Precocious puberty with congenital hypothyroidism

Precocious puberty associated with profound hypothyroidism is a rare condition. It is usually characterized by breast development, vaginal bleeding, lack of pubic hair and delayed bone age. Multicystic ovaries in profound hypothyroid patients with precocious puberty have been rarely described. Vaginal bleeding in adolescent girls should be considered as a clinical significance particularly when it is prolonged or heavy, whereas vaginal bleeding in younger girls, regardless of its duration and quantity is always of clinical importance. Bleeding in such patients could be caused by local causes such as vulvar or vaginal lesions, or it could be from the endometrium, which is usually a sign of systemic hormonal disturbance [1]. In this report a rare case of vaginal bleeding, large, multicystic ovaries, precocious puberty and delayed bone age in a 7 years old girl with profound hypothyroidism is described.     

Precocious or early puberty and growth failure in girls treated for acute lymphoblastic leukaemia

We have studied 41 children with early or precocious puberty who have been treated for acute lymphoblastic leukaemia with prophylactic cranial irradiation (1,800-2,400 cGy) accompanied by intrathecal methotrexate and systemic chemotherapy. Mean age at radiotherapy was 3.9 years (range 1.7-7.7) in the girls and 4.8 years (range 2.6-7.8) in the boys. Mean age at the onset of puberty was 8.6 years (range 6.7-9.7) in the girls and 9.3 years (range 7.8-10.3) in the boys. Of the 41 children with early puberty (greater than 1.4 SD from the mean) 36 were females and 5 were males. 21 of the 36 girls had an absent or inadequate growth acceleration of puberty. 7 of 12 girls who had a pharmacological test of growth hormone (GH) secretion had GH insufficiency (peak level less than 20 mU/l). Early or precocious puberty combined with GH insufficiency may produce severe growth failure and we have used a treatment regimen of a gonadotrophin-releasing hormone analogue, in order to reduce the rate of epiphyseal maturation, combined with biosynthetic GH to increase or sustain growth rate. We have treated 4 girls in this manner. During a mean treatment period of 0.86 years, height SDS for bone age rose from a mean of -1.06 to -0.59. Longer treatment periods will be required to assess the effect on final height.     

Precocious puberty associated with partial trisomy 18q and monosomy 11q

We report a 10-years-old female patient with a partial trisomy 18q and monosomy 11q due to a maternal translocation. The phenotype of our proband is partially common with Jacobsen syndrome and duplication 18q but she has also some atypical anomalies such as precocious puberty, a retinal albinism and hypermetropia. Based on cytogenetics and FISH analysis, the karyotype of the proband was 46,XX,der(11)t(11;18)(q24;q13). To the best of our knowledge, this is the first report of precocious puberty associated with either dup(18q) or del(11q) syndromes.     

Precocious puberty secondary to cranial irradiation for tumors distant from the hypothalamo-pituitary area

This retrospective study is the first report of the occurrence of central precocious puberty in 6 children having received cranial irradiation. Pubertal development took place at a mean age of 7 5/12 years (6 10/12-7 10/12 years in 5 girls and at 9 years in 1 boy). They had received 2,400-4,500 rad at a mean age of 5 2/12 years. In addition, 5 children had GH deficiency so that their growth spurt was blunted and 3 of them were left with an extremely short stature. This condition would require a therapeutic approach combining the use of an LHRH analogue and hGH therapy when necessary in order to protect from too rapidly progressing bone maturation.     

Resolution of apparent growth hormone-dependent growth failure during puberty: a case report

A prepubertal boy with apparent growth hormone (GH)-dependent growth failure displayed a marked increase in growth velocity, normal GH responses to arginine/insulin infusion and a fourfold increase in spontaneous 24-hour GH secretion following the onset of normal puberty. The case supports earlier observations of a transient form of GH insufficiency in some short prepubertal children, but represents the first evidence that puberty restores spontaneous as well as stimulated GH secretion in such patients.     

Intrauterine growth retardation and puberty in girls.

