Persistent Pseudohypoaldosteronism in a 7-Year-Old Boy

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Persistent

Pseudohypoaldosteronism

in a

7-Year-Old

Boy

Sataya

Satayaviboon,

MD,

Francis

Dawgert,

MD,

Patricia

L. Monteleone,

MD,

and

James

A. Monteleone,

MD

From the Cardinal Glennon Memorial Hospital for Children and Department of Pediatrics, St Louis University School of Medicine, St Louis

ABSTRACT. Pseudohypoaldosteronism has been

de-scribed as a syndrome presenting early in life with

pro-found salt wastage, failure to thrive, and lethargy. The

mechanism of sodium loss is renal, not related to aldoste-rone production. Previous cases have been transient, re-spondmg to supplemental salt therapy which was discon-tmued after one to two years. A child whose

pseudohy-poaldosteronism was first diagnosed in infancy and whose

salt loss persisted to 7 years of age is described. Pediatrics 69:458-462, 1982; pseudohypoaldosteronism,

aldoste-rone, renin, hyponatremia, hyperkalemia.

Pseudohypoaldosteronism was first described in

1958.1 It occurs during early infancy and is

charac-terized by severe urinary sodium loss, despite

nor-mal renal and adrenal function. It has been

postu-lated that the mechanism of this sodium loss is

unresponsiveness of the renal tubule to aldosterone

and other mineralocorticoids!3 It has been stated

that this disorder seems to be self-limiting and that

treatment is unnecessary after 1 or 2 years of

age.”2’4’5

We report a child whose

pseudohypoaldosteron-ism was diagnosed during infancy, and who at 7

years of age stifi had marked urinary sodium loss

and required large sodium supplementation to

maintain normal sodium levels and normal growth

and development. Sodium excretion by sweat,

sa-liva, and tears was measured.

CASE REPORT

An 8-week-old white male infant was admitted to Car-dinal Glennon Memorial Hospital for Children for failure

Received for publication March 16, 1981; accepted May 29, 1981. Reprint requests to (JAM.) Department of Pediatrics, Cardinal

Glennon Memorial Hospital for Children, 1465 South Grand

Boulevard, St Louis, MO 63104.

American Academy of Pediatrics.

to thrive. The patient’s birth weight was 3,742 gm. At 6

weeks of age, he weighed 4,111 gm. Weight was 3,827 gm

at the time of admission.

The mother was a 21-year-old woman (gravida 1, para 1, aborts 0) whose pregnancy, labor, and delivery were

uncomplicated. She noted that the child had always been a poor feeder. The diet consisted of Enfamil, 3 oz every

four hours. The patient had had three to four loose stools

per day for two days prior to admission. There was no history of vomiting or foul-smelling stools.

On physical examination the vital signs were within normal limits; body weight was less than third percentile; length 25th percentile; head circumference less than third

percentile. The patient was a pale child who appeared

dehydrated. There were two testes of normal size in the

scrotum; the penis was normal in size. Admission studies

revealed the following laboratory values: sodium 110

mEg/liter; potassium 7.5 mEq/liter; chloride 84 mEq/

liter; CO, 11.3 mEq/liter; pH 7.36, BUN 45 mg/100 ml;

creatinine 1 mg/100 ml; blood glucose 104 mg/100 ml; a complete blood count and chest roentgenogram were normal.

Concentrations of urine pregnanetriol, 17-ketosteroids

and 17-hydroxy-steroids, and serum cortisols were nor-mal, as were levels of urine catecholamines and vanillyl-mandelic acid.

Electrolytes were corrected with intravenous fluids and the child gained weight (Figure).

In preparation for a roentgenographic series of the

upper gastrointestinal tract the patient was allowed

noth-ing by mouth overnight. During this 12-hour period, he

lost 340 gm and became clinically dehydrated again. He

was maintained on intravenous normal saline. Oral

hy-drocortisone therapy, 4 mg twice daily (40 mg/sq rn/day),

was begun, then changed to cortisone acetate, 4 mg twice

daily intramuscularly (IM). This dosage was decreased to

4 mg once a day. On the 25th hospital day,

deoxycorti-costerone treatment, 2 mg IM once per day, was begun.

