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PubMed2004

Cytokinins induce photomorphogenic development in dark-grown gametophytes of Ceratopteris richardii.

The cytokinins benzylaminopurine, kinetin and isopentenyladenine induce photomorphogenesis in dark-grown gametophytes of the fern Ceratopteris richardii. At sub-nanomolar concentrations each altered the rate and pattern of cell division, elongation and differentiation, mimicking aspects of the light-mediated transition from filamentous to prothallial growth. Untreated dark-grown gametophytes grow as narrow, elongate, asexual filaments with an apical meristem. Cytokinin treatments as low as 10(-12) M reduced the length-to-width ratio through decreased cell elongation, increased periclinal cell division and induced the formation of rhizoid initials in the cells immediately below the apical meristem. Higher concentrations (10(-9)-10(-8) M) induced conversion of the meristem from apical to notch morphology. Cytokinins induced both red- and blue-light-mediated photomorphogenic events, suggesting stimulation of both phytochrome and cryptochrome signaling; however, cytokinin treatment only partially substituted for light in that it did not induce hermaphroditic sexual development or spore germination in the dark. Additionally, cytokinins did not increase chlorophyll synthesis in dark-grown gametophytes, which unlike angiosperms are able to produce mature chloroplasts in the dark. Cytokinin treatment had only slight effects on light-grown gametophytes. These results suggest evolutionary conservation between angiosperms and pteridophytes in the role of cytokinins in regulating photomorphogenesis.

Cytokinins↗
PubMed1985

Pituitary gonadotropin-independent male-limited autosomal dominant sexual precocity in nine generations: familial testotoxicosis.

A recently described, distinct form of male sexual precocity is characterized by premature Leydig and germinal cell maturation in the absence of pituitary gonadotropin stimulation. Analysis of a nine-generation kindred with at least 28 affected males supports sex-limited autosomal dominant transmission. Three boys, with precocious sexual development at 1 to 4 years of age, had low basal plasma gonadotropin values without pubertal-type pulsatility and a minimal rise in luteinizing hormone after acute stimulation with luteinizing hormone releasing factor or its potent analog D-Trp6-Pro9-NEt-LRF, distinguishing them from boys with true precocious puberty. Two affected adults had a mature luteinizing hormone response to LRF. Testicular biopsies showed a progression of abnormalities in the seminiferous tubules from childhood to maturity; in one adult this disorder was associated with marked oligospermia and selective elevation of plasma follicle-stimulating hormone. The findings are consistent with an inherited intratesticular defect. Furthermore, the majority of cases of familial male sexual precocity seem to be examples of this disorder rather than central or true precocious puberty.

Child↗
PubMed2005

Endocrine (sexual) disruption is not a prominent feature in the pike (Esox lucius), a top predator, living in English waters.

The high incidence of intersex roach (Rutilus rutilus) in some United Kingdom rivers that has been associated with exposure to sewage treatment works (STWs) effluent led us to hypothesize that top predator fish also may be affected by estrogenic chemicals, because they are likely to bioaccumulate lipophilic compounds through a predator-prey relationship. To investigate this possibility, pike (Esox lucius) were sampled both upstream and downstream of STWs and then examined for total estrogenic activity of their bile, as measured using a yeast-based estrogen assay to determine the degree of recent exposure of the pike to estrogens and vitellogenin induction, and for possible disruption of sexual development, as measured using histological analysis of the gonads. No evidence of severe disruption was found in the sampled fish, which came from 16 sampling sites that were representative of English rivers. However, 14% of pike were intersex, of which 15 of 16 showed patches of male germ cells among predominantly female gonadal tissue. The incidence of masculinization was independent of whether the pike had been sampled upstream or downstream of STWs. Although pike are gonochoristic, it is not known if this masculinization of presumptive female pike is normal or, instead, indicative of endocrine disruption. Vitellogenin concentrations were not elevated in male pike at sites either upstream or downstream of STWs. The results suggest that sexual disruption is not common in pike, a fish at the top of the food chain in the freshwaters of England.

Animals↗
PubMed1986

Use of a potent, long acting agonist of gonadotropin-releasing hormone in the treatment of precocious puberty.

