Transsphenoidal surgery for pituitary gigantism and galactorrhea in a 3.5 year old child.

The management of pituitary macroadenomas which lead to gigantism may require multiple therapeutical approaches, including medical treatment, surgery, and radiation therapy. Transsphenoidal surgery (TSS) during early childhood that achieves total removal of a growth hormone (GH) secreting tumor is rarely reported. The surgeon is confronted with special problems regarding the infantile anatomy. In this case, a 3.5 year old child, the youngest successfully treated by TSS so far, suffered from a GH- and prolactin (PRL) secreting macroadenoma of the pituitary gland. The girl initially presented with an increasing growth rate, later with breast development, and finally, at the age of 2.8 years, with galactorrhea and secretion of blood from the nipples. Increased levels of GH [122 micrograms/l], insulin-like growth factor (IGF-1) [830 micrograms/l], insulin-like growth factor binding protein 3 (IGFBP-3) [8.6 mg/l] and PRL [590 micrograms/l] were found. MRI scans revealed a macroadenoma of 2.7 cm diameter. An eight-week trial of relatively low dose dopamine agonists led to a reduction of PRL, while the GH- and IGF-1 levels remained unchanged; the tumor showed only little shrinkage. Since there was chiasma compression, we opted for early TSS. A complete tumor removal was achieved despite the difficulties of a narrow approach. After TSS, low levels of GH, IGF-1, and PRL documented a complete tumor removal, but persistent diabetes insipidus and anterior lobe deficits resulted from surgery. In summary, if primary medical therapy alone is unable to adequately reduce hormone hypersecretion and tumor size in early childhood, TSS is recommended. Thus, radiation therapy may be reserved for surgical failure.

Clinical and molecular spectrum of somatic mosaicism in androgen insensitivity syndrome.

We recently found that postzygotic de novo mutations occur at the expected high rate of an X-linked recessive mutation in androgen insensitivity syndrome. The resulting somatic mosaicism can be an important molecular determinant of in vivo androgen action caused by expression of the wild-type androgen receptor (AR). However, the clinical relevance of this previously underestimated genetic condition in androgen insensitivity syndrome has not been investigated in detail as yet. Here, we present the clinical and molecular spectrum of somatic mosaicism considering all five patients with mosaic androgen insensitivity syndrome, whom we have identified since 1993: Patient 1 (predominantly female, clitoromegaly), 172 TTA(Leu)/TGA(Stop); patient 2 (ambiguous), 596 GCC(Ala)/ACC(Thr); patient 3 (ambiguous), 733 CAG(Gln)/ CAT(His); patient 4 (completely female), 774 CGC(Arg)/TGC (Cys); and patient 5 (ambiguous), 866 GTG(Val)/ATG(Met). Serum sex hormone binding globulin response to stanozolol, usually correlating well with in vivo AR function, was inconclusive for assessment of the phenotypes in all tested mosaic individuals. An unexpectedly strong virilization occurred in patients 1, 3, and 5 compared with phenotypes as published with corresponding inherited mutations and compared with the markedly impaired transactivation caused by the mutant ARs in cotransfection experiments. Only the prepubertal virilization of patients 2 and 4 matched appropriately with transactivation studies (patient 4) or the literature (patients 2 and 4). However, partial pubertal virilization in patient 4 caused by increasing serum androgens and subsequent activation of the wild-type AR could not be excluded. We conclude that somatic mosaicism is of particular clinical relevance in androgen insensitivity syndrome. The possibility of functionally relevant expression of the wild-type AR needs to be considered in all mosaic individuals, and treatment should be adjusted accordingly.

Feminizing Sertoli cell tumors associated with Peutz-Jeghers syndrome: an increasingly recognized cause of prepubertal gynecomastia.

Testicular sex cord tumors with annular tubules are an increasingly recognized cause of prepubertal gynecomastia typically accompanied by accelerated linear growth and advanced bone maturation. Serum estrogen levels may be elevated. Testicular ultrasound and biopsy are diagnostic, and mastectomy is indicated. Although these tumors can occur independently, causing gynecomastia in 10 percent of cases, they usually occur in patients with Peutz-Jeghers syndrome. In any Peutz-Jeghers syndrome patient developing gynecomastia, a testicular tumor should be sought. Conversely, because a significant proportion of all reported prepubertal gynecomastia patients have Peutz-Jeghers syndrome with testicular tumors, this syndrome must be considered for all young boys in whom the cause of gynecomastia is not otherwise apparent. When Peutz-Jeghers syndrome is suspected, gastroscopy, colonoscopy, and testicular biopsies can be performed under one anesthetic at the time of mastectomy.

