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The welfare of unwanted horses presents a significant concern for the equine industry. However, there is a lack of research on how unwanted horses are affected by major crises. The drastic changes that resulted from the COVID-19 pandemic presented ample opportunity to investigate how unwanted horses are impacted by challenging circumstances. Study objectives were to evaluate the COVID-19 pandemic's impact on the unwanted horse population and determine the current perceptions of horses in-transition. A 23-question online survey designed using Qualtrics TM was administered electronically to adults living in the United States. Questions pertained to effects on equine ownership, equine management, event participation, and perceptions of unwanted horses. Frequency analysis combined with Chi-squared analyses and analyses of variance identified the impacts of COVID-19 on horse owners, non-horse owners, and equine professionals. From survey results, equine ownership, management practices, and time spent with horses proved to be unaffected (P < 0.001) by the coronavirus pandemic. A decreased ability to participate in equine events was evident across all groups (P ≤ 0.03). Financial hardship, unmanageable behavior, and injury were cited as leading causes for horses becoming "in-transition." Euthanasia was the transitioning method perceived as most accessible, while donation to an equine program was least accessible. Based on results, the COVID-19 pandemic had negligible impact on the number of unwanted horses in the United States. Long-term effects of COVID-19 on equine ownership and management decisions should be considered to provide a deeper base of knowledge for how major crises affect the horse in-transition population., Competing Interests: Declaration of competing interest None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper., (Copyright © 2024. Published by Elsevier Inc.)

The COVID-19 pandemic has increased the availability of virtual horse showing opportunities. The objectives of this study were to describe survey participants' personal characteristics and participation in virtual and in-person horse shows, level of satisfaction, attitude toward technology and motivation to participate, and internal and external factors influencing the decision to participate in virtual horse shows. A survey was distributed to a target audience of adult horse show participants and/or adults supporting youth horse show participants via Qualtrics (n = 251). A majority of respondents (91.2%) reported benefits to participating in virtual horse shows, and 59.8% plan to continue showing virtually when in-person shows resume. The opportunity to show virtually has resulted in 76.1% of respondents anticipating increasing their participation in showing (in-person or virtual). An improvement in attitude toward technology (M =1.6; SD = 0.4; Range = 1.0-2.3) and an increase in motivation to participate, ride and show (M = 1.4; SD = 0.4; Range = 1.0-2.8) was also reported. In addition, respondents indicated they were somewhat likely to be influenced to participate in virtual shows by internal factors such as their budget and ability to record the ride. External factors such as feedback from judges, available divisions, and awards were extremely likely to influence their decision to participate. In conclusion, virtual horse shows have provided a satisfactory outlet to keep people engaged in the industry. Additional research should be done to determine if the current popularity of virtual horse showing persists once in-person shows have fully resumed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

The COVID-19 pandemic affected the economic status of all sectors of the global economy including the horse show industry. Reporting the impact of COVID-19 on in-person horse shows and an early assessment of its impact on the economy was the objective of this study. A Qualtrics survey instrument was disseminated to horse show participants through social media pages and email (n = 251). A majority of respondents were females (95.6%) representing a cross-section of the United States (84.0%). Participants reported planning to attend an average of 9.7 (SD = 7.15) in-person horse shows in 2020 but were unable to attend an average of 4.17 (SD = 3.11) due to COVID-19 restrictions. Participants reported spending a mean of $991 (SD = $648.26) per show on horse show-related expenses, or $9,609 annually. The American Horse Council (2018) reported that 1,227,986 horses comprise the competition sector, with each horse owner showing 1.57 horses.  This participation generates $7.5B in expenses annually. The reduced attendance at in-person shows resulted in a decrease in annual expenditures, suggesting economic losses of $3.23 billion. The quantified direct effects were used in the IMPLAN input-output model to estimate the total economic impact. The reduced attendance resulted in a reduction of $7.2 billion, and a reduction of approximately 50,000 jobs within the horse show industry. Additionally, the industry's contribution to GDP (value added) was reduced by $3.95 billion. Early assessments of the economic impact associated with a reduction of in-person horse showing is vital to understanding the long-term implications for the industry., (Copyright © 2021. Published by Elsevier Inc.)