Studies utilizing the administration of GnRH in various GnRH-deficient models have revealed the critical importance of the dose and mode of delivery of this releasing factor in determining the subsequent pituitary response. Chronic administration of long acting GnRH agonists (GnRHa), like continuous infusion of high doses of the native peptide, results in suppression of pituitary gonadotropin secretion. This selective and reversible suppression of gonadotropin secretion suggested several therapeutic applications for these analogs, particularly in the treatment of central precocious puberty (CPP), a disorder for which the previously available therapies lacked uniform efficacy and were associated with potential side effects. In our series, 74 children with CPP have been treated during the last 5 yr with the potent GnRH agonist, [D-Trp6, Pro9-ethylamide(NEt)]GnRH. Having selected a dose and route of administration that produced uniform suppression of spontaneous and stimulated pituitary gonadotropin secretion, GnRHa therapy resulted in a fall of gonadal sex steroid levels into the prepubertal range, a halting or regression of secondary sexual development, and a complete cessation of menses. Growth velocity slowed during therapy, with this slowing more pronounced during prolonged treatment periods and among those patients with more advanced chronological and skeletal ages. Skeletal maturation was retarded to a greater degree than linear growth, with resultant increases in the predictions for adult stature. Moreover, these benefits have been achieved in the absence of significant side effects. Complete reversal of the suppression of gonadarche has followed discontinuation of therapy; however, patterns of growth and skeletal maturation after discontinuation of GnRHa administration remain to be characterized. Thus, the impact of GnRHa therapy on final height must await further longitudinal study. The selective nature of GnRHa suppression of gonadarche also permits an investigation of the natural history of adrenarche and its discrete influences upon skeletal growth and maturation. In addition, GnRHa therapy of CPP provides a unique opportunity to study the effects of gonadal sex steroids on GH secretion and somatomedin-C (Sm-C) generation during sexual maturation. Finally, the detailed characterization of children with precocious puberty has helped to define more precisely a subset of patients whose precocity occurs in the absence of demonstrable gonadotropin secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Glands↗
PubMed1986

Peripheral anosmia affects puberty-influencing chemosignals in mice: donors and recipients.

A series of five experiments tested the effects of peripheral anosmia on both donors and recipients of urinary chemosignals that accelerate and delay puberty in female mice. Control tests determined that the manipulations, in and of themselves, did not bring about any changes in release or reception of the chemosignals. Rendering mice peripherally anosmic using a solution of zinc sulfate did result in effects on both donors and recipients. For donors, release of the substances in male urine, urine from females in estrus, or urine from pregnant or lactating females, all of which accelerate female puberty, were not influenced by peripheral anosmia. Peripheral anosmia did, however, bring about the cessation of release of the substance in the urine of grouped adult females that delays sexual maturation in conspecific females. Peripherally anosmic young female recipients of the chemosignals were accelerated in their sexual development when the treatment applied involved urine from pregnant or lactating females. However, the acceleratory effects normally produced by male urine or urine from females in estrus did not occur in peripherally anosmic young females. The substance in the urine of grouped adult females did not produce delays in puberty when the recipient females were rendered peripherally anosmic prior to urine treatment.

Animals↗
PubMed1994

Physiology of puberty.

Puberty is not a single event but one stage in development. The endocrine events of puberty in many ways recapitulate previous changes in the fetus. It is currently not known what triggers puberty at an appropriate time. It appears that puberty is restrained by higher central nervous system controls, but the restraint can be eliminated by injury or tumor growth resulting in premature puberty. The first endocrine event of puberty is an increase in the amplitude of gonadotropin pulses at night due to increased pulsatile release of hypothalamic gonadotropin-releasing hormone (GnRH) into the hypothalamic-pituitary portal system. This is reflected by an increase in luteinizing hormone secretion after a bolus of exogenous GnRH. Gonadal steroids are produced due to increased gonadotropin stimulation, and secondary sexual development follows a well-described pattern of changes. The pubertal growth spurt results from an increase in growth hormone secretion induced by sex steroids as well as from local production of growth factors. Positive feedback leads to the onset of menses and ovulation in girls by mid-puberty or later. This physical and reproductive maturity occurs in an orderly pattern, of which the physiology is described and in large part understood.

Female↗
PubMed1977

Plasma gonadotropins and estrogens in girls with idiopathic precocious puberty.

