Rare case of pseudohypoaldosteronism in a neonate secondary to congenital hydrometrocolpos
- 1 Health Education England West Midlands, Edgbaston, UK
- 2 Department of Paediatrics and Neonatology, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK
- Correspondence to Dr Helen McDermott; helen.mcdermott@nhs.net
Abstract
Pseudohypoaldosteronism (PHA) due to obstructive uropathy, urinary tract infections and congenital urogenital malformations has been reported in the literature; however, there are no reports of PHA associated with hydrometrocolpos due to a common urogenital tract. Hydrometrocolpos is a condition resulting in distension of the vagina and uterus due to accumulation of secretions (other than blood), caused by increased oestrogenic stimulation and vaginal outflow obstruction. We report on a neonatal case of PHA caused by recurrent hydrometrocolpos presenting with vomiting and poor weight gain. There was significant hyponatraemia, hyperkalaemia, and anaemia requiring medical stabilisation prior to surgery. The mechanism by which PHA occurs in obstruction involves renal tubular dysfunction due to pressure from hydronephrosis and the release of intrarenal cytokines. In addition, there is an immature or resistant renal tubular responsiveness to aldosterone during infancy. Clinicians should be aware of this uncommon but serious presentation.
Background
Hydrometrocolpos is a condition resulting in distension of the vagina and uterus due to accumulation of secretions (other than blood), caused by increased oestrogenic stimulation and vaginal outflow obstruction. Hence, this condition presents at extremes of childhood, at birth when maternal-circulating hormones are raised and at menarche when oestrogen production commences. One of the most common causes of vaginal tract obstruction is imperforate hymen, due to failure of disintegration of the epithelial cells that occlude the Müllerian ducts during embryological development. Other causes include transverse vaginal septum and vaginal atresia. The incidence in term neonates is 0.00014%–0.001%,1 and is more prevalent in populations with a greater occurrence of consanguinity due to associated autosomal recessive syndromes. Other than a localised defect in development, the presentation can be as a part of an underlying disorder, such as McKusick-Kauffman or Bardet-Biedl syndrome.2
Case presentation
A female baby, 35 weeks gestation, was born before arrival to hospital, a birth weight of 2100 g to non-consanguineous parents. There was routine antenatal history and normal antenatal scans including a growth scan at 28 weeks. She was born in a poor condition requiring resuscitation, including chest compressions by paramedics en route to the hospital. On admission to the neonatal intensive care unit, she was noted to have abdominal distention. A mass was palpable on examination, and the abdominal girth increased over the course of 24 hours. She was initially managed on nasal continuous positive airway pressure until around 24 hours of age, when she was intubated due to her ongoing increased work of breathing, largely due to splinting of the diaphragm secondary to the increasing abdominal girth. She also needed inotropic support for low blood pressure, presumed to be due to intra-abdominal caval compression.
Her abdomen was investigated initially by an abdominal X-ray (figure 1), which showed a large area of opacity in a midline position. An ultrasound was performed which showed a thin-walled, round, central abdominopelvic cystic mass measuring at least 8×6.4×6.5 cm. The size of the mass extended beyond the range of the probe. The fluid in the cyst was anechoic and had no septations. There was no connection to the bladder discernible or to the liver. The uterus and upper abdominal organs were difficult to visualise due to the large size of the cyst. There was bilateral renal major pelvic–calyceal dilatation with hydronephrosis secondary to the mass restricting urine output.
Initial chest and abdominal plain film. Marker demonstrates paucity of any bowel gas in the central area, pushed out to around the outer edges.
This was reflected in the blood results as she had raised creatinine levels (86 µmol/L), although she had normal electrolytes (sodium 136 mmol/L, potassium 5.2 mmol/L). At this time, she also had a raised alpha-fetoprotein of 16 000 kU/L, which later increased to 23 339 kU/L (normal range (NR) 0–60 750 IU/L).3 She was noted to be on the 0.4th to 2nd centile for weight with some soft dysmorphic features (low-set ears, hypertelorism). Her external genitalia appeared normal. A microarray genetic test showed no abnormalities.
Given her findings, she was urgently transferred to a tertiary centre for specialist input. An MRI (figure 2) was performed that demonstrated huge distention of the vagina and uterus with compression of adjoining structures consistent with hydrometrocolpos. Cystoscopy–vaginoscopy was done in theatre that revealed a single perineal opening with the track dividing to lead to bladder and vagina. Catheters were inserted to drain both the bladder and vaginal collections. She remained an inpatient for 13 days and was discharged on trimethoprim for renal prophylaxis. At this time, her C-reactive protein (CRP) was 1 mg/L (NR 0–5 mg/L),4 with urea and electrolytes within the NR.
