Growth Hormone Excretion Research Articles

Urinary excretion of human growth hormone in children with short stature: Correlation with pituitary secretion of human growth hormone

Thirty-five children with short-stature underwent insulin-loading and sleep tests for assessment of secretion of human growth hormone. Correlations between the levels of human growth hormone in the serum and urine during the tests were examined to elucidate the clinical significance of urinary human growth hormone levels in short children. The concentration and total amount of human growth hormone in the urine correlated significantly with the peak concentration of serum human growth hormone (r = 0.81, p less than 0.001 and r = 0.80, p less than 0.001, respectively) and the integrated concentration of human growth hormone (r = 0.85, p less than 0.001 and r = 0.85, p less than 0.001, respectively) in the insulin-loading test. The concentration and total amount of human growth hormone in the morning urine also correlated significantly with the peak concentration of serum human growth hormone (r = 0.80, p less than 0.001 and r = 0.70, p less than 0.001, respectively) and the integrated concentration of serum human growth hormone (r = 0.80, p less than 0.001 and r = 0.72, p less than 0.001, respectively) in the sleep test. The concentration or total amount of human growth hormone in the urine differed significantly among children with human growth hormone deficiency, those with nonendocrine short stature, and those with normal stature (p less than 0.05). These data suggest that measurement of human growth hormone in the urine may be used to assess secretion of human growth hormone, serving as a screening test for human growth hormone deficiency in children.

Relationship between urinary and serum growth hormone and pubertal status.

Urinary growth hormone (uGH) excretion and serum growth hormone concentrations have been compared in three groups of children. Group 1 consisted of 21 children who had had cranial irradiation as part of their treatment for acute lymphoblastic leukaemia; group 2, 18 normal children; and group 3, 12 boys with constitutional delay in growth and puberty who were in early puberty. Children in groups 1 and 2 each had a 24 hour serum growth hormone profile (sampling every 20 minutes) and concurrent urine collection. The 12 boys in group 3 had a total of 21 profiles (sampling every 15 minutes for 12 hours) and concurrent urine collections. In the prepubertal children (n = 17), in both groups 1 and 2, there was a significant correlation between mean serum growth hormone and total uGHng/g creatinine. There were also significant correlations between total uGHng/g creatinine and both peak serum growth hormone and mean amplitude of the pulses in the growth hormone profile. In the pubertal children (n = 22), in groups 1 and 2, whether combined or in separate groups, there was no significant correlation between total uGHng/g creatinine and mean serum growth hormone, peak serum growth hormone, or mean amplitude of the pulses in the growth hormone profile. In group 3 there were significant correlations between total uGHng/g creatinine and both the mean serum growth hormone and mean amplitude of the pulses in the profile. Therefore uGH estimations appear to correlate well with serum growth hormone profiles in children who are prepubertal or in early puberty, but not in those further advanced in pubertal development. These results may reflect a variation in the renal handling of growth hormone during pubertal development. uGH estimation may be an unreliable screening investigation for growth hormone sufficiency in mid to late puberty.

Chemical pathology of growth disorders

Growth disorders are characterized by two parameters - the absolute height measurement and the height velocity. The causes of growth failure can be classified as follows : endocrine, psychological, iatrogenic, chromosomal, nutritional, intrauterine, chronic disease and skeletal. I shall concentrate on the endocrine causes of disordered growth, in particular, abnormalities in the production of growth hormone (GH). Other endocrine abnormalities causing short stature include deficiency of thyroxine, excess Cortisol and delay in the production of sex steroids at puberty. GH is released from the anterior pituitary in a pulsatile fashion, with the greatest secretion occurring about one hour after the onset of sleep. Secretion of GH is stimulated by growth hormone releasing hormone (GHRH) and inhibited by somatostatin, both these peptides being released from the hypothalamus. GH exerts its growth promoting effects principally by acting on tissues, such as cartilage and muscle, to produce insulin-like growth factor I (IGFI) which probably acts locally in a paracrine fashion to stimulate growth. The clinical features of severe GH deficiency are relatively easy to recognize, but are less apparent in the child with partial lack of GH. The approach to the diagnosis of abnormal secretion of GH must include a complete clinical assessment, with appropriate auxological data and bone age. Provocation tests, to establish either partial or complete deficiency of GH, are based on either pharmacological or physiological stimuli. Other tests, used mainly for research, include measurement of the GH pulses over 24 hours, GHRH stimulation test and urinary GH excretion. 1GF1 measurement is of limited value in GH deficiency, but useful in states of GH excess. The introduction of biosynthetic GH has resulted in a broader spectrum of patients with growth disorders receiving treatment, and there is no longer the risk of transmission of slow virus infection, as occurred with the use of GH extracted from human pituitaries.

