An 81-Year-Old Man Presenting with Asthenia and Anorexia After an Alcohol-Induced Hypoglycemic Coma and a Diagnosis of Central Adrenal Insufficiency: A Case Report.

BACKGROUND Alcohol abuse inhibits the ability of the liver to release glucose into the bloodstream, primarily by inhibiting gluconeogenesis, so chronic alcohol abusers exhibit hypoglycemia after drinking alcohol without eating; this is called alcohol-induced hypoglycemia. Central adrenal insufficiency (AI) is characterized by cortisol deficiency due to a lack of adrenocorticotropic hormone. It is challenging to diagnose central AI, as it usually presents with nonspecific symptoms, such as asthenia, anorexia, and a tendency toward hypoglycemia. Here, we report a rare case of central AI that presented with AI symptoms shortly after an alcohol-induced hypoglycemic coma. CASE REPORT An 81-year-old Japanese man who had been a moderate drinker for >40 years developed a hypoglycemic coma after consuming a large amount of sake (alcohol, 80 g) without eating. After the hypoglycemia was treated with a glucose infusion, he rapidly recovered consciousness. After stopping alcohol consumption and following a balanced diet, he had normal plasma glucose levels. However, 1 week later, he developed asthenia and anorexia. The endocrinological investigation results indicated central AI. He was started on oral hydrocortisone (15 mg/day), which relieved his AI symptoms. CONCLUSIONS Cases of central AI associated with alcohol-induced hypoglycemic attacks have been reported. Our patient developed AI symptoms following an alcohol-induced hypoglycemic attack. His alcohol-induced hypoglycemic attack likely occurred in combination with a developing cortisol deficiency. This case highlights the importance of considering central AI in chronic alcohol abusers presenting with nonspecific symptoms, including asthenia and anorexia, especially when patients have previously experienced alcohol-induced hypoglycemic attacks.

Hypoglycemic Hemiplegia Associated with Reversible Narrowing of the Contralateral Middle Cerebral Artery in a Patient with Adrenal Insufficiency.

A 56-year-old man with a 2.5-month history of anorexia developed sweating, weakness, and left hemiplegia and hemispatial neglect. Brain magnetic resonance imaging detected no abnormalities, but magnetic resonance angiography revealed narrowing of the right middle cerebral artery (MCA). The focal neurological signs and narrowing of the MCA resolved after detection and correction of hypoglycemia. Endocrinological examinations indicated adrenal insufficiency. Hemiplegia is a rare but important neurological manifestation of hypoglycemia, although the mechanisms involved remain unknown. Combined hypoglycemia and decreased MCA blood flow associated with vasospasm probably induced regionally severe neuroglycopenia with ischemia, which presented as focal neurological symptoms.

A 75-Year-Old Woman with a 5-Year History of Controlled Type 2 Diabetes Mellitus Presenting with Polydipsia and Polyuria and a Diagnosis of Central Diabetes Insipidus.

BACKGROUND Central diabetes insipidus (CDI) is a rare disorder characterized by large volumes of dilute urine because of a lack of antidiuretic hormone. Co-existing CDI and diabetes mellitus without inherited disorders such as Wolfram syndrome are rare. It is both important and challenging to diagnose this combination because the 2 conditions present with thirst, polydipsia, and polyuria. A few cases of CDI developing in patients with type 2 diabetes mellitus (T2D) have been reported. We report an unusual case of CDI that developed in an older patient with T2D. The aims of this report are to share the clinical course and discuss clues to the early diagnosis of CDI in T2D. CASE REPORT A 70-year-old Japanese woman developed T2D with hyperglycemia symptoms, including thirst, polydipsia, and polyuria. After starting medical treatment, the hyperglycemia and its symptoms improved. The glycated hemoglobin level decreased from 9% to 6%. However, 5 years later (at 75 years of age), she re-exhibited thirst, polydipsia, and polyuria despite stable glycemic control. Her urine volume was large (6.3 L/day). A urine glucose test was negative. The plasma osmolality was high (321 mOsm/kg), while the urinary osmolality was low (125 mOsm/kg). A significant increase in urinary osmolality following vasopressin administration indicated a diagnosis of CDI. Desmopressin therapy effectively relieved the symptoms. CONCLUSIONS This case highlights the need to consider CDI as a rare but important comorbid disorder in patients with diabetes mellitus, including T2D, particularly those presenting with thirst, polydipsia, and polyuria despite well-controlled glycemia.

