Browse

You are looking at 1 - 10 of 21 items

Nele Van Roy Department of Diabetes and Endocrinology, Vitaz, Sint-Niklaas, Belgium

Search for other papers by Nele Van Roy in
Google Scholar
PubMed
Close
,
Sylvester Heerwegh Department of Diabetes and Endocrinology, Vitaz, Sint-Niklaas, Belgium

Search for other papers by Sylvester Heerwegh in
Google Scholar
PubMed
Close
,
Dashty Husein Department of Diabetes and Endocrinology, Vitaz, Sint-Niklaas, Belgium

Search for other papers by Dashty Husein in
Google Scholar
PubMed
Close
,
Joke Ruys Department of Ophthalmology, Vitaz, Sint-Niklaas, Belgium

Search for other papers by Joke Ruys in
Google Scholar
PubMed
Close
, and
Peter Coremans Department of Diabetes and Endocrinology, Vitaz, Sint-Niklaas, Belgium

Search for other papers by Peter Coremans in
Google Scholar
PubMed
Close

Summary

Bardet–Biedl syndrome (BBS) is a rare, autosomal recessive, multisystem non-motile ciliopathy of progressive onset. It is primarily characterised by rod–cone dystrophy, early-onset obesity and related complications, postaxial polydactyly, renal and genitourinary abnormalities, learning disabilities, and hypogonadism. The diagnosis is based on Beales’ modified diagnostic criteria. We present a case of two monozygotic female twins, 17 years of age at presentation, referred for obesity since childhood. The initial hormonal work-up was negative and no dysmorphic features were noted. They were diagnosed with exogenous obesity. However, after ophthalmologic problems became apparent, rod–cone dystrophy was observed and genetic testing was performed. A mutation in the BBS2 gene led to the diagnosis of BBS, although the full diagnostic criteria were not met. This case not only highlights the need to raise awareness for BBS but also exposes two limitations of the current diagnostic standard. The first limitation is the low sensitivity of the clinical diagnostic model, due to the progressive onset and the high variability of the syndrome. The second limitation is the unclear role of genetic testing. As genetic testing becomes more widely available, genetic diagnosis preceding clinical diagnosis will become more common, leading to a diagnostic conundrum. We propose an update of the diagnostic model. A less strict application in the presence of confirmed genetic mutations should be applied, as this could facilitate earlier diagnosis and intervention. This is important because therapeutic agents are being developed that could have a significant impact on quality of life and prognosis.

Learning points

  • Due to the low prevalence, the significant inter-and intrafamilial variation, and the slowly evolving phenotype, monogenic forms of obesity such as Bardet–Biedl syndrome are difficult to diagnose. Despite advances in the understanding of the presentation, pathophysiology and access to accurate genetic characterisation, a substantial number of diagnoses are still made by ophthalmology, as recognition of BBS in other departments of medicine, remains limited.

  • Clinical diagnosis of BBS is based on Beales’ modified diagnostic criteria which require the presence of four primary features or three primary features plus two secondary features. This model has its limitations. Due to the progressive onset of clinical symptoms, patients generally do not meet the diagnostic criteria early in life, leading to a delay in diagnosis. In addition, the role of genetic testing remains controversial. However, as it becomes more widely available, genetic diagnosis may precede a full clinical diagnosis.

  • BBS has an impact on the quality of life and prognosis of both the patient and the family. Obesity management strategies are an important part of the multidisciplinary approach, as there is no cure available. Setmelanotide has shown promising results in a phase 3 trial, but its effect in clinical practice remains unproven.

Open access
Jananie Suntharesan Department of Endocrinology, Alder Hey Children’s Hospital, Eaton Road, Liverpool, UK

Search for other papers by Jananie Suntharesan in
Google Scholar
PubMed
Close
,
Louise Apperley Department of Endocrinology, Alder Hey Children’s Hospital, Eaton Road, Liverpool, UK

Search for other papers by Louise Apperley in
Google Scholar
PubMed
Close
, and
Senthil Senniappan Department of Endocrinology, Alder Hey Children’s Hospital, Eaton Road, Liverpool, UK

