Diagnosis and management of pediatric adrenal insufficiency

Uçar, Ahmet; Baş, Firdevs; Saka, Nurçin

doi:10.1007/s12519-016-0018-x

Cited by 18 publications

(19 citation statements)

References 90 publications

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“…Moreover, at present, there are no available biomarkers which may assist clinicians in the early detection of impeding adrenal insufficiency. 56 , 57 This is important since these data may increase our understanding of pathogenesis and guide corticosteroid replacement therapy. 58 – 60 …”

Section: Discussionmentioning

confidence: 99%

Salivary biomarkers may measure stress responses in critically ill children

et al. 2018

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Objective:Measurement of salivary biomarkers can provide important information regarding hypothalamic–pituitary–adrenal axis activity both under normal conditions as well as in response to psychological or physical stress. Our aim was to correlate salivary stress markers, such as cortisol, α-amylase and immunoglobulin A, with the Pediatric Risk Index Score of Mortality, underlying disease (pathologic, trauma and postoperative), need for mechanical ventilation/sedation and time lag between onset of illness and admission in children admitted in the pediatric intensive care unit.Methods:We enrolled 79 pediatric intensive care unit patients (2–14 years) over a 2-year period, which satisfy the including criteria, but finally salivary biomarkers were evaluated in 65 patients. Saliva samples were collected within 24 h of admission at 8 a.m., 2 p.m. and 8 p.m. to examine potential disruption of circadian rhythm.Results:Overall, the salivary biomarkers were increased; specifically, median values were (a) cortisol at 8 a.m.: 50.04 nmol/L, 2 p.m.: 30.69 nmol/L and 8 p.m.: 247.12 nmol/L; (b) α-amylase: at 8 a.m.: 22.567 U/L; 2 p.m.: 22.702 U/L and 8 p.m.: 21.484 U/L and (c) IgA at 8 a.m.: 95.10 mg/dL, 2 p.m.: 88.55 mg/dL and 8 p.m.: 80.80 mg/dL. Significantly higher levels were demonstrated in children younger than 6 years and those with Pediatric Risk Index Score of Mortality ⩾8 upon admission. Disturbances in circadian rhythm were observed. Cortisol circadian rhythm disturbance was observed only in children with Pediatric Risk Index Score of Mortality score ⩾8 upon admission while maintaining normal α-amylase circadian rhythm, which was associated with less than 3 days hospitalization in pediatric intensive care unit. No daily variance in IgA was observed.Conclusion:Salivary biomarkers may serve, in critically ill children, as a sensitive, non-invasive method, important for the early recognition of those at high risk and guiding intervention, before clinical deterioration, promoting the quality of health care in pediatric population.

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Section: Discussionmentioning

confidence: 99%

Salivary biomarkers may measure stress responses in critically ill children

et al. 2018

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“…Biochemical criteria for AI diagnosis include very low serum cortisol levels (<80 nmol/L), and elevated ACTH plasma levels (>200 pmol/L) (Neary and Nieman ; Ucar et al. ).…”

Section: Discussionmentioning

confidence: 99%

“…Adrenal insufficiency (AI) is characterized by defects in cortisol, aldosterone, and sexual hormone production (Miller 2017). Common manifestations of the disease include hyperpigmentation, hypoglycemia, lethargy, fatigue, muscle weakness, weight loss, dizziness and hypotension (Ucar et al 2016). Biochemical criteria for AI diagnosis include very low serum cortisol levels (<80 nmol/L), and elevated ACTH plasma levels (>200 pmol/L) (Neary and Nieman 2010;Ucar et al 2016).…”

Section: Discussionmentioning

confidence: 99%

A novel splice site variant in CYP11A1 in trans with the p.E314K variant in a male patient with congenital adrenal insufficiency

