Adolese Pediatr Gyneeol (1992) 5:51-52
Adolescent and Pediatric Gynecology © 1992 Springer-Verlag New York Inc.
World Literature Reviewed by Selma F. Siegel and Peter A. Lee, M.D., Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA. Radiotelemetric Monitoring of Hypothalamic Gonadotropin-Releasing Hormone Pulse Generator Activity Throughout the Menstrual Cycle of the Rhesus Monkey. O'Byrne KT, Thalabard J-C, Grosser PM, Wilson RC, Williams CL, Chen M-D, Ladendorf D, Hotchkiss J, Knobil E. Endocrinology 1991; 129:12071214. An electrophysiological technique utilizing radiotelemetry was used to monitor the electrical activity of the gonadotropin-releasing hormone (GnRH) "pulse generator" in the mediobasal hypothalamus of five regularly cycling unrestrained Rhesus monkeys. The authors have made major prior contributions to reproductive physiology including the demonstration that volleys of such electrical activity correspond to a luteinizing hormone pulse in the peripheral circulation. The present study reports decreased frequency of hypothalamic multiunit electrical activity at night during the follicular phase of the menstrual cycle and just prior to the mid-cycle LH surge. Administration of subcutaneous estradiol benzoate on day 4 of the cycle to simulate the spontaneous preovulatory estradiol increase was, likewise, associated with decreased electrical activity prior to the occurrence of the estradiol-induced LH surge. Exogenous progesterone given to mimic the spontaneous preovulatory increase in progesterone levels, however, did not significantly affect the electrical activity of the mediobasal hypothalamus. The authors suggest that escape from the inhibitory effects of progesterone causes the increased "pulse generator" frequency observed during the transition from late luteal to early follicular phase. These electrophysiological data support the authors' previous observation of an absence of a distinct pulsatile LH pattern during the LH surge. Others have reported data showing high frequency LH pulses in the late follicular phase in monkeys and women. Nevertheless, the occurrence of the LH surge despite decreased frequency of electrical activity is consistent with past laboratory and clinical observations that an ovulatory menstrual cycle can be maintained by the administtation of exogenous GnRH at unvarying frequency and amplitude.
Clinical Correlation. This study provides electrophysiological data reflecting the activity of the GnRH pulse generator in relation to LH secretion throughout an ovulatory menstrual cycle. Indeed, the pulse generator itself may be a consequence of the electrical properties of a communicating network of GnRH secreting neurons which fire and release GnRH simultaneously. Though decreased hypothalamic multiunit activity during the midcycle LH surge has been shown to follow and, thus, has been attributed to the preovulatory increased estradiol levels, the full significance of the pulse generator in the physiology of the mid cycle LH surge remains to be elucidated. Growth Prognosis and Growth after Menarche in Primary Hypothyroidism. Pantsiotou S, Stanhope R, Uruena M, Preece MA, Grant DB. Arch Dis Child 1991; 66:838-840. Twenty girls and nine boys with acquired hypothyroidism were followed from diagnosis until they achieved adult height. For the girls, mean age at diagnosis was 8.8 years with mean bone age of 5.4 years. For the boys, mean chronologic and bone ages at diagnosis were 9.5 and 6.3 years respectively. Patients received thyroxine 100 J.Lg/m2/day. Puberty began later in the affected girls compared with the growth standards of Tanner and Whitehouse.1.2 Mean menarcheal age was 13.8 ± 1.7 years. Although linear growth continued longer after menarche than usual, final adult heights were less than expected. Skeletal maturation progressed more rapidly than chronologic age. Despite adequate thyroxine replacement therapy, final adult height was compromised in children with acquired hypothyroidism similar to the findings previously reported. 3 There is no apparent explanation for the compromised height after acquired primary hypothyroidism of childhood. There may be irrevocable loss of height potential during the interval of hypothyroidism. The authors comment that bone age assessments may be underestimated because of the disproportionate effect of hypothyroidism upon the epiphysis. If this is true, height potential may be less than assumed despite a bone age that has been interpreted to be more significantly delayed than the height age. If bone ages are consistently underestimated, height potential may have already been irrevocably lost during the period of hypothyroidism.
