptoms in 70%. Resolution of OIAI occurred following opioid cessation or reduction.

2.
Neurosurgery ; 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32267504

RESUMO

BACKGROUND: Stereotactic radiosurgery (SRS) is a safe and effective treatment for acromegaly. OBJECTIVE: To improve understanding of clinical and dosimetric factors predicting biochemical remission. METHODS: A single-institution cohort study of nonsyndromic, radiation-naïve patients with growth hormone-producing pituitary adenomas (GHA) having single-fraction SRS between 1990 and 2017. Exclusions were treatment with pituitary suppressive medications at the time of SRS, or <24 mo of follow-up. The primary outcome was biochemical remission-defined as normalization of insulin-like growth factor-1 index (IGF-1i) off suppression. Biochemical remission was assessed using Cox proportional hazards. Prior studies reporting IGF-1i were assessed via systematic literature review and meta-analysis using random-effect modeling. RESULTS: A total of 102 patients met study criteria. Of these, 46 patients (45%) were female. The median age was 49 yr (interquartile range [IQR] = 37-59), and the median follow-up was 63 mo (IQR = 29-100). The median pre-SRS IGF-1i was 1.66 (IQR = 1.37-3.22). The median margin dose was 25 Gy (IQR = 21-25); the median estimated biologically effective dose (BED) was 169.49 Gy (IQR = 124.95-196.00). Biochemical remission was achieved in 58 patients (57%), whereas 22 patients (22%) had medication-controlled disease. Pre-SRS IGF-1i ≥ 2.25 was the strongest predictor of treatment failure, with an unadjusted hazard ratio (HR) of 0.51 (95% CI = 0.26-0.91, P = .02). Number of isocenters, margin dose, and BED predicted remission on univariate analysis, but after adjusting for sex and baseline IGF-1i, only BED remained significant-and was independently associated with outcome in continuous (HR = 1.01, 95% CI = 1.00-1.01, P = .02) and binary models (HR = 2.27, 95% CI = 1.39-5.22, P = .002). A total of 24 patients (29%) developed new post-SRS hypopituitarism. Pooled HR for biochemical remission given subthreshold IGF-1i was 2.25 (95% CI = 1.33-3.16, P < .0001). CONCLUSION: IGF-1i is a reliable predictor of biochemical remission after SRS. BED appears to predict biochemical outcome more reliably than radiation dose, but confirmatory study is needed.

4.
Am J Clin Pathol ; 152(4): 502-511, 2019 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-31305880

RESUMO

OBJECTIVES: Long-term follow-up is important for determining performance characteristics of thyroid fine-needle aspiration (FNA). METHODS: Histologic or 3 or more years of clinical follow-up was used to calculate performance characteristics of thyroid FNA before and after implementation of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) classification was also investigated. RESULTS: Follow-up was obtained for 1,277/1,134 and 1,616/1,393 aspirates/patients (median clinical follow-up, 9.9 and 4.4 years, pre- and post-TBSRTC, respectively). Nondiagnostic, suspicious for follicular neoplasm, and suspicious for malignancy (SFM) diagnoses decreased and benign diagnoses increased post-TBSRTC, while atypical rate remained less than 1%. Negative predictive value for benign nodules and positive predictive value (PPV) for SFM increased significantly. Eleven nodules were reclassified as NIFTP, slightly decreasing PPV/risk of malignancy (ROM). CONCLUSIONS: Appropriate ROM for thyroid FNA can be achieved through application of TBSRTC terminology with minimal use of atypical category.


Assuntos
Adenocarcinoma Folicular/patologia , Câncer Papilífero da Tireoide/patologia , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , Biópsia por Agulha Fina , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade
5.
Endocr Pract ; 25(10): 1012-1021, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31170362

