Transcriptomic Profiling of Lactotroph Pituitary Neuroendocrine Tumors via RNA Sequencing and Ingenuity Pathway Analysis.

INTRODUCTION: Lactotroph pituitary neuroendocrine tumors (PitNETs) are common pituitary tumors, but their underlying molecular mechanisms remain unclear. This study aimed to investigate the transcriptomic landscape of lactotroph PitNETs and identify potential molecular mechanisms and therapeutic targets through RNA sequencing and ingenuity pathway analysis (IPA). METHODS: Lactotroph PitNET tissues from five surgical cases without dopamine agonist treatment underwent RNA sequencing. Normal pituitary tissues from 3 patients served as controls. Differentially expressed genes (DEGs) were identified, and the functional pathways and gene networks were explored by IPA. RESULTS: Transcriptome analysis revealed that lactotroph PitNETs had gene expression patterns that were distinct from normal pituitary tissues. We identified 1,172 upregulated DEGs, including nine long intergenic noncoding RNAs (lincRNAs) belonging to the top 30 DEGs. IPA of the upregulated DEGs showed that the estrogen receptor signaling, oxidative phosphorylation signaling, and EIF signaling were activated. In gene network analysis, key upstream regulators, such as EGR1, PRKACA, PITX2, CREB1, and JUND, may play critical roles in lactotroph PitNETs. CONCLUSION: This study provides a comprehensive transcriptomic profile of lactotroph PitNETs and highlights the potential involvement of lincRNAs and specific signaling pathways in tumor pathogenesis. The identified upstream regulators may be potential therapeutic targets for future investigations.

Lung adenocarcinoma metastasis within a pituitary neuroendocrine tumor: a case report with review of literature.

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.

Comparison of prophylactic antibiotics for endonasal transsphenoidal surgery using a national inpatient database in Japan.

BACKGROUND: The choice of prophylactic antibiotics for use in endonasal transsphenoidal surgery (ETSS) lacks universal standards. This study aimed to investigate the effectiveness of cefazolin, ampicillin and third-generation cephalosporins for preventing postoperative meningitis and secondary outcomes (in-hospital death and the combination of pneumonia and urinary tract infection) in patients who have undergone ETSS. METHODS: The study used data from the Diagnosis Procedure Combination database in Japan. Data from 10 688 patients who underwent ETSS between April 2016 and March 2021 were included. Matching weight analysis based on propensity scores was conducted to compare the outcomes of patients receiving cefazolin, ampicillin or third-generation cephalosporins as prophylactic antibiotics. RESULTS: Of the 10 688 patients, 9013, 102 and 1573 received cefazolin, ampicillin and third-generation cephalosporins, respectively. The incidence of postoperative meningitis did not significantly differ between the cefazolin group and the ampicillin group (OR, 1.02; 95% CI, 0.14-7.43) or third-generation cephalosporins group (OR, 0.81; 95% CI, 0.10-6.44). Similarly, in-hospital death and the composite incidence of pneumonia and urinary tract infection did not differ between the cefazolin group and the ampicillin or third-generation cephalosporins group. CONCLUSIONS: Cefazolin, ampicillin and third-generation cephalosporins as perioperative prophylactic antibiotics for ETSS do not differ significantly in terms of preventing meningitis.

Concurrent IgG4-related hypophysitis and clinically nonfunctioning gonadotroph pituitary neuroendocrine tumor.