MRI abdomen images showing extent of the mass of hydrometrocolpos within the abdomen. Markers demonstrate the lesion.
Re-admission
This infant subsequently presented at 10 days corrected (6 weeks chronologically) to a district general hospital with vomiting and poor weight gain. On examination, she was tachycardic but afebrile, blood pressure was within normal limits for her age and she had apparent tenderness in the lower abdomen but no distension.
A gas and blood were performed based on her previous history and showed significant anaemia (haemoglobin (Hb) 69 g/L; NR 95–125 g/L), hyperkalaemia (7.1 mmol/L) (NR 3.5–5.0 mmol/L) and hyponatraemia with sodium level of 117 mmol/L (135–145 mmol/L), a urea of 10.9 mmol/L (NR 2.5–7.0 mmol/and creatinine of 45 µmol/L (NR for children aged between 2 weeks and <1 year was 14–48 µmol/L). She also had significant thrombocytosis with platelets of 1314×109/L; NR 150–450×109/L). The acid–base balance demonstrated a compensated metabolic acidosis and a lactate of 2.8 (NR 0.5–2.2 mmol/L). CRP was 31 mg/L.4 No chloride was available. Urine examination showed microscopic haematuria but no suggestion of infection. A repeat ultrasound (figure 3) on that day confirmed an increase in the size of the presumed haematocolpos since her last scan 3 weeks prior. It now measured maximum 7.2 cm dimension (previously 6.8 cm) with a depth of 3.8 cm (3.1 cm) and width 5.6 cm (3.8 cm). In addition, there was a much greater degree of echogenic debris within the presumed haematocolpos compared with previously and even within the debris there were different shades of echogenicity. In addition, during the scan, swirls of debris were seen, which were highly concerning for active bleeding. The haematocolpos proceeded to cause bilateral renal pelvicalyceal dilatation (this had previously resolved), with right-sided renal pelvis diameter of 3.9 mm and left-sided anteroposterior diameter (APD) of 3.3 mm.
The ultrasound scan of abdomen on re-presentation. Markers demonstrate centre of the lesion.
She was initially treated as for a possible adrenal crisis due to blood results with a 10 mL/kg bolus of 0.9% sodium chloride, hydrocortisone and bicarbonate, with intravenous calcium gluconate and salbutamol for treatment of hyperkalaemia, and a blood transfusion. She had serial blood gases showing deteriorating bicarbonate levels, becoming more acidotic and her presentation was discussed with nephrologist at the tertiary centre who advised catheterisation and urgent transfer for ongoing management. She was transferred on fludrocortisone, intravenous broad-spectrum antibiotics and maintenance fluids. She had been treated with a 0.9% sodium chloride drip in addition and, by the time of transfer, her electrolytes had recovered to a sodium 131 mmol/L, potassium 5.0 mmol/L, urea 9.5 mmol/L and creatinine 53 µmol/L with an improving bicarbonate and acid–base balance. It was assumed that the anaemia was likely related to a presumed haematocolpos and electrolyte disturbance likely due to pseudohypoaldosteronism (PHA) secondary to renal obstruction.
Treatment
She underwent another vaginostomy and cystovaginoscopy. This showed no haematocolpos and only milky appearing fluid. Her antibiotics were discontinued following negative cultures and she received dietician input due to failure to thrive. She was reviewed by a haematologist and her anaemia thought to be secondary to nutritional deficit. As her electrolytes normalised, sodium bicarbonate was discontinued, and she was discharged home with a plan to repeat her blood work and having ongoing community dietician input and follow-up.
Outcome and follow-up
Her endocrine investigation blood taken on admission demonstrated high aldosterone of 41 600 pmol/L (1000–3500 pmol/L),4 renin >550 mU/L (<312 mU/L),3 cortisol 729 nmol/L (200–700 nmol/L)4 and a normal 17OH-progesterone of 3.8 nmol/L (<8.0 nmol/L),5 confirming that there was no diagnosis of congenital adrenal hyperplasia (CAH). Urinary electrolytes were also all within the NRs. These results and resolution of signs following surgery demonstrate a PHA. Along with her slightly elevated cortisol, her raised platelet count and CRP were likely secondary to on-going inflammation in the genitourinary tract and physiological stress response. However, she was treated for potential infection with antibiotics. No further genetic testing has currently been undertaken, after discussion with local genetics team. Blood were not sent at the time for a possible genetic cause for a primary endocrine cause of hyperaldosteronism and were held off once the secondary diagnosis seemed more likely.
