Society for Endocrinology UK guidance on the initial evaluation of an infant or an adolescent with a suspected disorder of sex development (Revised 2015).

It is paramount that any child or adolescent with a suspected disorder of sex development (DSD) is assessed by an experienced clinician with adequate knowledge about the range of conditions associated with DSD. If there is any doubt, the case should be discussed with the regional DSD team. In most cases, particularly in the case of the newborn, the paediatric endocrinologist within the regional team acts commonly as the first point of contact. This clinician should be part of a multidisciplinary team experienced in management of DSD and should ensure that the affected person and parents have access to specialist psychological support and that their information needs are comprehensively addressed. The underlying pathophysiology of DSD and the strengths and weaknesses of the tests that can be performed should be discussed with the parents and affected young person and tests undertaken in a timely fashion. Finally, in the field of rare conditions, it is imperative that the clinician shares the experience with others through national and international clinical and research collaboration.

Are serotonin metabolite levels related to bone mineral density in patients with neuroendocrine tumours?

BACKGROUND: Bone mineral density (BMD) is influenced by multiple factors. Recent studies have highlighted a possible relationship between serotonin and BMD. Patients with neuroendocrine tumours (NETs) frequently have elevated urinary 5-hydroxy-indoleacetic acid (5-HIAA) levels, a serotonin metabolite. Evaluation of the relationship between 5-HIAA and BMD in patients with NETs may provide insights into the relationship between serotonin and BMD. METHODS: One-year audit of consecutive patients with NETs within two institutions. Relationships between urinary 5-HIAA and dual X-ray absorptiometry (DEXA)-scan-measured BMD were investigated by group comparisons, correlation and regression. RESULTS: Of 65 patients with NETs, 19 did not participate or were excluded. Of 46 subjects evaluated (48·9% males, 63·8 ± 10·5 years, BMI 26·6 ± 4·4 kg/m(2) ) with 32 gastrointestinal, 9 pancreatic, 3 pulmonary and 2 ovarian NETs, 72·3% had the carcinoid syndrome. Median interval from diagnosis was 4·0 years (IQR 2·0-6·0); 41·3% had osteoporosis and 32·6% osteopaenia (WHO definition). The group with a higher urinary 5-HIAA had a lower hip BMD (total T-score and Z-score), confirmed on individual analysis (Spearman's rank correlation -0·41, P = 0·004; -0·44, P = 0·002, respectively); urinary 5-HIAA was not found to be an independent predictor for BMD on multiple linear regression analysis. CONCLUSION: These data of patients with NETs with higher serotonin metabolites having a lower BMD at the hip in group and individual comparisons, warrants further evaluation. Urinary 5-HIAA measurement alone cannot be used to predict future BMD. A larger cohort with prospective design including fractures as a clinical outcome will aid these data in determining whether patients with NETs should be subject to targeted osteoporosis prevention.

Norethisterone interference in testosterone assays.

BACKGROUND: This article describes three patients in whom measured serum testosterone concentrations were found to be artifactually high due to interference from norethisterone medication. This interference was investigated further by distributing samples containing norethisterone through an external quality assessment scheme. METHODS: Serum samples containing different concentrations of norethisterone were distributed to participants in the UK external quality assessment scheme (UK NEQAS) for female testosterone in order to assess the degree of interference from norethisterone in different commercially available immunoassay and liquid chromatography-tandem mass spectrometry methods for measurement of testosterone. RESULTS: The results have shown that apparent serum testosterone concentrations in excess of 5 nmol/L may be obtained using the Roche E170 Modular immunoassay method for samples collected from patients taking norethisterone medication and this interference can be reproduced by adding norethisterone to serum samples. CONCLUSIONS: Although the biggest interference is seen with the Roche system, there is a small effect in the Siemens ADVIA Centaur assay and some of the other immunoassays may also be affected to a much lesser extent. Norethisterone does not interfere in testosterone measurements obtained by liquid chromatography-tandem mass spectrometry.

UK guidance on the initial evaluation of an infant or an adolescent with a suspected disorder of sex development.

