Oksana Hamidi, DO, Associate Professor at the University of Texas Southwestern Medical Center, discusses 2-year data on crinecerfont for the treatment of patients with congenital adrenal hyperplasia (CAH).

CAH refers to a group of genetic conditions that affect the adrenal gland production of hormones, particularly, the production of cortisol and androgen hormones. Persons with severe forms of the condition can be dramatically impacted. For example, females with a severe form of the condition may have ambiguous genitalia at birth and if not properly diagnosed, develop dehydration, poor feeding, diarrhea, vomiting and other health problems soon after. People with milder forms may not be diagnosed with the condition until adolescence or adulthood when they experience early signs of puberty or fertility problems. Excess androgens can also cause accelerated bone age maturation, leading to reduced adult height.

Crinecerfont Improves Weight-Related Outcomes and Insulin Resistance in Adults with Classic CAH: 2-Year Results from the CAHtalyst Adult Study

This study evaluated outcomes related to body weight and insulin resistance (IR) in CAHtalyst Adult (NCT04490915) participants who received up to 2 years of crinecerfont. Crinecerfont is a first-in-class corticotropin releasing factor type 1 receptor antagonist that is approved by the US Food and Drug Administration (FDA) as an adjunct to glucocorticoid replacement to control androgens in patients with classic CAH, including both salt-wasting and simple virilizing forms, thereby enabling glucocorticoid dose reduction.

A total of 182 randomized participants had a baseline mean daily glucocorticoid dose of 17.6 mg/m2/d hydrocortisone equivalents (HCe). At baseline, mean body weight was 79.3 kg, mean BMI was 29.8 kg/m2 and 71% were overweight or obese. Mean homeostatic model assessment of insulin resistance (HOMA-IR) was 3.2 and 42% had IR. Glucocorticoid dose decreased from baseline by a mean±SEM of -37±1% to 10.9±0.3 mg/m2/d HCe at month 12 and was maintained at month 24. In all participants, mean reductions from baseline in weight and BMI at month 12 were sustained at month 24.

Sustained reductions in BMI were also observed in participants who were overweight or obese at baseline, and 31% and 38% of this subgroup achieved greater than 5% reduction in weight at months 12 and 24, respectively. At both time points, these participants had mean decreases in fat mass exceeding that in lean mass, with reductions of -1.5±0.5 kg versus -0.8±0.2 kg, respectively, at month 12 and -1.6±0.7 kg versus -0.8±0.3 kg, respectively, at month 24. Mean reductions from baseline in HOMA-IR were sustained from month 12 and month 24 in all participants overall and in participants with IR at baseline.

Crinecerfont was well tolerated, and no new safety signals were observed during long-term treatment.

Adults with Classic CAH Taking Crinecerfont Demonstrated Sustained Decreases in Glucocorticoid Doses: 2-Year Results from the Cahtalyst Adult Study
This study evaluated changes in glucocorticoid doses in adults who received up to 2 years of crinecerfont in the phase 3 CAHtalyst Adult trial (NCT04490915).

Of a total of 182 enrolled participants, the mean total daily glucocorticoid dose at baseline was 17.6 mg/m2/d, and mean androstenedione after morning glucocorticoid dose was 349 ng/dL. The mean percent change from baseline in glucocorticoid dose while maintaining or improving androstenedione relative to baseline was -26% at month 12, -28% at month 18, and -25% at month 24.

Additionally, 45% of participants achieved a glucocorticoid dose of 11 mg/m2/d or less while maintaining or improving androstenedione at month 24. The observed mean percent decrease from baseline in glucocorticoid dose (without imputation based on androstenedione) was -38% at month 18 and -38% at month 24, with observed mean glucocorticoid doses of 10.6 mg/m2/d at month 18 and 10.6 mg/m2/d at month 24. In addition, 71% and 69% of participants achieved a glucocorticoid dose in the physiologic range at months 18 and 24, respectively, without imputation based on androstenedione. Even with these decreases in glucocorticoid dose, mean changes from baseline in androstenedione were -11.5 ng/dL at month 18 and 56.6 ng/dL at month 24.

Crinecerfont was overall well tolerated and no new safety signals were observed during long-term treatment.