BACKGROUND: Some patients develop immunoglobulin G4 (IgG4)-related hypophysitis associated with systemic diseases. More than 30 cases of IgG4-related hypophysitis have been reported. However, biopsy has rarely been performed in these patients, and none have had an associated pituitary neuroendocrine tumor (PitNET). We present a case of concurrent IgG4-related hypophysitis and PitNET. CASE PRESENTATION: A 56-year-old Japanese man arrived at the hospital with visual impairment, bitemporal hemianopia, and right abducens nerve palsy. Magnetic resonance imaging revealed pituitary body and stalk swelling as well as a small poorly enhanced right anterior lobe mass. Laboratory and loading test results suggested hypopituitarism. Because IgG4 level was elevated, a systemic examination was performed; multiple nodules were found in both lung fields. The diagnosis was based on an endoscopic transnasal biopsy of the pituitary gland. A histopathological examination revealed a marked infiltration of plasma cells into the pituitary gland, which was strongly positive for IgG4. The histological features of the resected tumor were consistent with those of gonadotroph PitNET, which was immunohistochemically positive for follicle-stimulating hormone-ß and steroidogenic factor-1, and no plasma cell infiltration was observed. Based on the histopathological examination results, steroid therapy was initiated, which reduced pituitary gland size and serum IgG4 levels. DISCUSSION AND CONCLUSIONS: This is the first reported case of IgG4-related hypophysitis with PitNET. Although no pathological findings indicating a relationship between the two conditions were found, we were able to preoperatively differentiate multiple lesions via detailed diagnostic imaging.

Endoscopic spinal cord untethering using a 1 cm skin incision technique in pediatrics: a technical case report.

BACKGROUND: Spinal cord untethering by sectioning the filum terminale is commonly performed in tethered cord syndrome patients with minor abnormalities such as filar lipoma, thickened filum terminale, and low conus medullaris. Our endoscopic surgical technique, using the interlaminar approach, allows for sectioning the filum terminale through a very small skin incision. To our knowledge, this procedure has not been previously reported. This is the first case report involving a 1 cm skin incision. CASE PRESENTATION: A 9-month-old male patient was referred to our neurosurgical department due to a coccygeal dimple. MRI revealed a thickened fatty filum. After considering the treatment options for this patient, the parents agreed to spinal cord untethering. A midline 1 cm skin incision was made at the L4/5 vertebral level. Untethering by sectioning the filum terminale was performed by full endoscopic surgery using the interlaminar approach. The procedure was uneventful and there were no postoperative complications. CONCLUSIONS: In terms of visibility and minimizing invasiveness, our surgical technique of using the interlaminar approach with endoscopy allows for untethering by sectioning the filum terminale through a very small skin incision.

Outcomes After Endoscopic Evacuation Versus Evacuation Using Craniotomy or Stereotactic Aspiration for Spontaneous Intracerebral Hemorrhage: Analysis Using a Japanese Nationwide Database.

BACKGROUND: Various surgical methods are available for managing large intracerebral hemorrhage. This study compared the prognosis of patients with spontaneous intracerebral hemorrhage who underwent endoscopic evacuation, stereotactic aspiration, and craniotomy by using a nationwide inpatient database in Japan. METHODS: Using the Diagnosis Procedure Combination database, we identified patients who underwent surgery for spontaneous intracerebral hemorrhage within 48 h after admission between April 2014 and March 2018. Eligible patients were classified into three groups according to the type of surgery (endoscopic surgery, stereotactic surgery, and craniotomy). Propensity score matching weight analysis was conducted to compare poor modified Rankin Scale score at discharge (severe disability or death) and hospitalization cost among the groups. RESULTS: Among 17,860 eligible patients, craniotomy, stereotactic surgery, and endoscopic surgery were performed in 14,354, 474, and 3,032 patients, respectively. In the matching weight analysis, all covariates were well balanced. Compared with the endoscopic surgery group, the proportion of poor prognosis (modified Rankin Scale score at discharge of 5 or 6) was significantly higher in craniotomy groups (odds ratio 2.51, 95% confidence interval 1.11-5.68; p = 0.028). Subgroup analysis based on hemorrhage location and consciousness level at the time of admission showed no significant difference between the surgical procedures. Hospitalization costs were significantly higher in the craniotomy group than in the endoscopic surgery group (difference US $9,724, 95% confidence interval 2,169-17,259; p = 0.011). CONCLUSIONS: Endoscopic surgery for spontaneous intracerebral hemorrhage was associated with improved prognosis compared with craniotomy at the hospital discharge. Future large-scale clinical trials are needed to evaluate the optimal surgical techniques for intracerebral hemorrhage.

Endoscopic surgery versus craniotomy for spontaneous intracerebral hemorrhage in the late elderly patients.