She has remained well since and only required review by orthopaedic for developmental dysplasia of the hip, requiring a harness between 2 and 4 months of age. Her repeat abdominal scans have been normal and her bloodwork has improved markedly (Hb 108 g/L) with normalised renal function and electrolytes. Her cranial ultrasound was also within normal limits.
Discussion
While PHA is widely reported in the literature due to obstructive uropathy, urinary tract infections and congenital urogenital malformations,6–8 particularly in neonates and infants, there are far fewer reports of obstruction secondary to hydrometrocolpos specifically. The incidence in the UK is unknown; however, the estimated incidence for the Irish population of transient PHA due to urinary tract abnormality was 1 per 13 200 live births per year in a 2-year period.9 An imperforate hymen has been known to cause congenital hydrometrocolpos; however, this presentation was due to a common urogenital tract. In previous reports, this presentation has been in association with the Bardet-Biedl or the rare McKusick-Kaufmann syndrome (encompassing vaginal atresia, hydrometrocolpos, postaxial polydactyly and congenital heart defects).1
PHA due to obstruction was first reported in 1983,7 and since then, other congenital causes such as bilateral ectopic ureter and urinary tract malformations have been found. PHA is categorised into type 1 (primary and secondary) and type 2.10 Primary type 1 and type 2 are both genetic. Autosomal dominant PHA-I is caused by a heterozygous mutation in the mineralocorticoid receptor gene (NR3C2) on chromosome 4q31.11 Autosomal recessive PHA-I can be caused by homozygous or compound heterozygous mutation in any one of three genes encoding subunits of the epithelial sodium channel: the α subunit (SCNN1A) on chromosome 12, the β subunit (SCNN1B) or the γ subunit (SCNN1G), both on chromosome 16. PHA-II is a genetically heterogenous group of disorders.12
In this case, microarray was normal and molecular studies looking for mutations associated with PHA type 1 and type 2 were not obtained, following review by consultant geneticist, as her phenotype was more in keeping with secondary PHA associated with obstructive uropathy rather than PHA type 1. There were no other clinical features of the above syndromes. Failure to thrive, such as is seen in this case, has been reported as a common feature at presentation, in addition to emesis (also seen) and also other features such as lethargy.
Secondary can be due to obstruction or drugs. The mechanism by which PHA occurs in obstruction involves renal tubular dysfunction due to pressure from hydronephrosis and the release of intrarenal cytokines. In addition, there is an immature or resistant renal tubular responsiveness to aldosterone during infancy.7 This leads to a picture with high circulating aldosterone levels, but hyponatraemia and hyperkalaemia. In most cases, infection alone is insufficient to cause PHA but is often found in the context of PHA with urogenital tract malformations.8 In this case, there was no evidence of infection at any time. In other cases as well as ours, high doses of fludrocortisone have been shown to normalise sodium and potassium levels, leading to speculation that high levels of mineralocorticoids can overcome transient tubular resistance. It is thought that as neonates and infants have a low sodium-containing diet, and that they have a reduced capacity to compensate in comparison to older children, and hence is seen more commonly. Trimethoprim has been associated with electrolyte disturbances, particularly hyperkalaemia but sometime hyponatraemia, noted as a ‘common’ side effect in the British National Drug Formulary.13 It inhibits the potassium elimination in the distal nephron. It has been reported in multiple articles, predominantly affecting adults with comorbidities or polypharmacy, and specifically in combination with sulfamethoxazole.14 In this case, the patient had been on trimethoprim following initial discharge, although at a prophylactic (lower) dose for urinary tract infection rather than at treatment dose. This was continued following recovery and the PHA has not recurred, suggesting it was not linked to the administration of trimethoprim. On initial presentation, these children are understandably usually treated as if for CAH, a condition with life-threatening salt-wasting crises until PHA becomes more apparent and the cause treated. Urinary sodium can be helpful in differentiating PHA from CAH. As in our case, the aldosterone and other hormone levels are often only reported after the acute phase.
Learning points
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A presentation of hyponatraemia and hyperkalaemia, especially in an infant, must be treated as a salt-wasting crisis of congenital adrenal hyperplasia and investigated thoroughly until confirmatory results are reported.
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This is an unusual cause for pseudohypoaldosteronism secondary to obstructive uropathy.
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Hydrometrocolpos can recur despite surgery.
Acknowledgments
We are grateful to Claire Keaney for radiology support and to Julie Oliver for administration.
Footnotes
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Contributors The manuscript was written by SKu and HM, reviewed and contributed to by JCA and SKa. Patient consent was taken by SKu.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Competing interests None declared.
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Patient consent for publication Parental/guardian consent obtained.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.
References
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