Influence of irradiance on photosynthesis, morphology and growth of mangosteen (Garcinia mangostana L.) seedlings.

The influence of shading intensity on growth, morphology and leaf gas exchange of mangosteen (Garcinia mangostana L.) seedlings was investigated over a 2-year period. Diurnal gas exchange studies revealed significantly higher carbon gain for leaves grown in 20 or 50% shade compared to leaves grown in 80% shade. Seedlings grown in 20 or 50% shade accumulated significantly more dry weight than seedlings grown in 80% shade during the 2-year study period. Seedlings grown in decreased shade showed decreased leaf size, increased leaf thickness, lower specific leaf area (SLA) and higher stomatal frequency. Less shaded seedlings also allocated relatively more dry matter to roots than shaded seedlings and exhibited a significant reduction in leaf area relative to total plant dry weight (leaf area ratio). Increased leaf number, enhanced branching and shorter internodes resulted in a more compact appearance of less shaded seedlings. Irrespective of light conditions, mangosteen seedlings exhibited inherently slow growth because of low photosynthetic rates per unit leaf area, low SLA, low leaf area ratios and inefficient root systems.

Gas exchange characteristics of mangosteen (Garcinia mangostana L.) leaves.

Gas exchange responses of mangosteen (Garcinia mangostana L.) leaves to photosynthetic photon flux density (PPFD), internal CO(2) concentration (C(i)), leaf-air vapor pressure deficit (VPD), leaf temperature (T(l)) and time of day were investigated in plants grown in three shade treatments. Maximal photosynthetic rate (P(n(max))) per unit leaf area at light saturation did not differ significantly among plants grown in the different shade treatments despite significant morphological differences. Light compensation point (9-15 micro mol m(-2) s(-1)) and quantum yield (0.022-0.023) did not differ significantly among treatments, whereas light saturation point was significantly higher for leaves grown in 20% shade than for leaves grown in 50 or 80% shade (951, 645 and 555 micro mol m(-2) s(-1), respectively). Shade treatments significantly affected assimilation responses to varying CO(2) concentrations. At CO(2) concentrations between 600 and 1000 micro mol mol(-1), leaves from the 20% shade treatment recorded higher P(n) (6.44 micro mol m(-2) s(-1)) than leaves from the 80% shade treatment (4.57 micro mol m(-2) s(-1)). Stomatal conductance (g(s)) decreased with increasing CO(2) concentrations. Vapor pressure deficits higher than 2.5 kPa significantly decreased P(n) and g(s), whereas P(n) remained steady over a 24-33 degrees C temperature range in leaves in 80% shade and over a 27-36 degrees C range in leaves in 20 and 50% shade. Highest carbon gain during a 12-hour photoperiod was observed for leaves grown in 50% shade. The results imply that mangosteen is a shade-tolerant, lower canopy tree adapted to humid tropical lowlands. Providing low VPD in the nursery may result in maximal growth. However leaves of seedlings grown in 50 or 20% shade tolerated high VPD and temperatures better than leaves of seedlings grown in 80% shade, indicating some adaptability to the seasonally wet and dry tropics of northern Australia.

[Psychological development of children with hypothyroidism. I. Psychometric results in relation to clinical features (author's transl)]. / Die psychische Entwicklung von Kindern mit Hypothyreose. I. Psychometrische Ergebnisse in ihrer Beziehuhg zu klinischen Faktoren.

Thirty-two children suffering from congenital or late acquired hypothyroidism were studied with respect to intelligence, motor development, visuo-motor coordination, and social maturity. Psychological test results are represented for the group as a whole as well as in their relation to age at onset of symptoms and therapy, ataxia, and speech disorders.

[Psychological development of children with hypothyroidism. II. Motor development and psychopathology (author's transl)]. / Die psychische Entwicklung von Kindern mit Hypothyreose. II. Motorik und psychopathologische Symptome.

In addition to a preceeding report the relation of motor development to ataxia and age at onset of symptoms and therapy as well as psychopathological symptoms in relation to intelligence and sex in 32 children with hypothyroidism are reported.

Estrogen treatment in tall girls.

36 tall girls aged 10.3 to 15.5 years were treated with ethinylestradiol (0.5 mg/day) and norethisterone (15 mg/day). To date treatment for seventeen girls has been completed. Before treatment their bone age ranged from 11.0 to 13.5 years and mean height prediction was 185.19 cm (181.40-193.00 cm). After about two years of treatment their final height averaged 178.96 cm (171.60-183.50 cm). Predicted height was reduced by an average of 6.23 cm. The reduction in final height was significantly greater when therapy was started before a bone age of 12 years. Thirteen girls, re-examined after discontinuation of therapy, all had regular menstrual bleeding within six months. There were no serious or irreversible side effects during the period of observation.

