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Updates in Pediatric Endocrinology and Diabetes in 2018
Kaitlyn Shank1, B.S. & Kanika Shanker1,2*, M.B.B.S., M.D.
1Penn State College of Medicine, Penn State Health, Milton S. Hershey Medical Center, Hershey, Pennsylvania
2Clinical Assistant Professor of Pediatrics, Summit Endocrinology, Summit Physician Services, Summit Health,
Chambersburg
*Correspondence to: Dr. Kanika Shanker, Clinical Assistant Professor of Pediatrics, Summit Health, USA.
Copyright © 2019 Dr. Kanika Shanker, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 19 February 2019
Published: 07 March 2019
Keywords: Updates; Diabetes; Endocrinology; Insulin; FDA
Published: 07 March 2019
Keywords: Updates; Diabetes; Endocrinology; Insulin; FDA
Abstract
Pediatric endocrinology deals largely with the very common diseases of childhood and adolescence such as diabetes, rickets and obesity along with more rare and nuanced diseases such as congenital adrenal hyperplasia and disorders of sexual differentiation. Technology rapidly advances the treatment of diabetes and guidelines are constantly changing for the treatment of many common endocrine conditions. In this succinct review, we present the most updated recommendations and guidelines provided by the nationally and internationally recognized regulatory bodies such as The Endocrine Society, The Pediatric Endocrine Society and the USA Food and Drug Administration. Through this mini review, we hope to provide important updates and knowledge to the providers taking care of neonates, young children and adolescents worldwide.
Background
In this ever-changing world, it is sometimes difficult to keep up with the recent advances in the field of
pediatric endocrinology and diabetes. In this review article, we briefly discuss clinical guideline updates in
pediatric endocrinology followed by a succinct overview of the advancements in diabetes technology and
medication. We have tried to provide concise and accurate developments in the field in the year 2018.
Methods
References for this review were identified through searches of PubMed, Medline, and Embase for articles
published until December 2018 using the terms “updates, diabetes, endocrinology” [MeSH Terms] OR
“insulin” [All Fields] OR “continuous glucose monitors, FDA” [All Fields]. The reference lists of the articles
thus identified were also searched. The search was not restricted to English-language literature.
The U.S. Food and Drug Administration (FDA) in April 2018, approved Crysvita (burosumab-twza). It is
the first drug approved to treat adults and children ages 1 year and older with X-linked hypophosphatemia
(XLH). XLH, a rare inherited form of rickets, with biochemical presentation of low levels of phosphorus in
the blood. It leads to impaired bone growth and development along with problems in bone mineralization
for children and adolescents. Burosumab-twza is a monoclonal antibody against the phosphaturic hormonefibroblast
growth factor-23. The peak plasma effect comes at 8-11 days.
Defined as excessive hair growth in women in a male-pattern hair distribution. It is a common disorder in
females and affects 5%-10% of the females. The polycystic ovarian syndrome, the most common cause [2].
Evaluation and Treatment of Hirsutism in Premenopausal Women:
An Endocrine Society Clinical Practice guideline came out in April 2018. Prior to that guidelines came in 2008, the 2018 guidelines has widened the evaluation guidelines. The 2018 guideline suggests:
i) Testing for elevated androgen levels in all women with an abnormal hirsutism score. The androgen levels
include total and free testosterone levels and other sex hormones such as dehydroepiandrostenedione levels.
The hirsutism score, also known as the Ferriman-Gallwey Hirsutism score, is an assigned number with
progressive increases in the score depending on the intensity of hair growth in nine body parts.
ii) Added the recommendation to screen women for nonclassic congenital adrenal hyperplasia (NCCAH)
due to 21-hydroxylase deficiency by measuring early morning 17-hydroxyprogesterone levels in the follicular
phase or on a random day for those with amenorrhea or infrequent menses.
iii) Against testing for elevated androgen levels in females with normal menstrual periods and normal
hirsutism score.
iv) Recommended against solo antiandrogen monotherapy with medications such as spironolactone unless
adequate contraception is used due to the potential risk of teratogenicity.
v) Against using insulin-lowering drugs such as metformin for the sole indication of hirsutism unless
metabolic indications are there.
