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 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 Adrenal cortex function impairment in chronic fatigue syndrome

2003 ◽  
Vol 131 (9-10) ◽  
pp. 370-374 ◽  
Author(s):  
Milos Zarkovic ◽  
Milorad Pavlovic ◽  
Ana Pokrajac-Simeunovic ◽  
Jasmina Ciric ◽  
Biljana Beleslin ◽  
...  
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Adrenal Insufficiency ◽  
Response Curve ◽  
Low Dose ◽  
Chronic Fatigue ◽  
Cortisol Response ◽  
Acth Test ◽  
Secondary Adrenal Insufficiency ◽  
Acth Stimulation ◽  
Fatigue Syndrome

Chronic fatigue syndrome (CFS) is defined as constellation of the prolonged fatigue and several somatic symptoms, in the absence of organic or severe psychiatric disease. However, this is an operational definition and conclusive biomedical explanation remains elusive. Similarities between the signs and symptoms of CFS and adrenal insufficiency prompted the research of the hypothalamo-pituitary-adrenal axis (HPA) derangement in the pathogenesis of the CFS. Early studies showed mild glucocorticoid deficiency, probably of central origin that was compensated by enhanced adrenal sensitivity to ACTH. Further studies showed reduced ACTH response to vasopressin infusion. The response to CRH was either blunted or unchanged. Cortisol response to insulin induced hypoglycaemia was same as in the control subjects while ACTH response was reported to be same or enhanced. However, results of direct stimulation of the adrenal cortex using ACTH were conflicting. Cortisol and DHEA responses were found to be the same or reduced compared to control subjects. Scott et all found that maximal cortisol increment from baseline is significantly lower in CFS subjects. The same group also found small adrenal glands in some CFS subjects. These varied and inconsistent results could be explained by the heterogeneous study population due to multifactorial causes of the disease and by methodological differences. The aim of our study was to assess cortisol response to low dose (1 ?g) ACTH using previously validated methodology. We compared cortisol response in the CFS subjects with the response in control and in subjects with suppressed HPA axis due to prolonged corticosteroid use. Cortisol responses were analyzed in three subject groups: control (C) secondary adrenal insufficiency (AI), and in CFS. The C group consisted of 39 subjects, AI group of 22, and CFS group of nine subjects. Subject data are presented in table 1. Low dose ACTH test was started at 0800 h with the iv injection of 1 ?g ACTH (Galenika, Belgrade, Serbia). Blood samples for cortisol determination were taken from the iv cannula at 0,15, 30, and 60 min. Data are presented as mean standard error (SE). Statistical analysis was done using ANOVA with the Games-Howell post-hoc test to determine group differences. ACTH dose per kg or per square meter of body surface was not different between the groups. Baseline cortisol was not different between the groups. However, cortisol concentrations after 15 and 30 minutes were significantly higher in the C group than in the AI group. Cortisol concentration in the CFS group was not significantly different from any other group (Graph 1). Cortisol increment at 15 and 30 minutes from basal value was significantly higher in C group than in other two groups. However there was no significant difference in cortisol increment between the AI and CFS groups at any time of the test. On the contrary, maximal cortisol increment was not different between CFS and other two groups, although it was significantly higher in C group than in the AI group. Maximal cortisol response to the ACTH stimulation and area under the cortisol response curve was significantly larger in C group compared to AI group, but there was no difference between CFS and other two groups. Several previous studies assessed cortisol response to ACTH stimulation. Hudson and Cleare analysed cortisol response to 1 ?g ACTH in CFS and control subjects.They compared maximum cortisol attained during the test, maximum cortisol increment, and area under the cortisol response curve.There was no difference between the groups in any of the analysed parameters. However, authors commented that responses were generally low. On the contrary Scott et all found that cortisol increment at 30 min is significantly lower in the CFS than in the control group. Taking into account our data it seems that the differences found in previous studies papers are caused by the methodological differences. We have shown that cortisol increment at 15 and 30 min is significantly lower in CFS group than in C group. Nevertheless, maximum cortisol attained during the test, maximum cortisol increment, and area under the cortisol response curve were not different between the C and CFS groups. This is in agreement with our previous findings that cortisol increment at 15 minutes has the best diagnostic value of all parameters obtained during of low dose ACTH test. However, there was no difference between CFS and AI group in any of the parameters, although AI group had significantly lower cortisol concentrations at 15 and 30 minutes, maximal cortisol response, area under the cortisol curve, maximal cortisol increment, and maximal cortisol change velocity than C group. Consequently reduced adrenal responsiveness to ACTH exists in CFS. In conclusion, we find that regarding the adrenal response to ACTH stimulation CFS subjects present heterogeneous group. In some subjects cortisol response is preserved, while in the others it is similar to one found in secondary adrenal insufficiency.

scholarly journals Polyuria in a Patient With a Pituitary Mass

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A602-A603
Author(s):  
Sowjanya Naha ◽  
Joseph Theressa Nehu Parimi ◽  
Rajani Gundluru ◽  
John Chen Liu ◽  
Hasan Syed ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Replacement Therapy ◽  
Urine Output ◽  
Laboratory Evaluation ◽  
Secondary Adrenal Insufficiency ◽  
Pituitary Mass ◽  
Maximum Serum ◽  
Water Excretion ◽  
Daily Urine ◽  
Daily Urine Output

