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Biomedical subjects

S LaFranchi

Publications and source records attributed to S LaFranchi.

At least 19 recordsLinked to original sources
PubMed2000

Growth hormone use in transitioning patients--clinician and payer concerns.

Determining which patients with childhood-onset growth hormone (GH) deficiency will require continuing GH therapy into and/or throughout adulthood raises clinical and economic issues, such as retesting, appropriate dosing, and the risks and benefits of uninterrupted GH treatment versus the discontinuation of therapy. In his review of the evaluation and management of patients transitioning from GH therapy in childhood to GH therapy in adulthood, Dr. Stephen LaFranchi focuses on the odds of having ongoing GH deficiency, the changes that occur when therapy is discontinued, appropriate follow up of patients who discontinue treatment, and issues regarding the reinitiation of therapy. Dr. Margaret H. MacGillivray addresses appropriate monitoring and follow up of patients in transition, as well as their classification by etiology and severity of GH deficiency. Dr. Pete Fullerton explores new issues regarding GH deficiency treatment from a managed care perspective.

Adolescent↗
PubMed1999

Thyroid function in the preterm infant.

Thyroid gland function develops and matures during fetal life, with production of serum thyroxine (T4) concentrations beginning around 12 weeks gestation and increasing to term. Infants born prior to term have lower cord serum T4 concentrations that correlate with gestational age or birth weight. This is partially the result of lower thyroxine-binding globulin (TBG) concentrations. The cord serum free thyroxine (FT4) concentrations also correlate with gestational age, but they are not proportionately as low as the cord T4 concentration. Preterm infants have a postnatal thyrotropin (TSH) surge and rise in serum T4 and triiodothyronine (T3), which is qualitatively similar to, but quantitatively smaller than, term infants. In contrast to term infants, preterm infants often experience a fall in serum T4 and T3 in the first week of life to below birth levels. This drop appears to be the result of many factors, including nutritional problems and decreased hepatic TBG production, immaturity of hypothalamic-pituitary control of the thyroid gland, immaturity of the thyroid gland itself, and increased tissue utilization of T4. These changes are impacted by complications of prematurity, such as respiratory distress syndrome (RDS), which result in nonthyroidal illness-like changes. Again, serum FT4 seems less affected, and when measured by equilibrium dialysis may be in the normal range for age. Several studies have correlated different measures of morbidity and mortality in the preterm infant with lower serum T4 concentrations. However, as with adults, it may be that low serum T4 concentrations are a marker of the sickest preemies. Also, as with adults, this has led to speculation that T4 treatment might be beneficial in improving these complications of prematurity, in particular the neurological outcome. While some studies appear to show improvement in some facet of medical complications with T4 treatment, most show no effect. Regarding neurological outcome, the 2 best controlled trials do not show improvement in neuropsychiatric testing outcome assessed up to 2 years of age. One study, however, showed an IQ that was 18 points higher in the T4-treated subgroup less than 27 weeks gestational age. It may be that the most preterm infants, eg, those less than 27 weeks of age, are at a disadvantage compared with their intrauterine counterparts, in that they lack the maternal thyroid hormone contribution and are forced to adapt to extrauterine life before their hypothalamic-pituitary-thyroid axis is mature enough to deal with tissue thyroxine demands. Further controlled studies are needed to determine if this subgroup of infants indeed may benefit from transient thyroid hormone supplementation.

Gestational Age↗
PubMed1999

Congenital hypothyroidism: etiologies, diagnosis, and management.

