Takuya Kitamura

The ectopic secretion of growth hormone (GH) or growth hormone-releasing hormone (GHRH) is responsible for fewer than 1% of acromegaly cases. Furthermore, within this small population, GHRH-secreting pheochromocytomas/paragangliomas (PPGLs) are even rarer. A 57-year-old Japanese woman presented to our hospital for treatment of a large left-sided pheochromocytoma (PCC). A physical examination revealed enlargement of the nose and lips as well as macroglossia, thereby raising the suspicion of acromegaly, which was biochemically confirmed by a 75-g oral glucose tolerance test. Magnetic resonance imaging demonstrated a slightly enlarged pituitary gland but no definitive tumor. A left adrenalectomy was performed after careful dose titration of doxazosin and metyrosine. Postoperative biochemical improvement of GH excess and immunohistochemical analysis of the resected tumor confirmed the diagnosis of GHRH-secreting PCC. Given the possibility that PPGLs produce various ectopic hormones and peptides, thorough physical examinations remain fundamental for the accurate diagnosis and optimal management of patients with these tumors.

Urinary bladder paraganglioma is a rare tumor associated with a risk of catecholamine‐induced hypertensive crisis during tumor manipulation. The optimal surgical approach remains uncertain, particularly for larger tumors or those with suspected local invasion. We report four cases managed at our institution. All tumors were diagnosed preoperatively by magnetic resonance imaging and ¹²³ I‐metaiodobenzylguanidine scintigraphy, and all patients received preoperative α‐blockade. Three tumors (1.0–1.5 cm) without extravesical extension were treated with laparoscopic partial cystectomy without conversion. One larger tumor (4.3 cm) with suspected local invasion was managed using a planned open procedure and was associated with marked intraoperative hypertension and technical difficulty. These findings suggest that laparoscopic partial cystectomy is technically feasible in selected patients with small, localized bladder paragangliomas, whereas tumor size and suspected local invasion may influence surgical planning. The technical requirements for complete resection and catecholamine‐related hemodynamic risk should be assessed separately.

Familial partial lipodystrophy (FPLD) is a rare inherited disorder characterized by limb adipose tissue atrophy and metabolic abnormalities, including severe insulin resistance. However, diagnosis is often delayed because the characteristic physique can be difficult to recognize without a high index of suspicion. We present the case of a 19-year-old Japanese woman diagnosed with FPLD type 2 (FPLD2). She had a history of irregular menses and hirsutism since adolescence. The FPLD2 diagnosis was prompted by her concerns about axillary and inguinal pigmentation. Her mother’s online search first suggested acanthosis nigricans (AN). After including “muscular limb” as an additional search term, they suspected lipodystrophy, prompting a consultation with an endocrinologist. Clinical examination revealed impaired glucose tolerance, severe insulin resistance, dyslipidemia, fatty liver, and polycystic ovary syndrome. Genetic testing identified a heterozygous LMNA p.R482Q variant, confirming the diagnosis. This case demonstrates that AN, a skin manifestation of insulin resistance, is an important diagnostic clue for FPLD. Although women with FPLD frequently present with menstrual irregularities and hirsutism in their late teens, their insulin levels are rarely measured before diabetes onset. Consequently, the underlying severe insulin resistance is frequently overlooked. Although reported cases of FPLD2 in Japan are limited, many cases may remain undiagnosed. Therefore, clinicians should examine the friction-prone areas in non-severely obese individuals with metabolic or menstrual irregularities. The absence of AN does not rule out insulin resistance. Therefore, even without AN, the presence of other features of insulin resistance warrant consideration of FPLD and careful evaluation for limb fat loss, facilitating early diagnosis.

The widespread use of imaging studies has led to an increased detection rate of adrenal incidentalomas. Among adrenal incidentalomas, mild autonomous cortisol secretion (MACS) is a common etiology. Development of overt Cushing syndrome (CS) from MACS is a rare event with an estimated prevalence of <1%. Herein, we report a case of cortisol-producing adenoma that demonstrated clinical and biochemical progression, resulting in the development of overt CS. A 50-year-old Japanese woman was referred for the evaluation of CS because of elevated blood pressure and peripheral edema. She had been followed for her left adrenal tumor and MACS before but was lost to follow-up for 2 years and 9 months. At presentation, she had cushingoid features. The 1-mg overnight dexamethasone suppression test indicated greater severity of autonomous cortisol secretion than that in the initial assessment. Imaging studies revealed that her left adrenal tumor increased in size. She underwent laparoscopic left adrenalectomy. Histologic and immunohistochemical examinations confirmed a cortisol-producing adenoma. Sequencing analysis identified a somatic GNAS variant (p.Arg201Cys) in the tumor. Patients with MACS can demonstrate clinical and biochemical progression over time. Considering the high prevalence of MACS, predictive tools such as biomarkers to identify these cases are highly desired.