Background: Many patients with childhood-onset growth hormone (GH) deficiency do not fulfill diagnostic criteria for GH deficiency (GHD) after attainment of adult height and may not require long-term GH treatment. Patients with history of idiopathic GHD (IGHD) pose the greatest management dilemma, as data regarding factors predictive of persistent GHD in this group are lacking., Objectives: The objective of this study was to assess potential predictors of persistent GHD in a US patient cohort during transition from childhood to adulthood, particularly in patients with history of IGHD., Methods: We studied 73 US patients with history of childhood-onset GHD screened at 21 US pediatric endocrine centers for a randomized clinical trial of GH replacement after attainment of adult height. The cohort comprised 42 boys/men and 31 girls/women aged14-22 years, who had received ≥1 year of GH treatment and had completed linear growth. The main outcome measures were sensitivity, specificity, positive and negative predictive values (PPV, NPV) of clinical and hormonal factors for persistent GHD (defined a priori in this study as peak GH < 5 μg/L)., Results: For the cohort as a whole, the best predictors of persistent GHD (100% PPV) were history of organic hypothalamic-pituitary disorder or ≥2 additional pituitary hormone deficiencies (PHD). Best predictors of persistent GHD in patients with childhood history of IGHD were standard deviation scores (SDS) for serum insulin-like growth factor binding protein-3 (IGFBP-3) below -2.0, and for insulin-like growth factor-I (IGF-I) below -5.3 (measured ≥6 weeks after completion of GH treatment; PPV 100% for both), and age <4 years at original diagnosis (PPV 89%). IGF-I above -1.6 SDS had 100% NPV., Conclusions: US patients with an organic cause of childhood-onset GHD or ≥2 additional PHDs may not require GH stimulation testing to reconfirm GHD after completion of childhood treatment. In contrast, patients with idiopathic childhood-onset GHD almost invariably require retesting, as GHD persists in only a minority (those who were very young at initial diagnosis and those who have subnormal IGFBP-3 or extremely low IGF-I after completion of childhood treatment). Subnormal posttreatment IGF-I (<-2.0 SDS) lacked predictive power for persistent GHD, whereas IGF-I > -1.6 SDS was 100% predictive of GH sufficiency.

Context: Typically, growth failure in Turner syndrome (TS) begins prenatally, and height sd score (SDS) declines progressively from birth., Objective: This study aimed to determine whether GH treatment initiated before 4 yr of age in girls with TS could prevent subsequent growth failure. Secondary objectives were to identify factors associated with treatment response, to determine whether outcome could be predicted by a regression model using these factors, and to assess the safety of GH treatment in this young cohort., Design: This study was a prospective, randomized, controlled, open-label, multicenter clinical trial (Toddler Turner Study, August 1999 to August 2003)., Setting: The study was conducted at 11 U.S. pediatric endocrine centers., Subjects: Eighty-eight girls with TS, aged 9 months to 4 yr, were enrolled., Interventions: Interventions comprised recombinant GH (50 mug/kg.d; n = 45) or no treatment (n = 43) for 2 yr., Main Outcome Measure: The main outcome measure was baseline-to-2-yr change in height SDS., Results: Short stature was evident at baseline (mean length/height SDS = -1.6 +/- 1.0 at mean age 24.0 +/- 12.1 months). Mean height SDS increased in the GH group from -1.4 +/- 1.0 to -0.3 +/- 1.1 (1.1 SDS gain), whereas it decreased in the control group from -1.8 +/- 1.1 to -2.2 +/- 1.2 (0.5 SDS decline), resulting in a 2-yr between-group difference of 1.6 +/- 0.6 SDS (P < 0.0001). The baseline variable that correlated most strongly with 2-yr height gain was the difference between mid-parental height SDS and subjects' height SDS (r = 0.32; P = 0.04). Although attained height SDS at 2 yr could be predicted with good accuracy using baseline variables alone (R(2) = 0.81; P < 0.0001), prediction of 2-yr change in height SDS required inclusion of initial treatment response data (4-month or 1-yr height velocity) in the model (R(2) = 0.54; P < 0.0001). No new or unexpected safety signals associated with GH treatment were detected., Conclusion: Early GH treatment can correct growth failure and normalize height in infants and toddlers with TS.

