PEDIATRICS Vol. 107 No. 4 April 2001, pp. 744-754
Evaluation of Growth and Hormonal Status in Patients Referred to the International Fanconi Anemia Registry
Received Jun 5, 2000; accepted Nov 15, 2000.
,,
From the * Department of Pediatrics and Children's Clinical
Research Center, New York Presbyterian Hospital-Cornell University
Medical Center, New York, New York, and Laboratory of Human Genetics
and Hematology, Rockefeller University, New York, New York.
Objectives. 1) To determine the extent of short stature in patients with Fanconi anemia (FA); 2) to determine the extent and nature of endocrinopathy in FA; 3) to assess the impact on height of any endocrinopathies in these patients; and 4) to study the correlation, if any, between height, endocrinopathy, and FA complementation group.
Study Design. Fifty-four patients with FA, 30 males and 24 females from 47 unrelated families, were prospectively evaluated in a Pediatric Clinical Research Center. The patients ranged in age from 0.1-31.9 years, with the mean age at assessment 8.6 years.
Results. Endocrine abnormalities were found in 44 of the
54 FA patients tested (81%), including short stature, growth hormone
(GH) insufficiency, hypothyroidism, glucose intolerance,
hyperinsulinism, and/or overt diabetes mellitus. Twenty-one of 48 (44%) participants had a subnormal response to GH stimulation; 19 of
53 (36%) had overt or compensated hypothyroidism, while 8 of 40 participants had reduced thyroid-hormone binding. Two patients were
diabetic at the time of study; impaired glucose tolerance was found in 8 of 40 patients (25%), but most surprisingly, hyperinsulinemia was
present in 28 of 39 (72%) participants tested. Significantly, spontaneous overnight GH secretion was abnormal in all patients tested
(n = 13). In addition, participants demonstrated a
tendency toward primary hypothyroidism with serum tetraiodothyronine
levels at the lower range of normal, while also having thyrotropin
(thyroid-stimulating hormone) levels at the high end of normal. Sixteen patients were assigned to FA complementation group A, (FA-A),
12 to FA-C, and 5 to FA-G; 10 of the 12 participants in FA-C were
homozygous for a mutation in the intron-4 donor splice site of the
FANCC gene. Patients in groups FA-A and FA-G were relatively taller than the group as a whole (but still below the mean
for the general population), whereas those in FA-C had a significantly
reduced height for age. GH response to stimulation testing was most
consistently normal in participants from FA-G, but this did not reach
statistical significance. The tendency toward hypothyroidism was more
pronounced in participants belonging to complementation groups FA-C and
FA-G, whereas insulin resistance was most evident in patients in FA-G,
and least evident in those in FA-C.Short stature was a very common finding among the patients with a mean
height >2 standard deviations below the reference mean (standard
deviation score: 
2.35 ± 0.28). Patients with subnormal GH
response and those with overt or compensated hypothyroidism were
shorter than the group with no endocrinopathies. The heights of those
participants with glucose or insulin abnormalities were less severely
affected than those of normoglycemic, normoinsulinemic participants,
although all were significantly below the normal mean. The mean height
standard deviation score of patients with entirely normal endocrine
function was also >2 standard deviations below the normal mean,
demonstrating that short stature is an inherent feature of FA.
Conclusion. Endocrinopathies are a common feature of FA, primarily manifesting as glucose/insulin abnormalities, GH insufficiency, and hypothyroidism. Although short stature is a well-recognized feature of FA, 23 patients (43%) were within 2 standard deviations, and 5 of these (9% of the total) were actually above the mean for height for the general population. Those patients with endocrine dysfunction are more likely to have short stature. These data indicate that short stature is an integral feature of FA, but that superimposed endocrinopathies further impact on growth. The demonstration of abnormal endogenous GH secretion may demonstrate an underlying hypothalamic-pituitary dysfunction that results in poor growth. Key words: endocrine, function, Fanconi anemia, height, short stature, GH deficiency, hypothyroidism, diabetes mellitus, glucose intolerance, insulin resistance.
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