In vivo
 secretory potential and the effect of combination therapy with octreotide and cabergoline in patients with clinically non-functioning pituitary adenomas

OBJECTIVES: The authors present a case report that proposes the use of cabergoline treatment in silent ACTH adenoma, an unusual member of the heterogeneous group of the so-called clinically non-functioning pituitary adenomas. DESIGN: Following the clinical and radiological improvement of a recurrent silent ACTH adenoma in a 77-year-old patient treated with cabergoline (0.5 mg every 2 days for 2 years), in vitro studies of the original tumor were performed. METHODS: The original tumor from the patient was studied by in situ hybridization and dopamine D2 receptor autoradiography. It was compared with four macroprolactinomas and two macroadenomas from patients with Cushing's disease. RESULTS: The D2 receptor mRNA signal of the reported case was intense and of the same order of magnitude as that observed in control prolactinomas. Dopamine D2 receptor autoradiography was twice that of control corticotroph adenomas and was close to that observed in prolactinomas. CONCLUSIONS: This is the first description of an in vivo shrinkage of an ACTH silent adenoma under cabergoline. We demonstrate in vitro, the presence of D2 receptors in the primitive tumor in concentrations similar to those found in control prolactinomas. These results suggest that therapeutic trials with cabergoline might be undertaken in recurring cases of ACTH silent tumors and more generally, non-functioning pituitary adenomas.

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FSH secretion predominates in vivo and in vitro in patients with non-functioning pituitary adenomas

Acta Endocrinologica ◽

10.1530/eje.1.01854 ◽

2005 ◽

Vol 152 (3) ◽

pp. 363-370 ◽

Cited By ~ 8

Author(s):

P L Hanson ◽

S J B Aylwin ◽

J P Monson ◽

J M Burrin

Keyword(s):

Cell Cultures ◽

Pituitary Adenomas ◽

Molecular Mechanisms ◽

Pituitary Tumour ◽

Pituitary Cell ◽

Pituitary Cells ◽

Functional Studies ◽

Non Functioning Pituitary Adenomas

Objective: Non-functioning pituitary adenomas (NFPAs) are characterised by the lack of symptoms of hormone hypersecretory syndromes but in vitro studies have demonstrated that tumour cells may stain for gonadotrophins and/or their α- or β-subunits. In this study, we aimed to examine the pattern of secretion of LH and FSH from a series of pituitary adenomas cultured in vitro and where data were available to relate the results to pre-operative serum gonadotrophin levels. Methods: The in vitro secretion of LH and FSH was measured from 46 cultured NFPAs and compared with pre-operative serum gonadotrophin levels in 38 patients. Peritumorous ‘normal’ pituitary cell cultures from 20 additional pituitary tumour patients were used for comparison with the NFPA group. Results: A median pre-operative LH:FSH ratio of 0.33:1 was found in 38 patients with NFPAs. Preferential secretion of FSH was also documented from media of 46 NFPAs cultured in vitro with a median LH:FSH ratio of 0.32:1. A significant correlation (r = 0.43, P < 0.01) was observed between serum and media levels of FSH but not LH. Peritumorous ‘normal’ pituitary cells released LH and FSH in a reversed ratio (median LH:FSH ratio = 3.6:1, P < 0.01 compared with NFPAs). Conclusions: This study has evaluated pre-operative serum gonadotrophin levels and in vitro release of hormones in cultures of surgically removed tissue from patients with NFPAs. The data suggest preferential secretion of FSH occurs both in vitro and in vivo. By demonstrating that NFPAs cultured in vitro reflect the in vivo situation of preferential secretion of FSH, it may be possible in future to perform functional studies using this system to elucidate the cellular and molecular mechanisms involved in the development of an imbalance in gonadotroph cells preferentially overproducing FSH in NFPAs.

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Hypersecretion of the α-subunit in clinically non-functioning pituitary adenomas: Diagnostic accuracy is improved by adding α-subunit/gonadotropin ratio to levels of α-subunit

Clinical & Investigative Medicine ◽

10.25011/cim.v33i3.13727 ◽

2010 ◽

Vol 33 (3) ◽

pp. 203 ◽

Cited By ~ 2

Author(s):

Marianne Andersen ◽

Joanna Ganc-Petersen ◽

Jens OL Jørgensen ◽

Søren Mellemkjær ◽

Per H Petersen ◽

...

Keyword(s):

Pituitary Adenomas ◽

Simple Calculation ◽

Serum Levels ◽

Reference Intervals ◽

Healthy Adults ◽

Α Subunit ◽

Patient Gender ◽

Non Functioning Pituitary Adenomas

Background: In vitro, the majority of clinically non-functioning pituitary adenomas (NFPAs) produce gonadotropins or their α-subunit; however, in vivo, measurements of α-subunit levels may not accurately detect the hypersecretion of the α-subunit. Aim: We wanted to estimate the reference intervals and decision limits for gonadotropin α-subunit, LH and FSH levels, and aratio (α-subunit/LH+FSH), especially taking into consideration patient gender and menstrual status. Furthermore, we wanted to examine if the diagnostic utility of α-subunit hypersecretion was improved when the α-ratios, rather than simply the α-subunit levels, were measured in patients with NFPAs. Material and Methods: Reference intervals for gonadotropin α-subunit serum levels and α-ratios were established in 231 healthy adults. The estimated cut-off limits were applied to 37 patients with NFPAs. Gonadotropin α-subunit, LH and FSH levels were measured and α-ratios were calculated. Results: In healthy adults, the cut-offs for α-subunit levels were significantly different between men and pre- and postmenopausal women: the cut-offs were 1.10, 0.48 and 3.76 IU/l, respectively. Using these estimated cut-offs, increased α-subunit levels were identified in 10 out of 37 (27%) patients with NFPAs. By adding α-ratio, in combination with α-subunit levels, 23 patients out of 37 (62%) were identified as having elevated α-subunit hypersecretion, and 22 out of these 23 patients (96%) had increased α-ratios. One premenopausal patient out of 23 had elevated α-subunit level but a normal α-ratio. Conclusion: Our data suggest that adding the simple calculation of α-ratio improves the ability of detecting gonadotropin α-subunit hypersecretion and thereby indentifying patients with NFPAs.

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