Twenty-four-hour plasma growth hormone (GH) profiles, urinary GH excretion, and plasma insulin-like growth factor-I and -II levels in prepubertal children with chronic renal insufficiency and severe growth retardation

We studied 24-h plasma GH profiles, maximal GH responses to arginine provocation and insulin-like growth factor-I (IGF-I) and IGF-II levels in plasma in 22 euthyroid prepubertal children (mean age, 9.5 yr) with chronic renal insufficiency (glomerular filtration rate, <20 mL/min-1.73 m2) and severe growth retardation [mean (±SD) height SD score (SDS), −2.8 (1.1)]. The 24-h GH profiles were analyzed using the Pulsar program. Girls had significantly higher 24-h GH secretion than boys (P < 0.004). Children with end-stage nephrotic syndrome had higher baseline GH levels and total area under the curve (AUCo) than patients with dysplastic kidneys (P < 0.05), while the area under the curve above baseline (AUCb) was similar in all types of renal diseases. The type of treatment (conservative, peritoneal, hemodialysis) did not significantly influence the 24-h GH secretion. No correlation was found between 24-h GH profiles and age, height SDS for chronological age, height velocity SDS for bone age, and weight for hei...

Urinary Growth Hormone Excretion During Puberty in Type 1 (Insulin‐dependent) Diabetes Mellitus

The excretion of urinary growth hormone was measured by a highly sensitive direct immunoradiometric assay in a cross-sectional study during puberty in 70 children with Type 1 (insulin-dependent) diabetes mellitus and 94 normal children. In normal children (n = 24) and diabetic children (n = 17) overnight urinary growth hormone excretion correlated significantly with the mean overnight plasma concentration (r = 0.70, p less than 0.001, and r = 0.70, p less than 0.001), indicating that urinary GH excretion reflects the circulating endogenous GH level. Overnight urinary growth hormone excretion increased during puberty. In normal and in diabetic children there was a peak in boys at genital stage 4 (both p less than 0.01), and in girls at breast stage 2 (both p less than 0.02). The diabetic children excreted more urinary growth hormone than the normal children at every pubertal stage. Excretion of albumin, retinol binding protein and N-acetyl-beta-D-glucosaminidase was measured in urine from 38 diabetic children. Urinary growth hormone correlated weakly with urinary albumin (r = 0.49, p less than 0.01), retinol binding protein (r = 0.42, p less than 0.01), and N-acetyl-beta-D-glucosaminidase (r = 0.43, p less than 0.01). Urinary GH excretion was not related to blood glucose control (HbA1) in boys (n = 31) or girls (n = 39). The measurement of urinary growth hormone provides an assessment of endogenous growth hormone during puberty in normal and diabetic children. However, caution must be exercised in interpreting urinary growth hormone data from diabetic patients with increased excretion of albumin and retinol binding protein.

Urinary Growth Hormone Excretion in 657 Healthy Children and Adults: Normal Values, Inter- and Intraindividual Variations

Urinary growth hormone (u-GH) excretion was measured in 547 healthy children and 110 adults by ELISA with a detection limit of 1.1 ng/l u-GH after prior concentration of the urine samples (20- to 30-fold). u-GH excretion values were significantly dependent on the pubertal stage (p less than 0.0001) with maximum values in Tanner stage 3 for girls and 4 for boys. This corresponded to a peak in u-GH excretion between 11.5-14.5 years in girls and 12.5-16 years in boys. Additionally, u-GH excretion in adults was significantly higher than in prepubertal children (p less than 0.001). The day/night ratio of u-GH excretion (pg/h) was significantly higher in females than in males (p less than 0.01). In Tanner stages 1-4, u-GH excretion during the day was lower than that at night, whereas the opposite was true in late puberty and in adult women. The interindividual variation of u-GH excretion within the same Tanner stage was considerable and approximately double the intraindividual variation. The day-to-day variation could be further reduced by collection of three consecutive urine samples. The variations were larger if night samples instead of 24-hour samples were considered. The expression of u-GH excretion in nanograms per gram creatinine did not diminish the observed variation and blunted the pubertal increase in u-GH excretion. In conclusion, (1) u-GH excretion depends significantly on age, sex and pubertal maturation as does the day/night ratio of u-GH excretion. (2) The interindividual variation in u-GH excretion is considerable.(ABSTRACT TRUNCATED AT 250 WORDS)

Increase in urinary growth hormone excretion in puberty.