It is paramount that any child or adolescent with a suspected disorder of sex development (DSD) is assessed by an experienced clinician with adequate knowledge about the range of conditions associated with DSD. If there is any doubt, the case should be discussed with the regional team. In most cases, particularly in the case of the newborn, the paediatric endocrinologist within the regional DSD team acts as the first point of contact. The underlying pathophysiology of DSD and the strengths and weaknesses of the tests that can be performed should be discussed with the parents and affected young person and tests undertaken in a timely fashion. This clinician should be part of a multidisciplinary team experienced in management of DSD and should ensure that the affected person and parents are as fully informed as possible and have access to specialist psychological support. Finally, in the field of rare conditions, it is imperative that the clinician shares the experience with others through national and international clinical and research collaboration.

Unmasking of central hypothyroidism following growth hormone replacement in adult hypopituitary patients.

BACKGROUND: The effect of GH replacement on thyroid function in hypopituitary patients has hitherto been studied in small groups of children and adults with conflicting results. OBJECTIVE: We aimed to define the effect and clinical significance of adult GH replacement on thyroid status in a large cohort of GH-deficient patients. PATIENTS AND METHOD: We studied 243 patients with severe GH deficiency due to various hypothalamo-pituitary disorders. Before GH treatment, 159 patients had treated central hypothyroidism (treated group) while 84 patients were considered euthyroid (untreated group). GH dose was titrated over 3 months to achieve serum IGF-1 concentration in the upper half of the age-adjusted normal range. Serial measurements of serum T4, T3, TSH and quality of life were made at baseline and at 3 and 6 months after commencing GH replacement. RESULTS: In the untreated group, we observed a significant reduction in serum T4 concentration without a significant increase in serum T3 or TSH concentration; 30/84 patients (36%) became hypothyroid and needed initiation of T4 therapy. Similar but lesser changes were seen in the treated group, 25 of whom (16%) required an increase in T4 dose. Patients who became hypothyroid after GH replacement had lower baseline serum T4 concentration, were more likely to have multiple pituitary hormone deficiencies and showed less improvement in quality of life compared with patients who remained euthyroid. CONCLUSION: GH deficiency masks central hypothyroidism in a significant proportion of hypopituitary patients and this is exposed after GH replacement. We recommend that hypopituitary patients with GH deficiency and low normal serum T4 concentration should be considered for T4 replacement prior to commencement of GH in order to provide a robust baseline from which to judge the clinical effects of GH replacement.

Low IGF-I and elevated testosterone during puberty in subjects with type 1 diabetes developing microalbuminuria in comparison to normoalbuminuric control subjects: the Oxford Regional Prospective Study.

OBJECTIVE: To describe longitudinal variations in pubertal hormonal variables in subjects with and without microalbuminuria (MA). RESEARCH DESIGN AND METHODS: Blood samples collected annually from subjects recruited at diagnosis of type 1 diabetes and followed prospectively through puberty (median follow-up 9.3 years, range 4.7-12.8) were analyzed for total and free IGF-I, IGF binding protein-1, testosterone, sex hormone-binding globulin, and HbA(1c). A total of 55 subjects who developed MA (MA(+) group) were compared with 55 age-, sex-, and duration-matched control subjects who did not develop MA (MA(-) group). RESULTS: For female subjects, total IGF-I (MA(+) 1.2 mU/l vs. MA(-) 1.4 mU/l, P = 0.03) and free IGF-I levels (MA(+) 1,767 ng/l vs. MA(-) 2010 ng/l, P = 0.002) were lower, whereas the free androgen index (MA(+) 2.4 vs. MA(-) 2.0, P = 0.03) was higher in those with MA. These changes were less pronounced in male subjects. For both sexes, in a Cox model after adjusting for puberty, the presence of MA was associated with lower free IGF-I levels, higher testosterone standard deviation score (SDS), and poor glycemic control. We found that 22 of 55 case subjects (40%) developed persistent MA, whereas 33 (60%) had transient MA. In the persistent MA group compared with the transient and control groups, total IGF-I levels were lower (1.1 vs. 1.3 vs. 1.4 mU/l, P = 0.002) as were free IGF-I levels (1,370.9 vs. 1,907.3 vs. 1,886.7 ng/l, P < 0.001), whereas HbA(1c) levels were higher (11.8 vs. 10.3 vs. 9.9%, P < 0.001). CONCLUSIONS: Poor glycemic control and differences in IGF-I levels and androgens, particularly in female subjects, accompany development of MA at puberty. These differences may in part account for the sexual dimorphism in MA risk during puberty and could relate to disease progression.