Cottonoids (neurosurgical patties, neurosurgical pads, or micropatties) as effective instruments for safe and successful endoscopic transsphenoidal adenomectomy.

BACKGROUND: Neurosurgical cottonoids (also known as neurosurgical patties, pads, or micropatties) have been commonly used in microsurgical procedures to protect the surface of the brain, nerves, and vasculature and to aspirate blood, flushing solution, and cerebrospinal fluid. This article describes the unique applications of cottonoids in endoscopic transsphenoidal adenomectomy (eTSA). METHODS: Several sizes of cottonoids have been used in eTSA to enhance safe surgical procedures and clear the operative field. The roles of cottonoids in eTSA are divided into three types: to serve as view-ensuring devices, to protect tissue, and to function as instruments or assist with the use of other instruments. RESULTS: Appropriate cottonoid use provides a well-visualized operative field, allows easy identification of bleeding areas, enables effective adenoma detachment from the cleavage layer (tumour-hypophysis interface), and permits sensitive procedures to be performed around critical structures. CONCLUSIONS: To achieve safe and successful neurovascular-hypophysis-protective eTSA, cottonoids play an effective role in every type of eTSA procedure, in various applications, performed under higher-resolution endoscopic vision.

Primary Aldosteronism Presenting with Hypertension Five Days after Delivery: A Case Report and Literature Review.

A 35-year-old Japanese woman with no history of hypertension developed hypertension 5 days after normal delivery. Endocrinological and radiological examinations indicated primary aldosteronism (PA) and a 1.4-cm left adrenal tumor. The patient underwent laparoscopic adrenalectomy, and a diagnosis of aldosterone-producing adenoma was confirmed immunohistochemically. Her plasma aldosterone concentration and blood pressure normalized. Cases of PA presenting with hypertension in the postpartum period have been reported. This case suggests that PA should be considered in women with postpartum hypertension, especially in those with blood pressure that suddenly increases shortly after delivery, even if they were normotensive before and throughout pregnancy.

Central Diabetes Insipidus after Syndrome of Inappropriate Antidiuretic Hormone Secretion with Severe Hyponatremia in a Patient with Rathke's Cleft Cyst.

A 49-year-old man developed severe hyponatremia associated with transient headache and was diagnosed with syndrome of inappropriate antidiuretic hormone secretion (SIADH). Fluid restriction and sodium supplementation corrected the hyponatremia. However, several days later, the patient exhibited hypernatremia with thirst and polyuria. A detailed examination indicated central diabetes insipidus (CDI) with an intrasellar cystic lesion indicative of Rathke's cleft cyst (RCC). A case of RCC exhibiting headache, hyponatremia, and subsequent hypernatremia has been reported. Our case shows that CDI may appear after SIADH in patients with RCC, especially in those with serum sodium levels that unexpectedly increase rapidly beyond the reference range.

"Vascular" Korsakoff Syndrome With Bilaterally Damaged Mammillothalamic Tracts: Insights Into the Pathogenesis of "Acute" Korsakoff Syndrome As Acute-Onset Irreversible Anterograde Amnesia.

The structural pathogenesis of Wernicke-Korsakoff syndrome remains debatable. Wernicke encephalopathy is acute and often reversible whereas Korsakoff syndrome (KS) is chronic and may be irreversible. The cognitive deficits observed in KS are considered to be primarily due to damage to the anterior nucleus of the thalamus, mammillary bodies, and corpus callosum. We present an extremely rare case of non-alcoholic "vascular" KS (vKS) as acute-onset amnesia. A 97-year-old man living alone was brought to our hospital, complaining of sudden-onset behavioral changes with amnesia. Diffusion-weighted images (DWIs) showed fresh cerebral infarction in the right thalamus involving the right mammillothalamic tract (MTT). T2*-weighted images (T2*WIs), in addition, revealed a microbleed scar over the left MTT. This case supports the hypothesis that bilateral MTT dysfunction can lead to KS. Furthermore, in collaboration with a prior report about non-alcoholic "acute" KS due to cerebral infarction, this case supports the existence of vascular KS as an acute-onset amnestic syndrome, as well as insight into the pathogenesis of KS as an irreversible amnestic syndrome.