Abstract Background: Hypocortisolism can develop in patients with a pituitary mass because of hypopituitarism and is appropriately managed with steroid replacement. However, these patients often have co-existing endocrine derangements that can become clinically evident after administration of steroids. Clinical Case: A sixty-year-old Caucasian female with known non-small cell lung cancer on chemoimmunotherapy was admitted for management of an enlarging suprasellar mass. Her symptoms included nausea, vomiting and multiple syncopal episodes over the preceding three weeks. At the time of admission, physical examination was unremarkable. She was noted to be hypotensive with systolic blood pressure in the high 70s and was treated with intravenous fluids. Laboratory evaluation showed low random cortisol (0.99 ug/dL, n: 0.4-22.6 ug/dL), undetectable ACTH (<5 pg/mL, n: 7.2-63 pg/mL), low free thyroxine (1.01 ug/dL, n: 0.93-1.7 ug/dL), low free T3 (1.6 pg/mL, n: 2-4.4 pg/mL) and low TSH (0.023 ug/dL, n: 0.27-4.2 ug/dL), consistent with central hypothyroidism and secondary adrenal insufficiency. Importantly, she was normonatremic and normokalemic at admission. She was started on stress dose hydrocortisone (100 mg IV q8h) for presumed adrenal crisis. Following institution of steroid replacement therapy, the patient rapidly became polyuric while simultaneously developing hypernatremia. Her daily urine output peaked at 4400 mL corresponding temporally to a maximum serum sodium of 160 mmol/L. A single dose of 0.5 mg of desmopressin resulted in immediate lowering of daily urine output to 750 mL and appropriate improvement in urine osmolality from 147 mOsm/kg to 565 mOsm/kg, confirming a diagnosis of central diabetes insipidus (cDI). Conclusion: Hypocortisolism is known to impair free water excretion by stimulating arginine vasopressin (AVP) secretion through renal sodium loss and consequent volume depletion as well as direct feedback stimulation of corticotrophin releasing hormone (CRH) and AVP within the hypothalamus. Conversely steroid replacement leads to loss of feedback stimulation, unmasking cDI. This unique convergence of cDI with hypocortisolism is most often encountered in patients with hypopituitarism. Hence patients with secondary adrenal insufficiency should be carefully monitored for cDI after initiation of steroid replacement therapy.

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

Abstract #476 Coming in from the Cold: Unusual Presentation of Secondary Adrenal Insufficiency

2019 ◽  
Vol 25 ◽  
pp. 232-233
Author(s):  
Richard Pinsker ◽  
Tahmina Jahir ◽  
Sudheer Chauhan ◽  
Narinder Kukar
Keyword(s):  
Adrenal Insufficiency ◽  
Unusual Presentation ◽  
Secondary Adrenal Insufficiency

Adrenal crisis in patients with primary and secondary adrenal insufficiency

2006 ◽  
Vol 114 (S 1) ◽  
Author(s):  
S Hahner ◽  
M Löffler ◽  
D Weismann ◽  
AC Koschker ◽  
M Fassnacht ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Adrenal Crisis ◽  
Secondary Adrenal Insufficiency

Acute illness in children with secondary adrenal insufficiency

2021 ◽  
Author(s):  
Rosemary Louise Rushworth ◽  
Nikki Gouvoussis ◽  
Thomas Goubar ◽  
Ann Maguire ◽  
Craig F. Munns ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Acute Illness ◽  
Secondary Adrenal Insufficiency

scholarly journals Immune checkpoint inhibitor combination therapies very frequently induce secondary adrenal insufficiency

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Katsunori Manaka ◽  
Junichiro Sato ◽  
Maki Takeuchi ◽  
Kousuke Watanabe ◽  
Hidenori Kage ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Adrenal Insufficiency ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Delayed Diagnosis ◽  
Secondary Adrenal Insufficiency ◽  
Acth Deficiency ◽  
Life Threatening ◽  
Inhibitor Combination

AbstractImmune checkpoint inhibitors (ICIs) are potent therapeutic options for many types of advanced cancer. The expansion of ICIs use however has led to an increase in immune-related adverse events (irAEs). Secondary adrenal insufficiency (AI) can be life-threatening especially in patients with delayed diagnosis. We retrospectively investigated secondary AI in ICI-treated patients. A total of 373 cancer patients treated with ICIs were included and evaluated. An adrenocorticotropic hormone (ACTH) deficiency was described in 13 patients. Among 24 patients with a combination of nivolumab and ipilimumab therapy, 7 patients (29%) developed secondary AI in a median time of 8 weeks during the combination therapy and 2 of 15 patients (13%) developed isolated ACTH deficiency during maintenance nivolumab monotherapy following the combination therapy. More than half of the patients (4/7) with a combination therapy-induced multiple anterior hormone deficiencies was diagnosed as secondary AI based on regular ACTH and cortisol tests with slight subjective symptoms. Secondary AI can arise frequently and rapidly in cancer patients receiving a combination ICI therapy, and thus we speculate active surveillance of AI using regular ACTH and cortisol tests during the combination therapy might be useful for avoiding life-threatening conditions due to secondary AI.

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