Antonella Giampietro

Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first generation somatostatin analogues: an immunohistochemical study

AIMnTo gather data regarding factors predicting responsiveness to pasireotide in acromegaly.nnnPATIENTS AND METHODSnSSTR2a, SSTR3, SSTR5, AIP, Ki-67 and the adenoma subtype were evaluated in somatotroph adenomas from 39 patients treated post-operatively with somatostatin analogues (SSAs). A standardized SSTR scoring system was applied (scores 0-3). All patients received first-generation SSAs, and 11 resistant patients were subsequently treated with pasireotide LAR.nnnRESULTSnNone of the patients with negative or cytoplasmic-only SSTR2a expression (scores 0-1) were responsive to first-generation SSAs, as opposed to 20% (score 2) and 50% of patients with a score of 3 (P=0.04). None of the patients with an SSTR5 score of 0-1 were responsive to pasireotide, as opposed to 5/7 cases with a score of 2 or 3 (P=0.02). SSTR3 expression did not influence first-generation SSAs or pasireotide responsiveness. Tumours with low AIP were resistant to first-generation SSAs (100 vs 60%; P=0.02), while they had similar responsiveness to pasireotide compared to tumours with conserved AIP expression (50 vs 40%; P=0.74). Tumours with low AIP displayed reduced SSTR2 (SSTR2a scores 0-1 44.4 vs 6.7%; P=0.006) while no difference was seen in SSTR5 (SSTR5 scores 0-1 33.3 vs 23.3%; P=0.55). Sparsely granulated adenomas responded better to pasireotide compared to densely granulated ones (80 vs 16.7%; P=0.04).nnnCONCLUSIONnThe expression of SSTR5 might predict responsiveness to pasireotide in acromegaly. AIP deficient and sparsely granulated adenomas may benefit from pasireotide treatment. These results need to be confirmed in larger series of pasireotide-treated patients.

DIAGNOSIS OF ENDOCRINE DISEASE: Primary empty sella: a comprehensive review

Primary empty sella (PES) is characterized by the herniation of the subarachnoid space within the sella, which is often associated with variable degrees of flattening of the pituitary gland in patients without previous pituitary pathologies. PES pathogenetic mechanisms are not well known but seem to be due to a sellar diaphragm incompetence, associated to the occurrence of upper sellar or pituitary factors, as intracranial hypertension and change of pituitary volume. As PES represents in a majority of cases, a neuroradiological findings without any clinical implication, the occurrence of endocrine, neurological and opthalmological symptoms, due to the above describes anatomical alteration, which delineates from the so called PES syndrome. Headache, irregular menses, overweight/obesity and visual disturbances compose the typical picture of PES syndrome and can be the manifestation of an intracranial hypertension, often associated with PES. Although hyperprolactinemia and growth hormone deficit represent the most common endocrine abnormalities, PES syndrome is characterized by heterogeneity both in clinical manifestation and hormonal alterations and can sometime reach severe extremes, as occurrence of papilledema, cerebrospinal fluid rhinorrhea and worsening of visual acuity. Consequently, a multidisciplinary approach, with the integration of endocrine, neurologic and ophthalmologic expertise, is strongly advocated and recommended for a properly diagnosis, management, treatment and follow-up of PES syndrome and all of the related abnormalities.

Bone mineral density in pre-climateric obese women pre- and post biliopancreatic diversion (BPD)

Study Methods: There was a selected group of women in premenopausal period (N=19), aging 39.Oe8.0 suffering from differentiated thyroid gland carcinoma. To all of them, the total thyroidectomy was done and the thyroxine suppression therapy was introduced. The duration of the suppression therapy from the beginning of the research amounted to 9.4e6.4 years. Laboratory results have excluded other possible factors for secondary osteoporiosis. The prospective study of the bone densiometry was done to all of the examinees using the method of dual photon x-ray absorptiometry (DXA) of the spine and the femoral neck, and also by the method of single-photon absorptiometry (SPA) of the distal radius. Results: In the beginning of this study, while the patients were treated for 10 years osteopeny was found in the spine and the femoral neck in two examinees for every region. On the distal radius osteopeny was found in 4 examinees. The total was 8 out of 19 with statistically significant loss o f bone mass was in any region of skeleton. However, looking at the individual scores, osteopeny was found in 6 examinees on the distal radius but on the spine and the femoral neck, there was bone loss in several women but not to the point that would create osteopeny. But, after the 4 years of measurement, t-test had shown some significant loss of bone mass on the distal radius. The period of one year is not enough to record significant bone loss. Conclusions: We can come to the decision that women who begin with a long-term thyroxine therapy (about 10 years) in premenopausal period can develop osteopeny in the beginning of menopause. In that case, those women should complete a mammography test and bone densitometry before hormone replacement therapy is used.