scholarly journals SUN-276 Pembrolizumab-Induced Secondary Adrenal Insufficiency Presenting as Severe Hyponatremia in an 80-Year-Old Male

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Leslie Daphne R Kawaji ◽  
Mary Grace M Villanueva ◽  
Michael L Villa
Keyword(s):  
Adverse Events ◽  
Adrenal Insufficiency ◽  
Endocrine System ◽  
Stage Iv ◽  
Blood Chemistry ◽  
Oral Feeding ◽  
Low Grade ◽  
Thyroid Function Tests ◽  
Secondary Adrenal Insufficiency ◽  
Severe Hyponatremia

Abstract Background Pembrolizumab is an anti-programmed death 1 (PD-1) antibody designed to incite an immune response against malignant cells. By virtue of this mechanism of action, its use has given rise to immune-related adverse events including those affecting the endocrine system. Adrenal insufficiency can occur rarely with anti-PD-1 therapy, and symptoms are usually non-specific. Clinical Case An 80-year-old male, known case of non-small cell lung cancer stage IV presented with a 2-week history of progressive body weakness with anorexia, shortness of breath and low-grade fever. He had just received the 4th cycle of pembrolizumab prior to the onset of symptoms. Past medical history was significant for hypertension and type 2 diabetes mellitus which were both controlled, and pulmonary tuberculosis with completed treatment. On physical examination, he was drowsy but oriented. He was normotensive (110/70 mmHg) and tachypneic (28 cpm) with rales on both lung fields. Baseline capillary glucose level was 107 mg/dL. Chest radiograph showed hazy opacities in the right upper to middle region. Blood chemistry revealed severe hyponatremia (114 mmol/L, NV 135-145 mmol/L) and low serum osmolality (247 mOsm/kg, NV 280-300 mOsm/kg). Random (taken 1230H) ACTH and cortisol were <5.00 pg/mL (NV <46 pg/mL) and 2.00 μg/dL (NV 4.30-22.40 μg/dL), respectively. Such levels were judged to be low in the background of an acute illness. Thyroid function tests were normal – TSH 0.993 μIU/mL (NV 0.55-4.78 uIU/mL), FT3 3.890 pg/mL (2.30-4.20 pg/mL), FT4 1.450 ng/dL (0.89-1.76 ng/dL). Magnetic resonance imaging of the pituitary gland did not show abnormal parenchymal enhancement or enlargement. Pembrolizumab-induced secondary adrenal insufficiency was the most probable cause of the hyponatremia. He was started on IV hydrocortisone, as well as piperacillin-tazobactam for pneumonia. Oxygen support via nasal cannula was given. Feeding via nasogastric tube was decided to ensure nutrition and prevent aspiration. He was transferred to the intensive care unit for careful monitoring. Serum sodium level was corrected gradually, with marked clinical improvement thereafter. Within 48 hours, he was transferred to regular room and oral feeding commenced. Hydrocortisone was shifted to prednisone on discharge, with steroid tapering schedule and close follow-up with endocrinologist advised. Conclusion We presented a case of secondary adrenal insufficiency which likely resulted from hypophysitis induced by pembrolizumab. Hypophysitis following anti-PD1 treatment occurs in <1% of patients on immunotherapy. In such cases, ACTH deficiency is usually isolated and pituitary imaging is frequently normal. Since more patients are being placed on immune-checkpoint inhibition, clinicians should be vigilant for these adverse events, particularly the endocrinopathies which may have non-specific symptoms and may be irreversible.

scholarly journals Two Cases of Pembrolizumab-Induced Secondary Adrenal Insufficiency

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A162-A162
Author(s):  
Akinori Kanzaki ◽  
Taiichirou Otsuki ◽  
Tohru Arii ◽  
Hidenori Koyama ◽  
Satoru Katayama
Keyword(s):  
Adrenal Insufficiency ◽  
Stage Iv ◽  
Japanese Patients ◽  
Pituitary Cell ◽  
Hla Typing ◽  
Test Results ◽  
Secondary Adrenal Insufficiency ◽  
Acth Stimulation ◽  
Cell Antibody ◽  
Anterior Pituitary Function

