Neonatal diabetes mellitus with pancreatic agenesis in an infant with homozygous IPF-1 Pro63fsX60 mutation.

Permanent neonatal diabetes mellitus is a rare disorder known to be caused by activating mutations in KCNJ11 or ABCC8, inactivating mutations in INS, or very rarely in GCK or insulin promotor factor-1 (IPF-1) genes. We report a patient with permanent neonatal diabetes mellitus and severe exocrine pancreatic insufficiency. Ultrasound examination revealed pancreatic agenesis with a suggestion of a small amount of tissue in the head of the pancreas. Genetic testing revealed that the neonate had a homozygous Pro63fsX60 IPF-1 mutation. This is the second reported case of neonatal diabetes mellitus secondary to a homozygous mutation in the IPF-1 gene and supports the previously proposed biological role of IPF-1 in the pancreatic development in human.

11-Ketotestosterone Is the Dominant Circulating Bioactive Androgen During Normal and Premature Adrenarche.

Context: Adrenarche refers to the rise of dehydroepiandrosterone sulfate (DHEA-S) associated with the development of a functional adrenal zona reticularis. Clinical features of adrenarche include onset of body odor, axillary hair, and pubic hair, which reflect increased androgen action. An early rise in adrenal androgens, or premature adrenarche (PremA), is a risk factor for adverse metabolic profiles in adolescence and adulthood. The bioactive androgens associated with adrenarche and PremA remain poorly understood. The adrenal gland is a potential source of testosterone (T) and the 11-oxygenated derivatives 11ß-hydroxytestosterone (11OHT) and 11-ketotestosterone (11KT). Objective: The objective of this study was to characterize the adrenal androgen biome contributing to adrenarche and PremA. Participants and Methods: With the use of mass spectrometry, 19 steroids including the 11-oxygenated derivatives of T were measured in sera obtained from girls with PremA (n = 37; 4 to 7 years) and age-matched girls (n = 83; 4 to 10 years). Results: In reference population girls, dehydroepiandrosterone, DHEA-S, androstenediol-3-sulfate, T, and 11KT all increased at the onset of adrenarche (6 to 8 years) and beyond (9 to 10 years) (P < 0.05 vs younger subjects 4 to 5 years). T, 11OHT, and 11KT were further elevated in PremA vs age-matched girls (P < 0.001). Circulating concentrations of 11KT during adrenarche and PremA exceeded those of T and 11OHT (11KT > T ≥ 11OHT). Androgen receptor activity and nuclear translocation studies demonstrated that 11KT is a potent androgen similar to T. Conclusions: Our findings suggest that 11KT is the dominant bioactive androgen in children during adrenarche and PremA. Its androgenic capacity suggests that it may be responsible for the phenotypic changes seen in these phenomena.

Relationships among body mass index, parental perceptions, birthweight and parental weight after referral to a weight clinic.

OBJECTIVE: We sought to determine whether, in a specialty referral clinic, parental perceptions of their child's obesity were commensurate with the child's body mass index z score. Secondarily, we examined the impact of birth weight and parental body mass index on their child's body mass index z score and review results of an intake questionnaire. DESIGN: Cross-sectional study SETTING: University of Michigan from March 21, 2003 through June 30, 2004 PARTICIPANTS: Eighty-two children ages 1-20.2 years of age INTERVENTION: Body mass index z score for all participants was calculated. An intake questionnaire was completed by caregivers in which they were asked to describe their child as little overweight, overweight, very overweight or obese. OUTCOME MEASURES: Mean body mass index z score was compared to each parental descriptor. Regression analysis related body mass index z score to birthweight and parental body mass index. RESULTS: Body mass index z score was not related to parental descriptors. Maternal body mass index and child birthweight were predictors of the child's body mass index z score (r2=0.15, p<0.05; and r2=0.11, p<0.05, respectively). Both together produced a better model than either alone (r2=0.23, p<0.05). There was no relationship between paternal and child body mass index z score (p>0.05). CONCLUSIONS: There is a divergence between the parental perception of childhood obesity and the clinical definition that persists even in the context of an explicit referral. Given the significant impact of maternal weight on childhood overweight, education for prevention of overweight youth should encompass prenatal, early childhood and adolescent health maintenance.

Prevalence of overweight and obesity in a U.S. pediatric surgical population.