To learn more about CAH and other rare endocrine disorders, visit https://checkrare.com/diseases/endocrine-disorders/

CHAPTERS
Introduction 00:00
Cardiometabolic Problems in CAH 00:13
Disease Severity and Treatment Effectiveness 1:05
2-Year Data on Crinecerfont 2:16
Next Steps 6:20

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Elif Oral, MD, Professor at the University of Michigan, discusses advances in lipodystrophy research presented at ENDO 2026.

Lipodystrophies are rare metabolic disorders characterized by the loss of adipose tissue. This leads to complications such as insulin resistance, diabetes mellitus, hypertriglyceridemia, and fatty liver. Lipodystrophies generally begin in childhood and have an underlying autoimmune component associated with its etiology. The disorder can be genetic or acquired. Symptoms that may indicate lipodystrophy include thin arms and legs, prominent muscular veins, cutaneous fat around the abdomen, and difficult to treat diabetes. Current management of patients includes cosmetic surgery, diet, and drug therapy for control of diabetes and dyslipidemia. Leptin replacement therapy is the only lipodystrophy-specific treatment.

New research presented at ENDO 2026 highlighted progress in the treatment, diagnosis, and clinical understanding of lipodystrophy, with studies examining long-term metreleptin therapy, ongoing clinical trials in partial lipodystrophy, disease characterization, and new approaches to earlier diagnosis.

Long-term findings from a 36-month phase 4 study evaluated the immunogenicity of metreleptin in patients with generalized lipodystrophy (GL). Although most participants developed anti-drug antibodies and transient neutralizing antibody activity, these responses generally declined over time and did not appear to have a lasting impact on treatment safety or metabolic efficacy. The findings provide additional reassurance regarding the long-term use of metreleptin despite the development of immune responses.

Researchers also presented baseline data from the METRE-PL phase 3 trial, the first randomized, placebo-controlled study evaluating metreleptin in familial partial lipodystrophy (FPLD). The enrolled population demonstrated a substantial metabolic disease burden, with nearly all patients having diabetes or hypertriglyceridemia and many experiencing complications such as pancreatitis and diabetic neuropathy. The ongoing trial will determine whether metreleptin can improve glycemic control and triglyceride levels in this underserved patient population.

Data from the LD-Lync natural history study revealed important differences between acquired and genetic forms of lipodystrophy. While patients with genetic lipodystrophy experienced higher rates of metabolic complications—including hypertriglyceridemia, fatty liver disease, and polycystic ovary syndrome—those with acquired lipodystrophy were more likely to have autoimmune disorders, inflammatory conditions, and cancer, often diagnosed at younger ages. These findings emphasize the need for subtype-specific management strategies, including greater attention to cancer surveillance and immune evaluation in acquired disease.

Finally, investigators from the RADIANT study reported a new clinical prediction model designed to identify lipodystrophy among patients with atypical diabetes using routinely collected clinical and laboratory data. The model demonstrated high specificity while maintaining good sensitivity after threshold adjustment, suggesting it could serve as an effective screening tool to help clinicians recognize patients who may benefit from specialized evaluation and genetic testing. Researchers noted that future refinements incorporating biomarkers and genomic data may further improve diagnostic accuracy.

Together, these studies presented at ENDO 2026 underscore continued progress in improving the diagnosis and management of lipodystrophy. From supporting the long-term safety profile of metreleptin to advancing clinical trials, refining disease characterization, and developing practical screening tools, the research reflects a growing effort to enable earlier diagnosis and more personalized care for patients with these rare disorders.

To learn more about lipodystrophy and other rare metabolic disorders, visit https://checkrare.com/diseases/metabolic-disorders/

CHAPTERS
Introduction 00:00
Lipodystrophy Treatment History 00:11
Lipodystrophy Overview 1:58
Research Presented at ENDO 2026 3:28
Recognizing Different Types of Lipodystrophy 9:23
Acknowledging Patients 12:26

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Evelien Gevers, PhD, MD, Consultant Pediatrician and Reader in Endocrinology and Diabetes at Barts Health NHS Trust, discusses effects of diazoxide choline extended release (DCCR) on hyperphagia in patients with Prader-Willi syndrome (PWS).

PWS is a rare genetic condition that affects many parts of the body but its most dominant symptom is overwhelming hyperphagia. Infants with PWS also have severe hypotonia, feeding difficulties, slow growth, short stature, hypogonadism, developmental delays, cognitive impairment, and distinctive behavioral characteristics such as temper tantrums, stubbornness, and obsessive-compulsive tendencies. PWS is caused by missing or non-working genes on chromosome 15.

