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1.
Pituitary ; 27(4): 381-388, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38833044

RESUMEN

PURPOSE: A series of consensus guidelines on medical treatment of acromegaly have been produced in the last two decades. However, little information is available on their application in clinical practice. Furthermore, international standards of acromegaly care have not been published. The aim of our study was to report current standards of care for medical therapy of acromegaly, using results collected through an audit performed to validate criteria for definition of Pituitary Tumor Centers of Excellence (PTCOE). METHODS: Details of medical treatment approaches to acromegaly were voluntarily provided by nine renowned international centers that participated in this audit. For the period 2018-2020, we assessed overall number of acromegaly patients under medical treatment, distribution of patients on different treatment modalities, overall biochemical control rate with medical therapy, and specific control rates for different medical treatment options. RESULTS: Median number of total patients and median number of new patients with acromegaly managed annually in the endocrinology units of the centers were 206 and 16.3, respectively. Median percentage of acromegaly patients on medical treatment was 48.9%. Among the patients on medical treatment, first-generation somatostatin receptor ligand (SRL) monotherapy was used with a median rate of 48.7%, followed by combination therapies with a median rate of 29.3%. Cabergoline monotherapy was used in 6.9% of patients. Pegvisomant monotherapy was used in 7 centers and pasireotide monotherapy in 5 centers, with median rates of 7.9% and 6.3%, respectively. CONCLUSIONS: Current standards of care in PTCOEs include use of first-generation SRLs as the first medical option in about 50% of patients, as recommended by consensus guidelines. However, some patients are kept on this treatment despite inadequate control suggesting that cost-effectiveness, availability, patient preference, side effects, and therapeutic inertia may play a possible role also in PTCOE. Moreover, at odds with consensus guidelines, other monotherapies for acromegaly appear to have a marginal role as compared to combination therapies as extrapolated from PTCOE practice data. Presence of uncontrolled patients in each treatment category suggest that further optimization of medical therapy, as well as use of other therapeutic tools such as radiosurgery may be needed.


Asunto(s)
Acromegalia , Neoplasias Hipofisarias , Nivel de Atención , Acromegalia/tratamiento farmacológico , Acromegalia/terapia , Humanos , Neoplasias Hipofisarias/terapia , Neoplasias Hipofisarias/tratamiento farmacológico , Femenino , Masculino , Cabergolina/uso terapéutico , Persona de Mediana Edad , Adulto
2.
Pituitary ; 26(5): 583-596, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37640885

RESUMEN

PURPOSE: The Pituitary Society established the concept and mostly qualitative parameters for defining uniform criteria for Pituitary Tumor Centers of Excellence (PTCOEs) based on expert consensus. Aim of the study was to validate those previously proposed criteria through collection and evaluation of self-reported activity of several internationally-recognized tertiary pituitary centers, thereby transforming the qualitative 2017 definition into a validated quantitative one, which could serve as the basis for future objective PTCOE accreditation. METHODS: An ad hoc prepared database was distributed to nine Pituitary Centers chosen by the Project Scientific Committee and comprising Centers of worldwide repute, which agreed to provide activity information derived from registries related to the years 2018-2020 and completing the database within 60 days. The database, provided by each center and composed of Excel® spreadsheets with requested specific information on leading and supporting teams, was reviewed by two blinded referees and all 9 candidate centers satisfied the overall PTCOE definition, according to referees' evaluations. To obtain objective numerical criteria, median values for each activity/parameter were considered as the preferred PTCOE definition target, whereas the low limit of the range was selected as the acceptable target for each respective parameter. RESULTS: Three dedicated pituitary neurosurgeons are preferred, whereas one dedicated surgeon is acceptable. Moreover, 100 surgical procedures per center per year are preferred, while the results indicated that 50 surgeries per year are acceptable. Acute post-surgery complications, including mortality and readmission rates, should preferably be negligible or nonexistent, but acceptable criterion is a rate lower than 10% of patients with complications requiring readmission within 30 days after surgery. Four endocrinologists devoted to pituitary diseases are requested in a PTCOE and the total population of patients followed in a PTCOE should not be less than 850. It appears acceptable that at least one dedicated/expert in pituitary diseases is present in neuroradiology, pathology, and ophthalmology groups, whereas at least two expert radiation oncologists are needed. CONCLUSION: This is, to our knowledge, the first study to survey and evaluate the activity of a relevant number of high-volume centers in the pituitary field. This effort, internally validated by ad hoc reviewers, allowed for transformation of previously formulated theoretical criteria for the definition of a PTCOE to precise numerical definitions based on real-life evidence. The application of a derived synopsis of criteria could be used by independent bodies for accreditation of pituitary centers as PTCOEs.


