Hashimoto’s thyroiditis, hypoparathyroidism and coeliac disease: lessons from a rare association

We present the case of a 36 years old woman, affected by euthyroid Hashimoto’s thyroiditis (HT) from the age of 20. She reported the following symptoms for three years: weight reduction, abdominal pain, alternate constipation and diarrhoea, tiredness, paresthesias and cramps. Biochemical evaluation revealed low iron levels (21 ug/dl, with microcytic anemia) and hypocalcemia (6.6 mg/dl), first attributed to coeliac disease (EMA IgG, AGA IgG-A and tTG IgA positivity; Marsh-Oberhuber 3a/3b type at duodenal biopsy). TSH, PTH and 25-OHD3 were in the normal range. Although the patient was on a gluten-free diet for the second year, cramps persisted and facial spasms and tetanic crises appeared. One year later she came to our attention with severe hypocalcemia (Ca 5.1 mg/dl, Ca++ 0.6 nmol/L) and low PTH (2.5 pg/ml). A diagnosis of primary hypoparathyroidism was made and conventional treatment was started. In the following months, symptomatic hypocalcemia persisted (6.7 mg/dl, Ca++ 0.7 nmol/L), despite the gradual increase of calcium and calcitriol supplements. Gastro-intestinal re-evaluation demonstrated gluten contamination, so as to hypothesize that the scarce dietary compliance had caused persistent malabsorption and had made the hypocalcemia difficult to manage. The observation of these three disorders coexisting in a single patient, never reported by the literature, warns us about the virtually unlimited possibilities of autoimmune disease clustering. Clinicians should be aware of the increased risk of developing additional AIDs in patients with one autoimmune disorder

The External Genitalia Score (EGS): A European Multicenter Validation Study

CONTEXT: Standardized description of external genitalia is needed in the assessment of children with atypical genitalia. OBJECTIVES: To validate the External Genitalia Score (EGS), to present reference values for preterm and term babies up to 24 months and correlate obtained scores with anogenital distances (AGDs). DESIGN, SETTING: A European multicenter (n = 8) validation study was conducted from July 2016 to July 2018. PATIENTS AND METHODS: EGS is based on the external masculinization score but uses a gradual scale from female to male (range, 0-12) and terminology appropriate for both sexes. The reliability of EGS and AGDs was determined by the interclass correlation coefficient (ICC). Cross-sectional data were obtained in 686 term babies (0-24 months) and 181 preterm babies, and 111 babies with atypical genitalia. RESULTS: The ICC of EGS in typical and atypical genitalia is excellent and good, respectively. Median EGS (10th to 90th centile) in males < 28 weeks gestation is 10 (8.6-11.5); in males 28-32 weeks 11.5 (9.2-12); in males 33-36 weeks 11.5 (10.5-12) and in full-term males 12 (10.5-12). In all female babies, EGS is 0 (0-0). The mean (SD) lower/upper AGD ratio (AGDl/u) is 0.45 (0.1), with significant difference between AGDl/u in males 0.49 (0.1) and females 0.39 (0.1) and intermediate values in differences of sex development (DSDs) 0.43 (0.1). The AGDl/u correlates with EGS in males with typical genitalia and in atypical genitalia. CONCLUSIONS: EGS is a reliable and valid tool to describe external genitalia in premature and term babies up to 24 months. EGS correlates with AGDl/u in males. It facilitates standardized assessment, clinical decision-making and multicenter research

Efficacy and safety of growth hormone treatment in children with short stature: the Italian cohort of the GeNeSIS clinical study

Purpose: We examined auxological changes in growth hormone (GH)-treated children in Italy using data from the Italian cohort of the multinational observational Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS) of pediatric patients requiring GH treatment. Methods: We studied 711 children (median baseline age 9.6&nbsp;years). Diagnosis associated with short stature was as determined by the investigator. Height standard deviation score (SDS) was evaluated yearly until final or near-final height (n&nbsp;=&nbsp;78). Adverse events were assessed in all GH-treated patients. Results: The diagnosis resulting in GH treatment was GH deficiency (GHD) in 85.5&nbsp;% of patients, followed by Turner syndrome (TS 6.6&nbsp;%). Median starting GH dose was higher in patients with TS (0.30&nbsp;mg/kg/week) than patients with GHD (0.23&nbsp;mg/kg/week). Median (interquartile range) GH treatment duration was 2.6 (0.6\u20133.7) years. Mean (95&nbsp;% confidence interval) final height SDS gain was 2.00 (1.27\u20132.73) for patients with organic GHD (n&nbsp;=&nbsp;18) and 1.19 (0.97\u20131.40) for patients with idiopathic GHD (n&nbsp;=&nbsp;41), but lower for patients with TS, 0.37 ( 120.03 to 0.77, n&nbsp;=&nbsp;13). Final height SDS was&nbsp;&gt; 122 for 94&nbsp;% of organic GHD, 88&nbsp;% of idiopathic GHD and 62&nbsp;% of TS patients. Mean age at GH start was lower for organic GHD patients, and treatment duration was longer than for other groups, resulting in greater mean final height gain. GH-related adverse events occurred mainly in patients diagnosed with idiopathic GHD. Conclusions: Data from the Italian cohort of GeNeSIS showed auxological changes and safety of GH therapy consistent with results from international surveillance databases

Availability, usage, and preferences of estradiol and progestogen preparations for puberty induction from a multicentral perspective

Introduction: Natural oestrogen administration as oral or transdermal 17β-estradiol is recommended for pubertal induction in girls with hypogonadism. However, suitable low-dose formulations are not consistently available globally. This questionnaire study aimed to identify the current availability of oestrogen and progesterone preparations worldwide. Methods: Endorsed by the ESPE Turner Syndrome Working Group, the questionnaire targeted paediatric endocrinologists. Questions focused on accessibility of oral/transdermal 17β-estradiol and progestogen preparations. Responses were collected through a SurveyMonkey survey disseminated via ESPE channels, direct outreach, and conferences from June 2020 to December 2022. Results: Participation included 229 healthcare professionals from 45 countries. Oral and transdermal 17β-estradiol in adult dosage was highly accessible (86.5% and 84.3%), with transdermal administration the preferred form (62.8%). Most commonly available estradiol preparations included 50 μg patches (32 countries) and 1 or 2 mg tablets (65.8% and 71.1% countries). However, 0.5 mg 17β-estradiol tablets were available in only 20% of respondents from 8 countries. Patches delivering 14 or 25 μg/day of 17β-estradiol were available in 3 and 20 countries, respectively. Oral progestogen had widespread availability (96.0%) and preference (87.0%), while transdermal usage was limited to 15.2% of respondents. Conclusion: This study highlights global challenges in accessing suitable hormone preparations for female pubertal induction. In most countries, the lowest dose of the estradiol is 50 μg for patches and 2 mg for tablets. Appropriate low-dose 17β-estradiol tablets are much less available than low-dose patches. Our survey underscores the importance of adapting guidelines to local availability, and the need for improved accessibility to address these global disparities