Oral Hydrocortisone Research Articles

A CASE REPORT ON ATYPICAL PRESENTATION OF CONGENITAL ADRENAL HYPERPLASIA

We report a case of 52-day old infant presented to casualty with complaint of failure to gain weight,10-day history of regurgitation of feeds, poor acceptance of feed and lethargy from one day, not passed urine in last 8hours. On examination baby had tachycardia with signs of dehydration, blood gas shows metabolic acidosis with serum sodium- 124meq/l, serum potassium- 6.2meq/l. A probable diagnosis of failure to thrive with severe sepsis, inborn errors of metabolism (IEM), and CAH was considered and baby was treated with intravenous fluids, antibiotics, calcium gluconate, salbutamol nebulisation and hydrocortisone. Following the above interventions, babys hydration status and ECG changes improved. The diagnosis of CAH was considered as 17- hydroxyprogesterone levels were elevated. Genetic analysis was not done due to patients economic constraints and baby was discharged with oral Hydrocortisone, Fludrocortisone and table salt (Nacl). Currently baby is thriving well with adequate weight gain.

P-04 Adrenocortical carcinoma case with long-term follow-up

Abstract Description Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy with an incidence of 0.7–2.0 cases/million/year. We present a case of ACC that we followed for a long period of approximately 5.5 years. Clinical Case A 50-year-old female patient was referred to our hospital because of a left adrenal mass. She had no complaints except left flank pain. There were no features on her resume. There were no findings related to hypercortisolemia on physical examination. Hormone levels were examined (Table 1). In the upper abdomen tomography, a 9×13×10.8 cm sized, sharply defined, lobulated contoured, heterogeneous-enhancing mass lesion with central cystic components was observed in the left adrenal region (Figure 1). The patient underwent left adrenalectomy and left partial nephrectomy. Pathology was reported as adrenocortical carcinoma. Weis score was 6/9, and the Ki-67 index was 15-20%. She was evaluated as a stage 2 disease according to ENSAT staging and followed up with thoracoabdominal CT. A 30*15 mm recurrent mass lesion was detected in the first-year postoperative follow-up. The patient underwent implant excision, left nephrectomy, and left paraaortic lymphadenectomy. Then the patient was given 6 cycles of Cisplatin-Etoposide-Adriamycin chemotherapy. On follow-up imaging after chemotherapy, a mass of approximately 13 mm in diameter was detected adjacent to the small intestine. Bridectomy and malignant soft tissue resection were performed on the patient. Mitotane treatment was started after the operation. After 6 weeks, the target mitotane level was reached. The patient was followed closely for glucocorticoid needs. Oral hydrocortisone treatment was started in the patient who complained of fatigue and nausea in the 8th month of mitotan. Since there was no hyponatremia/hyperkalemia and clinically no hypotension/orthostatic hypotension, mineralocorticoid therapy was not initiated. While under mitotane treatment, liver function tests, thyroid function tests, complete blood count and lipid parameters were evaluated intermittently. She was hospitalized 4 times in total with the clinic of infection and adrenal insufficiency. At that time, mitotane treatment was interrupted and parenteral steroid treatment was started. The patient received 4.5 years of mitotane therapy. No recurrence was detected in the follow-up scans during mitotane treatment and 6 months after the treatment was discontinued. PET-CT imaging was performed in the 1st year while the patient was in the follow-up without treatment. In the retroperitoneal region, 38×21 mm focal increased activity involvement was observed (SUV Max: 17.82). Left hemicolectomy operation was performed on the patient and chemotherapy was planned. Conclusion In conclusion, we presented a case that we followed for a long time without recurrence under mitotane treatment. It can be thought that mitotane treatment keeps ACC disease under control. Figure 1. 9×13×10.8 cm left adrenal mass. Table 1

Cases: Decompensated Heart Failure Secondary to Hypopituitarism in an Elderly Patient.

Hypopituitarism is difficult to diagnose because of its non-specific symptoms, especially in the presence of comorbidities. A 77-year-old woman with worsening anorexia and exertional dyspnea was initially diagnosed with decompensated dry cold-type heart failure. Hormonal laboratory tests indicated secondary hypothyroidism as a part of the evaluation of heart failure. Furthermore, pituitary magnetic resonance imaging revealed thickening of the pituitary stalk and a loss of signal intensity in the posterior pituitary, thus suggesting lymphocytic hypophysitis. Oral hydrocortisone and levothyroxine improved the persistent anorexia. In this case, hypopituitarism occasionally presented as dry cold-type heart failure, thus making a prompt diagnosis challenging in the setting of concurrent heart failure.

