Development and internal validation of a predictive score for the diagnosis of central adrenal insufficiency when morning cortisol is in the grey zone

Bioletto, Fabio; Berton, Alessandro Maria; Varaldo, Emanuele; Cuboni, Daniela; Bona, Chiara; Parasiliti-Caprino, Mirko; Prencipe, Nunzia; Ghigo, Ezio; Grottoli, Silvia; Maccario, Mauro; Gasco, Valentina

doi:10.1007/s40618-022-01926-z

Cited by 4 publications

(3 citation statements)

References 44 publications

(55 reference statements)

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“…These features provide valuable information that can be used as a proxy for estimating the probability of GHD prior to stimulation tests. The correct choice of the clinical gold standard seems to be confirmed by the clinical differences between GHD and noGHD observed at baseline: it is not surprising that hypopituitary patients were those who more frequently presented a morpho-structural alteration of the hypothalamic-pituitary region or who more frequently had undergone neurosurgical and/or radiotherapy treatment [39][40][41][42]. Moreover, the higher prevalence of overweight and obese subjects in GHD group is in line with the finding that hypopituitary patients are usually characterized by an alteration in body composition similar to that of the metabolic syndrome [43].…”

Section: Discussionmentioning

confidence: 99%

GHRH + arginine test and body mass index: do we need to review diagnostic criteria for GH deficiency?

Gasco

Cuboni

Varaldo

et al. 2023

J Endocrinol Invest

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Introduction The proportion of patients with low GH response to provocative tests increases with the number of other pituitary hormone deficiencies, reason why in panhypopituitary patients GH stimulation tests may be unnecessary to diagnose GH deficiency (GHD) Purpose To re-evaluate the diagnostic cut-offs of GH response to GHRH + arginine (ARG) test related to BMI, considering the patients’ pituitary function as the gold standard for the diagnosis of GHD. Methods The GH responses to GHRH + ARG were studied in 358 patients with history of hypothalamic-pituitary disease. GHD was defined by the presence of at least 3 other pituitary deficits (n = 223), while a preserved somatotropic function was defined by the lack of other pituitary deficits and an IGF-I SDS ≥ 0 (n = 135). The cut-off with the best sensitivity (SE) and specificity (SP), was identified for each BMI category using the ROC curve analysis. To avoid over-diagnosis of GHD we subsequently searched for the cut-offs with a SP ≥ 95%. Results The best GH cut-off was 8.0 μg/l (SE 95%, SP 100%) in lean, 7.0 μg/l (SE 97.3%, SP 82.8%) in overweight, and 2.8 μg/l (SE 84.3%, SP 91.7%) in obese subjects. The cut-off with a SP ≥ 95% was 2.6 μg/l (SE 68.5%, SP 96.6%) in overweight and 1.75 μg/l (SE 70.0%, SP 97.2%) in obese subjects. Conclusions This is the first study that evaluates the diagnostic cut-offs of GH response to GHRH + ARG related to BMI using a clinical definition of GHD as gold standard. Our results suggest that with this new approach, the GHRH + ARG cut-offs should be revised to avoid GHD over-diagnosis.

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Section: Discussionmentioning

confidence: 99%

GHRH + arginine test and body mass index: do we need to review diagnostic criteria for GH deficiency?

Gasco

Cuboni

Varaldo

et al. 2023

J Endocrinol Invest

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“…To avoid performing ITT, Gasco et al in their study aimed to detect the morning serum cortisol cut-off with a specificity or a sensitivity above 95% that could identify those patients who should not be tested with ITT, finding that the cut-off of morning serum cortisol concentration that best predicted a normal response to ITT was >16.11 µg/dL (76). Moreover, a multiparametric score has been recently proposed for the prediction of CAI when morning cortisol is in the grey zone; this score might be helpful for a finer tailoring of the diagnostic process, as it might avoid the execution of a stimulation test in approximately one-fourth of the patients in which morning cortisol values are 'per se' non-diagnostic (77). Although the medical history and some symptoms could help the clinician in discerning ICAI from PAI, in dubious cases, ACTH measurement is also recommended (78).…”