RESUMO

Objective: Opioid-induced adrenal insufficiency (OIAI) is reported in up to 29% of chronic opioid users through suppression of the hypothalamus-pituitary-adrenal axis. Unrecognized adrenal insufficiency leads to increased morbidity and potentially death; thus, healthcare provider (HCP) awareness of OIAI is crucial. The aim of the present study was to assess the knowledge and current practices of HCPs regarding OIAI and to identify factors associated with decreased awareness. Methods: We carried out a cross-sectional, anonymous survey of HCPs in internal medicine specialties that prescribe or care for patients taking chronic opioids. Results: Of 91 (30%) participants who completed the survey, 51 (56%) were men and 52 (57%) were in training. Most responders were general internal medicine providers (n = 33, 36%), followed by endocrinologists (n = 13, 14%) and various other specialties (n = 45, 49%). While 61 (67%) of respondents prescribed opioids, only 17 (19%) were comfortable in their knowledge of opioid side effects. Among nonendocrine providers, 53 (68%) identified adrenal insufficiency as a known opioid-induced endocrinopathy. Compared to other providers, endocrinologists were more likely to recognize opioid-related endocrinopathies (69% versus 24%, P = .01) and to identify the correct symptoms for OIAI (38% versus 9%, P <.001). One in four nonendocrine providers reported discomfort in managing glucocorticoid replacement therapy. The majority (60%) of providers indicated that online resources and continuing medical education lectures would improve knowledge of OIAI. Conclusion: Our study identified several deficiencies in HCP knowledge of opioid-induced endocrine effects, especially in nonendocrine providers. As many symptoms of OIAI overlap with those of underlying conditions, OIAI could be potentially missed, highlighting the need to further educate providers about opioid-induced endocrinopathies. Abbreviations: ACTH = adrenocorticotropic hormone; AI = adrenal insufficiency; CME = continuing medical education; HCP = healthcare professional; OIAI = opioid-induced adrenal insufficiency.


Assuntos
Insuficiência Adrenal , Dor Crônica , Analgésicos Opioides , Estudos Transversais , Feminino , Pessoal de Saúde , Humanos , Masculino
6.
Endocr Pract ; 25(4): 340-352, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30995432

RESUMO

Objective: To describe outcomes of patients with giant prolactinoma (≥4 cm) and identify predictors of therapeutic response. Methods: In this retrospective study, complete biochemical and structural response were defined as prolactin (PRL) ≤25 ng/mL and no visible tumor at follow-up, respectively. Results: Giant prolactinoma (median size, 4.8 cm [range, 4 to 9.8 cm]; median PRL, 5,927 ng/mL [range, 120 to 100,000 ng/mL]) was diagnosed in 71 patients. Treatments included: dopamine agonists (DAs) (n = 70, 99%), surgery (n = 30, 42%), radiation (n = 10, 14%), and somatostatin analogs (n = 2, 3%). Patients treated with DA monotherapy were older compared with those who received subsequent therapies (47 years vs. 28 years; P = .003) but had similar initial PRL and tumor size. Surgically managed patients were younger compared with the nonsurgical group (35 years vs. 46 years; P = .02) and had lower initial PRL (3,121 ng/mL vs. 6,920 ng/mL; P = .02), yet they had similar tumor response. Hypopituitarism was more common following surgery compared to medical management: adrenal insufficiency (69% vs. 27%; P<.001), hypothyroidism (67% vs. 38%; P = .02), growth hormone deficiency (24% vs. 6%; P = .04), and diabetes insipidus (17% vs. 3%; P = .04). Therapeutic response did not correlate with sex, age, initial PRL, tumor size, or first-line therapy mode. At median follow-up of 4.8 years, the median PRL was 18.3 ng/mL (range, 0.6 to 12,680 ng/mL), and final volume was 0.9 cm3 (range, 0 to 43.0 cm3). In those with available data, 36/65 (55%) patients achieved PRL normalization, and 16/61 (26%) had no visible tumor at follow-up. Conclusion: Most patients with giant prolactinoma have excellent response to DA. Sex, age, initial PRL, and tumor size do not predict therapeutic response. Abbreviations: BRC = bromocriptine; CAB = cabergoline; CSF = cerebrospinal fluid; DA = dopamine agonist; MRI = magnetic resonance imaging; PRL = prolactin.