Some, albeit not all studies on the relationship between intrauterine growth retardation (IUGR) and female pubertal development have found an earlier and rapidly progressing puberty as well as concomitant disorders of related functional systems such as polycystic ovary syndrome and short stature. These pubertal changes are part of a growing list of IUGR-related diseases, which includes non-insulin dependent diabetes mellitus and coronary heart disease. A pulsatile release of gonadotropin releasing hormone is thought to be a conditio-sinne-qua-non for the initiation of puberty. In the absence of prospective studies on gonadotropin releasing hormone pulse patterns in IUGR-children other markers of pubertal development such as age at menarche have been deployed. From these studies it is not clear, however, whether the findings of an earlier onset of puberty in IUGR-girls merely reflect a more rapid progression of puberty. Both the role for IUGR and the mechanisms behind the onset of puberty are still elusive. Assuming a connection between IUGR and pubertal development, parallels can be drawn between hypotheses on the longterm consequences of IUGR and hypotheses on the initiation of puberty. For example, the somatometer concept proposes a role for fat mass in the initiation of puberty, which is compatible with the hypothesis on non-skeletal catch-up growth after IUGR. The debate on the origins of puberty and the role of IUGR mainly focuses on nature and nurture. Judgmentally, studies in mono- and dizygotic twins discordant for birth weight may be of particular help.     

The psychological outcome of constitutional delay of growth and puberty

Does being of short stature (SS) matter? Growth studies are important because endocrinologists need to be able to give not only diagnostic but also prognostic indication to those of SS, and give advice for or against treatment. Studies on body height may give significant insight into the behavioural-hypothalamic-pituitary axis underlying the surface effect on social behaviour. This research presents adult follow-up studies of 49 males who attended at a growth clinic as children and who were diagnosed as having the condition of maturational delay short stature (MDSS). From the psychological perspective, the elements of diagnosis and prognosis, attitudinal influences both social and individual, treatment, and psychological issues which could have bearing on SS are drawn together. Where there is a poor psychosocial outcome finding, the MDSS patients seem to be more like those with growth hormone (GH) deficiency. With GH deficiency (GHD), a poor psychosocial outcome of SS has been demonstrated with greater certainty. The current situation is that there remains divergence between previous SS outcome studies. Differing research SS psychosocial outcomes are analysed and a methodological explanation of past divergent outcomes is presented, being: (1) differences in sensitivity between psychological assessment tools; (2) Invalidation by confounding the psychological with sociological outcomes, and (3) confounding of results by failure to control for psychological states. An innovative new approach of changing the methodology of past SS research from the biological to the psychological perspective is employed: previous SS research has appointed height status as the independent variable, with psychosocial outcome as the dependent variable. The innovative approach in this research is to reverse that order and psychological status has been made the independent variable for both the MDSS and for a predetermined psychologically and physically healthy (PPH) comparison group of males. The results of the follow-up studies in this research indicate that there is an association between psychological distress and attained height which supports other studies where the findings indicate a poor psychological outcome associated with SS. It can therefore be concluded that the psychological status of children should be determined when they attend a growth clinic with concerns of SS.     

Constitutional delay of growth and puberty: do they really reach their target height?

We compared the final adult height (FH) of patients with classic constitutional delay of growth and puberty with their target height (TH) and with the height prediction by the Bayley-Pinneau method (BP). 20 patients and their parents were included in our study: 6 females (mean age 19.1 years) and 14 males (mean age 20.6 years). No significant difference could be detected between TH, FH and BP prognosis. This is in contrast to recent studies using height data partly obtained by self-estimation. We measured our patients and their parents ourselves and were accurately able to calculate their genetically determined TH. This proceeding could explain our results. Our study shows that adolescents with true constitutional delay do not need treatment and that height prediction seems to be accurate.     

