Gonadotropin-Releasing Hormone Analogs for Treatment of Central Precocious Puberty in Children Younger than 2 Years of Age.

Although gonadotropin-releasing hormone analogs are the standard of care for the treatment of central precocious puberty, they are not approved for children/< age 2 years. We reviewed experience with the use of gonadotropin-releasing hormone analogs in 47 children younger than age 2 years, which revealed efficacy and safety comparable with that in older children.

Variability in Oral Desmopressin Dose Requirements in Children with Central Diabetes Insipidus.

There is inconsistency in the amount of oral desmopressin that children with central diabetes insipidus require. We investigated whether clinical characteristics influenced desmopressin dose requirements in 100 children with central diabetes insipidus. Extremely large doses were associated with acquired etiology (P = .04), greater body mass index z score, intact thirst, and additional pituitary hormone deficiencies (P < .001).

Prevalence of Nephrocalcinosis in Pseudohypoparathyroidism: Is Screening Necessary?

The prevalence of nephrocalcinosis in persons with pseudohypoparathyroidism has not been systematically examined. We conducted a retrospective study of renal imaging and biochemical results in 19 patients with pseudohypoparathyroidism with 49 imaging assessments. No cases of nephrocalcinosis were identified. Routine screening for nephrocalcinosis in pseudohypoparathyroidism may not be necessary.

Resumption of puberty in girls and boys following removal of the histrelin implant.

OBJECTIVES: To determine time to menarche in girls and testicular volume increase in boys after removal of a histrelin implant, which causes profound hypothalamic-pituitary-gonadal axis suppression. STUDY DESIGN: Medical records of patients treated with a histrelin implant were reviewed. Seventy-one patients (56 girls) treated with the histrelin implant were identified, of these patients, 37 explanted girls (68% naïve) and 6 explanted boys (83% naïve) were included in the analysis. Time to menarche after explantation in girls and time to testicular volume increase after explantation in boys were determined. Additional variables investigated included indication for and duration of treatment, history of menarche (girls), previous therapy, and age at beginning and end of histrelin treatment. RESULTS: Of the girls, 30 were treated for central precocious puberty (CPP), 26 had menarche at an average of 12.75 months after explantation. Of the 30, 7 were treated for other indications, of whom 6 had reached menarche. In girls with CPP, older age at explantation correlated with sooner menarche (P = .04). All boys achieved spontaneous testicular enlargement within 1 year of explantation. CONCLUSIONS: This study documented resumption of puberty after histrelin explantation in treatment naïve and non-naïve boys and girls with and without CPP. Menarche in girls with CPP occurs within a similar timeframe to that observed after other treatment approaches.

A single histrelin implant is effective for 2 years for treatment of central precocious puberty.

We investigated whether a "yearly" histrelin implant would provide pubertal suppression when left in place for 2 years. Equivalent suppression was observed when comparing 12 and 24 months in 33 children with central precocious puberty. A single implant for 2 years reduces cost and number of implant procedures.

Random luteinizing hormone often remains pubertal in children treated with the histrelin implant for central precocious puberty.

OBJECTIVE: To investigate the use of random ultrasensitive (US) luteinizing hormone (LH) levels to monitor children being treated with a histrelin implant for central precocious puberty (CPP). STUDY DESIGN: This was a prospective, uncontrolled, observational study at a pediatric endocrinology tertiary center. Thirty-three children (26 girls; mean age 7.2 ± 2.5 years) treated with a histrelin implant for CPP were enrolled. A random US LH measurement was obtained at 6 months, and a gonadotropin-releasing hormone analog stimulation test was performed at 12 months. Clinic visits occurred at baseline and at 6-month intervals. RESULTS: In 59% of the patients (17 of 29), the 6-month random US LH exceeded the prepubertal range of ≤0.3 IU/L. In contrast, gonadotropin-releasing hormone analog stimulation tests revealed complete hypothalamic-pituitary-gonadal axis suppression (peak LH <4 IU/L) in all 31 patients who underwent testing. US LH levels were highly correlated with peak stimulated LH levels. The mean peak stimulated LH level was higher in patients with a pubertal random LH than in those with a prepubertal random LH (1.2 ± 0.5 IU/L vs 0.5 ± 0.1 IU/L; P < .01). No patient had clinical evidence of pubertal progression. CONCLUSION: The random US LH level does not revert to a prepubertal range in more than one-half of patients with a histrelin implant and documented hypothalamic-pituitary-gonadal axis suppression. Long-term studies are needed to elucidate the optimal strategy for monitoring treatment in children with CPP.

Incidence and characteristics of pseudoprecocious puberty because of severe primary hypothyroidism.

Severe primary hypothyroidism is a presumed rare cause of pseudoprecocious puberty (PsPP). Here, we report a 24% incidence of PsPP among 33 children with profound hypothyroidism. Those with PsPP were older and trended toward a higher thyroid stimulating hormone. Increased awareness of PsPP can hasten diagnosis and appropriate treatment.

Combined central precocious puberty and primary gonadal failure after treatment of childhood malignancy in two boys: a diagnostic and therapeutic conundrum.

Central precocious puberty and primary gonadal failure are known sequelae of childhood cancer or its treatment. Here we report two boys with coexistent central precocious puberty and primary gonadal failure after treatment for childhood malignancies.

Newborn screening results in children with central hypothyroidism.

OBJECTIVE: To investigate newborn screening results in children with congenital hypopituitarism, including central hypothyroidism, and to determine whether there were differences between children who had abnormal results and children with normal newborn screening results. STUDY DESIGN: Medical records of children with central hypothyroidism observed in our pediatric endocrinology clinics from 1990 to 2006 were reviewed. RESULTS: Forty-two subjects (22 boys) were identified. Eight children (19%) had a low total thyroxine level (<5.0 mcg/dL) on the newborn screening test. The average total thyroxine level in the remaining 34 subjects was 9.8 +/- 3.4 mcg/dL. Thyrotropin levels were within the reference range in all children. No differences were found in the 2 groups for birth history, jaundice (53% overall), hypoglycemia (36% overall), or micropenis (43% of boys). Fifty-seven percent of children had septo-optic dysplasia, and 98% had multiple pituitary hormone deficiencies. Children with an abnormal newborn screening results were initially examined by a pediatric endocrinologist at an average age of 4.6 +/- 5.0 months, and children with normal newborn screening results were initially examined at an average age of 16.9 +/- 26.7 months (P = .037). CONCLUSIONS: Most children with congenital central hypothyroidism have normal thyroid function at birth. Normal newborn screening results can be falsely reassuring and may contribute to a delay in diagnosis of hypopituitarism despite classic clinical features.

Unexpected recovery of ovarian function many years after bone marrow transplantation.

Premature ovarian failure as a consequence of childhood cancer treatment is considered permanent when present long after the initial insult. We report spontaneous recovery of ovarian function occurring 8 years after bone marrow transplantation in a girl with history of leukemia and growth hormone deficiency. Clinical management challenges are discussed.

Presentation and clinical progression of pseudohypoparathyroidism with multi-hormone resistance and Albright hereditary osteodystrophy: a case series.

Anthropometric and biochemical features were retrospectively evaluated in 12 patients with pseudohypoparathyroidism, Albright hereditary osteodystrophy, and multi-hormone resistance. Hypothyroidism and subcutaneous calcifications were presenting features in younger children. Temporal trends in stimulatory hormone resistance included early thyroid-stimulating hormone elevation and progression from parathyroid hormone elevation to hyperphosphatemia and hypocalcemia.

Hashitoxicosis in children: clinical features and natural history.

OBJECTIVE: To determine the incidence, natural history, and clinical characteristics of Hashitoxicosis (Htx) in pediatric patients with autoimmune thyroiditis. STUDY DESIGN: Medical records of children diagnosed with Hashimoto thyroiditis between 1993 and 2002 were reviewed. The clinical course of patients presenting with hyperthyroidism was determined. Variables including sex, age, family history, thyroid hormone levels, anti-thyroid antibody titers, 123 I thyroid scan results, and presenting features were investigated as possible predisposing factors for the development of Htx. RESULTS: Out of 69 patients with autoimmune thyroiditis, 8 were diagnosed with Htx. The duration of hyperthyroidism ranged from 31 to 168 days. Three patients became hypothyroid after an average of 46.3 +/- 13.2 days, and 5 patients became euthyroid after an average of 112.8 +/- 59.8 days. Additional findings included an elevated thyroid stimulating immunoglobulin (TSI) titer in 3 of the 8 patients with Htx, and increased uptake on 123 I scan in 2 patients. CONCLUSION: Htx is an uncommon yet important cause of hyperthyroidism in children that has a variable clinical course. The diagnosis may be complicated, as presenting features sometimes exhibit significant overlap with Graves' disease. No factors predisposing to the development of Htx were identified.

A randomized, controlled study of insulin pump therapy in diabetic preschoolers.

OBJECTIVE: To compare glycemic control, safety, and parental satisfaction in preschool-aged diabetic children randomized to treatment either with continuous subcutaneous insulin infusion (CSII) or intensive insulin injection therapy. STUDY DESIGN: This clinical trial enrolled 42 patients <5 years of age who had been diagnosed with diabetes for at least 12 months. Children were randomly assigned to CSII (n = 21) or intensive insulin injection therapy (n = 21). Hemoglobin A1c (HbA1c) level was measured at baseline, 3, and 6 months. Secondary outcomes included severe hypoglycemic events, meter-detected hypoglycemia, blood sugar variability, body mass index (BMI), and satisfaction with therapy. RESULTS: Thirty-seven patients completed 6 months of therapy. There was a significant decrease in HbA1c during the study period for both groups (from 8.9% +/- 0.6% to 8.6% +/- 0.6% at 3- and 6-month visits). At 3 months, children using pumps had a significantly lower HbA1c than the injection group (8.4% vs 8.8%); however, by 6 months the two groups were similar (8.5% vs 8.7%). No differences in pre-meal blood sugar variabilities were seen between groups. Children on pumps had increases in the number of meter-detected episodes of hypoglycemia. Pump therapy was safe and well tolerated. No episodes of ketoacidosis occurred in either group, whereas one hypoglycemic seizure occurred in each group. Parents reported satisfaction with CSII, with 95% of families continuing on CSII beyond the 6-month study period. CONCLUSION: Pump therapy in preschool-aged children was not associated with clinically significant differences in glycemic control as compared with intensive injection therapy. The rationale for initiating CSII in this age group should be based on patient selection and lifestyle preference.

