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Virginie Atquet, Orsalia Alexopoulou, and Dominique Maiter

Objectives: We aimed to investigate the clinical, biochemical, histological and radiological characteristics as well as the response to somatostatin analogs (SSA) in a large cohort of acromegaly patients with a paradoxical GH response (PR) to oral glucose tolerance test (OGTT).

Design: retrospective study.

Methods: Of 110 patients with acromegaly included in our study, 30 (PR+; 27%) had a paradoxical GH increase of more than 25% relative to basal GH levels during OGTT.

Results : At diagnosis, PR+ patients were older than PR- patients (52 ± 16 vs 44 ± 14 years, p<0.05) and had smaller pituitary tumours (40% microadenomas vs 19%, p<0.05), which were less often invasive (17 vs 35%, p<0.05), overall more secreting (IGF-1/tumoural surface: 2.35 ULN/cm² [0.28-9.06] vs 1.08 [0.17- 7.87], p=0.011), and more often hypointense on T2-weighted MRI (92 vs 48%, p=0.001). While the rate of remission after surgery was similar in the two groups (69%), a better response to SSA treatment was observed in PR+ patients, either before (IGF-1 reduction of > 50% after 3-6 months in 77 vs 49%, p=0.023) or after surgery (normalization of IGF-1 in 100 vs 44%, p=0.011).

Conclusions: Our study demonstrates that in acromegaly, a paradoxical GH increase during OGTT is associated with particular features of somatotroph adenomas and with a better prognosis in terms of response to somatostatin analogs.

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Pascale Abrams, Orsalia Alexopoulou, Roger Abs, Dominique Maiter, and Johan Verhelst

Abstract

Background

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.

Results

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.

Conclusion

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.

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John Yango, Orsalia Alexopoulou, Stephane Eeckhoudt, Cedric Hermans, and Chantal Daumerie

Background

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.

Objective

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.

Methods

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).

Results

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.

Conclusion

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.

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Sophie Brochier, Françoise Galland, Michèle Kujas, Fabrice Parker, Stephan Gaillard, Christian Raftopoulos, Jacques Young, Orsalia Alexopoulou, Dominique Maiter, and Philippe Chanson

Context

Adequate postoperative management of nonfunctioning pituitary macroadenomas (NFMAs) remains a challenge for the clinician.

Objective

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.

Results

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.

Conclusion

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.

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France Devuyst, Paraskevi Kazakou, Danielle Balériaux, Orsalia Alexopoulou, Agnès Burniat, Sylvie Salenave, Philippe Chanson, Bernard Corvilain, and Dominique Maiter

Context

Association of central diabetes insipidus (CDI) and pituitary stalk thickening (PST) may have several etiologies (including malignancies) and differential diagnosis remains often difficult.

Objective

The purpose of this study was to identify which clinical, biochemical or radiological features could help clinicians to make an etiological diagnosis, especially distinguishing neoplastic from non-neoplastic pituitary stalk lesions.

Design and methods

We retrospectively analyzed clinical, biochemical, radiological and histological data of 38 adult patients diagnosed with CDI and PST of proven etiology.

Results

Of the 38 pituitary stalk lesions included, 11 (29%) were neoplastic. A histopathological diagnosis was obtained in 22/38 (58%) patients. The three most frequently observed etiologies of PST were neuroinfundibulitis (34%), germinoma (21%) and histiocytosis (18%). Pituitary stalk thickness was larger for neoplastic lesions, particularly germinomas. Male gender and a very young age were statistically associated with a risk of germinoma. At least one anterior pituitary deficit was observed in nearly 60% of patients. Patients with neoplastic PST were more affected by multiple anterior pituitary dysfunction than patients with benign PST. A high serum prolactin level was individually the best predictor of a neoplastic origin (90% sensitivity and 60% specificity for a serum prolactin level 1.27-fold above the normal upper limit (ULN)).

Conclusion

We confirm a relatively high risk of malignancy in adult patients presenting with the association of CDI and PST. Young age, male gender, a very large thickening of the stalk, multiple anterior pituitary deficits and prolactin above 1.3× ULN increase the likelihood of a neoplastic origin.

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France Devuyst, Paraskevi Kazakou, Danielle Balériaux, Orsalia Alexopoulou, Agnès Burniat, Sylvie Salenave, Philippe Chanson, Bernard Corvilain, and Dominique Maiter