Intense sympathetic nerve activity in adults with hypopituitarism and untreated growth hormone deficiency

Perturbations in the sympathetic nervous system may be anticipated in adults with hypopituitarism and untreated GH deficiency, because the syndrome is associated with both peripheral and central factors known to modulate sympathetic traffic. The higher prevalence of hypertension and increased cardiovascular morbidity/mortality reported in GH-deficient patients may suggest increased activity of the sympathetic nervous system. We recorded muscle sympathetic nerve activity (MSNA) in 10 hypopituitary adults with adequate hormonal replacement therapy except GH and in 10 healthy controls matched for age, gender, and body mass index to test whether hormonal aberrations in hypopituitarism and untreated GH deficiency are associated with an increase in sympathetic nerve traffic. Blood samples for insulin-like growth factor I, free T4, and TSH were taken after an overnight fast, followed by an oral glucose tolerance test. Direct intraneural recordings of MSNA were performed with a tungsten microelectrode from the peroneal nerve. The hypopituitary subjects had markedly increased MSNA (54 +/- 4 bursts/min vs. 34 +/- 4 in controls; P < 0.002), which was not related to abdominal obesity or altered glucose metabolism. When assessed for the whole study group, MSNA was inversely correlated to serum insulin-like growth factor I (r = -0.59; P < 0.006) and TSH (r = -0.46; P < 0.04). MSNA was positively correlated to diastolic blood pressure (r = 0.80; P < 0.0005) in patients, but not in controls. The intense sympathetic discharge is suggested to be of central origin and may be an important underlying mechanism for the secondary hypertension and increased cardiovascular morbidity/mortality in this patient group.     

MR imaging in idiopathic growth hormone deficiency

Oltipraz and related dithiolethiones are an important class of chemopreventive agents. Studies were undertaken to identify cancer chemopreventive dithiolethiones more active than oltipraz. Largely based upon enzyme induction activities in vitro, 17 dithiolethiones, including oltipraz, were analyzed for their ability to induce hepatic phase II enzyme activities in vivo. Of these compounds, 15 produced greater induction of NAD(P)H:quinone reductase and 11 yielded greater induction of glutathione S-transferase than oltipraz. All 17 dithiolethiones were then tested for their ability to inhibit acute hepatotoxicity by aflatoxin B1 (AFB1), which previously has been shown to be an intermediate predictor of chemopreventive activity. Rats were pretreated with dithiolethiones (0.3 mmol/kg body wt, three times a week per os) and challenged with two acutely toxic doses of AFB1 (0.5 mg/kg body wt, once daily for two successive days per os). Inhibition of hepatotoxicity was measured by changes in body weight gain during AFB1 challenge, reduction in levels of hepatic enzymes in serum and diminution of bile duct cell proliferation. Nine dithiolethiones spanning a range of responses in this toxicity screen were further tested for their ability to prevent AFB1-induced tumorigenicity, as assessed by a reduction in hepatic burden of putative preneoplastic foci. Six dithiolethiones were found to be considerably more effective than oltipraz in preventing AFB1-induced tumorigenesis. In general, dithiolethiones that were very effective in inhibition of acute hepatotoxicity were also found to be effective in prevention of hepatic tumorigenesis.     

Gorham disease: correlation of MR findings with histopathologic changes

Gorham disease is a rare disorder of unknown etiology characterized by bone destruction and abnormal proliferation of thin-walled vascular channels including lymphatic capillaries. Starting monocentrically in a single bone, the angiomatous masses in this disease extend to adjacent bones and soft tissues without respecting articular barriers. Herein we report a case of Gorham disease with its MR and histopathologic appearance.     

Sonographic findings of rotator cuff tears: correlation with MR imaging

Sonography was performed in 41 patients with symptoms referable to the rotator cuff. Sonography was performed immediately after MR imaging, so that the information obtained by MR imaging could be applied to sonographic diagnosis. Twenty patients were diagnosed from T2-weighted images as having complete tears of the rotator cuff. Sonography showed full-thickness anechoic areas in 12 of the 20 patients, heterogeneous hyperechoic areas in seven, and no abnormal findings in the other one. Thirteen patients were diagnosed as having incomplete tears with MR imaging. Sonography showed heterogeneous hyperechoic areas in 12, but no abnormal findings in one of the 13. Hyperechoic areas in the rotator cuff were shown in four of eight patients who had been diagnosed from T2-weighted images as not having tears. We consider full-thickness anechoic areas to be specific findings of complete tears, although some patients with rotator cuff tears did not show this finding.     

