S. Douglas Frasier

Gonadoblastoma associated with pure gonadal dysgenesis in monozygous twins

Monozygous twins with pure gonadal dysgenesis and associated gonadoblastoma are presented. There were no signs of Turners syndrome and chromosome analysis revealed a 44A-XY karyotype. The literature regarding gonadoblastoma is reviewed. The association between gonadal tumors and abnormalities of gonadal differentiation is emphasized.

Successful Outcome of Pregnancy in Women with Hypothyroidism

Published data on the influence of hypothyroidism on fertility, gestation, and the offspring are controversial. We studied nine hypothyroid women during 11 pregnancies. Mean serum values for thyroxine, triiodothyronine (T3), resin T3 uptake ratio, and thyroid-stimulating hormone were 2.3 microgram/dL, 82 ng/dL, 0.64, and 105 mU/mL, respectively. Four patients had iatrogenic hypothyroidism (three remote thyroidectomy, one remote 131I therapy), two Hashimotos thyroiditis, and three idiopathic primary hypothyroidism. Seven patients first presented untreated after the 24th week of gestation. Two patients needed cesarean section; seven delivered vaginally. There was one stillborn infant in the only patient with pre-eclampsia. Another infant had Downs syndrome and an ostium primum defect (mothers age, 41 years). The remaining nine infants were normal at birth. All placentas were normal. Follow-up in seven infants up to 2.7 years showed normal thyroid function and somatic development. Infants of hypothyroid mothers may be normal because their hypothalamic-pituitary thyroid axis develops independently from the mother.

The serum growth-hormone response to hypoglycemia in dwarfism

The serum growth-hormone response to insulin-induced hypoglycemia has been measured in control subjects and patients with dwarfism of various causes. The normal response has been defined and applied to the assessment of growth-hormone function in patients with growth retardation. Definitive evaluation of growth-hormone responsiveness was possible in 58 of 59 patients with dwarfism.

The not-so-good old days : Working with pituitary growth hormone in North America, 1956 to 1985

Before 1985 the use of growth hormone (GH) was governed by a philosophy of scarcity and conservation of resources. Between 1956 and 1959 human pituitary GH was shown to be effective. The competition for gland collection and extraction that followed benefited only certain patients with motivated parents and only a few investigators. To maximize gland collection, the distribution of GH for clinical investigation, and the number of patients who could be treated, the National Institutes of Health and the College of American Pathologists formed the National Pituitary Agency (NPA). In Canada a similar program was developed by the Canadian Medical Research Council. For more than 20 years the NPA supervised most of the GH treatment in the United States. Commercial pituitary GH entered the U.S. market in 1976, and competition soon appeared. Patients treated through the NPA were subjects in clinical studies for part of the first year of treatment, after which the limited availability of GH dictated treatment for only part of the year and caps on final heights. By 1984 treatment was year round and the height caps largely unenforced. In the last year of its distribution NPA GH was used in 2450 patients in the United States and commercial pituitary GH was used in 600 to 800; slightly more than 300 patients were being treated in Canada. And then, in 1985, came Creutzfeldt-Jacob disease. While the not-so-good old days are gone and need not be lamented, there remains virtue in a conservative therapeutic philosophy. If anything can be learned from the use of pituitary GH in children, it is a healthy respect for the law of unintended consequences.

Degenerative neurologic disease in patients formerly treated with human growth hormone

One or more lots of pituitary GH supplied by the NHPP may have been contaminated with CJD pathogen. If so, it is probable that the contaminated hormone was dispensed before 1978, and there is reason to believe that it was dispensed in the late 1960s. The contamination may have been limited to one lot of GH, but this is not known with certainty. Purification methods used by the NHPP since 1978 probably exclude the CJD pathogen, but this is not yet certain. The risk to patients treated since 1978, therefore, probably is low. There is no evidence to date that GH from either of the pharmaceutical suppliers has been or is contaminated. Purification procedures used by these sources also should exclude the pathogen. To exclude the possibility that they are contaminated with the CJD pathogen, 1 1/2 to 3 years will be required to test batches of the pituitary GH used previously. The experiment needed to show that the purification method used by NHPP excludes the scrapie agent will take up to 1 year. Planning for epidemiologic studies in patients treated with pituitary GH is under way. Biosynthetic GH prepared by recombinant DNA techniques has been in clinical trial in the United States for 3 1/2 years. It has been shown to be as effective as pituitary GH in promoting growth. However, it produces a higher incidence of GH antibodies than pituitary GH preparations do. Pediatric endocrinologists support the FDA in its effort to gather the information needed to approve biosynthetic GH for treatment of GH deficiency at an early date.

Adolescent acromegaly: Studies of growth- hormone and insulin metabolism

Growth-hormone and insulin metabolism have been investigated in an adolescentmale subject with acromegaly. The serum concentration of growth hormone was elevated and unresponsive to changes in the concentration of blood glucose. The insulin response to glucose loading was increased, both preoperatively and seven months following surgical therapy.

Buccal smears in the newborn female

Buccal smears obtained from newborn females on the first day of life showed a significantly lower incidence of chromatin-positive cells than smears obtained from normal older females. A low chromatin count on the first few days of life may be normal. By the fourth day of life, the incidence of chromatin-positive cells was no longer low; a decreased chromatin count at this time may indicate an abnormality of the sex chromosomes.

Dwarfism and mental retardation: the serum growth hormone response to hypoglycemia.

Summary The serum growth hormone response to insulin-induced hypoglycemia was studied in 58 institutionalized mentally deficient subjects with growth retardation and in 23 institutionalized mentally retarded subjects with normal height. The fasting, peak, and increased serum concentrations of growth hormone were the same in these 2 groups. These studies indicate that functional abnormalities in growth hormone secretion do not play a role in the pathogenesis of dwarfism associated with mental retardation.

EPISODIC SECRETION OF GONADOTROPINS IN CHILDREN AND ADOLESCENTS

The concentrations of LH and FSH were determined in serum samples obtained from 7 normal girls (ages 9.5-16.5 years) and 8 normal boys (ages 9.0-16.8 years) at 15 minute intervals during a 4 hour period. An episodic pattern of LH but not FSH secretion was seen in all subjects. The number of episodes per subject ranged from 1 to 3. Time of occurrence of secretion episodes ranged from 0 (initial sample) to 240 minutes with a mean (± SD) of 133.8 ± 65.7 minutes. The incremental rise in LH concentration ranged from 1.1-5.3 mIu/ml with a mean (± SD) of 2.8 ± 1.3 mIu/ml. The mean (± SD) percentage increment was 41.6 ± 9.8% with a range of 31.3-58.0%. No sex difference in the number of secretion episodes, incremental rise in LH concentration or time of occurrence of secretion episode was demonstrated. Mean LH and FSH concentrations increased with age and stage of sexual development. All LH and FSH concentrations were within the range previously reported for normal girls and boys. This data indicates that FSH is not secreted episodically in normal children and adolescents. The previous observation of episodic LH secretion is confirmed. It is speculated that differential feedback of the sex steroids is responsible for the lack of concurrence in LH and FSH secretion patterns.

Cryohypophysectomy for Acromegaly.

Excerpt Stereotaxic transnasal, transphenoidal cryoblation was performed in seven patients with pituitary adenomas causing symptomatic acromegaly. The pituitary tumors were proved by needle biopsy ...