Briefly noted: Selective Serotonin Reuptake Inhibitors (SSRIs) and Linear Growth

Posted on October 27, 2018 by gutsandgrowth

CA Calarge et al. J Pediatr 2018; 201: 245-51. This study analyzed data from 4 separate trials with a total of 267 boys treated with risperidone. In this cohort, 71% had taken an SSRI.

Key finding: The duration and cumulative dose of SSRI was inversely associated with height z score, especially during Tanner 3 and 4 stages. The effect was approximately 1 cm for every year of treatment.

The authors speculate that SSRIs could “alter serotonin signaling, which is known to control GH secretion.”

My take:

This study shows an association between SSRIs and linear growth but it remains unclear if this affects adult height (could postpone growth).
This potential adverse effect needs to be considered in the clinical picture of the severe impairment and distress that can occur due to untreated depression and anxiety.

Lake Louise, Banff

Why some kids are short & understanding linear growth

Posted on June 15, 2016 by gutsandgrowth

If you want to explore the biological basis for short stature, then an excellent review (YH Jee, J Bacon. J Pediatr 2016; 173: 32-7) is worthwhile.

The article begins by explaining the reasons why linear growth is rapid in infancy, slows in childhood and accelerates in adolescence through a process of growth plate chondrogenesis. In addition, the idea that growth plate fusion causes growth cessation is not accurate. Fusion of the growth plate occurs because of growth cessation. In addition, in many with “catch-up growth” the “delay in maturation appears to be driven by subtle undernutrition due to diminished appetite.”

Altered Growth Plate Chondrogenesis:

Nutritional intake -excess and inadequate nutrient intake affects growth, often through modulation of endocrine hormones. Overnutrition accelerates linear growth “but the adult height is not substantially affected.”
Hormones –thyroid hormones, growth hormone, IGF-1, androgen, and estrogen all positively regulate linear growth. Glucocorticoids negatively regulate linear growth.
Inflammatory cytokines –these cytokines (including TNF-α, IL-6, IL-1β) negatively regulate chondrogenesis
Paracrine growth factors, Extracellular Matrix, Intracellular Proteins –local growth factors can be deficient in those with specific genetic mutations: FGFR3 -achondroplasia, GNAS -Albright hereditary osteodystrophy, PTH1R -Blomstrand chrondrodysplasia, PTPN11 (& others) -Noonan, SHOX -Langer mesmeric dysplasia. SHOX mutations accounts for 2-5% of children with formerly idiopathic short stature. SHOX gene is also involved in Turner syndrome short stature. More listed in their Table (pg 35).

My take: It is cool to see the evolved understanding of the various factors affecting stature. While the authors conclude that exome sequencing will alter the diagnostic approach to children with severe short or tall stature, it seems that a genetic panel would be quite practical and less expensive than many endocrinological evaluations.

Here’s Why Biologic Therapy for Crohn’s Helps Adolescents Grow

Posted on May 5, 2016 by gutsandgrowth

It is well-recognized that Crohn’s disease is associated with delays in the onset and progression of puberty with the potential for stunted growth, impaired bone accrual, and diminished quality of life.

Now, a study (MD DeBoer et al. J Pediatr 2016; 171: 146-52) shows that initiation of anti-tumor necrosis factor α (anti-TNFα) treatment results in a rapid increase in sex hormone and gonadotropin levels.

In 72 adolescents, this observational study followed levels of sex hormones, gonadotropin levels, dual-energy x-ray absorptiometry, along with cytokine/inflammatory markers at initiation of anti-TNFα therapy, at 10 weeks and at 12 months.

Key findings:

By week 10 , testosterone z scores in males increased from a median of -0.36 to 0.40 (P<0.05)
By week 10 , estradiol z scores in females increased from a median of -0.35 to -0.02 (P<0.01)

My take (from the authors): This study suggests that “systemic inflammation suppresses gonadotropin-stimulated production of sex hormones” and that treatment of this inflammation with anti-TNFα agents allows rapid resumption normal production.

Related blog posts:

Law Quad, Univeristy of Michigan

Being Short -Not Pathologic

Posted on October 30, 2013 by gutsandgrowth

A recent retrospective review from Cincinnati Children’s showed a surprisingly low level of underlying disease in asymptomatic short children (J Pediatr 2013; 163: 1045-51).

The authors reviewed 1373 consecutive cases of short stature referrals (endocrinology) between 2008-2011. In this cohort, there were 235 who met inclusion criteria as having height <3rd percentile and otherwise well.

Results:

“Nearly 99% of patients were diagnosed as possible variants of normal growth: 23% with familial short stature, 41% with constitutional delay…and 36% with idiopathic short stature”
New pathology: 1 patient with biopsy-proven celiac disease, 1 patient with unconfirmed celiac diease, and 1 patient with potential insulin-like growth factor I receptor defect.
Cost for each new diagnosis: >$100,000

One important caveat from the study was the focus was not on those with growth failure –height velocity less than 5 cm/year; this study analyzed those with short stature only. In all short (growth failure and isolated short stature) patients, previous studies have identified a much higher rate of organic pathology. The authors also note that only 37% of their patients had appropriately maintained growth records forwarded (even after requests). One other point that I found interesting: “Contrary to common belief, short stature has not been shown to result in impaired quality of life.”

Conclusions: “healthy short children do not warrant non directed, comprehensive screening.” The authors advocate for revision of pediatric endocrine guidelines for evaluation of these children. Reference: J Clin Endocrinol Metab 2008; 93: 4210-7.

These conclusions should be applied ONLY to those without symptoms and with normal exams (which should include a perianal examination).

Where is the Journal Editor?

Posted on February 7, 2013 by gutsandgrowth

A recent article is titled “Determination of Bone Age in Pediatric Patients with Crohn’s Disease Should Become Part of Routine Care” (Inflamm Bowel Dis 2013; 19: 61-65). (Thanks to Ben Gold for suggesting this reference.)

Does the study merit the authors’ conclusion that ‘determination of bone age (BA) should become the standard of care in pediatric Crohn’s disease (CD) patients, allowing clinically meaningful interpretation of growth…leading to improved treatment recommendations?’

No. This small study (n=49, 84% Caucasian) simply showed that a lot of pediatric CD patients have a delayed bone age. This is not a novel finding.

Specifically, the mean BA Z score was -1.40 ± 1.5 in this population and 41% had a BA Z score of < -2.0. This cross-sectional study was conducted between 2007-2009. Patients were consecutively approached for enrollment during this time period.

Clinical factors associated with delayed bone age included Caucasian race, Tanner stage 1-3, history of steroid exposure, colonic disease location, azathioprine/6-mercaptopurine usage, and female sex. Interestingly, these variables are not entirely consistent with prior studies in which male sex was associated with delayed bone age.

The reason why the conclusion is a far-reach is that there is no data in the study showing how bone age influences any clinical decision-making in these patients. There is no information on cost-effectiveness of their proposed “standard of care.” There is no longitudinal data to suggest that the delayed BA or the recognition of a delayed BA resulted in a different outcome.

My conclusion:

Many pediatric patients with CD have delayed BA and some may benefit from a BA determination. I think extrapolating a much broader conclusion from this study is not warranted.

gutsandgrowth

Pediatric Gastroenterology

Tag Archives: short stature