Abstract Title: Two cases of pembrolizumab-induced secondary adrenal insufficiency Background: Although few cases regarding pembrolizumab-induced secondary adrenal insufficiency were reported, it has recently been published that significantly higher prevalence of human leucocyte antigen (HLA)-DR15, B52, and Cw12 was revealed in 11 Japanese patients with immune checkpoint inhibitor-induced secondary adrenal insufficiency as compared with healthy controls and DR15 might be a predictive marker. This is based on the evidence that DR15 has associations with IL-17-mediated autoimmune disease such as Hashimoto’s thyroiditis, and that anti-programmed death 1 (PD-1) inhibitors activate the Th1 and Th17 pathways. We here introduce two Japanese patients with pembrolizumab-induced secondary adrenal insufficiency from a viewpoint of their HLA typing test results. Clinical Case: Case 1. A 52-year old male diagnosed with stage IV lung cancer (squamous non-small cell lung cancer) was treated with chemotherapy consisting of carboplatin, nab-paclitaxel, and pembrolizumab. Six days after the fourth cycle of pembrolizumab, he suffered from hypoglycemia and hyponatremia. Endocrinological examination findings showed ACTH and cortisol deficiency throughout the day, after which a diagnosis of secondary adrenal insufficiency was made based on no response shown in insulin tolerance, anterior pituitary function, and rapid ACTH stimulation tests. Pituitary cell antibody-1 was negative, and no evidence of a swollen/atrophied pituitary gland or space occupying lesion was observed in magnetic resonance imaging (MRI) results. Furthermore, Hashimoto’s thyroiditis was suspected based on anti-thyroid peroxidase antibody positivity. HLA typing test results highly corresponded with the reported results (A24, B52, Cw12, DR4, DR15). Case 2. A 70-year old male was treated with pembrolizumab for recurrence of lung squamous cell carcinoma (stage IV). Two weeks after completion of five cycles, severe diarrhea occurred, suspected to be a side effect of pembrolizumab, which was relieved with temporary use of prednisolone. However, diarrhea recured accompanied with a high fever, eosinophilia, and acute hyponatremia. Based on results showing deficiency of ACTH and cortisol, adrenal insufficiency was suspected. Anterior pituitary function and rapid ACTH stimulation test results supported that diagnosis, while pituitary cell antibody-1 was negative and MRI findings were not remarkable. Notably, completely different HLA typing test results were observed. Conclusion: Similar to the previous report, HLA-A24, B52, Cw12, DR4, and DR15 were found in case 1, whereas all subtypes including HLA-DR15 were lacking in case 2. We think that it should not be given low priority for cases lacking DR15 and the possibility of an association with IL-17 in such cases is required in feature study.

scholarly journals Biotin Supplementation Creates the Misleading Diagnosis of Secondary Adrenal Insufficiency

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A120-A121
Author(s):  
Hooman Motahari ◽  
Soumya Thumma ◽  
Lakshmi Menon
Keyword(s):  
Adrenal Insufficiency ◽  
Laboratory Testing ◽  
Daily Intake ◽  
Chronic Fatigue ◽  
Water Soluble ◽  
Laboratory Evaluation ◽  
Thyroid Function Tests ◽  
Secondary Adrenal Insufficiency ◽  
Hormone Levels ◽  
Biotin Supplementation