Search for other papers by Senthil Senniappan in
Google Scholar
PubMed
Close

Summary

A male phenotype accompanied by a 45,X karyotype is rare. It may occur due to Y chromosomal translocation or insertion to X/autosome. Clinical presentation may vary depending on the presence of the Y chromosomal locus and the degree of loss of autosome material. 45,X males can present with short stature and Turner syndrome phenotype due to haploinsufficiency of genes which are normally expressed in both X and Y chromosomes. The presence of the sex-determining region Y (SRY) gene leads to the differentiation of bipotential gonads to testis. Most individuals go through puberty normally, but some may need pubertal induction for delayed puberty. Rarely some can have a pubertal arrest. The risk of gonadoblastoma is minimal in these individuals due to functioning testicular tissue. The azoospermia factor (AZF) region is found on the long arm of the Yq chromosome and is needed for spermatogenesis. In a 45,X male with unbalanced translocation of Y chromosome, spermatogenesis can be affected due to the lack of AZF leading to Sertoli cell-only syndrome. This will have an implication on fertility in adult life. We present a 14-year-old boy with developmental delay, learning difficulties and subtle dysmorphic features who was diagnosed with 45,X,der(2)t(Y:2)(?:p25). Fluorescence in situ hybridisation analysis revealed translocation of SRY (Yp11.3) to the terminal part of the short arm of chromosome 2 resulting in the deletion of most of the Y chromosome (Yp11.2-q12) and part of chromosome 2(2p25.3). This is the first case where SRY translocation to chromosome 2 presents with the above clinical presentation.

Learning points

  • 45,X karyotype is rare in male.

  • It may occur due to SRY translocation or an insertion to X/autosome.

  • SRY gene translocation to chromosome 2 has been not reported in the literature.

  • Clinical presentation can be varied due to degree of loss of chromosomal material.

  • Due to loss of AZF region found on the long arm of the Yq, spermatogenesis can be affected. Loss of 2p25 leads to learning difficulty and obesity.

Open access
Maha Khalil Abass Pediatric Endocrinology Division, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates

Search for other papers by Maha Khalil Abass in
Google Scholar
PubMed
Close
,
Aisha Al Shamsi Clinical Genetics Department, Tawam Hospital, Al Ain, United Arab Emirates

Search for other papers by Aisha Al Shamsi in
Google Scholar
PubMed
Close
,
Iftikhar Jan Paediatric Surgery Division, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates
College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates

Search for other papers by Iftikhar Jan in
Google Scholar
PubMed
Close
,
Mohammed Suhail Yasin Masalawala Clinical Trial Unit, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates

Search for other papers by Mohammed Suhail Yasin Masalawala in
Google Scholar
PubMed
Close
, and
Asma Deeb Pediatric Endocrinology Division, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates
College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates

Search for other papers by Asma Deeb in
Google Scholar
PubMed
Close

Summary

The most frequent causes of pancreatitis classically have been known to be gallstones or alcohol. However, genetics can also play a key role in predisposing patients to both chronic and acute pancreatitis. The serine protease inhibitor Kazal type 1 (SPINK 1) gene is known to be strongly associated with pancreatitis. Patients with these underlying genetic mutations can have severe diseases with a high morbidity rate and frequent hospitalization. We report an Arab girl who presented with acute pancreatitis at the age of 7 years progressing to recurrent chronic pancreatitis over a few years. She had severe obesity from the age of 4 years and developed type 2 diabetes at the age of 12. She had a normal biliary system anatomy. Genetic analysis showed that she had combined heterozygous mutations in the SPINK1 gene (SPINK1, c.101A>G p.(Asn34Ser) and SPINK1, c.56-37T>C). Her parents were first-degree cousins, but neither had obesity. Mother was detected to have the same mutations. She had type 2 diabetes but never presented with pancreatitis. This case is the first to be reported from the Arab region with these combined mutations leading to recurrent chronic pancreatitis. It illustrates the importance of diagnosing the underlying genetic mutation in the absence of other known causes of pancreatitis. Considering the absence of pancreatitis history in the mother who did not have obesity but harboured the same mutations, we point out that severe obesity might be a triggering factor of pancreatitis in the presence of the mutations in SPINK1 gene in this child. While this is not an assumption from a single patient, we show that not all carriers of this mutation develop the disease even within the same family. Triggering factors like severe obesity might have a role in developing the disease.