Hydrocortisone Differentially Affects Reinstatement of Pain-related Responses in Patients With Chronic Back Pain and Healthy Volunteers

Despite the crucial role of effective and sustained extinction of conditioned pain-related fear in cognitive-behavioral treatment approaches for chronic pain, experimental research on extinction memory retrieval in chronic pain remains scarce. In healthy populations, extinction efficacy of fear memory is affected by stress. Therefore, we investigated the effects of oral hydrocortisone administration on the reinstatement of pain-related associations in 57 patients with non-specific chronic back pain (CBP) and 59 healthy control (HC) participants in a differential pain-related conditioning paradigm within a placebo-controlled, randomized, and double-blind design. Participants’ skin conductance responses indicate hydrocortisone-induced reinstatement effects in HCs but no observable reinstatement in HCs receiving placebo treatment. Interestingly, these effects were reversed in patients with CBP, that is, reinstatement responses were only observed in the placebo and not in the hydrocortisone group. Our findings corroborate previous evidence of stress-induced effects on extinction efficacy and reinstatement of fear memory in HCs, extending them into the pain context, and call for more research to clarify the role of stress in fear extinction and return of fear phenomena possibly contributing to treatment failure in chronic pain treatment. PerspectiveOpposing effects in HCs and patients with non-specific CBP may be associated with changes in the patients’ stress systems. These findings could be of relevance to optimizing psychological, extinction-based treatment approaches.

FRI256 The Clinical Impacts Of Bi-allelic Germline Pathogenic Variant In TP53 In Two Patients With Li-Fraumeni Syndrome

Abstract Disclosure: V. Petry: None. D. Cohn: None. R.R. Oppenheimer: None. M.D. Estevez-Diz: None. A. Latronico: None. B.B. Mendonca: None. M.Q. Almeida: None. M.C. Fragoso: None. Background: Li-Fraumeni syndrome is an autosomal dominant cancer predisposition due to a heterozygous germline TP53 mutation. This mutation is related to different types of cancer; mainly adrenocortical carcinomas (ACC), soft tissues and bone sarcomas, breast cancer, choroid plexus carcinoma and leukemias at early ages. Although little is known about the impact of this TP53 variant in the homozygous form. Methods: We described the clinical presentation and the follow-up of 2 patients with a TP53 (p.R337H) homozygous pathogenic variant inherited from their parents. Case 1: A two year old patient presented with a headache, vomiting and nuchal stiffness, and was taken to the ER where she had a CNS CT scan. The CT scan revealed a mass located at left intraventricular region She then had surgery to remove the tumor and the histological finding confirmed the diagnosis of choroid plexus carcinoma. She underwent adjuvant systemic chemotherapy Headstart III protocol. This was the first case of cancer within this family. The child was seen by a medical geneticist and a genetic test revealed a homozygous pathogenic variant (p.R337H) in TP53. Afterwards her parents were tested and both were heterozygous for the p.R337H mutation. The patient is now 4 years old and free of oncologic disease. Case 2: A 9 months old female patient presented with Cushing´s syndrome and heterosexual precocious puberty. The MRI revealed a right adrenal tumor and she underwent laparoscopic adrenalectomy. Oral hydrocortisone was initiated postoperatively as glucocorticoid replacement therapy and was gradually tapered off over 6 months. Both parents of the patient were heterozygous for the p.R337H mutation in TP53 and they reported several cases of cancer within the family. The patient inherited both mutated alleles TP53 p.R337H. She had normal puberty development and she reached the target height. The patient did not develop further neoplasms during long-term follow-up (23 years). Conclusions: We described 2 cases with a biallelic pathogenic variant in TP53 (p.R337H) who were diagnosed with cancer at early ages and who did not develop further neoplasms during the follow-up period. There is a previous case description in the literature of a patient with a homozygous p.R337H mutation in TP53 who developed ACC at an early age and he did not develop other neoplasms during 8 years of follow-up. These two cases draw your attention to the early age for the development of choroid plexus carcinoma and adrenocortical tumors as well as the published case by Giacomazzi et al. Whether the bi-allelic pattern of the TP53 variant influences the tumor’s behavior remains unclear, there are potentially broad implications for clinical surveillance and genetic counseling for patients and their families. Presentation: Friday, June 16, 2023