Disturbed release of growth hormone in mature dogs: a comparison with congenital growth hormone deficiency

An acquired defect in growth hormone secretion in mature dogs has been associated with some forms of generalised alopecia. In an attempt to elucidate the pathogenesis of the disturbance in growth hormone release, the plasma concentrations of growth hormone and insulin-like growth factor I (IGF-I) were measured in two seven-year-old poodles with alopecia and, for comparison, in two young German sheperd dogs with congenital hyposomatotropism (pituitary dwarfism). In the poodles the basal concentrations of growth hormone were low, although often above the detection limit of the assay. The concentrations of IGF-I were in the reference range for healthy poodles. No growth hormone could be detected in the plasma of the German sheperd dogs and the concentrations of IGF-I were very low. Stimulation with clonidine and growth hormone releasing hormone (GHRH) before and after repeated injections of GHRH did not result in significant increases in growth hormone concentrations in plasma. The concentrations of growth hormone in the poodles fluctuated at low levels during the test period. In the German sheperd dogs the levels of growth hormone remained unmeasurable during the stimulation tests. It was concluded that in the two poodles the basal concentrations of growth hormone were sufficient to maintain normal IGF-I concentrations, and thus the release of growth hormone was considered appropriate. Based upon measurements of urinary corticoids and a review of the literature it is suggested that the lack of a growth hormone response to stimulation was due to the enhanced release of somatostatin as a result of mild and fluctuating hyperadrenocorticism.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interrelation of the therapeutic effects of growth hormone and testosterone on growth in hypopituitarism

The present study evaluates the modifying effect of growth hormone on the growth-promoting action of testosterone in boys at pubertal bone age. Growth and bone maturation were analyzed in 42 boys with primary or secondary Leydig cell insufficiency who had been treated with testosterone in an attempt to induce puberty and the accompanying growth spurt. The dosage given was considered normal or high for physiologic replacement therapy at puberty. Sixteen boys had normal GH secretion (seven had isolated gonadotropin deficiency, nine had congenital anorchia); 26 were GH and Gn deficient (20 idiopathic, six craniopharyngiomas). Of the GH-deficient patients, 12 received hGH simultaneously, while 14 received only testosterone. Results from each group were compared with the normal pubertal growth spurt in 15 untreated healthy boys. In isolated Gn deficiency and in congenital anorchia, the growth rates increased to above normal during the first six months of treatment, indicating that the testosterone dosage was probably too high for the beginning of puberty. During two subsequent six-month treatment periods, the rates leveled off close to normal. The same was true in the GH- and Gn-deficient patients on adequate hGH replacement. For contrast, there was minimal or no stimulation of growth when an even higher testosterone dose was given to GH- and Gn-deficient boys without hGH therapy. Bone maturation was normal in the boys with normal GH secretion or with hGH replacement, but was subnormal in the GH-deficient boys not treated with hGH. We conclude that testosterone exerts its full growth-promoting action only in the presence of normal endogenous GH secretion or with sufficient hGH replacement and that both hormones should be continued simultaneously until final adult height is achieved.     

MR imaging of the anterior cruciate ligament: frequency of discordant findings on sagittal-oblique images and correlation with arthroscopic findings

OBJECTIVE: The purposes of this study were to determine the frequency of discordant MR findings of the anterior cruciate ligament (ACL) using sagittal-oblique images and the arthroscopic integrity of the ACL in knees with a discordant MR appearance. MATERIALS AND METHODS: The frequency of discordant MR features was determined by independently reviewing the sagittal-oblique images of 53 consecutive patients undergoing subsequent arthroscopic surgery. The first 25 consecutive knees were examined using a conventional, dual-echo, T2-weighted spin-echo (SE) sequence; the subsequent 28 consecutive knees were examined using both a T1-weighted SE(T1) and a fat-suppressed, fast spin-echo (FSE) T2-weighted sequence. Two examiners who were unaware of patient identification and arthroscopic results evaluated only the sagittal images that included the ACL. Each reviewer graded the ACL as torn or intact. The MR appearance was considered discordant when one MR sequence showed disrupted or poorly seen ACL fibers and the other sequence showed intact ACL fibers. The arthroscopic integrity of the ACL was determined for the 20 knees with a discordant MR appearance. RESULTS: A discordant MR appearance of the ACL was seen in 20 of the 53 knees (38%), including 10 knees evaluated using conventional T2-weighted sequences (40%) and 10 knees using T1/FSE T2 (36%) sequences. Arthroscopic examination of these knees showed intact ACL fibers in all 20 knees; the ACL was normal in 18 knees and a partial tear was questioned in two knees. CONCLUSION: A discordant appearance of the ACL was frequently encountered (38%) using either conventional T2-weighted sequences or T1 and FSE MR sequences in the sagittal-oblique plane. Intact ACL fibers were found during arthroscopy in all 20 knees with a discordant MR appearance.     

