Trends of correlations between serum levels of growth hormone and insulin-like growth factor-I in general practice.

Serum levels of growth hormone (GH) and insulin-like growth factor (IGF)-I are crucial in the diagnosis and management of GH-related diseases. However, these levels are affected by nutritional and metabolic status. To elucidate the correlations between GH and IGF-I in various conditions, a retrospective analysis was performed for adult patients in which GH levels were examined by general practitioners during the period from January 2019 to December 2021. Of 642 patients, 33 patients were diagnosed with acromegaly, 21 were diagnosed with GH deficiency (GHD), and 588 were diagnosed with non-GH-related diseases (NGRD). In contrast to the positive correlations found between the levels of GH and IGF-I in patients with acromegaly (R=0.50; P<0.001) and patients with GHD (R=0.39; P=0.08), a negative correlation was found in the NGRD group (R=-0.23; P<0.001). In that group, the results of multivariable analysis showed that GH levels were predominantly influenced by gender and body mass index (BMI), whereas IGF-I levels were modulated by albumin in addition to age and GH. Of note, in the NGRD group, there was an enhanced negative correlation between GH and IGF-I under conditions of BMI < 22 and albumin < 4.0 g/dL (R=-0.45; P<0.001), and the negative correlation between GH and IGF-I was reinforced by excluding patients with other pituitary diseases and patients taking oral steroids (R=-0.51; P<0.001 and R=-0.59; P<0.001, respectively). Collectively, the results indicate that attention should be given to the presence of a negative correlation between serum levels of GH and IGF-I, especially in lean and low-nutritious conditions.

Occult endocrine disorders newly diagnosed in patients with post-COVID-19 symptoms.

Determination of long COVID requires ruling out alternative diagnoses, but there has been no report on the features of alternative diagnoses. This study was a single-center retrospective study of outpatients who visited our clinic between February 2021 and June 2023 that was carried out to determine the characteristics of alternative diagnoses in patients with post-COVID-19 symptoms. In a total of 731 patients, 50 patients (6.8%) were newly diagnosed with 52 diseases requiring medical intervention, and 16 (32%) of those 50 patients (2.2% of the total) were considered to have priority for treatment of the newly diagnosed disorders over long COVID treatment. The proportion of patients with a new diagnosis increased with advance of age, with 15.7% of the patients aged 60 years or older having a new diagnosis. Endocrine and metabolic diseases and hematological and respiratory diseases were the most common, being detected in eight patients (16%) each. Although 35 of the 52 diseases (67%) were related to their symptoms, endocrine and metabolic diseases were the least associated with specific symptoms. Other disorders that require attention were found especially in elderly patients with symptomatic long COVID. Thus, appropriate assessment and differentiation from alternative diagnoses are necessary for managing long COVID.

Association Between Choroidal Thickness and Myopic Maculopathy in a Japanese Population: The Hisayama Study.

Purpose: To examine the association between choroidal thickness and myopic maculopathy in a general Japanese population. Design: Population-based cross-sectional study. Participants: A total of 2841 residents of a Japanese community aged ≥ 40 years, who consented to participate and had available data of choroidal thickness and fundus photographs, were enrolled in this study. Methods: The choroidal thickness was measured by swept-source OCT. Participants were divided into quartiles of choroidal thickness. Myopic maculopathy was defined according to the classification system of the Meta-analysis of Pathologic Myopia Study Group. Main outcome measures were odds ratios (ORs) of choroidal thickness for prevalent myopic maculopathy. The ORs and 95% confidence intervals (CIs) were estimated using a logistic regression model. Main Outcome Measures: Prevalent myopic maculopathy. Results: Eighty-one participants had myopic maculopathy (45 diffuse chorioretinal atrophy, 31 patchy chorioretinal atrophy, and 5 macular atrophy). Individuals in the lowest quartile of choroidal thickness had a significantly greater OR for the presence of myopic maculopathy than those in the highest quartile of choroidal thickness (OR: 4.78 [95% CI: 1.78-16.72]) after adjusting for confounders, including axial length. The sensitivity analysis among the 1176 myopic individuals with axial length of ≥ 24.0 mm also showed that thinner choroidal thickness was significantly associated with prevalent myopic maculopathy. Conclusions: The present study demonstrated the significant inverse association between choroidal thickness and the likelihood of myopic maculopathy, suggesting that the measurement of choroidal thickness in addition to axial length would be useful for assessing the risk of myopic maculopathy and elucidating its pathogenesis. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Secular trends in the prevalence, incidence, and progression of diabetic retinopathy: the Hisayama Study.

