Using a small dose of growth hormone, growth responsiveness was evaluated in preadolescent short children with a diagnosis of hypopituitarism (N = 35) and/or idiopathic short stature (N = 59) who were studied before and during growth hormone therapy. Within each group, four dosage groups were established using a growth hormone dose of either 0.15 mg/kg or 0.30 mg/kg per week. No significant differences in any of the pretreatment parameters were noted, except for the endogenous growth hormone levels in the hypopituitary patients. Growth rates of the two diagnostic groups and the four dosage groups did not differ significantly. It is suggested that auxology rather than testing for levels of endogenous growth hormone should be the criterion for growth hormone therapy in the treatment of significantly short children.

The growth promoting effects of once nightly subcutaneous injections of growth hormone releasing hormone (GHRH) 1-29 (30 microg/kg) for 6 months were studied in 16 slowly growing prepubertal children with idiopathic short stature (ISS; Group 1) and 8 similar children with growth hormone neurosecretory dysfunction (GHND; Group 2). Each child underwent endogenous growth hormone evaluation using both pharmacological and physiological testing; each had stimulated values > 10 microg/l and were subsequently placed into one of two groups based on pooled 12-hour overnight GH of < or > or = 3 microg/l. Each patient was followed every three months for one year. There were no significant differences in the two groups throughout the study with the exception of the endogenous GH levels. Both groups responded to GHRH therapy with similar significant increases in their rates of growth. Although a subset of patients (6 of 21) continued to grow at a rate significantly greater than the pre-therapy rate of growth, overall rates of growth were not significantly different from the pre-therapy growth rates 6 months following the discontinuation of GHRH treatment. We conclude that GHRH 1-29, given in the doses provided, leads to similar changes in growth rates in short, slowly growing children who are GH sufficient and those with GHND. Despite prior reports to the contrary, GHND patients do not experience a sustained increased in growth rate upon discontinuation of GHRH.

Ambiguous genitalia and sex reversal are well recognized anomalies associated with a number of malformation syndromes /1,2/. When genital ambiguity or complete sex reversal is noted as part of a syndrome diagnosis, an underlying hormonal disturbance is often not considered as the primary etiology of the ambiguity; rather, the genital abnormality is thought to be one of multiple malformations resulting from a primary defect in overall development. This does not, however, reduce the necessity for a complete endocrine evaluation, especially when the syndrome diagnosis is unclear or has not yet been established clinically. A newborn infant with multiple congenital anomalies, including complete sex reversal, was diagnosed with the Smith-Lemli-Opitz syndrome, Type II (SLO-II). Although the patient expired before the endocrine evaluation was completed, sufficient data were obtained to allow for a hypothesis concerning the biochemical pathophysiology of the sex reversal.

The minimal effective dose of growth hormone (GH) to promote growth in children on dialysis or following renal transplantation remains unsettled. In order to study the issue, "low-dose" GH was administered to children with end-stage renal disease (ESRD) receiving chronic automated peritoneal dialysis (APD, n = 6, 4 males, 2 females) or following renal transplantation (T, n = 9, 8 males, 1 female). No APD patient was GH deficient, while 1 T patient (no. 2) had data consistent with GH deficiency, although he was obese (body mass index = 34 kg/m2). The mean dose of GH after 6 and 12 months of treatment was 0.16 +/- 0.02 and 0.22 +/- 0.07 versus 0.16 +/- 0.03 and 0.27 +/- 0.21 mg/kg per week for APD and T patients, respectively. When analyzing all patients, there were no significant differences before or after 6 and 12 months of GH therapy within or between the two groups, in terms of height velocity, bone age, renal function (in the T group) and height Z-scores (Z-Ht). However, the height velocity Z-score (Z-HV) increased significantly at 6 and 12 months compared with baseline in the APD patients only (P < 0.05). When the 2 T patients with the most impaired renal function were excluded from the analysis, Z-HV also increased significantly in the T patients after 12 months of GH (P < 0.02). We conclude that following "low-dose" GH therapy, children with ESRD treated with APD or T have similar increases in HV, allowing maintenance of Z-Ht but not "catch-up" growth.