During the pubertal years the overnight urinary excretion rate of growth hormone (hGHu) increases to three to four times the prepubertal rate, reaching a peak in girls at 13 years and in boys at 15 years. After puberty the mean rate of overnight hGHu is twice that before puberty.

Comparison of Urinary Growth Hormone and IGF-I Excretion in Small- and Appropriate-for-Gestational-Age Infants and Healthy Children

The output of urinary growth hormone (GH) and IGF-I were quantitated by RIA in 12-h urine collections obtained from infants who were preterm, small for gestational age (PT-SGA, n = 13); preterm, appropriate for gestational age (PT-AGA, n = 27); full term, small for gestational age (FT-SGA, n = 13); and full term, appropriate for gestational age (FT-AGA, n = 29); and from normal children (n = 33). The amounts of GH and IGF-I (mean +/- SEM) excreted by the PT-SGA and FT-SGA infants were not significantly lower than those excreted by the PT-AGA and FT-AGA groups, respectively [GH (micrograms/kg): PT-SGA 13.7 +/- 3.1 versus PT-AGA 14.0 +/- 2.2, FT-SGA 7.8 +/- 2.4 versus FT-AGA 6.6 +/- 1.8; IGF-I (nmol/kg): PT-SGA 0.52 +/- 0.09 versus PT-AGA 0.53 +/- 0.04, FT-SGA 0.31 +/- 0.05 versus FT-AGA 0.35 +/- 0.04]. All infant groups exhibited significantly greater outputs of urinary GH and IGF-I compared with the children (p less than 0.01). The plasma concentrations of GH in all infant groups were high, whereas the plasma IGF-I levels were low. Microalbumin and beta-2 microglobulin excretion did not correlate with urinary GH and IGF-I output. Despite the higher microalbumin output in FT babies, urinary GH and IGF-I excretion was lower in these groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of Activity in Postoperative Acromegalics Plasma Growth Hormone Levels during Oral Glucose Tolerance Test, Daytime Blood Sampling and Urinary GH Excretion.

Plasma growth hormone (GH) levels during oral glucose tolerance test (OGTT) and during the daytime (0900-1700 h) and urinary GH excretion were determined in 6 normal subjects and 10 patients with postoperative acromegaly by means of a highly sensitive enzyme immunoassay (EIA). Acromegalic patients were divided into two groups according to their GH responses during OGTT. In group I patients plasma GH was suppressed below 1.0 microgram/l as in normal subjects, whereas GH levels persisted above 1.0 microgram/l in group II patients. Plasma GH profiles during the daytime were characterized by low nadir GH levels in normal subjects (0.21 +/- 0.10 microgram/l and group I patients (0.38 +/- 0.10 microgram/l) when compared with those in group II patients (4.7 +/- 2.0 microgram/l). Nadir GH levels during the daytime coincided with those during OGTT. Urinary GH excretions in group I patients (median 12 ng/day, range 4.3-29 ng/day) were within normal limits (2.6-20 ng/day) and significantly lower than those in group II patients (median 40 ng/day, range 19-130 ng/day.) Determination of plasma GH levels during OGTT and urinary GH excretion by the highly sensitive enzyme immunoassay is useful in evaluating the activity of postoperative acromegaly.

Urinary growth hormone excretion as a screening test for growth hormone deficiency.

Overnight urinary growth hormone secretion was measured by an immunoradiometric assay incorporating commercially available reagents, in 41 normal prepubertal school-children from three age groups: 3-5 years, 6-7 years, and 9-10 years. There was no significant difference between the groups expressing the results as total microU/specimen and so they have been combined to provide a prepubertal reference range of 2.25-10.50 microU/night. Prepubertal children with growth hormone deficiency who had not been receiving growth hormone treatment for two days had overnight urinary growth hormone concentrations well below this range. Urinary growth hormone was assayed in 49 children undergoing investigation for short stature with conventional provocative testing, and those shown to have growth hormone deficiency had correspondingly low overnight urinary growth hormone concentrations. There was, in addition, a strong correlation between overnight urinary growth hormone concentrations and peak serum response to provocation. This simple urine assay may provide a useful screening test for growth hormone deficiency.

