Isolated Adrenocorticotropic Hormone Deciency Accompanied by Impaired Cognitive Function: A Case Report

Background: Isolated adrenocorticotropic hormone (ACTH) deciency (IAD) is an adrenal insuciency caused by a decrease in ACTH alone among the anterior pituitary hormones. IAD is often overlooked because it causes nonspecic symptoms. We report a case of IAD diagnosed after the appearance of mild cognitive impairment (MCI). Case presentation: Our department was consulted on a case of a 46-year-old man for whom dementia was suspected because he was speaking incoherently, wiped his nose with his hands and showed mild brain atrophy on MRI. He was previously diagnosed with some psychiatric diseases, such as narcolepsy and adjustment disorder. He could not continue working due to somnolence, general fatigue and appetite loss. At the examination, he had diculty concentrating and sustaining attention, exhibited restlessness, and scored 25 points on the Mini Mental State Examination-Japanese (MMSE-J); MCI was observed. Blood tests showed decreased ACTH, cortisol and free thyroxine and increased thyroid-stimulating hormone levels. He received further evaluation, and he was diagnosed with IAD and primary hypothyroidism. Hydrocortisone (15 mg) was started, after which his physical problems and his diculty concentrating disappeared. His MMSE-J score also increased to 30. His cognitive functions completely recovered. He returned to work and continued to work stably. Conclusion: This patient was diagnosed with IAD and treated with adrenocortical hormone replacement therapy. His cognitive functions recovered, his physical and mental disorders were alleviated, and he returned to society. It is important not to miss neurological and psychiatric symptoms that can be cured by physical treatment.

Blood tests showed decreased ACTH, cortisol and free thyroxine and increased thyroid-stimulating hormone levels. He received further evaluation, and he was diagnosed with IAD and primary hypothyroidism. Hydrocortisone (15 mg) was started, after which his physical problems and his di culty concentrating disappeared. His MMSE-J score also increased to 30. His cognitive functions completely recovered. He returned to work and continued to work stably.
Conclusion: This patient was diagnosed with IAD and treated with adrenocortical hormone replacement therapy. His cognitive functions recovered, his physical and mental disorders were alleviated, and he returned to society. It is important not to miss neurological and psychiatric symptoms that can be cured by physical treatment.

Introduction:
Isolated adrenocorticotropic hormone (ACTH) de ciency (IAD) is a cause of adrenal insu ciency in which secretion of only ACTH is impaired, while secretion of other anterior pituitary hormones is maintained. Diagnosis is often delayed due to nonspeci c symptoms such as general fatigue, appetite loss, weight loss, hypoglycemia, and hypotension. We herein report a case of a Japanese man with IAD complicated by primary hypothyroidism presenting with several neuropsychiatric symptoms, especially cognitive dysfunction, before diagnosis who showed complete improvement of cognitive function after administration of hydrocortisone.

Case Presentation:
A 46-year-old Japanese man who had cognitive impairment visited our department. He began working after nishing vocational school at the age of 20, but he changed jobs often beginning at the age of 25.
He started to doze off and make careless mistakes during the daytime despite sleeping well at night. He visited the psychiatrist and was diagnosed with narcolepsy at the age of 38. He was administered moda nil, and his symptoms were relieved. Moda nil was discontinued. He was able to work at the age of 40. He started to become fatigued easily, exhibited anorexia and weight loss and was diagnosed with eosinophilic gastroenteritis and hypereosinophilia at the Department of Internal Medicine, A Hospital, at the age of 44. Afterwards, the anorexia improved, but the fatigue was so severe that he took a leave of absence from work. He temporarily returned to work, but due to fatigue and somnolence, he was placed on leave again. He visited the psychiatrist, and he was diagnosed with adjustment disorder. He received rehabilitation and returned to work at the age of 45. He began to make incoherent remarks and wipe his nose with his hand, which were not appropriate behaviors for his age, at the age of 46. His Mini Mental  (Table 1). IAD was diagnosed because secretion of other anterior pituitary hormones was maintained. With regard to hypothyroidism, the FT4 level was low, the TSH level was high, and the thyrotropin-releasing hormone (TRH) stress test showed a positive response to TSH, leading to the diagnosis of primary hypothyroidism (Table 1). He was started on hydrocortisone (15 mg) as adrenal corticosteroid replacement therapy. By 1 month after starting hydrocortisone, his physical complaints, including anorexia, somnolence, and general fatigue, had disappeared, as had his forgetfulness and di culty concentrating. His cognitive functions had recovered, and his MMSE-J score was 30/30. The WAIS-III scores improved (Full-Scale IQ 81, Verbal IQ 92, Performance IQ 72, Verbal Comprehension Index 92, Perceptional Organization Index 66, Working Memory Index 98, Processing Speed Index 81) after 3 months of hydrocortisone treatment. The hydrocortisone dose was decreased to 10 mg because his body weight increased during the same period.
He returned to work after 5 months of hydrocortisone treatment and has been working stably since then with 10 mg of hydrocortisone. Hypothyroidism also recovered 7 months of hydrocortisone treatment.

Discussion:
IAD is a pituitary disorder characterized by decreased secretion of ACTH, which causes secondary adrenal insu ciency (AI). The main symptoms of IAD are caused by glucocorticoid de ciency. Steinberg reported the rst case of IAD in 1954. Patients with IAD present with general fatigue, weight loss and hypoglycemia, which improve after ACTH administration [1]. The prevalence of IAD was found to be 1.91-7.3 per 100,000 persons in a Japanese cohort [2][3]. Individuals with IAD primarily present with symptoms of AI, such as general fatigue, loss of appetite, nausea, and vomiting. IAD is often misdiagnosed as a psychological disorder when patients have psychological symptoms, including apathy, depression, delusion and abnormal behavior [4]. In this case, the patient was diagnosed with some neuropsychiatric disorders, including narcolepsy, adjustment disorder, and mild cognitive impairment. Nagai reported that a 69-year-old man was admitted because of abdominal pain with IAD accompanying dementia [5]. Matsuo reported cognitive impairment and a depressive state caused by IAD in a 45-year-old Japanese man 6 . Goto reported an IAD case presenting with gait disturbance necessitating differential diagnosis from idiopathic normal pressure hydrocephalus 7 . Cognitive dysfunction is considered to be one of the symptoms of IAD. This case showed complete recovery of cognitive function after the administration of hydrocortisone. The neuropsychiatric symptoms were also improved, such as di culty in sustaining attention, impulsiveness and restlessness. The MMSE-J and WAIS-scores increased. Since cognitive dysfunction resulting from IAD is treatable, clinicians should keep IAD in mind when assessing patients with impaired cognitive functions.

Conclusion:
Adrenocortical hormone replacement therapy is dramatically effective for the symptoms of IAD. This patient recovered from his cognitive dysfunction and physical and mental disorders and returned to society. The patient had IAD accompanied by impaired cognitive functions and dramatically improved after treatment with adrenocortical hormone replacement therapy. Clinicians must consider the possibility of IAD when assessing patients with impaired cognitive functions. Declarations: