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Rethinking Male Bias in Pediatric Growth Hormone Deficiency

Rethinking Male Bias in Pediatric Growth Hormone Deficiency 1024 683 JoAnna Pendergrass, DVM

Although males have historically been over-represented in pediatric growth hormone deficiency (GHD) cases, this predominance does not hold true across various classifications of GHD.

 

Referrals for short-stature evaluations are common in pediatric endocrinology despite the rarity of growth hormone deficiency (GHD). Historically, boys predominate these referrals, which are conducted to rule out GHD.

Yet, according to a recent retrospective study led by Rohan Henry, MD, MS, a pediatric endocrinologist at Nationwide Children’s Hospital, this male predominance is not present across several GHD classifications.

Study results were published in Clinical Endocrinology.

“There are three main biases that impact the sex distribution of patients attending the endocrinology clinic for l growth evaluation: selection bias, referral bias and provider bias,” Dr. Henry explains.

Selection bias occurs when parents are more concerned about boys’ stature than girls’ stature. Referral bias indicates the predominance of boys being referred for growth concerns. Provider bias is the tendency for providers to perform more short-stature evaluations on boys than girls.

“This study,” he says, “is the first attempt to demonstrate the true incidence of GHD in boys and girls by limiting male sex bias for GHD evaluation and testing.”

 

Study design

The study included 399 patients (292 boys, 107 girls) aged 3 to 16 referred to a pediatric endocrinologist for short-stature evaluation between January 1, 2012, and December 31, 2019.

Data collected from the patients’ electronic medical records included sex, pituitary magnetic resonance imaging (MRI) results and peak stimulated growth hormone (pGH) levels during growth hormone provocative testing (GH PT).

The researchers used pGH levels to define GHD severity and stratify the patients into three groups:

  • Group A (< 5 ng/ml): n=138
  • Group B (5.0 to 7.4 ng/ml): n=120
  • Group C (7.5 to 9.9 ng/ml): n=141

The researchers also categorized the patients as having isolated GHD (IGHD; the only pituitary hormonal deficiency) or multiple pituitary hormone deficiencies (MPHD; GHD + other pituitary hormonal deficiencies).

 

Male predominance observations

 Boys predominated over girls for short-stature referrals, those who underwent GH PT and had a GHD diagnosis.

Also, significantly more boys than girls were observed within each GHD severity group, but the sex distribution within the groups was not significant. For example, of the 138 patients in group A, 100 were boys (34.2% of boys in the study) and 38 were girls (35.5% of girls in the study).

In addition, more boys than girls had IGHD (n=261 versus n=88), suggesting that either boys have an overdiagnosis of IGHD or girls have an underdiagnosis of IGHD, Dr. Henry says.

MPHD was more commonly observed in boys than girls (n=31 versus n=19), but this difference was not statistically significant.

The frequencies of anatomical pituitary abnormalities observed on MRI between boys and girls were similar and not significant.

“The MRI findings highlight the need to acquire pituitary imaging in boys and girls when evaluating for short stature,” Dr. Henry says.

 

Future plans

Dr. Henry discussed the benefit of a prospective multicenter study to validate the current study’s findings, given the limitations of a retrospective study. A multicenter study could also help determine whether the current study’s findings would be similar beyond a single research center.

“It would also be useful to examine the relative impact of GH supplementation on growth velocity and overall height between males and females,” he adds.

 

 

Reference: 

Henry, RK, Mamilly L, Chaudhari M, Klamer BG, Nikahd M, Pyle-Eiolola AL. Beyond the bias! Sex distribution is paediatric growth hormone deficiency reexamined. Clinical Endocrinology. 2024;100:441-446.

 

About the author

JoAnna Pendergrass

JoAnna Pendergrass, DVM, is a veterinarian and freelance medical writer in Atlanta, GA. She received her veterinary degree from the Virginia-Maryland College of Veterinary Medicine and completed a 2-year postdoctoral research fellowship at Emory University’s Yerkes Primate Research Center before beginning her career as a medical writer.

As a freelance medical writer, Dr. Pendergrass focuses on pet owner education and health journalism. She is a member of the American Medical Writers Association and has served as secretary and president of AMWA’s Southeast chapter.

In her spare time, Dr. Pendergrass enjoys baking, running, and playing the viola in a local community orchestra.

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