Effect of Chronic Clonidine Treatment on Urinary Growth Hormone Excretion and Linear Growth in Children with Short Stature

Eleven prepubertal children with short stature were treated with clonidine (0.15 mg/m2 daily) for a period of 1 year. The effect of this drug was evaluated on both clinical (growth velocity, height standard deviation scores for chronological age and bone age) and hormonal (urinary growth hormone excretion and insulin-like growth factor I) parameters. Our study shows that long-term clonidine administration in children with short stature did not result in significant differences in growth velocity, height standard deviation scores for chronological age and bone age, insulin-like growth factor I or in urinary growth hormone excretion.

Urinary excretion of human growth hormone: daily variation and relationship with albumin and α1-microglobulin in urine

Urinary excretion of growth hormone during night-time was measured by a highly sensitive enzyme immunoassay in 6 normal men for 18-24 days. Urinary GH excretion distributed widely from 0.12 to 4.7 pg/mumol creatinine and the coefficient of variation in each subject ranged from 37 to 57% (mean 49%). Urinary excretion of albumin and alpha 1-microglobulin also showed moderate day-to-day variations (mean coefficients of variation: 37 and 42%, respectively). No correlation was found among urinary excretion of GH, albumin and alpha 1-microglobulin. Plasma and urinary GH levels were determined every 5 min and 2 h, respectively, from 09.00 h to 17.00 h in 4 normal men. Urinary GH excretion every 2 h during daytime closely reflected the change of plasma GH levels in each subject, suggesting that physiological GH secretory dynamics are reflected on the urinary GH excretion. Repeated measurements of urinary GH excretion are required to evaluate GH secretory capacity.

Quantification of urinary growth hormone (GH) excretion by centrifugal ultrafiltration and radioimmunoassay: appraisal of the relationship between 24 h urinary GH and mean 24 h serum GH levels in normal and abnormal states of GH secretion.

We have applied a simple method for the quantification of 24 h urinary GH excretion (24 h UGH), combining centrifugal ultrafiltration and radio-immunoassay (RIA), to an appraisal of the relationship between 24 h UGH and mean 24 h serum GH levels in normal and abnormal states of GH secretion. Forty-four subjects, comprising 13 normal adults, 12 short-statured subjects and 19 subjects with active acromegaly, underwent blood sampling at 20-min intervals and concurrent urine collection for 24 h. Mean 24 h serum GH and 24 h UGH were also determined in four post-menopausal women before and during cyclical oestrogen replacement therapy, and 24 h UGH was measured in six normal men prior to and following the subcutaneous administration of biosynthetic GH (0.2 IU/kg). Each subject's mean 24 h serum GH level was determined by assaying a 'pooled' sample, derived from equal aliquots of the 73 serum samples obtained during the 24 h study. The method for quantification of 24 h UGH employs centrifugal microconcentrators, and involves a 50-fold concentration of urine, followed by dialysis and RIA. Surface adsorptive hormone loss during sample collection and ultrafiltration is minimized by the prior addition of bovine serum albumin to the urine collection container. Immunoreactive GH in ultrafiltered urine dilutes in parallel with the RIA standard curve. GH is stable in urine stored at - 20 degrees C for at least 12 months. There was a highly significant correlation between 24 h UGH and mean 24 h serum GH values obtained from the combined population of normal adults (including the post-menopausal women during oestrogen therapy) and short-statured subjects (r = 0.69, P less than 0.0001). A significant correlation was also found in short-statured subjects alone (r = 0.63, P less than 0.05). In contrast, there was no significant correlation between 24 h UGH and mean 24 h serum GH in subjects with active acromegaly, and their 24 h UGH values were not distinguishable from those of the 'non-acromegalic' subjects. A significant increase in 24 h UGH occurred in the post-menopausal women given cyclical oestrogen replacement therapy (9.7 +/- 2.6 (mean +/- SE) to 24.6 +/- 1.0 muIU/mmol creatinine, P less than 0.02), reflecting the increase in their mean 24 h serum GH levels (0.8 +/- 0.3 to 5.3 +/- 0.7 mIU/l, P less than 0.01). Twenty-four hour UGH increased from 4.6 +/- 0.6 to 17.1 +/- 2.1 muIU/mmol creatinine (P less than 0.002) in the men given biosynthetic GH. Twenty-four hour UGH measurements reflect mean 24 h serum GH levels in normal adults and short-statured subjects. While the measurement of 24 h UGH shows promise as an investigative tool, our results cast doubt on its use in the diagnosis of acromegaly.