Learning points

  • Acute recurrent pancreatitis and chronic pancreatitis are uncommon in children but might be underdiagnosed.

  • Biliary tract anomalies and dyslipidaemias are known causative factors for pancreatitis, but pancreatitis can be seen in children with intact biliary system.

  • Genetic diagnosis should be sought in children with pancreatitis in the absence of known underlying predisposing factors.

  • SPINK1 mutations can predispose to an early-onset severe recurrent pancreatitis and acute pancreatitis.

Open access
Caroline Schulmeister Pediatric Endocrinology, University of California at San Francisco, San Francisco, California, USA
Pediatric Endocrinology, University of California at Davis, Sacramento, California, USA

Search for other papers by Caroline Schulmeister in
Google Scholar
PubMed
Close
,
Jason Lee Pediatric Nephrology, University of California at San Francisco, San Francisco, California, USA
Pediatric Nephrology, University of Pennsylvania, Philadelphia, Pennsylvania, USA

Search for other papers by Jason Lee in
Google Scholar
PubMed
Close
,
Farzana Perwad Pediatric Nephrology, University of California at San Francisco, San Francisco, California, USA

Search for other papers by Farzana Perwad in
Google Scholar
PubMed
Close
,
Roger Long Pediatric Endocrinology, University of California at San Francisco, San Francisco, California, USA

Search for other papers by Roger Long in
Google Scholar
PubMed
Close
, and
Shylaja Srinivasan Pediatric Endocrinology, University of California at San Francisco, San Francisco, California, USA

Search for other papers by Shylaja Srinivasan in
Google Scholar
PubMed
Close

Summary

Skeletal abnormalities with delayed bone age and decreased linear bone growth are commonly found in children with prolonged juvenile hypothyroidism. However, rachitic bone abnormalities have not been previously reported in children with acquired hypothyroidism. Here, we present a case of newly found rickets in an 8-year-old female with untreated acquired hypothyroidism secondary to Hashimoto’s thyroiditis. Laboratory finding for abnormalities in calcium/phosphorus homeostasis and hormones that regulate skeletal health was normal. Her radiographic anomalies resolved with levothyroxine treatment alone, suggesting that hypothyroidism was the etiology of the rickets. To our knowledge, this is the first case report of rickets associated with long-standing severe acquired hypothyroidism that resolved exclusively with thyroid repletion.

Learning points

  • Thyroid hormone plays an important role in bone mineralization.

  • Prolonged hypothyroidism can result in rachitic bone abnormalities noted on radiographs.

  • Hypothyroidism should be considered in the evaluation of a child with rickets.

Open access
Jay Nguyen Lincoln Memorial University-DeBusk College of Osteopathic Medicine, Harrogate, Tennessee, USA

Search for other papers by Jay Nguyen in
Google Scholar
PubMed
Close
and
Dennis Joseph Endocrinology Center of Lake Cumberland, Somerset, Kentucky, USA

Search for other papers by Dennis Joseph in
Google Scholar
PubMed
Close

Summary

Increased intracranial pressure (ICP) can present with symptoms of headache, vomiting, visual changes, and tinnitus. Papilledema may be seen on physical exam. Thyroid disease has been a rare secondary cause of increased ICP. We present a 16-year-old female who had a worsening headache for 6 months. She was found to have signs, symptoms, physical exam findings, and diagnostic studies consistent with both increased ICP and previously undiagnosed Graves’ disease. The patient was treated with a 19-month course of methimazole 40 mg daily. Her headache and papilledema resolved shortly after medication initiation. The timeline of symptoms and resolution of her increased ICP symptoms with treatment of Graves’ disease suggests that hyperthyroidism was the underlying cause of her increased ICP. Clinicians should consider Graves’ disease as the etiology in pediatric patients presenting with signs and symptoms of increased ICP with papilledema.

Learning points

  • Symptoms of increased intracranial pressure (ICP) include headache, vomiting, transient visual changes, and tinnitus.

  • Secondary causes of increased ICP should be considered in males, young children, older patients, and those not overweight.