SAT624 Neurosarcoidosis Presenting With Panhypopituitarism

Abstract Disclosure: E.M. Niedzialkowska: None. T. Blazin: None. K. Strubchevska: None. M. Kozyk: None. N. Saini: None. Introduction: Neurosarcoidosis is estimated to occur in approximately 5-15% patients with sarcoidosis. Pituitary involvement may be present in up to 5% of those cases and can manifest as hypothalamus, adenohypophysis dysfunction or arginine vasopressin deficiency (AVP-D) in isolated fashion or variedly combined. Clinical case: 32 year old male presented with chief complaint of worsening bilateral lower extremity weakness, urinary incontinence, polyuria and polydipsia. 9 months prior to admission the patient was diagnosed with neurosarcoidosis. At that time brain MRI showed diffuse leptomeningeal enhancement, chest CT showed hilar lymphadenopathy, lumbar puncture with CSF analysis showed protein 227 mg/dl (N<38), ACE 6 U/l (N <2.5), WBC 10 (N<5) with 88% lymphocytes. Hilar lymph node biopsy was consistent with non-caseating granuloma. The patient was diagnosed with neurosarcoidosis and started on prednisone and methotrexate. The patient was referred to our institution for further evaluation. On examination gait ataxia and gynecomastia were noted. Laboratory results showed urine specific gravity of 1.001, LH 0.4 mIU/ml (N 0.6-1.2), FSH 1.1 mIU/ml (N 1-12), ACTH <5 pg/ml (N 6-46), cortisol 2.1 ug/dl (N 2.9-19.4), prolactin 10.5 ng/ml (N 2-18), total testosterone 4 ng/dl (N 240-1080), free testosterone 0.1 ng/dl (N 4.8-19), TSH 0.58 uIU/ml (N 0.4-4.5), free ft3 1.5 pg/ml (N 1.7-3.7), free ft4 0.6 ng/dl (N 0.7-1.5), IGF-1 52 ng/ml (N 71-234), Copeptin proAVP of <2.8 pmol/l( N>13.2), urine osmolality of 72 mOsmol/kg, blood osmolality of 297 mOsmol/kg (N <295), vit D 25-OH 9 ng/ml (N 30-100), vit D 1,25-OH 57.3 pg/ml (N 19.9-79.3). MRI of the spine showed extensive nodular enhancement of the leptomeninges of the cervical, thoracic spine and lumbar cauda equina nerve roots. Brain MRI was positive for numerous small nodular enhancement involving leptomeninges and pituitary stalk. The patient was started on desmopressin with significant improvement of symptoms and increase in urine osmolality to 709 mOsmol/kg. Due to risk of hypercalcemia and normal vit D 1,25-OH vitamin D supplementation was not initiated. For neurosarcoidosis the patient was started on pulse dose methylprednisolone and infliximab infusion. Upon discharge he was transitioned to oral hydrocortisone and started on levothyroxine and testosterone replacement therapy. Conclusion: We present a case of pituitary neurosarcoidosis presenting with AVP-D, secondary hypothyroidism, secondary adrenal insufficiency, hypogonadism and growth hormone deficiency. Panhypopituitarism with complete anterior and posterior pituitary dysfunction is extremely rare and might be found in up to 13% cases of pituitary sarcoidosis. The diagnosis should be considered in patients with sarcoidosis and endocrine dysfunctions. Presentation: Saturday, June 17, 2023

FRI312 Diplopia And Headache After Treatment With GnRH Agonist

Abstract Disclosure: A.A. Zakkar: None. M. Al Mushref: None. M. Fadanelli: None. Case Report: The Patient is a 46-year-old male with past medical history of hypertension and prostate cancer, currently undergoing treatment with leuprolide acetate injections, who presented to the emergency department with a complaint of worsening headache. He received his second injection 3 days prior to admission and within hours he developed a headache in the frontal area that was continuous and worsening over time, increasing with positional changes of his head. One day after the treatment he developed persistent double vision. The patient reported that he has had worsening vision over the last year and was to see an ophthalmologist but was diagnosed with prostate cancer at the same time so he became more focused on the oncologic care. He also reported poor balance, excessive thirst and increased urination of large volumes of urine every hour with nocturia several times. On exam the vital signs were normal, he was A&Ox4 and in no distress. He had left abducens and oculomotor nerve palsy but an otherwise benign exam. MRI of the brain revealed a sellar mass measuring 2.2 x 1.7 x 2.3 cm consistent with pituitary macroadenoma extending into the suprasellar cistern, compressing the pituitary stalk and the optic chiasm. Patient was evaluated by ophthalmology who noted +2 optic nerve edema of the left eye. Laboratory evaluation revealed low ACTH of 6 pg/mL at 5:30AM along with corresponding cortisol level of only 1.6 mcg/dL. FSH was low and LH undetectable as expected with GnRH agonist therapy. Growth hormone level, IGF-1, l and prolactin levels were all normal. The TSH was 0.50 microunits/mL with a freeT4 of 1.0. Urinalysis revealed dilute urine with specific gravity <1.006. Serum sodium on admission was 137 mmol/L and after overnight fasting was 140 mmol/L. The patient was started on desmopressin 0.1 mg po at bedtime and on intravenous dexamethasone 4 mg q6hrs. He was evaluated by neurosurgery and ENT who recommended trans-sphenoidal resection of the mass. Pathology report of the specimen was consistent with a pituitary adenoma with infarction without hemorrhage. The patient reported an improvement in his left eye vision and lateral rectus palsy. He was transitioned to oral hydrocortisone 20 mg daily and 10 mg every afternoon prior to discharge. On follow up with endocrinology several months later he was found to have persistent adrenal insufficiency and developed central hypothyroidism that required treatment. Conclusion: Patients with an undiagnosed pituitary adenoma are at risk of tumor expansion and mass effect as well as pituitary apoplexy during treatment with GnRH agonists. In our case clinical presentation was consistent with pituitary apoplexy without evidence of pituitary hemorrhage soon after GnRH agonist. A full ophthalmologic exam may be an appropriate screening prior to initiation of such therapy. Presentation: Friday, June 16, 2023

FRI225 Clinical Course Of Late-onset Adrenal Insufficiency Due To Treatment Of Childhood Acute Lymphoblastic Leukemia