Editorial comment

The distribution of ghrelin-like immunoreactive cells in amphioxus (Branchiostoma belcheri) was investigated by using immunohistochemical staining with rabbit antiserum against synthetical mammalian ghrelin. The results showed that ghrelin-like immunoreactive cells were distributed widely in the nervous system, Hatschek’s pit, wheel organ, digestive tract and gonads (ovary and testis). In nervous system, ghrelin-like immunoreactive neurons and their protrusions were distributed specifically on the dorsal side, ventral side and funnel part of brain vesicle, with a few dispersive immunoreactive nerve cells and their fibers in nerve tube. Ghrelin-like immunoreactivities were also detected in Hatschek’s pit epithelial cells and wheel organ cells, with positive substance located along cell membrane. In digestive tract, ghrelin-like immunoreactive cells existed in hepatic diverticulum, anterior and posterior region of midgut, and could be classified into two types, closed- and opened-type endocrine cells. The number of positive cells was most in hepatic diverticulum, secondary in posterior region of midgut and least in anterior region of midgut. In gonads, ghrelin-like immunoreactive substance was detected in oogonia, oocytes and follicle cells in ovary at the small and large growth stages and in early spermatogenic cells and Sertoli cells in testis. The extensive distribution of ghrelin-like cells in amphioxus suggested that these kinds of cells are conservative in evolution and diversified in function. At the same time, we found for the first time that ghrelin-like immunoreactive cells existed in brain vesicle and Hatschek’s pit, which provided new morphological evidence for the existence of an activation pathway between brain vesicle and Hatschek’s pit for the regulation of growth hormone excretion.

Use of Bacteriocin Release Protein in E. Coli for Excretion of Human Growth Hormone into the Culture Medium

Because of the outer membrane barrier, the gram–negative bacterium E. coli is generally not considered to be an appropriate host for the excretion of proteins into the culture medium. However, we have been able to efficiently excrete a mammalian protein, human growth hormone (hGH), into the E. coli culture medium using E. coli cells harboring two vectors, the hGH secretion vector pOmpA–hGH2 and the pCloDF 13–derived bacteriocin release protein (BRP) expression vector pJL3. Both vectors contain, in tandem, the E. coli lpp and the E. coli lac promoter–operator system. The tandem promoter drives the expression of BRP and hGH and the expression of both proteins is regulated by the E. coli lac represser. In the presence of isopropyl–1–thio–β–D–galactopy ranoside (IPTG) at a low concentration (20 μM), both the BRP and the OmpA–hGH hybrid protein were expressed and mature hGH was released into the culture medium. The excreted hGH contained the correct amino terminus corresponding to the amino terminus of hGH derived from the human pituitary gland, indicating the correct processing of the OmpA signal peptide. The excretion of hGH was efficient and it was purified from the culture medium to greater than 98% purity using a single step of reversed–phase column chromatography.

Nocturnal urinary growth hormone excretion in children with short stature.

Nocturnal urinary growth hormone levels in children with short and normal stature were measured by a sensitive enzyme immunoassay. Urinary GH excretion during sleep correlated positively with peak plasma GH values during pharmacological (r = 0.74, P less than 0.001) and sleep (r = 0.85, P less than 0.001) tests. The amounts of urinary GH excretion during sleep differed significantly from each other in the following groups: complete GH deficiency (mean +/- SEM: 0.1 +/- 0.1 ng/m2 of body surface area; range: less than 0.1-0.4), partial GH deficiency (1.6 +/- 0.3 ng/m2; 0.2-3.1), and short stature without GH deficiency (3.7 +/- 0.6 ng/m2; 0.7-11.5). No significant difference was found between short stature without GH deficiency and normal stature (5.0 +/- 0.5 ng/m2; 2.1-10.5). Measurement of nocturnal urinary GH excretion is a simple method for screening of GH excretion and may be helpful in the differentiation of the various etiologies of short stature in children.

Quantitation of urinary growth hormone in children with normal and abnormal growth.