Hypothalamic-pituitary and growth disorders in survivors of childhood cancer: An Endocrine Society
Clinical Practice guideline was released in August 2018. The guideline outlined the following:
i) Radiation-induced hypothalamic-pituitary dysfunction is both dose- and time-dependent; doses to the
hypothalamus-pituitary <30 Gy are associated primarily with growth hormone deficiency and precocious
puberty whereas deficits of luteinizing hormone/follicle stimulating hormone, thyroid stimulating hormone
and adrenocorticotropic hormone are seen following hypothalamic-pituitary doses >30 Gy, often years after
the completion of cancer therapy.
ii) Impaired linear growth and short adult height are most commonly seen in survivors exposed at a young
age to central nervous system, spinal or total body irradiation.
iii) Hypothalamic-pituitary dysfunction is frequently observed in childhood cancer survivors, especially in
those with tumors involving the hypothalamic-pituitary region or those previously exposed to radiation to
the central nervous system.
iv) Key differences and unique features that are specific to cancer survivors such as not relying solely on
serum IGF-I levels in childhood cancer survivors exposed to HP axis radiotherapy to make the diagnosis
of growth hormone deficiency.
v) Recommend against using testicular volume as the primary or sole indicator of degree of sexual development
in male childhood cancer survivors previously treated with gonadotoxic agents, such as alkylating agents or
testicular radiotherapy.
Congenital Adrenal Hyperplasia occurs due to Steroid 21-Hydroxylase Deficiency. The clinical presentation
of CAH depends on the degree of the genetic mutations mediating the conversion of 17 hydroxyprogesterone
to 11 deoxycortisol [4]. An Endocrine Society Clinical Practice guideline was released in November 2018,
highlighting the following. Prior to these guidelines, it was published in 2010.
1. Shared decision making among congenital adrenal hyperplasia patients, their families, and healthcare
professionals in regard to the medical, surgical, and psychological management of the disorder is emphasized.
2. Detailed protocols for adults, especially pregnant women, are included.
3. Advice against using experimental treatment approaches outside of formally approved clinical trials,
categorized as an upgraded “Good Practice Statement”, is provided.
Food Labelling [5]
i) In 2018, menu labeling provisions of the Affordable Care Act took effect, covering approximately 300,000
food retail establishments nationwide; FDA estimates this will save approximately $8 billion in health costs
over the next two decades.
ii) The vending machine rule, an effort to promote calorie labeling of articles of food in vending machines,
came into effect in 2016, but for some products sold in glass-front vending machines, the rule was delayed
until July 2018.
Wearables
iii) The year 2018 proved to be productive in further developing market space for wearables measuring
physical activity: Besides step tracking, the newer devices can monitor heart rate, sense an impending fall
and even conduct an electrocardiogram. So far we do not have randomized control trials to prove which
device is best for collecting data points from the user. The utility of these devices is certainly based on the
user’s motivation and provides objectivity to the user.
iv) GLP-1 agonists are widely used for the management of type 2 diabetes in the adult population. This class
of medication has demonstrated an effect in suppressing appetite by working at the level of the hypothalamus,
hence decreasing caloric intake. Two large adolescent clinical trials evaluating GLP-1 receptor agonists are
projected to conclude before the end of 2019, which are expected to shed light on the safety and efficacy of
this drug in the pediatric population.
Physical Activity [7]
The physical activity guidelines for Americans in 2018 were published by the US federal government. It
provided the first physical activity standards for children ages 3-5 years. The recommended target is at least
three hours of varied physical activity per day, consistent with the existing guidelines in Australia, Canada
and the United Kingdom.
The prominent advantages and disadvantages of this section are illustrated in Table 1.
*CGM = Continuous Glucose Monitor
*MDI = Multiple Daily Injections
a) On June 27, 2018, the FDA approved the t:slim X2 Insulin Pump with Basal-IQ, a predictive low-glucose
suspend feature that stops insulin delivery when the anticipated glucose falls into the hypoglycemic range
and automatically resumes when levels begin to rise, predicting 30 minutes in advance. This was the first
integrated CGM-pump system by Tandem (with Dexcom G6) and is approved for use in type 1 diabetics
ages 6 years through adulthood. The PROLOG trial (a 6-week randomized crossover trial) showed a 31%
reduction in hypoglycemia in this integrated system compared to sensor-augmented therapy alone [8].