Six days later this was decreased to 1 rng IM/day (Figure). These medications had no effect on the patient’s serum

sodium concentration. Urinary aldosterone and plasma

renin levels were obtained and were markedly elevated

(Table 1). A high sodium diet was begun and the patient

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145 135

mEq/l 125

115

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(kg.)

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3OmEq/d #{149} 34mEq/d ‘ 42 SmEg/ci

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Figure. Laboratory values for 7-year-old boy with persistent pseudohypoaldosteronism.

HOSPITAL DAY

ARTICLES

459

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high levels of urinary sodium (Figure). Intravenous

py-elogram was normal as were other renal studies.

Deter-minations ofsweat chloride, urine, and serum amino acids

were normal. Chromosome analysis was 46,XY.

Roent-genograms of the abdomen, skull, and upper gastrointes-tinal tract were normal. During his hospital stay, the patient gained weight (Figure) and his blood pressure

remained stable and normal. After discharge he did well

on a high sodium supplement diet, 55 mEq/day.

The second admission was at 6 months of age. Salivary

sodium was measured while the patient was receiving high salt supplement after which salt supplement was

discontinued for one day (Table 2). Salivary sodium

con-tent decreased. Serum sodium content also decreased and

the patient lost weight. Two random 24-hour stool

collec-tions revealed stool sodium excretion to be 2.7 and 3.0

mEq/24 hr, respectively, and potassium 2.4 and 2.6 mEq/

24 hr, respectively. Normal stool sodium excretion is 0.5

to 12.5 rnEq/24 hr and potassium 3.3 to 19.3 mEq/24 hr.6

At 9 months of age the patient was admitted a third time for urine aldosterone and plasma renin activity tests.

While he was receiving a high salt supplement diet (105

mEq/day), tests showed abnormally high aldosterone and renin levels with normal serum sodium and potassium

(Table 1). Sweat sodium was 14 mEq/liter and 25 mEq/

liter (normal 0 to 30 mEq/liter).7

The patient was lost to follow-up until he was 7years

old, when he was seen in the endocrine clinic at the

request of the private orthopaedic surgeon for

reevalua-tion. The child had been craving salt and salted his food

heavily. He tired easily and experienced frequent leg

cramps. His weight was 20.5 kg (45.1 lb) (40th percentile), height was 1 1 1.9 cm (443/4 in) (20th percentile). Physical

examination revealed mild scoliosis to the left and flat

feet. Studies revealed a normal complete blood count

(CBC), BUN, creatinine, electrolytes (sodium, potassium,

chloride, C02), and intravenous pyelogram (IVP). While

the patient was on a low sodium diet, serum sodium

decreased from 133 to 128 mEq/liter. Urinary sodium and

potassium and serum aldosterone and plasma renin

activ-ity were measured (Table 1). Sodium concentration of

tears was 150 mEq/liter (normal 142 mEq/liter).8 The

child still required high salt supplementation to maintain

sodium balance.

DISCUSSION

The salt-wasting syndrome in infancy,

pseudo-hypoaldosteronism, was first recognized by Cheek

and Perry’ in 1958. They described an apparent

inability of the renal tubule to respond to high

levels of mineralocorticoids. The sodium loss in

urine is not corrected by exogenous

mineralocorti-coid such as deoxycorticosterone or aldosterone.

Rates of aldosterone secretion are high as are

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TABLE 1. Laboratory Data*

Admission No. and Day Aldosterone

Urine Serum

Plasma

Renin

Activity:

Serum

So-

Potas-Urine

So- Potas- Na/K (g/24 (ng/ Recum- dium sium dium sium Ratio

hr) 100 bent (mEq/ (mEq/ (mEq/ (mEq/ ml) Normal liter) liter) liter) liter)

Salt In-take (ng/

ml/hr)

First

9 21 . .. 138 6.5

27 20 13.5 137 5.4

39 20 14.49 143 6.6

44 56 12 132 ...

Third (108 mEq Na/ day)

3 55 23.5 133 5.8

4 55 22.4 . . . ...

5 69 .. . . ...

Fourth (low salt diet)

Admission 3 18 . . . ...