Calvarium Subperiosteal Hematoma in a 12-Year-Old Boy.

Calvarium subperiosteal hematoma (C-SPOH) is extremely rare in juveniles. We present an extremely rare case of juvenile C-SPOH and a review of the literature. A 12-year-old boy hit his head hard against another player's head during a soccer game. On the next day of the game (Day 02), he noticed a soft bump on the left parietal region. On Day 04, he saw a local physician and was diagnosed with a subgaleal hematoma. The hematoma grew larger, up to twice the size of that on Day 04 and it became more painful over the next five days. A CT scan on Day 10 showed a subcutaneous hematoma that did not cross the suture lines. Aspiration using a syringe with an 18-gauge needle obtained about 45 mL liquefied hematoma and caused the bump collapse with relief of the pain. On Day 12, however, he presented the same bump with similar pains as on Day 10. CT angiography revealed no vascular anomalies or disruptions. A blood sampling test demonstrated normal blood coagulation ability without thrombocytopenia or malnutrition. A second aspiration obtained 45 mL liquefied hematoma. In the second procedure, the hematoma cavity was irrigated with normal saline solution (about 5 mL x 4). He took 250 mg tranexamic acid three times a day and 5 mg prednisolone three times a day for four days. On Day 15, his C-SPOH was not tense and not painful. On Day 22, the periosteal hematoma remained soft and shrunk. A follow-up CT scan showed the complete disappearance of the subperiosteal hematoma on Day 57. The boy has returned to soccer-playing activity without sequelae. This case suggests that 1) C-SPOH can be found in healthy juveniles; 2) Neovascularization along the wall of the C-SPOH cavity may contribute to the formation of the C-SPOH; 3) A simple aspiration of the liquefied SPOH may fail to cure it in juveniles.

Isolated Adrenocorticotropic Hormone Deficiency Associated with Severe Hyperkalemia During Pembrolizumab Therapy in a Patient with Ureteral Cancer and an Ileal Conduit: A Case Report and Literature Review.

BACKGROUND Immune checkpoint inhibitors (ICIs) are anticancer medications that enhance the antitumor immune response. The clinical benefit afforded by ICIs, however, can be accompanied by immune-related adverse events (IRAEs). One of the common endocrine IRAEs is hypophysitis, which often causes hypopituitarism with secondary adrenal insufficiency (AI). Secondary AI, including isolated adrenocorticotropic hormone (ACTH) deficiency (IAD), is often associated with hyponatremia. Here, we report an unusual case of ICI-related IAD associated with severe hyperkalemia. CASE REPORT A 78-year-old woman who had an ileal conduit, chronic kidney disease, type 2 diabetes mellitus, and hypertension and was taking an angiotensin II receptor blocker began treatment for advanced ureteral cancer with the anti-programmed cell death protein 1 inhibitor pembrolizumab. The therapy effectively controlled the cancer, but 4 1/2 months after starting it, the patient developed anorexia, general weakness, and muscle pain and was diagnosed with IAD associated with severe hyperkalemia and hyperchloremic metabolic acidosis. She recovered after prompt administration of corticosteroids and treatment with sodium bicarbonate, glucose/insulin, and cation exchange resins. CONCLUSIONS Hyperkalemia is a common symptom of primary AI but is less common in patients with central AI because a lack of ACTH does not cause aldosterone deficiency and mineralocorticoid action is preserved. The present case demonstrates the need for physicians to be aware of severe hyperkalemia as a life-threatening complication of secondary AI induced by ICIs, particularly in patients with predisposing factors, such as kidney dysfunction, diabetes mellitus, an ileal conduit, and renin-angiotensin-aldosterone system inhibitor use.

Impact of Phase Angle on Physical Function in Patients with Acute Stroke.