OBJECTIVE: To describe the prevalence of overweight and obesity in a pediatric surgical population from a large teaching hospital in the United States. METHODS AND PROCEDURES: We carried out a retrospective review of the perioperative database for the period January 2000 to December 2004 at the University of Michigan. Using directly measured height and weight, we computed body mass index (BMI) on 6,017 children. Overweight and obesity were defined using age- and gender-specific cut-off according to the National Center for Health Statistics (NCHS)/Centers for Disease Control and Prevention (CDC) (2000) growth charts. We also examined the type of surgical procedures most commonly performed on overweight and obese children, and the distribution of overweight and obese patients by preoperative American Society of Anesthesiologist (ASA) classification. RESULTS: We found a somewhat "heavy" pediatric population with a mean BMI of 21.6kg/m(2). The mean BMI in males was 21.7 kg/m(2) and 21.6 kg/m(2) in females. BMI showed a positive correlation with age overall (r=0.48, p < 0.01), and in both males and females. The overall prevalence of overweight and obesity using age-specific criteria was 14.4% and 17.2%, respectively. Approximately 10% of the children met adult criterion for obesity (BMI > or =30 kg/m(2)). Orthopedic and otolaryngological procedures were the most common surgeries in this cohort of overweight and obese children. We further found that 35.3% of obese and 20.6% of morbidly obese children were classified as ASA I. CONCLUSION: The prevalence of overweight and obesity is high in this pediatric surgical population. Follow-up studies examining the impact of overweight and obesity on perioperative outcome are needed.

Age-dependent Increases in Adrenal Cytochrome b5 and Serum 5-Androstenediol-3-sulfate.

CONTEXT: Adrenal production of dehydroepiandrosterone sulfate (DHEA-S) increases throughout childhood owing to expansion of the zona reticularis (ZR). ZR features cells with a steroidogenic phenotype distinct from that of the adjacent zona fasciculata, with higher expression of cytochrome b5 type A (CYB5A) and steroid sulfotransferase type 2A1 but decreased 3ß-hydroxysteroid dehydrogenase type 2 (HSD3B2). In addition to DHEA-S, three adrenal Δ5-steroid sulfates could provide additional tools to define adrenal maturation. OBJECTIVE: This study sought to simultaneously measure serum levels of four adrenal Δ5-steroid sulfates, pregnenolone sulfate (Preg-S), 17α-hydroxypregnenolone sulfate (17OHPreg-S), DHEA-S, and 5-androstenediol-3-sulfate (Adiol-S) as a function of age and relate their production to the age-dependent adrenal localization of CYB5A. PARTICIPANTS AND METHODS: Δ5-steroid sulfates were quantified by liquid chromatography-tandem mass spectrometry in sera from 247 normal children (129 males,118 females) age 1.5-18 y and 42 adults (20 males, 22 females). Immunofluorescence localized HSD3B2 and CYB5A in normal adrenal glands from subjects age 2-35 y. Finally, HAC15 adrenocortical cells were transduced with lentiviral short hairpin RNA to suppress CYB5A expression. RESULTS: Of the Δ5-steroid sulfates quantified, DHEA-S was most abundant. Adiol-S increased in parallel with DHEA-S. Steroid ratios (17OHPreg-S/DHEA-S) suggested increases in 17,20-lyase activity during childhood. Immunofluorescence analysis showed age-related increases in ZR CYB5A immunoreactivity. Furthermore, silencing CYB5A in HAC15 adrenocortical cells significantly reduced DHEA-S and Adiol-S production. CONCLUSION: Adiol-S shows a similar age-related increase to that of DHEA-S. This likely results from the childhood expansion of CYB5A-expressing ZR, which enhances 17,20-lyase activity and the production of DHEA-S and Adiol-S.

Incomplete modified fast in obese early pubertal girls leads to an increase in 24-hour growth hormone concentration and a lessening of the circadian pattern in leptin.