Patterns of ovarian growth and development in cattle with a growth hormone receptor deficiency

Nutritionally induced changes in growth hormone (GH) and IGF-I are associated with decreased ovarian function and may partially explain infertility and anestrus in undernourished cattle. The reproductive importance of GH and IGF-I was tested in cattle with a GH receptor deficiency (GHRD) that have reduced blood IGF-I. Blood was collected daily for plasma, and ovaries were examined daily by ultrasonography for 3 wk during an estrous cycle (estrus = d 0) in GHRD (n = 8) and control (n = 8) cattle. On d 18, blood samples were collected every 10 min for 6 h to measure LH. The GHRD cattle had fewer small antral ovarian follicles (2 to 5 mm, P < .01). After estrous cycle d 5, the first-wave dominant follicle stopped growing in GHRD but continued growing in controls (P < .001). Size of the CL was equivalent for GHRD and controls until d 5, after which CL development slowed in GHRD (P < .01). Likewise, plasma progesterone concentrations were less in GHRD (P < .001). During the luteal phase, GHRD cattle failed to develop follicles greater than 10 mm in diameter (endocrine status x day, P < .05). Size and rate of growth of preovulatory follicles, plasma estradiol, plasma FSH, and plasma LH (d 18 bleed) were similar in GHRD and controls. In conclusion, an important role for GH, GH receptor, and IGF-I in ovarian function was supported because GHRD cattle had distinctly different patterns of ovarian development compared with control cattle.     

Action of growth hormone on erythropoiesis: changes in red blood cell enzyme activities in growth-retarded patients with and without growth hormone deficiency

Fifteen red cell enzyme activities of growth-retarded patients with and without growth hormone (GH) deficiency were investigated before and after GH administration. The 15 enzymes were Hexokinase, phosphoglucomutase, glucose phosphate, isomerase, phosphofructokinase, fructose diphosphate aldolase, glyceraldehyde-3-phosphae dehydrogenase, triosephosphate isomerase, 2,3-diphosphoglycerate mutase, 3-phosphoglycerate kinase, 3-phosphoglycerate mutase, enolase, pyruvate kinase, glycose-6-phosphate dehydrogenase, 6-phosphogluconic dehydrogenase, glutathione reducase. Sixty-six subjects were studied: 30 normal control subjects (group N) and 36 patients (aged 5-23 years) with short stature. Complete endocrine evaluation showed 21 (group I) to have GH deficiency (10 patients with isolated GH deficiency) and 15 (group II) to have normal hypothalamic and pituitary function except for two patients with a moderate hypothyroidism. Both had been receiving thyroid hormone treatment for a long time before our studies. All 36 patients were treated with 2 mg human growth hormone intramuscularly for 7 days. Before GH treatment no significant difference was observed between hematologic data in group I (GH deficiency) and group II (no GH deficiency). After GH therapy there was a significant increase in reticulocyte count in both groups of patients with short stature. The mean pretreatment value in group I was 1.294% +/- 0.084 (SEM); the mean post-treatment value was 2.081% +/- 0.287 (SEM)< P less than 0.005. The mean pretreatment value in group II was 1.0% 0.184 (SEM); the mean post-treatment value was 1.407% +/- 0.193 (SEM), P less than 0.01. In group II (no GH deficiency) mean pretreatment erythrocyte enzyme activities were not significantly different from those activities observed in normal control subjects (group N). However, in patients who lacked GH, the pretreatment activities of five red cell enzymes (glucose phosphate isomerase, triosephosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase, 2,3-diphosphoglycerate mutase, 3-phosphoglycerate kinase) were significantly decreased before GH administration compared with the values in normal control subjects...     

