Risk of Mental Illnesses in Patients With Hypopituitarism: A Nationwide Population-Based Cohort Study

I-Hua Wei,Chih-Chia Huang 대한신경정신의학회 2022 PSYCHIATRY INVESTIGATION Vol.19 No.6

Objective The associations of mental illnesses and hypopituitarism have been reported. But, pituitary disorders are rare. The epidemiological studies have rarely addressed these associations between pituitary disorder and mental illnesses. Until now, no cohort study has been conducted to investigate the association.Methods We performed a nationwide, retrospective cohort study using the Taiwanese National Health Insurance Program dataset to analyze this relationship. In total, 1,194 patients diagnosed with hypopituitarism between 2000 and 2013 were identified. For the control group, 4,776 individuals without hypopituitarism and psychotic diseases were matched (1:4) according to age, sex, and index date. A Cox proportional hazards model was used to determine the adjusted hazard ratio (aHR).Results Patients with hypopituitarism had a significantly higher risk of incident depression and anxiety disorders than those without hypopituitarism. The aHRs of depressive and anxiety disorders were 2.98 and 1.67, respectively, for the hypopituitarism cohort. Furthermore, the risk of both hypopituitarism-associated depressive and anxiety disorders was significantly high in female subjects and subjects aged ≥18 years. A statistically significant increase was not observed in the risk of bipolar disorders, dementia, or schizophrenia in the hypopituitarism group compared with the control group.Conclusion Although psychiatric morbidities were uncommon for the hypopituitarism cohort, the risk of developing depressive and anxiety disorders was significantly higher in those with hypopituitarism than in those without hypopituitarism.

Nonalcoholic Fatty Liver Disease in Children with Hypopituitarism

윤정민,고재성,서정기,신충호,양세원,문진수,양혜란,장주영,Yoon, Jung-Min,Ko, Jae-Sung,Seo, Jeong-Kee,Shin, Choong-Ho,Yang, Sei-Won,Moon, Jin-Soo,Yang, Hye-Ran,Chang, Ju-Young The Korean Society of Pediatric Gastroenterology 2010 Pediatric gastroenterology, hepatology & nutrition Vol.13 No.1

목 적: 뇌하수체저하증 환아들은 비만, 당불내성, 고지질혈증을 포함한 대사증후군의 양상을 보인다. 이 연구의 목적은 뇌하수체저하증과 연관된 소아 지방간질환의 임상 양상과 간조직 소견을 알아보는 것이다. 방 법: 뇌하수체저하증 환자 중에서 비알코올성 지방간질환으로 진단된 소아 11명의 임상자료를 조사하였다. 결 과: 뇌하수체저하증 진단 시 연령은 10.4${\pm}$3.2세였다. 지방간질환 진단 시 연령은 13.1${\pm}$2.7세였다. 두 개인 두종이 뇌하수체저하증의 기저질환 중 가장 흔하였다. 지방간질환 진단 당시 체질량지수 85백분위수 이상이 9명(82%), 금식 시 고혈당이 5명(45%), 고지질혈증이 9명(82%)에서 발견되었다. 신장의 표준편차 점수의 평균은 뇌하수체저하증 진단 시보다 지방간질환 진단시에 유의하게 낮았다. 간생검을 실시한 6명 중에서 1명은 간경변, 2명은 연결 섬유화가 동반된 지방간염, 2명은 경도의 간문맥 섬유화가 동반된 지방간염, 1명은 단순 지방간으로 진단되었다. 결 론: 뇌하수체저하증을 가진 소아는 저신장, 비만, 고지질혈증, 비알코올성 지방간질환이 발생할 위험이 높다. 간조직의 진행된 섬유화가 흔하기 때문에 뇌하수 체저하증 환아에서 지방간질환의 조기 진단이 중요하다. Purpose: It has been reported that children with hypopituitarism have features of metabolic syndrome, including obesity, impaired glucose tolerance, and dyslipidemia. The aim of this study was to investigate the clinical features and liver histology of pediatric non-alcoholic fatty liver disease (NAFLD) associated with hypopituitarism. Methods: We reviewed the clinical data of 11 children diagnosed with NAFLD among patients with hypopituitarism. Results: The mean age at the time of diagnosis of hypopituitarism was 10.4${\pm}$3.2 years, and the mean age at the time of diagnosis of NAFLD was 13.1${\pm}$2.7 years. A craniopharyngioma was the most common cause of pituitary dysfunction. At the time of diagnosis of NAFLD, 9 patients (82%) had a body mass index greater than the 85th percentile, 5 patients (45%) had elevated fasting blood glucose levels, and 9 patients (82%) had hypertriglyceridemia. The mean height SD score was significantly lower at the time of diagnosis of NAFLD than at the time of diagnosis of hypopituitarism. Of the six patients who were biopsied, one had cirrhosis, two had non-alcoholic steatohepatitis (NASH) with bridging fibrosis, two had NASH with mild portal fibrosis, and one had simple steatosis. Conclusion: Children with hypopituitarism are at risk of short stature, obesity, dyslipidemia, and NAFLD. The early diagnosis of NAFLD is important in children with hypopituitarism because advanced fibrosis is common.