Context: Little information exists regarding FSH values in very young girls with Turner syndrome (TS)., Objectives: The objective of the study was to evaluate the pattern, natural progression, and karyotype-related differences in FSH secretion in young, prepubertal girls with TS., Study Design: FSH was measured at study entry and annually for 2 yr., Setting: The Toddler Turner study was conducted at 11 U.S. pediatric endocrine centers., Study Participants: Eighty-eight girls with karyotype-proven TS aged 9 months to 4 yr participated in the study., Main Outcome Measures: By-karyotype differences in FSH concentration and age-related changes in FSH were measured., Results: Mean (+/- SD) FSH was markedly elevated in the 45,X (n = 56: 68.3 +/- 36.0 IU/liter) and Other groups [n = 15 (excluding three subjects with Y-containing karyotypes): 52.7 +/- 50.8 IU/liter] but was minimally elevated in girls with 45,X/46,XX mosaicism (n = 14: 10.1 +/- 13.5 IU/liter, P < 0.005 both comparisons). Over the 2-yr period, FSH declined in the 45,X group (-13.4 IU/liter.yr, P < 0.0001). Nonetheless, only three of 159 FSH values fell within normal range for age at any time during the 2-yr study. FSH decline was similar in the Other group (-14.3 IU/liter.yr, P = 0.0032). In contrast, no significant decrease in FSH with age was observed in the 45,X/46,XX group., Conclusions: In contrast to the original report of FSH concentrations in individuals with TS, this study demonstrates distinct differences in patterns of FSH secretion between young girls with monosomy TS, who have persistent elevation of FSH to age 6 yr, and those with 45,X/46,XX mosaicism, whose FSH values suggest retained ovarian function in the majority. These findings have implications for patient management and family counseling.

The purpose of this study was to determine whether GH treatment of cystic fibrosis (CF) patients can result in an anabolic effect, i.e., increased weight gain, improved growth rate, nitrogen retention, and improved pulmonary function. Nine prepubertal endocrinologically normal CF patients (3 girls, 6 boys; chronological age (CA) 5.5-9.8 years, and bone age (BA) 4.5-9.0 years), received recombinant human growth hormone (rhGH) 0.3 mg/kg/week subcutaneously for a period of 12 months (N = 8) or 9 months (N = 1). Normal glucose tolerance was determined before treatment. Pulmonary function studies and anthropometric measurements were done every 3 months. Thyroid status, somatomedin C (SmC), BA, and routine chemistries were evaluated every 6 months. The pretreatment growth velocity averaged 5.7 +/- 0.3 (SE) cm/year and significantly increased to 7.8 +/- 0.4 (SE) cm/year during therapy, (P < 0.01). Standard deviation scores (SDS) for height significantly increased during rhGH therapy as compared with pretreatment, (P < 0.05). Weight of the patients during rhGH therapy did not significantly change during or after rhGH therapy. After therapy, all patients showed a significant increase in arm muscle area (AMA) and a significant decrement in arm fat area (AFA) (P < 0.01). Net nitrogen anabolism was negative in all subjects before therapy but became more positive in five patients during rhGH therapy. Three patients achieved positive nitrogen retention. SmC values significantly increased from a mean value of 0.62 +/- 0.1 (SE) U/ml to 1.6 +/- 0.6 (SE) U/ml after therapy. BA advanced 1.0 +/- 0.1 SE per year after treatment. Of the seven patients able to perform adequate pulmonary function testing, improvement occurred in FVC, FEV1.0, and PEFR in 5, 5, and 4 patients, respectively, but these changes did not reach statistical significance. We conclude that biosynthetic rhGH therapy had a significant anabolic effect in CF patients as shown by increased growth velocity, SmC values, increased protein and decreased fet stores, and a positive or less negative net nitrogen retention in five of the patients.