Luteinizing hormone (LH), follicle-stimulating hormone (FSH) estrone, and estradiol were measured radioimmunologically in more than 60 plasma specimens of 34 girls suffering from idiopathic precocious puberty. Although the median values of both gonadotropins in the plasma of the patients (LH = 1.0 ng/ml; FSH = 1.6 ng/ml) were higher than those from healthy prepubertal girls (LH = 0.6 ng/ml; FSH = 0.5 ng/ml), only 23 out of 64 LH levels and 30 out of 64 FSH levels exceeded the upper normal limit for age. While the median value of plasma estrone (13 pg/ml) was found to lie within the normal range for prepubertal girls (7-29 pg/ml) and only 13 out of 75 estrone values were pathologically elevated, the median value of plasma estradiol (22 pg/ml) was nearly 3 times higher than the normal median for prepuberty (8 pg/ml). Of 75 estradiol levels, 35 were above normal for age. Grouping the values according to the stage of sexual development revealed considerably lower gonadotropin and estrogen levels in the patients than in normally maturing girls of the same developmental stage. However, patients who were examined repeatedly at short intervals over a 1-month period showed an almost cyclic sequence of their estradiol levels similar to the pattern observed in healthy pubertal girls.

Age Factors↗
PubMed1998

Androgen receptor expression in the testes and epididymides of prenatal and postnatal Sprague-Dawley rats.

The androgen receptor (AR) plays a critical role in sexual differentiation and in the virilization of the male reproductive system. A clear understanding of AR expression at the early stages of sexual development will help elucidate the sensitivity of perinatal animals to endocrine modulation by external agents, such as some environmental chemicals. Immunohistochemistry was used in this study to localize the AR in the differentiating testis and epididymis of Sprague-Dawley rats starting from gestation day 15 until postnatal day 21. Positive AR staining was found on gestation day 15 in the mesenchymal as well as in the epithelial cells in the mesonephros. Weak staining was also observed in a small number of interstitial cells in the primordial testis at this age. The fetal interstitial and peritubular myoid cells showed positive AR immunoreactivity early in development, but the Sertoli cells did not overtly express the receptors until postnatal day 5. The intensity of staining and number of AR-positive cells in the testis and epididymis increased over time. The epithelium in the mesonephros-derived tissues, including rete testis and epididymis, appeared to exhibit a higher capacity to express AR than the rest of the testicular tissue. The results demonstrate that AR expression in the primordial male reproductive system is highly specific to time and cell type and modify previous understanding on the timing of AR expression in the testicular tissue. Since AR-positive cells at various developmental stages may be potential sites of interaction with chemicals that adversely affect sexual differentiation, improved understanding of AR ontogeny will help in investigating the effects of AR-reactive agents, such as environmental antiandrogens, with respect to specific windows of sensitivity.

Animals↗
PubMed2003

Extracellular matrix and sex-inducing pheromone in Volvox.

During evolution of multicellularity it was imperative to create a complex, multifunctional extracellular matrix (ECM) out of the simple cell wall of a unicellular ancestor. The green alga Volvox represents one of the simplest multicellular organisms, but even so, it already has a highly developed ECM. This ECM is mainly composed of an assortment of glycoproteins, many of which are hydroxyproline rich and extensively sulfated. Several ECM proteins are cross-linked and might have only structural functions. However, the ECM does not represent a static but rather a dynamic and multifunctional interface between a cell and its neighboring cells or its environment. It not only provides protection and structural support for the shape of each cell and the organism as a whole, but also plays a broad range of biological roles in growth, development, reproduction, and responses to environmental stress or wounding. The variety of functions of the ECM requires many glycoproteins to do the work. To attain a high flexibility and adaptability, almost all ECM glycoproteins from Volvox consist of modules, defined as functional subunits that form modular mosaic proteins with an outstanding combinatorial potential. The ECM's functions are not only extensive but also change under developmental control or by environmental incidents. The changing scope of duties necessitates a permanent ECM turnover and remodeling. In Volvox carteri one particularly challenging trigger of such ECM modifications is a sex-inducing pheromone, which is one of the most potent biological effector molecules known: the glycoprotein pheromone is fully effective for inducing sexual development in males and females at concentrations as low as 10(-16) M. The earliest detectable response to the pheromone is the synthesis of ECM glycoproteins.

Amino Acid Sequence↗
PubMed1994

Intrinsic secretory characteristics of luteinizing hormone and prolactin episodic release during pubertal development.