Abstract Disclosure: M. Iwabuchi: None. Background: Some people who were treated for cancer during childhood may develop endocrine problems as because of changes in the function of endocrine system. Acute lymphoblastic leukemia is the most common type of cancer and leukemia in children and components of ALL treatment are induction, consolidation, maintenance, and central nervous system prophylaxis. It is recommended that people who had irradiation in a dose of 40 Gy or higher to the central area of the hypothalamic-pituitary axis should have a blood test done to check the cortisol level and should be done yearly for at least 15 years since this complication can occur many years after irradiation. Clinical Case: A man in his 40s was admitted with symptoms of diarrhea, low-grade fever, and drowsiness. The serum sodium level that caused his symptoms decreased to 100 mEq/L and was adequately corrected. Endocrinological examination confirmed the diagnosis of central adrenal insufficiency. Soon after starting hormonal replacement therapy with hydrocortisone, his general conditions improved. After establishing our relationship, he confessed to having a history of ALL in childhood. According to his medical records at the time, he underwent induction therapy with vincristine-prednisone in 1977, maintenance therapy with 6-mercaptopurine, and radiation therapy to the central nervous system of 25 Gy in 1983. In 2023, 40 years have passed since radiation therapy. He was able to lead a normal life on oral hydrocortisone 20 mg/day without recurrence of adrenal insufficiency. Clinical Lesson: A 40-old male survivor of ALL developed adrenal insufficiency in 30 years after cranial irradiation during childhood. Undiagnosed adrenal insufficiency is often the cause of death. We should consider childhood cancer survivors have the risk of a central adrenal insufficiency. The Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers (COG LTFU Guidelines) are a resource for healthcare professionals who provide ongoing care to survivors of pediatric malignancies. The screening recommendations in these guidelines are appropriate for asymptomatic survivors of childhood, adolescent, or young adult cancer presenting for routine exposure-based medical follow-up. It is recommended that people who had irradiation in a dose of 40 Gy or higher to the central area of the hypothalamic-pituitary axis should have a blood test done to check the cortisol level and should be done yearly for at least 15 years since this complication can occur many years after irradiation. This case highlights the importance of long-term follow-up of cancer survivors after irradiation and the delayed presentation of adrenal insufficiency. This is the first report of the subsequent treatment course of late-onset adrenal insufficiency that developed 30 years after irradiation for childhood central nervous system ALL. Presentation: Friday, June 16, 2023

FRI255 Polyglandular Autoimmune Syndrome Type 2 Presenting With Severe Hyponatremia

Abstract Disclosure: A. West: None. A.N. Davis: None. A. Warner: None. S. Salcin: None. Introduction: Polyglandular autoimmune syndrome type 2 (PAS-2) is a polygenic autoimmune syndrome which presents with two or more specific autoimmune manifestations. The combination of Addison’s disease and Hashimoto’s thyroiditis has been referred to as Schmidt Syndrome. Treatment of hypothyroidism without recognition of concomitant adrenal insufficiency may result in exacerbation of adrenal insufficiency (AI). We present a case of PAS-2 presenting with severe hyponatremia. Case: A 28-year-old male presented to an outside hospital with fatigue and weakness. His sodium was 121mEq/L and TSH >356mcIU/mL, and he was admitted for management of hyponatremia. He was started on oral levothyroxine, urea tablets, and fluid restriction. In the weeks following discharge, the patient had worsening fatigue, weakness, dizziness, nausea, and weight loss, and he presented to our ED. His vital signs were stable without tachycardia or hypotension. He was lethargic but fully oriented. Hyperpigmented areas of the tongue and nose were noted. Laboratory evaluation revealed sodium 111mEq/L, potassium 4.5mEq/L, TSH 43.56 (0.4-4.7mcIU/mL), and free T4 of 1.12 (0.58-1.76ng/dL). He was admitted to the medical intensive care unit for management of severe hyponatremia. Repeat sodium was 112mEq/L with serum cortisol 4.57mcg/dL. Hypertonic saline was given without improvement in hyponatremia. Cortisol level was determined to be inappropriately normal in the setting of severe hyponatremia. Cosyntropin stimulation test was performed with baseline, 30 minute, and 60 minute cortisol levels of 5.31, 6.17, and 6.26, respectively, consistent with AI. ACTH level was not obtained due to the blood sample being hemolyzed. Other results include positive 21-hydroxylase antibody, TPO antibody >900 IU/mL, and undetectable GAD 65 antibody. He received IV stress dose steroids with resolution of his symptoms and his hyponatremia. Oral hydrocortisone replacement therapy was started prior to discharge. Discussion: Patients with one autoimmune endocrinopathy are at risk of developing a second one. Our patient’s hyponatremia was initially attributed to his hypothyroidism without recognition of concomitant AI. Early diagnosis of AI is important prior to initiation of levothyroxine, as treatment of hypothyroidism may exacerbate AI. The sodium level in our patient worsened from 121mEq/L at the previous admission to 111mEq/L when he presented to our hospital, related to worsening of his AI while being treated for his hypothyroidism. Timely diagnosis of associated AI requires high index of suspicion in such patients, particularly in patients with signs or symptoms which may overlap with hypothyroidism, such as hyponatremia in our patient. AI should be considered in any patient who presents with hyponatremia, even those who lack other classic features such as hypotension, hyperkalemia, and hypoglycemia. Presentation: Friday, June 16, 2023

Oral cortisol and dexamethasone intake: Differential physiology and transcriptional responses in the marine juvenile Sparus aurata

This study approached the long-term oral administration of cortisol (F) and dexamethasone (DEX), two synthetic glucocorticoids, compared to a control group (CT) in the juveniles of a marine teleost, the gilthead seabream (Sparus aurata). Physiologically, DEX treatment impaired growth, which appears to be linked to carbohydrate allocation in muscle and liver, hepatic triglycerides depletion, and reduced hematocrit. Hypophyseal gh mRNA expression was 2-fold higher in DEX than in CT or F groups. Similarly, hypothalamic trh and hypophyseal pomcb followed this pattern. Plasma cortisol levels were significantly lower in DEX than in CT, while F presented intermediate levels. In the posterior intestine, measured short circuit-current (Isc) was more anion absorptive in CT and F compared to the DEX group, whereas Isc remained unaffected in the anterior intestine. The derived transepithelial electric resistance (TEER) significantly differed between intestinal regions in the DEX group. These results provide new insights to understand better potential targeted biomarkers indicative of the differential glucocorticoid or mineralocorticoid-receptors activation in fish.