OBJECTIVE: Phase angle, an assessment of muscle quality, might be a possible predictor of physical function in patients with an acute stroke; however, the evidence for the same is limited. Therefore, this study aimed to investigate whether phase angle is associated with improved physical function at discharge. METHODS: In this observational cohort study, we determined the phase angle in patients with an acute stroke using a portable, noninvasive multifrequency bio-impedance device. The primary objective was the assessment of physical function using the Functional Independence Measure motor (FIM-motor) at discharge in the acute phase. The secondary outcome was home discharge. Multiple regression analysis was used to determine the association between phase angle, FIM-motor score, and home discharge. RESULTS: The study included 129 patients (78 men; mean age 75.2 years). Multiple linear regression analysis showed that the phase angle was independently associated with FIM-motor score at discharge in all models (Model 1: ß= 0.27, p < 0.001; Model 2: ß = 0.234, p < 0.001; Model 3: ß = 0.201, p = 0.017). However, multiple logistic regression analysis showed that the phase angle was not associated with home discharge (p = 0.464). CONCLUSIONS: The phase angle at the onset of a stroke, is an independent predictor of physical function at discharge in the acute phase. Our findings highlight the importance of determining the phase angle in patients with an acute stroke.

Prolonged Postoperative Pyrexia and Transient Nonnephrogenic Vasopressin-Analogue-Resistant Polyuria following Endoscopic Transsphenoidal Resection of an Infundibular Epidermoid Cyst.

Prolonged postoperative pyrexia (PPP) due to Mollaret's meningitis following endoscopic transsphenoidal surgery (eTSS) for an intracranial epidermoid cyst can be confused with postoperative meningeal infection after transsphenoidal resection, especially in the middle of the COVID-19 pandemic. Anosmia, as well as dysgeusia, cannot be evaluated in patients of eTSS for a while after surgery. We report a case of an infundibular epidermoid cyst with post-eTSS Mollaret's meningitis (MM). The post-eTSS MM caused vasopressin-analogue-resistant polyuria (VARP) in synchronization with PPP. A 59-year-old man experiencing recurrent headaches and irregular bitemporal hemianopsia over three months was diagnosed with a suprasellar tumor. The suprasellar tumor was an infundibular cyst from the infundibular recess to the posterior lobe of the pituitary, which was gross-totally resected including the neurohypophysis via an extended eTSS. Since awakening from general anesthesia after the gross total resection (GTR) of the tumor, the patient continuously had suffered from headache until the 13th postoperative day (POD13). The patient took analgesics once a day before the surgery and three times a day after the surgery until POD11. Pyrexia (37.5-39.5 degree Celsius) in synchronization with nonnephrogenic VARP remitted on POD18. Intravenous antibiotics had little effect on changes of pyrexia. Serum procalcitonin values (reference range <0.5 ng/mL) are 0.07 ng/mL on POD12 and 0.06 ng/mL on POD18. His polyuria came to react with sublingual desmopressin after alleviation of pyrexia. He left the hospital under hormone replacement therapy without newly added neurological sequelae other than hypopituitarism. After GTR of an infundibular epidermoid cyst, based on values of serum procalcitonin, post-eTSS MM can be distinguished from infection and can be treated with symptomatic treatments. The postoperative transient nonnephrogenic VARP that differs from usual central diabetes insipidus can react with sublingual desmopressin after alleviation of PPP in the clinical course of post-eTSS MM. An infundibular epidermoid cyst should be sufficiently resected in one sitting to minimize comorbidities, its recurrence, or postoperative MM to the utmost.

[Pituitary Hypertrophy].

Pituitary adenomas are the most common cause of sellar masses although there are a number of other neoplastic, infectious, inflammatory, developmental, and vascular etiologies that should be considered. Pregnancy promotes a physiological increase in the size of the maternal pituitary gland, especially adenohypophysis. The normal maturation sequence of the pituitary gland apparently involves a period of physiological hypertrophy in teenagers. As most incidentalomas in pediatric patients are not associated with hormonal hypersecretion or hypopituitarism, and structural progression is not common, it is hypothesized that the extensive follow-up assessment recommended for adults might not be necessary for children. Patients presenting with a pituitary lesion should undergo a complete history and physical examination that includes evaluations for evidence of hypopituitarism and hormone hypersecretion syndrome. Patients with evidence for either of these conditions should undergo an appropriately directed biochemical evaluation. All patients presenting with a pituitary lesion abutting the optic nerves or chiasm on magnetic resonance imaging should undergo a formal visual field examination. Emergencies in pituitary disease can result from the failure of the pituitary gland to secrete one or more pituitary hormones or from neuro-ophthalmological symptoms due to the mass effect of an expanding hypothalamic-pituitary lesion. Early diagnosis and prompt treatment of endocrine emergencies are mandatory.