Vitamin A deficiency and growth hormone in children

Proliferating trichilemmal tumors are benign epitheliomas that may show malignant transformation. We present a trichilemmal tumor 15 x 15 x 10 cm in size and emphasize malignant transformation criteria.     

Elderly patients with adult-onset growth hormone deficiency are not osteopenic

The age-related decline in GH secretion has been implicated in the development of osteoporosis. GH-deficient adults show a significant reduction in bone mineral density (BMD), which is greater in those with childhood-onset GH deficiency than in those with GH deficiency occurring in adult life. To determine whether GH deficiency in late adult life causes a reduction in BMD beyond the decline observed with increasing age, we studied 21 patients over the age of 60 yr with GH deficiency caused by organic pituitary disease and 23 controls of similar age and sex distribution and BMI. Dual energy x-ray absorptiometry was used to determine total bone mass and BMD at the hip and in the lumbar spine. Serum osteocalcin was determined in all subjects and urinary deoxypyridinoline/creatinine ratio in 19 patients and 21 controls. The median (range) known duration of GH deficiency in the patients was 8 yr (range, 4-41 yr). The median (range) total bone mass was 2774 g (range, 1534-3734) in the patients and 2717 g (range, 1235-3549) in the controls (P = 0.42). Specific measurements of BMD made at L2-L4, the right femoral neck, the right femoral trochanter, and Ward's triangle were 1.234 (range, 0.778-1.507) vs. 1.144 g/cm2 (range, 0.809-1.466; P = 0.48), 0.921 (range, 0.605-1.372) vs. 0.96 g/cm2 (range, 0.534-1.315; P = 0.62), 0.92 (range, 0.523-1.229) vs. 0.915 g/cm2 (range, 0.353-1.313; P = 0.68), and 0.773 (range, 0.408-1.289) vs. 0.806 g/cm2 (range, 0.353-1.154; P = 0.81) in the patients and controls, respectively. The median (range) serum osteocalcin was 11.5 (range, 3.6-23.0) vs. 15.1 ng/mL (range, 0.7-40.5; P = 0.019) in the patients and controls, respectively. The median (range) deoxypyridinoline cross-links/creatinine ratio was 3.5 micromol/mol (range, 0.8-8.3) in the patients and 4.9 micromol/mol (range, 3.0-9.7) in the controls (P 0.038). There was a significant correlation between serum insulin-like growth factor I and total bone mass in the controls, but not in the patients. These data demonstrate that BMD is not significantly altered in GH-deficient adults over the age of 60 yr. Markers of bone formation and resorption are decreased, however, suggesting that bone turnover is reduced. Further studies are required to determine whether the reduction in bone turnover in these patients is of benefit.     

Combined deficiency of thyroid stimulating hormone and growth hormone in a diabetic patient with Hashimoto thyroiditis

We report the case of a 36-year-old female patient with insulin dependent diabetes who developed hypothyroidism of pituitary origin after giving birth. She had low levels of free T4 and TSH with no response to i.v. TRH. Antimicrosome antibodies were increased (1/25000), suggesting Hashimoto's thyroiditis. The other hormones were normal except for a low level of growth hormone and insulin growth factor 1. There were no antibodies against the pituitary. MRI of the pituitary was normal. We suspect a vascular origin for this partial pituitary deficiency.     

Arthritic temporomandibular joint: correlation of macromolecular contrast-enhanced MR imaging parameters and histopathologic findings

PURPOSE: To assess the utility of macromolecular contrast material-enhanced magnetic resonance (MR) imaging parameters for determining the histopathologic severity of temporomandibular joint (TMJ) arthritis. MATERIALS AND METHODS: Ovalbumin was used to induce arthritis in the TMJs of 10 previously sensitized adult white rabbits. Five rabbits composed the sham-treated control group. Dynamic spin-echo imaging was performed immediately before and for 30 minutes after injection of macromolecular contrast medium. Histologic specimens of TMJ were assessed quantitatively for arthritis. Changes in MR signal intensity were derived from the synovial and subsynovial tissues of the TMJ, and plasma volume (PV) and permeability surface area product (PS) were calculated. These MR parameters and the arthritic scores were compared between sham-treated and antigen-challenged TMJs. The relationships between MR parameters and histopathologic indexes were also determined. RESULTS: Arthritic TMJs showed marked enhancement of the synovial and subsynovial tissues over the imaging period. PS and all histopathologic indexes of arthritis were significantly greater (P < .005) in antigen-challenged than in sham-treated TMJs. PS demonstrated strong positive relationships with all histologic parameters of arthritis, indicating its utility for assessing the severity of joint inflammation. CONCLUSION: Macromolecular contrast-enhanced MR imaging enables quantification of PS and PV in inflamed joints. This technique may provide insights into the pathogenesis of joint inflammation and noninvasive monitoring of disease severity and treatment response in arthritis.     