We studied nutrition and GH in eight obese girls, aged 6-11 yr. Blood was sampled every 15 min for 24 h. A 48-h diet providing 25% of assumed caloric needs was imposed, with repeat sampling during the last 24 h. Six nonfasting lean girls were also studied, and their mean GH was 3 times that of the obese girls in the fed state (P = 0.024). Dieting increased mean GH by 60% (P = 0.0028). There was no difference in pulse number for either group, but total secretion for lean girls was 3.9 times greater than that in obese girls during the fed state. With dieting, obese girls increased their total GH secretion by 60% (P = 0.010), but maintained lower total secretion, approximately 40% that of lean girls (P = 0.014). Mean leptin in obese girls in the fed state was 6.2 times greater than mean leptin in lean girls (P = 0.0001), with higher concentrations at night (P < 0.05) and lowering of total mean leptin while dieting. We conclude that in early pubertal obese girls, short-term caloric restriction partially reverses the low GH state that is characteristic of obesity. The change is concomitant with a decrease in leptin and a lessening of circadian differences.

Differential effects of raloxifene and estrogen on insulin sensitivity in postmenopausal women.

OBJECTIVES: To test the hypothesis that both raloxifene and estrogen would improve insulin sensitivity in postmenopausal women and that the magnitude of the effect would be similar for both drugs. DESIGN: Placebo-controlled, double-blind, randomized study. SETTING: The General Clinical Research Center of the University of Michigan Medical Center, a university hospital. PARTICIPANTS: Forty-four healthy postmenopausal women 73 +/- 7 years old (mean age +/- standard deviation) who were not receiving hormone replacement therapy. INTERVENTION: Eight weeks of drug therapy with randomization to raloxifene (n = 16), estrogen (n = 14), or placebo (n = 14). MEASUREMENTS: These subjects underwent a frequently sampled intravenous glucose tolerance test to determine insulin sensitivity (SI) and total and regional (central) body composition measurements by dual-energy x-ray absorptiometry at baseline and after 8 weeks of drug therapy. RESULTS: There were no statistically significant differences in age, body mass index, total or central fat mass, or SI between the three groups at baseline. The major outcome variable was SI. After 8 weeks of drug therapy, there was no significant change in SI in the placebo group or in the estrogen group and a significant decrease in SI in the raloxifene group, P =.003. CONCLUSION: In contrast to estrogen's ability to maintain insulin sensitivity, raloxifene decreases insulin sensitivity in healthy nondiabetic postmenopausal women. The clinical significance of this effect of raloxifene to impair insulin sensitivity in postmenopausal women warrants further evaluation in future studies.

Androgenicity and obesity are independently associated with insulin sensitivity in postmenopausal women.

An increase in androgenicity may contribute to the development of insulin resistance in postmenopausal women. Increased androgenicity in women has been found to be associated with the development of type 2 diabetes. In addition, obesity and central obesity are associated with greater androgenicity. Insulin sensitivity, androgenicity, and body composition were characterized in 34 nondiabetic postmenopausal women age 72 +/- 1 years (mean +/- SEM) to test the hypothesis that androgenicity is a predictor of insulin sensitivity independent of measures of obesity. Androgenicity was measured using levels of sex hormone-binding globulin (SHBG), total and free testosterone, dehydroepiandrosterone sulfate (DHEA-S), androstenedione, and free androgen index (FAI). Insulin sensitivity (S(I)) was determined from a frequently sampled intravenous glucose tolerance test. Body composition measures included body mass index (BMI) and dual energy x-ray absorptiometry measurements of total and central fat mass. S(I) was found to be associated with total fat mass (r = -.51, P =.002), central fat mass (r = -.62, P =.0001), BMI (r = -.55, P =.0008), SHBG levels (r =.65, P =.0001), and FAI (r = -.41, P =.01). SHBG levels were inversely correlated with central fat mass (r = -.59, P =.0002). Using multiple regression, SHBG and central fat mass were the only significant independent predictors of S(I), accounting for 50% of its variance (r =.71, P =.0001); total fat mass, BMI, total and free testosterone, DHEA-S, androstenedione, and FAI did not enter the model. We conclude that there is a significant association between insulin sensitivity and androgenicity in postmenopausal women that is independent of obesity. Interventions to decrease androgenicity may therefore be useful in improving insulin sensitivity in postmenopausal women.

Differences in endocrine function with varying fitness capacity in postpubertal females across the weight spectrum.