Congenital hypothyroidism is a common preventable cause of mental retardation. The overall incidence is approximately 1:4000; females are affected about twice as often as males. Approximately 85% of cases are sporadic, while 15% are hereditary. The most common sporadic etiology is thyroid dysgenesis, with ectopic glands more common than aplasia or hypoplasia. While the pathogenesis of dysgenesis is largely unknown, some cases are now discovered to be the result of mutations in the transcription factors PAX-8 and TTF-2. Loss of function mutations in the thyrotropin (TSH) receptor have been demonstrated to cause some familial forms of athyreosis. The most common hereditary etiology is the inborn errors of thyroxine (T4) synthesis. Recent mutations have been described in the genes coding for the sodium/iodide symporter, thyroid peroxidase (TPO), and thyroglobulin. Transplacental passage of a maternal thyrotropin receptor blocking antibody (TRB-Ab) causes a transient form of familial congenital hypothyroidism. The vast majority of infants are now diagnosed after detection through newborn screening programs using a primary T4-backup TSH or primary TSH test. Screening test results must be confirmed by serum thyroid function tests. Thyroid scintigraphy, using 99mTc or 123I, is the most accurate diagnostic test to detect thyroid dysgenesis or one of the inborn errors of T4 synthesis. Thyroid sonography is nearly as accurate, but it may miss some cases of ectopic glands. If maternal antibody-mediated hypothyroidism is suspected, measurement of maternal and/or neonatal TRB-Ab will confirm the diagnosis. The goals of treatment are to raise the serum T4 as rapidly as possible into the normal range, adjust the levothyroxine dose with growth to keep the serum T4 (or free T4) in the upper half of the normal range and the TSH normal, and maintain normal growth and development while avoiding overtreatment. An initial starting dose of 10-15 microg/kg per day is recommended; this dose will decrease on a weight basis over time. Serum T4 (or free T4) and TSH should be monitored every 1-2 months in the first year of life and every 2-3 months in the second and third years.

Congenital Hypothyroidism↗
PubMed1997

Adult height in growth hormone (GH)-deficient children treated with biosynthetic GH. The Genentech Growth Study Group.

Near-adult height (AH) was determined in 121 children (72 males and 49 females) with GH deficiency (GHD) who were prepubertal when they began treatment with recombinant DNA-derived preparations of human GH. AH as a SD score was -0.7 +/- 1.2 (mean +/- SD), significantly greater than the pretreatment height SD score (-3.1 +/- 1.2), the predicted AH SD score (-2.2 +/- 1.2; Bayley-Pinneau method), and the height SD score at the start of puberty (-1.9 +/- 1.3). In contrast to studies of GH treatment outcome, which used pituitary-derived GH (pit-GH) in lower doses, we found that males did not have a higher AH SD score than females, spontaneous puberty did not diminish AH, and AH was significantly greater than that predicted at the start of GH treatment. In a multiple regression equation, the statistically significant variables (all P < 0.0001) related to AH (r2 = 0.70) were the following: duration of treatment with GH, sex (males were taller than females, as expected for the normal population), age (younger children had a greater AH) and height at the start of GH, and growth rate during first year of GH. For the AH SD score (r2 = 0.47), pretreatment predicted AH, duration of GH, and bone age delay were significant (P < 0.0002) explanatory variables. Bone age delay (chronological age-bone age) had a negative impact on the AH SD score. Target height, etiology of GHD, previous treatment with pituitary GH, and the presence or absence of spontaneous puberty did not significantly improve the prediction of AH. Early diagnosis of GHD and continuous treatment with larger doses of GH to near AH should improve the outcome in children with short stature due to GHD.

Body Height↗
PubMed1996

Sponastrime dysplasia: five new cases and review of nine previously published cases.

Sponastrime dysplasia (SD) is a dwarfing autosomal recessive short-limb bone dysplasia. The diagnosis is established by a combination of clinical and radiological findings of which the radiological are the more specific. The current diagnostic criteria are ambiguous as demonstrated by the fact that, in our opinion, three of the five patients reported since the original article do not have this condition. Comparison of our five patients and the 9 published patients has led to development of more specific diagnostic criteria. Previously undescribed complications of this condition are subglottic stenosis and tracheo-broncho-malacia, developmental coxa vara, and avascular necrosis of the capital femoral epiphyses.

Adolescent↗
PubMed1996

Physician and clinic charges for diagnosing growth hormone deficiency.

