scholarly journals Primary Adrenal Insufficiency During Lenvatinib or Vandetanib and Improvement of Fatigue After Cortisone Acetate Therapy

2018 ◽  
Vol 104 (3) ◽  
pp. 779-784 ◽  
Author(s):  
Carla Colombo ◽  
Simone De Leo ◽  
Marta Di Stefano ◽  
Guia Vannucchi ◽  
Luca Persani ◽  
...  
Keyword(s):  
Adverse Event ◽  
Thyroid Cancer ◽  
Adrenal Insufficiency ◽  
Replacement Therapy ◽  
Dosage Reduction ◽  
Adrenal Function ◽  
Cortisone Acetate ◽  
Drug Discontinuation ◽  
Primary Adrenal Insufficiency ◽  
Common Cause

Abstract Context Two tyrosine kinase inhibitors (TKIs), lenvatinib and vandetanib, are often used to treat advanced radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) and medullary thyroid cancer (MTC), respectively. Fatigue is a common adverse event during treatment with these and other TKIs and a common cause of drug discontinuation or dosage reduction. Cases Description We evaluated the basal and stimulated adrenal function in 12 patients with advanced RAI-R DTC and MTC treated with lenvatinib or vandetanib, respectively. Ten patients complaining of fatigue showed a progressive ACTH increase with normal cortisol levels. Moreover, six of 10 patients had a blunted cortisol response after ACTH stimulation, thus confirming the diagnosis of primary adrenal insufficiency (PAI). The causal relationship between TKIs and PAI onset was also demonstrated by the repeated testing of adrenal function before and during treatment. Patients with PAI received cortisone acetate replacement therapy, with a substantial and prompt improvement in the degree of fatigue, as assessed by the Common Terminology Criteria for Adverse Events version 4.03, thus supporting the major impact of impaired adrenal function in the genesis of this adverse event. Conclusions We show that the occurrence of PAI may be a common cause of fatigue during lenvatinib and vandetanib treatment, and we therefore recommend testing adrenal function for a prompt start of replacement therapy to avoid treatment discontinuation, dosage reduction, and potentially severe PAI complications.

scholarly journals MON-537 Primary Adrenal Insufficiency During Tyrosine Kinase Inhibitors Treatment in Advanced Thyroid Cancer Patients

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Laura Valerio ◽  
Antonio Matrone ◽  
Laura Agate ◽  
Valeria Bottici ◽  
David Viola ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tyrosine Kinase ◽  
Adrenal Insufficiency ◽  
Replacement Therapy ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Treatment Initiation ◽  
Stimulation Test ◽  
Pathological Features ◽  
Primary Adrenal Insufficiency

Abstract Objective: Tyrosine kinase inhibitors (TKIs) are used for the treatment of metastatic differentiated (DTC), poorly differentiated (PDTC) and medullary (MTC) thyroid cancer. Several adverse events (AEs) have been reported in almost all patients (pts) treated with TKIs. One of the less known AE related to the use of these drugs is the primary adrenal insufficiency (PAI). Methods: We analyzed the basal and stimulated adrenal function, ACTH levels, adrenal antibodies and electrolytes levels in 82 thyroid cancer pts treated with TKIs (vandetanib and cabozantinib in MTC pts, lenvatinib and sorafenib in DTC and PDTC pts) and we correlated these results with the clinical-pathological features of our pts. Results: In our series, 25/82 (30.5%) pts showed a PAI after stimulation test with a progressive ACTH increase in 14/25 (56%) pts. Thirteen/25 (52%) pts with PAI were DTC, 8/25 (32%) pts were MTC and 4/25 (16%) pts were PDTC. Sixteen/25 (64%) pts were treated with lenvatinib, 8/25 (32%) were treated with vandetanib and 1/25 (4%) was treated with cabozantinib at the time of stimulation test. In 5/25 (20%) pts PAI occurred within 12 months from the TKIs treatment initiation, in 9/25 (36%) within 36 months and in 11/25 (44%) after 36 months of treatment. Eighteen/25 pts with PAI were older than 55 years. Twenty/25 (80%) of these pts were treated with cortisone acetate replacement therapy with the improvement of fatigue in a small part of these while other 5 pts were untreated due to the mild degree of PAI and the absence of specific symptoms (i.e fatigue). Moreover, in our pts the evaluation of adrenal antibodies was negative and the electrolytes levels were in the normal range. We also correlated the presence of PAI with the clinical-pathological features of our pts but we didn’t observe any significant correlation. Conclusions: We observed that PAI, mainly subclinical, can occur during TKIs treatment in thyroid cancer pts. The appearance of fatigue, the typical symptom of PAI, could be multifactorial in these pts due also to the direct effect of TKIs treatment. Thus, in these cases is very difficult to recognize the cause of fatigue and to decide the appropriate treatment (cortisone acetate replacement therapy vs TKIs dose reduction). Moreover, the time of PAI appearance is variable since it can be early (<12 months) or late (>36 months) after TKIs treatment initiation and the adrenal function must be monitored during all TKIs treatment period. More studies are needed to know the pathophysiology of this “adverse event” during TKIs treatment and to improve the acknowledgments regarding the differential diagnosis and treatment of these pts, regardless of symptoms.