Section: Diagnosismentioning

confidence: 99%

Isolated anterior pituitary dysfunction in adulthood

et al. 2023

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Hypopituitarism is defined as a complete or partial deficiency in one or more pituitary hormones. Anterior hypopituitarism includes secondary adrenal insufficiency, central hypothyroidism, hypogonadotropic hypogonadism, growth hormone deficiency and prolactin deficiency. Patients with hypopituitarism suffer from an increased disability and sick days, resulting in lower health status, higher cost of care and an increased mortality. In particular during adulthood, isolated pituitary deficits are not an uncommon finding; their clinical picture is represented by vague symptoms and unclear signs, which can be difficult to properly diagnose. This often becomes a challenge for the physician. Aim of this narrative review is to analyse, for each anterior pituitary deficit, the main related etiologies, the characteristic signs and symptoms, how to properly diagnose them (suggesting an easy and reproducible step-based approach), and eventually the treatment. In adulthood, the vast majority of isolated pituitary deficits are due to pituitary tumours, head trauma, pituitary surgery and brain radiotherapy. Immune-related dysfunctions represent a growing cause of isolated pituitary deficiencies, above all secondary to use of oncological drugs such as immune checkpoint inhibitors. The diagnosis of isolated pituitary deficiencies should be based on baseline hormonal assessments and/or dynamic tests. Establishing a proper diagnosis can be quite challenging: in fact, even if the diagnostic methods are becoming increasingly refined, a considerable proportion of isolated pituitary deficits still remains without a certain cause. While isolated ACTH and TSH deficiencies always require a prompt replacement treatment, gonadal replacement therapy requires a benefit-risk evaluation based on the presence of comorbidities, age and gender of the patient; finally, the need of growth hormone replacement therapies is still a matter of debate. On the other side, prolactin replacement therapy is still not available. In conclusion, our purpose is to offer a broad evaluation from causes to therapies of isolated anterior pituitary deficits in adulthood. This review will also include the evaluation of uncommon symptoms and main etiologies, the elements of suspicion of a genetic cause and protocols for diagnosis, follow-up and treatment.

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“…In this context, the most recent studies stressed the importance of selecting patients to test according to the pretest probability of SAI that should be quantified by evaluating the patients’ clinical background and the morning cortisol levels [ 14 , 15 ]. Bioletto et al proposed an integrated score for the prediction of SAI when morning cortisol is in the grey zone based on morning cortisol levels, sex, and the presence of at least three other pituitary deficits, trying to narrow even more the patients that need to be tested [ 16 ].…”

Section: Patients To Be Tested and Timing For Testingmentioning

confidence: 99%

ACTH Stimulation Test for the Diagnosis of Secondary Adrenal Insufficiency: Light and Shadow

et al. 2023

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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 harmful. The gold standard test for assessing the hypothalamus-pituitary-adrenal axis (HPA) is the insulin tolerance test (ITT), but due to safety issues is not widely used. Conversely, the ACTH stimulation test is a safer and well-tolerated tool for SAI diagnosis. However, data about its diagnostic accuracy show great variability due to both technical and interpretative aspects, such as dose, route of administration, the timing of the test, and assay used for cortisol measurements. Consequently, the clinical background of the patient and the pretest probability of HPA axis impairment become of paramount importance. We aimed to summarize the recent literature evidence in the conduction and interpretation of the ACTH stimulation test for the diagnosis of SAI to provide updated insights on its correct use in clinical practice.

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Development and internal validation of a predictive score for the diagnosis of central adrenal insufficiency when morning cortisol is in the grey zone

Cited by 4 publications

References 44 publications

GHRH + arginine test and body mass index: do we need to review diagnostic criteria for GH deficiency?

GHRH + arginine test and body mass index: do we need to review diagnostic criteria for GH deficiency?

Isolated anterior pituitary dysfunction in adulthood

ACTH Stimulation Test for the Diagnosis of Secondary Adrenal Insufficiency: Light and Shadow

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