The intrinsic characteristics of LH and prolactin (PRL) episodic secretion were evaluated in a group of 18 children (8M and 10F). The children were divided into two groups according to the Tanner stage: Group A (Tanner < or = 1, N = 7, 3M and 4F, 6-10 years of age) and group B (Tanner 2-3, N = 11, 5M and 6F, 9-11 years of age). A pulsatility study of 4 h, sampling every 10 min, was carried out in all children. LH and PRL plasma levels were assayed by IFMA and RIA respectively. LH and PRL secretory episodes were then identified on plasma determinations using the program DETECT. Instantaneous secretory rates (ISR) were then computed for both LH and PRL using the specific algorithm within the DETECT program. Plasma LH levels were different between the two groups of children. Group A children showed undetectable LH plasma levels (below the minimal detectable dose of 0.1 mIU/ml), while group B demonstrated LH plasma levels in the normal range of values for age and sexual development (1.5 +/- 0.3 mIU/ml, mean +/- SEM). LH pulse frequency for group B was 3.2 +/- 0.4 peaks/4 h. No significant differences in mean plasma PRL levels, pulse frequency and pulse amplitude were observed between the two groups of children. Computation of ISR for LH (group B only) and PRL (both groups) identified the intrinsic episodic characteristics of the two hormones. No significant differences in LH and PRL pulse frequencies were observed when comparing the results estimated on ISR with those estimated on plasma concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1996

Deletion of the Cochliobolus heterostrophus mating-type (MAT) locus promotes the function of MAT transgenes.

Cochliobolus heterostrophus has alternate genes (MAT-1 and MAT-2) at its mating-type locus. Transformants of a MAT-1 or a MAT-2 strain carrying a transgene of opposite mating type can self and are dual maters; the transgene, however, promotes development of pseudothecia only, not ascospores. To determine if the resident gene interferes with the function of the transgene, transformation vectors were designed to delete different amounts (2.5 kb, 5.7 kb, and 6.3 kb) of DNA at the MAT locus. Deletions occurred at a higher frequency (about 90% of transformants) with linearized plasmid than with circular plasmid (about 15% of transformants), and all three vectors were equally efficient at gene replacement. Both MAT-1 and MAT-2 could be deleted with the same set of vectors. Re-transformation of deletion strains (regardless of deletion size) with a wild-type copy of MAT restored full mating ability, indicating that the resident MAT gene interferes with function of the MAT transgene. Moreover, sexual development was normal whether the MAT transgene integrated at the homologous or at an ectopic site.

Ascomycota↗
PubMed1998

Ovarian function after bone marrow transplantation during childhood.

Ovarian failure is often brought about by the conditioning protocol used for bone marrow transplantation (BMT). We monitored ovarian function in 31 girls conditioned for BMT at 10.3 +/- 0.6 (s.e., 3.2-17.5) years by chemotherapy alone (group 1, n = 8) or chemotherapy plus body irradiation (12 Gy, fractionated in group 2, n = 9, or 10 Gy single total body in group 3, n = 7, and 5 or 6 Gy single thoraco-abdominal in group 4, n = 7, irradiation) at 13.4 +/- 0.4 (11.7-18.6) years. Breast development was normal (n = 11), did not occur (n = 14), or did not progress spontaneously (n = 2) after BMT. The other four girls who menstruated before BMT had permanent amenorrhea. Basal plasma gonadotropin concentrations were measured in 29; follicle-stimulating hormone was increased in them all and luteinizing hormone in 23. At the last clinical evaluation at 16.3 +/- 0.4 (12.1-21.6) years, 23 girls had complete ovarian failure, two had partial ovarian failure, and six had normal ovarian function. Three of these were the youngest group 1 patients and those who had not received busulfan. We conclude that conditioning for BMT given during childhood frequently prevents normal estrogen secretion at puberty. Adequate substitutive treatment may be necessary to induce growth acceleration and sexual development.

Adolescent↗
PubMed2001

Two-generation reproductive toxicity study of tributyltin chloride in female rats.

A two-generation reproductive toxicity study of the effects of tributyltin chloride (TBTCl) was conducted in female rats using dietary concentrations of 5, 25, and 125 ppm TBTCl. Reproductive outcomes of dams (number and body weight of pups and the percentage of live pups) and the growth of female pups (the day of eye opening and body weight gain) were significantly decreased in the 125 ppm TBTCl group. A delay in vaginal opening and impaired estrous cyclicity were also observed in the 125 ppm TBTCl group. However, an increase in anogenital distance was found in all TBTCl groups on postnatal d 1. A dose-effect relationship was observed in TBTCl-induced changes in anogenital distance. These results indicate that the whole-life exposure to TBTCl affects the sexual development and reproductive function of female rats. In addition, the TBTCl-induced increase in anogenital distance seems to suggest it may exert a masculinizing effect on female neonates. However, the concentrations of TBTCl used in this study are not environmentally relevant.