  • Clinicians should consider Graves’ disease as the etiology in pediatric patients presenting with signs and symptoms of increased ICP with papilledema. They should assess for orbitopathy and thyromegaly and inquire about symptoms that would be indicative of hyperthyroidism.

Open access
Hidekuni Takahashi Department of Pediatrics and Adolescent Medicine, Tokyo Medical University, Tokyo, Japan

Search for other papers by Hidekuni Takahashi in
Google Scholar
PubMed
Close
,
Shigeo Nishimata Department of Pediatrics and Adolescent Medicine, Tokyo Medical University, Tokyo, Japan

Search for other papers by Shigeo Nishimata in
Google Scholar
PubMed
Close
,
Atsushi Kumada Department of Pediatrics and Adolescent Medicine, Tokyo Medical University, Tokyo, Japan

Search for other papers by Atsushi Kumada in
Google Scholar
PubMed
Close
,
Gaku Yamanaka Department of Pediatrics and Adolescent Medicine, Tokyo Medical University, Tokyo, Japan

Search for other papers by Gaku Yamanaka in
Google Scholar
PubMed
Close
,
Yasuyo Kashiwagi Department of Pediatrics and Adolescent Medicine, Tokyo Medical University, Tokyo, Japan

Search for other papers by Yasuyo Kashiwagi in
Google Scholar
PubMed
Close
, and
Hisashi Kawashima Department of Pediatrics and Adolescent Medicine, Tokyo Medical University, Tokyo, Japan

Search for other papers by Hisashi Kawashima in
Google Scholar
PubMed
Close

Summary

We encountered a case of childhood-onset lymphocytic infundibuloneurohypophysitis, based on the MRI and endocrinological findings, with decreased function of the anterior and posterior lobes of the pituitary. Three years after the diagnosis, the patient developed non-alcoholic steatohepatitis (NASH), which was effectively treated by growth hormone (GH) supplementation. The present case demonstrated that NASH can be effectively treated by short-term GH supplementation, even in late childhood.

Learning points

  • In recent years, the efficacy of growth hormone replacement therapy in normalizing the liver function of adult-onset growth hormone deficiency patients with non-alcoholic steatohepatitis (NASH) has been reported.

  • Lymphocytic infundibuloneurohypophysitis is a very rare disease, particularly in childhood.

  • We here presented a rare case of a child with lymphocytic infundibuloneurohypophysitis who developed NASH and showed substantial improvement in liver function after growth hormone treatment.

Open access
Darija Tudor Department of Pediatrics, University Hospital of Split, Split, Croatia

Search for other papers by Darija Tudor in
Google Scholar
PubMed
Close
,
Iva Kolombo Department of Pediatrics, Šibenik General Hospital, Šibenik, Croatia

Search for other papers by Iva Kolombo in
Google Scholar
PubMed
Close
,
Ana Tot Department of Pediatrics, University Hospital of Split, Split, Croatia

Search for other papers by Ana Tot in
Google Scholar
PubMed
Close
,
Drasko Cikojevic Department of Otorhinolaryngology, University Hospital of Split, Split, Croatia

Search for other papers by Drasko Cikojevic in
Google Scholar
PubMed
Close
,
Marko Simunovic Department of Pediatrics, University Hospital of Split, Split, Croatia
Department of Pediatrics, University of Split School of Medicine, Split, Croatia

Search for other papers by Marko Simunovic in
Google Scholar
PubMed
Close
, and
Veselin Skrabic Department of Pediatrics, University Hospital of Split, Split, Croatia
Department of Pediatrics, University of Split School of Medicine, Split, Croatia

Search for other papers by Veselin Skrabic in
Google Scholar
PubMed
Close

Summary

This is a case report of a child with chronic hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) as a paraneoplastic manifestation of olfactory neuroblastoma (OFN). We hereby report a clinical presentation as well as a pragmatic approach to one of the most common electrolytic disorders in the pediatric population and have emphasized the necessity of involving the sinonasal area in the diagnostic procedure while evaluating possible causes of SIADH. This report indicates that the chronicity of the process along with the gradual onset of hyponatremia occurrence is responsible for the lack of neurological symptoms at the moment of disease presentation.

Learning points

  • Hyponatremia is not infrequently attributed to SIADH.

  • Paraneoplastic syndromes are uncommon but they should be considered in the differential diagnosis of pediatric SIADH.

