Payal Patel, M.D.

Pediatric Endocrinology Fellow

December 4, 2014

4-week-old F with hyponatremia

Chief Complaint

4-week-old F presents to our endocrine clinic for evaluation

of hyponatremia.

HPI

Due to suboptimal weight gain following birth, pt was closely

being monitored by her PCP

Weight decreased from 15%ile to <10%ile

Admitted to an OSH at 2.5 wks of age for monitoring of

growth

Started on EBM + Enfamil 22 kcal/oz, 2 oz Q2-3 hrs

Na found to be 125 neo consult

Started on PO NaCl 6.2 mEq/d (1.7 mEq/kg/d)

Hospital day 3: wt increased to 7 lbs, Na increased to 131

HPI

Continued PO NaCl until 3.5 wks of age (11 total doses)

2 days later: Na of 130 at PCP’s office

No changes in UOP reported

Per PCP’s discussion with peds nephrology:

Endo evaluation recommended given that she has no clinical or

laboratory evidence of renal dysfunction

ROS

Constitutional: – fever, activity change, appetite change,

decreased responsiveness

Endo: – polyuria, oliguria, polydipsia.

HEENT: – congestion, rhinorrhea, trouble swallowing

CVS: – fatigue or cyanosis with feeds

Resp: – apnea, cough, choking

GI: – distension, vomiting, constipation, diarrhea

MSK: – deformity, edema

Skin: – rash, color change, or pallor

Neuro: – seizure. +alert when awake

Further History

PMH: Born at term via C/S

for failure to progress

AGA for weight and length

Maternal meds: Clomid to

help conceive and

Metformin x3 months

D/C’ed on DOL 3

PSH: None

Meds: PO NaCl

Allergies: NKA

FH:

PCOS- mother

Thyroid disorder- MGGM,

maternal aunt

T2DM- PGF

Unexplained death- paternal

uncle

SH: Lives at home with

parents, cat and dog.

Physical Exam Vitals: T 36.2°C, Wt 3.48 kg (8%ile), Lt 50.2 cm (3%ile)

General: Well-developed, well-nourished, no distress, active

HEENT: AFSOF. No cranial deformity or facial anomaly, clear

oropharynx. PERRL, EOMI. No nasal discharge.

Neck: Supple. Thyroid not palpable.

CV: RRR, strong distal pulses, cap refill < 3 sec

Pulm/Chest: CTAB, Tanner 1 breasts

GI: S/ND/NT, +BS. No HSM, no hernia

GU: nL prepubertal F genitalia

Neuro: alert, no focal deficits, nL strength, nL muscle tone

Skin: Warm, nL turgor, no mottling or pallor

OSH Labs

Hospital Day Na K Cl CO2 BUN Cr glc Ca

1 (venous draw) 125 6.2 92 22.2 17 0.3 92 11.2

1 (heel stick) 126 10 98 18.2 19 0.7 75 12.6

1 (arterial or heel stick) 126 5.4 93 17.7 19 0.2 88 10.8

3 (arterial draw) 131 4.8 97 19.8 21 <0.2 87 11.2

1 wk later (PCP office) 130 7.6 94 21.5 9 0.2 91 11.1

Day 1: CBC, liver panel- WNL

Day 1: TSH 2.79 IU/mL, FT4 11.8 ug/dL

Day 2: UA- 6.5, 1.005, WNL

Differential Diagnosis?

Hyponatremia DDx

Hypovolemic

GI losses

Diuretics/ACEIs

Primary AI

Cerebral salt wasting

Na-losing nephropathy

Cystic fibrosis

Skin losses

Third spacing

Euvolemic

SIADH

Hypothyroidism

Secondary AI

Hypoaldosteronism

Pseudohypoaldosteronism

Psychogenic polydipsia

Water intoxication

Hypervolemic

Congestive heart failure

Nephrotic syndrome

Renal failure

Cirrhosis

Excess hypotonic fluids

CMP: 133 95 9

5.4 11 0.2

Ca 11.4

Labs

72 CMP: 137 98 10

6.5 24 0.2

Ca 11.5

69

Serum osm: quant. insuff.

