An observational study in Cushing Disease, sponsored by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Recruiting at 1 site in United States. Open to participants aged 2 Years to 90 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-11-02.
Sponsored by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) · Observational
Background:
The pituitary gland produces hormones. A tumor in this gland can cause it to produce too much of the hormone cortisol. Too much cortisol in the body causes Cushing disease. This disease causes many problems. Some of these problems might persist after the disease is cured.
Objective:
To find out the long-term effects of exposure to high levels of cortisol during childhood and adolescence.
Eligibility:
People ages >=5 years who were diagnosed with Cushing disease before age 21 and are now cured and have normal or low cortisol levels
People related to someone with Cushing disease
Design:
Participants will be screened with a medical history.
Participants will complete an online survey. This will include questions about their or their child's physical and mental health.
All participants will be seen at 5 -year intervals after cure of Cushing disease (5yr, 10yr, 15yr, 20yr (last visit))
Participants who have a relative with Cushing disease will have a medical history and blood tests or cheek swabs.
Participants who have the disease will have:
Physical exam
Blood tests
Cheek swab
DXA scan: A machine will x-ray the participant's body to measure bone mineral content.
For participants who are still growing, a hand x-ray
Participants with the disease may also have:
Hormone stimulation test: Participants will get a hormone or another substance that will be measured.
Serial hormone sampling: Participants' blood will be measured several times through a thin plastic tube in an arm vein.
Urine tests: Participants' urine may be collected over 24 hours.
MRI: Participants may have a dye injected into a vein. They will lie on a table that slides into a machine. The machine will take pictures of the body.
Objective:
Cushing disease (CD) describes the state of hypercortisolemia secondary to cortisol producing pituitary adenomas. The rarity of the disease (2-5 new cases per million, 1 out of 10 in children) and the subtle initial findings result in prolonged undiagnosed hypercortisolemia, that increases the risk for significant complications, including obesity, height deceleration, hyperlipidemia, hyperglycemia, hypertension, osteoporosis, immunodeficiency, and others. Although hypercortisolemia usually resolves after successful resection of the pituitary adenoma, the reversal of the above-mentioned complications and the long-term effects of the previous prolonged exposure of the body to supraphysiologic levels of cortisol have not been clarified, especially when hypercortisolemia occurs during childhood.
Previous studies have addressed the possible complications after resolution of hypercortisolemia, but most of them refer to adult patients. Amongst the described complications, suppression of the pituitary hormones, such as the growth and thyroid hormone axes, and persistent increase of the body mass index (BMI) and abnormal fat distribution, have been described in limited number of pediatric patients followed for a few years after cure. Other complications, such as components of the metabolic syndrome or cardiovascular dysfunction, have not been extensively studied in children. Furthermore, equally important are the long-term effects of glucocorticoids on other aspects of health. For example, it has been previously described that the neurocognitive function of children with CD declines the first year after treatment. This can potentially result in impaired quality of life, lower education level, and lower job and life satisfaction in the future; however, the long-term neurocognitive sequelae of Cushing syndrome (CS) diagnosed in childhood have not been studied.
This study aims to provide novel insight on the long-term effects of hypercortisolemia on the developing child, their underlying pathogenetic mechanisms, their evolution over time, and the risk factors for developing them. This will assist in designing methods to closely monitor or prevent them in the future. Certain results of this study could potentially apply to children with iatrogenic CS, which is much more common due to the widespread use of pharmacologic doses of glucocorticoids in malignancies, autoimmune and atopic disorders.
Study population:
The study population will consist of patients that were previously successfully treated for CD before the age of 21 years. We aim to identify these patients through review of our current protocol 97-CH-0076 on "Clinical and genetic investigation of pituitary and hypothalamic tumors", which has been recruiting patients since 1997. We will also accept patients who have been diagnosed and successfully treated for pediatric CD at outside institutions after reviewing the medical records and confirming their diagnosis. The patients must not be hypercortisolemic at the time of their recruitment. Family members (any age) of patients with a family history of pituitary tumors may participate in the DNA/linkage analysis study.
Design:
We will evaluate patients at least 3 years after documented resolution of hypercortisolemia. Patients will be evaluated at least once, with optional follow-up visit(s) if indicated.