Diagnosis of intraductal spread of breast cancer by high-resolution MR imaging: correlation between MR imaging and pathohistological findings

The main purpose of this study was to investigate pathohistological factors that affect the MR findings of intraductal spread (IDS) of breast cancer. The subjects of the present study were 42 breast cancer patients who were examined by MR imaging. Fat-suppressed high-resolution T1-weighted spin-echo images [350/13/1 (TR/TE/excitations), 16-cm FOV, 5-mm section thickness, and 512 x 256 matrix] were obtained one minute after the intravenous administration of Gd-DTPA. In this protocol, contrast determination time was 1 min 48 sec. Of the 42 cases, IDS was found to be located more than 1 cm from the primary focus in 22 cases (52%). Rates of sensitivity, specificity and accuracy of MR imaging for the detection of IDS were 82%, 80%, and 81%, respectively. The probable cause of misdiagnosis was parenchymal enhancement due to severe fibrocystic disease and normal menstrual cycle. In 21 of 42 cases, the MR findings were precisely correlated with the pathohistologic findings of almost the same cross-section. The MR findings of IDS varied greatly with observation of linear, band-like, branch-like, plate-like and minute ring enhancements. These findings closely reflected the size, aggregation pattern, and distribution of intraductal lesions. In particular, minute ring enhancement was only observed in 4 comedo-type lesions. This pattern of enhancement is considered to reflect elevated intraductal cellular density with necrosis in the central region.     

High-resolution MR imaging of stage I cervical neoplasia with a dedicated transvaginal coil: MR features and correlation of imaging and pathologic findings

OBJECTIVE: The purposes of this study were to assess the appearance of stage 1 neoplasia of the cervix by high-resolution MR imaging with an enveloping transvaginal receiver coil and to correlate the imaging findings with the pathologic findings. SUBJECTS AND METHODS: Fifteen patients (25-73 years old; mean, 40 years old) with clinical stage I disease were examined with a 37-mm-diameter ring-design solenoid receiver coil placed around the cervix. Axial 2.5-mm contiguous slices were obtained with a field of view of 10-15 cm on a 1.0-T HPQ Vista scanner with T1-weighted (660/20 msec [TR/TE]) and T2- weighted (2500/80 msec) spin-echo sequences and dynamic gradient-echo sequences during injection of gadopentetate dimeglumine (0.1 mmol/kg). Ten patients subsequently underwent Wertheim's hysterectomy, two underwent radiotherapy, two underwent extended cone biopsy for microinvasive disease, and one underwent a punch biopsy. For seven of 10 patients who had a hysterectomy, the widths of the tumor and the residual stroma were measured at eight radial points on the transverse images and at corresponding points on the histologic specimens at 5, 10, 15, 20, and 25 mm from the ectocervix. We then compared the widths of the tumor and the stroma on images and histologic specimens at each of these 40 points. Tumor volumes were calculated from the MR imaging and pathologic data and compared. For the other three patients, detailed MR imaging-pathology correlation was not possible because of multifocal tumor distribution (two patients) and insufficient detailed pathologic data (one patient). RESULTS: Three carcinoma types were recognized. Squamous carcinoma (nine cases) was seen as a centrally expanding intermediate-signal-intensity mass, whereas oat (small)-cell carcinoma (one case) and clear-cell carcinoma (one case) showed a multifocal distribution. For patients who had a radical hysterectomy, we noted good agreement between the widths of the tumor and the stroma determined by MR imaging and histology. Tumor volumes were determined to be 0-28.2 cm3 by MR imaging and 0-18.4 cm3 by pathology. We observed tumor extension into the immediate parametrium in four patients by MR imaging; one of these cases was not confirmed at surgery. Parametrial extension was not underestimated by MR imaging in any case. CONCLUSION: High-resolution imaging of the cervix with a transvaginal coil provides accurate assessment of the intra- and extracervical extents of tumors in clinical stage 1 cervical neoplasia.     

