Beyond the bias! Sex distribution in paediatric growth hormone deficiency reexamined.

OBJECTIVES: Various biases pertaining to stature account for a male sex predominance in growth hormone deficiency (GHD) cases diagnosed by endocrinology clinics. This manuscript will assess the sex distribution when biases are minimised. METHODS: Retrospective chart review was conducted on patients diagnosed with GHD between 3 and 16 years of age. The sex distribution of cases was ascertained according to: (1) peak GH (pGH) by groups; based on growth hormone provocative testing, (2) pituitary gland imaging results, and (3) isolated GHD (IGHD) versus multiple pituitary hormone deficiencies (MPHD). The relative frequency of each sex was compared according to these subgroups with significance evaluated at α = .05 level. RESULTS: Of the 5880 clinic referrals for short stature, there were 3709 boys (63%) and 2171 girls (37%). Of these, 20% of boys (n = 745) and 15.3% of girls (n = 332) underwent provocative testing for GHD. Of those tested, 39.2% of boys (n = 292) and 32.2% of girls (n = 107) were diagnosed with GHD, all p < .001. There was a male predominance in GHD cases based on pGH or GHD severity. Though not significant, girls were more likely than boys to have MPHD (p = .056), even across pGH groups (p = .06). Both boys and girls had a similar distribution of imaging abnormalities. CONCLUSION: Stratifying by sex, we found similar percentages of pituitary imaging abnormalities (including tumours) and the number of pituitary hormone deficiencies in boys and girls as the cause of GHD. For these classifications, we did not find the historically reported male sex predominance.

The utility of a random cortisol level in determining neonatal central adrenal insufficiency.

OBJECTIVES: While it has been established within the first 4 months of life that there is no circadian rhythm, what is unclear is the usefulness of a random serum cortisol (rSC) level in determining neonatal central adrenal insufficiency (CAI). The objective of the study is to determine the utility of using rSC in infants less than 4 months old in the evaluation of CAI. DESIGN AND PATIENTS: Retrospective chart review of infants who underwent a low dose cosyntropin stimulation test ≤4 months of life with rSC taken as baseline cortisol before stimulation. Infants were divided into three groups: those diagnosed with CAI, those at risk for CAI (ARF-CAI) and a non-CAI group. Mean rSC for each group was compared, and ROC analysis was used to identify rSC cut-off for the diagnosis of CAI. RESULTS: Two hundred and fifty one infants with the mean age of 50.5 ± 38.08 days, and 37% of these were born at term gestation. The mean rSC were lower in the CAI group (1.98 ± 1.88 mcg/dl) as compared to the ARF-CAI (6.27 ± 5.48 mcg/dl, p = .002) and non-CAI (4.6 ± 4.02 mcg/dl, p = .007) groups. ROC analysis identified a cut-off of rSC level of 5.6 mcg/dL is associated with 42.6% sensitivity and 100% specificity for the diagnosis of CAI in term infants. CONCLUSIONS: This study demonstrates that though an rSC can be used within the first 4 months of life, its value is best when done ≤30 days of life. Moreover, a diagnostic cut-off for CAI using rSC levels was identified for term infants.

Preterm to term infant postmenstrual age reference intervals for thyroid-stimulating hormone and free thyroxine.