Pancreatic enzyme elevations in children with diabetic ketoacidosis.

The incidence of pancreatic enzyme elevations in children with diabetic ketoacidosis (DKA) compared with children with newly diagnosed diabetes without DKA was assessed in a prospective study. Pancreatic enzyme elevations, particularly hyperlipasemia, are common but not associated with significant symptomatology. Acute pancreatitis was diagnosed in 2% of children with DKA.

Definitive diagnosis in children with congenital hypothyroidism.

OBJECTIVES: To investigate the definitive diagnosis and underlying causes of congenital hypothyroidism (CH) in eligible children through the use of a standardized protocol. STUDY DESIGN: Children > or =3 years of age with CH without an identified permanent cause underwent a diagnostic algorithm. Eligible subjects had an anatomically normal thyroid or had not undergone imaging studies. After thyroxine was discontinued for 4 weeks, thyroid function tests and a thyroid ultrasound were obtained. An abnormal ultrasound was followed by a (99m)Tc thyroid scan. A perchlorate washout test was performed in subjects with a normal ultrasound but abnormal thyroid function tests. Children with normal results were followed for 1 year. RESULTS: Of 33 children, 17 were boys. Nine (27%) had an absent or ectopic thyroid, 12 (36%) had dyshormonogenesis, and 12 (36%) had transient CH. Average thyroxine dose before medication discontinuation was 2.9 +/- 0.83 microg/kg in permanent cases versus 2.0 +/- 0.53 microg/kg in transient (P <.002). No complications from discontinuation of thyroxine occurred. CONCLUSIONS: A significant percentage of children with CH have a transient requirement for thyroid hormone. A standardized protocol with thyroid ultrasonography is a safe and sensitive approach to a trial off of thyroxine in select patients.

Tamoxifen treatment for precocious puberty in McCune-Albright syndrome: a multicenter trial.

OBJECTIVE: We undertook a 1-year multicenter trial of tamoxifen treatment for precocious puberty in girls with McCune-Albright syndrome (MAS). STUDY DESIGN: Girls < or =10 years with classic or atypical MAS were recruited. Pretreatment history was collected for 6 months. Patients received 20 mg tamoxifen daily. Diaries were used to record bleeding. Evaluations included physical examination, bone age, pelvic ultrasound, hormone levels, and safety assessments. RESULTS: A total of 28 girls (2.9-10.9 years of age) were enrolled from 20 centers, of whom 25 completed 12 months of tamoxifen treatment. Compared with before the study, vaginal bleeding episodes decreased (3.42+/-3.36/year vs 1.17+/-1.41/year), growth velocity slowed (SDS 1.22+/-2.65 vs -0.59+/-3.06, P=.005), and rate of bone maturation decreased (1.21+/-0.78 vs 0.72+/-0.36, P=.02). Ovarian volumes were enlarged and asymmetric throughout the study, and uterine volumes were increased. No adverse events occurred. CONCLUSIONS: Tamoxifen treatment of precocious puberty in MAS results in a reduction of vaginal bleeding and significant improvements in growth velocity and rate of skeletal maturation.

Is McCune-Albright syndrome overlooked in subjects with fibrous dysplasia of bone?

OBJECTIVE: McCune-Albright syndrome (MAS) is characterized by a clinical triad of endocrinopathies, café au lait pigmentation, and polyostotic fibrous dysplasia of bone. We hypothesized that children diagnosed with fibrous dysplasia are not routinely being evaluated for coexisting endocrine dysfunction or MAS. Our objective was to prospectively screen subjects with fibrous dysplasia for endocrine disease and G(s)alpha gene (GNAS1 )-activating mutations. STUDY DESIGN: Nine subjects who presented with fibrous dysplasia and were followed in orthopedic clinics were evaluated for other manifestations of MAS. Genomic DNA was isolated from blood, and mutation analysis of GNAS1 was performed. RESULTS: On physical examination, 5 of 9 subjects were found to have café au lait pigmentation. Three of 9 subjects had TSH levels below the normal range. One of these subjects was found to have hyperthyroidism and was treated by total thyroidectomy. GNAS1 mutations were identified in 5 of 9 subjects with either monostotic or polyostotic fibrous dysplasia of bone. CONCLUSIONS: We conclude that a substantial proportion of children being followed for fibrous dysplasia of bone have unrecognized clinical and laboratory features of MAS. These children are at risk for endocrinopathy and should be screened accordingly.