Abstract Introduction: Biotin (vitamin B7) is a water-soluble vitamin and an essential cofactor for the metabolism of fatty acids, glucose, and amino acids. Cases of biotin interference with laboratory testing have been described, most of which involve interference with thyroid function tests. Interference with gonadal steroids, adrenal, and pituitary hormones are rare. We report a case of T3 thyrotoxicosis in which biotin supplementation created the appearance of secondary adrenal insufficiency (AI). Case: A 66-year-old woman was referred for the evaluation of low TSH. She had chronic fatigue, low libido, and dizziness on standing. Vitals were stable with BP 135/64 mmHg and BMI 23.5. No evidence of mucosal or cutaneous hyperpigmentation. Laboratory evaluation revealed low ACTH <5 (7.2–63.3 pg/mL), low morning cortisol 3.8 and high DHEA-S 174 (13–130 ug/dL). TSH was low at 0.32 (0.32–5.60 uIU/mL) with normal prolactin and appropriately elevated FSH and LH. The labs raised concern for secondary AI. Cosyntropin stimulation test (CST) was done with a peak cortisol of 17.4 ug/dL. In the setting of suppressed ACTH and failed CST, she was started on Hydrocortisone therapy. Subsequently, CT of abdomen was obtained due to high DHEA-S which showed normal appearance of both adrenals. Pituitary MRI was normal. A detailed review of the medication list revealed that the patient was taking a Biotin containing multivitamin. Repeat labs 1 week after stopping biotin showed normalization of ACTH 13.8 (7.2–63.3). Repeat CST showed a peak cortisol response of 24 ug/dL. Hydrocortisone was discontinued and the patient remained stable on subsequent follow-ups, without the need for further glucocorticoid replacement therapy. Thyroid lab abnormalities persisted after biotin cessation which led to the diagnosis of T3 thyrotoxicosis, the treatment of which caused resolution of the patient’s symptoms. Discussion: The recommended daily intake of biotin for adults is 30 µg/d. Many over-the-counter products, specifically those marketed for hair, skin, and nail growth, contain biotin 100-fold higher than the recommended intake. Biotin interference with competitive immunoassays can cause falsely elevated hormone levels, whereas biotin interference with immunometric “sandwich” assays falsely lowers hormone levels. In our case, low ACTH was clinically misleading, prompting numerous unnecessary radiographic and laboratory testing and treatment with hydrocortisone. The US Food and Drug Administration issued a safety communication regarding biotin interference with laboratory tests. Education and communication between laboratorians, providers, and patients play an important role in investigating potential lab interference and the need for alternative lab assays for an accurate diagnosis. Patients should be asked to stop taking biotin supplements for at least 48 hours prior to specimen collection if possible.

scholarly journals Severe hyponatremia due to hypopituitarism with adrenal insufficiency: report on 28 cases

2003 ◽  
pp. 609-617 ◽  
Author(s):  
S Diederich ◽  
NF Franzen ◽  
V Bahr ◽  
W Oelkers
Keyword(s):  
Adrenal Insufficiency ◽  
Antidiuretic Hormone ◽  
Hospital Admissions ◽  
Clinical Signs ◽  
University Hospital ◽  
Pituitary Hormone ◽  
Stressful Situation ◽  
Secondary Adrenal Insufficiency ◽  
Severe Hyponatremia ◽  
Underlying Disorder

OBJECTIVE: Severe hyponatremia due to hypopituitarism and adrenal insufficiency can be life-threatening, and treatment with glucocorticoids is very effective once the diagnosis of the underlying disorder has been made. In our experience, the diagnosis of hypopituitarism in hyponatremic patients is often overlooked. METHODS: In a retrospective study we screened the files of 185 patients with severe hyponatremia (<130 mmol/l) that had been seen in one endocrinological unit of a university hospital between 1981 and 2001 in order to describe the clinical spectrum of patients with hyponatremia and hypopituitarism including secondary adrenal insufficiency. RESULTS: In 139 cases it was possible to clearly ascribe the patients to the pathophysiological groups of (i) primary sodium deficiency, (ii) edematous disorders, and (iii) normovolemic disorders including the "syndrome of inappropriate secretion of antidiuretic hormone" (SIADH). Twenty-eight patients with severe "normovolemic hyponatremia" (serum sodium: 116+/-7 mmol/l, mean+/-s.d.) had hypopituitarism and secondary adrenal insufficiency as shown by basal cortisol measurements and dynamic tests of adrenal function. In 25 cases of this group hypopituitarism (mostly due to empty sella, Sheehan's syndrome and pituitary tumors) had not been recognized previously, and in 12 cases recurrent hyponatremia during previous hospital admissions (up to four times) could be documented. The mean age of these patients (21 women, seven men) was 68 Years. The most frequently occurring clinical signs were missing or scanty pubic and axillary hair, pale and doughy skin, and small testicles in the men. Frequent symptoms like nausea and vomiting, confusion, disorientation, somnolence or coma were similar to those in 91 patients with SIADH. Basal serum cortisol levels in the acutely ill state ranged from 20 to 439 nmol/l (mean+/-s.d.: 157+/-123), while in 30 other severely hyponatremic patients it ranged from 274 to 1732 nmol/l (732+/-351 nmol/l). In most patients with hyponatremic hypopituitarism, plasma antidiuretic hormone levels were inappropriately high, probably due to a failure of endogenous cortisol to suppress the hormone in a stressful situation. All patients recovered after low-dose hydrocortisone substitution. Most patients had other pituitary hormone deficiencies and were appropriately substituted subsequently. CONCLUSIONS: Hypopituitarism including secondary adrenal insufficiency seems to be a frequently overlooked cause of severe hyponatremia. A high level of suspicion is the best way to recognize the underlying disorder. Treatment with hydrocortisone is very effective.

