The Prescribing Practice for COPD: Relationship to Circadian Rhythm, Disease Severity, and Clinical Phenotype in the STORICO Observational Study.

INTRODUCTION: While selected clinical and laboratory findings are taken into account to find the best therapeutic strategies for chronic obstructive pulmonary disease (COPD), it is unknown whether the circadian rhythm of respiratory symptoms, a distinctive feature of COPD, affects the prescription pattern of pharmacological therapy. The main aim of this study was to verify whether the circadian rhythm of symptoms correlates with bronchodilating therapy prescribed to COPD patients as per clinical practice. A secondary objective was to assess the relationship between Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and circadian rhythm of symptoms and health status. METHODS: Five hundred sixty-six COPD patients were enrolled in the Italian multicenter STORICO study. Patients underwent a multidimensional assessment, and correlates of prescribed therapy were assessed through a multivariate multilevel model. RESULTS: As expected, patients in GOLD D stage were more likely to receive triple inhaled therapy than GOLD A-C patients, but the circadian rhythm of symptoms, assessed by the nighttime, morning, and daytime symptoms of the COPD questionnaire, was unrelated to the prescription pattern. The multivariate model showed that emphysematous (EM) patients had a 50% increased risk compared with patients affected by chronic bronchitis (CB) of being prescribed long-acting ß2-agonists (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combination (FDC) instead of triple therapy [relative risk (RR) EM versus CB 1.50, 95% CI 1.11, 2.03]. Symptoms, mainly in the early morning and daytime, were highly prevalent, even in GOLD B stage (76%). CONCLUSION: Even if we cannot infer about causality of the symptoms-therapy relationship, based on the structured recording of circadian symptoms clearly shows that symptoms are poorly controlled as the circadian rhythm of symptoms does not correlate with the prescription pattern, and many patients are symptomatic both at daytime and by nighttime. Thus, therapy should be better tailored to the individual needs, with special attention to control nocturnal symptoms. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03105999.

Impact of different cut-off limits of peak GH after GHRH-arginine stimulatory test, single IGF1 measurement, or their combination in identifying adult patients with GH deficiency.

OBJECTIVE: To evaluate the impact of different peak GH cut-off limits after GHRH-Arg test, IGF1 measurement, or their combination in identifying patients with GH deficit (GHD). DESIGN AND PATIENTS: Totally, 894 normal subjects (used for determining IGF1 normative limits) and 302 patients with suspected GHD were included. Different peak GH cut-off limits (used by European (depending on body mass index (BMI)) or North American (4.1 µg/l) Endocrine Societies, by HypoCCs (2.5 µg/l), or with 95% specificity (based on BMI), Method 1, 2, 3, or 4 respectively) and IGF1 were considered. METHODS: Peak GH after GHRH-Arg and IGF1. RESULTS: Different peak GH cut-off limits recognized different proportions of GHD (range, 24.8-62.9%). Methods 1 and 2 with high sensitivity recognized a higher proportion (95.5 and 92.5% respectively) of GHD among patients with three (T) pituitary hormone deficits (HD), whereas Method 4 (with high specificity) identified 96.7% normal subjects among those without pituitary HD; on the contrary, Method 4 identified only 75% GHD among patients with THD, whereas Method 1 recognized a high proportion (40%) of GHD among subjects without HD. Of the total patients, 82% with THD and 84.5% without HD were recognized as GHD or normal respectively by IGF1. Among the remaining patients with THD and normal IGF1, 75% was recognized as GHD by Method 1; among patients without HD and abnormal IGF1, 87.5% was identified as normal by Method 4. Overall, combination of IGF1 and Method 1 or Method 4 identified 95.5% GHD among patients with THD and 98.1% normal subjects among those without HD. CONCLUSIONS: Single peak GH cut-offs have limits to sharply differentiate GHD from normal subjects; IGF1 may be used for selecting patients to be submitted to the GHRH-Arg test; the peak GH cut-off limits to be used for identifying healthy or diseased patients depend mainly on the clinical context.

Changes in coagulation indexes and occurrence of venous thromboembolism in patients with Cushing's syndrome: results from a prospective study before and after surgery.