Precocious testicular growth in metamorphosis-arrested larvae of a salamander Hynobius retardatus: role of thyroid-stimulating hormone

Precocious maturation of testes occurs in goitrogen-treated larvae of a salamander Hynobius retardatus, a particular population of which has been reported to show a neotenic reproduction in a specific environment. Similar precocious growth of testes also was confirmed in thyroidectomized larvae in this study. A possible involvement of thyroid-stimulating hormone (TSH) in the precocious maturation of testes was examined in metamorphosis-arrested larvae whose thyroid or pituitary glands had been removed surgically at embryonic stages or which had been reared in goitrogens. The pituitary glands of both the thyroidectomized and goitrogen-treated larvae contained extraordinarily large number of TSH cells, which were called "thyroidectomy cells." When homogenates of the pituitary glands from the goitrogen-treated larvae were injected into the hypophysectomized larvae for a month, the testes grew larger than those in larvae injected with the pituitary glands from normally metamorphosed controls. These results are consistent with the idea that an extraordinarily high concentration of TSH, which is induced by either thyroidectomy or goitrogen-treatment, causes the precocious maturation of testes in the metamorphosis-arrested larvae of Hynobius retardatus. In contrast to the precocious testicular development, ovarian development in the metamorphosis-arrested larvae was almost identical to that in normally metamorphosed animals within our experimental period. This also suggests that in males the absence of thyroid hormones allows a gonadal response that in females may require another activator in addition to or following thyroid axis stimulation.     

Precocious flowering of juvenile citrus induced by a viral vector based on Citrus leaf blotch virus: a new tool for genetics and breeding

The long juvenile period of citrus trees (often more than 6 years) has hindered genetic improvement by traditional breeding methods and genetic studies. In this work, we have developed a biotechnology tool to promote transition from the vegetative to the reproductive phase in juvenile citrus plants by expression of the Arabidopsis thaliana or citrus FLOWERING LOCUS T (FT) genes using a Citrus leaf blotch virus‐based vector (clbvINpr‐AtFT and clbvINpr‐CiFT, respectively). Citrus plants of different genotypes graft inoculated with either of these vectors started flowering within 4–6 months, with no alteration of the plant architecture, leaf, flower or fruit morphology in comparison with noninoculated adult plants. The vector did not integrate in or recombine with the plant genome nor was it pollen or vector transmissible, albeit seed transmission at low rate was detected. The clbvINpr‐AtFT is very stable, and flowering was observed over a period of at least 5 years. Precocious flowering of juvenile citrus plants after vector infection provides a helpful and safe tool to dramatically speed up genetic studies and breeding programmes.     

Chemical genetics: where genetics and pharmacology meet

Genetics and pharmacology can elicit surprisingly different phenotypes despite targeting the same protein. This Essay explores these unexpected differences and their implications for biology and medicine.     

The molecular genetics of growth hormone deficiency

Although most cases of short stature associated with growth hormone (GH) deficiency are sporadic and idiopathic, some 5-30% have an affected first degree relative consistent with a genetic aetiology for the condition. Several different types of mutational lesion in the pituitary-expressed growth hormone (GH1) gene have been described in affected individuals. This review focuses primarily on the GH1 mutational spectrum and its unusual features, discusses potential mechanisms of mutagenesis and pathogenesis, and examines the correlation between mutant genotype and clinical phenotype. The characterization of pathological lesions in several other pituitary-expressed genes that are epistatic to GH1 (POU1F1, PROP1 and GHRHR) has identified additional causes of GH deficiency, the molecular genetics of which are also explored. Received: 13 May 1998 / Accepted: 18 June 1998     

Developmental quantitative genetics of growth in Populus

 Nursery growth and dry weight were analyzed for F₂ genotypes derived from Populus trichocarpa×P. deltoides that have been field tested with clonal replicates in three different environments. The correlations between nursery and plantation performance differed among the environments, with higher values at Boardman and Clatskanie (both planted with rooted cuttings) than Puyallup (planted with unrooted cuttings). At Puyallup, nursery height was more strongly associated with plantation growth than were nursery diameter and dry weight. Yet, this finding was not supported by QTL mapping. A single overdominant QTL on linkage group G affected the stem height of both seedlings and resprouts in the nursery but showed nonsignificant LOD scores for plantation height from ages 1 to 5 at Puyallup. A total of four QTLs were identified for nursery diameter, one of which on linkage group O also controlled plantation basal area at all ages. Two important nursery QTLs on linkage groups B and G were used to estimate the relative efficiency of marker-assisted selection for plantation productivity. Despite the fact that they were not detected in the plantation stage, these two QTLs could significantly increase the proportion of the phenotypic variance explained by plantation QTLs. Received: 5 February 1998 / Accepted: 1 April 1998