OBJECTIVES: To compare the prognosis of late elderly patients with spontaneous intracerebral hemorrhage (ICH) treated by endoscopic evacuation and craniotomy MATERIALS AND METHODS: Using the Diagnosis Procedure Combination database, we identified patients aged ≥ 75 years who underwent surgery for spontaneous ICH within 48 hours after admission between April 2014 and March 2018. Eligible patients were classified into two groups according to the type of surgery (endoscopic surgery and craniotomy). Propensity-score matching weight analysis was conducted to compare the good neurological outcome modified Rankin Scale (mRS) score (0-4) at discharge as the primary endpoint between the two groups. Secondary endpoints were postoperative meningitis, tracheostomy, reoperation within 3 days and total hospitalization costs. RESULTS: Among the 5,396 eligible patients, endoscopic surgery and craniotomy were performed in 895 and 4,501 patients, respectively. In the propensity-score matching weight analysis, all covariates were well balanced. The proportions of patients with a good prognosis (mRS score at discharge: 0-4) did not significantly differ between the surgical procedures (42.1% vs. 42.8%, p = 0.828). The proportions of meningitis, tracheostomy and reoperation were not significantly different between the two groups. Hospitalization costs were significantly higher in the craniotomy group than in the endoscopic surgery group (25,536 vs. 29,603 US dollars, p = 0.012). CONCLUSIONS: Inhospital outcomes did not differ between endoscopic and open surgeries for spontaneous ICH in the late-stage elderly patients aged ≥75 years. Hospitalization costs were significantly higher in the craniotomy group, suggesting that endoscopic surgery may be more acceptable.

Trends in surgical procedures for spontaneous intracerebral hemorrhage in Japan.

OBJECTIVES: Minimally invasive surgery for spontaneous intracerebral hemorrhage (ICH) has become increasingly popular in recent years. However, there are no reports on the recent trends in surgical procedures for spontaneous ICH. To investigate current trends in surgical methods for spontaneous ICH using a nationwide inpatient database from Japan. MATERIALS AND METHODS: Patients who underwent surgery for spontaneous ICH between April 2014 and March 2018 were identified in a nationwide inpatient database from Japan. We examined patient characteristics, diagnoses, types of surgery, complications, and discharge status. RESULTS: We identified 21,129 inpatients who underwent surgery for spontaneous ICH. The procedures were as follows: 16,256 (76.9%) transcranial hemorrhage evacuations, 3722 (17.6%) endoscopic hemorrhage evacuations, and 1151 (5.4%) stereotactic aspirations of hemorrhage. Patients tended to receive transcranial hemorrhage evacuations in hospitals with fewer surgical cases. The proportions of endoscopic hemorrhage evacuations increased annually, whereas those of stereotactic surgery decreased. The proportions of transcranial surgery remained almost unchanged. Tracheostomy and hospitalization costs were lower in the stereotactic aspirations of hemorrhage group, and the proportions of reoperation were higher in the endoscopic hemorrhage evacuations group. CONCLUSIONS: The use of endoscopic surgery for spontaneous ICH has increased in Japan. This study can form the basis of future clinical investigations into spontaneous ICH surgery.

Pituitary surgery's epidemiology using a national inpatient database in Japan.

BACKGROUND: Between 2010 and 2014, microscopic transsphenoidal surgery (mTSS) was performed more frequently than endoscopic TSS (eTSS) in the USA. However, few epidemiological studies on pituitary surgery are currently available. METHODS: We performed a retrospective study on patients who had undergone pituitary surgery between July 2010 and March 2016. To this end, a nationwide inpatient database in Japan was used. Patients' characteristics, diagnoses, types of surgery, complications, and discharge status were examined. RESULTS: A total of 16,253 inpatients who received pituitary surgery were identified. Patients were diagnosed with diseases for insurance claims described below: pituitary adenoma, hyperprolactinemia, other pituitary disorders (e.g., Rathke's cleft cyst), hyperpituitarism, craniopharyngioma, acromegaly, Cushing's disease, and pituitary cancer. Among them, pituitary adenomas, primarily the non-functioning ones, were the most frequent (66.9%). A total of 14,285 (88%) patients underwent TSS, while 1968 (12%) patients were treated using transcranial surgery. The number of patients undergoing TSS increased each year. The number of eTSS operations was 8140 (77%) and that of mTSS operations was 2419 (23%). Of note, eTSS increased each year. We found that high-volume hospitals more frequently selected eTSS. Compared with mTSS, eTSS was associated with a reduction of hyponatremia incidence (odds ratio, 0.69; p = 0.019). Additionally, it was not associated with other major complications. CONCLUSION: The present study showed that both TSS and eTSS increased on a yearly basis. We believe that the present study will be the basis of future epidemiological investigations of pituitary surgery.

