Resection of the Cavernous Sinus Medial Wall Improves Remission Rate in Functioning Pituitary Tumors: Retrospective Analysis of 248 Consecutive Cases.

BACKGROUND: The purpose of transsphenoidal surgery (TSS) for a functioning pituitary tumor (FPT) is to achieve endocrinological remission. The biggest challenge is aggressive tumor resection invading the cavernous sinus (CS). OBJECTIVE: To evaluate the effects of the medial wall of CS (MWCS) resection during FPT surgery. METHODS: Consecutive FPTs were reviewed for CS invasion (CSI) between April 2018 and December 2021. We operated on more than 250 FPTs, including 134 somatotroph tumors, 70 corticotroph tumors, 35 lactotroph tumors, and 9 thyrotroph tumors. RESULTS: The patients were classified into 3 groups based on the relationship between the tumor and the CS: group A (no clear wall invasion), in which MWCS was not removed because of no tumorous direct contact with MWCS (N = 92) and group B (possible wall invasion), where MWCS was removed because we were not confident of MWCS invasion (N = 102). Among these 102 patients, histological tumor invasion was confirmed in 45 of 79 patients (57%) for whom histology findings were available. Tumors invading the CS clearly during surgery were classified into the "clear CS invasion" (group C: N = 55) group. The overall complete remission rate in group B was 94%, which was as high as that in group A (87%). Moreover, we clarified that microscopic invasion of MWCS could not always be predicted from Knosp grading. CONCLUSION: MWCS invasion occurred in 57% of cases confirmed histologically where it was unclear during surgery, and its resection can improve the overall complete remission rate in FPT cases.

Apoplexy in sellar metastasis from papillary thyroid cancer: A case report and literature review.

Background: Pituitary metastasis from papillary thyroid cancer (PTC) is rare and only a few cases have been reported. Case Description: We report the case of a patient who presented with visual dysfunction and panhypopituitarism. Magnetic resonance imaging revealed a pituitary tumor and hydrocephalus. Transsphenoidal surgery had been indicated, but his surgery had been postponed due to COVID-19 pandemic. During that waiting period, he showed pituitary apoplexy with consciousness disturbance, resulting in acute adrenal insufficiency and diabetes insipidus. He was urgently hospitalized and underwent transsphenoidal surgery. Rapid and permanent pathological examinations have confirmed metastasis of PTC to the pituitary. The patient also underwent serial thyroidectomy. He was also suspected to have secondary hydrocephalus and underwent lumboperitoneal shunting after excluding cerebrospinal fluid metastasis. Thereafter, his cognitive dysfunction and performance status improved dramatically. Conclusion: To the best of our knowledge, this is the first patient with PTC who developed pituitary apoplexy secondary to metastasis.

Outcome After Resection of Craniopharyngiomas and the Important Role of Stereotactic Radiosurgery in Their Management.

OBJECTIVE: Experience with management of craniopharyngiomas (CPH) was evaluated retrospectively. METHODS: Between 1981 and 2012, 100 patients underwent removal of a CPH (the main surgical group), and an original tumor grading system was applied to these cases. The mean length of follow-up was 121 months. Additionally, 17 patients underwent removal of a CPH between 2012 and 2017 (the supplementary surgical group), and in 6 of them, CyberKnife radiosurgery was performed on a residual tumor (in 5 cases) or at the time of recurrence (in 1 case). RESULTS: In the main surgical group, the gross total resection (GTR) rate was 81%. The early and late disease-specific postoperative mortality rates were 0% and 2%, respectively. Tumor recurrence was never noted after GTR. There was a statistically significant increase in the Karnofsky Performance Scale (KPS) score after surgery. The tumor surgical grade was inversely associated with both the pre- and postoperative KPS scores, and was lower in cases operated on via the transnasal transsphenoidal approach, but was unrelated to the GTR rate. In the supplementary surgical group, the GTR rate was 65%. CyberKnife radiosurgery consistently resulted in tumor shrinkage. CONCLUSION: GTR is the preferred management option for CPH. The original surgical grading system developed at Tokyo Women's Medical University may be helpful for clinical decision-making. CyberKnife radiosurgery for residual and recurrent CPH is associated with high tumor response rates.

Revalidation of inferior petrosal sinus sampling: the latest results from a single-center experience.