출혈열콩팥증후군 후 발생한 생식샘저하증과 요추압박골절 1예 − 증례 보고 −

유승돈,김동환,유병선,최성혜,허기은 대한재활의학회 2009 Annals of Rehabilitation Medicine Vol.33 No.5

Male osteoporosis is known to progress slowly and is less severe compared to female osteoporosis, and the incidence of lumbar compression fracture is considerably lower in male population. Hypogonadism which can develop from various causes including hypopituitarism is a common cause for secondary male osteoporosis. Hypopituitarism as a late complication of severe form of hemorrhagic fever with renal syndrome (HFRS) is known to occur occasionally but its clinical symptoms rarely appear. A 75-year-old male patient who had recovered from HFRS 13 years ago was admitted due to severe low back pain. He presented with gradually developed symptoms of hypogonadism and hypothyroidism resulting from hypopituitarism. MRI revealed collapsed pituitary gland and empty sella. This case presents with a male patient with multiple lumbar compression fractures due to severe osteoporosis secondary to hypogonadism, which resulted from hypopituitarism as a late complication of HFRS.

Hypopituitarism Presenting as Osteoporotic Fracture after Cured Tuberculous Meningitis

Jung Yeop Lee,Mi Jung Kim,Min A Kim,Se Hyuk Kwon,Eun Kyoung Kim,Kyung Ae Lee 순천향대학교 순천향의학연구소 2016 Journal of Soonchunhyang Medical Science Vol.22 No.2

Tuberculous meningitis is a well-known cause of hypothalamic pituitary dysfunction. However, deficiencies of anterior pituitary hormones may only become evident years after recovery because symptoms are of insidious-onset and nonspecific. Pituitary hormones are essential for normal growth and sexual development in childhood, and for maintenance of healthy body composition. In addition, pituitary hormones and vitamin D are important for cardiovascular and bone health. Although evidence of the relationship between hypovitaminosis D and hypopituitarism is limited, some studies suggested that the incidence of vitamin D deficiency increased in hypopituitarism. We describe herein an unusual case of hypopituitarism and severe hypovitaminosis D presenting as osteoporotic fracture after cured tuberculous meningitis.

소아에서 특발성 뇌하수체저하증의 임상적 특성

김지현,이성용,정혜림,이선희,김재현,이영아,양세원,신충호 대한소아내분비학회 2010 Annals of Pediatirc Endocrinology & Metabolism Vol.15 No.1