[Adrenocortical adenoma in a 2 1/2 year old girl causing virilization and accelerated growth. Clinical and morphological results (author's transl)]. / Virilisierendes Nebennierenrindenadenom bei einem 2 1/2 jährigen Mädchen. Klinisch-endokrinologische und morphologische Befunde

A 2 1/2 year old girl with virilization and advanced bone age was found to have a leftsided adrenocortical adenoma. The secretion of mainly androgens besides estrogens was not suppressible with dexamethasone. Plasma cortisol levels were not elevated but did not show any circadian rhythm. The tumor was localized by retroperitoneal instillation of gas, intravenous urography and tomography. After complete removal of the tumor the originally strongly elevated excretion of 17-ketosteroids sank back to normal, the acceleration of skeletal development slowed down. The right adrenal cortex was not atrophic, 2 1/2 years after the operation the child is well and without evidence of recurrent disease. Differential diagnosis as well as ultrastructor and histology of the tumor are discussed with reference to the literature.

[More recent aspects of treatment for hypothyroidism and goitre in children and adolescents (author's transl)]. / Neuere Gesichtspunkte zur Behandlung der Hypothyreose und "blanden" Struma bei Kindern und Jugendlichen

According to more recent knowledge L-thyroxine alone is recommended for thyroid hormone replacement therapy, no longer the combination of L-thyroxine and triiodothyronin, since L-thyroxine is converted to triiodothyronine in the periphery of the body. Additional application of triiodothyronine causes unphysiological elevations of blood levels of triiodothyronine. When changing from the combined thyroid hormone therapy to treatment with L-thyroxine alone it is enough in most cases to replace the previous amount of L-thyroxine only; previous recommendations for the dosage of thyroid hormone were rather high. Average requirements of adults for L-thyroxine are around 170 mug per day. Children need about 90--100 mug per m2 body surface per day. -- When hypothyroidism is suspected in newborns or infants no protracted diagnostic procedures are justified with respect to brain development and its requirement of thyroid hormone during this period of life. Replacement therapy should be started within 1--2 days. The exact diagnosis can be established later, for instance during the third day of life when a temporary interuption of treatment for diagnostic purposes has no longer such negative effect on normal brain development. As long as physiological doses of L-thyroxine are used no side effects are to be expected for patients who later turn out to be euthyroid. -- Following exclusion of hyperthyroidism goitres in children and adolescents equally need thyroid hormone replacement therapy to reduce the size or prevent further enlargement or even the development of nodules within the gland. The dosage for this is about half to three quarters of the full replacement dose. The nature of thyroid nodules should be investigated, even surgically, since malignancies can develop in children and juveniles as well as in adults.

Cerebellar-ataxic syndrome in children and adolescents with hypothyroidism under treatment.

Animal experiments and observations on quantitative growth of human cerebellum suggest a critical period when its development is particularly vulnerable to hypothyroidism. Sixty-seven patients aged 7-24 years with hypothyroidism under long-term treatment were examined for ataxic symptoms. These were found in 24 of 39 patients (60%) hypothyroid before or during the third month of life. Only 4 of 18 patients (20%) hypothyroid later had cerebellar symptoms. Such symptoms could be evidence for the onset of hypothyroidism before or during the 3rd month of life. Seventeen (80%) of mentally retarded patients had cerebellar symptoms compared with 11 (30%) of 45 attending normal school. Even retrospectively, these data might permit a more accurate prognosis of further mental development in hypothyroid children.

[Recurrent urinary tract infection in childhood. Diagnosis, treatment, prognosis (author's transl)]. / Rezidivierende Harnwegsinfektionen im Kindesalter--Diagnose, Therapie, Prognose

Infection of the urinary tract in childhood is common. It may start already in neonates or infants. Clinical signs are not always present but asymptomatic socalled bacteriuria may occur at any age. The earlier a child contracts the infection the more common are uncharacteristic clinical signs like loss of appetite, a raised temperature, parenchymatous icterus and, finally signs of involvement of the central nervous system. During the last few years purposeful research has established the important fact that, if there has been a urinary tract infection particularly in the first months of life, recurrence may more often be asymptomatic than on the first occasion. A mid-stream specimen is diagnostically valuable. If this does contain any bacteria, then supapubic aspiration from the bladder is useful in enabling us to start a specific, if possible bactericidal, therapy. Asymptomatic bacteriuria may at any time lead to clinical signs of pyelonephritis, particularly during periods of stress. Such silent unrecognized cases of asymptomatic bacteriuria may, we feel, lead to pyelonephritic nephrosis in a so far unknown percentage of cases.