OBJECTIVES: To evaluate whether patients with Cushing's syndrome (CS) had i) changes in coagulative and fibrinolytic parameters associated with CS activity and ii) higher prevalence of venous thromboembolic events (VTE). DESIGN: Prospective study conducted on patients with CS evaluated at diagnosis and 12 months after surgery. PATIENTS AND METHODS: Forty patients with active CS (36 with Cushing's disease (CD) and 4 with an adrenal adenoma) were evaluated. Forty normal subjects and 70 patients with non-ACTH-secreting pituitary adenomas served as controls. All patients and controls underwent an assessment of coagulation and fibrinolysis indexes before and after surgery. RESULTS: CS patients at baseline had a hypercoagulative phenotype when compared with normal subjects (activated partial thromboplastin time (aPTT), fibrinogen, D-Dimer, von Willebrand factor (VWF), plasminogen activator inhibitor 1 (PAI-1 or SERPINE1), antithrombin III (ATIII or SERPINC1), P<0.0001, α(2) antiplasmin, P=0.0004, thrombin-antithrombin complex (TAT), P=0.01, factor IX (F9), P=0.03). Patients with still active disease after surgery had higher coagulative parameters than those in remission (VWF (P<0.0001), PAI-1 (P=0.004), TAT (P=0.0001), ATIII (P=0.0002) and α(2) antiplasmin (or SERPINF2; P=0.006)), whereas aPTT levels (P=0.007) were significantly reduced. VTE occurred in three patients with CD (7.5%): one had a pulmonary embolism and two patients had a deep venous thrombosis; no patients submitted to transsphenoidal surgery for non-Cushing's pituitary adenoma had VTE (P=0.04). CONCLUSIONS: Patients with CS have a procoagulative phenotype due to cortisol-associated changes in haemostatic and fibrinolytic markers, leading to increased incidence of VTE. Thromboprophylaxis seems to be appropriated in patients with active disease, particularly in the postoperative period.

Impact of lithium on efficacy of radioactive iodine therapy for Graves' disease: a cohort study on cure rate, time to cure, and frequency of increased serum thyroxine after antithyroid drug withdrawal.

CONTEXT: Radioactive iodine (RAI) is a common therapy for hyperthyroidism due to Graves' disease. A small but significant proportion of patients have recurrence of hyperthyroidism after RAI therapy. Lithium might increase RAI effectiveness by increasing RAI retention in the thyroid. However, whether lithium favorably affects the long-term outcome of RAI therapy is still a matter of argument. OBJECTIVE: The objective of the study was to compare the efficacy of RAI given with or without concomitant lithium treatment. DESIGN: This was a retrospective cohort study. SETTING: The study was conducted at a tertiary university center. PATIENTS: Six hundred fifty-one patients with newly diagnosed Graves' disease participated in the study. INTERVENTION: Two hundred ninety-eight patients were treated with RAI plus lithium (900 mg/d for 12 d) and 353 with RAI alone. MAIN OUTCOME MEASURES: Proportion of cured patients and time to achieve cure of hyperthyroidism during 1 yr of follow-up was measured. RESULTS: PATIENTS treated with RAI plus lithium had a higher cure rate (91.0%) than those treated with RAI alone (85.0%, P = 0.030). In addition, patients treated with RAI plus lithium were cured more rapidly (median 60 d) than those treated with RAI alone (median 90 d, P = 0.000). Treatment with lithium prevented the serum free T(4) increase after methimazole withdrawal and RAI therapy. Side effects after RAI therapy occurred in a subset of patients and were mild, transient, and without differences in the two groups. CONCLUSIONS: RAI combined with lithium is safe and more effective than RAI alone in the cure of hyperthyroidism due to Graves' disease.

A multimodal approach to the treatment of bilateral choroidal metastases from thyroid carcinoma.

A 58-year old man, affected by metastatic thyroid carcinoma, experienced a progressive bilateral visual impairment. Ophthalmic examination revealed the presence of a choroidal mass with an associated exudative retinal detachment in both eyes. Twelve years before, a diagnosis of metastatic thyroid carcinoma had been established and the patient had been subject to several therapeutic procedures.In May 2007, he received a radiotherapy treatment to the left eye with an episcleral plaque and bilateral bulbar injection of bevacizumab. The patient had a rapid and stable visual acuity recovery. Twenty months after treatment, the lesion treated with radiotherapy was still stable whereas the contra-lateral lesion had evolved and determined a vitreal hemorrhage.