The rapid skeletal maturation commonly seen during the catch-up phase may actually represent epiphyseal healing rather than true acceleration. The authors mention the possible use of GnRH analogue therapy for those patients who are progressing rapidly through puberty during the catch-up phase. This effort to regain height potential should be further investigated in an appropriate research setting. However, the optimal prevention of this initial loss is prompt diagnosis and treatment.
References 1. Tanner JM, Whitehouse RH, Takaishi M: Standards from birth to maturity for height, weight, height velocity and weight velocity: British children, 1965, part I. Arch Dis Child 1966; 41:454 2. Tanner JM, Whitehouse RH, Takaishi M: Standards from birth to maturity for height, weight, height velocity and weight velocity: British children, 1965, part II. Arch Dis Child 1966; 41:613 3. Rivkees SA, Bode HH, Crawford JD: Long-term growth in juvenile acquired hypothyroidism: the failure to achieve normal adult stature. N Engl J Med 1988; 318:599
Patterns of Pulsatile Luteinizing Hormone and Follicle-Stimulating Hormone Secretion in Prepubertal (Midchildhood) Boys and Girls and Patients with Idiopathic Hypogonadotropic Hypogonadism (Kallmann's Syndrome): A Study Using an Ultrasensitive Time-Resolved Immunofluorometric Assay. WU FCW, Butler GE, Kelnar CJH, Stirling HF, Huhtaniemi I. J Clin Endocrinol Metab 1991; 72:1229. Nocturnal plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH), drawn every 1020 minutes, were measured by time-resolved immunofluorometric assays in 22 prepubertal children and 8 men with Kallmann's syndrome. Gonadotropin responses to GnRH were also measured. Immunofluorometric assays (DELFIA) utilize two monoclonal antibodies directed against different sites on the gonadotropin molecules. This assay was more sensitive than an immunoradiometric assay (IRMA) based on comparison of LH values. Low amplitude gonadotropin pulses were detected in 20/22 prepubertal children, aged 4.4-8 years. Mean FSH Levels were greater in girls than boys, p < 0.05. Nocturnal LH and FSH pulses, as during early puberty, cluster at sleep onset. Though patients with Kallmann's syndrome had occasional pulses, nocturnal augmentation of pulsatile LH or FSH secretion was not observed. The authors suggest that not only does episodic release occur, but also a diurnal gonadotropin rhythm
exists in midchildhood. These observations add yet another item to the list of possible diagnostic procedures to distinguish hypogonadotropic hypogonadal individuals from those with constitutional delayed puberty. The former may have a lack of sleep-entrained gonadotropin pulses and poor synchronization between LH and FSH pulses. Clinical Correlation. This report adds to the concept that puberty is indeed a resurgence of amplitude of pulsatile release which persists during childhood. Whether this information helps with the differentiation between constitutional delayed puberty and hypogonadotropic hypogonadism remains to be seen. However, even if it does improve the discrimination between these two entities, such sampling is expensive and time consuming. Medical Management in HIV -Infected Adolescents. Hein K, Futterman D. J Pediatr 1991; 119:S18. AIDS is an increasing problem among the adolescent population. Many affected young adults were infected during adolescence. The epidemiology of human immunodeficiency virus (HIV) infection differs in adolescents because of increased heterosexual transmission. The trend for increasing incidence of HIV infection is likely to persist. This article recommends frequent outpatient visits for all HIV -infected adolescents. Complete medical histories including sexual, social, and substance use are important. The physical exam should include vital signs, assessment of general well-being, signs of lymphadenopathy, and genital examination. Recommended laboratory studies included complete blood count, platelet count, liver function studies, BUN, creatinine, sickle cell preparation, and urinalysis. Rubella and toxoplasmosis titers, screening test for syphilis, hepatitis B screen, and quantitative immunoglobulins should also be obtained. If indicated and consented to by the patient, HIV antibody test should be performed. CD4 (T4) and CD4/CD8 (T41T8) ratio should be obtained initially, and repeated every 6 months. An anergy screen and skin test for tuberculosis should be performed. In the sexually active adolescent, a pregnancy test and cultures for gonorrhea and Chlamydia should be obtained. Clinical Correlation. Therapeutic intervention must consider psychosocial well-being as well as medical problems. Counseling including "safe sex" and referral to the appropriate medical and social agencies is generally needed. This article concisely presents information necessary for the treatment of HIV-infected adolescents. Such guidelines may also be appropriate for all sexually active adolescents.