Physician and clinic charges for diagnosing growth hormone deficiency (GHD) in children are not generally known, whereas the charges for purchasing growth hormone (GH) are known. We recently surveyed the charges submitted to third-party payers for diagnosing GHD in five pediatric endocrine clinics throughout the United States: the Albert Einstein College of Medicine, Baylor College of Medicine, Health Science Schools of the State University of New York at Buffalo, Oregon Health Sciences University, and the University of Chicago. The financial data analyzed included charges for physician services and for GH testing. Different approaches to the medical examination of children with suspected GHD at these clinics prevented any comparison of physician or GH testing charges. However, the charges for diagnosing GHD could be determined for each pediatric endocrine clinic if the methods of examination were not considered. Contractual adjustments, net revenues, costs, and net margins were not surveyed. Subjective comments from the study sites suggest significantly reduced reimbursement amounts. We conclude that the total charges for diagnosing GHD submitted to third-party payers at these institutions averaged $1719.

Child↗
PubMed1994

Activating mutation in the stimulatory guanine nucleotide-binding protein in an infant with Cushing's syndrome and nodular adrenal hyperplasia.

Cushing's syndrome in infancy is uncommon. In this report, we describe an infant with ACTH-independent Cushing's syndrome in which an activating mutation in the stimulatory G-protein (Gs alpha) was detected. The patient presented at 3 months of age with Cushingoid features, poor linear growth, and elevated liver enzymes. Plasma ACTH and dexamethasone suppression test results were consistent with ACTH-independent Cushing's syndrome, and a subsequent adrenalectomy revealed bilateral adrenocorticonodular hyperplasia. Asymptomatic lesions consistent with fibrous dysplasia were later detected on bone scan. Genomic DNA was extracted from adrenal, liver, and blood and amplified by polymerase chain reaction with Gs alpha exon 8 primers. Using allele-specific oligonucleotide hybridization, the DNA was probed for known Gs alpha-activating mutations. A point mutation coding for an arginine to cysteine substitution at codon 201 of exon 8 was detected in genomic DNA from this infant's adrenal, liver, and leukocytes. The mutation was detected in nodular adrenal tissue, but was essentially absent in normal adrenal tissue. Activating mutations in the Gs alpha gene have previously been described in GH-secreting tumors, thyroid adenomas, and the McCune-Albright syndrome and are probably involved in the pathogenesis of adrenocorticonodular hyperplasia in this infant with Cushing's syndrome.

Adrenal Hyperplasia, Congenital↗
PubMed1994

Adolescent Thyroid Disorders.

Thyroid disorders are common in adolescents; in fact, they occurred in 3.7% of children between the ages of 11 and 18 in one study. Early recognition and treatment of these conditions can help to minimize their effects. Here, the author details the epidemiology, diagnosis, and clinical management of hypothyroidism, hyperthyroidism, thyroid nodules, and cancer.

Journal Article↗
PubMed1993

Thyroxine-binding globulin deficiency detected by newborn screening.

We examined the results of the Northwest Regional Screening Program from May 1975 to June 1991 to determine the prevalence of inherited thyroxine-binding globulin (TBG) deficiency and its effect on thyroid hormone concentrations in infants. Serum thyroxine (T4), triiodothyronine resin uptake (T3RU), and thyrotropin values were requested of physicians caring for all infants with a single filter paper T4 level < 38.6 nmol/L (3 micrograms/dl) or a T4 level < 3rd percentile on two filter paper tests (at birth and 2 to 6 weeks of age). From 1,367,724 infants screened in five states, TBG deficiency, an X-linked disorder, was identified in 317 infants (285 boys). For the entire screening program the calculated frequency of TBG deficiency was 1:4315 infants (1:2400 for boys). In Oregon, where 95% of infants have two screening tests performed, the calculated frequency was somewhat higher (1:3080 infants; 1712 boys) and is probably more accurate. The mean serum T4 concentration for TBG-deficient boys was 41.9 nmol/L (3.26 micrograms/dl); 31% had values < 25.7 nmol/L (2.0 micrograms/dl). The mean serum T4 concentration for TBG-deficient girls was 60.2 nmol/L (4.68 micrograms/dl), with none < 2.0 micrograms/dl. The mean T3RU value was 0.472 in TBG-deficient boys, and 0.412 in TBG-deficient girls; the T3RU value was > 0.55 in 24% of TBG-deficient boys but was > 0.55 in only one girl. Free serum T4 levels were normal in all 56 TBG-deficient infants studied, and TBG levels were low in all 20 infants studied. Inherited TBG deficiency is common in boys in the Northwest, with a frequency of 1:1700 and a male/female ratio of 8.9:1. Boys with TBG deficiency have mild, moderate, or severe alterations in total T4 and T3RU values, but severe deficiency is rare in girls.