scholarly journals Acute Primary Adrenal Insufficiency after Hip Replacement in a Patient with Acute Intermittent Porphyria

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Adele Latina ◽  
Massimo Terzolo ◽  
Anna Pia ◽  
Giuseppe Reimondo ◽  
Elena Castellano ◽  
...  
Keyword(s):  
Postmenopausal Woman ◽  
Adrenal Insufficiency ◽  
Replacement Therapy ◽  
Genetic Disease ◽  
Hip Replacement ◽  
Acute Intermittent Porphyria ◽  
Adrenal Hemorrhage ◽  
Primary Adrenal Insufficiency ◽  
Threatening Condition ◽  
Life Threatening

Adrenal insufficiency is a potentially life-threatening condition when it occurs acutely, as in adrenal hemorrhage. Generally it is not reversible and requires chronic replacement therapy. Acute intermittent porphyria (AIP) is a rare genetic disease characterized by alterations in heme biosynthesis that result in accumulation of precursors in tissues. A crisis can be triggered by many conditions such as surgery and infections. Symptoms are similar to those of acute hypoadrenalism. Moreover, both conditions are characterized by hyponatremia. We describe the case of a postmenopausal woman known to be affected by AIP who developed after surgery a primary adrenal insufficiency associated with adrenal enlargement; the latter completely reverted in six months.

Corticosteroid replacement: getting it right

1990 ◽  
Vol 28 (18) ◽  
pp. 71-72
Keyword(s):  
Adrenal Insufficiency ◽  
Cortisone Acetate ◽  
Adrenal Failure ◽  
Secondary Adrenal Insufficiency ◽  
Primary Adrenal Insufficiency ◽  
Acth Deficiency ◽  
Mineralocorticoid Activity

Glucocorticoid replacement is needed in primary and secondary adrenal insufficiency. Cortisol (hydrocortisone) is the most physiologically appropriate drug; prednisolone has little mineralocorticoid activity, and cortisone acetate suffers variable absorption and hepatic conversion to cortisol.1 Patients with primary adrenal insufficiency usually need additional mineralocorticoid replacement with fludrocortisone once a day. Patients with secondary adrenal failure (ACTH deficiency due to pituitary/hypothalamic disease) still produce aldosterone and so do not need fludrocortisone.

scholarly journals Prednisolone is associated with a worse bone mineral density in primary adrenal insufficiency

2018 ◽  
Vol 7 (6) ◽  
pp. 811-818 ◽  
Author(s):  
Kathrin R Frey ◽  
Tina Kienitz ◽  
Julia Schulz ◽  
Manfred Ventz ◽  
Kathrin Zopf ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Adrenal Insufficiency ◽  
Replacement Therapy ◽  
Bone Mineral ◽  
Immediate Release ◽  
Modified Release ◽  
Mineral Density ◽  
Primary Adrenal Insufficiency ◽  
Z Scores

Context Patients with primary adrenal insufficiency (PAI) or congenital adrenal hyperplasia (CAH) receive life-long glucocorticoid (GC) therapy. Daily GC doses are often above the physiological cortisol production rate and can cause long-term morbidities such as osteoporosis. No prospective trial has investigated the long-term effect of different GC therapies on bone mineral density (BMD) in those patients. Objectives To determine if patients on hydrocortisone (HC) or prednisolone show changes in BMD after follow-up of 5.5 years. To investigate if BMD is altered after switching from immediate- to modified-release HC. Design and patients Prospective, observational, longitudinal study with evaluation of BMD by DXA at visit1, after 2.2 ± 0.4 (visit2) and after 5.5 ± 0.8 years (visit3) included 36 PAI and 8 CAH patients. Thirteen patients received prednisolone (age 52.5 ± 14.8 years; 8 women) and 31 patients received immediate-release HC (age 48.9 ± 15.8 years; 22 women). Twelve patients on immediate-release switched to modified-release HC at visit2. Results Prednisolone showed significantly lower Z-scores compared to HC at femoral neck (−0.85 ± 0.80 vs −0.25 ± 1.16, P < 0.05), trochanter (−0.96 ± 0.62 vs 0.51 ± 1.07, P < 0.05) and total hip (−0.78 ± 0.55 vs 0.36 ± 1.04, P < 0.05), but not at lumbar spine, throughout the study. Prednisolone dose decreased by 8% over study time, but no significant effect was seen on BMD. BMD did not change significantly after switching from immediate- to modified-release HC. Conclusions The use of prednisolone as hormone replacement therapy results in significantly lower BMD compared to HC. Patients on low-dose HC replacement therapy showed unchanged Z-scores within the normal reference range during the study period.

scholarly journals Primary adrenal insufficiency replacement therapy

2000 ◽  
Vol 46 (3) ◽  
pp. 31-45
Author(s):  
V. V. Fadeev ◽  
G. A. Melnichenko
Keyword(s):  
Heart Failure ◽  
Adrenal Insufficiency ◽  
Replacement Therapy ◽  
Adrenal Cortex ◽  
Adrenal Glands ◽  
Pathological Process ◽  
Clinical Syndrome ◽  
Primary Adrenal Insufficiency ◽  
Adrenal System ◽  
System 2