Assuntos
Neoplasias Hipofisárias , Prolactinoma , Adulto , Bromocriptina , Agonistas de Dopamina , Ergolinas , Humanos , Pessoa de Meia-Idade , Prolactina , Estudos Retrospectivos
7.
Curr Opin Endocrinol Diabetes Obes ; 26(3): 133-138, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30870182

RESUMO

PURPOSE OF REVIEW: Despite the declaration of an opioid epidemic, opioid use remains prevalent. Side-effects of chronic opioid use continue to be problematic. Opioid-induced endocrinopathies have been well documented, yet opioid-induced adrenal insufficiency (OIAI) remains underappreciated. This review summarizes what is currently known regarding the prevalence, predictive factors for the development and effect of treatment of OIAI. RECENT FINDINGS: Although several case reports have highlighted the development of adrenal crisis among those receiving chronic opioids, only a few studies have systematically assessed patients for OIAI. The heterogeneity of these small studies presents challenges when trying to assess prevalence of or potential risk factors for OIAI. The estimated prevalence of OIAI among those treated with chronic opioids ranges from 8.3 to 29% and is more likely in those receiving higher doses of opioids. Reduced health-related quality of life variables and altered pain perception has been associated with lower cortisol levels; however, the effect of glucocorticoid replacement on the parameters remains unknown. SUMMARY: Further research is critical to better identify those at greatest risk and guide optimal management of OIAI. Frontline providers should remain vigilant for possibility of OIAI among chronic opioid users.


Assuntos
Insuficiência Adrenal/induzido quimicamente , Insuficiência Adrenal/epidemiologia , Analgésicos Opioides/efeitos adversos , Insuficiência Adrenal/complicações , Insuficiência Adrenal/tratamento farmacológico , Epidemias , Glucocorticoides/uso terapêutico , Terapia de Reposição Hormonal , Humanos , Transtornos Relacionados ao Uso de Opioides/complicações , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Prevalência , Qualidade de Vida
8.
Mayo Clin Proc ; 93(7): 937-944, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29976376

RESUMO

One in 10 Americans experience chronic pain. Although opioids do play a role in the management of pain, long-term opioid use may lead to adverse effects. Endocrine-related adverse effects have been described but remain poorly recognized. Opioid-induced adrenal insufficiency occurs because of suppression of hypothalamic-pituitary-adrenal communication and may be challenging to diagnose but has been reported in 9% to 29% of patients receiving long-term opiate therapy. Little data exist to guide case detection and patient management. Treatment includes cessation of opiates (the inciting factor) if possible and glucocorticoid replacement.


Assuntos
Insuficiência Adrenal/induzido quimicamente , Insuficiência Adrenal/diagnóstico , Analgésicos Opioides/efeitos adversos , Insuficiência Adrenal/terapia , Humanos
9.
Endocr Pract ; 24(7): 668-676, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30048170

RESUMO

OBJECTIVE: Uncontrolled acromegaly is associated with increased morbidity and mortality. Despite multimodal therapeutic options, adequate control can be challenging and lead to prolonged exposure to growth hormone excess. The aim of this study was to assess treatment patterns and outcomes in patients with acromegaly following surgery at a single institution. METHODS: A retrospective analysis of response to treatment modalities for patients with a new diagnosis of acromegaly at the Mayo Clinic in Rochester, Minnesota, from 1995-2015. RESULTS: A total of 245 patients with newly diagnosed acromegaly (mean age at diagnosis, 47 ± 14 years; mean follow-up, 5.5 ± 5 years) were evaluated. Primary surgical intervention was performed in 236 patients; 117 (54%) did not achieve remission. Among those with ≥3 months follow-up, 76/217 (35%) patients required three or more forms of treatment. Mean tumor size at diagnosis was 1.6 ± 0.8 cm (80% macroadenomas), and 35% (75/217) had cavernous sinus invasion on pre-operative imaging. The most common second-line treatment was radiation treatment (RT) (50%, 59/117). Among those with persistent disease following surgery, a normal insulin-like growth factor 1 (IGF-1) was achieved in 52% (61/117), with a median time to acromegaly control of 4.5 years. The rate of IGF-1 normalization was 2.1-fold higher in those who received RT compared to those who did not. CONCLUSION: In patients with persistent acromegaly following surgery, multiple treatment modalities, including RT, may be required to achieve remission. Treatment outcome uncertainty and the need for multiple interventions add to the disease burden associated with persistent acromegaly. ABBREVIATIONS: CI = confidence interval; GH = growth hormone; IGF-1 = insulin like growth factor-1; KM = Kaplan-Meier; RT = radiation treatment.


