Collision tumors involving the metastasis of malignant neoplasms to pituitary neuroendocrine tumors (PitNETs) are extremely rare. We herein report a case involving a patient with lung adenocarcinoma metastasis within a PitNET who exhibited relatively rapid progression of neurological symptoms. A 75-year-old man who underwent tumor resection 36 and 18 years prior to presentation for bladder and colon cancer, respectively, without recurrence presented with bitemporal hemianopsia, ptosis, and diplopia of the right eye. Subsequent magnetic resonance imaging (MRI) revealed a tumor 3.2 cm in diameter that extended from the anterior pituitary gland to the suprasellar region. Gadolinium-enhanced MRI of the tumor showed heterogeneous contrast enhancement. Considering the relatively rapid progression of neurological symptoms, semi-emergency endoscopic endonasal transsphenoidal surgery was performed. Histopathological examination revealed a group of thyroid transcription factor-1- and napsin A-positive papillary proliferating cells intermingled with α-subunit- and steroidogenic factor-1-positive PitNET cells. Thus, the patient was diagnosed with lung adenocarcinoma metastasis within a gonadotroph PitNET. Genetic testing revealed the presence of an EGFR (Ex-19del) mutation, after which chemotherapy was initiated. Additional stereotactic radiotherapy was performed for the residual tumor in the sella turcica. With continued chemotherapy, good control of both the primary and metastatic tumors was noted after 24 months after surgery. Cases of malignant neoplasm metastasis within a PitNET are difficult to diagnose. In the case of a sella turcica tumor with relatively rapid progression of neurological symptoms, early surgical intervention is recommended given the possibility of a highly proliferative tumor and the need to obtain pathologic specimens.
Dr. Koji Suzuki and colleague report in the March issue an extremely rare case of metastatic lung adenocarcinoma within a gonadotroph pituitary neuroendocrine tumor (PitNET), representing a considerably expeditious progression of a variety of neurological symptoms. This excellent report provides us with invaluable insight into diagnosis and therapeutics for coexisting primary and metastatic tumors in pituitary gland.
Accumulating evidence suggests that cellular heterogeneity in organs and cell-cell and tissue-tissue interactions are crucial for maintaining physical homeostasis and disease progression. Endocrine organs also exhibit cellular heterogeneity and comprise multiple cell types. For instance, the pituitary gland comprises five types of pituitary hormone-producing cells as well as non-hormone-producing supporting cells, such as fibroblasts, endothelial cells, and folliculostellate cells. However, the functional roles of the interactions between hormone-producing and non-producing cells in the pituitary gland remain incompletely understood. Over the past decade, emerging technologies such as single-cell and spatial transcriptomics have provided excellent tools for studying cellular heterogeneity and their interactions; however, the application of these technologies in endocrine research remains limited. This review provides an overview of these technologies and discusses their strengths and limitations. Additionally, we also summarize the potential future applications of single-cell and spatial transcriptomics in the study of endocrine organs and their disorders.
As well known, endocrine organs including pituitary gland, adrenal gland and pancreatic islet of Langerhans et cetera consist of heterogenous cells, and pathophysiological interplay among hormone-producing cells and non-hormone-producing cells within tissue is crucial, at least in part, for molecular basis of a variety of endocrine diseases. In the February issue, Dr. Ryusaku Matsumoto and Takuya Yamamoto provide a comprehensive, fascinating review article focusing on the update of single-cell and spatial transcriptomics in endocrine research. Our editorial team has a firm belief that this review is a must-read for all dedicating clinicians and scientists on endocrinology.
Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) in several organs including endocrine glands. Among endocrine irAEs, thyroid and pituitary irAEs are frequently observed, followed by primary adrenal insufficiency, insulin-dependent diabetes mellitus, and hypoparathyroidism. These conditions could lead to life-threatening consequences, such as adrenal crisis and diabetic ketoacidosis. On the other hand, several types of irAEs including thyroid and pituitary irAEs are reported to be associated with better overall survival. Therefore, it is important to understand and manage endocrine irAEs, which differ depending on the ICI regimen used. In this review, we describe the clinical features, potential biomarkers, management strategies, and possible mechanisms of thyroid and pituitary irAEs.
It is widely recognized that some cases of immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) result in life-threatening consequences including adrenal crisis and fatal diabetic ketoacidosis. In this issue, Dr. Tomoko Kobayashi and colleague contribute an insightful and well-organized review article on promising biomarkers to predict the onset of endocrine irAEs, particularly underscoring the mechanism-based management strategies and future prospect for pituitary and thyroid irAEs.
In adrenal fasciculata cells stimulated by ACTH, Ca2+ and cAMP play indispensable roles as second messengers in cortisol production. However, whether their second messengers cooperatively or independently participate in steroid production remains unclear. We focused on the roles of Ca2+ and cAMP in cortisol production in bovine adrenal fasciculata cells stimulated by ACTH for a relatively short period (1 h). Incubation of the cells with 100 pM ACTH in Ca2+-containing (normal) medium for 1 h increased cortisol production without affecting cAMP content. In contrast, treatment of the cells with the peptide at a higher concentration (1 nM) significantly augmented both cortisol production and cAMP content. However, ACTH did not increase either of them in the Ca2+-free medium. ACTH rapidly increased the intracellular free Ca2+ concentration ([Ca2+]i) in the normal medium, but did not influence [Ca2+]i in the Ca2+-free medium, indicating that ACTH caused Ca2+ influx into the cells. ACTH-induced Ca2+ influx and cortisol production were suppressed by a voltage-sensitive L-type Ca2+ channel blocker but not by a T-type, N-type, or P-type Ca2+ channel blocker. In contrast, dibutyryl cAMP, a cell-permeable cAMP analog, greatly enhanced cortisol production in the normal or Ca2+-free medium and slowly caused Ca2+ influx into the cells. These results strongly suggest that Ca2+, as a second messenger, is more critical than cAMP for cortisol production. However, both second messengers jointly participate in the production in adrenal fasciculata cells stimulated by ACTH.