Applicability of Anti-Human Estrogen Receptor ß Antibody PPZ0506 for the Immunodetection of Rodent Estrogen Receptor ß Proteins.

Several lines of controversial evidence concerning estrogen receptor ß (ERß) remain to be solved because of the unavailability of specific antibodies against ERß. The recent validation analysis identified a monoclonal antibody (PPZ0506) with sufficient specificity against human ERß. However, the specificity and cross-reactivity of PPZ0506 antibody against ERß proteins from laboratory animals have not been confirmed. In the present study, we aimed to validate the applicability of PPZ0506 to rodent studies. The antibody exhibited specific cross-reactivity against mouse and rat ERß proteins in immunoblot and immunocytochemical experiments using transfected cells. In immunohistochemistry for rat tissue sections, PPZ0506 showed immunoreactive signals in the ovary, prostate, and brain. These immunohistochemical profiles of rat ERß proteins in rat tissues accord well with its mRNA expression patterns. Although the antibody was reported to show the moderate signals in human testis, no immunoreactive signals were observed in rat testis. Subsequent RT-PCR analysis revealed that this species difference in ERß expression resulted from different expression profiles related to the alternative promoter usage between humans and rats. In conclusion, we confirmed applicability of PPZ0506 for rodent ERß studies, and our results provide a fundamental basis for further examination of ERß functions.

Characterization of rodent constitutively active estrogen receptor α variants and their constitutive transactivation mechanisms.

Estrogen receptor α (ERα) mRNAs exhibit remarkable heterogeneity owing to complicated alternative splicing. Some encode C-terminally-truncated ERα proteins, which display ligand-independent transactivation or dominant-negative activity. We previously characterized C-terminally-truncated ERα mRNA variants with cryptic sequences in humans and mice, and demonstrated that helices in the ligand-binding domains (LBDs) of ERα variants contribute to ligand-independent transcriptional activity. However, existence of non-conventional coding exons and generation of constitutively active ERα variants have remained to be examined in rats. To comparatively analyze modular organization and splicing profiles of the ERα genes, the range of C-terminally-truncated ERα variants was explored in rats and mice using rapid amplification of cDNA ends and RT-PCR cloning. Furthermore, their functions were determined in transiently transfected cells using expression constructs and luciferase reporter assays. Multiple cryptic exons and C-terminally-truncated ERα variant mRNAs were identified in rats and mice. Naturally occurring and artificially truncated variants/constructs lacking helix 5 potentially exhibited gain-of-function in transfected cells. Although cryptic exons and splicing profiles were poorly conserved among humans, mice, and rats, constitutively active variants were generated from the ERα genes. Moreover, the primary mechanism of ligand-independent activation by C-terminally-truncated ERα variants is C-terminus to helix 5 deletion in the LBD. This comparative study documented the complexity of ERα genes, mRNAs, and proteins, and further determined the underlying structural basis of ligand-independent activation by C-terminally-truncated ERα variants.

Radiological findings of transorbital penetrating intracranial injury in a child.

In penetrating injuries, woods are known to be difficult to detect with radiological imaging studies, because the wood density are known to be extremely close to the value of air on CT. Adjustment of CT window and reconstruction of a 3D image from CT images allowed us to more accurately distinguish wood from air and to find the fragment of the wooden chopstick. It is particularly useful in transorbital penetrating injury.

Fascia patchwork closure for endoscopic endonasal skull base surgery.