Analysis of Variance↗
PubMed1997

Characterization and developmental expression patterns of testicular androgen-binding protein in the Djungarian hamster (Phodopus sungorus).

Studies were conducted to characterize Djungarian hamster androgen-binding protein and examine its expression during development. The cDNA encoding the full length testicular androgen-binding protein was cloned and, except for two suspected polymorphisms, shared a common primary sequence with hepatic sex hormone-binding globulin. A single androgen-binding protein/sex hormone-binding globulin gene was identified and a 1.7 kb mRNA encoding androgen-binding protein/sex hormone-binding globulin was present in both the testis and liver. Testicular homogenates contained specific 5 alpha-dihydrotestosterone-binding activity that was identified as androgen-binding protein. In the prepubertal testis, immunoreactive androgen-binding protein/sex hormone-binding globulin subunits ranged from 46 kDa to 60 kDa, with the majority of isoforms > 50 kDa. These subunits were distinct from the major 55 kDa and 51 kDa isoforms of sex hormone-binding globulin present in the serum of prepubertal hamsters. Deglycosylation studies demonstrated that size heterogeneities were the result of developmentally specific glycosylation patterns. Expression of androgen-binding protein by the testis was upregulated during puberty and coincided with a decline in serum sex hormone-binding globulin activity. The tissue- and age-dependent expression of specific androgen-binding protein and sex hormone-binding globulin variants suggests that these proteins play different roles in steroid-mediated sexual development.

Amino Acid Sequence↗
PubMed1982

Responsiveness of gonadotropin secretion to infusion of an opiate-receptor antagonist in hypogonadotropic individuals.

We tested the hypothesis that suppressive effects of endogenous opiate substances are involved in certain hypogonadotropic states. For this purpose, we studied gonadotropin secretion in idiopathic hypopituitarism (five children), constitutionally delayed adolescence (five boys), and Kallmann's syndrome (three men). Endogenous opiate pathways were antagonized by the iv infusion of naloxone hydrochloride at a dose previously shown to elicit a prompt and significant increase in serum levels of LH in normal men. Under these conditions, naloxone did not increase serially sampled serum concentrations or mean urinary levels of LH: or FSH in eight patients with idiopathic hypopituitarism or Kallmann's syndrome. Gonadotropin concentrations in four of five patients with constitutional delay of adolescence also were unaffected. In one boy with clinical and biochemical indices of late pubertal development, naloxone elicited a significant increase in LH levels in blood and urine, similar to the pattern observed in normal men. In contrast to results in experimental animals, naloxone did not suppress serum PRL concentration significantly in any subject. These observations suggest that: 1) endogenous opiate mechanisms are unlikely to constitute a principal factor in maintaining hypogonadotropism in idiopathic hypopituitarism, delayed adolescence, or Kallmann's syndrome, at least acutely; 2) endogenous opiate mechanisms also cannot be implicated in the acute regulation or PRL secretion in children; and 3) the capability of adult men, but not early pubertal boys, to respond with increased gonadotropin secretion during inhibition of opiate receptors suggests that maturation of the opiate-related neuroendocrine system occurs during the course of sexual development in the human.

Adolescent↗
PubMed1997

Short stature and failure of pubertal development in thalassaemia major: evidence for hypothalamic neurosecretory dysfunction of growth hormone secretion and defective pituitary gonadotropin secretion.

UNLABELLED: In patients with beta-thalassaemia major, frequent blood transfusions combined with desferrioxamine chelation therapy lead to an improved rate of survival. Endocrine disorders related to secondary haemosiderosis such as short stature, delayed puberty and hypogonadism are major problems in both adolescent and adult patients. A total of 32 patients with beta-thalassaemia major undergoing treatment at the Children's Hospital, University of Göttingen were examined. Fourteen of these were short in stature. Growth hormone (GH) secretion was investigated in 13 patients exhibiting either a short stature or reduced growth rate. The stimulated GH secretion of 10 patients in this subgroup lay within the normal range. Studies of their spontaneous GH secretion during the night revealed that these patients had a markedly reduced mean GH and reduced amplitudes in their GH peaks. Low insulin-like growth factor (IGF)-I levels were seen in the growth-retarded thalassaemic patients. Eight were subjected to an IGF generation test and showed a strong increase in both IGF-I and insulin-like growth factor binding protein (IGFBP)-3 levels indicating intact IGF-I generation by the liver. Hypogonadotropic hypogonadism was found to be present in both the male and female patients with impaired sexual development. After priming with LH-releasing hormone (GnRH) per pump in 2 female and 5 male patients, no change in either their serum oestradiol or testosterone levels or in LH/FSH response to GnRH was observed suggesting that they were suffering from a severe pituitary gonadotropin insufficiency. Three male patients at the age of puberty but exhibiting short stature. low GH, low IGF-I and hypogonadism received low dose long-acting testosterone. After 3 12 months of therapy there was a marked growth spurt, higher nocturnal GH levels and an increase in both IGF-I and IGFBP-3. CONCLUSION: Reduced GH secretion and low IGF-I in thalassaemic patients are related to a neurosecretory dysfunction due to iron overload rather than to liver damage. Hypogonadotropic hypogonadism is caused by the selective loss of pituitary gonadotropin function. In patients with both GH deficiency and hypogonadism, low dose sexual steroid treatment should be considered either as an alternative or an additional treatment before starting GH therapy.

