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Posted by on Oct 17, 2008 in Neuropsychiatry

More Lab Values From Geier and Geier Are Examined

More Lab Values From Geier and Geier Are Examined

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The discovery of questionable values for transsulfuration metabolites in the recently published studies by Geier et al (in Neurochemical Research and the Journal of the Neurological Sciences) prompts further investigation into the published work of the respective lead and anchor authors, David and Mark Geier. Specifically both recent articles reference a study of the father-son duo that was published in Hormone Research in 2006.

Information in this article has been dissected in detail at the neurodiversity blog, particularly with respect to the validity of son David’s academic affiliation, the curious makeup of the IRB that approved the study, and father Mark Geier’s limited experience in pediatric endocrinology, to name just three.

Evidently one of the Geiers’ favored hypotheses in the pathogenesis of autism concerns the nexus of transsulfuration metabolism, androgen synthesis, and mercury toxicity, and they refer to their speculation on the subject in a 2005 Medical Hypothesis article, which was used to justify the measurement of several hormone levels and transsulfuration metabolites in the Hormone Research study.

In this study, the Geiers examined 16 children (14 boys, 2 girls) with autism spectrum disorder (ASD) who presented to the Genetic Centers of America (which is evidently located at the residential address of Mark Geier, 14 Redgate Ct, Silver Spring, MD).* The children underwent clinical examination, presumably by Mark Geier, to assess traits consistent with “hyperandrogenicity.” These traits included, according to the Geiers, “early growth spurt, increased body and facial hair, aggressive behavior, and early secondary sexual changes.” The Geiers also measured selected hormone levels (at LabCorp, Inc) and transsulfuration metabolites (at the Great Smokies Diagnostic Laboratory) in these children. A control population was not included in the study. The serum/plasma values of the study subjects were compared with reference values from the particular laboratory used.

So, in essence, the Geiers assessed selected serum/plasma values in 16 children with ASD, from 3 to 10 years of age, whom they believed to display signs of androgen excess (in 15 of the 16 children). However, several of the clinical traits noted by the authors do not, in and of themselves, necessarily indicate endocrine abnormalities in childrenincluding masturbation, growth spurt, and an interest in female sexual organs among boys. A 10-year-old girl is noted to exhibit body hair and sexual development, which is not unusual given the age range of normal sexual development in girls. A 4-year-old boy is noted to exhibit male-pattern baldness, a dubious proposition without further clinical information or documentation. In only one case is the Tanner stage noted by the authors (although it is not indicated whether it is in respect to pubic hair or genitalia).

The subjects of Geier and Geier were tested for “androgen metabolites,” including serum testosterone (n = 16), serum/plasma DHEA (n = 11), and serum FSH (n = 14). (Although FSH has androgenic properties in males, the glycoprotein is not, despite the Geiers’ description, an androgen metabolite.)

FSH: In all 16 cases, serum FSH levels were within age- and sex-dependent reference ranges of LabCorp, which are consistent with pediatric FSH levels found elsewhere (eg, Pediatric Reference Ranges). However, the authors inexplicably concluded that the mean value of FSH in the 16 children with ASD was significantly decreased (35% of the normal reference). It should be noted that in 5 of these cases, LabCorp was unable to detect FSH in serum samples, and the authors therefore assumed that the value was equal to the lowest level that could be measured by LabCorp.

Testosterone: Geier and Geier reported elevated serum testosterone levels (ng/dL) in 12 of the 16 subjects (all boys). The reference ranges provided by LabCorp are consistent with pediatric ranges provided online by the University of IowaAddendum: According to Kaplowitz, prepubertal testosterone levels are generally less than 30 ng/dL; although levels ranging from 11 to 30 ng/dL may represent early puberty. The testosterone levels in all subjects of Geier and Geier were 25 ng/dL or lower.

DHEA: Geier and Geier reported elevated DHEA levels (ng/dL) in 10 (8 boys, 2 girls) of 11 subjects (Table). However, when these values are compared with age-dependent reference values from the University of Iowa, instead of LabCorp values, all 11 subjects fall within normal ranges. The Iowa reference advises that DHEA values “begin to increase progressively at about six years of age prior to any physical evidence of puberty.”

Patient No.

