Unexpected Widespread Hypophosphatemia and Bone Disease Associated with Elemental Formula Use in Infants and Children

OBJECTIVE: Hypophosphatemia occurs with inadequate dietary intake, malabsorption, increased renal excretion, or shifts between intracellular and extracellular compartments. We noticed the common finding of amino-acid based elemental formula [EF] use in an unexpected number of cases of idiopathic hypophosphatemia occurring in infants and children evaluated for skeletal disease. We aimed to fully characterize the clinical profiles in these cases. METHODS: A retrospective chart review of children with unexplained hypophosphatemia was performed as cases accumulated from various centres in North America and Ireland. Data were analyzed to explore any relationships between feeding and biochemical or clinical features, effects of treatment, and to identify a potential mechanism. RESULTS: Fifty-one children were identified at 17 institutions with EF-associated hypophosphatemia. Most children had complex illnesses and had been solely fed Neocate® formula products for variable periods of time prior to presentation. Feeding methods varied. Hypophosphatemia was detected during evaluation of fractures or rickets. Increased alkaline phosphatase activity and appropriate renal conservation of phosphate were documented in nearly all cases. Skeletal radiographs demonstrated fractures, undermineralization, or rickets in 94% of the cases. Although the skeletal disease had often been attributed to underlying disease, most all improved with addition of supplemental phosphate or change to a different formula product. CONCLUSION: The observed biochemical profiles indicated a deficient dietary supply or severe malabsorption of phosphate, despite adequate formula composition. When transition to an alternate formula was possible, biochemical status improved shortly after introduction to the alternate formula, with eventual improvement of skeletal abnormalities. These observations strongly implicate that bioavailability of formula phosphorus may be impaired in certain clinical settings. The widespread nature of the findings lead us to strongly recommend careful monitoring of mineral metabolism in children fed EF. Transition to alternative formula use or implementation of phosphate supplementation should be performed cautiously with as severe hypocalcemia may develop

Long-Term Follow-up of Hypophosphatemic Bone Disease Associated With Elemental Formula Use: Sustained Correction of Bone Disease After Formula Change or Phosphate Supplementation

In this article, we describe the long-term outcomes of children who were previously reported to have developed hypophosphatemic bone disease in association with elemental formula use. An extended chart review allowed for an updated report of 34 children with regard to severity/duration of bone disease, extent of recovery, and time to correction using radiology reports and biochemical data. After implementation of formula change and/or phosphate supplementation, we found that serum phosphorus concentration increased and serum alkaline phosphatase activity decreased in all patients, normalizing by 6.6 ± 4.0 (mean ± SD) months following diagnosis. The decrease in serum alkaline phosphatase from diagnosis to the time of correction was moderately correlated with the concurrent increase in serum phosphorus (R = 0.48, P < .05). Age at diagnosis significantly correlated with time to resolution (R = 0.51, P = .01). This study supports the earlier report that bone disease associated with hypophosphatemia during elemental formula use responds to formula change and/or phosphate supplementation

Graves’ Thyrotoxicosis Leading to Adrenal Decompensation and Hyperandrogenemia in a Pediatric Patient with Salt-Wasting Congenital Adrenal Hyperplasia

Introduction. Thyroid hormone is known to accelerate glucocorticoid turnover. In a thyrotoxic state, individuals with adrenal insufficiency are unable to increase endogenous cortisol production to compensate for increased turnover, placing them at risk for symptoms of glucocorticoid deficiency and adrenal crisis. In patients with salt-wasting congenital adrenal hyperplasia (SW-CAH), hyperandrogenemia is a measurable reflection of relative glucocorticoid insufficiency. Case Presentation. A 12-year-old girl with SW-CAH reported 3 recent episodes of vomiting without diarrhea, and accompanying tachycardia, responsive to stress dose steroids. In the previous 9 months, she unintentionally lost 2.6 kg. She had tachycardia and new thyromegaly. Labs showed suppressed TSH, elevated free T4 and total T3, and elevated thyroid stimulating immunoglobulin (TSI) consistent with Graves’ disease. Adrenal androgens were markedly elevated. Maintenance hydrocortisone dose was 25 mg/m2/day and was not changed. Methimazole was initiated. Four weeks later, free T4 and adrenal androgens normalized. She had no further vomiting episodes. Conclusions. Thyrotoxicosis must be included in the differential diagnosis of individuals with SW-CAH who present with episodes concerning for adrenal crises, escalating hydrocortisone requirements, and/or inadequate suppression of adrenal hormones