It is well known that both Ca2+ and cAMP play critical roles in ACTH-driven cortisol production by adrenal fasciculate cells. However, the division of role for Ca2+ and cAMP in this paradigm still remains obscure. In the December Issue, Dr. Masahiko Kutsukake and colleague elegantly unraveled such a long-standing enigma via sophisticated cellular experiments, demonstrating that cortisol production under steady state is preferentially mediated by Ca2+, but cAMP also participates under stressful conditions where ACTH demand is increased to adapt exaggerated stress.
Immune checkpoint inhibitors (ICIs) are used for various malignancies, although they frequently cause immune-related adverse events involving the thyroid gland (thyroid irAEs). We conducted a retrospective cohort study to elucidate thyroid function outcomes. Fifty of 639 patients who received PD-1 blockade therapy met criteria and were divided into the following groups: thyrotoxicosis with subsequent hypothyroidism (Toxic-Hypo, n = 21); thyrotoxicosis without subsequent hypothyroidism (Toxic, n = 9); and hypothyroidism without prior thyrotoxicosis (Hypo, n = 20). The Toxic-Hypo group developed thyroid irAEs earlier than the Toxic group (26 vs. 91 days; p < 0.001), and had higher serum free T4 levels (3.210 vs. 1.880 ng/dL; p = 0.011). In addition, positive anti-thyroglobulin antibodies (TgAbs) at thyroid irAE onset were more common in the Toxic-Hypo group (93.3%) than in the Toxic group (0.0%; p = 0.005) and Hypo group (44.4%; p = 0.007). The Toxic-Hypo group developed severe hypothyroidism and required larger levothyroxine (LT4) doses than the Hypo group (75 vs. 25 μg/day; p = 0.007). We predicted that patients with positive TgAbs who developed severe thyrotoxicosis within 4 weeks after the first ICI administration would develop subsequent hypothyroidism. We treated 4 such patients with prompt LT4 replacement, characterized by LT4 initiation after thyrotoxicosis improvement and quick dose titration. Their euthyroid state was successfully maintained, in contrast with patients receiving conventional replacement. In conclusion, rapid-onset severe thyrotoxicosis in patients with TgAbs correlated with a high likelihood of subsequent hypothyroidism. Accordingly, prompt LT4 replacement is suggested to prevent a severely hypothyroid state.
As well known, immune checkpoint inhibitors (ICIs) sometimes cause immune-related adverse events in the thyroid gland (thyroid irAEs). Dr. Ichiro Yamauchi and colleague conducted an elaborate retrospective cohort study demonstrating that patients with rapid-onset severe thyrotoxicosis as well as with positive TgAbs titers were highly likely to develop subsequent hypothyroidism. This study provides us with a message that expeditious replacement of levothyroxine is a crucial precaution against severely hypothyroid state.
Effects of pre- and post-pubertal dihydrotestosterone treatment on penile length in 5α-reductase type 2 deficiency
Released on J-STAGE: September 28, 2019 | Volume 66 Issue 9 Pages 837-842
Goro Sasaki, Tomohiro Ishii, Naoaki Hori, Naoko Amano, Keiko Homma, Seiji Sato, Tomonobu Hasegawa
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Effects of 50 mg vildagliptin twice daily vs. 50 mg sitagliptin once daily on blood glucose fluctuations evaluated by long-term self-monitoring of blood glucose
Released on J-STAGE: April 29, 2017 | Volume 64 Issue 4 Pages 417-424
Hiroshi Nomoto, Kimihiko Kimachi, Hideaki Miyoshi, Hiraku Kameda, Kyu Yong Cho, Akinobu Nakamura, So Nagai, Takuma Kondo, Tatsuya Atsumi
Views: 656
Effects of berberine on blood glucose in patients with type 2 diabetes mellitus: a systematic literature review and a meta-analysis
Released on J-STAGE: January 28, 2019 | Volume 66 Issue 1 Pages 51-63
Yaping Liang, Xiaojia Xu, Mingjuan Yin, Yan Zhang, Lingfeng Huang, Ruoling Chen, Jindong Ni
Views: 624
Comprehensive analysis of the safety of semaglutide in type 2 diabetes: a meta-analysis of the SUSTAIN and PIONEER trials
Released on J-STAGE: June 28, 2021 | Volume 68 Issue 6 Pages 739-742
Dao-Gen Yin, Liang-Liang Ding, Hai-Rong Zhou, Mei Qiu, Xue-Yan Duan
Views: 600
Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men
Released on J-STAGE: February 28, 2020 | Volume 67 Issue 2 Pages 153-160
Junichiro Irie, Emi Inagaki, Masataka Fujita, Hideaki Nakaya, Masanori Mitsuishi, Shintaro Yamaguchi, Kazuya Yamashita, Shuhei Shigaki, Takashi Ono, Hideo Yukioka, Hideyuki Okano, Yo-ichi Nabeshima, Shin-ichiro Imai, Masato Yasui, Kazuo Tsubota, Hiroshi Itoh
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