An abstract presented at ENDO 2026 evaluated long-term reductions in hyperphagia with DCCR in patients with PWS. DCCR is a potent activator of the adenosine triphosphate (ATP)-sensitive potassium channel. It was approved in March 2025 by the US Food and Drug Administration (FDA) as a treatment for hyperphagia in patients 4 years of age and older with PWS.

Results for up to 3 years from participants who received DCCR compared to real-world natural history data from the PATH for PWS study (PATH) were included.

A total of 352 participants were evaluated. Baseline Hyperphagia Questionnaire for Clinical Trials (HQ-CT) total scores were 21.6 ± 6.7 and 18.2 ± 5.0 for DCCR and PATH groups. Significant reductions in hyperphagia occurred at all time points for DCCR compared to the PATH cohort. Change in HQ-CT from Baseline between DCCR and PATH was -6.2 at year 1, -6.5 at year 2, and -6.2 at year 3.

To learn more about PWS and other rare endocrine conditions, visit https://checkrare.com/diseases/endocrine-disorders/

CHAPTERS
Introduction 00:00
Prader-Willi Syndrome Overview 00:25
Early Signs and Symptoms 1:11
Diagnostic Challenges 1:54
Current Treatment 3:23
Diazoxide Choline Extended Release Clinical Trials 3:51
Measuring Hyperphagia 11:20
The Future of Prader-Willi Treatment 12:47

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Robert Rapaport, MD, Professor of Pediatric Endocrinology, and Director of the Comprehensive Growth Center at the Icahn School of Medicine, Mount Sinai Medical Center, New York City, discussed the differences between severe, primary IGF-1 deficiency and growth hormone (GH) deficiency in patients with short stature.

In young patients with short stature, GH deficiency is the most common cause. However, in a small subset of patients, the underlying problem is not GH deficiency but an abnormality in insulin-like growth factor-1 (IGF-1) levels. This peptide hormone was first discovered 50 years ago, and IGF-1 deficiency has been found to be caused by mutations in the GH receptor and defects in the IGF-1 gene. In patients with a specific subtype of severe, primary IGF-1 deficiency (SPIGF1D) called Laron syndrome, the specific cause is GH-receptor mutations.

Severe, primary IGF-1 deficiency is generally associated with the following patient characteristics: severe postnatal growth failure, short limb length, typical facial features (e.g., small forehead), and delays in sexual development and skeletal maturation. Crucially, affected children do not respond to a GH stimulation test.

Patients who have abnormally low GH levels can also be considered IGF-1 deficient. On the other hand, if the patient has normal GH levels, IGF-1 concentrations may still be abnormally low. According to Dr. Rapaport, patients with IGF-1 deficiency may be found to have abnormal IGF-1 levels across a spectrum from borderline low to extremely low, the latter of which represents the main feature of SPIGF1D (IGF-1 levels are 5–6 standard deviations below the mean for healthy individuals).

The only effective treatment for SPIGF1D is IGF-1 supplementation, with mecasermin, a human recombinant IGF-1 preparation. Although mecasermin is proven to increase patients’ growth velocity, patients taking the product are expected to attain “near normal” adult height only. It is given twice daily, and it does carry a risk of hypoglycemia, as IGF-1 lowers blood glucose levels. It is thus important that patients and their caregivers are well educated about avoiding this dangerous adverse effect.

CHAPTERS
Introduction 00:00
Primary IGF-1 Deficiency Overview 00:44
Severe IGF-1 Deficiency 3:32
Diagnosis in Children 4:42
Treatment for Severe IGF-1 Deficiency 5:29
Safety Considerations 8:07
Unmet Needs 8:56
Take Home Message 9:36

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Robert Rapaport, MD, Professor of Pediatric Endocrinology, and Director of the Comprehensive Growth Center at the Icahn School of Medicine, Mount Sinai Medical Center, New York City, discussed the differences between severe, primary IGF-1 deficiency and growth hormone (GH) deficiency in patients with short stature.

In young patients with short stature, GH deficiency is the most common cause. However, in a small subset of patients, the underlying problem is not GH deficiency but an abnormality in insulin-like growth factor-1 (IGF-1) levels. This peptide hormone was first discovered 50 years ago, and IGF-1 deficiency has been found to be caused by mutations in the GH receptor and defects in the IGF-1 gene. In patients with a specific subtype of severe, primary IGF-1 deficiency (SPIGF1D) called Laron syndrome, the specific cause is GH-receptor mutations.