PURPOSE: To examine the secular trends in the prevalence, incidence, and progression rates of diabetic retinopathy (DR) in a Japanese community. METHODS: Community-dwelling Japanese residents aged ≥ 40 years with diabetes participated in comprehensive systemic and ophthalmological surveys, including an examination for DR, in 1998 (n = 220), 2007 (n = 511), 2012 (n = 515), and 2017 (n = 560). DR was assessed using colour fundus photographs after pupil dilation according to the modified Airlie House classification system. To compare the frequencies of newly developed or progressed DR between the studied decades, two eye cohorts were established (the 2000s cohort included 145 participants examined in 1998 and 2007; the 2010s cohort included 255 participants examined in 2007, 2012, and 2017). Trends in the prevalence, incidence, and progression rate of DR were tested by logistic regression analysis with a generalised estimating equation. RESULTS: The age-adjusted prevalence of DR among individuals with diabetes decreased significantly with time from 1998 to 2017 (27.4% in 1998, 22.8% in 2007, 12.8% in 2012, and 6.4% in 2017; p for trend < 0.001). During this period, the prevalence of DR was decreasing in every haemoglobin A1c category, but it remained constant in the high systolic blood pressure category. In addition, the rates of new-onset of DR were significantly lower in the 2010s compared to the 2000s (p < 0.001). CONCLUSION: Our findings suggest that the prevalence and incidence of DR among diabetic people significantly decreased with time over the past two decades in a general Japanese population.

Genome-Wide Association Study of Age-Related Macular Degeneration Reveals 2 New Loci Implying Shared Genetic Components with Central Serous Chorioretinopathy.

PURPOSE: To investigate the genetic architecture of age-related macular degeneration (AMD) in a Japanese population. DESIGN: Genome-wide association study (GWAS). PARTICIPANTS: Three thousand seven hundred seventy-two patients with AMD and 16 770 control participants from the Japanese population were enrolled in the association analyses. METHODS: We conducted a meta-analysis of 2 independent GWASs that included a total of 2663 patients with AMD and 9471 control participants using the imputation reference panel for genotype imputation specified for the Japanese population (n = 3541). A replication study was performed using an independent set of 1109 patients with AMD and 7299 control participants. MAIN OUTCOME MEASURES: Associations of genetic variants with AMD. RESULTS: A meta-analysis of the 2 GWASs identified 6 loci significantly associated with AMD (P < 5.0 × 10-8). Of these loci, 4 were known to be associated with AMD (CFH, C2/FB, TNFRSF10A, and ARMS2), and 2 were novel (rs4147157 near WBP1L and rs76228488 near GATA5). The newly identified associations were confirmed in a replication study (P < 0.01). After the meta-analysis of all datasets, we observed strong associations in these loci (P = 1.88 × 10-12 and P = 1.35 × 10-9 for meta-analysis for rs4147157 and rs76228488, respectively). When we looked up the associations in the reported central serous chorioretinopathy (CSC) GWAS conducted in the Japanese population, both loci were associated significantly with CSC (P = 4.86 × 10-3 and P = 4.28 × 10-3 for rs4147157 and rs76228488, respectively). We performed a genetic colocalization analysis for these loci and estimated that the posterior probabilities of shared causal variants between AMD and CSC were 0.39 and 0.60 for WBP1L and GATA5, respectively. Genetic correlation analysis focusing on the epidemiologically suggested clinical risk factors implicated shared polygenic architecture between AMD and smoking cessation (rg [the measure of genetic correlation] = -0.33; P = 0.01; false discovery rate, 0.099). CONCLUSIONS: Our findings imply shared genetic components conferring the risk of both AMD and CSC. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Prevalence of Glaucoma and Its Systemic Risk Factors in a General Japanese Population: The Hisayama Study.