A 65-Year-Old Man with Bilateral Adrenal Hemorrhage Following Prophylaxis for Postoperative Deep Vein Thrombosis with Rivaroxaban.

BACKGROUND Direct oral anticoagulant (DOAC) agents, such as rivaroxaban, treat and prevent venous thrombosis. Although adrenal hemorrhage due to DOACs has previously been reported, this is a rare condition that can present as an emergency. In this case report, we present a 65-year-old man who recently had bilateral knee arthroplasty and was started on rivaroxaban 10 mg daily for deep vein thrombosis (DVT) prophylaxis following the surgery. CASE REPORT Ten days after bilateral knee arthroplasty and starting rivaroxaban, the patient presented to the Emergency Department with severe, sudden abdominal pain. Abdominal computed tomography detected significantly enlarged bilateral adrenals, with ill-defined heterogeneous density extending to the upper part of perinephric and paranephric spaces, suggesting bilateral adrenal hemorrhage. A cosyntropin stimulation test was used to confirm the suspicion of adrenal insufficiency. Cortisol levels were 66 nmol/L before stimulation and 83 nmol/L 60 min after cosyntropin administration. Hydrocortisone was started intravenously at a dose of 50 mg every 8 h. After his symptoms improved, he was discharged on oral hydrocortisone at 10 mg in the morning and 5 mg in the evening. Seven weeks after discharge, follow-up abdominal ultrasonography showed that the bilateral adrenal hemorrhage had resolved. CONCLUSIONS This case supports previous cases of adrenal hemorrhage as a rare but serious association with rivaroxaban and highlights the importance of rapid diagnosis using imaging and monitoring of patients for this possible adverse effect. Practitioners must remain vigilant when prescribing anticoagulation therapy, especially in patients who are at an increased risk for adrenal hemorrhage.

Case of nivolumab-induced delayed adrenal insufficiency during the treatment of renal cell carcinoma.

Nivolumab is an immune checkpoint inhibitor used to treat advanced renal cell carcinoma (RCC). Adrenal insufficiency has been reported as an adverse event associated with nivolumab. We report a case of adrenal insufficiency that occurred more than 1 year after the initiation of nivolumab while patient was still receiving treatment. The patient was a 90-year-old Japanese woman. Fatigue and decreased cortisol levels were observed after 15 courses of nivolumab. The symptoms improved with the initiation of oral hydrocortisone 30 mg once a day. Nivolumab was not resumed, and the patient is still under outpatient observation. This is the first report of RCC with adrenal insufficiency occurring more than 1 year after the initiation of the nivolumab regimen. Symptoms of adrenal insufficiency are similar to those of cancer progression. When symptoms of fatigue occur in patients receiving nivolumab, adrenal insufficiency should be suspected, regardless of the duration from nivolumab initiation.

Patients with Hypocortisolism Treated with Continuous Subcutaneous Hydrocortisone Infusion (CSHI): An Option for Poorly Controlled Patients.

Despite appropriate oral glucocorticoid replacement therapy, patients with hypocortisolism often suffer from impaired health and frequent hospitalizations. Continuous subcutaneous hydrocortisone infusion (CSHI) has been developed as an attempt to improve the health status of these patients. The objective of this study was to compare the effects of CSHI to conventional oral treatment on hospitalizations, glucocorticoid doses, and subjective health status. Patients. Nine Danish patients (males: 4 and females: 5) with adrenal insufficiency (AI) were included, with a median age of 48 years, due to Addison (n = 4), congenital adrenal hyperplasia (n = 1), steroid induced secondary adrenal insufficiency (n = 2), morphine induced secondary adrenal insufficiency (n = 1), and Sheehan's syndrome (n = 1). Only patients with severe symptoms of cortisol deficit on oral treatment were selected for CSHI. Their usual oral hydrocortisone doses varied from 25-80 mg per day. The duration of follow-up depended on when the treatment was changed. The first patient started CSHI in 2009 and the last in 2021. A retrospective case series comparing hospitalizations and glucocorticoid doses before and after treatment with CSHI. In addition, patients were retrospectively interviewed about their health-related quality of life (HRQoL) after the change of treatment modality. Patients significantly reduced their daily dose of glucocorticoids by 16.1 mg (p = 0.02) after changing to CSHI. The number of hospital admission due to adrenal crisis decreased by 1.3 per year on CSHI, which was a 50% reduction (p = 0.04). All patients found it easier to handle an adrenal crisis with CSHI, and almost all patients found it easier to overcome everyday activities and had fewer symptoms of cortisol deficit such as abdominal pain and nausea (7-8 out of 9 patients). The change of treatment from conventional oral hydrocortisone to CSHI resulted in a reduced daily dose of glucocorticoids and a reduced number of hospitalizations. Patients reported regain of energy, achievement of better disease control, and better handling of adrenal crisis.

