Hepatocellular carcinoma associated with precocious puberty and oral contraceptives. A case report

A 36-year-old woman presented with sudden abdominal pain and vomiting. Computed tomography showed a tumour of the right hepatic lobe with possible signs of acute haemorrhage. Her medical history revealed precocious puberty when she was a 5-year-old and the use of oral contraceptives for 18 years. Bisegmentectomy was performed and histological examination revealed hepatocellular carcinoma. The role of male and female sex hormones in the development of hepatic tumours has been well documented but, to our knowledge, association with precocious puberty has not yet been described.     

A super long-acting LH-RH analogue induces regression of hypothalamic hamartoma associated with precocious puberty

We treated a 1-year-old female with a hypothalamic hamartoma and precocious puberty with leuprolide acetate depot, a super long-acting hormone-releasing hormone analogue (Tap-144-SR; [D-Leu6-[des-Gly10-NH2] LH-RH ethylamide acetate). The infant's major symptoms were genital bleeding and gynaecomastia. The LH-RH analogue (30 micrograms/kg) was injected subcutaneously once every 4 weeks. Clinical and laboratory manifestations of precocious puberty showed marked improvement. A follow-up after 16 months of treatment, the size of the tumour decreased significantly and remained unchanged for 2 years of further follow-up. To the best of our knowledge, this is the first hypothalamic hamartoma case in whom a decrease of tumour size under treatment with LH-RH analogue has been documented. But, because diagnosis of hamartoma is only based on neuroradiological and not on histological examinations, the possibility of a gangliocytoma cannot be excluded with certainty.     

Gonadotrophin and prolactin secretory dynamics in girls with normal puberty, idiopathic precocious puberty and precocious puberty due to hypothalamic hamartoma

OBJECTIVE: This study was designed to test the hypothesis that hypothalamic hamartoma causes precocious puberty through a different neuroendocrine mechanism than that of normal puberty or of idiopathic precocious puberty. DESIGN AND PATIENTS: We compared the pattern of gonadotrophin secretion among 4 girls with precocious puberty due to hypothalamic hamartoma, 27 girls with idiopathic precocious puberty, and 14 girls with normal puberty. All subjects were breast stage 3 or 4. Blood samples were obtained every 20 min for 4 h during the day (1.000 hours to 1400 h) and night (22.00 hours to 0200 h). MEASUREMENTS: LH, FSH, and prolactin were measured in each blood sample. Girls also underwent LHRH-stimulation with measurement of LH and FSH before and after stimulation. RESULTS: There were no significant differences in mean LH level, LH peak amplitude, or LH or FSH peak frequency during either the day or the night among the three diagnostic groups. However, the mean +/- SD LHRH-stimulated peak LH levels were greater in girls with hypothalamic hamartoma than in girls with normal puberty or with idiopathic precocious puberty (194 +/- 142 vs 85 +/- 60 or 66 +/- 54 IU/l, respectively, P < 0.05). The LHRH-stimulated peak FSH level in girls with hypothalamic hamartoma exceeded the level for the normal pubertal girls (31 +/- 19 vs 17 +/- 7 IU/l, P < 0.05), but not the level for the girls with idiopathic precocious puberty (25 + 12 IU/l). The peak LH to peak FSH ratio in the girls with hypothalamic hamartoma exceeded the ratio for the girls with idiopathic precocious puberty (7.3 +/- 3.9 vs 2.6 +/- 3.0 IU/l, P < 0.05), but not the ratio for the normal pubertal girls (5.0 + 2.9). There were no significant differences in mean prolactin level, peak amplitude or frequency, or in the ratio of mean night to mean day prolactin, among the 3 diagnostic groups. CONCLUSIONS: We conclude that spontaneous gonadotrophin and prolactin secretion are similar among girls with hypothalamic hamartoma, idiopathic precocious puberty, or normal puberty. However, the increased LHRH-stimulated peak LH in the girls with hypothalamic hamartoma suggests subtle differences in neuroendocrine regulation that may underlie their more rapid pubertal maturation.     