From 3 million to 4 million children in America have lead poisoning. This environmental toxin affects 1 in every 6 children younger than 6 years of age in the United States. The marked effects of lead toxicity on the central nervous system are well known, ie, lowering IQ and impairing memory, reaction time, and the ability to concentrate. Children are at greatest risk for the central nervous system effects of lead because the central nervous system is at its peak in development during the first few years of life. The negative correlation of stature and blood lead level (bPb) found in the National Health and Nutrition Examination Survey directed the authors to evaluate the possible neuroendocrine effects of this toxin in children. Twelve children were studied during toxic (greater than or equal to 40 micrograms/dL) and low bPb (less than 40 micrograms/dL). Classic provocative stimuli, L-dopa (15 mg/kg by mouth) and insulin (0.1 U/kg given intravenously), were used to determine human growth hormone (hGH) responses during toxic bPb and after chelation therapy in six of the subjects. An additional four subjects were studied during low bPb. In two patients LGH levels were determined every 20 minutes for 24 hours during toxic bPb. Thyroid-stimulating hormone and prolactin responses to thyrotropin-releasing hormone were also determined. All children studied showed growth retardation during toxic bPb. Mean peak hGH responses to provocative stimuli were lower during toxic bPb, but the responses were all within normal limits.(ABSTRACT TRUNCATED AT 250 WORDS)

GH influences the immune response. The mechanism is not known; however, the presence of receptors for GH on human lymphocytes as well as its ability to influence and modulate immune responses in animals suggest an association between GH and immune function in man. We evaluated the effect of recombinantly derived natural sequence human GH (hGH) on lymphocyte surface antigen expression, response to mitogenic stimulation, expression of interleukin-1 receptors, and production of anti-hGH antibodies in GH-deficient children. The only observed changes were a decrease in the percentage of B-cells and a transient increased reactivity to phytohemagglutinin stimulation. It appears from the results of our studies that the administration of hGH has a selective effect on lymphocyte immune function; however, we cannot eliminate a role for hGH in the initiation or regulation of antigen-mediated immune responses.

Bone mineral measurements of the forearm and spine were made in 63 patients under treatment in the Eating Disorders Program of the University of Nebraska Medical Center, 26 with anorexia nervosa (AN), 11 with bulimia nervosa (BU) and 26 with features of both AN and BU (AN/BU). Comparison was made with a group of 211 normal women of similar age. Spinal bone mineral content (BMC) of L2-4 was 45.1 +/- 5.7 g in the normals, 38.0 +/- 7.5 in the AN's, 40.3 +/- 6.6 g in the AN/BU's and 44.4 +/- 6.9 g in the BU's. The AN and AN/BU averages were both significantly different from normal (p less than 0.0005), but the BU average was not. BMC was correlated with body weight in each group and weakly correlated with age in the patients under age 30 in the AN and AN/BU groups combined. Forearm bone mineral measurements in the AN's and AN/BU's were also significantly lower than normal, but the differences were not as great as for the spine. We conclude that bone mineral is reduced in these patients, severely in some of them, and that reduced body weight plays a role. Menstrual disturbances, inhibition of growth and development, and malnutrition remain open as causal factors. Potential for recovery from reduced bone mineral was not demonstrated in this study.

The purpose of this study was to determine if endogenous hGH release, hence growth, in hypopituitary children could be potentiated by therapy with dopaminergic (DA) drugs namely, L-dopa or bromocriptine. The effect of DA therapy on other endocrine function was also examined. Subjects were nine prepubertal children (four girls and five boys) with bone ages (BA) ranging from 1.5-9.5 yr. They were diagnosed as having idiopathic GH deficiency on the basis of: 1) failure to grow at normal rates 2) lack of GH response to two provocative stimuli (oral L-dopa, and insulin-induced hypoglycemia) and 3) low somatomedin-C concentrations for sex and age. They were divided into two groups. Group I (n = 4) received L-dopa (15 mg/kg, orally, every 6 h) for 6 months. Group II (n = 5) received bromocriptine (1.25 mg, orally, every 12 h) for 6 months. At the end of 6 months of DA therapy, both groups received human GH (hGH) im (0.1 IU/kg, thrice weekly) for 6 months. The growth rate in group I increased to 5.7 +/- 0.6 (+/- SE) cm/yr during the 6 months from a pretreatment rate of 3.4 +/- 0.2 cm/yr. Individual increments ranged from 30-94% above pretreatment growth rates. Three of the four children had significantly increased height increments, and two children achieved growth rates normal for their BA. Similarly, the growth rate in group II increased to 4.8 +/- 0.8 cm/yr from the pretreatment rate of 2.9 +/- 0.3 cm/yr. Individual increments ranged from 46-100% above pretreatment growth rates. Three children in group II had significantly increased height increments, and two children had normal growth rates for BA. The growth increments during L-dopa therapy occurred in the three children who had significant increases in hGH and somatomedin-C; of the three children with significant growth increments during bromocriptine therapy, two had increases in somatomedin-C, and one achieved a normal peak hGH value. hGH therapy caused further acceleration of growth velocities in the majority of patients. DA therapy had no significant effect on basal gonadotropin, gonadal steroids, T4, TSH, or morning cortisol concentrations in the majority of children compared with their pretreatment values. The following conclusions were reached. Dopaminergic therapy by itself, i.e. L-dopa or bromocriptine administration, induced linear growth in some hypopituitary children without significantly affecting basal concentrations of LH, FSH, gonadal steroids, T4, TSH, or cortisol. The effect this therapy could have in potentiating exogenous GH and/or possible GRH therapy is worthy of further investigation.