With the development of endoscopic technology and surgery, resection of midline skull base tumors has been achieved using endoscopic endonasal skull base (EESB) approaches. EESB approaches reportedly have a greater risk of postoperative cerebrospinal fluid (CSF) leakage. Recently, the introduction of the nasoseptal flap (NSF) decreased dramatically the incidence of CSF leakage, but the use of an NSF increases the risk of disturbing the function of the nose. Here, we report our new technique called "fascia patchwork closure" for closure after EESB surgery and its outcome. All 48 cases involved midline skull base tumors resected via EESB approaches. Of them, 32 cases were closed by the fascia patchwork technique after tumor resection, and there was no incidence of CSF leakage. Moreover, 6 of the 32 cases were closed without the use of an NSF, indicating that the fascia patchwork closure approach is effective as part of a multilayer closure for the prevention of CSF leakage. The establishment and popularization of this technique might result in the further development of EESB surgery and also an improvement of postoperative nasal function.

Primary ciliary dyskinesia diagnosed on nasal mucosal biopsy in two newborns.

Primary ciliary dyskinesia (PCD) is a genetic disease that causes abnormalities in ciliary structure and/or function. Ciliated cells line the upper and lower respiratory tracts and the Eustachian tube. Impairment of mucus clearance at these sites leads to sinusitis, repeated pulmonary infections, bronchiectasis, and chronic otitis media. Situs inversus occurs randomly in approximately 50% of subjects with PCD. The triad of situs inversus, bronchiectasis and sinusitis is known as Kartagener syndrome. PCD is usually an autosomal recessive disease, but occasional instances of X-linked transmission have been reported. Specific diagnosis requires examination of ciliary function or structure on light and electron microscopy. Early diagnosis and respiratory management are important in order to prevent the development of bronchiectasis and deterioration in lung function. We report early diagnosis of PCD on nasal mucosal biopsy in two newborns who presented with prolonged respiratory distress and rhinorrhea.

Pediatric mumps with laryngeal edema.

Mumps virus infection primarily affects the salivary glands and may incur various complications. Laryngeal edema is such a rare complication that few adult cases have been reported. We report the first known pediatric patient with mumps with laryngeal edema. An 8-year-old boy developed dyspnea after a rapidly progressive swelling of his face and neck. Laryngoscopy revealed edematous changes in the supraglottic and subglottic regions, and computed tomography confirmed significant laryngeal edema in addition to swelling of the cervical soft tissue and the salivary glands. Laboratory findings revealed a high serum amylase level and confirmed the diagnosis of mumps. Intravenous steroid administration alleviated the dyspnea, although the patient required temporary tracheal intubation to maintain airway patency. He did not need tracheotomy and did not experience any other complications. Laryngeal edema must be regarded as a rare, potentially life-threatening complication of mumps. When mumps is diagnosed with significant swelling of the neck, an emergency airway should be established to prevent airway obstruction.

Estrogen Receptor α Isoforms Generated by Alternative Use of Cryptic Exons.

Estrogen receptor α (ERα) regulates several physiological functions. In pathophysiological conditions, ERα is involved in the development and progression of estrogen-sensitive tumors. The ERα gene contains multiple 5'-untranslated exons and eight conventional coding exons and presents multiple isoforms generated by alternative promoter usage and alternative splicing. This gene also possesses non-conventional exons in the 3'- and intronic regions, and alternative use of cryptic exons contributes to further diversity of ERα mRNAs and proteins. Recently, the genomic organization of ERα genes and the splicing profiles of their transcripts were comparatively analyzed in humans, mice, and rats, and multiple ERα isoforms with distinct structures and functions were identified. These transcripts contain cryptic sequences that encode insertion-containing or truncated ERα proteins. In particular, alternative cryptic exons with in-frame stop codons yield transcripts encoding C-terminally-truncated ERα proteins. The C-terminally-truncated ERα isoforms lack part or all of the ligand-binding domain but possess an isoform-specific sequence. Some of these isoforms exhibit constitutive transactivation and resistance to estrogen receptor antagonists. Although numerous studies have reported conflicting results regarding their functions, the critical determinant for their gain-of-function has been identified structurally. Here we review recent progress in ERα variant research concerning the genomic organization of ERα genes, splicing profiles of ERα transcripts, and transactivation properties of ERα isoforms.