Seven children with significant idiopathic short stature (SISS) whose heights were significantly below the third percentile (SD score for height —2.5 to —3.5) and who had normal levels of growth hormone (GH) were treated with growth hormone releasing hormone (GH‐RH) in a dose of 30 /μg/kg/day. Therapy was discontinued if patients failed to increase their rates of growth by more than 2.0 cm/year over their pre‐therapy growth rate. Treatment was discontinued in two of the patients after 12 months but was continued in the other five for 24 months. These data demonstrate that some patients with SISS grow well during the first 2 years of treatment with GH‐RH.

In an attempt to rest the beta cells of newly diagnosed children with type I diabetes mellitus (IDDM) and thus possibly preserve beta cell function, ten children were given Octreotide, a somatostatin analog, for the first 21 days after diagnosis. Ten age-matched diabetic children served as controls. Although there were no differences in either insulin requirements or in hemoglobin A1 levels, there were significant increases in the glucagon-stimulated C-peptide levels of the experimental group at six and 12 months after diagnosis, compared to control patients.

A 14.8 year old boy was evaluated for galactorrhea of two months duration and growth deceleration for greater than three years. He was 3.7 standard deviations (SD) below the mean for age in height and euthyroid with uncompromised vision, bilateral galactorrhea, and pubertal arrest. MRI demonstrated a 10 x 8 mm left pituitary mass. Bone age was 11.5 years. Serum prolactin (PRL) decreased by more than 85% after 5 weeks of treatment with bromocriptine (Br). After five months, the prolactinoma (PRLoma) measured 5 x 4 mm. Hypothalamic-pituitary function indicated growth hormone (GH) deficiency and hypogonadotropic hypogonadism as assessed by ITT-TRH-GnRH-clonidine. After nine months of Br, despite return of adequate gonadotropin and GH secretion as assessed by repeat ITT-TRH-GnRH-clonidine, pooled 12 hour nocturnal spontaneous GH secretion, and clinical progression of puberty, there was no linear ''catch-up growth'' (growth rate = 4.4 cm/yr and height 4.2 SD below the mean for age). Growth rate increased following supplemental GH administration without untoward effect. We conclude that there may be discordance/lag between reduction in secretion and size of PRLomas and growth despite resolution of other anterior pituitary dysfunction. Other possibilities are discussed.

A variety of tumor products (glycoproteins, enzymes, and hormones), as well as oncofetal and cell-surface antigens, have been used as tumor markers, ie, as sensitive (but nonspecific) tools to determine the presence of a tumor. One such marker is alpha-fetoprotein (AFP), a 70 000–molecular weight glycoprotein that is produced by the yolk sac, fetal liver, and intestinal epithelium. The circumstances that cause false elevations in the serum concentration of AFP are not completely certain. In addition to decreased levels of thyroxine (T4) and triiodothyronine, hypothyroidism is associated with a variety of biochemical perturbations, including diminished urinary excretion of calcium, low serum concentrations of alkaline phosphatase and insulin-like growth factor I, and elevated serum concentrations of triglycerides and cholesterol. A patient with hepatoblastoma, acquired hypothyroidism, and a persistent elevation in AFP prompted this investigation of the effect of hypothyroidism on serum concentrations of AFP in children. Patient Report. A 15-month-old

Adrenal abnormalities are rarely recognized in association with the nephrotic syndrome. This report describes the hospital course of an 11-week-old child with congenital nephrotic syndrome secondary to diffuse mesangial sclerosis, in addition to hypothyroidism and hypoadrenocorticism.

