Hypogonadism in the Prader-Willi syndrome from birth to adulthood: a 28-year experience in a single centre.

BACKGROUND: Hypogonadism is a key feature of Prader-Willi syndrome (PWS) but clear strategies for hormone replacement are lacking. OBJECTIVE: To evaluate gonadal status and outcome in patients attending a Scottish PWS clinic from 1991-2019. METHODS: In 93 (35F:56M) patients, median follow-up 11.2 years, gonadal and pubertal status were assessed clinically. Pelvic ultrasound findings and basal/stimulated gonadotrophins were compared with age-matched controls. RESULTS: Females: Of 22 patients aged >11, 9 had reached B4-5, while 5 were still at B2-3, and 6 remained prepubertal. Eight patients experienced menarche aged 9.8-21.4 years, none with a normal cycle. Uterine length and ovarian volumes were normal but uterine configuration remained immature, with low follicular counts. Gonadotrophins were unremarkable, serum estradiol 129 (70 - 520) pmol/L. Only 5 patients received oestrogen replacement. Males: Fifty-four (96%) patients were cryptorchid (9 unilateral). Weekly hCG injections resulted in unilateral/bilateral descent in 2/1 of 25 patients. Of 37 boys aged >11, 14 (9 with failed/untreated bilateral cryptorchidism) failed to progress beyond G1, 15 arrested at G2-3 (testes 3-10 ml), and 8 reached G4-5. Gonadotrophins were unremarkable except in boys at G2-5 in whom FSH was elevated: 12.3/27.3 vs 3.25/6.26 U/L in controls (p<0.001). In males aged >13, testosterone was 3.1 (0.5-8.4) nmol/L. Androgen therapy, given from 13.5-29.2 years, was stopped in 4/24 patients owing to behavioural problems. CONCLUSION: Despite invariable hypogonadism, few females and only half the males with PWS in this study received hormone replacement. Double-blind placebo-controlled crossover trials of sex steroids are required to address unproven behavioural concerns.

Involving Individuals with Disorders of Sex Development and Their Parents in Exploring New Models of Shared Learning: Proceedings from a DSDnet COST Action Workshop.

The level of connection between health care professionals and people who experience a condition that affects sex development is variable. These people and associated support groups need to be included in discussions about research and healthcare delivery. The aim of this study was to understand the experiences of individuals with disorders of sexual development (DSD), their parents, health care providers, and support groups. Workshop planning, preparation, delivery, and evaluation involved members of working groups from the COST Action DSDnet. A coordinator, in collaboration with a support group representative, led the workshop design and delivery. Our successful, facilitated workshop involved 33 attendees from 8 EU countries. The workshop provided individuals with DSD, parents, advisory groups, and professionals with an opportunity for shared learning. Outputs focused on 7 key areas, including diagnosis, childhood, and transition to adult care as well as fostering discussion around registries, future research topics, consent processes, and information needs across the life course. The importance of trustworthy and knowledgeable providers, time to understand such rare conditions, and the place support groups have in a life course approach were valuable learning points for all attendees. In conclusion, workshops can be designed and delivered in meaningful ways for all those involved in care of individuals with rare conditions.

Neonatal Features of the Prader-Willi Syndrome; The Case for Making the Diagnosis During the First Week of Life

Objective: Early diagnosis is of proven benefit in Prader-Willi syndrome (PWS). We therefore examined key perinatal features to aid early recognition. Methods: Data were collected from case records of subjects attending a multi-disciplinary clinic and from a retrospective birth questionnaire. Results: Ninety patients (54 male-36 female) were seen between 1991-2015, most with paternal deletion (n=56) or maternal isodisomy (n=26). Features included cryptorchidism in 94% males, preterm birth (26%), birthweight <2500 g (24%), polyhydramnios (23%), breech presentation (23%) and need for nasogastric feeding (83%). Reduced fetal movements (FM) were reported in 82.5% patients compared with 4% healthy siblings. Of 35 children born since 1999, 23 were diagnosed clinically within 28 days while diagnosis in 12 was >28 days: 1-12 months in seven; and 3.75-10.5 years in five. Typical PWS features in these 12 infants included hypotonia (100%), feeding difficulties (75%), cryptorchidism (83% males) and reduced FM (66%). Causes other than PWS including neuromuscular disease were considered in nine patients. Conclusion: Neonatal hypotonia, reduced FM, feeding difficulties and cryptorchidism should immediately suggest PWS, yet late diagnosis continues in some cases. Awareness of the typical features of PWS in newborn units is required to allow prompt detection even in the presence of confounding factors such as prematurity.

Virtual Networks for Exchanging Information and Biomaterials: Future Directions.

Clinical and research networks for rare conditions are increasingly common nowadays. Given the rarity of many such conditions, there is a need to cover more conditions, yet there is also a need to sustain and improve the quality and effectiveness of existing networks. This review will discuss the qualities that are required by a virtual network using some international clinical and research networks that are currently active in the field of rare endocrine conditions affecting sex and adrenal development as exemplars.

Long-term outcome of thyrotoxicosis in childhood and adolescence in the west of Scotland: the case for long-term antithyroid treatment and the importance of initial counselling.

BACKGROUND: Thyrotoxicosis is both rarer and more severe in children than in adults, rendering management difficult and often unsatisfactory. OBJECTIVE: To ascertain outcome in a geographically defined area of Scotland between 1989 and 2014. METHOD: Retrospective case note review with follow-up questionnaire to family doctors for patients with Graves' disease and Hashimoto's thyroiditis. RESULTS: Sixty-six patients (58 females:8 males) comprising 53 with Graves' disease and 13 with Hashimoto's thyroiditis were diagnosed at median 10.4 (2.9-15.8) years and followed up for 11.8 (2.6-30.2) years. Antithyroid drug (ATD) therapy was stopped electively in 35 patients after 4.5 (1.5-8.6) years, resulting in remission in 10/13 Hashimoto's thyroiditis and 10/22 Graves' disease. Side effects occurred in 12 patients receiving carbimazole, six of whom changed to propylthiouracil; no adverse events occurred in the latter patients.Second-line therapy was given to 37 patients (34 with Graves' disease), comprising radioiodine (22) at 15.6 (9.3-24.4) years for relapse (6), poor control/adherence (14) or electively (2); and surgery (16) at 12 (6.4-21.3) years for relapse (4), poor control/adherence (5) and electively (7). Adherence problems with thyroxine replacement were reported in 10/33 patients in adulthood. CONCLUSIONS: Hashimoto's thyroiditis should be distinguished from Graves' disease at diagnosis since the prognosis for remission is better. Remission rates for Graves' disease are low (10/53 patients), time to remission variable and adherence with both ATD and thyroxine replacement often problematic. We recommend (a) the giving of long-term ATD rather than a fixed course of treatment in GD and (b) meticulous and realistic counselling of families from the time of diagnosis onwards.