Summary Functioning gonadotroph tumors are rare neoplasms that can cause ovarian hyperstimulation syndrome (OHSS) in women of reproductive age. Here, we present a case of a follicle-stimulating hormone (FSH)-producing pituitary neuroendocrine tumor (PitNET) with irregular menstrual cycles and OHSS in a Japanese woman. A 34-year-old woman with bilateral multi-cystic ovarian mass was referred to our hospital for ovarian surgery. The imaging feature of magnetic resonance imaging (MRI) of the ovary and elevated estradiol levels with normal FSH and low luteinizing hormone (LH) levels led us to suspect the presence of a functioning gonadotroph PitNET. MRI revealed a 19-mm pituitary tumor, and increased tracer uptake was observed in the pituitary lesion on ¹¹¹In-pentetreotide scintigraphy. Transsphenoidal tumor resection resulted in the resolution of the ovarian enlargement, normalization of her menstrual cycles, and spontaneous pregnancy. Immunohistochemistry (IHC) of the resected tumor for pituitary transcription factors, including steroidogenesis factor 1 (SF1) and estrogen receptor alpha, demonstrated positive immunoreactivity, whereas IHC for pituitary-specific positive transcription factor 1 was negative, suggesting that the tumor belonged to the SF1 lineage of PitNETs (gonadotroph tumor). The tumor cells showed positive expression of FSHβ, while LHβ was mostly negative. Consistent with the high pituitary tumor uptake observed on ¹¹¹In-pentetreotide scintigraphy, the pituitary tumor showed positive expression of somatostatin receptor 2A. Detailed clinical and histological evaluations will provide useful information to understand these rare functioning gonadotroph tumors better. Learning points Functioning gonadotroph tumors are very rare neuroendocrine tumors of pituitary origin. Women of reproductive age presenting with bilateral multi-cystic ovarian enlargement, irregular menstrual cycles, and hyperestrogenemia under unsuppressed follicle-stimulating hormone (FSH) levels should be evaluated for FSH-producing tumor. Raising awareness of OHSS due to functioning gonadotroph tumors is crucial to prevent unnecessary ovarian surgery. Comprehensive histological analysis may provide useful information to better understand the characteristics of functioning gonadotroph tumors. Abstract Summary Functioning gonadotroph tumors are rare neoplasms that can cause ovarian hyperstimulation syndrome (OHSS) in women of reproductive age. Here, we present a case of a follicle-stimulating hormone (FSH)-producing pituitary neuroendocrine tumor (PitNET) with irregular menstrual cycles and OHSS in a Japanese woman. A 34-year-old woman with bilateral multi-cystic ovarian mass was referred to our hospital for ovarian surgery. The imaging feature of magnetic resonance imaging (MRI) of the ovary and elevated estradiol levels with normal FSH and low luteinizing hormone (LH) levels led us to suspect the presence of a functioning gonadotroph PitNET. MRI revealed a 19-mm pituitary tumor, and increased tracer uptake was observed in the pituitary lesion on ¹¹¹In-pentetreotide scintigraphy. Transsphenoidal tumor resection resulted in the resolution of the ovarian enlargement, normalization of her menstrual cycles, and spontaneous pregnancy. Immunohistochemistry (IHC) of the resected tumor for pituitary transcription factors, including steroidogenesis factor 1 (SF1) and estrogen receptor alpha, demonstrated positive immunoreactivity, whereas IHC for pituitary-specific positive transcription factor 1 was negative, suggesting that the tumor belonged to the SF1 lineage of PitNETs (gonadotroph tumor). The tumor cells showed positive expression of FSHβ, while LHβ was mostly negative. Consistent with the high pituitary tumor uptake observed on ¹¹¹In-pentetreotide scintigraphy, the pituitary tumor showed positive expression of somatostatin receptor 2A. Detailed clinical and histological evaluations will provide useful information to understand these rare functioning gonadotroph tumors better. Learning points Functioning gonadotroph tumors are very rare neuroendocrine tumors of pituitary origin. Women of reproductive age presenting with bilateral multi-cystic ovarian enlargement, irregular menstrual cycles, and hyperestrogenemia under unsuppressed follicle-stimulating hormone (FSH) levels should be evaluated for FSH-producing tumor. Raising awareness of OHSS due to functioning gonadotroph tumors is crucial to prevent unnecessary ovarian surgery. Comprehensive histological analysis may provide useful information to better understand the characteristics of functioning gonadotroph tumors.