  • Chronic insidious hyponatremia may not be associated with clear neurological symptoms despite its severity.

Open access
Priya Darshani Chhiba University of the Witwatersrand, Wits Donald Gordon Medical Centre, Johannesburg, South Africa

Search for other papers by Priya Darshani Chhiba in
Google Scholar
PubMed
Close
and
David Segal University of the Witwatersrand, Wits Donald Gordon Medical Centre, Johannesburg, South Africa

Search for other papers by David Segal in
Google Scholar
PubMed
Close

Summary

Recombinant human growth hormone therapy (rhGH) has been available since 1985 for a variety of conditions and has expanded the indications for rhGH therapy and the number of patients receiving therapy. The very nature of the therapy exposes individuals to years of injections. There are a number of well-known adverse events, however, a lesser-known and rarely reported adverse event of rhGH therapy is localized lipoatrophy. We report nine cases of localized lipoatrophy during rhGH therapy accounting for 14.5% of patients taking rhGH presenting to a single centre for routine follow-up over just a 2-month period. The development of localized lipoatrophy does not appear to be age, indication or dose-related but rather related to repeated administration of rhGH into a limited number of sites. The most likely putative mechanism is the local lipolytic action of growth hormone (GH) itself, although the possibility of an excipient-based interaction cannot be excluded. Given the high prevalence of this adverse event and the potential to prevent it with adequate site rotation, we can recommend that patients be informed of the possible development of localized lipoatrophy. Doctors and nurses should closely examine injection sites at each visit, and site rotation should be emphasized during injection technique education.

Learning points

  • There are a number of well-known adverse events, however, a lesser-known and rarely reported adverse event of rhGH therapy is localized lipoatrophy.

  • Examination of the injection sites at each visit by the treating healthcare practitioner.

  • To advise the parents/caregivers/patients to change their injection site with each injection.

  • To advise the parents/caregivers/patients to change the needles after every use.

  • For parents, caregivers and patients to self-inspect their injection sites and have a high alert for the development of lipoatrophy and to then immediately report it to their doctor.

Open access
Ashwini Maudhoo Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK

Search for other papers by Ashwini Maudhoo in
Google Scholar
PubMed
Close
,
Avinaash Maharaj Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK

Search for other papers by Avinaash Maharaj in
Google Scholar
PubMed
Close
,
Federica Buonocore Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, London, UK

Search for other papers by Federica Buonocore in
Google Scholar
PubMed
Close
,
Gabriel Angel Martos-Moreno Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Madrid, Spain
Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain
Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain

Search for other papers by Gabriel Angel Martos-Moreno in
Google Scholar
PubMed
Close
,
Jesús Argente Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Madrid, Spain
Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain
Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
CEI UAM + CSIC, IMDEA Food Institute, Madrid, Spain

Search for other papers by Jesús Argente in
Google Scholar
PubMed
Close
,
John C Achermann Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, London, UK

Search for other papers by John C Achermann in
Google Scholar
PubMed
Close
,
Li F Chan Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK

Search for other papers by Li F Chan in
Google Scholar
PubMed
Close
, and
Lou A Metherell Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK

Search for other papers by Lou A Metherell in
Google Scholar
PubMed
Close

Summary

Congenital isolated ACTH deficiency (IAD) is a rare condition characterised by low plasma ACTH and serum cortisol with normal production of other pituitary hormones. TBX19 (also known as TPIT) is a T-box pituitary restricted transcription factor important for POMC gene transcription and terminal differentiation of POMC-expressing cells. TBX19 gene mutations have been shown to cause neonatal-onset congenital IAD. We report a neonate of Romanian origin, who presented at 15 h of life with respiratory arrest and hypoglycaemia which recurred over the following 2 weeks. Biochemical investigations revealed IAD, with undetectable serum cortisol (cortisol < 1 μg/dL; normal range (NR): 7.8–26.2) and plasma ACTH levels within the normal range (22.1 pg/mL; NR: 4.7–48.8). He responded to hydrocortisone treatment. Patient DNA was analysed by a HaloPlex next-generation sequencing array targeting genes for adrenal insufficiency. A novel homozygous synonymous mutation p.Thr96= (Chr1:168260482; c.288G>A; rs376493164; allele frequency 1 × 10−5, no homozygous) was found in exon 2 of the TBX19 gene. The effect of this was assessed by an in vitro splicing assay, which revealed aberrant splicing of exon 2 giving rise to a mutant mRNA transcript whereas the WT vector spliced exon 2 normally. This was identified as the likely cause of IAD in the patient. The predicted protein product would be non-functional in keeping with the complete loss of cortisol production and early presentation in the patient.