OBJECTIVE: To relate endocrine and nutritional correlates of fitness in postpubertal physically active females across the normal weight spectrum to identify markers and how these might serve as associations of exercise-related endocrine disruption. DESIGN: Cross-sectional study analyzed by repeated-measures analysis of variance for frequent blood sampling. SETTING: A general clinical research center. SUBJECTS: Twenty-two healthy postpubertal female subjects recruited 2 years or more after menarche. MAIN OUTCOME MEASURES: Maximum oxygen consumption was determined as an index of fitness and daily caloric intake was calculated from a 3-day food diary. During the follicular phase of the cycle, luteinizing hormone was sampled every 10 minutes during a 24-hour period, while follicle-stimulating hormone and cortisol were sampled hourly. RESULTS: For every 1-unit increase in maximum oxygen consumption, cortisol concentration increased by 2% (P =.005; 95% confidence interval, 1%-3%). However, there was no association between mean gonadotropin concentrations and fitness. Hormone concentrations were not significantly associated with body mass index or percentage of body fat. Higher mean caloric intake from a 3-day summary was inversely related to mean luteinizing hormone concentration, which decreased by 5.5% for every 100-kcal increase (P =.03; 95% confidence interval, 1%-10%). With every 1-year increase in age at menarche, follicle-stimulating hormone concentration decreased by 12% (P =.01; 95% confidence interval, 4%-19%) and cortisol concentration increased by 7% (P =.03; 95% confidence interval, 1%-12%). CONCLUSIONS: In active adolescents, increased cortisol concentration may represent an adaptive change to exercise that may precede gonadotropin changes seen with higher levels of fitness.

Effects of denosumab treatment and discontinuation on human growth plates.

CONTEXT: Denosumab is a humanized monoclonal antibody to receptor activator of nuclear factor-κB ligand used primarily for postmenopausal osteoporosis and skeletal-related events from metastatic cancer. Its safety in children has not been established. OBJECTIVE: The objective of the study was to investigate the effects of denosumab treatment on skeletal growth and histology. DESIGN: This was an observational case report with radiological and histopathological analyses. SETTING: The study was conducted at a clinical research center. PATIENTS: A 9-year-old boy with fibrous dysplasia treated with a 7-month course of denosumab participated in the study. INTERVENTION: Histological analyses were performed and compared on growth plates from limbs that had been amputated before and 17 months after denosumab treatment. MAIN OUTCOME MEASURES: Skeletal radiographs and bone histopathology from before and after treatment were measured. RESULTS: After initiating denosumab, sclerotic metaphyseal bands appeared on radiographs. Posttreatment radiographs revealed migration of the bands away from the growth plates, consistent with continued linear growth. Histologically, the bands were composed of horizontally arranged trabeculae containing calcified cartilage. This cartilage appeared to derive from unresorbed primary spongiosa as a result of osteoclast inhibition by denosumab, similar to what has been observed with bisphosphonates. By 17 months after treatment, active bone resorption and formation had returned, as evidenced by the presence of active osteoclasts in resorption pits and osteoid surfaces. CONCLUSIONS: Further studies are needed to determine the safety of denosumab on the growing skeleton. However, in this child there was continued epiphyseal activity both during and after treatment and reversal of bone turnover suppression after treatment discontinuation, suggesting that denosumab did not have significant adverse effects on growth.

Denosumab treatment for fibrous dysplasia.

Fibrous dysplasia (FD) is a skeletal disease caused by somatic activating mutations of the cyclic adenosine monophosphate (cAMP)-regulating protein, α-subunit of the Gs stimulatory protein (G(s) α). These mutations lead to replacement of normal bone by proliferative osteogenic precursors, resulting in deformity, fracture, and pain. Medical treatment has been ineffective in altering the disease course. Receptor activator of NF-κB ligand (RANKL) is a cell-surface protein involved in many cellular processes, including osteoclastogenesis, and is reported to be overexpressed in FD-like bone cells. Denosumab is a humanized monoclonal antibody to RANKL approved for treatment of osteoporosis and prevention of skeletal-related events from bone metastases. We present the case of a 9-year-old boy with severe FD who was treated with denosumab for a rapidly expanding femoral lesion. Immunohistochemical staining on a pretreatment bone biopsy specimen revealed marked RANKL expression. He was started on monthly denosumab, with an initial starting dose of 1 mg/kg and planned 0.25 mg/kg dose escalations every 3 months. Over 7 months of treatment he showed marked reduction in pain, bone turnover markers (BTMs), and tumor growth rate. Denosumab did not appear to impair healing of a femoral fracture that occurred while on treatment. With initiation of treatment he developed hypophosphatemia and secondary hyperparathyroidism, necessitating supplementation with phosphorus, calcium, and calcitriol. BTMs showed rapid and sustained suppression. With discontinuation there was rapid and dramatic rebound of BTMs with cross-linked C-telopeptide (reflecting osteoclast activity) exceeding pretreatment levels, accompanied by severe hypercalcemia. In this child, denosumab lead to dramatic reduction of FD expansion and FD-related bone pain. Denosumab was associated with clinically significant disturbances of mineral metabolism both while on treatment and after discontinuation. Denosumab treatment of FD warrants further study to confirm efficacy and determine potential morbidity, as well as to determine the mechanism of RANKL in the pathogenesis of FD and related bone marrow stromal cell diseases.