Purpose: To estimate the prevalence of glaucoma and its risk factors in a Japanese community. Methods: This study included 3405 Japanese community dwellers who were ≥40 years of age and enrolled in the Hisayama Study. This population-based, cross-sectional study was conducted from 2017 to 2018. A glaucoma screening test was performed using stereo fundus images and swept-source optical coherence tomography. Glaucoma was defined based on the International Society of Geographical and Epidemiological Ophthalmology criteria. Results: The prevalence of glaucoma was 7.6% (95% confidence interval [CI], 6.7-8.6) overall. The prevalence of primary open-angle glaucoma (POAG) was 5.8% (95% CI, 5.0-6.6); that of primary angle-closure glaucoma (PACG) was 0.7% (95% CI, 0.5-1.1); and that of exfoliation glaucoma was 1.1% (95% CI, 0.7-1.4). In addition to aging, lower estimated glomerular filtration rate (eGFR) (odds ratio [OR] = 1.15; 95% CI, 1.02-1.33), higher intraocular pressure (OR = 1.06; 95% CI, 1.01-1.12), longer axial length (OR = 1.44; 95% CI, 1.31-1.59), and thinner central corneal thickness (CCT) (OR = 1.09; 95% CI, 1.04-1.15) were significant risk factors for POAG. Diabetes (OR = 2.81; 95% CI, 1.19-6.62) was a significant risk factor for PACG, and diabetes (OR = 2.15; 95% CI, 1.03-4.47) and thinner CCT (OR = 1.14; 95% CI, 1.02-1.28) were significant risk factors for exfoliation glaucoma. Conclusions: The prevalence of glaucoma was approximately 8%, probably due to the increase in the Japanese aging population. Not only ocular factors but also lower eGFR for POAG and diabetes for PACG and exfoliation glaucoma were risk factors in a general Japanese population. Translational Relevance: Systemic factors such as eGFR and diabetes must also be considered when implementing preventive measures against glaucoma.

Cohort Profile: The Ganka-Ekigaku Network (GEN), a Network of Japanese Ophthalmological Epidemiology Studies.

PURPOSE: Japan has been known as a super-aged society, and ageing is a well-known risk factor for blinding eye diseases. However, epidemiological studies in ophthalmology are still scarce in Japan, and the sizes of the cohorts are relatively small. "Ganka-Ekigaku Network" (GEN, an acronym for the epidemiological network in ophthalmology in Japanese) is established to develop a capacity to boost each epidemiological study and enrich a potential inter-study collaboration to identify risk factors of visual impairment in aged society. METHODS: We reviewed cohort studies in Japan with the inclusion criteria as: (1) at least n = 1000 at baseline, (2) multiple modalities of ophthalmic data, and (3) diagnosis reviewed by ophthalmologist(s), and (4) ophthalmologists are involved in the investigators group. As of January 2020, GEN includes 4 individual Japanese epidemiological studies namely, Hisayama study, Yamagata Study (Funagata), Tsuruoka Metabolomics Cohort study, and the Nagahama Prospective Genome Cohort for Comprehensive Human Bioscience. RESULTS: GEN includes approximately 25,000 Japanese participants. The baseline surveys started from 1998 to 2012, and since then the data has been prospectively collected approximately every 5 years. A variety of ophthalmic measurements and other factors have been collected in each study in GEN: ophthalmic measurements (fundus photography, optical coherence tomography, etc.), systemic conditions (laboratory data, etc.), and others (DNA, etc.). CONCLUSION: GEN is an open platform for observational ophthalmic epidemiological studies to share standardized methodologies. While each study in GEN pursues specific and original research questions, standardization of the methods will enable us to conduct reliable meta-analysis/pooled data analyses.

Adult-onset Still's disease accompanying noninfective endocarditis.

Adult-onset Still's disease can develop valve lesions. Since AOSD may complicate valvular lesion, differentiation of endocarditis in patients with AOSD is required.

Disseminated Mycobacterium genavense infection mimicking TAFRO syndrome.