Glass Fragment Injury to the Craniocervical Junction with Interatlantooccipital Penetration to the Subarachnoid Space: Not-To-Be-Missed Important Aspects of Craniocervical Trauma Even in the Middle of the COVID-19 Pandemic: Case Report and Review of Literature.

BACKGROUND: Nonmissile penetrating injuries to the craniocervical junction caused by a glass fragment are rare, and a standard management strategy has not been established. CASE DESCRIPTION: A 75-year-old Japanese man was brought into our emergency department after receiving a left retroauricular stab wound by broken glass fragments. After spinal immobilization, a computed tomography (CT) scan revealed glass fragments penetrating at the right craniocervical junction to the interatlantooccipital subarachnoid space. CT angiography showed that both vertebral arteries were not injured. Magnetic resonance imaging demonstrated that the glass fragments did not penetrate the cervical cord or medulla oblongata. These glass fragments were removed via a midline incision from the external occipital protuberance to the C7 and with laminectomy without suboccipital craniectomy. Five of the glass fragments were found and removed in total. The dural defect was patched with a free fascia autograft. His postoperative course was uneventful. Postoperative CT angiography showed that both vertebral arteries were intact and the glass fragments had been removed completely. CONCLUSIONS: CT graphical diagnosis is useful for the management of penetrating craniocervical junction trauma, and it should be considered in the evaluation of patients who have suffered craniocervical penetrating injury even in the absence of major wounds or bleeding. Spinal immobilization of patients with craniocervical penetrating injuries is crucial to avoid not only secondary neurologic damage but also secondary critical vascular damage. Incomplete or inadequate assessment of craniocervical stab wounds results in unexpected hazards that are preventable.

Traumatic Nonmissile Penetrating Transnasal Anterior Skull Base Fracture and Brain Injury with Cerebrospinal Fluid Leak: Intraoperative Leak Detection and an Effective Reconstruction Procedure for a Localized Skull Base Defect Especially After Coronavirus Disease 2019 Outbreak.

BACKGROUND: Cerebrospinal fluid (CSF) leakage after penetrating skull base injury is relatively rare compared with close head injuries involving skull base fractures. CASE DESCRIPTION: We report the case of a 65-year-old man who had presented with epistaxis and serous rhinorrhea. When he had fallen to the ground near his bee boxes, a garden pole had poked into his right nostril. He had instantly removed the pole from his nostril himself. However, immediately after removal of the pole, he had developed nasal bleeding and serous rhinorrhea. He then drove to our emergency room. Computed tomography showed pneumocephalus with a minor cerebral contusion in the left frontal lobe and a penetrating injury in the left anterior skull base. His CSF leakage had not resolve spontaneously within 1 week after the injury with strict bed rest. We repaired the CSF leakage using a fat (adipose tissue)-on-fascia autograft plug and caulked the defect in the anterior skull base with the fat-on-fascia graft (FFG) plug through the left nostril with endoscopic guidance. The CSF rhinorrhea was successfully controlled. Intranasal local application of fluorescein aided in the detection of the direction of flow of the CSF leakage. CONCLUSIONS: Endonasal endoscopic caulking of a skull base defect using an FFG plug can be useful to treat CSF leakage due to the localized skull base defect, especially in the coronavirus disease 2019 pandemic. It is simple, inexpensive, and timesaving. It requires no special skills nor sophisticated instruments that can cause aerosolization, reducing the risk of infection during the surgery.

Isolated Adrenocorticotropic Hormone Deficiency and Primary Hypothyroidism in a Patient Undergoing Long-Term Hemodialysis: A Case Report and Literature Review.