Female↗
PubMed1992

Human growth hormone. Who is a candidate for treatment?

The one accepted indication for human growth hormone (hGH) treatment is classic hGH deficiency, and girls with Turner's syndrome will soon be added to this category. The unlimited supply of recombinant hGH has expanded investigational trials to include many growth disorders and metabolic conditions, but continued investigation and accumulation of information through well-designed and controlled studies are required for these uses. I believe there is no indication to treat short, normally growing children whose predicted adult height is normal for their genetic potential. Physicians must remember that even if only children under the third percentile on growth charts are treated with hGH, a new population will be created that falls below that percentile. Two excellent, recent reviews of current use of hGH therapy are available for further reading on this subject.

Child↗
PubMed1991

Constitutional delay of growth: expected versus final adult height.

Constitutional delay of growth and puberty is believed to represent a variation of normal growth, and it is expected that children with this condition will grow for a longer duration than average and reach a height that is normal for their genetic potential. The records of children with constitutional delay of growth and puberty who were initially seen in the Pediatric Endocrine Clinic at the Oregon Health Sciences University between 1975 and 1983 were retrospectively reviewed. Criteria for study included a height more than 2 SD below the mean, a significantly delayed bone age, and a normal growth velocity on follow-up. Forty-two subjects were located and final adult height measurements were obtained. AT contact, the 29 male subjects (mean age = 23.9 years) were 169.5 +/- 4.5 cm tall (mean +/- SD), and the 13 female subjects (mean age = 20.5 years) were 156 +/- 3.8 cm tall. Adult height predictions during follow-up, using either the Bayley-Pinneau or Roche-Wainer-Thissen method, were close to final adult heights. The males were 1.2 SD and the females 1.3 SD below the 50th percentile as adults. This finding was not fully explained by genetic short stature; the males fell 5.1 cm and the females 5.3 cm below target heights based on midparental heights. It is concluded that this discrepancy is most likely explained by a selection bias of the shortest children referred to and observed in a subspecialty clinic, although a defect in human growth hormone secretion or function in children at the far end of the spectrum of constitutional delay of growth and puberty cannot be excluded.

Adult↗
PubMed1987

Is Angelman syndrome an alternate result of del(15)(q11q13)?

Two unrelated females, age 15 and 5 years respectively, were studied cytogenetically because of severe mental retardation, seizures and ataxia-like incoordination. A similar deletion of the proximal long arm of chromosome 15 was found in both patients. Re-evaluation showed no voracious appetite or obesity; normal size of hands and feet, minimal to no hypotonia by history or examination and facial features not typical of the Prader-Willi syndrome. However, the facial appearance of the girls was similar to each other with mild hypertelorism. The similarity of these girls and dissimilarity to Prader-Willi syndrome suggest a different syndrome, perhaps the result of deletion of a different segment of 15q. The findings of ataxic-like movements, frequent, unprovoked and prolonged bouts of laughter and facial appearance are more compatible with the diagnosis of Angelman syndrome.

Adolescent↗
PubMed1987

Hypoglycemia of infancy and childhood.