De novo mutations of the growth hormone gene: an important cause of congenital isolated growth hormone deficiency?

OBJECTIVES: To determine the epidemiological features of injuries associated with fireworks. DESIGN: A retrospective study of reported cases. SUBJECTS: Subjects were those who attended selected Victorian hospital emergency departments (n = 17) and those admitted for firework related injuries (n = 16). RESULTS: The mean (SD) age of attenders at emergency department between January 1988 and June 1996, was 8.9 (6.2) years and most (88%) were under 18 years of age. Males accounted for 71% of the cases. The most common anatomical sites and types of injury were head (47%) and burns (88%), respectively. About 53% of the injuries were caused by firecrackers, the remainder by sparklers and penny bangers. Among those admitted to hospital between July 1987 and June 1996, the mean (SD) age was 22.9 (14.8) years and 50% were under 18 years of age. Males accounted for 87% of the cases. There was a significant difference in mean age between those admitted and not admitted to hospital, the former being significantly older. CONCLUSIONS: Although relatively rare, injuries from fireworks still occur in Victoria after legislative restrictions on their sale in 1985. Consequently, there is a potential risk for injuries among children, particularly from firecrackers. More enforcement of the regulations, education, and parental supervision are needed to prevent injuries from fireworks.     

Breast lesions: correlation of contrast medium enhancement patterns on MR images with histopathologic findings and tumor angiogenesis

PURPOSE: To compare qualitative and quantitative magnetic resonance (MR) mammographic features of breast lesions with histopathologic findings, especially tumor angiogenesis. MATERIALS AND METHODS: Seventy-three patients (72 women, one man; aged 30-78 years; mean age, 51.0 years) with suspicious breast lesions underwent MR imaging. Noncontrast medium-enhanced localization imaging and then gadolinium-enhanced dynamic fast spoiled gradient-recalled-echo (SPGR) imaging were performed in all patients. In selected patients, subtraction fast SPGR images were obtained. The Pearson and Spearman correlation tests were used to determine the strength of the relationships between enhancement parameters and microvessel determinations. RESULTS: Time intensity curve type correlated with microvessel density grade (Spearman rank correlation test: r = .90, P < .001). The steepest slope of contrast medium uptake correlated with microvessel counts (Pearson correlation test; r = .83, P < .001). Peripheral enhancement in invasive carcinomas (n = 9) correlated with high peripheral and low central microvessel densities, which were associated with desmoplasia and/or necrosis. Internal septations (n = 2) were seen only in fibroadenomas. CONCLUSION: The density and distribution of microvessels may play major roles in the determination of the initial rate of contrast medium uptake and the heterogeneity of tumor enhancement.     

Normal intelligence with severe insulin-like growth factor I deficiency due to growth hormone receptor deficiency: a controlled study in a genetically homogeneous population

Superior school performance was reported for 52 Ecuadorian probands with severe deficiency of insulin-like growth factor I (IGF-I) due to GH receptor deficiency (GHRD) resulting from homozygosity for the E180 splice mutation of the GHR. In contrast, subnormal intelligence was reported in a study of 18 genetically heterogeneous Israeli patients, attributed to frequent hypoglycemia or IGF-I dependence of brain development. This study is the first controlled evaluation of the intellectual ability of patients with GHRD. We compared the intelligence of 18 patients of school age (mean +/- SD age, 11.5 +/- 2.8 yr), 42 of their relatives (11.5 +/- 2.8 yr), and 28 community controls (10.0 +/- 0.8 yr), using a battery of intelligence tests that have been validated in cross-cultural research, designed to minimize the effects of physical size, motor coordination, and cultural background. Because all patients had the same GHR mutation, for which the carrier state could be determined, this study also investigated whether heterozygosity for mutation of the GHR among unaffected relatives is associated with intelligence. The intellectual ability of the patients with GHRD was not significantly different from that of their relatives (P > 0.05) on the psychometric tests of intelligence and was comparable to that of the community controls on the chronometric tests. Homozygosity or heterozygosity for the mutation in the GHR gene common to Ecuadorian patients was unrelated to intelligence (P > 0.05). These results indicate that the gene defect causing GHRD is not related to intelligence in the Ecuadorian population. They also indicate that GH-induced IGF-I production is not required for normal brain growth in utero or for postnatal intellectual development.