Purpose: The purpose of this study was to evaluate the clinical evolution and endocrine features of idiopathic hypopituitarism. Methods: We reviewed the medical records of 33 patients with idiopathic hypopituitarism who had been followed up from 1982 to 2008, attained their adult final height, and received appropriate hormonal replacement therapy. Results: 28 of these patients (85%) were male, 26 patients (79%) were delivered by breech presentation, and 18 (55%) were firstborns. The mean age at diagnosis was 10.1±4.6 years, and bone age was delayed a mean of 4.9±3.0 years. The mean standard deviation score (SDS) for height at diagnosis was -3.6±2.9. Deficiencies of pituitary hormones were observed in the following order of frequency: growth hormone (100%), thyroid- stimulating hormone (97.0%), luteinizing hormone/follicle-stimulating hormone (81.8%), adrenocorticotropic hormone (45.5%), and antidiuretic hormone (12.1%). Deficiencies of 4 hormones were observed in 14 (42.4%); 3 hormones, in 11 (33.3%); 2 hormones, in 5 (18.2%); and 5 hormones, in 2 (6.1%). Spontaneous onset of puberty occurred in 6 boys (21.4%), and there were no significant differences in the clinical presentations of pituitary hormone deficiency between these boys and those with gonadotropin-releasing hormone deficiency. Conclusion: Idiopathic hypopituitarism should be considered in patients of short stature who are delivered by breech presentation, and their hormone levels should be monitored periodically. 목 적: 특발성 뇌하수체저하증은 호르몬 분비 장애에 의해 높은 이환율과 사망률을 보이는 질환임에도 불구하고 국내에서 그 원인과 특성에 대해 기술된 보고가 없었다. 이에 저자들은 뇌의 기질적 병변이 없는 뇌하수체저하증 환자를 대상으로 임상적 특징 및 내분비학적 특성을 알아보고자 하였다. 방 법: 2008년 5월까지 서울대학교 병원에서 특발성 뇌하수체저하증으로 진단 받은 뒤 적절한 호르몬 대체 요법을 시행 받고 있으면서 최종 성인키에 도달한 환자를 대상으로 하였다. 결 과: 관찰 대상은 총 33명으로 이 중 남자는 28명, 여자는 5명이었다. 둔위 분만이 26명으로 79%였고, 첫째 아이로 출생한 경우는 18명으로 55%였다. 내원 당시 평균 연령은 10.1±4.6세였고, 역연령에 비해 골 연령은 평균 4.9±3.0세가 지연되었으며 진단 시 키 표준편차는 -3.6±2.9였다. 성장호르몬 결핍은 모두에서 관찰되었고 갑상선자극호르몬 결핍은 97%, 성선자극호르몬 결핍은 81.8%, 부신피질자극호르몬 결핍은 45.5%, 항이뇨호르몬 결핍은 18.2%에서 나타났다. 결핍된 뇌하수체 호르몬의 종류가 2가지인 경우가 6명(18%), 3가지 결핍은 11명(33%), 4가지 결핍은 14명(43%)이었으며 5가지 호르몬 모두가 결핍된 경우는 2명(6%)이었다. 자발적으로 사춘기가 발현된 경우는 6명으로 (21.4%) 모두 남자였으며, 자발적으로 사춘기가 시작된 군과 사춘기 발현이 없어 호르몬 대체 요법을 시행 받은 군 사이에서 성선자극호르몬 결핍을 제외한 다른 호르몬의 분비 장애 정도에는 유의한 차이가 없었다. 결 론: 저신장을 주소로 내원한 환아들 중 둔위 분만으로 출생한 경우에는 특발성 뇌하수체저하증의 가능성을 염두에 두어 적절한 시기에 자극 검사를 시행하여 호르몬 결핍 여부를 확인하는 것이 필요하다.

A Case of Primary Central Nervous System Lymphoma : an Unusual Presentation with Hormonal Abnormalities and Good Prognosis after Chemo-radiotherapy

박진주 외 중앙대학교 의과대학 의학연구소 2011 中央醫大誌 Vol.36 No.3/4

Here, an unusual case of primary central nervous system lymphoma (PCNSL) with a suprasellar lesion involving the thalamus and hypothalamus is reported; the lesion caused diabetes insipidus (DI) and hypopituitarism. A complete type of central diabetes insipidus and hypopituitarism were diagnosed by water deprivation and vasopressin challenge test, and a combined pituitary stimulation test. After high dose methotrexate based chemotherapy and radiotherapy, the lymphoma showed complete remission. Pituitary hormones were replaced with hydrocortisone, levothyroxine and desmopressin. Though the symptoms and signs of DI and hypopituitarism have been persisted partially over the past 3 years, the hormone requirements have been decreased gradually. This case demonstrated that the endocrine abnormalities could gradually recover after the primary tumor was treated.