Previous studies have concluded that surgical exploration is unnecessary in genetic male subjects with nonpalpable tests who fail to respond to human chorionic gonadotropin. Lack of response suggested absent testicular tissue. We report on 2 patients thought to have anorchia because of lack of response to human chorionic gonadotropin stimulation. Testes were found in both patients. Genetic and phenotypic male subjects with nonpalpable testes who fail to have increased testosterone after human chorionic gonadotropin stimulation should undergo laparoscopy. If testicular structures are present at laparoscopy surgical exploration is indicated. Unresponsiveness to human chorionic gonadotropin may be evidence of nonexistent or dysfunctional Leydig cells rather than evidence of complete absence of testicular tissue.

Three siblings with congenital lipodystrophy were studied extensively for endocrine abnormalities. A severe disturbance in carbohydrate metabolism was observed. Plasma concentrations of glucagon and insulin were markedly elevated both in the basal state and in response to provocative stimuli. In addition, marked resistance to exogenous insulin and a diabetic oral glucose tolerance test were demonstrated. Lipid metabolism, GH, and ACTH secretion were normal...

Dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), androstenedione (A), testosterone (T), estrone (E1), estradiol (E2) and gonadotropins were measured in 3 normal adult men before and after administration of 50 mg ovine prolactin for 5 days. No significant change as a result of ovine prolactin administration was observed in any of the parameters examined.

The purpose of this study was to determine if combined therapy with dopaminergic drugs (DA), i.e. L-dopa or bromocriptine, and exogenous human GH (hGH) could increase growth velocity in hypopituitary children. Twelve prepubertal hypopituitary children (eight boys and four girls; bone age, 1.5-9.5 yr), divided into two groups, each received hGH alone, DA alone, and DA and hGH. Group I (n = 6) received L-dopa (15 mg/kg, orally) at 6-h-intervals during DA and combined DA and hGH therapy. Group II (n = 6) received bromocriptine (1.25 mg, orally) every 12 h during DA and combined DA and hGH therapy. Both groups were given hGH (0.1 IU/kg) three times per week during hGH and combined hGH and respective DA treatment. The study included three 6-month treatment periods of DA, hGH, and combined DA and hGH therapy. The mean growth rates (centimeters per 6 months, +/- SD) before treatment and during the three study periods for group I were 1.7 +/- 0.2, 3.3 +/- 0.8, 3.4 +/- 0.4, and 3.9 +/- 0.7, respectively. Group II results were 1.4 +/- 0.3, 2.3 +/- 0.8, 5 +/- 1.6, and 3.7 +/- 1.1. Mean and peak hGH concentrations, measured every 30 min for 9 h at the end of each study period, increased significantly in five patients, from 15 +/- 3 (+/- SE) ng/ml during hGH therapy to 30 +/- 5 ng/ml during DA and hGH treatment. The mean peak hGH values rose from 24 +/- 4 to 45 +/- 5 (+/- SE) ng/ml. In conclusion, addition of dopaminergic agents to hGH therapy potentiates growth in some hypopituitary children. The increased growth and hGH responses to L-dopa or bromocriptine suggest impaired endogenous GH release. Dopaminergic therapy alone or in combination with exogenous hGH may be efficacious in some hypopituitary children.