Cortisol Stimulates Secretion of Dehydroepiandrosterone in Human Adrenocortical Cells Through Inhibition of 3βHSD2

Context: Initiating factors leading to production of adrenal androgens are poorly defined. Cortisol is present in high concentrations within the adrenal gland, and its production rises with growth during childhood

Bacteremia in a Newborn with Hypocalcemic Seizures and Vitamin D Deficiency

Infants with neonatal hypocalcemia often present with seizures, and neonatal hypocalcemia can be due to parathyroid (PTH) insufficiency or resistance. Causes of hypocalcemia with PTH elevation include increased phosphate load, vitamin D deficiency (VDD) or defects in metabolism, renal dysfunction, hypomagnesemia, genetic mutations resulting in end-organ resistance to PTH, or critical illness. Hypocalcemia has also been shown to be associated with Gram-negative bacteremia and sepsis in adults. We present the case of a full-term, formula-fed newborn presenting with late-onset hypocalcemic seizures and VDD in the setting of Klebsiella pneumoniae bacteremia. This case highlights that newborns presenting with hypocalcemic seizures should undergo a workup for sepsis

Central precocious puberty in Boston boys: A 10-year single center experience.

OBJECTIVE:Recent studies in the US and abroad suggest that boys are undergoing puberty at a younger age. It is unknown if this secular trend extends to boys with central precocious puberty (CPP), who sit at the extreme end of the pubertal spectrum, and if neuroimaging should remain a standard diagnostic tool. STUDY DESIGN:Retrospective chart review of all boys with CPP seen by Endocrinology at a US pediatric hospital from 2001-2010. RESULTS:Fifty boys had pubertal onset at an average age of 7.31 years (95CI 6.83-7.89), though many did not present until nearly one year thereafter, by which time 30% were mid-to-late pubertal. Boys were predominantly non-Hispanic White and 64% were overweight/obese. The majority (64%) of boys had neurogenic CPP (CNS-CPP) with neurofibromatosis type I being the most common diagnosis. Diagnosis of CPP led to discovery of a neurogenic lesion in only 3 of 32 (9%) CNS-CPP cases. The remaining boys, with idiopathic CPP (36%), were indistinguishable from those with CNS-CPP aside from four boys who endorsed a family history of PP (22% vs. 0% among CNS-CPP cases). Importantly, there was no change in the incidence of male CPP after accounting for the increase in clinic volume during this time period. CONCLUSION:In this contemporary Boston-based cohort of 50 boys with CPP, most cases were neurogenic, consistent with older literature. Several idiopathic cases had a family history of PP but were otherwise indistinguishable from CNS-CPP cases. Thus, neuroimaging remains a critical diagnostic tool. We find no evidence for an increase in the prevalence of male CPP

Occult Metastatic Papillary Thyroid Cancer in an Adolescent

Background/Objective: Occult papillary thyroid carcinoma (PTC) is PTC with metastasis but without identification of primary thyroid cancer on preoperative ultrasonography. Published reports on occult PTC in children are limited. Case Report: We describe a 16-year-old female with occult PTC who initially presented with a painless left sided cystic neck mass. Diffuse sclerosing variant papillary thyroid cancer was found in the resected neck mass and thyroid ultrasound did not show any nodules or features of carcinoma. After total thyroidectomy, pathological examination of the thyroid revealed papillary thyroid microcarcinoma. Discussion: We describe a rare case of occult diffuse sclerosing variant papillary thyroid cancer presenting as a cystic neck mass mimicking a second branchial cleft cyst in an adolescent patient. When metastatic PTC is found without evidence of nodule on thyroid imaging, occult PTC of the thyroid is the likely diagnosis. Conclusion: Total thyroidectomy ± neck dissection followed by TSH suppression and radioactive iodine therapy remains the appropriate diagnostic and therapeutic interventions

Baseline characteristics of the cohort.

<p>Baseline characteristics of the cohort.</p

Baseline LH, FSH, and total testosterone (Testo) levels and testicular volume in CNS-CPP and iCPP cases.

<p>Means and 95CI overlay raw data points. Red dots represent measures from the 3 patients in whom the diagnosis of CPP unmasked a brain neoplasm. Gray lines represent assay lower limits of detection. P-values reflect group comparisons using generalized linear models. To convert to SI units, multiple Testo by 0.0347.</p

Inclusion flow diagram of the male CPP cohort.

<p>Inclusion flow diagram of the male CPP cohort.</p