TAFRO syndrome is a rare variant of idiopathic multicentric Castleman's disease, for which disseminated non-tuberculous mycobacteria (NTM) infection must be excluded. However, due to the slow and fastidious growth of the organisms, identification of the pathogen is often challenging. We herein describe a case of disseminated Mycobacterium genavence infection, in which manifestations of the patient were confusingly similar to those of TAFRO syndrome. A 69-year-old Japanese man presented with prolonged fever accompanying pain in his back and ribs on the right side. Systemic investigations revealed thrombocytopenia, marked elevation of alkaline phosphatase, anasarca (pleural effusion and ascites), megakaryocytosis in the bone marrow, and hepatomegaly. Magnetic resonance imaging (MRI) showed diffuse, T1-and T2-low-intensity spotted lesions on his vertebral bodies, but biopsy showed inconclusive results. The patient met the diagnostic criteria of TAFRO syndrome and was started on prednisolone, which improved his general condition shortly thereafter. Blood culture after 42 days of incubation revealed the presence of Mycobacterium; however, we considered it a contamination at that time because no organisms grew on conventional agars, and the patient was discharged. Ten weeks after the isolation of Mycobacterium, he developed persistent fever and was readmitted. This time, vertebral bone mallow biopsy demonstrated a large amount of mycobacterium, which was later successfully identified as M. genavense by sequencing analysis. Under a final diagnosis of disseminated M. genavense infection, we treated the patient with clarithromycin, rifampicin, and ethambutol. This case highlighted that disseminated NTM infection may follow a similar clinical course as that of TAFRO syndrome.

Five-Year Incidence of Myopic Maculopathy in a General Japanese Population: The Hisayama Study.

Importance: Myopic maculopathy is a leading cause of irreversible visual impairment worldwide. Moreover, the burden of myopic maculopathy has been expected to increase owing to the rising prevalence of myopia globally. However, there is limited epidemiologic evidence regarding the incidence of and risk factors for myopic maculopathy. This study from Japan, with a relatively high prevalence of myopia, could provide valuable information related to these issues. Objective: To estimate the incidence of myopic maculopathy and its risk factors in Hisayama in southwestern Japan. Design, Setting, and Participants: A population-based prospective cohort study in a Japanese community in Hisayama, Japan. The study included a total of 2164 residents 40 years or older who had no myopic maculopathy at the baseline eye examination in 2012 and underwent follow-up eye examinations in 2017. Main Outcomes and Measures: Incidence of myopic maculopathy. The grades of myopic maculopathy were categorized based on the criteria of the Meta-analysis of Pathologic Myopia Study Group classification system. Results: The mean (SD) age of the study participants was 62.4 (10.9) years, and the proportion of men was 42.5% (920 participants). In the follow-up examination in 2017, 24 patients developed myopic maculopathy. The 5-year cumulative incidence of myopic maculopathy was 1.1% (95% CI, 0.6-1.5) overall, 1.4% (95% CI, 0.6-2.2) for men, and 0.9% (95% CI, 0.4-1.4) for women. Multiple logistic regression analysis showed that older age (per 1 year; odds ratio [OR], 1.06; 95% CI, 1.01-1.11) and longer axial length (per 1 mm; OR, 2.94; 95% CI, 2.19-3.95) were associated with incident myopic maculopathy. Conclusions and Relevance: Twenty-four study participants (1%) developed myopic maculopathy during the 5-year study period, which is much higher than the rate in a previous study on a Chinese population. We also confirmed that aging and longer axial length were independent and significant risk factors for myopic maculopathy. These findings should be reviewed among various populations in other parts of the world.

Coronary Spastic Angina Induced by Adrenal Insufficiency.

Adrenal insufficiency patients are treated with glucocorticoid replacement therapy. However, mimicking the in vivo circadian rhythm of cortisol levels is challenging, and suboptimal replacement increases the risk of mortality from cardiovascular disease. We herein report a case of coronary spastic angina (CSA) with simultaneous low early-morning serum cortisol levels in a patient undergoing corticosteroid replacement therapy for primary adrenal insufficiency. Steroid therapy is reportedly effective for refractory angina, but underlying adrenal deficiency has never been revealed. Our case intimates the probable risk of CSA as a complication of relative adrenal insufficiency and highlights the effectiveness of dexamethasone in these patients.

A rare case of oncocytic adrenocortical carcinoma clinically presented as an incidentaloma.