Asunto(s)
Enfermedades de la Hipófisis , Neoplasias Hipofisarias , Humanos , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/cirugía , Proyectos Piloto , Hipófisis
3.
Pituitary ; 24(6): 943-953, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34173129

RESUMEN

PURPOSE: Results are presented from 2 to 3 trials investigating oral octreotide capsules (OOC) as an alternative to injectable somatostatin receptor ligands (iSRLs) in the treatment of acromegaly. METHODS: CH-ACM-01 was an open-label trial (N = 155) and CHIASMA OPTIMAL was a double-blind placebo-controlled (DPC) trial (N = 56), both investigating OOC as maintenance therapy for patients with acromegaly who were biochemical responders receiving iSRLs. RESULTS: Baseline characteristics in both trials reflected those expected of patients with acromegaly responding to treatment and were similar between trials, despite differences in inclusion criteria. OOC demonstrated a consistent degree of biochemical response across trials, with 65% of patients in CH-ACM-01 maintaining response during the core period and 64% of patients in CHIASMA OPTIMAL at the end of the DPC. Mean insulin-like growth factor I (IGF-I) levels remained within inclusion criteria at the end of treatment in both trials. Of 110 patients entering the fixed-dose phase in CH-ACM-01, 80% maintained or improved acromegaly symptoms from baseline to the end of treatment. Over 85% of patients in both trials elected to continue into the extension phases. OOC were found to be well tolerated across both trials, and no dose-related adverse events were observed. CONCLUSIONS: OOC demonstrated remarkably consistent results for biochemical response, durability of response, and preference to continue with oral treatment across these 2 complementary landmark phase 3 trials, despite differences in the design of each. Trial registration NCT03252353 (August 2017), NCT01412424 (August 2011).


Asunto(s)
Acromegalia , Hormona de Crecimiento Humana , Acromegalia/tratamiento farmacológico , Cápsulas , Humanos , Factor I del Crecimiento Similar a la Insulina , Octreótido/uso terapéutico , Somatostatina
4.
Pituitary ; 23(5): 498-506, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32451986

RESUMEN

PURPOSE: Pegvisomant (PEG) is an effective therapy for acromegaly. Its safety in women seeking fertility and during pregnancy has been scarcely reported. METHODS: A retrospective chart review was performed in three patients with acromegaly who received PEG while attempting to conceive. Published studies regarding this topic were analyzed. RESULTS: Four pregnancies in three women with acromegaly are reported. In the first patient, PEG was withdrawn three days before embryo transfer in her first pregnancy and 2 weeks prior to transfer in the second pregnancy. Each transfer resulted in a healthy full-term newborn. In the second and third patients, PEG was withdrawn at diagnosis of pregnancy. No fetal complications occurred during gestations which resulted in three full-term newborns (one single and one twin pregnancy). No abnormalities in development were found in the five live births described. Few cases of pregnancies in women exposed to PEG have been reported and therefore safety cannot be clearly established. In this series, all four pregnancies had good outcomes with discontinuation of the drug before or at first knowledge of conception. A review of the literature reveals no evident drug-related abnormalities in the offspring, even in the few women with continued use of PEG throughout pregnancy. CONCLUSION: Preconception therapy with PEG resulted in successful fertility outcomes. Although few cases have been reported, these four pregnancies with PEG use prior to or at the time of conception were not associated with significant maternal or fetal complications. More studies are needed to establish the safety of PEG preconception.


Asunto(s)
Acromegalia/tratamiento farmacológico , Hormona de Crecimiento Humana/análogos & derivados , Acromegalia/metabolismo , Adulto , Femenino , Hormona del Crecimiento , Hormona de Crecimiento Humana/efectos adversos , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Persona de Mediana Edad , Embarazo
6.
J Clin Endocrinol Metab ; 81(12): 4388-95, 1996 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-8954047

RESUMEN

Despite recent advances in the understanding of the pathophysiology of Kallmann's syndrome (KS), the patterns of inheritance in the majority of cases of GnRH deficiency in human subjects remain unclear. To define further the genetic and phenotypic variability of this syndrome, detailed family histories were reviewed in 106 cases of GnRH deficiency with or without anosmia [i.e. KS or idiopathic hypogonadotropic hypogonadism (IHH)]. The great majority of cases appeared to be sporadic, with only 19 probands (18%) having at least 1 family member with GnRH deficiency. However, of the families in which the proband was the sole member affected by KS or IHH, 9 had individuals with isolated anosmia, and 8 had a strong history of delayed puberty. If these phenotypes were considered as alternative manifestations of the same genetic defect that presented as KS or IHH in the proband, 34% of the cases in the present series could be considered familial. In these families, the most likely modes of transmission were assessed in several ways, including analysis of probands with KS as a distinct subset, and separate determinations based upon whether the phenotypes of isolated anosmia and/or delayed puberty were considered relevant to the inheritance of KS or IHH. The proportion of familial cases that could be attributable to an X-linked mode of inheritance was no greater than 36% in any of these analyses. We conclude that 1) most cases of GnRH deficiency in humans are sporadic and, thus, could represent new mutations; 2) the X-linked form is the least common among familial cases of KS or IHH; 3) defects in at least two autosomal genes can results in GnRH deficiency; and 4) associated clinical defects may well represent clues to the nature and/or location of these autosomal genes.