Cushing's disease (CD), which manifests as excess cortisol secretion, is caused by adrenocorticotrophic hormone (ACTH)-secreting pituitary adenomas. Such adenomas are occasionally difficult to identify on magnetic resonance imaging (MRI), and thorough endocrinological examination may be required to detect them. Inferior petrosal sinus (IPS) sampling (IPSS) has been the gold standard test for distinguishing CD from ectopic ACTH syndrome (EAS). However, IPSS is an invasive procedure, and proper catheterization is occasionally challenging due to anatomical variations. Thus, there have been ongoing debates regarding the necessity of this procedure. Here, we present our recent IPSS data derived from the analysis of 65 patients who were referred to us for possible CD between April 2018 and December 2020 after undergoing meticulous endocrinological testing. Even with detailed MRI, no obvious lesions were identified in 19 patients. IPSS performed on these 19 individuals identified an IPS-to-peripheral ACTH gradient in 15 of them. The four patients who lacked this gradient were subjected to a classical algorithm using concurrently measured prolactin levels, the results of which were consistent with their ultimately confirmed diagnoses: two true-positive and two true-negative diagnoses. These findings support the validity of the algorithm and demonstrate that the prolactin-adjusted IPS-to-peripheral ACTH ratio can improve the differentiation between CD and EAS. We had no false-negative results, but three patients were false-positive. Consequently, those three patients in which no apparent tumor was clarified during surgery could not have any endocrinological improvement postoperatively.

Click emission in Dall's porpoise Phocoenoides dalli, focusing on physical properties of tissues.

Dall's porpoise (Phocoenoides dalli) is one of most common North Pacific porpoise species, for which information on sound-emitting processes is limited. To evaluate the mechanism of click emission in the head of this porpoise, the distribution of acoustic impedance in head tissues was calculated using density and Young's modulus'which is a measure of linear resistance to linear compression. Two Dall's porpoise heads were examined: one for macroscopic dissection, and one for investigating the distribution of acoustic impedance calculated from CT-measured density, and Young's modulus measured by creep meter. Acoustic impedance increased from the dorsal bursae to the melon's emitting surface, with impedance matching observed at the boundary between the emitting surface and seawater, and was more similar in distribution to Young's modulus than it was to density. The distribution of acoustic impedance differed from that of harbor porpoise (Phocoena phocoena), despite similarities in the sound-producing organs in the heads of Dall's and harbor porpoises. A comparison of the physical properties of Dall's and harbor porpoise head tissues suggests that hypertrophic vestibular sacs and an oval emitting surface are common characteristics in Phocoenidae.

Tissue physical property of the harbor porpoise Phocoena phocoena for investigation of the sound emission process.

The process by which sound is propagated in the head of a toothed whale is still a subject of discussion. Investigating the distribution of acoustic impedance calculated by density and Young's modulus is effective for quantitative comprehension because acoustic impedance determines the reflection coefficient of a sound wave. However, the sound propagation process of the toothed whale has been mainly examined by either anatomical techniques or the measurement of density or sound velocity. In the current study, the acoustic impedance of head tissue of harbor porpoise was measured. Results of this study should be a helpful information for further discussion about the relationship between the structure of sound-producing organ and clicks property.

A case of corticotroph carcinoma that caused multiple cranial nerve palsies, destructive petrosal bone invasion, and liver metastasis.

A 52-year-old woman experienced sudden onset of double vision due to a right abducens nerve palsy and was diagnosed as having a pituitary macroadenoma that invaded into the right cavernous sinus. Otherwise, she was asymptomatic despite marked elevation of ACTH (293 pg/ml) and cortisol (24.6 µg/dl) levels. The patient underwent transsphenoidal surgery followed by γ-knife radiosurgery (GKR), which healed the diplopia and ameliorated the hypercortisolemia. The excised tumor was diffusely stained for ACTH with a high (15%) Ki-67 labeling index. Early tumor recurrence occurred twice thereafter, producing right lower cranial nerve palsies with petrosal bone destruction at 8 months and an ipsilateral oculomotor nerve palsy at 12 months after GKR; all palsies resolved completely with the second and third GKRs. Hypercortisolemia worsened rapidly soon after the third GKR, and the patient developed marked weight gain, hypokalemia, and hypertension. Multiple liver lesions were incidentally detected with computer tomography and identified as metastatic pituitary tumor on immunohistochemistry. An ACTH-producing adenoma should be followed carefully for early recurrence and/or metastatic spread when the tumor is an invasive macroadenoma with a high proliferation marker level. The unique aggressive behavior and high potential for malignant transformation of this case are discussed.

Vitamin D deficiency in two young adults with biochemical findings resembling pseudohypoparathyroidism type I and type II.