The study will include an online survey offered to all patients, as well as an on-site short visit for those willing to travel to NIH.
The online survey will include questionnaires on assessment of various aspects of health: Current medical diagnoses, Medication use, History of endocrine disorders, Fertility, Quality of life, Behavioral and emotional symptomology, and Socioeconomic and Demographic information. The survey will be developed and distributed with the help of CTDB and will be sent with secure email to all the patients and/or their parents (for patients who are \<18yo at the time of evaluation) after consent and eligibility have been confirmed.
The short on-site visit at NIH will be offered to all the patients willing to travel. Blood tests, imaging studies (MRI pituitary/brain and DXA scan), and neurocognitive screening and patient reported outcome questionnaires will be performed.
Outcome measures:
The primary outcome measure of the study is the difference of the Body Mass Index (BMI) z-score of the patients previously treated for pediatric CD compared to the general population, as calculated by data derived from the NHANES study.
The secondary outcomes will be to describe the prevalence of other endocrine and non-endocrine abnormalities after successful treatment of CD in childhood, including growth hormone, thyroid, gonadal, adrenal function; bone mineral density; glucose metabolism; lipid profile; cardiovascular abnormalities; immunologic changes; coagulation function; psychiatric diseases, behavioral symptomology; neurocognitive function; and quality of life.
64 studies on the registry are indexed under Pituitary ACTH Hypersecretion; 16 are open to participants now.
This study's planned enrollment of 240 is above the median of 131 across 20 observational studies indexed under Pituitary ACTH Hypersecretion.
Browse Pituitary ACTH Hypersecretion studies →Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is the lead sponsor of 422 studies on the registry; 24 are open to participants now.
Of its 14 completed or terminated interventional studies of FDA-regulated products, 11 (79%) have results posted.
Counted across the registry records on this site, refreshed daily.
The criteria were revised on the registry on Oct 27, 2026. See what changed
The study population will consist of patients that were previously successfully treated for CD before the age of 21 years. We aim to identify these patients through review of our current protocol 97-CH-0076 on "Clinical and genetic investigation of pituitary and hypothalamic tumors", which has been recruiting patients since 1997. We will also accept patients who have been diagnosed and successfully treated for pediatric CD at outside institutions after reviewing the medical records and confirming their diagnosis. The patients must be normocortisolemic at the time of their recruitment. Family members of subjects who are survivors of pediatric Cushing disease will be invited to participate in the DNA/linkage analysis study.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Males and females >=5 years of age or older (subjects) who were previously diagnosed and had successful treatment of CD before the age of 21 years old. Patients who have undergone therapies other than surgical resection (such as radiation or medical treatment) will be eligible to participate.
Patients or a legal guardian (in case of cognitively impaired adults or children) must provide assent/consent at the time of the recruitment.
Or,
EXCLUSION CRITERIA:
Pregnancy: Pregnancy will be evaluated only in participants of reproductive age (from 10 years old until 60 years of age unless menopause has already occurred per clinical report of the participant).
For participants enrolled as external participants or under the Linkage study (where research activities include no more than blood draws), any female who could possibly become pregnant will be screened using clinical criteria (history, with pregnancy testing only if indicated) for exclusion and this information will be documented in the consent process note in EMR. If a participant has initially been registered as external location and then presents on-site, then pregnancy test will be performed if within the reproductive age group.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Family member of survivor of pediatric Cushing disease
survivor of pediatric Cushing disease
Difference in body mass index z-score of subjects previously treated for Cushing disease compared to general population
The primary outcome measure of the study is the difference in the Body Mass Index (BMI) z-score of the patients previously treated for pediatric CD compared to the general population, as calculated by data derived from the NHANES study.
Time frame: baseline, 5, 10, 15, 20 years
Prevalence of endocrine and non-endocrine abnormalities
The secondary outcomes will be to describe the prevalence of other endocrine and non-endocrine abnormalities after successful treatment of CD in childhood, including: growth hormone, thyroid, gonadal, adrenal function; bone mineral density; glucose metabolism; lipid profile; cardiovascular abnormalities; immunologic changes; coagulation function; psychiatric diseases, behavioral symptomology; neurocognitive function; and quality of life.
Time frame: baseline, 5, 10, 15, 20 years
Plan to share: Undecided
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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