Abstract:Secondary Adrenal Insufficiency (SAI) is a condition characterized by inappropriately low ACTH secretion due to a disease or injury to the hypothalamus or the pituitary. The evaluation when suspected is often challenging for the non-specific symptoms, the rarity of the disease, and the pitfalls associated with laboratory tests. A prompt and correct diagnosis of SAI is essential because although an adequate hormonal replacement therapy could be lifesaving, inappropriate life-long therapy with steroids can be ha… Show more
“… Figure 1 Cortisol levels at baseline and at 30 and 60 min after stimulation test performed through infusion of 250 μg ACTH in 26/36 patients (18 LENV, 6 VAND and 2 SELP). Peak cortisol levels <15 μg/dL (dotted line) at 30 or 60 min indicate primary adrenal insufficiency, according to new cut-off proposed for new cortisol assays ( 23 , 24 , 25 ). Cortisol response to the ACTH 250 μg stimulation test was reduced in 5/26 patients (19%): 3/18 (17%) on lvatinib and 2/6 (33%) on vandetanib.…”
Section: Resultsmentioning
confidence: 99%
“…Current guidelines consider a peak cortisol level > 18.1 μg/dL (500 nmol/L) at 30 or 60 min after ACTH injection as appropriate, allowing for the exclusion of PAI ( 22 ). Nevertheless, since cortisol assays have recently become more sensitive and a new cutoff of 15 μg/dL has been proposed ( 23 , 24 , 25 ), we calculated the prevalence of PAI accordingly.…”
Background: Fatigue is a frequent adverse event during systemic treatments for advanced thyroid cancer, often leading to reduction, interruption or discontinuation. We were the first group to demonstrate a correlation between fatigue and primary adrenal insufficiency (PAI).
Aim: To assess the entire adrenal function in patients on systemic treatments.
Methods: ACTH, cortisol and all the hormones produced by the adrenal gland were evaluated monthly in 36 patients (25 on lenvatinib, 6 on vandetanib, and 5 on selpercatinib). ACTH stimulation test was performed in 26 cases.
Results: After a median treatment period of 7 months, we observed an increase in ACTH values in 80-100% of patients, and an impaired cortisol response to ACTH test in 19% of cases. Additionally, dehydroepiandrosterone sulphate, ∆-4-Androstenedione and 17-OH progesterone levels were below the median of normal values (n.v.) in the majority of patients regardless of the drug used. Testosterone in females and oestradiol in males were below the median of n.v. in the majority of patients on lenvatinib and vandetanib. Finally, aldosterone was below the median of the n.v. in most cases, while renin levels were normal. Metanephrines and normetanephrines were always within the normal range. Replacement therapy with cortisone acetate improved fatigue in 14/17 (82%) patients with PAI.
Conclusions: Our data confirm that systemic treatments for advanced thyroid cancer can lead to an impaired cortisol secretion. A reduction in the other hormones secreted by the adrenal cortex has been firstly reported and should be considered in the more appropriate management of these fragile patients.
“… Figure 1 Cortisol levels at baseline and at 30 and 60 min after stimulation test performed through infusion of 250 μg ACTH in 26/36 patients (18 LENV, 6 VAND and 2 SELP). Peak cortisol levels <15 μg/dL (dotted line) at 30 or 60 min indicate primary adrenal insufficiency, according to new cut-off proposed for new cortisol assays ( 23 , 24 , 25 ). Cortisol response to the ACTH 250 μg stimulation test was reduced in 5/26 patients (19%): 3/18 (17%) on lvatinib and 2/6 (33%) on vandetanib.…”
Section: Resultsmentioning
confidence: 99%
“…Current guidelines consider a peak cortisol level > 18.1 μg/dL (500 nmol/L) at 30 or 60 min after ACTH injection as appropriate, allowing for the exclusion of PAI ( 22 ). Nevertheless, since cortisol assays have recently become more sensitive and a new cutoff of 15 μg/dL has been proposed ( 23 , 24 , 25 ), we calculated the prevalence of PAI accordingly.…”
Background: Fatigue is a frequent adverse event during systemic treatments for advanced thyroid cancer, often leading to reduction, interruption or discontinuation. We were the first group to demonstrate a correlation between fatigue and primary adrenal insufficiency (PAI).
Aim: To assess the entire adrenal function in patients on systemic treatments.
Methods: ACTH, cortisol and all the hormones produced by the adrenal gland were evaluated monthly in 36 patients (25 on lenvatinib, 6 on vandetanib, and 5 on selpercatinib). ACTH stimulation test was performed in 26 cases.