Adolescent↗
PubMed2006

Effect of temporary transfers to 14 h on age at first egg in domestic pullets reared on 8-h photoperiods.

1. Brown-egg pullets were reared on 8-h photoperiods and temporarily transferred at 80 d of age to 14-h photoperiods for 2, 4, 6, 8, 10 or 12 d. Controls were either maintained on 8 h or permanently transferred to 14 h at 80 d. 2. Pullets given 8 or 12 long days matured 8-9 d earlier than constant 8-h controls, but 22-23 d later than pullets transferred permanently to long days. Mean age at first egg for the groups given 2, 4, 6 or 10 d of 14-h days were not significantly different from the 8-h controls. The mean weight of first egg and body weight at first egg for the temporarily-photostimulated groups were not significantly different from constant 8-h controls, but egg weights were > or = 5.1 g and body weights at first egg > or = 200 g heavier than the birds transferred permanently to 14 h. 3. It is concluded that up to 6 temporary long days may be given (from 80 d of age) without affecting the timing of sexual maturity, but that the provision of 8 or more long days will accelerate sexual development, thought not to the extent of a permanent transfer, in most birds within a flock. A regression analysis of the ages at which the first and last birds in the groups given 6, 8, 10 or 12 long days matured suggested that about 20 d of photostimulation are required to achieve a mean age at first egg similar to that of birds permanently transferred to long days.

Animal Husbandry↗
PubMed2003

The endocrinology of hypothalamic hamartoma surgery for intractable epilepsy.

Intractable epilepsy has replaced central precocious puberty (CPP) as the main indication for surgery in patients with hypothalamic hamartoma (HH). However, concern about endocrine complications and the paucity of published endocrine data may dissuade clinicians from recommending HH surgery. We report the preoperative endocrine status and postoperative endocrine findings of patients undergoing HH surgery at our centre. Twenty-nine patients aged 4-23 years (mean 10 years) underwent detailed clinical assessment and biochemical testing of the hypothalamic-pituitary axis before and after transcallosal resection of their HH. The perioperative evaluation included comprehensive evaluation of pubertal status, growth, weight, thyroid and adrenal function, and osmoregulation. Forty-five percent of patients had CPP at presentation and this was not altered by HH surgery. Asymptomatic deficiencies in thyroid hormone, growth hormone and cortisol response were identified in several patients prior to surgery, and biochemical CPP was present in four, clinically prepubertal children. Free thyroxine fell after surgery in the majority, and to clinically significant levels prompting treatment in 5 patients. Low growth hormone was present in 5/8 patients who had had previous HH surgery and in 6/29 following transcallosal surgery at our centre; short stature did not result during the period of follow-up. Hypernatraemia developed in most patients postoperatively with sodium >150 mmol/L seen in 16 (55%) patients; however, this was asymptomatic, not often associated with polyuria, and transient; no patient required ongoing antidiuretic hormone replacement. Appetite stimulation and early postoperative weight gain occurred in 45% patients, but resolved in half. Disturbance of endocrine function may be clinically silent and should be routinely evaluated prior to HH surgery for intractable epilepsy. Following surgery, hypernatraemia, low thyroxine, low growth hormone, and weight gain are the main endocrine problems encountered. Prior, unsuccessful surgery may be a risk factor for endocrinopathy. Except for weight gain in some patients, these postoperative endocrine disturbances appear to be transient, mild or asymptomatic, and easily treated where necessary. Long term follow-up of growth and sexual development in a large series of patients is required.

Adolescent↗

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