Two patients with hypothalamic hamartoma presented with isosexual precocious puberty. LHRH challenge showed a pubertal LH response in both cases. Serum FSH responses to LHRH were pubertal in case 1, but prepubertal for case 2. Computed tomography revealed isodense noncontrast-enhancing retrosellar mass lesions in both cases. The tumors were composed of mature neurons and neuroglial tissue. Electron microscopy of the lesions failed to demonstrate dense core (neurosecretory) granules in either case. Subtotal removal of the harmartomas resulted in decreased LH responsiveness to LHRH in both cases. Serum FSH responsiveness to LHRH was not significantly suppressed postoperatively in case 1, and FSH responsiveness to LHRH in case 2 showed exaggerated levels, more typical of very young prepubertal girls. Postoperative magnetic resonance imaging (MRI) scans of both patients are also presented.

Somatic, endocrine, and behavioral correlates of growth and levels of voluntary running activity were measured in adult hamsters with hippocampal transections (HIPPO cuts) or in controls with transections of overlying cortex. Significant increase in serum concentration of growth hormone (GH) and decrease in pituitary concentration of GH were measured in HIPPO hamsters with a homologous radioimmunoassay method for hamster GH. HIPPO hamsters had increased: serum insulin concentration in fed state, food consumption, ponderal and linear growth, and percentage of body fat, and decreased levels of voluntary activity. Similarities between growth acceleration after HIPPO cuts and lesions of rostral medial septum suggest that fibers interconnecting, or passing through, the hippocampal formation and septum inhibit growth in adult hamsters.

In a previous study we reported stimulation of growth velocity in hypopituitary children by dopaminergic therapy (DA), i.e. either L-dopa or bromocriptine. The purpose of the present study was to determine if DA stimulated endogenous GH release and growth in children with intrauterine growth retardation (IUGR), who also had microcephaly and psychomotor retardation. The effect of DA on serum LH, FSH, gonadal steroids, cortisol, T4, and TSH also was examined. Six prepubertal children [four girls and two boys; bone age (BA), 1.5-4 yr] with IUGR were divided into two study groups. Group I (n = 3) received L-dopa (15 mg/kg) orally every 6 h for 6 months. Group II (n = 3) received bromocriptine (1.25 mg) orally every 12 h for 6 months. At the end of the 6 months of DA therapy, both groups received human GH (hGH) (0.1 IU/kg) im thrice weekly for 6 months. The growth rate in group I was 6.5 +/- 0.1 (+/-SD) cm/yr after 6 months of DA compared with a pretreatment growth rate of 4.1 +/- 0.7 cm/yr. Individual increments ranged from 38-80%. All three children achieved normal growth rates for their BA. Similarly, the growth rate in group II increased to 7.7 +/- 0.9 cm/yr from a pretreatment growth velocity of 4.2 +/- 1.6 cm/yr. The growth increments of group II ranged from 43-133%. Two children of group II achieved normal growth rates for their BA, and all had a significant increase in height (P less than 0.05). Four of the six children achieved normal growth velocities after 6 months of hGH therapy. Five of the six children significantly increased their mean hGH responses to L-dopa or bromocriptine during chronic DA therapy compared with the pretreatment period. Maximum serum hGH values in group I increased from a pretreatment mean (and range) of 12 +/- 4 (+/-SE) ng/ml (5-18 ng/ml) to 46 +/- 12 ng/ml (21-64 ng/ml). The maximum hGH concentrations in group II increased from a pretreatment mean and range of 21 +/- 7 ng/ml (11-34 ng/ml) to 48 +/- 4 (42-56 ng/ml). Also, four of the six children had correspondingly increased somatomedin-C concentrations after DA therapy. The findings of this preliminary study indicate that dopaminergic therapy, i.e. L-dopa or bromocriptine, induced linear growth in patients with a form of IUGR associated with microcephaly and psychomotor retardation. DA therapy perhaps may be useful in treating other various forms of IUGR.