BACKGROUND Patients with end-stage renal disease undergoing long-term maintenance hemodialysis are more likely than the general population to exhibit primary hypothyroidism. Only a few cases of isolated adrenocorticotropic hormone deficiency (IAD) among hemodialysis patients have been reported. We herein report an unusual case of a patient undergoing long-term hemodialysis who exhibited both IAD and primary hypothyroidism. CASE REPORT A 82-year-old male with end-stage renal disease secondary to immunoglobulin A nephropathy, undergoing hemodialysis for 20 years, was found to have primary hypothyroidism without obvious symptoms and consequently began thyroid hormone replacement therapy with oral levothyroxine. At 84 years of age, he developed anorexia, fatigue, and lethargy. A systemic workup using computed tomography and gastrointestinal endoscopy detected no abnormalities. He did not exhibit electrolyte imbalances, such as hyponatremia or hyperkalemia, and had normal morning blood levels of cortisol and adrenocorticotropic hormone. However, he exhibited hypoglycemic coma 4 months later. Detailed endocrinological examinations using dynamic function tests indicated IAD. After commencement of corticosteroid replacement therapy, his symptoms resolved without complications. CONCLUSIONS To our knowledge, this is the first report of a hemodialysis patient with both IAD and primary hypothyroidism. This case highlights the importance of regular assessments of thyroid function for primary hypothyroidism in hemodialysis patients, even when they are asymptomatic. Furthermore, timely dynamic endocrine testing of hypothalamic-pituitary-adrenal function is needed to diagnose possible IAD in hemodialysis patients with symptoms suggestive of adrenal insufficiency, even in the absence of abnormal laboratory findings such as electrolyte imbalances or low morning blood levels of cortisol or adrenocorticotropic hormone.

Isolated Adrenocorticotropic Hormone Deficiency Presenting with Severe Hyponatremia and Rhabdomyolysis: A Case Report and Literature Review.

BACKGROUND Isolated adrenocorticotropic hormone deficiency (IAD) is a rare disorder characterized by central adrenal insufficiency (AI) but normal secretion of pituitary hormones other than adrenocorticotropic hormone. IAD usually presents with unspecific symptoms of AI, such as anorexia and fatigue, but some patients present with a variety of atypical manifestations. Rhabdomyolysis is a potentially life-threatening clinical syndrome caused by skeletal muscle injury with the release of muscle cell contents into the circulation. A wide variety of disorders can cause rhabdomyolysis. Herein, we report an unusual case of IAD presenting with hyponatremia and rhabdomyolysis. CASE REPORT A 67-year-old Japanese woman with a 2-month history of anorexia and fatigue was diagnosed with severe hyponatremia (serum sodium, 118 mEq/L) and rhabdomyolysis (serum creatine phosphokinase, 6968 IU/L), after 2 days of vomiting and muscle weakness. Physical and laboratory findings did not show dehydration or peripheral edema. Her rhabdomyolysis resolved with normalization of serum sodium levels during administration of sodium chloride. However, her anorexia and fatigue remained unresolved. After reducing the amount of sodium chloride administered, the patient still had hyponatremia. Detailed endocrinological examinations indicated IAD; her hyponatremia was associated with inappropriately high plasma arginine vasopressin levels. The patient received corticosteroid replacement therapy, which resolved her anorexia, fatigue, excessive arginine vasopressin, and hyponatremia. CONCLUSIONS This case highlights the importance of considering the possibility of central AI in patients with hyponatremia and excessive arginine vasopressin levels. In addition, rhabdomyolysis associated with hyponatremia can be an important manifestation of IAD.

Detectability of the choroid plexus of the third ventricle with magnetic resonance ventriculography.

PURPOSE: To clarify the detectability of the choroid plexus of the third ventricle (ChPl3V) with magnetic resonance ventriculography (MRVn) employing a steady-state free precession (SSFP) sequence in comparison to surgical endoscopic movies as a golden standard, as we encountered some clinical cases of total agenesis of corpus callosum (ACC) where we could not recognize the choroid plexus of the third ventricle and found no previous article addressing this problem. MATERIALS AND METHODS: This retrospective study included consecutive patients from 2010 to 2016 for whom endoscopic evaluation of the third ventricle was conducted. The anterior portion of the right and left streaks of ChPl3V was evaluated in 8 patients on 16 sites, while the posterior portion of both streaks of ChPl3V was evaluated in 13 patients on 26 sites. Sensitivity of MRVn to visualize ChPl3V with endoscopic movies as the golden standard was calculated. RESULTS: Sensitivity of MRVn in visualizing the anterior portion of ChPl3V was 0.813, and that for the posterior portion 0.692. The anterior portion of ChPl3V was visualized in all cases where no tumor contacted the foramen of Monro. CONCLUSION: MRVn visualizes the anterior portion of ChPl3V with significant sensitivity and the posterior portion with lower one.

