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      Clinicopathological characteristics and therapeutic outcomes in thyrotropin-secreting pituitary adenomas: a single-center study of 90 cases

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          Abstract

          Object

          The aim of this study was to analyze clinicopathological characteristics and treatment outcomes in a large single-center clinical series of cases of thyrotropin (TSH)–secreting pituitary adenomas.

          Methods

          The authors retrospectively reviewed clinical, pathological, and treatment characteristics of 90 consecutive cases of TSH-secreting pituitary adenomas treated with transsphenoidal surgery between December 1991 and May 2013. The patient group included 47 females and 43 males (median age 42 years, range 11–74 years).

          Results

          Sixteen tumors (18%) were microadenomas and 74 (82%) were macroadenomas. Microadenomas were significantly more frequent in the more recent half of our case series (12 of 45 cases) (p = 0.0274). Cavernous sinus invasion was confirmed in 21 patients (23%). In 67 cases (74%), the tumors were firm elastic or hard in consistency. Acromegaly and hyperprolactinemia were observed, respectively, in 14 (16%) and 11 (12%) of the 90 cases. Euthyroidism was achieved in 40 (83%) of 48 patients and tumor shrinkage was found in 24 (55%) of 44 patients following preoperative somatostatin analog treatment. Conventional transsphenoidal surgery, extended transsphenoidal surgery, and a simultaneous combined supra- and infrasellar approach were performed in 85, 2, and 3 patients, respectively. Total removal with endocrinological remission was achieved in 76 (84%) of 90 patients, including all 16 (100%) patients with microadenomas, 60 (81%) of the 74 with macroadenomas, and 8 (38%) of the 21 with cavernous sinus invasion. None of these 76 patients experienced tumor recurrence during a median follow-up period of 2.8 years. Stratifying by Knosp grade, total removal with endocrinological remission was achieved in 34 of 36 patients with Knosp Grade 0 tumors, all 24 of those with Grade 1 tumors, 12 of the 14 with Grade 2 tumors, 6 of the 8 with Grade 3 tumors, and none of the 8 with Grade 4 tumors. Cavernous sinus invasion and tumor size were significant independent predictors of surgical outcome. Immunoreactivity for growth hormone, prolactin, or both hormones was present in 32, 9, and 24 patients, respectively. The Ki-67 labeling index was less than 3% in 71 (97%) of 73 tumors for which it was obtained and 3% or more in 2. Postsurgery pituitary dysfunction was found in 15 patients (17%) and delayed hyponatremia was seen in 9.

          Conclusions

          TSH-secreting adenomas, particularly those in the microadenoma stage, have increased in frequency over the past 5 years. The high surgical success rate achieved in this series is due to relatively early diagnosis and relatively small tumor size. In addition, the surgical strategies used, such as extracapsular removal of hard or solid adenomas, aggressive resction of tumors with cavernous sinus invasion, or extended transsphenoidal surgery or a simultaneous combined approach for large/giant multilobulated adenomas, also may improve remission rate with a minimal incidence of complications.

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          Most cited references31

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          A consensus on criteria for cure of acromegaly.

          The Acromegaly Consensus Group met in April 2009 to revisit the guidelines on criteria for cure as defined in 2000. Participants included 74 neurosurgeons and endocrinologists with extensive experience of treating acromegaly. EVIDENCE/CONSENSUS PROCESS: Relevant assays, biochemical measures, clinical outcomes, and definition of disease control were discussed, based on the available published evidence, and the strength of consensus statements was rated. Criteria to define active acromegaly and disease control were agreed, and several significant changes were made to the 2000 guidelines. Appropriate methods of measuring and achieving disease control were summarized.
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            Pituitary tumours: TSH-secreting adenomas.

            Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of hyperthyroidism and account for less than 2% of all pituitary adenomas. In the last years, the diagnosis has been facilitated by the routine use of ultra-sensitive TSH immunometric assays. Failure to recognise the presence of a TSHoma may result in dramatic consequences, such as improper thyroid ablation that may cause the pituitary tumour volume to further expand. The diagnosis mainly rests on dynamic testing, such as T3 suppression tests and TRH, which are useful in differentiating TSHomas from the syndromes of thyroid hormone resistance. The first therapeutical approach to TSHomas is the pituitary neurosurgery. The medical treatment of TSHomas mainly rests on the administration of somatostatin analogues, such as octreotide and lanreotide, which are effective in reducing TSH secretion in more than 90% of patients with consequent normalisation of FT4 and FT3 levels and restoration of the euthyroid state.
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              The changing spectrum of TSH-secreting pituitary adenomas: diagnosis and management in 43 patients.

              Our aim was to report the recent changes in diagnosis and management of TSH-secreting pituitary adenomas. We retrieved 43 consecutive patients with TSH-secreting pituitary tumors (23 male and 20 female) among 4400 pituitary adenomas followed between 1976 and 2001 in six Belgian and French centers. TSH was elevated in 18/43 and alpha subunit in 13/32 patients. In patients with intact thyroid (n=30), mean free tri-iodothyronine was 13.1 pmol/l (range 3.5-23) and mean free thyroxine was 38.4 pmol/l (range 10.2-62.7). Hyperprolactinemia and acromegaly were associated in 9/43 and 8/43 cases. The number of associated hypersecretions was higher in macroadenomas than in microadenomas (Chi square = 11.2, P<0.01). Two women had sporadic multiple endocrine neoplasia type 1-associated syndrome. The proportion of microadenomas versus macroadenomas was 1/11 (period 1974-1986) and 8/32 (period 1987-2001). Bilateral petrosal sinus sampling, (111)In-pentreotide scintigraphy and ((11)C)-l-methionine positron emission tomography scan confirmed diagnosis in four questionable microadenomas. Macroadenomas with extrasellar extension (31 cases) had a tendency to be medially located. Medical treatment with somatostatin analogs was initiated as first-line treatment in 26 patients. TSH levels were reduced by more than 50% in 23/26 cases. A tumoral shrinkage of more than 20% was observed in 5/13 cases. Surgery was performed in 36 patients. After 1 year, 21 of them (58.3%) met the criteria of surgical favorable outcome. Pituitary radiotherapy (n=8) and somatostatin analogs allowed normalization in cases not cured by surgery. Ultrasensitive methods for TSH measurement led to an earlier recognition of TSH-secreting pituitary tumors. In this series, we observed that TSH-secreting pituitary tumors are today more frequently found at the stage of microadenomas, medially located, without associated hypersecretions and needing new exploration methods as compared with older series. This changing spectrum in the presentation of TSH-secreting pituitary tumors and the excellent response to somatostatin analogs has been accompanied by an improvement in the prognosis of the disease.

                Author and article information

                Journal
                Journal of Neurosurgery
                Journal of Neurosurgery Publishing Group (JNSPG)
                0022-3085
                1933-0693
                December 2014
                December 2014
                : 121
                : 6
                : 1462-1473
                Article
                10.3171/2014.7.JNS1471
                25237847
                bea4fd74-a2a4-4841-ae32-8da55a199538
                © 2014
                History

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