Basal-IQ technology was officially launched in August 2018.
a) The Dexcom G6 was the first FDA-permitted CGM approved for making treatment decisions without
confirmatory finger sticks or calibrations. The sensors are approved for 10-day wear and data from the device
can be shared with 5 smart devices. It has been shown to reduce night time hypoglycemic events by 79% in
clinical studies. The G6 is approved for children ages two years and older and is not contraindicated with
acetaminophen use, as with the G5 transmitters.
a) Fiasp was first approved by the FDA for adults with diabetes on September 29, 2017, as an injectable
ultrafast acting insulin. It is a formulation of Aspart insulin with the addition of Niacinamide (vitamin B3)
which augments its absorption into the bloodstream from the subcutaneous tissue in only 2.5 minutes. It
can be dosed at the beginning of a meal or 20 minutes in and has proven to show greater glucose-lowering
ability (and lower A1c) than the fast-acting insulins, though there is still limited data for its clinical utility in
insulin pumps. It is offered as a FlexTouch prefilled delivery pen and a 10 mL vial. Currently, it is not FDAapproved
for use in insulin pumps in the US, but it has been approved for pump use in several European
countries.
a) Eversense was FDA-approved on June 21, 2018, as the first CGM sensor permitted for up to three
months use, with no weekly sensor self-insertions. A fluorescence-based sensor is implanted into the arm
of the patient and responds to interstitial glucose with fluorescent light that is measured and translated
into a blood glucose value. The sensor must be calibrated at least twice daily and is approved for ages 18
and older. The device is contraindicated with use of dexamethasone, mannitol, sorbitol and tetracycline. The
2018 PRECISE II trial demonstrated that the Eversense CGM system provided accurate glucose readings
through the 90-day sensor with favorable safety outcomes [9,10].
a) The Guardian Connect by Medtronic Minimed was FDA approved on March 8th, 2018 for ages 14 and
older. The sensor readings are not intended to directly inform blood glucose management, but rather to
provide an indication of when a finger stick may be required. It alerts users 10-60 minutes in advance of a
hypoglycemic event. The Sugar.IQ assist software offers in-depth analysis of blood glucose trends from data
acquired through the sensor. This is the first Smart CGM system for people on insulin injections and it uses
the guardian sensor 3 from Medtronic. It can be worn up to 7 days and is contraindicated with Tylenol,
many NSAIDs, cold medicine or paracetamol.
a) The Medtronic MiniMed 670G hybrid closed loop system using the SmartGuard automated insulin
delivery insulin pump and integrated guardian 3 sensor was FDA approved in July 2018 for use in pediatric patients ages 7-13. In a 3-month in-home study on the closed loop system, clinical trials showed time
in glycemic range for pediatric patients increased from 56.2 to 65.0% with an A1c reduction from 7.9 to
7.5% compared to management on traditional pump therapy alone. Additional clinical trials are currently
underway to assess safety in pediatric patients ages 2-6 for the Medtronic MiniMed 670G.
a) The American Diabetes Association publishes standards of medical care in diabetes every year. The new
standards that came out in January 2019 highlight the following points:
i) Screening for eating disorders in children with diabetes starting between the ages of 10-12 years.
ii) The target hemoglobin A1c should be individualized depending on the needs of the child and the family.
iii) The importance of screening high risk children for type 2 diabetes, including associated comorbidities,
and maintaining awareness for rapid progression and severity of this diagnosis.
Conclusion
There were a myriad of advancements and updates in the realm of pediatric endocrinology and diabetes in the year 2018. We have highlighted the latest monoclonal antibody targeted therapy for X-linked hypophosphatemia as well as the updated clinical guidelines for the diagnosis and treatment of hirsutism, the treatment of endocrine disorders in childhood cancer survivors, and the evaluation and management of congenital adrenal hyperplasia. We have elucidated both the medical and technological advancements as well as guidelines improved to better address childhood obesity. Finally, we have discussed the latest advancements in pump, continuous glucose monitor and insulin therapy for type 1 diabetic pediatric patients in addition to advantages and contraindications for each.
Bibliography
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