Leptin levels in children with central precocious puberty

Several studies have suggested that sufficient serum leptin levels may be involved in the initiation of puberty. To assess further the relationship between leptin and the onset of puberty in humans, we measured the serum leptin concentration in children with central precocious puberty (CPP). We studied 65 children with either idiopathic (IPP; n = 50 girls and 3 boys) or neurogenic central precocious puberty (NPP; n = 5 girls and 7 boys). The serum leptin levels in these patients were compared with normative data from healthy children and adolescents using SD scores that adjust for body mass index (BMI) and Tanner stage. The mean SD scores of IPP and NPP girls were +0.4 +/- 0.1 and +1.0 +/- 0.5, respectively, compared with that of age-matched prepubertal girls and +0.7 +/- 0.2 and +1.6 +/- 0.6 compared with that of girls matched for pubertal stage. The CPP girls with lower BMIs contributed larger SD scores, such that the leptin SD score was negatively correlated with BMI. A similar, modest increase in leptin levels in the CPP girls was evident when additional normative data were considered. The mean leptin SD scores of IPP and NPP boys were -0.9 +/- 0.5 and +0.7 +/- 0.3, respectively, compared with that of normal boys at Tanner stage 3-4. Serum leptin levels in the boys with CPP were not different from those in healthy boys in any of the normative studies. These data should be interpreted cautiously, but they suggest that girls with CPP have modestly elevated serum leptin concentrations compared with those in healthy children and adolescents. In addition, the negative correlation between the leptin SD score and BMI suggests that sufficient leptin levels may be associated with initiation of puberty in girls.     

Adult height in girls with idiopathic true precocious puberty

GnRH analogs are used to suppress pituitary-gonadal activity in children with true precocious puberty. The indications for therapy in this situation are not established, as some girls have a slow evolutive form, and the capacity of GnRH analogs to preserve the adult height has not been evaluated. This study analyzes the growth and adult heights of 2 groups of girls with idiopathic true precocious puberty, 1 with a predicted height of 155 cm or less (group 1, 19 cases) and the other with a predicted height of more than 155 cm (group 2, 15 cases). Group 1 patients were treated with a long-acting GnRH analog (D-Trp6-GnRH), and group 2 patients were followed without therapy. Group 1 showed greater clinical signs of estrogenization, vaginal maturation index (P < 0.03), plasma estradiol (P < 0.0004), and ratio of LH/FSH peaks (P < 0.01) at the initial evaluation than did group 2. The mean target heights were similar (difference, 0.9 cm). In group 1, the adult height (159 +/- 1.1 cm) was greater than the predicted height before therapy (152 +/- 1.4 cm; P < 0.0001). The difference between the adult height and the predicted height before therapy (mean, 6.5 cm) correlated positively with the bone age advance (P < 0.01), negatively with the predicted height (P < 0.05), and positively with the difference between the target and predicted heights (P < 0.001) before therapy. In group 2, the adult height (162 +/- 1.4 cm) was similar to the predicted height at the initial evaluation (162.5 +/- 1.4 cm). Adult heights correlated with target height in group 1 and with predicted height at the initial evaluation in group 2. In conclusion, some girls with true precocious puberty and poor adult height prediction who are treated with GnRH analog achieve an adult height more comparable to their target height. However, the lack of effect on height in girls with predicted height at the onset of therapy similar to their target height and preservation of the growth potential in the slow evolutive forms suggest that these forms might not require immediate therapy. Careful follow-up before therapy may be a better way of evaluating their natural course.     

Echographic and sonographic study of ovaries in girls with precocious puberty

The aim of this study is the biometrical and morphological evaluation of the ovaries by sonography and the study of the haemodynamics of the ovarian artery flow by doppler ultrasound in 14 girls with precocious puberty and in 33 control subjects. All people ranged in age from 5 to 7 years. The gonadian mean volume and the mean pulsatility index have been evaluated. A significant difference in the ovarian volume has been found between patients and controls. No index between the two groups. We conclude that the doppler ultrasound needs a larger number of cases to evaluate its validity in girls with precocious puberty.     

Efficacy of the subcutaneous reformulated triptorelin depot in children with central precocious puberty

The efficacy, safety and acceptance of newly formulated triptorelin s.c. (Decapeptyl Depot, DDsc) was compared to triptorelin i.m. (DDim) in seven children with central precocious puberty (CPP) in a prospective study. Both formulations were given for 6 months consecutively. During both treatment periods suppression of basal and gonadotropin-releasing hormone (GnRH)-stimulated levels of luteinizing hormone and follicle-stimulating hormone, suppression of sex steroids, arrest of the maturation of gonads and uterus, and slowing of bone maturation were achieved. The height standard deviation score for bone age increased significantly during DDsc treatment (-1.33+/-0.90 to 1.07+/-0.92, p < 0.05). The ratio bone age/chronological age decreased significantly during both treatment periods (1.25+/-0.24 to 1.20+/-0.23,p < 0.05, and 1.20+/-0.23 to 1.16+/-0.22, p < 0.05). With the injection of DDsc in the abdominal wall, a palpable, non-irritating resistance which gradually decreased in size occurred in one patient. With injection into the thigh no indurations were seen. No allergic reactions were encountered. Five of the patients considered DDsc therapy as more pleasant and described a definite decrease in fear of injections. All parents considered DDsc treatment as equal or better than DDim in respect to the suppression of their child' s puberty. It was concluded that DDsc is equipotent to DDim in the treatment of CPP. For the majority of patients DDsc was more acceptable than DDim. The thigh is recommended for the subcutaneous application of DD.     