BACKGROUND: Infants born preterm are affected by a hypothalamic-pituitary-thyroid axis that is immature and still developing as they progress closer to corrected term gestation. Multiple risk factors place preterm infants at risk for a hypothyroid state. However, there is variability in thyroid-stimulating hormone cutoff values and limited data on free thyroxine reference intervals to guide clinicians. METHODS: 1584 thyroid-stimulating hormone and 1576 free thyroxine laboratory samples that were originally collected to screen hospitalized infants for delayed-onset of hypothyroidism were retrospectively evaluated from a group of 1087 infants who ranged in postmenstrual age from 25 to 43 weeks gestation at the time of laboratory sample collection. Median thyroid hormone values and reference intervals were established using R and the mixtools package. RESULTS: Thyroid-stimulating hormone reference intervals remained similar across gestational ages from 0.340-9.681 µIU/mL in 25-27 6/7-week infants to 1.090-7.627 µIU/mL in 40-43-weeks infants. For the same age groups, free thyroxine reference intervals increased from 0.42-0.91 ng/dL to 0.87-1.32 ng/dL. CONCLUSION: The reference intervals identified suggest that infants <31 weeks gestation have a higher thyroid-stimulating hormone and lower free thyroxine level at baseline than previously anticipated. IMPACT: The increasing free thyroxine values in preterm to term infants indicate a maturing hypothalamic-pituitary-thyroid axis. Clinicians need thyroid hormone reference intervals that also vary by postmenstrual age to aid the evaluation of sick preterm infants who are at risk of a delayed hypothyroidism diagnosis that can be missed on the initial newborn screen. This study provides one of the largest samples of thyroid-stimulating hormone and free thyroxine data to establish reference intervals in preterm infants. Clinicians may utilize the identified postmenstrual age-based reference intervals to inform follow-up thyroid testing in preterm infants at several weeks postnatal age.

On a Different Page! Perceptions on the Onset, Diagnosis, and Management of Type 2 Diabetes Among Adolescent Patients, Parents, and Physicians.

To examine perceptions about the diagnostic process and post-diagnosis care of type 2 diabetes (T2D) from adolescent patients, parents, and diabetes care physicians, semi-structured interviews were conducted with 8 individuals from each group. Interview transcripts were coded using content analysis. Emerged categories were compared among 3 groups. Half of adolescent patients and parents were surprised by the T2D diagnosis, despite most reporting that patients experienced common symptoms of T2D prior to diagnosis. Adolescents and parents recognized diet, exercise, and weight gain as risk factors after diagnosis, whereas physicians noted weight gain as a common risk factor pre-diagnosis. All 3 groups noted the importance of maintaining a healthy lifestyle and adherence to T2D management, though physicians noted the challenges from socioeconomic structural inequalities. Adolescent and parents were surprised by the T2D diagnosis, suggesting the need for increasing awareness of risk factors and symptomatology of T2D among at-risk adolescents and parents.

The necessity of magnetic resonance imaging in the evaluation of pediatric growth hormone deficiency: Lessons from a large academic center.

BACKGROUND: Current guidelines indiscriminately recommend magnetic resonance imaging (MRI) of the pituitary gland in pediatric growth hormone deficiency (GHD). The relationship between abnormal MRI, most importantly a tumor, and peak GH levels is not well known. METHODS: In this retrospective chart review, pituitary MRI results of children, ages of 3-16 years with GHD were collected and divided into 3 groups according to peak stimulated GH levels; ≤5, 5-7.4 and 7.5-10 ng/mL, Groups A, B & C respectively. Clinical and MRI findings were compared between the groups. RESULTS: A total of 399 children were included. Abnormal MRI was found in 36.9% of group A subjects, compared to group B (16.7%) and group C (17.0%), both p values =0.0002. Children with multiple pituitary hormonal deficiencies (MPHD) had a higher rate of abnormalities than those with isolated GHD. Children with isolated GHD were more likely to have abnormal MRI with peak GH level < 5 ng/mL compared to those with levels, 5-7.4 & 7.5-10 ng/mL. 4 children in group A had a craniopharyngioma. ROC analysis comparing peak GH levels with abnormal MRI findings showed an area under the curve (AUC) of 0.614 and 0.728 for IGHD and MPHD, respectively. CONCLUSION: Although abnormal MRI was found in all 3 study groups, it was more likely at GH level < 5 ng/mL and in children with MPHD. To avoid missing a tumor, the importance of imaging in children with GHD and peak GH levels <5 ng/mL cannot be overemphasized.