터키안 주위 내경동맥 동맥류에 의해 발생한 뇌하수체기능저하증 1예

이수행 ( Soo Haeng Lee ),송재원 ( Jae Won Song ),조제연 ( Jae Yeon Cho ),김동석 ( Dong Suk Kim ),류영진 ( Young Jin Ryu ),박선영 ( Sun Young Park ),임성희 ( Sung Hee Ihm ) 대한내과학회 2016 대한내과학회지 Vol.91 No.1

터키안 주위에 생긴 뇌동맥류에 의한 뇌하수체기능저하증은 매우 드물게 보고되고 있으며, 전체 뇌하수체기능저하증의 원인 중 0.2% 미만을 차지한다. 현재까지 전 세계적으로 약 50예가 보고되고 있고, 국내에서는 최근 1예가 보고된바 있다. 저자들은 터키안 주위의 내경동맥 동맥류에 의해 뇌하수체기능저하증이 발생한 환자를 2년 추적 관찰하였던 경험을 문헌고찰과 함께 보고하는 바이다. Pituitary insufficiency due to a sellar aneurysm is relatively uncommon. The prevalence of this disorder was <0.2% in a large cohort of patients with panhypopituitarism. While uncommon, a vascular sellar lesion should be included as a differential diagnosis for a sellar mass resulting in hypopituitarism. We report herein a case of hypopituitarism with hyperprolactinemia secondary to a large (1.7-cm) saccular aneurysm at the left paraclinoid internal carotid artery. (Korean J Med 2016;91:66-69)

Hypopituitarism Presenting as Adrenal Insufficiency and Hypothyroidism in a Patient with Wilson’s Disease: A Case Report

이혜원,강진두,여창우,윤성운,이광재,최문기 대한의학회 2016 Journal of Korean medical science Vol.31 No.8

Wilson’s disease typically presents symptoms associated with liver damage or neuropsychiatric disturbances, while endocrinologic abnormalities are rare. We report an unprecedented case of hypopituitarism in a patient with Wilson’s disease. A 40-year-old woman presented with depression, general weakness and anorexia. Laboratory tests and imaging studies were compatible with liver cirrhosis due to Wilson’s disease. Basal hormone levels and pituitary function tests indicated secondary hypothyroidism and adrenal insufficiency due to hypopituitarism. Brain MRI showed T2 hyperintense signals in both basal ganglia and midbrain but the pituitary imaging was normal. She is currently receiving chelation therapy along with thyroid hormone and steroid replacement. There may be a relationship between Wilson’s disease and hypopituitarism. Copper deposition or secondary neuronal damage in the pituitary may be a possible explanation for this theory.

한국 소아 뇌하수체기능저하증 환자에서의 PROP1 유전자 분석에 관한 연구

이효성,황일태,황진순 대한소아내분비학회 2009 Annals of Pediatirc Endocrinology & Metabolism Vol.14 No.1