Pituitary hypoadrenocorticism and hypothyroidism after immunochemotherapy followed by salvage surgery for lung cancer: a case report

BackgroundImmune checkpoint inhibitors (ICIs) have been shown to prolong the survival of patients with non-small cell lung cancer (NSCLC) and have allowed complete resection for advanced lung cancer. However, immune-related adverse events (irAEs) have been recognized as concerning side effects of ICIs.Case presentationA 62-year-old man visited our hospital because of fever, dyspnea, and anorexia. A tumor was found in the right hilum of the lung. It compressed the left atrium and was also thought to be invading the esophagus and a vertebral body. A bronchoscopic biopsy revealed squamous cell carcinoma of the lung (cT4N2M0-IIIB). We thought that a complete resection was impossible because of the N2 status of the tumor and because it had invaded several organs. Radiotherapy was thought to be contraindicated because of the patient’s marked emphysema. Therefore, we administered 4 courses of pembrolizumab plus carboplatin plus nab-paclitaxel immunochemotherapy.After immunochemotherapy, the tumor was downstaged to ycT2bN0M0-IIA and was determined to be acceptable for salvage surgery. A right lower lobectomy and systematic dissection of the mediastinal lymph nodes were performed. The histopathological examination of the resected specimen found that the proportion of the remaining tumor cells was 5%, indicating achievement of a major pathologic response.On postoperative day 79, the patient visited the emergency room because of anorexia. Blood tests showed hyponatremia, hypoglycemia, and eosinophilia. The serum thyroid hormone and thyroid-stimulating hormone levels were low and high, respectively. A corticotropin-releasing hormone stimulation test revealed levels of adrenocorticotropic hormone and cortisol far below the normal ranges. We speculated that the patient had developed pituitary hypoadrenocorticism and hypothyroidism as irAEs associated with ICI treatment. We administered hydrocortisone and levothyroxine, with improvement in the patient’s appetite and normalization of the patient’s serum sodium level. The patient has been receiving ongoing supplementation with oral hydrocortisone and levothyroxine and is doing well 11 months after surgery.ConclusionsThe increasing numbers of patients treated with perioperative ICIs might lead to increasing numbers of patients who develop perioperative irAEs. Careful attention should be paid to the possible development of irAEs during the perioperative management of patients undergoing surgery for lung cancer.

Diagnosis and treatment approaches for simultaneous onset of subarachnoid hemorrhage and thyroid storm: a case report

BackgroundSubarachnoid hemorrhage and thyroid storm are similar in their clinical symptomatology, and diagnosis of these conditions, when they occur simultaneously, is difficult. Here, we report a rare case of concurrent subarachnoid hemorrhage and thyroid storm we encountered at our hospital.Case presentationThe patient was a 52-year-old woman. While bathing at home, the patient experienced a sudden disturbance of consciousness and was brought to our hospital. The main physical findings upon admittance were Glasgow Coma Scale score of E1V2M4, elevated blood pressure (208/145 mmHg), and tachycardia with atrial fibrillation (180 bpm) along with body temperature of 36.1 °C. Brain computed tomography revealed subarachnoid hemorrhage associated with a ruptured aneurysm of the posterior communicating artery branching from the left internal carotid artery, and aneurysm clipping was performed. Blood tests upon admission revealed high levels of free T3 and free T4 and low levels of thyroid-stimulating hormone. Upon determining that the patient had hyperthyroidism, thiamazole was administered. However, due to continuous impaired consciousness, fever, and persistence of tachycardia, the patient was diagnosed with thyroid storm. Oral potassium iodide and hydrocortisone were added to the treatment. The treatment was successful as the patient’s symptoms improved, and she became lucid.In this case, we believe that in the presence of untreated hyperthyroidism, the onset of subarachnoid hemorrhage induced thyroid storm. Tachycardia of 130 bpm or higher, which is the diagnostic criterion for thyroid storm, rarely occurs with subarachnoid hemorrhage. Therefore, we believe it is an important factor for recognizing the presence of the thyroid storm. In this case, clipping surgery was prioritized which resulted in a favorable outcome. However, it is possible that invasive surgery may have exacerbated thyroid storm, suggesting that treatment should be tailored as per patient’s condition.ConclusionIf a pulse rate of 130 bpm or higher is observed alongside subarachnoid hemorrhage, we recommend considering the possibility of concomitant thyroid storm and testing for thyroid hormone. If concomitant thyroid storm is present, we believe that a treatment plan tailored to the patient’s condition is critical, and early diagnosis will lead to a favorable outcome for the patient.