The utility of a random growth hormone level in determining neonatal growth hormone sufficiency.

BACKGROUND: Random growth hormone (GH) levels have been used in the neonate to investigate congenital growth hormone deficiency (GHD). The cut-off value for use in this diagnosis is yet to be established. METHODS: This is a retrospective chart review of all random GH levels obtained in neonates ≤28 days of age. Neonates were divided into three groups: those diagnosed with congenital GHD, those at risk for GHD (ARF-GHD) and a non-growth hormone deficient (non-GHD) group. Mean GH levels for each group were compared, and ROC analysis was used to identify a cut-off for the diagnosis of GHD. RESULTS: The study included 138 neonates with the mean age of 9.07 ± 6.6 days, and 65% of these were born at term gestation. Mean GH levels were lower in the GHD group (2.73 ± 1.19 ng/ml) as compared to the ARF-GHD (9.4 ± 7.96 ng/ml, p = .002) and non-GHD groups (14.86 ± 14.42 ng/ml, p = .027). GH values were not significantly different between non-GHD and ARF-GHD groups. ROC analysis identified a cut-off of serum random GH level of 4.5 ng/ml that achieved 100% sensitivity and 83% specificity for the diagnosis of congenital GHD. CONCLUSION: This study demonstrates that random GH levels obtained in the first 28 days of life can be useful in diagnosing congenital GHD. Moreover, a diagnostic cut-off for congenital GHD using random GH levels was identified.

In iodine-induced thyrotoxicosis, steroid therapy today could keep the surgical knife at bay.

BACKGROUND: Amiodarone-induced thyrotoxicosis (AIT) type 2, characterized as a destructive thyroiditis, is well described in the medical literature; however, iodine-induced thyrotoxicosis (IIT) is not, though the latter has similar features and can be managed similarly. CASE PRESENTATION: We present a 17-year-old female who presented with a history of an intermittent goiter with thyroid function tests (TFTs): thyroid-stimulating hormone (TSH)<0.015 (0.4-4 µU/mL), free thyroxine (T4)≥6 (0.7-2.1 ng/dL) and total triiodothyronine (T3) 651 (50-200 mg/dL). Thyroid antibodies were all negative. Despite methimazole therapy for 6 weeks, hyperthyroidism proved refractory to medical management. 123I scan uptake was suppressed. With hyperthyroidism being recalcitrant to therapy, a nutritional history revealed consumption of an iodine supplement containing at least 7 times the recommended daily allowance (RDA) for 5 years, contributing to the Jod-Basedow phenomenon. Urinary spot and 24-hour urinary iodine were both elevated. Though a surgical consult was obtained, surgery was cancelled once TFTs improved and then normalized with steroid therapy. The TFTs and urinary iodine levels remained normal post steroid therapy. CONCLUSIONS: We suggest that in addition to the need for a thorough nutritional history, a trial of corticosteroids should be utilized in the management of IIT which can present with findings similar to AIT type 2 which is recalcitrant to thionamide therapy. If successful, corticosteroids may delay or prevent surgical management thus avoiding possible complications with the latter approach.

Thyroid Function in the Neonatal Intensive Care Unit.

Patients in the neonatal intensive care unit (NICU) are at high risk for abnormal thyroid function testing because of illness and preterm birth. Preterm infants are born before hypothalamic-pituitary-thyroid axis maturation and the normal feedback mechanisms that regulate thyroid hormone production remain immature. Preterm and sick infants may develop hypothyroidism even if routine thyroid screening tests collected in the first several days after birth are normal. This article reviews normal hypothalamic-pituitary-thyroid axis maturation, thyroid hormone testing and interpretation in the NICU, and the current evidence for and against levothyroxine treatment of NICU patients with borderline abnormal thyroid function testing.

Testicular adrenal rest tumor screening and fertility counseling among males with congenital adrenal hyperplasia.