목 적:PROP1 유전자의 돌연변이는 성장호르몬, 갑상샘자극호르몬, 황체화호르몬과 여포자극호르몬, 프로락틴, 부신피질자극호르몬의 결핍을 특징으로 하는 복합 뇌하수체기능저하증, 또는 드물게 단독 성장호르몬결핍증을 일으킨다. 본 연구는 한국 소아 뇌하수체기능저하증 환아에서 PROP1 유전자를 분석하고자 하였다. 방 법:아주대병원 소아청소년과에서 선천성 뇌하수체기능저하증으로 진단받은 12명의 환아를 대상으로 하였다. 뇌하수체기능저하증의 임상 양상은 단독 성장호르몬결핍증과 복합 뇌하수체기능저하증을 포함하였다. 의무 기록을 열람하여 내분비학적, 신경방사선학적인 임상 정보를 후향적으로 조사하였고, 환아로부터 정맥혈을 채취하여 DNA를 추출하였으며, PCR 방법을 이용하여 PROP1 유전자를 검사하였다. PCR 산물은 직접 서열 분석을 하였다. 결 과:뇌하수체 자기공명영상에서 9명의 환아들이 이상 소견을 보였고, 3명의 환아들이 정상 소견을 보였다. 내분비학적으로는 7명에서 단독 성장호르몬결핍증, 5명에서 복합 뇌하수체기능저하증이었는데, 이들 중 성장호르몬결핍증과 동반된 황체화호르몬, 여포자극호르몬 결핍증이 3명, 성장호르몬에 동반된 갑상샘자극호르몬 결핍증과 부신피질자극호르몬 결핍증이 2명이었다. 본 연구에서는 PROP1 유전자의 돌연변이를 발견할 수 없었다. 그러나, 3개의 알려진 다형성을 발견할 수 있었는데, 총 24개의 대립 유전자(allele)들 중에서, 엑손 1번에서 27T→C (Ala9Ala)와 이것과 연관된 IVS1+3A→G을 25%(4명)에서 발견하였고, 엑손 3번에서 242G→A (Ala142Thr)을 4% (1명)에서 발견하였다. 결 론:본 연구는 PROP1 유전자의 돌연변이가 산발적으로 발생하는 뇌하수체기능저하증 환자에서는 드물게 발견된다는 선행 연구들의 보고들과 일치한다. 한국의 환자들에서 돌연변이가 적은 이유는 다른 밝혀지지 않은 유전자가 관여하기 때문일 수 있고, 인종적인 차이가 있을 가능성이 있다. 그러나, 본 연구의 환자수가 적어서 더 많은 한국 환자들의 PROP1 유전자 분석을 통해 질환과의 연관성을 밝히는 것이 필요하겠다. Purpose:Mutations of the PROP1 (Prophet of PIT1) gene lead to combined pituitary hormone deficiency (CPHD), which is characterized by a deficiency of growth hormone (GH), thyroid stimulating hormone (TSH), luteinizing hormone (LH)/follicle stimulating hormone (FSH), prolactin (PRL) and adrenocorticotropic hormone (ACTH). We studied the PROP1 mutations in Korean children with hypopituitarism. Methods:Twelve patients with congenital hypopituitarism were recruited from the Ajou University Hospital, Korea. The pituitary phenotype ranged from isolated growth hormone deficiency (IGHD) to CPHD. Clinical data, including endocrine and neuroradiological data were obtained from the medical records, and the DNA was collected and screened for mutations within PROP1 using polymerase chain reaction (PCR). The PCR products were sequenced directly. Results:Nine patients had abnormal pituitary gland and three patients showed normal pituitary gland in magnetic resonance imaging (MRI). Endocrinologically, seven patients had IGHD and five had CPHD. Three of CPHD had GHD and hypogonadotrophic hypogonadism and the other two had GHD, central hypothyroidism, and ACTH deficiency. We identified no mutations in the PROP1 gene. However, three known polymorphisms were identified: The 27T→C (Ala9Ala) and the associated IVS1+3A→G in exon 1 were found in 25% of patient alleles sequenced. The 424G→A (Ala142Thr) in exon 3 change was identified in 4% of those sequenced. Conclusion:This study corresponds to the previous reports that PROP1 mutations are rare in sporadic cases of CPHD. The low mutation frequency in Korean patients may be due to ethnic-specificity or other candidate genes causing this disease. It is necessary to study PROP1 gene and the involved genes in more Korean patients.

선천성 뇌하수체 기능저하증과 동반된 신생아 담즙정체 1례

양혜란,송은경,김정은,정수진,이경훈,신충호,양세원,고재성,강경훈,서정기,Yang, Hye-Ran,Song, Eun-Gyoung,Kim, Jeong-Eun,Jeong, Su-Jin,Lee, Gyoung-Hoon,Shin, Choong-Ho,Yang, Sei-Won,Ko, Jae-Sung,Kang, Gyeong-Hoon,Seo, Jeong-Kee 대한소아소화기영양학회 2002 Pediatric gastroenterology, hepatology & nutrition Vol.5 No.2

저자들은 반복되는 저혈당과 점차 진행하는 담즙정체를 보이는 3개월 된 여아에서 호르몬 검사와 뇌 자기공명영상으로 뇌하수체 기능저하증을 진단하고 이에 대한 갑상선호르몬과 부신피질호르몬 치료 후 담즙정체가 호전되는 것을 경험하였기에 이를 보고하는 바이다. Congenital hypopituitarism is a possible cause of neonatal cholestasis, but the mechanism is still unknown. The pathogenesis of cholestasis may be due to hormone deficiency, which has effects on the physiological maturation of bile acid synthesis and transport. We experienced a case presenting with cholestasis and recurrent hypoglycemia associated with congenital hypopituitarism. Cholestasis resolved with thyroxine and hydrocortisone replacement therapy.