scholarly journals Severe Symptomatic SIADH as a Sign of Unknow Hypopituitarism: A Case Report

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A609-A610
Author(s):  
Juliana Marques-Sá ◽  
Catarina Silva Araújo ◽  
Maria Joana Santos
Keyword(s):  
Adrenal Insufficiency ◽  
Rare Condition ◽  
Urine Osmolality ◽  
Serum Cortisol ◽  
Empty Sella ◽  
Secondary Adrenal Insufficiency ◽  
Severe Hyponatremia ◽  
Long Time ◽  
Remarkable Recovery ◽  
High Level

Abstract Background: SIADH due to secondary adrenal insufficiency is a rare condition that can be life-threatening. Treatment with glucocorticoids is highly effective, but, as symptomatology of hypopituitarism can be mild and unspecific, a high level of clinical suspicion is necessary. Clinical Case: A 64-year-old postmenopausal woman, with a previously diagnosed and treated hypothyroidism and depressive syndrome, presented at the emergency room with nausea, vomits, asthenia and recurrent syncopes over the past three weeks and weight loss in the last months. One week before, she had been admitted at other hospital due to the same complaints and a serum Na+ of 112mmol/L (N 135-145 mmol/L) was detected. One year earlier, she had reported the same symptomology and hyponatremia had also been found, but no etiologic study was performed. At admission, she was conscient, hydrated, pale, hemodynamically stable, with unremarkable cardiopulmonary auscultation. A severe hyponatremia was found (Na+ 111mmol/L), with low serum osmolarity (241mOsm/Kg, N 280-301mOsm/Kg), low urine osmolality (125mOsm/kg N 300-900 mOsm/Kg) and low urinary sodium (33mmol/24h, N 40-220mmol/24h). Treatment with saline fluids was initiated and the patient was admitted for etiological investigation, which showed a low morning serum cortisol (3.7 µg/dl)) with inappropriately low-normal ACTH level (12.2 pg/mL), low FSH (15.07 mUI/mL, N 23.0-116.3 mUI/mL) and LH (4.28 mUI/mL, N 15.9-54 mUI/mL), estradiol of 78.81 pmol/L (N &lt;118.2 pmol/L), undetectable IGF-1 (&lt;25 ng/mL, N 36-244 ng/mL) and PRL of 21.98 ng/mL (N 1.8-20.3 ng/mL). Under 50µg of levothyroxine, TSH was 2.5 µUI/mL (N 0.358-3.74 µUI/ml), and FT4 was 1.1 ng/dL (N 0.76-1.46 ng/dL). Anti-thyroglobulin and anti-TPO antibodies were negative. A pituitary MRI revealed an empty sella with arachnoidocele. Other differential diagnosis of SIADH were excluded. The patient was started on oral hydrocortisone 30 mg/day, with a remarkable recovery, with better mood, more energy and appetite, resolution of all symptoms and normalization of the natremia. Conclusion: Hypopituitarism due to an empty sella is a relative rare disorder, whose etiology may be difficult to prove. It usually develops insidiously, with unspecific symptoms, which often delays the diagnosis. In our patient, this severe hyponatremia likely developed over a long time, allowing adaptation to such low levels of Na+. Moreover, the presence of a previously diagnosed hypothyroidism raises the suspicion if this wasn’t the first manifestation of the pituitary disease and if treatment of levothyroxine did not worsen an undetected secondary adrenal insufficiency.

