The density of primordial follicles varied more than two orders of magnitude in cortical fragments from each of the three ovaries. Primordial follicles were very unevenly distributed throughout the cortex of these ovaries, although a significant linear correlation between age and follicular density was found.

A 18-year clinical follow-up period in a male patient with a germline TSH-R gene mutation (Met453Thr) is described. Nonautoimmune thyrotoxicosis was diagnosed at the age of 7 months. The patient had exophthalmus, failure to thrive, advanced bone age and no goiter. Long-term antithyroid drug treatment (ATD) was necessary during childhood. At the age of 7 years he developed a goiter. Subtotal thyroidectomy was performed at the age of 9 years, followed by repeated ablative radiotherapy at the age of 9.5–13 years due to a toxic multinodular goiter. After 13 years ATD could be discontinued and the patient was euthyroid until 16 years of age, where L-thyroxine substitution had to be started. The exophthalmus diminished, and had disappeared at the age of 18 years, when CT scan of the orbit was performed. Conclusion: TSH-R mutation must be considered in early nonautoimmune thyrotoxicosis. A very agressive treatment strategy is necessary.

Childhood cancer survivors with regular menstrual cycles and basal FSH <10 IU/l seem to have a diminished ovarian reserve. Consequently, they may have a shortened reproductive span and an early menopause.

Patient compliance is of vital importance for the outcome of any medical therapy. Compliance is especially a problem in long-term treatment of non-life threatening diseases, such as growth retardation in children. Until recently, all human growth hormone (hGH) products required a reconstitution process. Norditropin^® SimpleXx^TM is a liquid formulation of the biosynthetic hGH product Norditropin^®, and, together with an improved NovoPen^® 1.5, NordiPen^TM, and an auto-insertion device, PenMate^TM/NordiPenMate^TM, it has been developed in order to ease the injection process for patients. A randomized, open, multicentre, crossover trial compared Norditropin^® SimpleXx^TM/improved NovoPen^® 1.5 with freeze-dried Norditropin^® PenSet^®/Nordiject^®. A total of 67 children with GH deficiency, aged 5–18 years, were treated with either Norditropin^® SimpleXx^TM for 6 weeks followed by Norditropin^® for 6 weeks or the opposite (sequences I and II, respectively). Acceptability/convenience and pain perception were evaluated by questionnaire after each period. The function and handling of the PenMate^TM were evaluated in a Dutch trial by 27 GH-treated children with intrauterine growth retardation, aged 4–16 years, and their parents. All children were accustomed to using the Nordiject^® pen. The evaluation of the PenMate^TM was based on a questionnaire. A similar trial was conducted in England, in which the NordiPen^TM and the NordiPenMate^TM were evaluated by 25 GH-treated children and their parents. Norditropin^® SimpleXx^TM was found to be easier to inject by 64% of the children, and 98% of the children found the system easier to use overall. There was no difference in pain perception between the two administration systems, as judged by questionnaires and visual analogue scale score. Three out of four patients preferred to continue treatment with Norditropin^® SimpleXx^TM. The safety profiles of the two systems were similar. In the Dutch trial, the PenMate^TM was found to be easy and safe to handle, even for very young children (aged 4–5 years). Of patients who took a long time to get used to the injections, 73% found that the new pen would help. A total of 88% of the children would prefer to use the PenMate^TM in the future. Positive results of the handling tests were also reported in the British trial. The use of Norditropin^® SimpleXx^TM and the auto-insertion device may improve patient compliance.

Several reports have focused on the clinical features of the untreated GH-deficient adult and the effect of GH therapy. The results reported are strikingly unanimous. Untreated GH-deficient adults have been shown to have increased cardiovascular mortality, reduced exercise capacity, reduced muscle strength, subnormal glomerular filtration rate and renal plasma flow, defective sweat secretion and defective thermoregulation, reduced energy expenditure and basal metabolic rate, abnormal thyroid hormone metabolism, reduced myocardial function and clinical signs of premature atherosclerosis. Body composition has been found abnormal with increased fat mass, decreased lean body mass, decreased muscle fat ratio, visceral obesity, reduced extracellular fluid volume and reduced bone mineral content. Furthermore, two independent groups have reported impaired psychological wellbeing as compared to normal subjects. Apart from the observation on total mortality, all the above-reported abnormalities improve during GH substitution. The only recognisable side effect so far has been fluid retention, which is usually transient and dose-dependent. It is concluded that GH deficiency has distinct clinical consequences all of which can be totally or partially alleviated by GH replacement therapy.