Adrenal insufficiency is a clinical syndrome caused by insufficient secretion of hormones by the adrenal cortex, which is the result of a malfunction of one or more parts of the hypothalamic-pituitary-adrenal system [2]. Primary chronic adrenal insufficiency (1-CNI) develops as a result of the destruction of more than 90% of the cortex of both adrenal glands by a pathological process. The main causes of 1-CNN are currently autoimmune (80–85%) and tuberculosis (5–10%) destruction of the adrenal cortex [2, 3]. 1-CNN of the indicated etiology is better known as "Addison's disease." 1-CNN is a relatively rare disease (40-110 new cases per 1 million people per year) [2, 3], but it is of considerable importance in the practice of endocrinology. Without exception, all patients with a diagnosis of 1-chronic heart failure need lifelong replacement therapy with corticosteroids (CS), which will be discussed in this work.

scholarly journals Long-Term Outcomes of Conventional And Novel Steroid Replacement Therapy On Bone Health In Primary Adrenal Insufficiency

2021 ◽  
Author(s):  
Valentina Guarnotta ◽  
Claudia Di Stefano ◽  
Carla Giordano
Keyword(s):  
Alkaline Phosphatase ◽  
Lumbar Spine ◽  
Adrenal Insufficiency ◽  
Replacement Therapy ◽  
Bone Alkaline Phosphatase ◽  
Primary Adrenal Insufficiency ◽  
Z Scores ◽  
Group A ◽  
Group B

Abstract Purpose: To compare dual-release hydrocortisone (DR-HC) and conventional glucocorticoids (GCs) on bone metabolism in patients with primary adrenal insufficiency (PAI).Methods: Thirty-five patients with PAI maintained conventional GCs (group A), while other 35 were switched to DR-HC (group B). At baseline and after 18, 36 and 60 months of conventional GCs and DR-HC treatment, the clinical and bone metabolic parameters were evaluated. Results: After 60 months of follow-up, patients in group A had a significant increase in Body Mass Index (BMI) (p=0.004) and Waist Circumference (WC) (p=0.026) and a significant decrease in osteocalcin (p=0.002), bone alkaline phosphatase (p=0.029), lumbar spine bone mass density (BMD) T and Z scores (p<0.001 and p=0.001, respectively) than baseline. By contrast, patients in group B had a significant decrease in WC (p=0.047) and increase in bone alkaline phosphatase (p=0.019), lumbar spine BMD T score (p=0.032), femoral neck BMD T and Z scores (p=0.023 and p=0.036, respectively) than baseline. Conclusions: Long-term conventional steroid replacement therapy is associated with a decrease in BMD, notably at lumbar spine, and an increase in vertebral fractures rate. By contrast, DR-HC treatment is associated with improvement of BMD.

Reversibility of Acute Adrenal Insufficiency after hip Replacement: A Case Series

2020 ◽  
Vol 20 ◽  
Author(s):  
Adele Latina ◽  
Micaela Pellegrino ◽  
Alfonsina Chiefari ◽  
Pina Lardo ◽  
Anna Pia ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Orthopedic Surgery ◽  
Hip Replacement ◽  
Case Series ◽  
Adrenal Function ◽  
Cortisone Acetate ◽  
Acth Stimulation ◽  
Acute Adrenal Insufficiency ◽  
Adrenal Imaging ◽  
Major Orthopedic Surgery

Background: Acute adrenal insufficiency is a rare but potentially lethal condition that is important to identify promptly and treat with replacement therapy. It can be due to adrenal hemorrhage that can occur after major orthopedic surgery. Few data are available about potential recovery of adrenal function, as well as both timing and modality of cortisone acetate withdrawal, probably due to the assumption that adrenal failure is definitive. A not massive adrenal damage can justify a partial, or potentially complete, recovery of adrenal function. Methods: We had recently described a case of acute adrenal insufficiency, which developed shortly after hip replacement; the patient was able to discontinue cortisone acetate treatment 46 months after the diagnosis and remained untreated up to five years later. We found other two cases of acute adrenal insufficiency that developed about one week after major orthopedic surgery. We followed such patients for about three years, repeatedly reassessing adrenal imaging and cortisol response to 250 µg ACTH test, in order to ascertain the real need of lifetime substitutive treatment with cortisone acetate. Results: Acute adrenal insufficiency partially reverted during the follow up for both patients. We observed a reduction in adrenal glands’ volume and a progressive improvement of cortisol basal levels, without response (or with a poor one) to ACTH stimulation, as well as with ACTH basal levels persistently above the normal range after 36 and 28 months respectively after the acute event. Conclusions: The present finding suggests that patients developing acute adrenal insufficiency after major orthopedic surgery must undergo long-term surveillance, in order to establish if steroid replacement has to be continued, or if it can be safely withdrawn.

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