Severe, primary IGF-1 deficiency is generally associated with the following patient characteristics: severe postnatal growth failure, short limb length, typical facial features (e.g., small forehead), and delays in sexual development and skeletal maturation. Crucially, affected children do not respond to a GH stimulation test.

Patients who have abnormally low GH levels can also be considered IGF-1 deficient. On the other hand, if the patient has normal GH levels, IGF-1 concentrations may still be abnormally low. According to Dr. Rapaport, patients with IGF-1 deficiency may be found to have abnormal IGF-1 levels across a spectrum from borderline low to extremely low, the latter of which represents the main feature of SPIGF1D (IGF-1 levels are 5–6 standard deviations below the mean for healthy individuals).

The only effective treatment for SPIGF1D is IGF-1 supplementation, with mecasermin, a human recombinant IGF-1 preparation. Although mecasermin is proven to increase patients’ growth velocity, patients taking the product are expected to attain “near normal” adult height only. It is given twice daily, and it does carry a risk of hypoglycemia, as IGF-1 lowers blood glucose levels. It is thus important that patients and their caregivers are well educated about avoiding this dangerous adverse effect.

0 0

Robert Rapaport, MD, Professor of Pediatric Endocrinology, and Director of the Comprehensive Growth Center at the Icahn School of Medicine, Mount Sinai Medical Center, New York City, discussed the differences between severe, primary IGF-1 deficiency and growth hormone (GH) deficiency in patients with short stature.

In young patients with short stature, GH deficiency is the most common cause. However, in a small subset of patients, the underlying problem is not GH deficiency but an abnormality in insulin-like growth factor-1 (IGF-1) levels. This peptide hormone was first discovered 50 years ago, and IGF-1 deficiency has been found to be caused by mutations in the GH receptor and defects in the IGF-1 gene. In patients with a specific subtype of severe, primary IGF-1 deficiency (SPIGF1D) called Laron syndrome, the specific cause is GH-receptor mutations.

Severe, primary IGF-1 deficiency is generally associated with the following patient characteristics: severe postnatal growth failure, short limb length, typical facial features (e.g., small forehead), and delays in sexual development and skeletal maturation. Crucially, affected children do not respond to a GH stimulation test.

Patients who have abnormally low GH levels can also be considered IGF-1 deficient. On the other hand, if the patient has normal GH levels, IGF-1 concentrations may still be abnormally low. According to Dr. Rapaport, patients with IGF-1 deficiency may be found to have abnormal IGF-1 levels across a spectrum from borderline low to extremely low, the latter of which represents the main feature of SPIGF1D (IGF-1 levels are 5–6 standard deviations below the mean for healthy individuals).

The only effective treatment for SPIGF1D is IGF-1 supplementation, with mecasermin, a human recombinant IGF-1 preparation. Although mecasermin is proven to increase patients’ growth velocity, patients taking the product are expected to attain “near normal” adult height only. It is given twice daily, and it does carry a risk of hypoglycemia, as IGF-1 lowers blood glucose levels. It is thus important that patients and their caregivers are well educated about avoiding this dangerous adverse effect.

0 0

Robert Rapaport, MD, Professor of Pediatric Endocrinology, and Director of the Comprehensive Growth Center at the Icahn School of Medicine, Mount Sinai Medical Center, New York City, discussed the differences between severe, primary IGF-1 deficiency and growth hormone (GH) deficiency in patients with short stature.

In young patients with short stature, GH deficiency is the most common cause. However, in a small subset of patients, the underlying problem is not GH deficiency but an abnormality in insulin-like growth factor-1 (IGF-1) levels. This peptide hormone was first discovered 50 years ago, and IGF-1 deficiency has been found to be caused by mutations in the GH receptor and defects in the IGF-1 gene. In patients with a specific subtype of severe, primary IGF-1 deficiency (SPIGF1D) called Laron syndrome, the specific cause is GH-receptor mutations.

Severe, primary IGF-1 deficiency is generally associated with the following patient characteristics: severe postnatal growth failure, short limb length, typical facial features (e.g., small forehead), and delays in sexual development and skeletal maturation. Crucially, affected children do not respond to a GH stimulation test.

