Thyroidectomy in a two-year old for graves' disease.

INTRODUCTION: The most common cause of hyperthyroidism in children is graves' disease - an autoimmune disorder in which antibodies stimulate the thyrotropin receptor to signal growth thyroid gland by increasing thyroid hormone synthesis and release. It can be treated with medical therapy, radioactive iodine, or surgery. PRESENTATION OF CASE: JD was a two year old male who presented with severe diarrhea and diffuse neck enlargement. Laboratory work up was consistent with graves' disease. DISCUSSION: Despite maximal outpatient and inpatient treatment with methimazole, atenolol, prednisone, and SSKI, he suffered persistent thyrotoxicosis. He underwent near-total thyroidectomy without complication. CONCLUSION: This case is notable as it may represent the youngest patient in the literature who has undergone thyroidectomy for graves' disease.

Comparison of detection of normal puberty in girls by a hormonal sleep test and a gonadotropin-releasing hormone agonist test.

CONTEXT: The magnitude of sleep-related gonadotropin rise required to activate pubertal feminization is not established. OBJECTIVE: The objective of the study was to determine the normal relationship of pubertal hormone responses to sleep and to GnRH agonist (GnRHag) challenge across the female pubertal transition. DESIGN/SETTING: This was a prospective study in a General Clinical Research Center. PARTICIPANTS: Sixty-two healthy 6- to 13-year-old volunteer girls participated in the study. INTERVENTIONS: Interventions included overnight blood sampling followed by GnRHag (leuprolide acetate) injection. PRIMARY OUTCOME VARIABLES: The primary outcome variables included LH, FSH, and estradiol. RESULTS: LH levels rose steadily during sleep and after GnRHag throughout the prepubertal years. The LH response to sleep and GnRHag correlated well across groups (eg, r = 0.807, peak vs 4 h post-GnRHag value); however, this correlation was less robust than in boys (r = 0.964, P < .01). Sleep peak LH of 1.3 U/L or greater had 85% sensitivity and 2.1 U/L or greater 96% specificity for detecting puberty (thelarche). The LH 1-hour post-GnRHag value of 3.2 U/L or greater had 95% sensitivity and 5.5 U/L or greater 96% specificity for detecting puberty. Girls entered puberty at lower LH levels than boys. FSH levels rose day and night during the prepubertal years to reach 1.0 U/L or greater during puberty but discriminated puberty poorly. Estradiol of 34 pg/mL or greater at 20-24 hours after GnRHag was 95% sensitive and 60 pg/mL or greater was 95% specific for puberty. Thirty-six percent of overweight early pubertal girls had meager hormonal evidence of puberty. CONCLUSIONS: These data suggest that sleep-related pubertal hormone levels critical for puberty are normally reflected in the responses to GnRHag testing across the normal female pubertal transition. Inconsistencies between clinical and hormonal staging may arise from peripubertal cyclicity of neuroendocrine function and from excess adiposity.

Comparison of detection of normal puberty in boys by a hormonal sleep test and a gonadotropin-releasing hormone agonist test.

CONTEXT: The magnitude of sleep-related gonadotropin rise required to activate pubertal gonadal function is not established. OBJECTIVE: Our objective was to determine the normal relationship between sleep-related pubertal hormone levels and pituitary-testicular responsiveness to a GnRH agonist (GnRHag) test across the pubertal transition. DESIGN/SETTING AND PARTICIPANTS: We conducted a prospective study in a General Clinical Research Center with healthy 9- to 15-yr-old volunteer boys. INTERVENTIONS: INTERVENTIONS included overnight blood sampling followed by leuprolide acetate injection (10 µg/kg). PRIMARY OUTCOME VARIABLES: LH, FSH, and testosterone levels were evaluated. RESULTS: LH levels during sleep and post-GnRHag rose steadily during the late prepubertal years. Sleep peak LH correlated highly with the LH response to GnRHag across groups (r = 0.913). A sleep peak LH level of at least 3.7 U/liter predicted pubertal testicular activation with 100% accuracy. LH of at least 14.8 and at least 19.0 U/liter 4 h after GnRHag, respectively, predicted puberty with 100% sensitivity/94% specificity and 100% specificity/94% sensitivity. Overweight pubertal boys had transiently prolonged responses to GnRHag. FSH rose during both waking and sleeping hours during the prepubertal years, and all pubertal boys had an FSH level of at least 0.9 U/liter awake and at least 1.2 U/liter asleep. Sleep LH was more closely related than FSH to testicular size. CONCLUSIONS: These data suggest that a critical LH level during sleep (≥3.7 U/liter) heralds the onset of pubertal virilization and that this level is predictable by LH of at least 14.8-19 U/liter 4 h after GnRHag. These data also suggest that LH stimulation of testicular androgen production plays a role in stimulating testicular tubule growth once a critical level of FSH is achieved.