Adrenocortical carcinoma (ACC) is a rare aggressive tumor originating from adrenocortical parenchymal cells and its incidence is approximately 1 per million population per year. An oncocytic ACC is a recently identified entity among the several known histopathological variants of ACC, which is characterized by oncocytic cells, and only a few cases in the available literature have reported this tumor. In contrast to conventional ACCs, oncocytic ACCs usually manifest as solitary lesions presenting in adults without any sex predilection. We report a case of a 70-year-old Japanese man who presented with an incidentally discovered retroperitoneal mass without any evidence of excessive corticosteroid secretion. Laboratory and imaging studies, as well as transgastric endoscopic ultrasound-guided fine needle aspiration failed to establish a definitive diagnosis. Thus, the patient underwent surgical resection of the left-sided peritoneal tumor. Weiss score was positive in 6/9 points and the tumor met two major criteria of the Lin-Weiss-Bisceglia (LWB) system leading to a diagnosis of an oncocytic variant of ACC. Based on our findings in this patient, we conclude that a combination of the Weiss and LWB criteria is required to determine the malignant potential of oncocytic adrenal tumors because ACCs and oncocytomas could be frequently indistinguishable. Careful histopathological examination is pivotal in confirming the oncocytic component in the lesion and hence definitive diagnosis of ACCs.

Long-term regular exercise and intraocular pressure: the Hisayama Study.

PURPOSE: To investigate the association between long-term regular exercise (exercise frequency and exercise time) and 5-year changes in intraocular pressure in a general Japanese population. METHODS: This population-based, cohort study was conducted in 2007. A total of 3119 Japanese community dwellers aged ≥ 40 years underwent eye examinations including intraocular pressure measurement with a noncontact tonometer. Of these, 1871 subjects (801 men and 1070 women) who underwent intraocular pressure measurement in 2012 participated. We assessed the associations of exercise frequency and exercise time with intraocular pressure using a linear regression model, adjusted for age and possible risk factors that can affect intraocular pressure. RESULTS: The mean 5-year intraocular pressure change ± standard deviation was - 0.84 ± 1.9 mmHg. After adjustment for age, sex, systolic blood pressure, diabetes, total cholesterol, high-density lipoprotein cholesterol, body mass index, waist circumference, smoking habit, alcohol intake, work intensity levels, and intraocular pressure at baseline, we observed that increased exercise frequency (times/week) and increased exercise time (min/week) were both significantly associated with reduced intraocular pressure (p < 0.05 each). In the subgroup analyses based on the presence/absence of possible confounding risk factors, there was no evidence of heterogeneity among all subgroups (p for heterogeneity > 0.2). CONCLUSIONS: Increased exercise frequency levels and increased exercise time are both independently associated with reduced intraocular pressure levels after adjustment for confounding factors.

Trends in the Prevalence of Myopia and Myopic Maculopathy in a Japanese Population: The Hisayama Study.

Purpose: To examine trends in the prevalence of myopia and myopic maculopathy in a general Japanese population. Methods: Residents of a Japanese community aged 40 years and older participated in surveys conducted in 2005, 2012, and 2017. Each participant underwent comprehensive eye examinations that included measurements of refractive error, axial lengths, and color fundus photography. Myopic maculopathy was defined according to the criteria of the Meta-analysis of Pathologic Myopia Study Group classification system. Trends in the prevalence of myopia and myopic maculopathy were tested by using a logistic regression analysis fitted by generalized estimating equations to account for individuals submitting to repeated examination. Results: The age-adjusted frequencies of myopia increased significantly from 2005 to 2017 (myopia, 37.7%-45.8%; high myopia 5.8%-9.5%; all P for trend <0.001). The age-adjusted frequency of an axial length level of 26.5 mm or more increased significantly from 2005 to 2017 (3.6%-6.0%; P for trend <0.001). The age-adjusted prevalence of myopic maculopathy also increased significantly with time (1.6% in 2005, 3.0% in 2012 and 3.6% in 2017; P for trend <0.001). Upward trends were observed in the prevalence of diffuse chorioretinal atrophy and patchy chorioretinal atrophy (all P for trend <0.05). Conclusions: Our findings suggest that the prevalence of myopia and myopic maculopathy, especially diffuse chorioretinal atrophy and patchy chorioretinal atrophy, increased significantly over the past 12 years in a general Japanese population.

Association between Axial Length and Myopic Maculopathy: The Hisayama Study.