We report two patients with vitamin D deficiency due to unbalanced diet. The patients initially presented with severe hypocalcemia, normophosphatemia and markedly elevated serum PTH levels. Although nutritional vitamin D deficiency was suspected from their history of gastrointestinal problems and dietary restriction, we conducted Ellsworth- Howard test to exclude the possibility of pseudohypoparathyroidism (PHP). Both patients showed no incremental response of urinary phosphate excretion. However, the urinary cAMP response to exogenous PTH was different between the two. Case 1 showed a blunted response (5-fold and 1.54 micro mol/h increase) and case 2 showed a normal response (39-fold and 3.04 micro mol/h increase). According to the criteria of Ellsworth-Howard test, the data of case 1 was compatible with PHP type I, and of case 2 with PHP type II. The final diagnosis of vitamin D deficiency was established in both patients based on very low serum 25-hydroxyvitamin D levels (less than 5 ng/mL) and the effect of treatment. After calcium supplementation with or without vitamin D, their biochemical abnormalities disappeared. They maintained normocalcemia without medication after correction of their unbalanced diet. The present study indicated that patients with vitamin D deficiency occasionally showed biochemical findings suggestive of PHP and that such patients could exhibit not only PHP type II pattern of response to exogenous PTH but also of type I pattern. Thus our clinical observation suggests the complexity of PTH resistance in vitamin D deficiency and underscores the importance of diet to prevent the disorder.

Individualized high-dose cabergoline therapy for hyperprolactinemic infertility in women with micro- and macroprolactinomas.

CONTEXT: Cabergoline is effective for hyperprolactinemic hypogonadism. However, the rate of cabergoline-induced pregnancy in women with prolactinoma remains unknown. Also unknown is whether cabergoline can control tumor growth and thereby achieve successful pregnancy in patients with macroprolactinomas. METHODS: Eighty-five women with macroprolactinomas (n = 29) or microprolactinomas (n = 56) received prospective, high-dose cabergoline therapy for infertility based on individual prolactin suppression and/or tumor shrinkage. The patients included 31 bromocriptine-resistant, 32 bromocriptine-intolerant, and 22 previously untreated women. Conception was withheld until three regular cycles returned in women with microadenoma and until tumors shrank below 1.0 cm in height in women with macroadenoma. Cabergoline was withdrawn at the fourth gestational week. RESULTS: Cabergoline normalized hyperprolactinemia and recovered the ovulatory cycle in all patients. All adenomas contracted, and 11 macroadenomas and 29 microadenomas disappeared. Eighty patients (94%) conceived 95 pregnancies, two of which were cabergoline-free second pregnancies. The dose of cabergoline at the first pregnancy was 0.25-9 mg/wk overall and 2-9 mg/wk in the resistant patients. Of the 93 pregnancies achieved on cabergoline, 86 resulted in 83 single live births, one stillbirth, and two abortions; the remaining seven were ongoing. All babies were born healthy, without any malformations. No mothers experienced impaired vision or headache suggestive of abnormal tumor reexpansion throughout pregnancy. CONCLUSION: Cabergoline achieved a high pregnancy rate with uneventful outcomes in infertile women with prolactinoma, independent of tumor size and bromocriptine resistance or intolerance. Cabergoline monotherapy could substitute for the conventional combination therapy of pregestational surgery or irradiation plus bromocriptine in macroprolactinomas.

Anterior interhemispheric approach for 100 tumors in and around the anterior third ventricle.

OBJECTIVE: We report our experience with anterior interhemispheric approach for tumors in and around the anterior third ventricle, including surgical technique, instrumentation, pre- and postoperative hormonal disturbances, and resection rate. METHODS: One hundred patients with 46 craniopharyngiomas, 12 hypothalamic gliomas, 12 meningiomas, 6 hypothalamic hamartomas, and 24 other lesions were operated on using an anterior interhemispheric approach with or without opening of the lamina terminalis. This surgical approach involves no frontal sinus opening; a narrow (approximately 15-20 mm in width) access between the bridging veins, which is sufficient to remove the tumor totally; and sparing of the anterior communicating artery. Specially designed long bipolar forceps and scissors are necessary for this approach, and concomitant use of angled instruments (endoscope, aspirator, and microforceps) is required frequently. The postsurgical follow-up period varied from 4 months to 18 years. RESULTS: Total removal of the neoplasm was accomplished in 37 of 46 patients with craniopharyngiomas (80.4%), whereas subtotal resection was performed in hypothalamic gliomas. No significant differences in pre- and postoperative hormonal disturbances were observed in 37 craniopharyngiomas and 10 hypothalamic gliomas. There was no operative mortality. Visual acuity was preserved or improved in 68 of 75 patients assessed. The Karnofsky Performance Scale score did not deteriorate in 72 of 75 patients tested. CONCLUSION: The minimally invasive anterior interhemispheric approach, with or without opening of the lamina terminalis, is useful for removal of tumors in and around the anterior third ventricle, such as craniopharyngiomas and hypothalamic gliomas.

Prospective study of high-dose cabergoline treatment of prolactinomas in 150 patients.

