Full application for an addition of a test categories in the EDL Survey response 1 Response ID 54 Date submitted 2019-12-03 10:32:00 Last page 1 Start language en 1. Name of test category Name of the test category addressed in the original submission: Cortisol (serum) 2. Pre-submission information Please indicate your pre-submission response ID: [Pre-submission ID] 127 3. Applicant’s information (primary contact person): Contact person, name and information of the person submitting the application: [LAST NAME, First name] SILVA, Carolina Contact person, name and information of the person submitting the application: [Email address (...@....)] [email protected] Contact person, name and information of the person submitting the application: [Phone number (+country code) phone number no spaces] +1-604-875-2117 Contact person, name and information of the person submitting the application: [Other information] - 4. Applicant’s information (secondary contact person): [LAST NAME, First name] BARAKAUSKAS, Vilte [Email address (...@....)] [email protected] page 1 / 17 [Phone number (+country code) phone number no spaces] +1-604-875-2345 [Other information] - 5. Details of the organization making the submission (if applicable) Name of the organization making the submission (if applicable): [Name of the organisation] British Columbia Children’s Hospital Name of the organization making the submission (if applicable): [Address] Name of the organization making the submission (if applicable): [Department] Name of the organization making the submission (if applicable): [Website] www.bcchildrens.ca Name of the organization making the submission (if applicable): [Phone number] 6. Details of the organizations supporting the application: Please provide up to three organizations supporting your application including a. Organization name, b. Contact person, c. Email address: Global Pediatric Endocrinology and Diabetes (GPED, www.globalpedendo.org) 7. Public health impact of the disease/condition: page 2 / 17 Please detail the public health relevance of conditions addressed with the proposed test and add references: Cortisol is the main glucocorticoid hormone produced by the adrenal gland. It is secreted in response to stimulation of the adrenal gland by corticotropin hormone (ACTH), produced by the pituitary. Determination of serum cortisol is relevant to the diagnosis of two groups of conditions: adrenal hypofunction (central and primary adrenal insufficiency) and adrenal hyperfunction (Cushing syndrome, of central or adrenal origin). Adrenal hypofunction -- Adrenal insufficiency is characterized by insufficient secretion of cortisol. It is caused by either insufficient secretion of ACTH (central adrenal insufficiency) or by a non-functional adrenal gland (primary adrenal insufficiency, most commonly because of autoimmune destruction of the gland). The prevalence of central adrenal insufficiency is reported to be between 150-280/million, but is probably underestimated. It can be permanent (pituitary tumors, cranial injury from irradiation, surgery, trauma, infections) or transient (for weeks, months or even years, secondary to exogenous glucocorticoid withdrawal). This latter etiology has dramatically increased over the past decades. Glucocorticoids are largely used in general population worldwide (up to 2%), and adrenal insufficiency after discontinuation is not only common but usually unrecognized. There is no glucocorticoid administration form, dosing, treatment duration or underlying disease that could exclude the risk of transient adrenal insufficiency, although higher doses and longer use give the highest risk. In a meta analysis evaluating 3753 participants treated with corticosteroids for various conditions, the proportion of patients with adrenal insufficiency ranged from 4% for nasal administration to more than 50% for intra-articular administration. Stratified by disease, percentages ranged from slightly below 7% for asthma to 60% for hematological malignancies. The risk also varied according to dose and treatment duration. The prevalence of primary adrenal insufficiency (Addison’s disease) ranges between 82-144 cases per million. Autoimmunity is the most common cause in adults; other insults to the adrenal gland that lead to primary insufficiency include adrenal hemorrhage, cancer, infections (HIV, syphilis, tuberculosis, bacterial) and some medicines. Genetic causes, especially enzyme defects, are the most common cause in children. About half of pediatric cases can be attributed to congenital adrenal hyperplasia. Due to the diverse causes of adrenal insufficiency, no distinct group of individuals is at increased risk of disease. Cortisol is an essential hormone; its most important function is to help the body respond