Aldosterone 1220 ng/dL (5-90)

Renin 440 ng/mL/hr (2.35-37)

Aldo/PRA 2.8 (0.14-38)

ACTH 38.3 pg/mL (< 58)

Cortisol 19.1 mcg/dL

DHEAS < 15 ug/dL

Clinical Objectives

Review pseudohypoaldosteronism (PHA)

Discuss the management and prognosis of PHA

PHA

First reported in 1958 by Cheek and Perry in an infant

with severe Na-wasting

End-organ resistance to aldo

Clinical dx:

urinary Na excretion

PRA and aldo

nL aldo/PRA ratio

Unresponsive to mineralocorticoids

May confirm dx with genetic testing

PHA type 1

1 in 80,000 newborns

urine Na hyponatremia, hyperkalemia

Metabolic acidosis

inability to gain weight, dehydration, fatigue, weakness

PHA type 1

Defective transepithelial sodium transport

AD (Renal PHA1)- Mutation in NR3C2 gene

Renal Na loss

Mild clinical presentation, improves in early childhood

AR (generalized/systemic PHA1)- Mutation in SCNN1A,

SCNN1B, or SCNN1G gene

Na loss from the kidneys + other organs (sweat glands,

salivary glands, and colon)

More severe, does not improve with age

PHA1 AR

PHA1 AD

PHA type 2

Unknown prevalence

AD mutation in WNK1 or WNK4

Variable age of onset

Hyperkalemia, HTN, nL kidney fxn

Poss. hypercholeremia or metabolic acidosis

Nonspecific sx- n/v, fatigue, muscle weakness

Management

IV fluids

NaHCO3, Ca carbonate, glucose-insulin

PO Na supplementation

NaCl, NaHCO3

Life-long if type 2

Low-K diet

Cation-binding resin

Indomethacin

Dialysis if life-threatening K

Management

Cation-binding resin (Na polysterene sulfonate):

for persistent K resistant to Na replacement alone

1 g = 4.1 mEq Na, exchange capacity of ~1 mEq K

Given PO in 4-6 divided doses

Indomethacin

Thought to induce retention of solute and water via proximal

tubular reabsorption

Shown to decrease dose of Na supplementation

Not recommended for routine use given potential toxicity

Prognosis

AD (Renal PHA1)

Clinical signs and metabolic abnormalities w/improvement

early in childhood D/C of tx

AR (generalized/systemic PHA1)

Death in neonatal period is common w/o tx

Back to Our Patient...

Continue current NaCl supplementation

Weekly BMPs

Return to endocrine clinic in 2 months

Schedule appt with Dr. Waggoner (genetics)

Follow-up Labs

Date Na K Cl CO2 BUN Cr glc Ca

9/3 135 6.5 99 21 7 0.2 87 11.5

9/11 135 4.9 102 22.1 6 <0.2 89 10.9

9/22 136 4.7 103 21.4 6 0.2 81 10.9

9/29 138 4.7 104 24.6 9 <0.2 87 10.7

10/13 135 4.4 10.8

10/24 134 5.0 103

10/28 137 5.0

11/3 136 4.6

11/10 136 4.7

11/24 136 4.6 10.8

Initial clinic appt on 8/19

Summary

PHA1 is likely to present in the neonatal period with Na, K,

and metabolic acidosis

Dx with PRA and aldo but nL aldo/PRA ratio

DDx of PHA1 = adrenal disorders

Cortisol, 17-OHP, urinary steroid profile

Important to have a multidisciplinary team:

neonatologist/PCP, endocrinologist, dietician, neurologist

>= BID electrolyte monitoring during Na-wasting crisis

Regular pH monitoring if receiving NaHCO3

Outpatient: Regular BMPs and follow-up

References Hines EQ. Chapter 11: Fluids and Electrolytes. The Harriet Lane Handbook (19th ed). Philadelphia: Elsevier 2012;

271-292.

Pseudohypoaldosteronism type 2. ghr.nlm.nih.gov/condition/pseudohypoaldosteronism-type-2. Genetics Home

Reference 2014.

Pseudohypoaldosteronism type 1. ghr.nlm.nih.gov/condition/pseudohypoaldosteronism-type-1. Genetics Home

Reference 2014.

Chang SS, Grunder S, Hanukoglu A, Rosler A, Mathew PM, Hanukoglu I, Schild L, Lu Y, Shimkets RA, Nelson-

Williams C, Rossier BC, and Lifton RP. Mutations in the Subunits of the Epithelial Sodium Channel Cause Salt

Wasting with Hyperkalemia Acidosis, Pseudohypoaldosteronism Type 1. Nature Genetics 1996;12:248-253.

Geller DS, Zhang J, Zennaro MA, Vallo-Boado A, Rodriguez-Soriano J, Furu L, Haws R, Metzger D, Botelho B,

Karaviti L, Haqq AM, Corey H, Janssens S, Corvol P, and Lifton RP. Autosomal Dominant

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Mathew PM, Manasara KB, Hamden JA. Indomethacin and Cation-Exchange Resin in the Management of

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Guran T, Degirmenci S, Bulut IK, Say A, Riepe FG, and Guran O. J Clin Res Ped Endo 2011;3(2):98-100.

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