BACKGROUND: Reduced fertility is a common potential problem among males with congenital adrenal hyperplasia (CAH), with nearly half experiencing impaired sperm production. The major cause of oligo/azoospermia in CAH is testicular adrenal rest tumors (TARTs). Studies indicate that ultrasound screening for TARTs should begin during childhood, yet it remains unclear whether boys with CAH are routinely screened for TARTs and/or counseled about infertility risk and potential interventions such as fertility testing and/or preservation. OBJECTIVE: The purpose of this study was to examine TART screening and fertility counseling practices among boys with CAH. STUDY DESIGN: An IRB-approved retrospective chart review was conducted of all males with ICD-9/10 codes for CAH (2007-2016) at a large pediatric academic center to examine: age and indication for diagnosis; age at first and last documented pediatric endocrinology and urology visit; history of ultrasound examinations; and documentation of fertility counseling. RESULTS: Forty-six patients were included, of whom 38 had 21-hydroxylase deficiency. Median age at diagnosis was 2 weeks (range 7 days-10 years). Median age at the most recent pediatric endocrinology clinic visit was 14 years (range 2-42 years). Twenty-nine patients were >11 years old (63% of the sample) at the time of the study and 14 of these were >18 years old (30% of the sample). Seven patients (15%) had a screening ultrasound at some point in their care, of whom three had TARTs. Fertility was mentioned in the records of six subjects (13% of the sample). Six of the subjects (13%) had any mention of fertility in their records. None of the patients had biochemical testing or semen analysis to assess gonadal function, and none were offered fertility preservation. Only one patient was seen by a pediatric urologist. DISCUSSION: Despite the limitations of a single-center retrospective design, our findings highlight that TART screening and fertility counseling remain underutilized in boys with CAH. There is a need for increased awareness and development of practice guidelines within pediatric urology and endocrinology to address this common and understudied problem. CONCLUSION: In addition to a screening ultrasound in puberty and consideration of semen analysis after puberty, these boys may benefit from seeing a pediatric urologist independently or in an interdisciplinary program. Boys with CAH and their families should be educated about infertility risk and potential interventions, with the goal of improving reproductive outcomes in this population.

Type 2 diabetes mellitus among Florida children and adolescents, 1994 through 1998.

OBJECTIVES: This study was undertaken to examine the trends in the diagnosis of Type 2 diabetes mellitus among children and adolescents with new-onset diabetes seen from 1994 through 1998 at the three university-based diabetes centers in Florida. METHODS: Data were abstracted from medical records and patients were categorized as having Type 1 or Type 2 diabetes. RESULTS: There were 569 patients classified with Type 1 diabetes and 92 with Type 2 diabetes. The proportion of patients diagnosed with Type 2 diabetes increased over the five years from 9.4% in 1994 to 20.0% in 1998 (chi-square test for trend = 8.2; p=0.004). There was not an associated net increase in the total number of new diabetes patients referred over time (chi-square test for trend = 0.6, p=0.4). Those with Type 2 diabetes were more likely to have a body mass index in the 85th-94th percentile [odds ratio (OR) = 8.5; 95% confidence interval (CI) 2.5, 28.8], have a body mass index >or=95th percentile (OR = 6.8; 95% CI 2.6, 17.7), Hispanic ethnicity (OR = 6.2; 95% CI 2.2, 17.9), black race (OR = 2.8; 95% CI 1.3, 6.2), female gender (OR = 2.2; 95% CI 1.2, 4.3), and older age (OR = 1.4 for each one-year increment in age; 95% CI 1.3, 1.6), compared with those having Type 1 diabetes. CONCLUSIONS: From 1994 through 1998, there was a significant overall increase in the percentage of children referred with new-onset diabetes who were considered to have Type 2 diabetes. Factors associated with the diagnosis of Type 2 diabetes relative to Type 1 diabetes include body mass index >/=85th percentile, Hispanic ethnicity, black race, female gender, and older age.