2

Recumbent

3 PM 133 5.3 112 32 3.5

6PM 132 4.3 ... ... ...

10PM 128 4.2 . . . .. . ...

11PM 84 26 3.2

3PM 25 54

9PM 36 67

3

2 AM 39 240 128 4.7 74 33 2.2

9 AM 52 309 131 4.9 . . . . . . ...

lOAM 50 . .. 129 4.9 51 24 2.1

Follow-up (1 mo) 41

* Normal values are as follows: urine aldosterone, 2 to 26 tg/24 hi; plasma renin activity,

0.4 to 4.5 ng/ml/hr; serum aldosterone (ad libitum sodium diet 7 AM fasting recumbent),

3 to 16 ng/100 ml; serum sodium, 135 to 145 mEq/liter; serum potassium, 3.6 to 5.5 mEq/ liter.

TABLE 2. Concentration of S odium and Potassium in Saliva*

Admission No. and Day Saliva Serum

Sodium (mEq/ liter)

Potassium (mEq/ liter)

Na/K Ratio

Sodium (mEq/ liter)

Potassium (mEq/ liter)

Second

55 mEq Na added/day

Admission 16 16.9 0.95 137 6.5

Low salt diet started

2

9 AM ₉ _19.6 _0.46 . .. ...

1 PM 10 16 0.62 133 6.6

4PM 14 21.5 0.65 . .. ...

8PM 9.5 18 0.52 . .. ...

3

8 AM ₉ 17.2 0.52 129 7.2

4 PM ₇ _16.5 _0.42 ₁₂₇ _7.1

4

8 AM 8 22 0.36 130 6.3

*Normal values are as follows: saliva sodium, 10 to 25 mEq/liter; saliva potassium, 15 to 40 mEq/liter; serum sodium, 135 to 145 mEq/liter; serum potassium, 3.6 to 5.5 mEq/liter.

plasma renin concentrations. The biochemical and secretion rate remains high. The authors proposed

clinical features are usually corrected with sodium that the defect was due to a refractory state of the

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ARTICLES

461

mineralocorticoids. They demonstrated that orally

administered sodium chloride compensated for the

renal salt loss and that the disease was transitory.

Donnell et al2 found that aldosterone excretion was

high when the patient was receiving a standard

hospital diet, and returned to normal when 85 mEq/

liter of sodium chloride was added to the diet.

Lelong et al3 confirmed the hyperaldosteronuria,

and normalization of aldosterone excretion after

salt supplementation. Raine and Roy,4 and

Cor-beel,9 each added a new case. A sixth patient was

studied extensively by Royer et al’#{176}who first

pro-posed the term pseudohypoaldosteronism. The

sev-enth patient, the first girl with this disease, was

reported by Polonovski et al.” In this patient, as in

that of Royer, excretion of aldosterone was high

during the period of active salt loss but only slightly

elevated after treatment. Jeune et al,’2 Trung et

al,’3 and Proesmans et al5 showed in the syndrome

that the aldosterone secretion rate was very high

during the active phase of the disease and remained

so even after the serum electrolytes and the growth

rate had been normalized with salt

supplementa-tion. Plasma renin values taken during the active

phase of the disease in the patient of Trung et al

and in one of the patients of Proesmans et al were

very high. These investigators postulated that the

hyperaldosteronism was due to hyperactivity of the

renin-angiotensin system and that the high renin

values were attributable to salt depletion. In

ex-plaining the pathophysiology of this condition,

Proesmans et al cited two arguments against

unre-sponsiveness of the distal tubule to aldosterone. In

one case, the administration of spironolactone

pro-yoked tremendous aggravation of the salt ‘#{176}and

in the patient described by Proesman and associates

a decrease in salt intake produced some adaptation

in sodium excretion with a complete inversion of

the urinary sodium-potassium ratio. In six of eight

patients in whom aldosterone was measured, there

was an inverse correlation between sodium intake

and aldosterone production. This would suggest

that complete unresponsiveness of the tubule to

aldosterone is unlikely. This disease might be due

to a disturbance of sodium reabsorption in the

proximal tubule or in the descending limb of Henle’s

loop. A normal response of the distal renal tubule

to maximal aldosterone excretion could explain the

effect of spironolactone.5 This would be supported

by the observation by Postel-Vinay’4 who found

normal aldosterone receptor mechanism in the

in-testine. The normal sweat sodium and chloride

levels in several patients with

pseudohypoaldoster-onism are also in favor of normal responsiveness to

aldosterone. Froberg et al’5 described a patient with

this syndrome whose defect was due to sweat gland

dysfunction.