Learning points

  • Synonymous variants (a nucleotide change that does not alter protein sequence) usually thought to be benign may still have detrimental effects on RNA and protein function causing disease. Hence, they should not be ignored, especially if very rare in public databases.

  • In vitro splicing assays can be employed to characterise the consequence of intronic and exonic nucleotide gene changes that may alter splicing.

  • Establishing a diagnosis due to a TBX19 mutation is important as it defines a condition of isolated ACTH deficiency not associated with additional pituitary deficiencies.

Open access
Katsuo Tao Department of Pediatrics, Fukui Aiiku Hospital, Fukui, Japan

Search for other papers by Katsuo Tao in
Google Scholar
PubMed
Close
,
Midori Awazu Department of Pediatrics, Keio University School of Medicine, shinjyuku, Tokyo, Japan

Search for other papers by Midori Awazu in
Google Scholar
PubMed
Close
,
Misa Honda Department of Pediatrics, Keio University School of Medicine, shinjyuku, Tokyo, Japan

Search for other papers by Misa Honda in
Google Scholar
PubMed
Close
,
Hironori Shibata Department of Pediatrics, Keio University School of Medicine, shinjyuku, Tokyo, Japan

Search for other papers by Hironori Shibata in
Google Scholar
PubMed
Close
,
Takayasu Mori Department of Nephrology, Tokyo Medical and Dental University, Fukui, Japan

Search for other papers by Takayasu Mori in
Google Scholar
PubMed
Close
,
Shinichi Uchida Department of Nephrology, Tokyo Medical and Dental University, Fukui, Japan

Search for other papers by Shinichi Uchida in
Google Scholar
PubMed
Close
,
Tomonobu Hasegawa Department of Pediatrics, Keio University School of Medicine, shinjyuku, Tokyo, Japan

Search for other papers by Tomonobu Hasegawa in
Google Scholar
PubMed
Close
, and
Tomohiro Ishii Department of Pediatrics, Keio University School of Medicine, shinjyuku, Tokyo, Japan

Search for other papers by Tomohiro Ishii in
Google Scholar
PubMed
Close

Summary

We report a male infant with congenital nephrogenic diabetes insipidus (NDI) who presented with hypercalcemia and hyperphosphatemia since birth. Serum sodium started to increase at 39 days. Although there was no polyuria, urine osmolality was 71 mOsm/kg, when serum osmolality was 296 mOsm/kg with plasma arginine vasopressin 22.5 pg/mL. He was thus diagnosed as NDI. An undetectable level of urine calcium and unsuppressed intact parathyroid hormone suggested hyperparathyroidism including calcium-sensing receptor mutations that could cause hypercalcemia-induced NDI. Polyuria became apparent after the initiation of i.v. infusion for the treatment of hypernatremia. Low calcium and low sodium formula with hypotonic fluid infusion did not correct hypernatremia, hypercalcemia, or hyperphosphatemia. Hydrochlorothiazide and subsequently added celecoxib effectively decreased urine output and corrected electrolytes abnormalities. Normal serum electrolytes were maintained after the discontinuation of low calcium formula. The genetic analysis revealed a large deletion of the arginine vasopressin receptor-2 (AVPR2) gene but no pathogenic variant in the calcium-sensing receptor (CASR) gene. Whether hypercalcemia and hyperphosphatemia were caused by dehydration alone or in combination with other mechanisms remains to be clarified.

Learning points

  • Congenital NDI can present with neonatal hypercalcemia and hyperphosphatemia.

  • Hypercalcemia and hyperphosphatemia can be treated with low calcium and low sodium formula, hydration, hydrochlorothiazide, and celecoxib.

  • Genetic testing is sometimes necessary in the differentiating diagnosis of hypercalcemia associated with NDI.

Open access