Asunto(s)
Hormona Liberadora de Gonadotropina/deficiencia , Hipogonadismo/genética , Síndrome de Kallmann/genética , Femenino , Ligamiento Genético , Humanos , Masculino , Trastornos del Olfato/genética , Fenotipo , Cromosoma X
7.
J Clin Endocrinol Metab ; 81(10): 3520-5, 1996 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8855795

RESUMEN

To evaluate the physiology of inhibin B in the human male, we measured serum concentrations in normal adult men and men with isolated GnRH deficiency before and during long-term replacement with pulsatile GnRH. At baseline, inhibin B levels in the GnRH-deficient men (n = 31) were significantly lower than normal controls (85 +/- 10 pg/mL vs. 239 +/- 14 pg/mL; P < .01) and correlated positively with pretreatment testicular volume (r = .80, P = .001) and a history of spontaneous puberty, suggesting additional maturational influences on the both testicular volume and inhibin B secretion. Pulsatile GnRH administration was associated with significant increases in inhibin B, with levels averaging 108 +/- 7 pg/mL when serum LH, FSH, and T concentrations had reached the normal adult male range (n = 22; P = .02 vs. baseline). Continued GnRH administration for at least an additional year was not associated with further increases in inhibin B concentrations. Throughout the course of long-term pulsatile GnRH replacement, serum FSH levels were negatively correlated with inhibin B concentrations (e.g. r = -.71, P < 0.01; n = 14 treated 12 months after normalization of T). Although inhibin B concentrations did not correlated with sperm density during therapy, rates of fertility were higher in patients with higher baseline levels (inhibin B > or = 60 pg/mL). Increases in serum concentrations of inhibin B occurring during GnRH replacement demonstrate the gonadotropin regulation of gonadal inhibin B secretion. However, the variation in baseline inhibin B levels before GnRH administration suggests an additional gonadotropin-independent level of modulation. The negative correlation between FSH and inhibin B secretion in GnRH-deficient men receiving long-term GnRH replacement is consistent with a putative role of inhibin B in the negative feedback regulation of FSH, although direct confirmation of this role requires further investigation.


Asunto(s)
Hormona Liberadora de Gonadotropina/deficiencia , Hormona Liberadora de Gonadotropina/uso terapéutico , Hipogonadismo/tratamiento farmacológico , Inhibinas/metabolismo , Pubertad/fisiología , Testículo/patología , Adolescente , Adulto , Hormona Folículo Estimulante/sangre , Hormona Liberadora de Gonadotropina/administración & dosificación , Humanos , Hipogonadismo/patología , Hipogonadismo/fisiopatología , Hormona Luteinizante/sangre , Masculino , Periodicidad , Testosterona/sangre
8.
J Clin Endocrinol Metab ; 81(10): 3692-6, 1996 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8855824

RESUMEN

To examine the role of inhibin B in the feedback regulation of FSH secretion in the human male, we determined serial levels in 18 men with idiopathic hypogonadotropic hypogonadism (IHH) during their initial 8 weeks of GnRH replacement. Pulsatile GnRH was administered every 2 h, with the dose increased at 2-week intervals (5-50 ng/kg/bolus). Every 2 weeks, sera were assayed for inhibin B, FSH, LH, and testosterone. Serial comparisons were performed within the IHH group as well as vs. normal men (n = 20). The baseline inhibin B level in IHH patients averaged 68 +/- 11 pg/mL (mean +/- SEM), significantly less than that in normal men (239 +/- 14 pg/mL; P < 0.001). After 8 weeks of pulsatile GnRH, inhibin B levels in the IHH patients increased significantly to 118 +/- 14 pg/mL (P = 0.003). During GnRH replacement, FSH concentrations correlated negatively with inhibin B concentrations at all doses. Patients previously treated with testosterone began with somewhat lower inhibin B levels but demonstrated a significantly greater increase in serum concentrations than patients who had received prior gonadotropin or GnRH therapy. A history of cryptorchidism did not have a significant impact on inhibin B concentrations before or during GnRH replacement. The low inhibin B levels in IHH men at baseline and their prompt increase in response to pulsatile GnRH suggest acute regulation by gonadotropin stimulation of the testis. The variation in inhibin B levels at baseline and in response to GnRH suggest that prior gonadotropin exposure and seminiferous tubular development also modulate inhibin B secretion. The consistent negative correlation between FSH and inhibin B during the induction of sexual maturation with GnRH supports the role of gonadal inhibin B secretion as an important endocrine regulator of FSH in the human male.