Caffeine has been shown to markedly alter growth hormone (GH), thyroid stimulating hormone (TSH), and thyroid hormones in animal studies. Similar studies in the human are lacking. To determine the effect of theophylline treatment on endocrine function in neonates with apnea, 10 infants were studied prospectively pretreatment, immediately following therapeutic blood levels of theophylline, at 2, 4, and 6 weeks thereafter and finally 2 weeks after discontinuation of theophylline. T4, free T4, T3, GH, and basal and stimulated TSH were measured at each study period. Results show no significant difference consequent to theophylline therapy on basal thyroid or GH secretion and thyrotropin-releasing hormone (TRH) induced TSH response at any study interval. We conclude there is no evidence to suspect abnormality occurring in growth, thyroid function and GH secretion in neonates receiving theophylline for breathing disorders.

Decreased stature of children is epidemiologically associated with increased blood lead independent of multiple socioeconomic and nutritional variables. Since endocrine dysfunction occurs in adult lead workers, we studied two girls, 2 years of age, before and after calcium disodium edetate chelation for blood leads (PbB) of 19-72 micrograms/dl. The height of both children had crossed from the 50th to below the 10th percentile during the course of chronic lead toxicity. Basal free T4, T4, T3, cortisol, somatomedin C, and sex steroids were normal. A decrease in the growth hormone response and elevation of basal prolactin and gonadotropins were noted in one. Both children demonstrated blunted thyrotropin-stimulating hormone (TSH) responses to thyrotropin-releasing hormone (TRH) in six of seven challenges. This prompted in vitro studies of cultured cells from rat pituitaries. After incubation of pituitary cells with 0.1-10 microM Pb2+ for 2 hr, followed by the addition of TRH, there was a dose-dependent inhibition of TSH release. Lead did not interfere with the assay of TSH. To investigate the interaction of lead and calcium, 45Ca2+ kinetic analyses were done on rat pituitary slices after 1 hr incubation with 1.0 microM lead. The impaired late efflux was consistent with a decrease in the size and exchangeability of the tightly bound pool of intracellular microsomal or mitochondrial calcium. The rat pituitary cell model provides a model for the decreased TSH release of lead poisoning, supports the biological plausibility of a neuroendocrine effect on growth, and suggests that interference with calcium-mediated intracellular responses is a basic mechanism of lead toxicity.

Pseudotumor cerebri occurs in many diverse endocrine and nonendocrine disorders. We report what we believe is a new association following initiation of thyroxine (T4) replacement in hypothalamic hypothyroidism, as well as another occurrence following T4 replacement in primary hypothyroidism. The less than benign clinical course reported in these two patients suggests the need for careful neurologic and funduscopic evaluation during the initial months of T4 replacement in all cases of hypothyroidism.

Hypothyroidism is frequently associated with abnormal sexual development. To determine the longitudinal influence of thyroxine replacement on the hypothalamic pituitary gonadal axis, we studied five prepubertal hypothyroid girls and two boys before, and all the girls six weeks and one year after, thyroxine replacement. All girls showed significantly elevated basal gonadotrophin concentrations before treatment. Following one year of therapy, despite all girls having begun puberty, basal gonadotrophin concentrations were significantly decreased in the four euthyroid girls as compared with our normal pubertal girls. The fifth girl studied at one year was hypothyroid at the time of testing and her gonadotrophin values were increased even above previous basal values. Pretreatment serum TSH values inversely correlated with maximum pretreatment incremental LH (r = -0.54) and FSH (r = -0.52) responses to LHRH. Serum TSH values directly correlated with PRL concentrations (r = +0.82). Of the two hypothyroid boys evaluated, Patient 1 was mildly hypothyroid and showed normal prepubertal basal LH, FSH, testosterone and low normal LHRH responsiveness. Patient 2, who was more severely hypothyroid, had elevated basal gonadotrophin secretion and responsiveness to LHRH but prepubertal testosterone concentrations. These data indirectly show that thyroxine may increase the biological/immunological potency of gonadotrophins. The elevated gonadotrophin values in the hypothyroid state suggest that the metabolic clearance rate of gonadotrophins is prolonged. The more severe the elevation in TSH secretion, the more marked was the alteration in the hypothalamic pituitary axis in respect to PRL secretion and delta max LH and FSH response to LHRH. Replacement with thyroxine was followed by normal pubertal development, and normal pubertal oestradiol and PRL concentrations, despite low immunoreactive gonadotrophin secretion.