Age (y)

Sex

Geier and Geier DHEA (ng/dL)

LabCorp Ref (ng/dL)

U Iowa Ref (ng/dL)

7

3

M

107

26-72

20-130

9

3

M

85

26-72

20-130

4

4

M

120

26-72

20-130

16

4

F

94

19-42

20-130

10

5

M

118

29-66

20-130

12

5

M

100

26-72

20-130

13

7

M

148

29-66

20-275

15

7

M

67

29-66

20-275

11

8

M

181

53-135

20-275

6

9

M

284

53-135

31-345

8

10

F

251

234-529

150-570

A summary of the Geiers’ transsulfuration metabolite values is shown below (from Table 3). These values are compared with pediatric values from James et al (2006), a reference that was cited by Geier et al in their 2 recently published articles. In the cases of methionine and reduced glutathione, the values reported by the Geiers in Hormone Research (including reference values) are 1 and 2-3 orders of magnitude off, respectively, from those published in the literature.

Test

Geier and Geier,
Hormone Research (Reference Values)

James et al, 2006
Mean Control Values in Children (n = 73)

Plasma reduced glutathione, µmol/L (n = 10, 3-9 y)

585-911a
(911-1431)

2.2 ± 0.9

Plasma cysteine, µmol/L
(n = 10, 3-9 y)

185-331b
(223-355)

207 ± 22

Serum cystathione, µmol/L
(n = 11, 3-10 y, includes 2 girls)

0.072-0.309
(0.044-0.342)

0.19 ± 0.1

Serum homocysteine, µmol/L
(n = 12, 2-10 y, includes 2 girls)

2.9-9.9
(5.1-13.9)

6.0 ± 1.3

(5-15)c

Plasma methionine, µmol/L
(n = 9, 3-10 y, includes 2 girls)

1.2-1.9
(1.3-5.0)

28.0 ± 6.5

(6-40)c

a Equivalent to the reported 18-28 mg/dL, given the molecular weight of reduced glutathione, 307.43 µg/µmol.
b Equivalent to the reported 2.24-4.01 mg/dL, given the molecular weight of cysteine, 121.15 µg/µmol.

c AMA reference values.

The plasma cysteine levels of 4 of 10 children were below the lower limit of the Geiers’ laboratory reference range; but in all cases, they are well within the normal reference ranges provided by others in the literature (eg, see Han et al, figure 1A, along with others). In the case of serum cystathione, the values measured in the children with ASD were within the Geiers’ reference ranges. Nevertheless, the Geiers went on to conclude that serum cystathione was significantly decreased in these children. In the case of serum homocysteine, 4 children demonstrated values below the lower limit of the laboratory reference range (2.9, 4.0, 4.5, 5.0 µmol/L). The University of Iowa indicates a normal value for serum homocysteine of <10 µmol/L, and the AMA provides a range of 5-15 µmol/L. An assessment of serum homocysteine levels in more than 3500 adolescent children, published in JAMA, determined a range of 0.1-25.7 µmol/L, with a median value of 4.9 µmol/L.

The conclusions offered by Geier and Geier in Hormone Research, specifically that serum FSH, cysteine, cystathione, and homocysteine levels are significantly decreased and that DHEA levels are significantly increased in their subjects with ASD, are dubiousgiven that these levels (in every one of their ASD subjects) were within the normal laboratory ranges used by the Geiers or, in the case of DHEA, cysteine, and homocysteine, were within the normal ranges published by other sources. (Moreover, if the Geiers were proposing a kind of precocious puberty in children with ASD, then FSH would be expected to be elevated, not decreased.) In addition, the Geiers’ values for plasma reduced glutathione and methionine are suspect, given that they are at least 1 order of magnitude off those found in other sources.

In the case of serum testosterone, the individual values in the majority of Geiers’ ASD subjects were outside of the normal reference ranges (However, see Addendum above). Nevertheless, because of the noted concerns regarding some laboratory values in the Hormone Research article and the very liberal conclusions that Geier and Geier make from their data, confirmation of elevated testosterone levels in children with ASD is especially needed.

DHEA = dehydroepiandrosterone; FSH = follicle-stimulating hormone.

* And is also the address of the Institute of Chronic Illness.

bmartin (1127 Posts)

A native East Tennessean, Barbara Martin is a formerly practicing, board-certified neurologist who received her BS (psychology, summa cum laude) and MD from Duke University before completing her postgraduate training (internship, residency, fellowship) at the Hospital of the University of Pennsylvania in Philadelphia. She has worked in academia, private practice, medical publishing, drug market research, and continuing medical education (CME). For the last 3 years, she has worked in a freelance capacity as a medical writer, analyst, and consultant. Follow Dr. Barbara Martin on and Twitter.