scholarly journals Severe hyponatremia caused by secondary adrenal insufficiency in a patient with giant pituitary prolactinoma

2013 ◽  
Vol 2 (2) ◽  
pp. 184-189 ◽  
Author(s):  
Akimitsu Kobayashi ◽  
Yasushi Otsuka ◽  
Takeo Yoshizawa ◽  
Masuomi Tomita ◽  
Hideo Asada ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Secondary Adrenal Insufficiency ◽  
Severe Hyponatremia

scholarly journals Chronic Heroin Dependence Leading to Adrenal Insufficiency

2014 ◽  
Vol 2014 ◽  
pp. 1-2 ◽  
Author(s):  
Gautam Das
Keyword(s):  
Pain Relief ◽  
Adrenal Insufficiency ◽  
Hpa Axis ◽  
Negative Impact ◽  
Endocrine System ◽  
Multiple Organ ◽  
Drug Addicts ◽  
Secondary Adrenal Insufficiency ◽  
Long Period ◽  
Organ Systems

Opioids have been the mainstay for pain relief and palliation over a long period of time. They are commonly abused by drug addicts and such dependence usually imparts severe physiologic effects on multiple organ systems. The negative impact of opioids on the endocrine system is poorly understood and often underestimated. We describe a patient who developed severe suppression of the hypothalamic-pituitary adrenal (HPA) axis leading to secondary adrenal insufficiency due to long standing abuse of opioids.

scholarly journals Effects of SARS-CoV-2 on the endocrine system

2021 ◽  
Vol 5 (9) ◽  
pp. 575-578
Author(s):  
N.A. Petunina ◽  
◽  
A.S. Shkoda ◽  
M.E. Telnova ◽  
E.V. Goncharova ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Transmembrane Protein ◽  
Severe Disease ◽  
Endocrine System ◽  
Long Term Effects ◽  
Secondary Adrenal Insufficiency ◽  
Euthyroid Sick Syndrome ◽  
Obesity And Diabetes ◽  
Russian Medical

SARS-CoV-2 rapidly spread worldwide and resulted in an unprecedented pandemic. Considering the novelty of this disease, its potential effects on the endocrine system remain elusive. This virus is known to utilize the extracellular domain of angiotensin-converting enzyme (ACE) and transmembrane protein TMPRSS2. Broad expression of ACE-2 and TMPRSS2 is a potential cause of extrapulmonary manifestations of SARSCoV- 2, including endocrine ones. The most common presentations are direct or indirect damage of the endocrine part of the pancreas, hypothalamicpituitary- adrenal and hypothalamic-pituitary-thyroid axes, and possible long-term effects on the reproductive system. It was demonstrated that obesity and diabetes increase the risk of severe course and death in COVID-19. Similarly, patients with transitory hyperglycemia have a higher risk of severe disease course. Primary and secondary adrenal insufficiency of various origins potentially accounts for severity. The most common thyroid complications of the COVID-19 infection are euthyroid sick syndrome and transient destructive thyroiditis, including subacute thyroiditis. KEYWORDS: SARS-CoV-2, COVID-19, endocrinopathies, diabetes, adrenal insufficiency. FOR CITATION: Petunina N.A., Shkoda A.S., Telnova M.E. et al. Effects of SARS-CoV-2 on the endocrine system. Russian Medical Inquiry. 2021;5(9):575–578 (in Russ.). DOI: 10.32364/2587-6821-2021-5-9-575-578.

Abstract #514 Secondary Adrenal Insufficiency Due to the Immune Checkpoint Inhibitor Pembrolizumab

2019 ◽  
Vol 25 ◽  
pp. 256
Author(s):  
Mohammad Ansari ◽  
Ula Tarabichi ◽  
Hadoun Jabri ◽  
Qiang Nai ◽  
Anis Rehman ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Secondary Adrenal Insufficiency
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