Assuntos
Acromegalia , Adulto , Terapia Combinada , Hormônio do Crescimento Humano , Humanos , Fator de Crescimento Insulin-Like I , Pessoa de Meia-Idade , Minnesota , Estudos Retrospectivos , Resultado do Tratamento
10.
Thyroid ; 27(10): 1332-1334, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28747092

RESUMO

We describe a family with multiple endocrine neoplasia type 2A (MEN2A) caused by the D631Y RET mutation resulting in an atypical phenotype. The index case was a 24-year-old man with history of recurrent anaplastic ependymoma incidentally found to have the D631Y RET mutation. At first assessment, four family members had evidence of large pheochromocytomas. One patient was found to have micromedullary thyroid cancer at 79 years of age. None of the patients had primary hyperparathyroidism. Patients with MEN2A caused by a D631Y RET mutation most commonly present with pheochromocytomas. Medullary thyroid cancer is a less common part of the syndrome when compared with other RET mutations.


Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Neoplasia Endócrina Múltipla Tipo 2a/genética , Feocromocitoma/genética , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idoso , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 2a/patologia , Feocromocitoma/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto Jovem
11.
Endocr Pract ; 23(8): 923-928, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28614004

RESUMO

OBJECTIVE: The 72-hour fast is used to document Whipple's triad and understand the mechanism of hypoglycemia. Although hypoglycemia develops within 24 hours in the majority of fasts, identifying possible determinants of fast duration may help to predict the need for admission. Therefore, we determined the relation between anthropometric features on fast duration and assessed end of fast parameters on maximal tumor size, extent of disease, or tumor recurrence. METHODS: A retrospective analysis of patients with insulinoma in the past 25 years who underwent a 72-hour fast was conducted. Electronic medical records were reviewed to obtain anthropometric patient data and tumor characteristics. RESULTS: A total of 233 patients underwent the 72-hour fast. The mean age at diagnosis was 50 ± 16 years, with a body mass index (BMI) of 29 ± 7 kg/m2, and 66% (153 of 233) were female. Duration of fast was not associated with gender (P = .2), age (P = .3), or BMI (P = .7). A shorter fast duration was inversely related to end of fast C-peptide (P = .0075) but not insulin (P = .13) or proinsulin (P = .28) concentration. End of fast C-peptide was associated with increased tumor size (P = .036) and multiplicity (P =.01). Proinsulin was associated with increased tumor size (P<.01) and malignancy (P = .018). CONCLUSION: Duration of fast was not significantly related age, gender, weight, or BMI, although end-of-fast C-peptide and proinsulin may provide some information regarding tumor characteristics. Consequently, the duration of fast cannot be predicted a priori and should be allowed to run for the planned length unless hypoglycemia develops. Abbreviation: BMI = body mass index.


Assuntos
Glicemia/metabolismo , Peptídeo C/metabolismo , Jejum/metabolismo , Hipoglicemia/metabolismo , Insulina/metabolismo , Insulinoma/metabolismo , Neoplasias Pancreáticas/metabolismo , Adulto , Idoso , Antropometria , Índice de Massa Corporal , Feminino , Humanos , Insulinoma/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Proinsulina/metabolismo , Estudos Retrospectivos , Fatores de Tempo , Carga Tumoral
12.
Am J Med ; 130(5): 603-605, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28011308

RESUMO

BACKGROUND: Zollinger-Ellison syndrome is a rare cause of tumoral hypergastrinemia; 1 of 5 patients with this syndrome also has multiple endocrine neoplasia type 1. The diagnosis of this disease is complicated by the widespread use of proton pump inhibitors that can elevate serum gastrin levels, the cornerstone for biochemical diagnosis. Abrupt discontinuation of proton pump inhibitors could lead to adverse outcomes. Clinician awareness of the relationship between Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1 could lead to a safer diagnostic pathway. METHODS: We conducted a retrospective review of a cohort of patients with multiple endocrine neoplasia type 1. RESULTS: There were 287 patients with multiple endocrine neoplasia type 1 (73 with gastrinoma) evaluated between 1997 and 2014. Two patients experienced adverse events after proton pump inhibitor therapy was discontinued to re-measure serum gastrin level during the evaluation of severe peptic ulcer disease. In both cases, the diagnosis of multiple endocrine neoplasia type 1 was made after proton pump therapy was discontinued. CONCLUSION: Abrupt discontinuation of proton pump therapy can lead to adverse outcomes in patients with Zollinger-Ellison syndrome. Clinical assessment for features of multiple endocrine neoplasia type 1 (eg, serum calcium levels, personal and family history of hypercalcemia, pituitary or pancreatic tumors) could identify patients with higher risk for a tumoral source of hypergastrinemia where imaging studies can help support the diagnosis without the potential side effects of abrupt discontinuation of proton pump inhibitor therapy.