Urinary growth hormone (GH) excretion was quantitated in 12-h overnight urine collections obtained from 31 control children, ages 3 to 17 yr (group 1); 21 children, ages 5 to 19 yr with GH deficiency (group 2), and 30 subjects, ages 10 to 18 yr with idiopathic growth failure and normal GH stimulation tests (group 3). The output of urinary GH was measured in one acromegalic woman. The authenticity of urinary GH, 22 kDa, was confirmed by high-performance liquid chromatography. The elution pattern of urinary GH was identical to that of biosynthetic and pituitary-derived GH. The immunoreactive profiles characterized by monoclonal immunoradiometric GH assay and standard GH radioimmunoassay were identical. The quantity of GH (mean +/- SEM per kg body weight) in group 1 (0.27 +/- 0.02 ng/kg) was significantly greater than group 2 (0.08 +/- 0.02 ng/kg) or group 3 (0.17 +/- 0.02 ng/kg, p less than 0.01). Approximately 50% of the subjects in group 3 had urinary GH measurements indistinguishable from those observed in the GH-deficient population. Twelve hypopituitary patients (group 2) excreted significantly greater amounts of urinary GH in the first 12 h after GH administration compared to the baseline period (0.41 +/- 0.07 versus 0.12 +/- 0.02 ng/kg, p less than 0.01). Markedly elevated output of urinary GH (2.0 ng/kg) was documented in one acromegalic patient. The data suggest that measurements of urinary GH may be a useful, simple, and noninvasive screening test for identifying patients with GH deficiency or excess.

Abundant excretion of human growth hormone by recombinant-plasmid-transformed monkey kidney cells

A recombinant plasmid was constructed permitting the efficient synthesis of human growth hormone (hGH) in monkey cells. The plasmid contains the cDNA sequence of the hGH precursor and controlled by the SV40 early promoter, an intron, and the poly(A)-addition site of the mouse α-globin gene. To permit selection of transformed cells, a selectable marker (xanthine-guanine phosphoribosyl transferase; XGPRT) was also introduced into this plasmid. Transformation of an established monkey kidney cell line (VERO) permitted the isolation of cell lines excreting hGH. One of these strains (VEH 1) excreted hGH up to 5.6 μg per 10 6 cells per 24 h during exponential growth.

Removal and excretion of immunoreactive rat growth hormone by the isolated kidney.

The renal uptake of immunoreactive rat growth hormone (rGH), molecular weight 21,500 daltons, was examined in the isolated perfused rat kidney to determine whether peritubular removal of a protein greater than 12,000 daltons occurs and to assess the functional characteristics of renal GH uptake. Organ clearance of rGH (OCGH) in control kidneys was 1,039 +/- 99 microliters/min and was unaffected by an excess of insulin but markedly depressed by col (10 degrees C( and KCN. Although glomerular filtration rate (GFR) did not differ significantly from OCGH in the control rats, we suspected that filtration could not account for all the rGH removed because of glomerular protein sieving. However, GFR was significantly less than OCGH with cold and KCN treatment, indicating the occurrence of peritubular removal. In nonfiltering kidneys, rGH removal exceeded that of [14C]inulin (P less than 0.05), demonstrating peritubular rGH removal. Tubular absorption of rGH was unaffected by insulin but markedly depressed by cold and KCN. We conclude that rGH is removed from the renal circulation mainly by the glomerular filtration-tubular absorptive pathway, but, in addition, as with smaller proteins, that peritubular removal occurs.

Calcium and vitamin D metabolism in acromegaly.

Acromegalic subjects were found to have elevated serum levels of both 1,25-dihydroxyvitamin D (1,25-(OH)2D), 67 +/- 22 (SD) pg/ml) and 24.25-dihydroxyvitamin D (24.25-(OH)2D), (6.9 +/- 1.5 (SD) ng/ml). The serum concentration of 1,25-(OH)2D correlated positively (P less than 0.02, R = 0.56) to the 24 h urinary excretion of growth hormone, but not to the serum levels of parathyroid hormone, prolactin, thyroid hormones or the urinary excretion of free cortisol. Fourteen patients were treated with bromocriptine at doses from 15-45 mg/day for a period of about 6 months. This was accompanied by a significant decrease in the urinary excretion of growth hormone and calcium and in the serum concentrations of 1,25-(OH)2D and 24.25-(OH)2D. A relationship was demonstrated between the decrease in urinary calcium excretion and the decrease in serum 1,25-(OH)2D (P less than 0.02, R = 0.64). It is concluded that the serum concentration of 1,25-(OH)2D is elevated in acromegaly, perhaps as a consequence of a direct action of growth hormone on the renal 1 alpha-hydroxylase activity.