Impact of fatness, insulin, and gynecological age on luteinizing hormone secretory dynamics in adolescent females.

OBJECTIVE: To study the link between fatness and gonadotropin secretion. Overweight status is linked to polycystic ovary syndrome (PCOS) in adolescents. We postulated that heavier adolescents without symptoms would secrete LH with: [1] increased pulse frequency (LHPF) and [2] exaggerated integrated concentrations (LHAUC). DESIGN: Cross-sectional. SETTING: General clinical research center. PATIENT(S): Eighty-seven postmenarcheal cyclic adolescents from lean to overweight recruited during the follicular phase. INTERVENTION(S): Luteinizing hormone sampling: [1] every 10 minutes/24 hours; [2] at 20-minute intervals after a GnRH challenge. MAIN OUTCOME MEASURE(S): The LHPF and LHAUC (calculated by the CLUSTER algorithm). Hormonal and metabolic covariates included percent body fat (PercentBF), insulin-like growth factor-I (IGF-I), fasting insulin, and the insulin resistance index HOMA-IR. The SAS software was used for analyses. RESULT(S): The PercentBF and younger gynecological age predicted faster LHPF. Fatness was negatively linked to LHAUC, which was best predicted by PercentBF and IGF-1 in multivariate modeling (R(2) = 0.25). The PercentBF and insulin predicted a lower 20-minute LH response to GnRH. CONCLUSION(S): [1] Higher adiposity and younger gynecological age predict rapid LHPF. [2] The early years after menarche represent a vulnerable window for an exaggerated LHPF with weight gain. [3] In healthy adolescents, higher adiposity is linked to lower LHAUC, thereby preserving pituitary stores.

Elevated testosterone and hypergonadotropism in active adolescents of normal weight with oligomenorrhea.

STUDY OBJECTIVE: Oligomenorrhea in active adolescent females of normal weight is presumed to be related to hypoestrogenism secondary to physical activity and decreased fat mass. We hypothesized that active adolescents with oligomenorrhea would have lower estrogen levels than normal controls with similar levels of cardiovascular fitness. DESIGN/PARTICIPANTS: Twenty healthy participants between the ages of 16 and 20 years were recruited at least 2 years postmenarche. Adolescents reporting fewer than 9 cycles a year (n = 6) were compared to 14 controls with monthly menstrual cycles. Histories of eating disorder, hirsutism, severe acne, depression, or amenorrhea were cause for exclusion. MAIN OUTCOME MEASURES: Body composition and bone density were measured by total body dual x-ray absorpitometry. Cardiovascular fitness was evaluated by measuring oxygen consumption during exercise. Control subjects were matched by age, body mass index (BMI), and fitness level. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, progesterone, and estradiol were obtained. Statistical analysis was performed using SAS 9.1. RESULTS: Cardiovascular fitness in both groups was within normal limits for age. No significant differences in BMI, estradiol concentrations, or bone density were found, but trunk fat mass was lower in adolescents with oligomenorrhea who also reported more frequent exercise. Testosterone concentrations and LH/FSH ratios were significantly higher in participants with irregular menstrual cycles (P = 0.0018 and <0.001, respectively). CONCLUSION: Adolescents with oligomenorrhea were leaner, yet they had higher testosterone levels and a greater LH/FSH ratio than their BMI-matched, cyclic counterparts. We hypothesize that, in active adolescents of normal weight, elevated androgen and LH concentrations are linked to ovarian dysfunction, which can masquerade as exercise-induced oligomenorrhea.

Ghrelin concentrations reflect body mass index rather than feeding status in obese girls.