Lara-Velazquez

Perdomo‐Pantoja

Blackburn

et al. 2017

Molec Gen & Gen Med

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BackgroundThe CYP11A1 gene encodes the cytochrome P450 side‐chain cleavage enzyme, which is essential for steroid formation. Recessive variants in this gene can lead to impairment of sexual differentiation caused by a complete or partial loss of steroid hormone production. The phenotypic spectrum in affected 46XY males may vary from surgically repairable defects including cryptorchidism and hypospadias to complete feminization of external gonads, accompanied by symptoms of adrenal dysfunction.MethodsWhole‐exome sequencing (WES) of a 12‐year‐old male proband and his parents was performed after a protracted diagnostic odyssey failed to uncover the cause of his primary adrenal insufficiency. Of note, the proband had early symptomatology and corrective surgery for hypospadias, raising suspicion for a disorder of steroidogenesis.Results WES identified compound heterozygous variants in CYP11A1 including a novel canonical splice site variant (c.425+1G>A) and a previously reported p.E314K variant, which were consistent with a diagnosis of congenital adrenal insufficiency with partial 46XY sex reversal.ConclusionCongenital adrenal insufficiency with 46XY sex reversal is a rare disorder that is characterized by dysregulation of steroid hormone synthesis, leading to adrenal and gonadal dysfunction. In this report, we describe a patient with adrenal insufficiency, hypospadias, and skin hyperpigmentation who was found to have a novel c.425+1G>A variant in trans with the p.E314K variant in CYP11A1. We performed structural analyses to examine the effect of the p.E314K variant on protein function and show that it falls in the core of the protein may disrupt cholesterol binding in the active site.

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“…Central hypocortisolism causes the same signs and symptoms as Addison’s disease, but in contrast to primary hypocortisolism, it is characterized by normal or hypopigmented skin and normal mineralocorticoid reserve. In addition, the clinical phenotype may be milder and adrenal crisis at the time of diagnosis less frequent than in primary adrenal insufficiency [ 22 ]. Routine monitoring of adrenal sufficiency by measuring morning serum cortisol may minimize this risk in children with organic GHD.…”

Section: Introductionmentioning

confidence: 99%

Evolving pituitary hormone deficits in primarily isolated GHD: a review and experts’ consensus

et al. 2020

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Isolated growth hormone deficiency (GHD) is defined by growth failure in combination with retarded bone age, low serum insulin-like growth factor-1, and insufficient GH peaks in two independent GH stimulation tests. Congenital GHD can present at any age and can be associated with significant malformations of the pituitary-hypothalamic region or the midline of the brain. In rare instances, genetic analysis reveals germline mutations of transcription factors involved in embryogenesis of the pituitary gland and the hypothalamus. Acquired GHD is caused by radiation, inflammation, or tumor growth. In contrast to organic GHD, idiopathic forms are more frequent and remain unexplained. There is a risk of progression from isolated GHD to combined pituitary hormone deficiency (> 5% for the total group), which is clearly increased in children with organic GHD, especially with significant malformation of the pituitary gland. Therefore, it is prudent to exclude additional pituitary hormone deficiencies in the follow-up of children with isolated GHD by clinical and radiological observations and endocrine baseline tests. In contrast to primary disorders of endocrine glands, secondary deficiency is frequently milder in its clinical manifestation. The pituitary hormone deficiencies can develop over time from mild insufficiency to severe deficiency. This review summarizes the current knowledge on diagnostics and therapy of additional pituitary hormone deficits occurring during rhGH treatment in children initially diagnosed with isolated GHD. Although risk factors are known, there are no absolute criteria enabling exclusion of children without any risk of progress to combined pituitary hormone deficiency. Lifelong monitoring of the endocrine function of the pituitary gland is recommended in humans with organic GHD. This paper is the essence of a workshop of pediatric endocrinologists who screened the literature for evidence with respect to evolving pituitary deficits in initially isolated GHD, their diagnosis and treatment.

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Diagnosis and management of pediatric adrenal insufficiency

Abstract: Education of patients and health care professionals is mandatory for timely interventions for patients with adrenal crisis.

Cited by 18 publications

References 90 publications

Salivary biomarkers may measure stress responses in critically ill children

Salivary biomarkers may measure stress responses in critically ill children

A novel splice site variant in CYP11A1 in trans with the p.E314K variant in a male patient with congenital adrenal insufficiency

Evolving pituitary hormone deficits in primarily isolated GHD: a review and experts’ consensus

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