Patients who have abnormally low GH levels can also be considered IGF-1 deficient. On the other hand, if the patient has normal GH levels, IGF-1 concentrations may still be abnormally low. According to Dr. Rapaport, patients with IGF-1 deficiency may be found to have abnormal IGF-1 levels across a spectrum from borderline low to extremely low, the latter of which represents the main feature of SPIGF1D (IGF-1 levels are 5–6 standard deviations below the mean for healthy individuals).

The only effective treatment for SPIGF1D is IGF-1 supplementation, with mecasermin, a human recombinant IGF-1 preparation. Although mecasermin is proven to increase patients’ growth velocity, patients taking the product are expected to attain “near normal” adult height only. It is given twice daily, and it does carry a risk of hypoglycemia, as IGF-1 lowers blood glucose levels. It is thus important that patients and their caregivers are well educated about avoiding this dangerous adverse effect.

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Katie Gillick, Patient Advocate at Orsini Specialty Pharmacy, discusses the importance of patient and physician communication in the care of hypoparathyroidism.

Hypoparathyroidism is a rare endocrine disorder in which the parathyroid glands do not produce enough parathyroid hormone (PTH). Common signs and symptoms include cataracts, muscle cramps, tetany, pain in the face, legs, and feet, seizures, tingling sensation, and weakened tooth enamel.

Ms. Gillick’s journey began with thyroid cancer at age 23. After two surgeries to remove her thyroid, she began to experience symptoms of post-surgical hypoparathyroidism. Following her diagnosis, she was put on standard-of-care treatments which did not help control her symptoms. It was then that she decided to enroll in a phase 3 clinical trial of injectable parathyroid hormone. Ms. Gillick has now been on this medication for years with excellent management of her condition.

From both personal experience and patient survey results, Ms. Gillick describes brain fog as the biggest symptom burden of disease. This symptom affects nearly all aspects of daily life including relationships, ability to work, etc. However, because this symptom is hard to measure, it is not always properly addressed.

Ms. Gillick wishes that doctors knew that lab values do not always, and frequently do not, correspond with patients symptoms or lived experiences. It is therefore important for physicians to have good communication with their patients and not just brush things off when lab values look good.

Orsini Specialty Pharmacy dispenses over 70 different therapies for over 50 rare conditions, offering special handling and mail order options that retail pharmacies may not be able to offer, helping more patients get the medications they need.

For more information, visit https://www.hypopara.org/

To learn more about hypoparathyroidism and other rare endocrine disorders, visit https://checkrare.com/diseases/endocrine-disorders/

CHAPTERS
Introduction 00:00
Hypoparathyroidism Journey 00:16
What Physicians Should Know 2:13
Brain Fog and Symptom Burden 3:41
Speciality Pharmacies 5:12

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Maria Vogiatzi, MD, Division of Endocrinology at the Children's Hospital of Philadelphia, discusses the effect of Crenessity (crinecerfont) on bone age advancement in patients with congenital adrenal hyperplasia (CAH).

CAH refers to a group of genetic conditions that affect the adrenal gland production of hormones, particularly, the production of cortisol and androgen hormones. Persons with severe forms of the condition can be dramatically impacted. For example, females with a severe form of the condition may have ambiguous genitalia at birth and if not properly diagnosed, develop dehydration, poor feeding, diarrhea, vomiting and other health problems soon after. People with milder forms may not be diagnosed with the condition until adolescence or adulthood when they experience early signs of puberty or fertility problems. Excess androgens can also cause accelerated bone age maturation, leading to reduced adult height.

An abstract presented at ENDO 2026 aimed to describe changes in bone age advancement and predicted adult height in a subset of phase 3 CAHtalyst Pediatric (NCT04806451) participants. Crinecerfont is a first-in-class corticotropin-releasing factor type 1 receptor (CRF1) antagonist that is approved by the US Food and Drug Administration (FDA) as an adjunct to glucocorticoid replacement in patients 4 years of age and older with classic CAH.

A total of 103 participants were randomized and 41 had available assessments at baseline and month 24 of the study. Of these 41 participants, 63% had an advanced bone age at baseline. At month 24, 15% of these patients showed worsening bone age advancement, 31% showed no change, and 27% had improvements in bone age minus chronological age from 6 months up to 1 year. Additionally, 27% of participants had improvements in bone age minus chronological age of 1 year or more.

CHAPTERS
Introduction 00:00
CAH Overview 00:10
Treatment and Dosing Strategy 2:36
Growth Patterns in CAH 4:13
Effect of Crinecerfont on Bone Age Advancement 6:16
Crinecerfont Mechanism of Action 9:21

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