LH Dynamics in Overweight Girls with Premature Adrenarche and Slowly Progressive Sexual Precocity.

Background. Excess adiposity and premature adrenarche (PA) are risk factors for the development of polycystic ovary syndrome (PCOS). Methods. Girls with slowly progressive precocious breast development, who were overweight and had PA (SPPOPA, 6.2-8.2 years, n = 5), overweight PA (6.6-10.8 years, n = 7), and overweight premenarcheal controls (OW-PUB, 10.6-12.8 years, n = 8) underwent hormonal sleep testing and GnRH agonist (GnRHag) and ACTH tests. Results. Despite an insignificant sleep-related increase in LH and prepubertal baseline hormone levels, SPPOPA peak LH and estradiol responses to GnRHag were intermediate between those of PA and OW-PUB, the LH being significantly different from both. Conclusions. GnRHag tests indicate that SPPOPA is a slowly progressive form of true puberty with blunted LH dynamics. These results argue against the prepubertal hyperandrogenism of excess adiposity or PA enhancing LH secretion or causing ovarian hyperandrogenism prior to menarche. Excess adiposity may contribute to both the early onset and slow progression of puberty.

Evidence that obesity and androgens have independent and opposing effects on gonadotropin production from puberty to maturity.

Optimal fat mass is necessary for normal gonadotropin levels in adults, and both undernutrition and overnutrition suppress gonadotropins: thus, the gonadotropin response to relative adipose mass is biphasic. Adult obesity is associated with blunted luteinizing hormone (LH) pulse amplitude that is partially attributable to increased LH clearance rate. Testosterone appears to have a biphasic effect on gonadotropin production in females. Moderate elevations of testosterone appear to stimulate LH production at both the hypothalamic and pituitary level, while very high levels of testosterone suppress LH. Thus, obesity per se appears to suppress gonadotropin production, and moderate hyperandrogenemia in women appears to stimulate LH. The ordinary hypergonadotropic hyperandrogenism of obese women appears to be an exception to this model because it is usually due to polycystic ovary syndrome (PCOS), a condition in which intrinsic functional ovarian hyperandrogenism and excess adiposity share a common origin that involves insulin-resistant hyperinsulinemia. LH elevation seems to be secondary to hyperandrogenemia and is absent in the most obese cases. Overweight early pubertal girls have significant blunting of sleep-related LH production, which is the first hormonal change of puberty. The data are compatible with the possibility that excess adiposity may paradoxically subtly suppress hypothalamic-pituitary-gonadal function in early puberty although it is known to contribute to the early onset of puberty.

Blunted sleep-related luteinizing hormone rise in healthy premenarcheal pubertal girls with elevated body mass index.

OBJECTIVE: Our objective was to determine whether excessive adiposity is associated with alteration of the normal hormonal changes of early pubertal girls. DESIGN AND PARTICIPANTS: Healthy 6.4- to 9.5-yr-old, prepubertal (PRE, n = 20) and 9.4- to 13.0-yr-old pubertal premenarcheal volunteers (PUB, n = 20) were divided into excessive-weight (EW) or normal-weight (NW) groups according to the 85th percentile body mass index. INTERVENTIONS AND SETTING: Overnight blood sampling; GnRH agonist (GnRHag), low-dose ACTH, oral glucose tolerance tests, and pelvic ultrasonograms were performed in our Clinical Research Center. RESULTS: EW girls were similar in age and baseline and ACTH- and GnRHag-stimulated androgen levels to stage-matched NW girls. However, the sleep-related LH rise was blunted in EW-PUB girls compared with NW-PUB girls. The sleep-related rise of mean LH in EW-PUB [0.68 +/- 0.35 (sem) U/liter] was insignificant, less than that of NW-PUB (2.1 +/- 0.45, P < 0.05) and not significantly different from that of PRE girls (0.08+/-0.03). EW-PUB had slower LH pulse frequency and a lower rise in LH pulse amplitude during sleep than NW-PUB girls (both P < 0.05). Overnight FSH patterns paralleled LH patterns, whereas estradiol levels were similar in stage-matched NW and EW groups, differing between stages as expected. Early morning and peak LH, FSH, and estradiol responses to GnRHag were similar in EW-PUB and NW-PUB and significantly greater than those of PRE girls. CONCLUSIONS: Healthy EW-PUB girls have significantly blunted sleep-related LH production. These data suggest that excess adiposity, in the absence of sex steroid excess, may subtly suppress hypothalamic-pituitary-gonadal function in premenarcheal pubertal girls.