Pascale Abrams, Orsalia Alexopoulou, Roger Abs, Dominique Maiter and Johan Verhelst
Lanreotide-Autogel is a depot formulation of the somatostatin analog lanreotide used in the treatment of acromegaly. We investigated whether prolonging or shortening the interval between injections would offer any benefit.
Subjects and methods
The interval was prolonged from once every 4 weeks to once every 6 weeks when patients (n=9) had normal IGF-I and GH concentrations. When patients (n=12) had still elevated IGF-I or GH on the maximal dose of 120 mg every 4 weeks, the interval was shortened to once every 3 weeks. Serum IGF-I and GH were measured after 12 and 24 weeks to allow for dose adaptation. Symptoms and tumor volume were evaluated at baseline and after 36 weeks.
In seven of the nine subjects with normal IGF-I and GH, the interval could be extended to 6 weeks without loosing efficacy on IGF-I (195 vs 213 μg/l; not significant, NS) and GH concentrations (1.4 vs 1.3 μg/l; NS). The weekly dose could significantly be reduced (from 23.3 to 17.8 mg; P=0.002). In only 1 of the 12 not-controlled patients, reducing the interval to once every 3 weeks induced normalization of IGF-I and GH.
In subjects whose acromegaly is well controlled using lanreotide-Autogel, prolonging the time interval between injections can often be increased 4 to 6 weeks without loss of efficacy, thereby improving the subject's comfort and reducing the cost of treatment. On the other hand, in subjects whose acromegaly is not controlled on a dose of 120 mg every 4 weeks, reducing the interval to every 3 weeks is rarely beneficial.
John Yango, Orsalia Alexopoulou, Stephane Eeckhoudt, Cedric Hermans and Chantal Daumerie
Several hemostatic abnormalities have been described in hypothyroidism, such as modification of coagulation proteins and bleeding tendency. Although thyroid hormone deficiency is considered to be responsible for these changes, the underlying mechanisms have not yet been established.
To evaluate the respective influence of peripheral thyroid hormones (free thyroxine) and TSH on blood clotting by assessing coagulation parameters in patients with a history of total thyroidectomy for thyroid cancer, under three different conditions: induced hypothyroidism, euthyroid state, and following recombinant human TSH (rhTSH) administration.
Coagulation parameters (platelet count, fibrinogen, international normalized ratio, prothrombin time, thrombin time, activated partial thromboplastin time (APTT), factor VIII activity ((FVIII:C), as well as von Willebrand factor antigen (VWF:Ag) and VWF activity using collagen binding assay (VWF:CBA)) were measured in patients with severe hypothyroidism following withdrawal of thyroid hormone replacement therapy, and in the same patients with euthyroidism after restoring replacement treatment (group A), and before and after administering rhTSH (group B).
FVIII:C, VWF:Ag, and VWF:CBA were significantly decreased (P<0.001), whereas APTT was significantly increased (P<0.001) in patients with severe hypothyroidism compared with patients in the euthyroid state. No changes in clotting parameters were observed in patients who received rhTSH therapy.
This prospective study shows that severe short-term hypothyroidism is associated with significantly lower levels of VWF:Ag, VWF:CBA, and FVIII:C. Administration of exogenous TSH has no effect on coagulation parameters. These findings suggest that thyroid hormone deficiency is likely to be the main cause of coagulation alterations in patients with hypothyroidism.
Sophie Brochier, Françoise Galland, Michèle Kujas, Fabrice Parker, Stephan Gaillard, Christian Raftopoulos, Jacques Young, Orsalia Alexopoulou, Dominique Maiter and Philippe Chanson
Adequate postoperative management of nonfunctioning pituitary macroadenomas (NFMAs) remains a challenge for the clinician.
To identify predictive factors of NFMA relapse after initial surgery.
Patients and methods
This retrospective study included 142 patients operated for an NFMA in two academic centers (CHU Bicêtre in France and UCL St Luc in Belgium). The rate of tumor relapse, defined as recurrence after total surgical resection or regrowth of a surgical remnant, as well as predictive factors was analyzed.
During a mean follow-up of 6.9 years, 10 out of 42 patients (24%) who had complete macroscopic resection of their tumor had recurrence, and 47 out of 100 patients (47%) with a surgical remnant experienced regrowth. The overall relapse rates were 25, 43, and 61% at 5, 10, and 15 years respectively. Invasion of the cavernous sinus, absence of immediate radiotherapy after the first neurosurgery, and immunohistochemical features of the tumor (mainly positive immunostaining for several hormones or for hormones other than gonadotropins) were independent risk factors for tumor relapse. Incomplete excision was only associated with relapse when invasion was withdrawn from the analysis, suggesting that these two factors are closely linked.
NFMAs frequently recur/regrow after initial surgery, particularly when tumor is invasive, precluding complete removal. Immunohistochemical features such as positive immunostaining for several hormones or for hormones other than gonadotropins could help to predict undesirable outcomes.