PURPOSE: To assess the association between axial length (AL) and the prevalence of myopic maculopathy in a general Japanese population. DESIGN: Population-based cross-sectional study. PARTICIPANTS: A total of 2790 Hisayama residents 40 years of age or older who consented to participate and had available data of AL and fundus photographs for the right eyes were enrolled in this study. METHODS: Myopic maculopathy was defined as the presence of diffuse chorioretinal atrophy, patchy chorioretinal atrophy, or macular degeneration. The optimal cutoff values of axial length for identifying myopic maculopathy were estimated from the receiver operating characteristic curve. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a logistic regression analysis. MAIN OUTCOME MEASURES: Odds ratios of AL for prevalent myopic maculopathy and the optimal cutoff values of AL for detecting myopic maculopathy. RESULTS: Longer AL was associated significantly with prevalence of myopic maculopathy in both genders. The optimal cutoff values of AL for identifying myopic maculopathy were 25.9 mm in men and 25.3 mm in women. Participants with ALs of these values or longer showed a significantly higher OR for myopic maculopathy than those with AL of less than these values (men: OR, 21.23; 95% CI, 8.74-51.57; women: OR, 38.49; 95% CI, 18.03-86.49). CONCLUSIONS: The present study found that there was a positive association between AL and the likelihood of myopic maculopathy, and the cutoff levels of AL for identifying myopic maculopathy were 25.9 mm in men and 25.3 mm in women. Our findings suggest that patients with AL close to or longer than these values should undergo intensive treatment and detailed ophthalmic follow-up.

A novel case of myxoid variant of adrenocortical carcinoma in a patient with multiple endocrine neoplasia type 1.

Adrenocortical carcinoma (ACC) is a rare malignancy arising from adrenocortical parenchymal cells. Myxoid ACC is one of the newly identified, rare, but important histological variants of ACC, characterized by the presence of abundant extracellular Alcian Blue-positive myxoid material. Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant cancer predisposition syndrome, and the incidence of ACC in MEN1 patients has been reported to be between 1.4% and 6%. Here, we report the case of a 68-year-old Japanese woman harboring the past history of MEN1 associated with insulinoma, pituitary tumor, and hyperparathyroidism. She presented to our hospital with hypertension and hypokalemia. Imaging studies revealed a right adrenal tumor, and histological examination revealed myxoid ACC. Despite surgical resection of the tumor and mitotane therapy, the patient died 6 months after the surgery. To the best of our knowledge, this is the first reported case of the myxoid variant of ACC in a patient with MEN1. The patient's clinical course was characterized by the development of both multiple endocrine and non-endocrine neoplasm, hyperaldosteronism, and aggressive biological behavior. This case confirmed that myxoid morphology was also associated with aggressive behavior in ACC, but further studies are required to clarify the association between MEN1 and myxoid ACC.

Glucose Tolerance Levels and Circumpapillary Retinal Nerve Fiber Layer Thickness in a General Japanese Population: The Hisayama Study.

PURPOSE: To investigate the relationship between glucose tolerance levels and the circumpapillary retinal nerve fiber layer thickness (cpRNFLT) in a general Japanese population. DESIGN: Population-based, cross-sectional study. METHODS: In 2012 and 2013, a total of 2809 Japanese community dwellers aged 40-79 years in the Hisayama Study underwent eye examinations including cpRNFLT measurement with spectral domain optical coherence tomography. Of these, 1324 subjects (578 men and 746 women) were enrolled. Glucose tolerance levels were determined by a 75-g oral glucose tolerance test. We conducted an analysis of covariance to estimate the mean values of cpRNFLT according to the subjects' glucose intolerance status. RESULTS: The subjects with prediabetes or with diabetes mellitus had significantly lower age- and sex-adjusted mean cpRNFLT values than those with normal glucose tolerance (P = .04 and P = .0004, respectively). The age- and sex-adjusted mean values of cpRNFLT decreased significantly with elevating fasting plasma glucose and 2-hour postload glucose levels (all P for trend < .05). These associations were substantially unchanged after adjustment for potential confounding factors. The coexistence of poorer glucose tolerance and higher intraocular pressure levels was additively associated with thinner cpRNFLT. CONCLUSIONS: Our analyses revealed that poorer glucose tolerance was significantly associated with the reduction of cpRNFLT in a Japanese general population, suggesting that the loss of neural tissue in the eye begins at the prediabetic stage, and that hyperglycemia may play a role in the reduction of cpRNFLT.

A marked goiter involved in Marine-Lenhart syndrome.

Marine-Lenhart syndrome is rare disease defined as coexistence of Graves' disease and autonomously functioning thyroid nodule. We will introduce a case of Marine-Lenhart with a huge goiter.