to stress, such as surgery and illness, and recover from infections. The hormone also helps maintain blood pressure and cardiovascular functions and regulates the metabolism of proteins, carbohydrates and fatty acids. Aldosterone plays a key role in sodium and potassium balance. Patients with adrenal insufficiency, both central and primary, often present with hypotension, anorexia, vomiting, weight loss, fatigue and recurrent abdominal pain. Reproductive complaints typically occur in women (amenorrhea, loss of libido, decreased axillary, and pubic hair). In addition, when there is primary adrenal insufficiency, hyperpigmentation and salt craving are usually present. Patients may also manifest neuropsychiatric signs and symptoms. In children, weight loss with failure to thrive as well as hypoglycemic crisis with seizures can be seen. Biochemical findings include hyponatraemia, hyperkalemia (for primary adrenal insufficiency) and hypoglycemia. Adrenal insufficiency is a life- threatening disorder which, if not recognized, can lead to very high morbidity and mortality. In patients with adrenal insufficiency, regardless of its cause, any type of stress can precipitate an adrenal crisis; the most frequent precipitating factors are gastrointestinal and other infectious diseases. Patients with adrenal crisis usually present with unexplained shock refractory to vasopressors and fluids. In different studies, the frequency of adrenal crisis has been reported to be between 6 and 8 per 100 patient-years and mortality rates, 0.5 per 100 patient-years. Early identification and treatment of adrenal crisis significantly improves mortality rates seen during these episodes. Well-informed patients with primary adrenal insufficiency (Addison's disease) undergoing currently accepted replacement therapy are considered to have a normal survival rate. However, studies still show that mortality of patients with adrenal insufficiency is 1.5-2-fold higher compared to the general population, particularly for patients diagnosed at a young age. Increased mortality in primary adrenal insufficiency is linked to adrenal crisis and sudden death; as well as cardiovascular, malignant, and infectious diseases. In addition to this, there is significant morbidity and impact on quality of life. A model for measurement of the health burden in patients with congenital adrenal hyperplasia estimated that for adults with this condition, adrenal crisis result in a loss of 7.3 years of life, or 9 quality-adjusted life-years (QALYs) on average. Adrenal hyperfunction -- Cushing’s syndrome comprises a large group of signs and symptoms that reflect prolonged and inappropriately high exposure to glucocorticoids. The most common cause is iatrogenic, from medically prescribed corticosteroids. Endogenous Cushing can be caused by excess production of ACTH or by independent excessive production of cortisol by the adrenal gland. The reported total incidence of endogenous Cushing syndrome varies from 3 to 7 cases per million/year. However, estimates of the incidence of Cushing's syndrome are imprecise and likely underestimate the incidence of iatrogenic Cushing's, undiagnosed mild hypercortisolism, and ectopic ACTH syndrome. Thus, the incidence of Cushing's disease may be as high as 5 to 25 per million per year. The sex-related distribution of Cushing's syndrome varies with the cause. Men used to have a three times greater incidence of the ectopic ACTH syndrome, but the increasing incidence of lung cancer in cigarette-smoking women has narrowed that margin. Women are more likely than men to develop Cushing's disease, as well as either benign or malignant adrenal tumors. The age at presentation varies depending upon the cause of hypercortisolism. Incidence of ectopic ACTH syndrome increases rapidly after the age of 50 years, as lung cancer. Cushing's disease occurs mainly in women aged 25 to 45 years. Adrenal tumors have a bimodal age distribution, with small peaks in the first decade of life and major peaks at approximately 40- 50 years. Adrenal carcinoma is the cause of one-half of all cases of childhood Cushing's syndrome. Although Cushing’s syndrome is clinically unmistakable when full blown, the spectrum of clinical presentation is broad. Cushing's syndrome affects numerous systems, such as reproductive, dermatologic, metabolic, cardiovascular, musculoskeletal, neuropsychiatric, and infectious. Few, if any features of Cushing’s syndrome are unique, but some are more discriminatory than others, including reddish purple striae, plethora, proximal muscle weakness, easy bruising and unexplained osteoporosis. Other symptoms, such as fatigue, weight gain, depression, diabetes, hypertension, or menstrual irregularity are also common in individuals without the disorder,