Results: After a median treatment period of 7 months, we observed an increase in ACTH values in 80-100% of patients, and an impaired cortisol response to ACTH test in 19% of cases. Additionally, dehydroepiandrosterone sulphate, ∆-4-Androstenedione and 17-OH progesterone levels were below the median of normal values (n.v.) in the majority of patients regardless of the drug used. Testosterone in females and oestradiol in males were below the median of n.v. in the majority of patients on lenvatinib and vandetanib. Finally, aldosterone was below the median of the n.v. in most cases, while renin levels were normal. Metanephrines and normetanephrines were always within the normal range. Replacement therapy with cortisone acetate improved fatigue in 14/17 (82%) patients with PAI.
Conclusions: Our data confirm that systemic treatments for advanced thyroid cancer can lead to an impaired cortisol secretion. A reduction in the other hormones secreted by the adrenal cortex has been firstly reported and should be considered in the more appropriate management of these fragile patients.
“…The small number of participants was a limitation of the trial. A literature review published by Birtolo et al in 2023 seems to indicate a higher value of the 1 μg Synacthen test versus 250 μg [10]. The authors noticed that 14 protocols of the test have been described so far, and their diagnostic value varies [11].…”
far that analysed the incidence of hypopituitarism in patients with RCC and PESS differ in terms of study populations and testing methods for hormonal insufficiency.The insulin tolerance test (ITT) is the gold standard in the diagnosis of secondary adrenal insufficiency. However, it poses a risk for patients. In clinical practice, this test is often replaced with the tetracosactide stimulation test (Synacthen, cosyntropin). The classic version of the test uses the 250 μg Synacthen dose. However, some centres use a 1 μg dose because there is evidence for higher test sensitivity. Due to different laboratory methods used to determine cortisol levels, the cut-off value for the test is still disputable.In this study, we prospectively analysed a group of consecutive patients hospitalized at the
“…Negative results of the test with undetectable plasma cortisol suggested a secondary adrenal insufficiency in a 45-year-old male with bilateral foci of auricular ossifications (and negative endocrine autoimmunity) [ 28 ]. ACTH stimulation test remains a practical approach of the adrenal insufficiency diagnosis (including partial or latent forms) amid the presence of the rigid ears according to the general endocrine practice [ 59 , 60 , 61 , 62 , 63 ]. Another important issue included the evaluation of the metabolic features such as diabetes mellitus (four subjects within the endocrine cohort [ 1 , 21 , 34 , 38 ], but, also, two other patients in the non-endocrine cohort [ 46 , 50 ], had the condition, as well as one case of hypercholesterolemia [ 41 ]).…”
Section: Petrified Earsmentioning
confidence: 99%
“…Negative results of the test with undetectable plasma cortisol suggested a secondary adrenal insufficiency in a 45-year-old male with bilateral foci of auricular ossifications (and negative endocrine autoimmunity) [ 28 ]. ACTH stimulation test remains a practical approach of the adrenal insufficiency diagnosis (including partial or latent forms) amid the presence of the rigid ears according to the general endocrine practice [ 59 , 60 , 61 , 62 , 63 ].…”
Petrified ear (PE), an exceptional entity, stands for the calcification ± ossification of auricular cartilage (CAC/OAC); its pathogenic traits are still an open matter. Endocrine panel represents one of the most important; yet, no standard protocol of assessments is available. Our objective was to highlight most recent PE data and associated endocrine (versus non-endocrine) ailments in terms of presentation, imagery tools, hormonal assessments, biopsy, outcome, pathogenic features. This was a comprehensive review via PubMed search (January 2000–March 2024). A total of 75 PE subjects included: 46 case reports/series (N = 49) and two imagery-based retrospective studies (N = 26) with CAC/OAC prevalence of 7–23% (N = 251) amid routine head/temporal bone CT scans. Endocrine PE (EPE): N = 23, male/female ratio = 10.5; average age = 56.78, ranges: 22–79; non-EPE cohort: N = 26; male/female ratio = 1.88, mean age = 49.44; ranges: 18–75 (+a single pediatric case).The longest post-diagnosis follow-up was of 6–7 years. The diagnosis of PE and endocrine anomalies was synchronous or not (time gap of 10–20 years). A novel case in point (calcified EPE amid autoimmune poly-endocrine syndrome type 2 with a 10-year post-diagnosis documented follow-up) was introduced. We re-analyzed EPE and re-classified another five subjects as such. Hence, the final EPE cohort (N = 50) showed: adrenal insufficiency was the most frequent endocrine condition (36%) followed by hypopituitarism (22%) and hypothyroidism (18%); 39% of the patients with adrenal failure had Addison’s disease; primary type represented 72% of all cases with hypothyroidism; an endocrine autoimmune (any type) component was diagnosed in 18%. We propose the term of “endocrine petrified ear” and a workflow algorithm to assess the potential hormonal/metabolic background in PE.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