Isolated adrenocorticotropic hormone deficiency and thyroiditis associated with nivolumab therapy in a patient with advanced lung adenocarcinoma: a case report and review of the literature.

INTRODUCTION: Immune checkpoint inhibitors are a promising class of anticancer drugs. The clinical benefits afforded by immune checkpoint inhibitors can be accompanied by immune-related adverse events that affect multiple organs, and endocrine immune-related adverse events include thyroiditis and hypophysitis. Hypophysitis is less frequent and has a less severe clinical presentation in patients treated with other immune checkpoint inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, than in those treated with ipilimumab. However, studies have described isolated adrenocorticotropic hormone deficiency cases associated with nivolumab, pembrolizumab, and atezolizumab therapy, most of which occurred during the course of immune checkpoint inhibitor therapy. We report a rare case of patient with isolated adrenocorticotropic hormone deficiency that occurred after nivolumab therapy. CASE PRESENTATION: A 69-year-old Japanese woman with advanced lung adenocarcinoma developed painless thyroiditis with transient elevations of serum thyroid hormones during 3 months of cancer treatment with nivolumab and began thyroid hormone replacement therapy for subsequent primary hypothyroidism. Four months after nivolumab therapy was discontinued, she developed isolated adrenocorticotropic hormone deficiency; corticosteroid replacement therapy relieved her secondary adrenal insufficiency symptoms, such as anorexia and fatigue. Human leukocyte antigen typing revealed the presence of DRB1*04:05-DQB1*04:01-DQA1*03:03 and DRB1*09:01-DQB1*03:03-DQA1*03:02 haplotypes, which increase susceptibility to autoimmune polyendocrine syndrome associated with thyroid and pituitary disorders in the Japanese population. CONCLUSIONS: Our patient developed thyroiditis during cancer treatment with nivolumab and subsequently exhibited isolated adrenocorticotropic hormone deficiency 4 months after discontinuing the drug. Administration of nivolumab in combination with a genetic predisposition to polyglandular autoimmunity probably caused both the thyroiditis and hypophysitis, resulting in primary hypothyroidism and isolated adrenocorticotropic hormone deficiency, respectively, in our patient. The present case highlights the need for physicians to be aware that endocrine immune-related adverse events, including hypophysitis, can occur more than several months after discontinuing a drug.

Medial pontomedullary junctional infarction presenting vertigo, ipsilateral facial paresis, contralateral thermal hypoalgesia and dysphagia without lateral gaze palsy, curtain sign and hoarseness: a case presentation of a novel brain stem stroke syndrome with sensory disturbance-based dysphagia and review of the literature.

In this report, we describe unilateral medial pontomedullary junction (MPMJ) syndrome as a novel brain stem stroke syndrome. A 68-year-old woman suddenly developed vertigo, ipsilateral facial paresis, contralateral thermal hypoalgesia (TH) and dysphagia without lateral gaze palsy, curtain sign and hoarseness. Magnetic resonance (MR) imaging showed a small infarction at the right MPMJ. MR angiography did not show vertebrobasilar arterial dissection, thrombosis or vasospasm. Finally, her dysphagia regressed over 4 weeks in synchronization with recovery of TH. To the best of our knowledge and based on a review of the literature, this MPMJ syndrome associated with the unilateral MPMJ infarction is a novel brain stem stroke syndrome different from Foville syndrome, Millard-Gubler syndrome, Wallenberg syndrome or Dejerine's syndrome. In the MPMJ syndrome, transient, albeit severe, dysphagia based on the TH-impaired swallowing reflex bothered the patient more than hemiparesthesia of TH did.