Primary intrasellar mixed germ-cell tumor with precocious puberty and diabetes insipidus

A case-control study using data from the Baltimore-Washington Infant Study (BWIS) examined possible paternal risk factors in the etiology of isolated membranous ventricular septal defects (VSD). There were 641 total VSD case infants and 3,549 randomly selected control infants ascertained between 1981 and 1989. Isolated membranous VSDs were identified in 499 cases. Socio-demographic factors (such as parental age and race), social habits, and medical conditions were analyzed by multiple logistic regression in order to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Paternal age was not found to be a risk factor per se, but small positive associations were found for some social habits and maternal factors. Significant associations were found for paternal marijuana use (OR 1.36, 95% CI 1.05-1.76), African-American race of the infant (OR 1.34, 95% CI 1.09-1.65), and for cocaine use among older fathers (OR 3.92, 95% CI 1.30-11.86). These associations support a multifactorial etiologic hypothesis for isolated membranous VSDs and point to some interesting parental behavioral and medical considerations which may contribute to risk for this common birth defect.     

Hypothalamic hamartoma with skeletal malformations, gelastic epilepsy and precocious puberty

A child is described who has skeletal malformations, gelastic epilepsy, precocious puberty and a hypothalamic hamartoma. The skeletal abnormalities were detected at birth, she developed gelastic epilepsy at the age of 3 years 5 months and precocious puberty at 3 years 8 months. A hypothalamic hamartoma was found on MRI. The precocious puberty has been successfully medically managed, though her seizures are difficult to control. The combination of all four features has not been described previously.     

Mediastinal germ cell tumor in a child with precocious puberty and Klinefelter syndrome

An 8-year-old boy presented with precocious puberty and a mediastinal mass. A computer search showed that this rare presentation is most common with germ cell tumor of the mediastinum in children with Klinefelter syndrome. The tumor was completely resected after preoperative chemotherapy, and the patient is well 2 years after the operation. In patients with Klinefelter syndrome, germ cell tumors are 50 times more common than in patients without Klinefelter syndrome, usually contain nonseminomatous elements, present at an earlier age, and are seldom testicular in location.     

A case of atypical ectopic pregnancy

The authors hospitalized and treated in 1990-1994 at their Clinic 127 patients where giardiasis was the main or secondary diagnosis. They wanted to draw attention to the increasing prevalence of the disease, to clinical manifestations and problems associated with treatment. Clinicians should consider the possible presence of this disease in different gastrointestinal manifestations, chronic hepatitis, hepatopathies as well as in acute IgM anti-HAV, HBsAg and HCV negative hepatitis.     

Luteinizing hormone secreting adrenal tumour as a cause of precocious puberty

OBJECTIVE: This study examined whether a selective serotonin reuptake inhibitor (paroxetine) had comparable efficacy but greater tolerability than a tricyclic antidepressant (imipramine) in depressed patients with HIV infection. METHOD: Seventy-five HIV-positive patients (45% of whom had AIDS) were blindly and randomly assigned to receive paroxetine (N = 25), imipramine (N = 25), or placebo (N = 25) in a 12-week trial. The Hamilton Anxiety Rating Scale, the Hamilton Depression Rating Scale, the Clinical Global Impression scale, and the SAFETEE general inquiry (for safety and tolerability) were administered at weeks 2, 4, 6, 8, and 12. RESULTS: Fifty-six (75%) of the 75 patients completed 6 weeks and 34 (45%) completed 12 weeks of the trial. The mean daily doses of both paroxetine (33.9 mg) and imipramine (162.5 mg) were significantly more effective than placebo; they were comparably effective at weeks 6, 8, and 12 according to the intent-to-treat analysis and at week 8 according to the analysis for the subjects who completed the trial (for them, only imipramine was superior to placebo at week 12). There were significantly more dropouts due to side effects from imipramine (48%) than from both paroxetine (20%) and placebo (24%). CONCLUSIONS: Depressed patients with HIV infection responded to imipramine or paroxetine at a higher rate than to placebo irrespective of severity of immunosuppression. Because paroxetine was much better tolerated than imipramine, its overall effectiveness may be greater. However, because of the small study group and the high attrition rate, these findings cannot be generalized and may need replication in a larger study group.     