Assuntos
Neoplasia Endócrina Múltipla Tipo 1/diagnóstico , Síndrome de Zollinger-Ellison/diagnóstico , Adulto , Úlcera Duodenal/tratamento farmacológico , Feminino , Gastrinas/sangue , Refluxo Gastroesofágico/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/uso terapêutico , Estudos Retrospectivos , Suspensão de Tratamento , Síndrome de Zollinger-Ellison/sangue
13.
Endocr Pract ; 23(1): 37-45, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27682355

RESUMO

OBJECTIVE: Prolactinomas are primarily treated with medical therapy. Given the efficacy of dopamine agonists (DAs), surgery has remained a second-line treatment option. Despite medical therapy, some tumors display resistance and/or patients maybe intolerant of DA and require alternative treatment options. We examined the indications, efficacy, and safety of pituitary surgery for the treatment of prolactinomas. METHODS: We performed a retrospective analysis of all patients who had surgery for a prolactinoma at our institution from January 1993 to October 2014. RESULTS: Seventy-eight patients (46 females, mean age 32 years) with a median follow-up of 12 months were analyzed. Macroprolactinomas accounted for 65% (51/78) of tumors. The most common indication for surgery in microprolactinomas was medication intolerance (37%, 10/27) and medication failure (33%, 17/51) in macroprolactinomas. DA therapy had been tried in 76% (59/78) patients prior to surgery. Following surgery, long-term remission was seen in 72% (18/25) of micro-adenomas and 20% (10/49) of macro-adenomas (32% [10/32] in those without cavernous sinus invasion). Despite persistent disease in those with macro-adenomas (34% [13/38]) were able to remain off medication. Early surgical failure was more common in males (P = .004) and those with large (P≤.001) or atypical (P = .003) adenomas. CONCLUSION: Surgery can result in prolonged remission in 72% of microprolactinomas. Despite lower remission rates among macroprolactinomas, a third of patients with persistent disease did not require medical therapy. Therefore, surgery remains an alternative effective treatment option, particularly for those who are intolerant or resistant to medical therapy. ABBREVIATIONS: ACTH = adrenocorticotropic hormone CI = confidence interval CSF = cerebrospinal fluid DA = dopamine agonist IQR = interquartile range MIB-1 = methylation inhibiting binding protein-1 VF = visual field.


Assuntos
Procedimentos Neurocirúrgicos , Neoplasias Hipofisárias/cirurgia , Prolactinoma/cirurgia , Adulto , Bromocriptina/uso terapêutico , Cabergolina , Agonistas de Dopamina/uso terapêutico , Ergolinas/uso terapêutico , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/patologia , Prolactinoma/diagnóstico por imagem , Prolactinoma/tratamento farmacológico , Prolactinoma/patologia , Indução de Remissão , Estudos Retrospectivos , Falha de Tratamento , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
14.
Endocrine ; 56(2): 267-278, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27815769

RESUMO

Growth hormone replacement therapy has benefits for patients with hypopituitarism. The safety profile in regard to tumor recurrence or progression, development of secondary malignancies, or cerebrovascular stroke is still an area of debate. A comprehensive search of multiple databases-MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus was conducted through August 2015. Eligible studies that evaluated long-term adverse events in adult patients with hypopituitarism treated with growth hormone replacement therapy and reported development of pituitary tumor recurrence or progression, secondary malignancies, or cerebrovascular stroke were selected following a predefined protocol. Reviewers, independently and in duplicate, extracted data and assessed the risk of bias. Random-effects meta-analysis was used to pool relative risks and 95 % confidence intervals. We included 15 studies (published 1995-2015) that reported on 46,148 patients. Compared to non-replacement, growth hormone replacement therapy in adults with hypopituitarism was not associated with statistically significant change in pituitary tumor progression or recurrence (relative risk, 0.77; 95 % confidence interval, 0.53-1.13) or development of secondary malignancy (relative risk, 0.99; 95 % confidence interval, 0.70-1.39). In two retrospective studies, there was higher risk of stroke in patients who did not receive replacement (relative risk, 2.07; 95 % confidence interval, 1.51-2.83). The quality of evidence is low due to study limitations and imprecision. This systematic review and meta-analysis supports the overall safety of growth hormone therapeutic use in adults with hypopituitarism with no clear evidence of increased risk of pituitary tumor recurrence, malignancy, or stroke.