The influence of diabetic control on the secretion of sex-steroid hormones and gonadotropins in children and adolescents was evaluated in 24 boys (age at entry into the study: 10 10/12 to 17 2/12 yrs) and 19 girls (age at entry into the study: 10 1/12 to 17 4 /12 yrs). They were seen over a two year period during which we studied: LH, FSH, DHEAS, testosterone in the boys and estradiol in the girls. These hormonal levels were related in each patient to the glycosylated hemoglobin levels which ranged from 5.6-16.0% for the total study population. We were unable to demonstrate a correlation between the hormonal levels and the degree of clinical control. Whether this is indicative of a lack of influence of diabetes on the secretion of these hormones or whether the care of diabetic patients in medical centers was such that adverse effects were not seen, requires additional study. INTRODUCTION There are very few published reports on the effect of achieving good diabetic control on sexual development. In earlier studies delayed menarche was noted in girls who developed diabetes in the pre-pubertal period /1 -3/. The few published reports on the effect of attaining more rigid control over diabetes on the age of menarche show contrasting results. Some have noted that the age of menarche in well-controlled diabetics is now essentially normal /4 ,5/ , while others report no such improvement

Somatomedin-C (Sm-C) and growth hormone (GH) levels were determined before, during and after human growth hormone (hGH) treatment in 18 children with small-for-date short stature ( SDSS ), 7 children with significant idiopathic short stature ( SISS ) and 14 children with hypopituitarism. Data on the acute effects of hGH on Sm-C were compared to growth responses after 6 to 9 months therapy. Eleven of the 25 non-hypopituitary patients with normal basal and stimulated serum GH levels and normal basal Sm-C levels increased their rates of growth more than 3.0 cm/year. This compared with 11 of the 14 children with hypopituitarism who increased their rates of growth by at least 3.0 cm/year when treated with GH. Neither the basal somatomedin levels nor the GH-stimulated somatomedin levels correlated well with subsequent growth in the non-hypopituitary patients. These studies indicate that GH therapy may be effective in treating short stature in children without demonstrable GH deficiency.

A child with combined hypopituitarism and an undefined skeletal dysplasia is described. The hypopituitarism was manifested by post-natal growth failure, excessive sc fat, micropenis, and poor growth hormone response to provocative tests. Disproportionately short limbs, especially distally, and skeletal radiographs showing generalized brachydactyly, cone epiphyses of the phalanges and ossification defects in the proximal femoral metaphyses characterized the skeletal dysplasia. In contrast to the normal structure of the endochondral growth plate seen in hypopituitarism, the growth plate in this child was structurally abnormal; there was no differentiation of chondrocytes into hypertrophic and degenerative cells. Treatment with hGH for 8 months was associated with the appearance of chondrocyte differentiation, the restoration of growth plate structure to almost normal and a substantial increase in growth rate. There was no change in his disproportion or improvement in his radiographic abnormalities. These observations suggest that hGH may influence growth plate structure in certain instances and that this may be associated with increased linear growth.

From the Children’s Mercy Hospital, The University of Missouri, Kansas City School of Medicine, 24th at Gillham Road, Kansas City, Missouri 64108. Received for publication December 1, 1978; revised January, 1979 and accepted February 8, 1979. THYROID DYSFUNCTION in patients with I~o~vn’s syndrome has attracted the attention of investigators for many years. Although the majority of children with Down’s syndrome, appear to have normal thyroid function, hypoand hyperthyroidism, as we!! as demon-

The unique problems of three infants who developed diabetes mellitus at 13 months of age or younger are discussed. These problems include: the administration of small doses of insulin; the difficulty in attaining control; and the evaluation of urinary sugar content. Suggestions for care are made.

The findings in three children with ocular palsies are reported in this paper. Two had insulin-requiring diabetes and one demonstrated only an abnormal I.V. glucose tolerance test. In the first patient the condition resolved in four weeks; in the second it had not fully resolved after 21 months, and in the third patient surgery was required for correction after seven months. We suggest that any child who develops a sudden ocular palsy should be examined for diabetes mellitus.