A newly developing case of adrenal insufficiency developing after Coronavirus disease

Abstract Introduction Although some short and long-term effects of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection on the endocrine system are shown, there are still much more remaining to be clarified. A few case reports have shown that adrenal insufficiency can develop after COVID-19 infection due to adrenal hemorrhage or infarction. However, the exact effects of infection on cortisol dynamics are still poorly understood. This case report highlights an unusual case of acute adrenal insufficiency in a Covid-19. Clinical Case A 30-year-old female patient with no history of chronic disease applied with complaints of nausea, abdominal pain, and weakness for nearly 2 weeks. She was hospitalized. Her vitals were stable at the admission. Her initial laboratory evaluation showed serum sodium: 119 mEq/L, potassium: 5.38 mEq/L, creatinine: 1.35 mg/dL, aldosterone 2.33 ng/dL (1.46–17.4), plasma renin activity 40.56 ng/ml/h (0.06–4.69). Hemogram and liver function tests were normal. The basal ACTH value was measured 1142 pg/mL (7.2–63.3), and cortisol was 0.29 (6.24–18).The diagnosis of tuberculosis was ruled out with the quantiferon and the PPD test performed. In the detailed questioning of the patient, it was learned that she had Covid-19 infection about 3 months before the onset of symptoms. In this process, the patient's skin color was significantly darkened, and it was confirmed in comparison with the old photographs and from the patient's declaration. She was diagnosed with adrenal crisis, and corticosteroid therapy (80 mg/day intravenous methylprednisolone) and intravenous hydration were started. On the other hand, imaging and endoscopic evaluations were performed to exclude other intra-abdominal pathologies. No pathology was detected. Adrenal glands were normal in abdominal tomography. Stress dose steroid therapy was adjusted by reducing the daily dose. In the follow-up, the patient's complaints decreased and disappeared. Fludrocortisone was added to her treatment because electrolyte disturbances continued as hyponatremia and hyperkalemia. In the first week of treatment the patient's electrolyte disturbances improved and she was discharged with oral hydrocortisone and fludrocortisone treatment. The patient's skin color was observed lighter than before in the control examination, one week after discharge. Conclusion Although cases of adrenal insufficiency due to Covid-19 infection are found in the literature, their number is limited. The underlying causes are usually shown as hemorrhage and thrombosis. The absence of these findings in our case supports that the underlying cause is autoimmune and brought a different perspective to the issue. Our case also drives attention to the evaluation of patients in terms of adrenal insufficiency not only in the acute period but also in the later periods, since the diagnosis was made 3 months after the disease.

Immune checkpoint inhibitor-mediated hypophysitis: no place like home

Ambulatory emergency care forms a fundamental part of the strategy of trying to ensure safe and sustainable acute care services. Immune checkpoint inhibitor(ICI)-mediated hypophysitis is an important life-threatening complication of therapy. Patients presenting with clinical features and findings consistent with ICI-mediated hypophysitis were considered in the current study. In the absence of severe features (sodium <125 mmol/L, hypotension, reduced consciousness, hypoglycaemia and/or visual field defect), patients were administered a single intravenous dose of hydrocortisone (100 mg), observed for at least 4 h and then discharged on oral hydrocortisone (20 mg, 10 mg and 10 mg). Patients were then seen urgently in the endocrinology outpatient setting for further management. Fourteen patients (median age 64, 10 male) were managed using the pathway. All patients had biochemically confirmed adrenocorticotropic hormone (ACTH) deficiency. Seven of the 14 were treated with combination ICI therapy, with four having pan-anterior hypopituitarism. There were no 30-day readmissions or any associated hypophysitis-related mortality. All patients continued ICI therapy without interruption.

Strongyloidiasis infection in a borderline lepromatous leprosy patient with adrenocorticoid insufficiency undergoing corticosteroid treatment: a case report

Strongyloidiasis is a soil-transmitted helminthiasis mainly caused by Strongyloides stercoralis. It is endemic to the tropics and subtropics. Sri Lanka has a 0-1.6% prevalence rate. S. stercoralis infection was identified in a 33-year-old Sri Lankan male patient treated with corticosteroids for borderline lepromatous leprosy with adrenocortical dysfunction. In March 2020, a 33-year-old Sri Lankan (Sinhalese) male patient presented with watery diarrhea, lower abdominal pain, and post-prandial abdominal fullness. Previously, he was diagnosed with borderline lepromatous leprosy and was treated with rifampicin, clofazimine, and prednisolone 60mg daily since July 2019. After developing gastrointestinal symptoms, he had defaulted leprosy treatment including the prednisolone for 3months. Duodenal biopsy revealed numerous intraepithelial nematodes within the lumina of glands in the duodenum whose appearance favored Strongyloides. Fecal wet smear revealed numerous Strongyloidisstercoralis L1 rhabditiform larvae. Larval tracks were seen in the agar plate culture. L3 filariform larvae of Strongyloidis stercoralis were seen in the Harada-Mori culture. In addition, the short synacthen test revealed adrenocortical insufficiency, and oral hydrocortisone and fludrocortisone were started with albendazole treatment against strongyloidiasis. Fecal wet smear and culture repeated after treatment with albendazole were negative for Strongyloidisstercoralis. The patient was discharged in July 2020 on oral hydrocortisone. Onemonth later his condition was reviewed and the repeated fecal wet smear and agar plate culture was normal. He is being followed up every 3months. This is the first case of strongyloidiasis diagnosed in a patient with borderline lepromatous leprosy from Sri Lanka. The patient manifested symptoms of strongyloidiasis while on high-dose steroid therapy for his lepromatous reaction. Subsequently, the patient not only discontinued his steroid therapy, but also developed adrenocortical insufficiency as a complication of leprosy. Therefore, although diagnosis of strongyloidiasis was delayed, his subsequent low steroid levels probably protected him from disseminated disease. This is an interesting case where symptomatic strongyloidiasis was diagnosed in a patient who was initially treated with high-dose steroids but subsequently developed adrenocortical insufficiency. We emphasize the need to screen all patients prior to the commencement of immunosuppressive therapy.