46,XX/69,XXX diploid-triploid mixoploidy with hypothyroidism and precocious puberty

We report a 20 month old female patient with diploid-triploid mixoploidy (46,XX/69,XXX) syndrome with hypothyroidism and precocious puberty. The triploid cell line was only expressed in the fibroblast culture and comprised the majority (95%) of the cells. Chromosome analysis of the fetal blood sample and peripheral blood sample were normal. The patient shows typical features of full triploidy (growth and severe mental retardation, cranial and facial dysmorphism, complete syndactyly of fingers 3/4, partial syndactyly of toes 2/3) and facial but no body asymmetry. At the age of 5 months central hypothyroidism and precocious puberty were diagnosed. Thin pigmented streaks were visible on the wrists and legs of the patient at the age of 16 months. This is the first patient reported so far with 46,XX/69,XXX mixoploidy suffering from hypothyroidism and precocious puberty.     

A case of ectopic amylase-producing lung cancer

A case of amylase-producing lung cancer is reported. A 58-year-old man was admitted to our hospital because of abnormal shadow on chest X-rays. Transbronchial lung biopsy showed adenocarcinoma at the right upper lobe. Amylase levels were elevated to 915 IU/l in the serum and 960 IU/l in urine. Amylase isozyme pattern identified "salivary-type" amylase. Right upper lobectomy was performed. Both serum and urine, amylase levels were decreased within normal limits after operation. Enzyme labeled immunoperoxidase method on this specimen proved that tumor cells were producing amylase ectopically.     

Intrauterine ectopic pregnancy. A case report

Ratings and tests for the effectiveness of sunscreens are becoming more consistent and scientifically based. This reflects the growing recognition of the health hazards from sunburn and excessive tanning. Health professionals should be aware of the classic six skin types and their susceptibility to burning. As well as Sun Protection Factors (SPFs), long-wave ultra-violet radiation needs to be taken into account. UVA rays cause long-term damage to the skin. No agreed test for UVA protection exists as yet, but some manufacturers have introduced a star rating system for UVA protection. The more UVA stars, the greater the protection. Children's skin is more vulnerable to burning so they need special protection and a high SPF and UVA rating. The first line of defence is avoiding strong sunlight and covering the head and body. Remember that sunscreens need reapplying after swimming. Always follow the manufacturers' directions carefully.     

A case of ectopic breast tissue located in the axilla

Authors have presented a very rare case of young woman favourable surgically treated for morphologically correct breast tissue in the unilateral axilla. They have paid the peculiar attention to possibility of ectopically placed breast tissue malignancy of every that case.     

Irreversible increase of serum IGF-1 and IGFBP-3 levels in GnRH-dependent precocious puberty of different etiologies: implications for the onset of puberty

Contemporary prostheses have developed from small iterations on moderately successful archetypes. This has resulted in modern designs that can either be termed cosmetic or functional, with neither attribute being fully satisfied. A new strategy is needed to develop a generation of upper-limb prostheses that will integrate both cosmetic and functional requirements in a single device. It is hypothesized that design principles applicable to a new generation of prostheses will result from exploring close analogies to the human upper limb. A method of practice led design research has been adopted to explore appropriate analogies, using the production of physical models to elucidate the design problem to the design team and other interested parties. This method uses a consciously iterative approach whereby criticisms and lessons learnt in the development of early models are embodied in subsequent models. This paper describes the first iterative cycle. It includes a critical review of the devices currently available and a study of mechanical analogies to original anatomy which form two of the inputs to the development of a skeletal model hand. It details the lessons learnt from this study and concludes on the wider application of practice led design research in medical engineering.     

Type II ureteral triplication associated with ectopic ureter

We report a case of type II ureteral triplication associated with ectopic ureter. The ureter, draining the upper renal segment, entered the vagina, and the other two ureters, draining the middle and lower renal segments, had joined and entered the bladder. The anatomic findings are compatible with those predicted by the Weigert-Meyer law. A thorough evaluation of such an anomaly is essential for effective management.