Asunto(s)
Hormona Liberadora de Gonadotropina/deficiencia , Hormona Liberadora de Gonadotropina/uso terapéutico , Hipogonadismo/tratamiento farmacológico , Inhibinas/sangre , Adolescente , Adulto , Criptorquidismo/sangre , Retroalimentación , Hormona Folículo Estimulante/sangre , Hormona Folículo Estimulante/metabolismo , Hormona Liberadora de Gonadotropina/administración & dosificación , Humanos , Hipogonadismo/sangre , Hormona Luteinizante/sangre , Masculino , Periodicidad , Valores de Referencia , Testosterona/sangre
9.
Geriatrics ; 45(5): 24-9, 33-4, 1990 May.
Artículo en Inglés | MEDLINE | ID: mdl-2332176

RESUMEN

Heart disease is the leading cause of mortality and a major cause of morbidity in women in the United States. Premenopausal and postmenopausal risk factors for cardiac disease must be reduced to protect women from this major health hazard. The main coronary risk factors for premenopausal women are hypertension, smoking, hyperlipidemia, obesity, and diabetes. Postmenopausal women have these risk factors in addition to a lack of estrogen. Most studies have shown that replacing estrogen in the menopausal woman reduces cardiovascular disease, probably by increasing HDL and decreasing LDL.


Asunto(s)
Enfermedad Coronaria/etiología , Anciano , Enfermedad Coronaria/tratamiento farmacológico , Enfermedad Coronaria/prevención & control , Complicaciones de la Diabetes , Terapia de Reemplazo de Estrógeno , Estrógenos/deficiencia , Ejercicio Físico , Femenino , Humanos , Hiperlipidemias/complicaciones , Hipertensión/complicaciones , Hipertensión/etiología , Persona de Mediana Edad , Obesidad/complicaciones , Factores de Riesgo , Fumar/efectos adversos
10.
N Engl J Med ; 336(6): 410-5, 1997 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-9010147

RESUMEN

BACKGROUND: Men with isolated gonadotropin-releasing hormone (GnRH) deficiency typically present with an absence of pubertal development. We describe an adult-onset form of idiopathic hypogonadotropic hypogonadism that develops after puberty. METHODS: We studied 10 men (age, 27 to 57 years) with normal sexual maturation, idiopathic infertility, sexual dysfunction, low serum testosterone concentrations, and apulsatile secretion of luteinizing hormone on frequent blood sampling. All the men had otherwise normal anterior pituitary hormone secretion and sellar anatomy. We compared the results of semen analyses and measurements of testicular volume, serum testosterone, inhibin B, and gonadotropins in these men with the results in 24 men with classic GnRH deficiency before and during GnRH-replacement therapy and in 29 normal men of similar age. RESULTS: Serum gonadotropin concentrations in the men with adult-onset GnRH deficiency were similar before and during pulsatile GnRH administration to those in the men with classic GnRH deficiency. However, as compared with men with classic GnRH deficiency, men with adult-onset hypogonadotropic hypogonadism had larger mean (+/-SD) testicular volumes (18+/-5 vs. 3+/-2 ml, P<0.001), serum testosterone concentrations (78+/-34 vs. 49+/-20 ng per deciliter [2.7+/-1.2 vs. 1.7+/-0.7 nmol per liter], P=0.004), and serum inhibin B concentrations (119+/-52 vs. 60+/-21 pg per milliliter, P<0.001). Treatment with GnRH reversed the hypogonadism and restored fertility in each of the five men who received long-term therapy. CONCLUSIONS: The recognition of adult-onset hypogonadotropic hypogonadism in men as a distinct disorder expands the spectrum of GnRH deficiency and identifies a treatable form of male infertility.


Asunto(s)
Hormona Liberadora de Gonadotropina/deficiencia , Hipogonadismo , Infertilidad Masculina/etiología , Adulto , Edad de Inicio , Disfunción Eréctil/etiología , Hormona Liberadora de Gonadotropina/sangre , Hormona Liberadora de Gonadotropina/uso terapéutico , Gonadotropinas Hipofisarias/sangre , Humanos , Hipogonadismo/sangre , Hipogonadismo/complicaciones , Hipogonadismo/tratamiento farmacológico , Infertilidad Masculina/tratamiento farmacológico , Inhibinas/sangre , Libido , Masculino , Persona de Mediana Edad , Valores de Referencia , Testículo/anatomía & histología , Testosterona/sangre
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