Teriparatide (rhPTH) treatment in children with syndromic hypoparathyroidism.

BACKGROUND: Subcutaneous recombinant human parathormone [rhPTH (1-34)] has been introduced for hypoparathyroidism treatment, allowing avoidance of vitamin D and calcium side effects. OBJECTIVE: Our objective was to evaluate rhPTH (1-34) safety and efficacy in pediatric patients with genetically proved syndromic hypoparathyroidism. METHODS: The study was a 2.5-year self-controlled trial on six pediatric patients (four males, two females, age 9.8±5.1 years) with syndromic hypoparathyroidism including three with autoimmune polyendocrinopathy candidiasis ectodermal dysplasia (APECED) syndrome, two with DiGeorge syndrome, and one with hypoparathyroidism-deafness-renal dysplasia syndrome. We compared patients' clinical and biochemical outcome of conventional treatment based on oral administration of calcium (1-1.5 g/day in three doses) plus oral calcitriol (6.5-33 ng/kg per day in two to three doses) with the outcome obtained with rhPTH (1-34) (teriparatide, 12.5 µg bid). Therapy shift was conducted introducing rhPTH (1-34) while progressively withdrawing calcium and vitamin D. Blood calcium, phosphorus, alkaline phosphatase, and urinary calcium-to-creatinine ratio (mg/mg) before and during rhPTH therapy were compared. RESULTS: rhPTH treatment allowed complete calcium and vitamin D withdrawal in two patients, calcium withdrawal in three and reduction of vitamin D dose in two. During rhPTH (1-34), mean blood calcium, phosphorus, and alkaline phosphatase were not significantly modified, whereas significant reduction of the calciuria-to-creatininuria ratio (0.55±0.31 vs. 0.1±0.1, p=0.02) was obtained. The number of tetanic episodes was reduced in four patients during teriparatide treatment compared to conventional treatment. CONCLUSION: In children with syndromic hypoparathyroidism, substitutive treatment with rhPTH (1-34) maintains adequate blood calcium levels and allows prompt normalization of urinary calcium excretion, through direct action on the kidney and through calcium and vitamin D therapy layoff.

Improved sperm count and motility in young men surgically treated for cryptorchidism in the first year of life.

INTRODUCTION: The timing of surgery in cryptorchidism has been debated for a long time. Reports on histology suggest better fertility outcomes with early surgery, whereas evidence of long-term improved fertility still lacks sound data. The aim of this study is to analyze sperm count and motility in a cohort of young men operated on during the first 2 years of life for cryptorchidism. PATIENTS AND METHODS: A total of 78 young men (age, 18-26 years) surgically treated for cryptorchidism in the second year of life were recalled to evaluate testicular volume and sperm count and motility. Of the 78 young men, 51 accepted to participate to clinical and sperm evaluation. Relationship between total sperm count (TSC), sperm motility (SM), and age at surgery was investigated by Student t-test and Fisher test. Patients were divided into two groups: those patients who were submitted to surgery in their first year of life (Group A) and those patients who were submitted to surgery in their first and the second year of life (Group B). We investigated the ratio of those patients with normal sperm count to those patients with abnormal sperm count (we defined as normal TSC > 15 million and SM > 15%) and compared the mean TSC and SM in the two groups. RESULTS: TSC were slightly but not significantly higher in the first group (45.5 ± 15.5 million/mL vs. 36.5 ± 23.6 million/mL, p = 0.107) and SM (30.5% ± 11.3% vs. 26.5% ± 15.4%, p = 0.341). The percentage of patients with normal sperm count and motility were significantly higher in the first group: normal TSC was found in 26 of 27 patients (96.3%) in Group A versus 18 of 24 patients (75.0%) in Group B (p = 0.042), normal SM was found in 26 of 27 patients (96.3%) versus 16 of 24 patients (66.7%), respectively (p = 0.008). In the two groups, no statistically significant difference was found neither in the proportion of patients with bilateral cryptorchidism, in the position of the testes, nor in the ratio of subjects treated with hormonal therapy before being operated on. CONCLUSIONS: In formerly cryptorchid subjects submitted to surgery in the first 2 years of life, the percentage of patients with normal sperm count and motility is higher than 95%, with even better fertility prognosis if orchiopexy is performed in the first year of life.

Iatrogenic acute pancreatitis due to hypercalcemia in a child with pseudohypoparathyroidism.

Pancreatitis due to hypercalcemia is very rare in children, and its pathogenetic role is still debated. The following report describes a case of acute pancreatitis secondary to hypercalcemia in a 6-year-old boy with pseudohypoparathyroidism treated with calcium and vitamin D. Pseudohypoparathyroidism is characterized by parathormone (PTH) resistance, high PTH levels and hypocalcemia which need to be corrected with calcium and vitamin D supplementation. The patient was admitted for severe abdominal pain and vomiting associated with high plasma amylase, lipase and calcium levels. Hypercalcemia due to vitamin D and calcium overtreatment was probably responsible for the acute pancreatitis in this case. High serum calcium levels seem to sensitize patients to pancreatitis, even if the mechanism through which it happens is not completely understood. Moreover, the importance of concomitant predisposing factors, either acquired or especially genetic, needs to be further defined. Even though a rare occurance in childhood, hypercalcemia should be considered as a cause of pancreatitis and it should be examined together with the other etiologies that may contribute to the development of this disease.

Thyroid involvement in two patients with Bannayan-Riley-Ruvalcaba syndrome.

Bannayan-Riley-Ruvalcaba syndrome (BRRs) is an overgrowth disorder characterized by macrocephaly, pigmented maculae of the glans penis, and benign mesodermal hamartomas (primarily subcutaneous and visceral lipomas, multiple hemangiomas, and intestinal polyps). Dysmorphic features as well as delayed neuropsychomotor development can also be present. These patients have also a higher risk of developing tumors, as the gene involved in BRRs is phosphatase and tensin homologue (PTEN), and up to 30% of the patients have thyroid involvement consistent with multinodular goiter, thyroid adenoma, differentiated non-medullary thyroid cancer, or Hashimoto's thyroiditis. Here, we report two cases of BRRs at opposite ends of its phenotypic spectrum: clinical manifestations of the first patient were more severe, while the second one showed only few signs and had no family history of the disease. Both cases developed thyroid disorders detected by thyroid ultrasound screening. We believe that it is important for clinicians, specifically pediatric endocrinologists, to know that this syndrome can appear in very subtle ways and also to be aware that thyroid nodules and intestinal polyps seem to be its most frequently encountered features.