Assuntos
Hormônio do Crescimento Humano/efeitos adversos , Hipopituitarismo/tratamento farmacológico , Recidiva Local de Neoplasia/induzido quimicamente , Neoplasias Hipofisárias/induzido quimicamente , Acidente Vascular Cerebral/induzido quimicamente , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Recidiva Local de Neoplasia/patologia , Neoplasias Hipofisárias/patologia , Acidente Vascular Cerebral/patologia
15.
J Endocrinol ; 231(1): 71-80, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27519211

RESUMO

Insulin-like growth factors (IGFs) are implicated in the development of diabetic nephropathy (DN) and are shown to increase proliferation and extracellular matrix production in mesangial cells. The IGF system is complex and is composed of ligands, receptors, six binding proteins (IGF BPs) and a novel zinc metalloproteinase - pregnancy-associated plasma protein (PAPP)-A. PAPP-A increases the local bioavailability of IGF through the cleavage of IGF BP-4. Mesangial expansion is a major component of DN, and PAPP-A is shown to be increased in the glomeruli of patients with DN. Therefore, we determined the expression of PAPP-A and components of the IGF system in normal human mesangial cells (HMCs) and their regulation by factors known to be involved in DN. Under basal conditions, HMCs expressed PAPP-A, IGF1 receptor and all six IGF BPs. Interleukin (IL)-1ß was the most potent stimulus for PAPP-A expression (5-fold) followed by tumor necrosis factor (TNF)-α (2.5-fold). This PAPP-A was secreted, cell associated and proteolytically active. IL1ß also increased IGF BP-1expression (3-fold) with either reduction or no effect on other IGF BPs. Generally, TNF-α treatment decreased IGF BP expression. No treatment effect on PAPP-A or IGF BPs was seen with IL6, IGFs, advanced glycation end products or prolonged hyperglycemia. In addition, stimulation of HMCs with IGF1 alone or IGF1 complexed to wild-type, but not protease-resistant, IGF BP-4 led to increased [(3)H]-thymidine incorporation. In conclusion, these novel findings of PAPP-A and its regulation by proinflammatory cytokines, as well as the comprehensive analysis of the IGF system regulation in HMCs, suggest a mechanism by which inflammatory states such as DN can impact IGF activity in the kidney.


Assuntos
Nefropatias Diabéticas/metabolismo , Mesângio Glomerular/metabolismo , Proteína Plasmática A Associada à Gravidez/fisiologia , Animais , Citocinas/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Inflamação , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Camundongos , Receptor IGF Tipo 1/metabolismo
16.
Endocr Pract ; 20(10): 1032-6, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24793919

RESUMO

OBJECTIVE: Thyroglobulin (Tg) quantitation by immunometric assays is compromised by anti-thyroglobulin antibodies (TgAbs), potentially resulting in falsely low Tg concentrations. TgAb screening is recommended when measuring Tg, but current TgAb immunoassays do not detect all possible TgAbs in circulation. We assessed the impact of a change in TgAb assay on apparent disease status of patients with differentiated thyroid carcinoma (DTC). METHODS: Patients seen at the Mayo Clinic, Rochester, Minnesota, for follow-up of DTC, who had been tested using 2 different TgAb assays (Beckman Access and Roche Elecsys) were identified. Electronic medical records were reviewed to evaluate any impact the change in TgAb assay had on clinical disease status assessment and follow-up. RESULTS: A total of 1,457 patients were tested using both assays. A change in TgAb status was found in 124 (8.5%) patients; a total of 117 patients who were TgAb-negative on the Beckman assay became TgAb-positive with the Roche assay. Additional testing was performed in 5 of these patients. Seven patients previously considered TgAb-positive were now TgAb-negative. In all 7 cases, physicians documented that they considered these patients now to be truly TgAb-negative and free of disease. CONCLUSION: Discrepancies in TgAb status are seen when using different TgAb assays. Relying on Tg and TgAb measurements to determine disease status may lead to underestimation of residual cancer. A multimodal (clinical, biochemical, and radiologic) approach to follow up on patients with DTC should be continued, pending the development of Tg quantitation methods that are highly sensitive and not affected by TgAb interference.

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