Clinical characteristics of patients with unexplainable hypothalamic disorder diagnosed by the corticotropin-releasing hormone challenge test: a retrospective study

The corticotropin-releasing hormone (CRH) challenge test can distinguish the disorders of the hypothalamus from those of the pituitary. However, the pathophysiology of hypothalamic disorder (HD) has not been fully understood. This study aimed to elucidate the clinical characteristics of patients with unexplainable HD, diagnosed by the CRH challenge test. We retrospectively reviewed patients who underwent the CRH challenge test. Patients were categorized into four groups as follows: patients with peak serum cortisol ≥18 μg/dL were assigned to the normal response (NR) group (n = 18), among patients with peak serum cortisol < 18 μg/dL and peak adrenocorticotropic hormone (ACTH) increase ≥two-fold, patients without obvious background pathology were assigned to the unexplainable-HD group (n = 18), whereas patients with obvious background pathology were assigned to the explainable-HD group (n = 38), and patients with peak serum cortisol < 18 μg/dL and peak ACTH increase <two-fold were assigned to the pituitary disorder (PD) group (n = 15). Inter-group comparisons were performed based on clinical characteristics. In the CRH challenge test, the peak plasma ACTH levels were significantly lower in the unexplainable-HD group than in the NR group, despite more than two-fold increase compared to basal levels. The increase in serum cortisol was significantly higher in the unexplainable-HD group than in the explainable-HD and PD groups. Although patients in the unexplainable-HD group showed a clear ACTH response in the insulin tolerance test, some patients had peak serum cortisol levels of < 18 μg/dL. Furthermore, attenuated diurnal variations and low normal levels of urinary free cortisol were observed. Most patients in the unexplainable-HD group were young women with chronic fatigue. However, supplementation with oral hydrocortisone at physiological doses reduced fatigue only in some patients. Patients with unexplainable HD diagnosed by the CRH challenge test had hypothalamic-pituitary-adrenal (HPA) axis dysfunction and some patients had mild central adrenal insufficiency. Hydrocortisone supplementation reduced fatigue only in some patients, suggesting that HPA axis dysfunction may be a physiological adaptation. Further investigation of these patients may help elucidate the pathophysiology of myalgic encephalitis/chronic fatigue syndrome.

ODP030 Autoimmune Adrenalitis Following mRNA Covid- 19 Immunization In A Patient Without A Known Diagnosis Of Adrenal Insufficiency.

Abstract A 45-year-old female with a past medical history of Hashimoto thyroiditis and celiac disease presented after a syncopal episode that resulted in a motor vehicle accident. The patient had symptoms of fatigue, nausea, and anorexia for three weeks following the second dose of the Pfizer-BioNTech COVID-19 Vaccine. Initial laboratory tests revealed hyponatremia with serum sodium (Na) of 123mEq/L that worsened to 111mEq/L after receiving the normal saline infusion. Serum potassium was 3.4mEq/l, Thyroid-stimulating hormone level was 6.350mIU/l, free thyroxine level was 1.1 ng/dl and glucose were 85mg/dl. The PCR test for COVID-19 was negative. Vitals were unremarkable except for a low blood pressure of 90/60. On physical examination, the patient was alert and communicative and there was no hyperpigmentation of the skin. The patient denied personal and family history of adrenal insufficiency. She denied prior use of any steroid medications. Her prior outpatient serum Na levels were normal (138-140 mEq/L). The patient was admitted to the ICU for severe hyponatremia, where she was treated with fluid restriction and hypertonic saline. However, she remained hypotensive, and serum sodium failed to improve above 118mEq/l. Serum cortisol at 8: 00 am and 10: 00 am were 4.5 and 5.8 mcg/dl, respectively. She was started on stress doses of hydrocortisone 100 mg intravenous (IV) followed by hydrocortisone 50 mg IV every 8 hours and serum Na improved to 130m Eq/l. Steroids were tapered gradually to physiological doses. The levothyroxine dose was also increased from the home dose of 75mcg to 88 mcg daily due to the elevated TSH. Hormonal workup showed aldosterone of 0.3ng/dl, plasma renin activity of 20, and adrenocorticotropic hormone(ACTH) levels of &amp;gt;1250pg/ml. Gonadotropins, insulin-like growth factor-1, and prolactin were within normal limits. Cosyntropin stimulation test after holding steroids for 24 hours was abnormal, with pre-cosyntropin cortisol level 7. 0mcg/dl, and the 60-minute post-cosyntropin cortisol level 7.1mcg/dl. The diagnosis of autoimmune adrenalitis was confirmed with a positive 21-hydroxylase antibody test. The patient had an uneventful recovery and was discharged on oral hydrocortisone. Presentation: No date and time listed