CONTEXT: Cabergoline fails to normalize hyperprolactinemia in a considerable proportion of prolactinomas, especially macroadenomas. OBJECTIVE: We examined the effect of individualized high-dose cabergoline treatment on hyperprolactinemia in prolactinomas. PATIENTS: The study included 122 women and 28 men (93 microadenomas and 57 macroadenomas). Forty-seven had undergone transsphenoidal surgery. According to the preceding medical treatment, the participants were separated into untreated (group U; n = 60), intolerant (group I; n = 64), and resistant (group R; n = 26) groups. INTERVENTIONS: We promptly increased cabergoline dose on the basis of individual prolactin levels. Length of treatment was 1 yr. RESULTS: Cabergoline normalized hyperprolactinemia in all patients except one. The proportion of prolactin normalization in both groups U and I was 83% at 3 months and 95% at 6 months. By contrast, that in group R was 35% at 3 months and 58% at 6 months. Mean cabergoline dose in milligrams per week at the time of prolactin normalization was 2.0 +/- 0.3 in group U, 0.9 +/- 0.1 in group I, and 5.2 +/- 0.6 in group R. Prolactin normalization rate at the 3 mg/wk dose was 84% overall but only 35% in group R. Serum progesterone or testosterone levels, diminished in 122 women or 16 men, respectively, were recovered in all except one resistant and four postmenopausal or panhypopituitary patients. CONCLUSION: Individualized high-dose cabergoline treatment can normalize hyperprolactinemia and hypogonadism in nearly all prolactinomas irrespective of tumor size or preceding treatments. Hyperprolactinemia could be controlled in poor responders within 1 yr with doses higher than 3 mg/wk.

Symptomatic hypercalcemia due to painless thyroiditis after unilateral adrenalectomy in a patient with Cushing's syndrome.

We report a 53-year-old woman with Cushing's syndrome due to an adrenocortical adenoma, who underwent unilateral adrenalectomy and developed symptomatic hypercalcemia during the thyrotoxic period of painless thyroiditis, while tapering off a daily supplemented dose of cortisol. A study of patients with thyrotoxicosis and hypoadrenalism at our institute revealed that mild hypercalcemia was present in 9.9% of those with thyrotoxicosis and 5.0% of those with hypoadrenalism. The present case suggests that the simultaneous occurrence of thyrotoxicosis and hypoadrenalism may lead to overt hypercalcemia due to a synergistic increase in bone resorption and impaired urinary excretion of calcium.

Remarkable effects of cabergoline in a patient with huge prolactinoma resistant to high-dose bromocriptine: case report.

BACKGROUND: Cabergoline (CAB) has been proposed as the first-line treatment in the management of prolactin (PRL)-secreting tumors (prolactinoma [PRLoma]), including those resistant to standard dopamine agonist (DAA) therapy. The authors report remarkable effects of CAB in a case of huge PRLoma that had been resistant to a long-term, high-dose treatment with bromocriptine (BRC). CASE DESCRIPTION: A 28-year-old man was originally presented with oculomotor paresis when he was 9 years old. After 2 partial resections, he was treated with a maximum 60-mg/d dose of BRC for 18 years. Nonetheless, the tumor grew up to more than 8 cm in diameter, serum PRL increased over 60000 ng/mL, and his visual acuity deteriorated. Cabergoline normalized serum PRL level, shrank the tumor mass remarkably, and caused marked improvement of visual acuity. CONCLUSION: Prolactin normalization and significant tumor shrinkage could be achieved with CAB even in extremely BRC-resistant PRLomas. Surgical resection should be reserved only for patients who are resistant to cabergoline or who require urgent decompression in such emergency as massive intratumoral hemorrhage.

Frequent occurrence of protein isoforms with or without a single amino acid residue by subtle alternative splicing: the case of Gln in DRPLA affects subcellular localization of the products.

Protein isoforms with or without a single amino acid residue make a subtle difference. It has been documented on a few genes that alternative splicing generated such isoforms; however, the fact has attracted little attention. We became aware of a subtle sequence difference in DRPLA, a polyglutamine disease gene for dentatorubral pallidoluysian atrophy. Some reported cDNA sequences lacked 3 nucleotides (nt) (CAG), which were positioned apart from the expandable and polymorphic CAG repeats and also coded for glutamine. We experimentally confirmed that the difference was indeed generated by alternative splicing utilizing two acceptors separated by 3 nt. In DRPLA, the expression ratio of two mRNA isoforms was almost constant among tissues, with the CAG-included form being major. The glutamine-included protein isoform was more predominantly localized in the nucleus. Database searching revealed that alternative splice acceptors, as well as donors, are frequently situated very close to each other. We experimentally confirmed two mRNA isoforms of 3 nt difference in more than 200 cases by RT-PCR and found interesting features associated with this phenomena. Inclusion of 3 nt tends to result in single amino acid inclusion despite the phase of translational frame. The expression ratio sometimes varied extensively among tissues.