Growth during and after a trial of growth hormone releasing hormone 1-29 in children with idiopathic short stature or growth hormone neurosecretory dysfunction.

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.

Effects of long-term growth hormone releasing hormone 1-29 in significantly short children.

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 micrograms/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.

"Low-dose" growth hormone therapy during peritoneal dialysis or following renal transplantation.

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.

A randomized trial of a somatostatin analog for preserving beta cell function in children with insulin dependent diabetes mellitus.

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.

Prolactinoma associated with transient growth hormone deficiency but persistent growth retardation.

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.

Congenital nephrosis in association with hypothyroidism and hypoadrenocorticism.

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 oral contraceptives on hormonal and metabolic homeostasis in young adolescents.

In order to evaluate the effects of oral contraceptives on metabolic and endocrine function in teenagers, Norinyl 1/50 was begun in 46 12-17-year-old girls after a 16-hour-fasting blood sample was obtained for glucose, insulin, glucagon, growth hormone, luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, prolactin, gluconeogenic substrates, total lipids, and cholesterol. Sampling was repeated at 6 and 12 months of therapy. Of the 46 patients enrolled in the study, 23 returned for follow-up after 6 months, and 13 completed the study. Blood sampling after 6 and 12 months of therapy demonstrated no significant changes (p greater than 0.05). Our results suggest that there were no changes in the metabolic or endocrine functions studied at 6 and 12 months on a medium-dose contraceptive agent.

PIP: In order to evaluate the effects of oral contraceptives on metabolic and endocrine function in teenagers, Norinyl 1/50 was begun in 46 12-17-year-old girls after a 16-hour-fasting flood sample was obtained for glucose, insulin, glucagon, growth hormone, lutenizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, prolactin, gluconeogenic substrates, total lipids, and cholesterol. Sampling was repeated at 6 and 12 months of therapy. Of the 46 patients enrolled in the study, 23 returned for follow-up after 6 months, and 13 completed the study. Blood sampling after 6 and 12 months of therapy demonstrated no significant changes (p 0.05). Our results suggest that there were no changes in the metabolic or endocrine functions studied at 6 and 12 months on a medium-dose contraceptive agent. Study participants had requested an oral contraceptive and informed consent was obtained from all participants and their parents or guardians. The 36 black and 10 white patients ranged in age from 12.17 to 17.08 years with a mean of 15.0 years. Sexual development was Tanner stage 4 or 5. Mean gynecologic age was 2.83 years.

Neonatal genital reconstruction.

It is evident from studies of boys who suffered a surgical catastrophe at a young age and were then assigned a female sex role that cultural and environmental influence are a potent determinant of a child's gender identity. It is imperative that parents have their child's sex assignment firmly fixed in their minds as early as possible. Early surgical correction of a child with ambiguous genitalia to conform to the sex of assignment will serve greatly to reinforce appropriate behavior in the parent. Such surgical intervention for diagnostic and reconstructive purposes is both desirable and safe in the first weeks of life.

Comparison of growth and somatomedin C responses following growth hormone treatment in children with small-for-date short stature, significant idiopathic short stature and hypopituitarism.

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.

Skeletal changes following growth hormone treatment in a child with combined hypopituitarism and a skeletal dysplasia.

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.

Problems in the care of the infant diabetic patient.

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.

Ocular palsies in children with diabetes mellitus.

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.