Hypoglycemia of infancy and childhood represents a treatable cause of mental retardation and seizures. Most neonates with hypoglycemia have transient disorders, but with persistent hypoglycemia one must consider hyperinsulinism, hypopituitarism, or hereditary hepatic enzyme deficiencies. Outside of the neonatal period, ketotic hypoglycemia is the most common cause of hypoglycemia in childhood. One cannot overemphasize the value of obtaining certain diagnostic tests at the presentation of spontaneous hypoglycemia, including blood for insulin, cortisol, growth hormone, and urine for ketone bodies. Supportive treatment with intravenous glucose to maintain the blood glucose greater than 50 mg/dl is important until a diagnosis is established allowing specific therapy aimed at the underlying disorder.

Blood Glucose↗
PubMed1987

Diagnosis and treatment of hypothyroidism in children.

Congenital hypothyroidism is a relatively common endocrine disorder, affecting one in 4000 newborn infants. Undiagnosed and untreated congenital hypothyroidism will result in un-toward consequences, including mental retardation and other significant neurologic sequelae. For these reasons, programs to screen newborns were developed to detect congenital hypothyroidism before clinical features become obvious enough to suggest the diagnosis. The most common clinical features include prolonged jaundice, skin mottling, hypotonia, umbilical hernia, constipation, and macroglossia. Congenital hypothyroidism may be caused by several different disorders; ectopic thyroid glands represent the most common cause. There is accumulating evidence that autoimmune thyroid disease as manifested by TBII may be the cause of thyroid dysgenesis in some cases. The diagnosis is easily confirmed by finding a low serum free T4 or total T4 and elevated serum TSH concentration. The treatment of choice is levothyroxine; these infants must be followed carefully to ensure normal growth and development and maintenance of serum T4 and TSH within the normal ranges. With appropriate treatment and follow-up, the large majority of these infants have an excellent prognosis, with an IQ no different from comparison populations. However, it appears that there is still a small percentage of infants who are the most severely affected, who manifest the lowest serum T4 levels, thyroid aplasia, and retarded bone ages, and who may run the highest risk for some degree of retardation and other neurologic sequelae. Acquired hypothyroidism is also a relatively common disorder, occurring in one in 500 to one in 1000 school-age children. These children most commonly have a slowdown in growth, short stature, a goiter, and a drop in school performance. Other clinical features may be subtle or absent except in more severe or long-standing cases. The most common cause is chronic lymphocytic thyroiditis. The diagnosis is easily established by finding low serum-free T4 or total T4 and elevated serum TSH concentrations. Again, levothyroxine is the treatment of choice. With appropriate treatment and follow-up, all clinical features that develop after age 3 should be reversible and the prognosis should therefore be very good.

Child↗
PubMed1985

Effect of growth hormone replacement on development of hypothyroidism and hyperlipidemia.

To determine the frequency with which hypothyroidism develops during human growth hormone therapy and to corroborate its onset with blood lipid changes, we measured growth rate, serum T4 and T3, and plasma cholesterol, triglyceride, and lipoprotein concentrations at 4-month intervals for a year in two subgroups of hGH-deficient children. The first group was initially euthyroxinemic (n = 16), and the second was TSH deficient and therefore already receiving thyroxine (n = 15). Basal plasma concentrations of total and low-density lipoprotein cholesterol and, to a lesser extent, plasma triglycerides were increased in both groups compared with an age-matched reference group. Basal plasma cholesterol levels were not statistically different in the euthyroxinemic and thyroxine-treated subgroups, and hGH treatment for a year did not lower lipid values in either subgroup. With hGH replacement, 25% of the euthyroxinemic patients experienced a slowdown in growth rate (3.2 +/- 0.7 cm/yr) associated with decreasing T4 (4.8 +/- 1.1 micrograms/dl) and increasing cholesterol concentrations (218 +/- 23 mg/dl); with thyroxine treatment, the growth rate improved (6.9 +/- 2.2 cm/yr), T4 increased (10.0 +/- 4.0 micrograms/dl), and cholesterol decreased (173 +/- 44 mg/dl, P less than 0.05). Although our results do not justify routine thyroid replacement, they do indicate that hypothyroxinemia and hypercholesterolemia may precede the growth slowdown during hGH treatment, and the need to monitor thyroid function at this time.

Adolescent↗