Rosler et al’6 postulated two other mechanisms:

(1) a partial block between a postulated

intermedi-ate and aldosterone in the adrenal cortex of these

patients and (2) a partial defect in the enzymatic

conversion of angiotensin I to angiotensin II so that

the adrenal cortex is refractory to the aldosterone

secretory effects of angiotensin II.

Oberfield et al’7 reported a 7-month old male

infant with pseudohypoaldosteronism unresponsive

to mineralocorticoids and demonstrated multiple

target organ (kidney, colon, sweat and salivary

glands) insensitivity. In the most recent report of

this syndrome, Rosenberg et al’8 demonstrated

that an infusion of adrenocorticotropic hormone

(ACTH) produced natriuresis in their patient

sug-gesting the need for additional sodium

supplemen-tation during stress.

In the present patient, salivary sodium and

po-tassium concentrations and ratios were normal and

were consistent with data of other investigators.’95

Lauler et al2#{176}in a study of hypertensive patients

with and without aldosteronism found in the

non-aldosteronism group that the mean Na/K ratio was

1.47 with a range of 0.61 to 3.37. Patients with

aldosteronism had salivary ratios ranging between

0.21 and 0.60. Our patient while being treated with

salt supplementation was in the first range and as

the plasma sodium concentration decreased, was in

the aldosteronism range. This suggests

responsive-ness to aldosterone in our patient.

Urine sodium levels were increased but as the

serum sodium level decreased there was some renal

compensation with decreases in urine sodium

con-tent and in the Na/K ratio. This would support the

conclusion of Royer et al who demonstrated the

adverse effects of spironolactone on urinary sodium

loss and concluded that there was some renal

mm-eralocorticoid effect in these patients.

Although we did not evaluate sweat, colon, and

tear function as completely as urine and saliva

function, the normal values would suggest that the

defect in our patient was limited to the kidney. Our

patient differs from early patients, excluding the

patient of Oberfield et al,’7 in that the defect

ap-pears more severe as evidenced by urinary sodium

concentrations and Na/K ratios and that the defect

can persist beyond the first or second year of life.

This is supported by Postel-Vinay et al,2’ in a report

of a 9-year-old boy who had no evidence of

symp-tomatic hyponatremia; this child, when stressed

with spironolactone, developed significant

hypona-tremia, indicating that a persistent defect continued

to exist after his apparent spontaneous recovery

during infancy.

The patient demonstrating total

mineralocorti-coid unresponsiveness described by Oberfield et al

is the most severe in the spectrum.

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The syndrome of pseudohypoaldosteronism

rep-resents a range of possible abnormalities involving

a number of sites and varying in severity and

du-ration of involvement.

ACKNOWLEDGMENT

The authors thank Tanvagarn Pannavalee for her help

in preparing the manuscript.

REFERENCES

1. Cheek DB, Perry JW: A salt wasting syndrome in infancy. Arch Dis Child 33:252, 1958

2. Donnell GN, Litman N, Roldan M: Pseudohypo-adrenalo-corticism. Am J Dis Child 97:813, 1959

3. Lelong M, et al: Diab#{232}tesalin par insensibiit#{233} cong#{233}nitale

du tubule a l’Aldost#{233}rone: “Pseudohypoadr#{233}nocorticisme.” Rev Fr Etad Clin Biol 5:558, 1960

4. Raine DN, Roy J: A salt-losing syndrome in infancy:

Pseu-dohypoadrenocorticalism. Arch Dis Child 37:548, 1962 5. Proesmans W, Geussens H, Corbeel L, et al:

Pseudohypoal-dosteronism. Am J Dis Child 126:510, 1973

6. Sleisenger MH: Physiology of the colon, in Sleisenger MH, Fordtran JS (eds): Gastrointestinal Disease. Philadelphia,

WB Saunders, 1973, p 229

7. Robson AM: Parenteral fluid therapy, in Vaughan VC, McKay 1W Jr, Behrman RE (eds): Nelson Textbook of

Pediatrics, ed 11. Philadelphia, WB Saunders, 1979, p 284 8. Moses RA (ed): Adler’s Physiology of the Eye, ed 6. St

Louis, CV Mosby, 1975, p20

9. Corbeel L: Diab#{232}te satin due nourrison sans insuffisance surr#{233}nalienne. Pediatrie 18:557, 1963

10. Royer P, et al: Pseudo-hypoaldosteronisme. Ann Pediatr 39: 596, 1963

1 1. Polonovski C, Zittoun R, Mary F: Hypocorticisme global, hypoaldost#{233}ronisme et pseudo-hypoaldost#{233}ronisme du

nour-risson. Arch Fr Pediatr 22:1061, 1965

12. Jeune M, et al: Pseudohypoaldost#{233}ronisme. Arch Fr Pediatr 24:714, 1967

13. Trung PH, et al: Etude du taux de s#{233}cr#{233}tionde l’aldost#{233}rone et de l’activit#{233} de la refine plasmatique d’un cas de pseudo-hypoaldost#{233}ronisme. Arch Fr Pediatr 27:603, 1970

14. Postel-Vinay MC: Sodium balance, aldosterone excretion

and secretion rates: Study of colon receptors to aldosterone in a 9-year-old-boy known as a case of pseudo-hypoadreno-corticism. Acta Paediatr Scand 61:261, 1971

15. Froberg L, Sudhir KA, Northway JD, et al:

Pseudo-hypoal-dosteronism due to sweat gland dysfunction, abstracted.

Pediatr Res 8:368, 1974

16. Rosler A, Gagit E, Theodor R, et al: Salt wastage, raised

plasma-renin activity, and normal or high

plasma-aldoste-rone: A form of pseudohypoaldosteronism. Lancet 1:959,

1973

17. Oberfield SE, Levine LS, Robert RM, et al:

Pseudohypoal-dosteronism: Multiple target organ unresponsiveness to

mm-eralocorticoid hormones. J Clin Endocrinol Metab 48:228, 1979

18. Rosenberg 5, Franks RC, Ulick S: Mineralocorticoid unre-sponsiveness with severe neonatal hypoatremia and hyper-kalemia. J Clin Endocrinol Metab 50:401, 1980

19. Rice DH: Salivary gland physiology. Otolaryngol Clin North Am 10:273, 1977

20. Lauler DP, Hickler RB, Thorn GW: The salivary sodium-potassium ratio. N Engl J Med 267:1136, 1962

21. Postel-Vinay MC, Alberti GM, Ricour C, et al: Pseudohy-poaldosteronism: Persistence of hyperaldosteronism and ev-idence for renal tubular and intestinal responsiveness to

endogenous aldosterone. J Clin Endocrinol Metab 39:1038, 1974

THE DREADFUL OUTCOME OF EXPOSING CHILDREN TO DANCING AND

MUSIC,

AS VIEWED

IN 1583

Philip Stubbes

(fi.

1583-1591), and English Puritan pamphleteer, in his The

Anatomie of Abuses (1583), denounced the evil consequences of teaching

dancing and music to children as follows:

If you would have your son soft, womanish, unclean, smooth-mouth, affected to

bawdry, scurrility, filthy rimes, and unseemly talking; briefly if you would have him, as it were, transnatured into a woman or worse, and inclined to all kinds of whoredom and abomination, set him to dancing school and to learn music, and then you shall not fail of

your purpose. And if you would have your daughter riggish, bawdry and unclean, and a

filthy speaker, and suchlike, bring her up in music and dancing and my life for yours, you

have won the goal.’

REFERENCE

1. Scott AF: The Tudor Age. New York, Thomas Y Crowell, 1976, p 86

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1982;69;458

Pediatrics

Sataya Satayaviboon, Francis Dawgert, Patricia L. Monteleone and James A. Monteleone