Assessment of anterior pituitary reserve capacity based on growth hormone response to growth hormone-releasing peptide-2 test in the elderly.

OBJECTIVE: The growth hormone (GH)-releasing peptide-2 (GHRP-2) test is relatively safe among endocrine stimulation tests for the elderly. We investigated whether anterior pituitary function in elderly patients could be assessed on the basis of GH response to the GHRP-2 test. DESIGN: Sixty-five elderly patients aged 65 years and older with non-functioning pituitary neuroendocrine tumor (PitNET) who underwent pituitary surgery and preoperative endocrine stimulation tests were classified into the "GH normal group" and "GH deficiency group" based on GH response to the GHRP-2 test. The baseline characteristics and anterior pituitary function were compared between the groups. RESULTS: Thirty-two patients were assigned to the GH normal group and 33 to the GH deficiency group. The cortisol and adrenocorticotropic hormone (ACTH) results in the corticotropin-releasing hormone test were significantly higher in the GH normal group than in the GH deficiency group (p < 0.001). The relationship between the cortisol and ACTH results and the GH response revealed significant correlations (p < 0.001). In addition, receiver operating characteristic curve analysis identified that the optimal cut-off point for a peak GH level in the correlation between adrenocortical function and GH response to the GHRP-2 test was 8.08 ng/mL (specificity 0.868, sensitivity 0.852). CONCLUSION: The present study indicated that adrenocortical function was significantly correlated with GH response to the GHRP-2 test in elderly patients before pituitary surgery. For elderly patients with non-functioning PitNET, GH response to the GHRP-2 test may support in diagnosing adrenocortical insufficiency.

Creation of low cost, simple, and easy-to-use training kit for the dura mater suturing in endoscopic transnasal pituitary/skull base surgery.

Training kits for laparoscopes for deep suturing under endoscopes are commercially available; however, previously reported training kits for endoscopic transnasal transsphenoidal pituitary/skull base surgery (eTSS) were not available in the market. Moreover, the previously reported low cost, self-made kit has the drawback of being unrealistic. This study aimed to create a low cost training kit for eTSS dura mater suturing that was as close to real as possible. Most necessary items were obtained from the 100-yen store ($1 store) or from everyday supplies. As an alternative to the endoscope, a stick-type camera was used. Through the assembly of the materials, a simple and easy-to-use training kit was created, which is almost identical to the actual dural suturing situation. In eTSS, a simple and easy-to-use training kit for dural suturing was successfully created at a low cost. This kit is expected to be used for deep suture operations and the development of surgical instruments for training.

Exploring endocrinological pitfalls in pituitary surgery in the elderly.

Background: Endoscopic transsphenoidal surgery (ETSS) is performed more frequently in elderly patients. We investigated endocrinological pitfalls in pituitary surgery in the elderly by a comparative study focusing only on elderly patients. Methods: Ninety-nine elderly patients aged 65 years and over with non-functioning pituitary adenoma (NFPA) who underwent ETSS were retrospectively examined and classified into the early (aged 65-74 years) and late (aged 75 years and over) elderly groups. The baseline characteristics and anterior pituitary function were compared between the groups. Results: Seventy patients were assigned to the early elderly group and 29 to the late elderly group. Thyroid-stimulating hormone (TSH) response in preoperative and postoperative thyrotropin-releasing hormone (TRH) tests revealed a significant difference between the groups. Preoperative and postoperative TSH responses were significantly correlated in both groups. Residual analysis of the correlation between preoperative free triiodothyronine (T3) secretion quantity and preoperative TSH response in both groups, which was significant, indicated that preoperative TSH response was significantly normal when preoperative free T3 secretion quantity was normal in the early elderly group, but preoperative free T3 secretion quantity was significantly lower regardless of preoperative TSH response in the late elderly group. Conculsions: The present study suggested that preoperative and postoperative TSH secretory capacity was presumed to be normal when preoperative free T3 levels were normal in the early elderly patients with NFPA. On the other hand, TSH secretory capacity in the late elderly patients could only be assessed by the TRH test, which should be taken into account.