Ghrelin stimulates both appetite and secretion of growth hormone (GH). We hypothesized that fasting should increase ghrelin, thereby increasing GH concentrations in obesity. Eight obese girls underwent a 48-h fast, receiving 25% of calories for ideal body weight. Blood was obtained every 15 min for the last 24 h of the fast. Four months later, six obese girls had blood obtained in the fed state. Two additional obese and five lean girls had blood obtained in the fed state. Ghrelin was determined in 3-h pools. Mean ghrelin concentrations were 0.41 +/- 0.03 ng/mL for lean girls and 0.16 +/- 0.01 ng/mL in obese fed girls (p < 0.0001). Lean fed girls had diurnal variation of ghrelin whereas obese fed girls did not. Fasting neither increased ghrelin (0.18 +/- 0.01 ng/mL) nor restored diurnal variation. Ghrelin concentrations were related to the body mass index (BMI) SD score (SDS) (r = 0.45, p = 0.005). For the six obese girls who participated in both fasting and fed studies, change in mean ghrelin concentration between studies was related to change in BMI SDS but not fed or fasting state. Ghrelin concentrations are, thus, a function of BMI rather than feeding status in obese girls.

Childhood body mass index and perioperative complications.

BACKGROUND: Our aim was to describe the incidence of quality assurance events between overweight/obese and normal weight children. METHODS: This is a retrospective review of the quality assurance database of the Mott Children's Hospital, University of Michigan for the period January 2000 to December 2004. Using directly measured height and weight, we computed the body mass index (BMI) in 6094 children. Overweight and obesity were defined using age and gender-specific cut off according to the National Center for Health Statistics (NCHS)/Centers for Disease Control and Prevention (CDC) (2000) growth charts. Frequency of quality assurance events were compared between normal weight, overweight, and obese children. RESULTS: There were 3359 males (55.1%) and 2735 females (44.9%). The mean age for the entire population was 11.9 +/- 5.2 while the mean BMI was 21.6 +/- 6.7 kg x m(-2). The overall prevalence of overweight and obesity was 31.6%. Obesity was more prevalent in boys than girls (P = 0.016). Preoperative diagnoses of hypertension, type II diabetes, and bronchial asthma were more common in overweight and obese than normal weight children (P = 0.0001 for hypertension, P = 0.001 for diabetes and P = 0.014 for bronchial asthma). Difficult airway, upper airway obstruction in the postanesthesia care unit (PACU) and PACU stay longer than 3 h and need for two or more antiemetics were more common in overweight and obese than normal weight children (P = 0.001). There was no significant difference in the incidence of unplanned hospital admission following an outpatient surgical procedure between normal weight and overweight/obese children. DISCUSSION: Studies on perioperative aspects of childhood overweight and obesity are rare. Our report shows a high prevalence of overweight and obesity in this cohort of pediatric surgical patients. Certain perioperative morbidities are more common in overweight and obese than in normal weight children. There is a need for prospective studies of the impact of childhood overweight and obesity on anesthesia and surgical outcome.

The pattern of growth hormone secretion during the menstrual cycle in normal and depressed women.

OBJECTIVE: Major depression is associated to altered hypothalamic-pituitary function. Stress is linked to elevated cortisol as well as menstrual cycle disturbance; however, there is no known relationship between depression and menstrual cycle disruption. The aim of this study was to investigate changes of growth hormone (GH) secretion during the menstrual cycle in normal and depressed women. DESIGN: Case-control study. PATIENTS AND METHODS: Nineteen women affected with depression and 24 normal controls were included. The two groups had comparable body mass index (BMI), and age (29.4 +/- 9.8 vs. 28.6 +/- 9.7 years). Nine depressed and 10 controls were studied in the follicular phase, while 10 depressed and 14 controls were studied in the luteal phase of the cycle. GH was sampled every 10 min for 24 h, and the data were analysed by the cluster pulse detection method. RESULTS: There was no difference in 24-h mean GH concentrations between depressed and control subjects (P = 0.93), even after accounting for menstrual cycle phase (P = 0.38). GH pulse frequency was higher during the follicular phase of the cycle (P = 0.032), and nocturnal GH was higher in the follicular phase of the cycle (P = 0.05, and after adjusting for 24-h GH, P = 0.0138) regardless of whether the subjects were depressed or healthy. CONCLUSIONS: In studies of GH secretion in women with or without depression, it is necessary to control for the phase of menstrual cycle.