Congenital hypothyroidism affects renal growth, which improves on intake
of thyroxine supplements(1). Apart from growth, thyroid hormone also has
other effects on the kidney. We present here an interesting case of severe
congenital hypothyroidism with nephrocalcinosis.
An 8-year-old girl presented with history of delayed
milestones, severe malnutrition, decubitus ulcers over buttocks and
elbows, and severe constipation. She was a product of non-consanguineous
marriage with no significant perinatal history. On examination, she had
coarse facial features, bilateral convergent squint, thickened dry skin,
delayed dentition and non pitting pedal edema. She had severe growth
failure (weight 9.3 kg (-4.4 SDS); height 75 cm (-8.77 SDS); upper
segment: lower segment ratio 1.2:1. The child’s developmental age was
about 6 months.
Investigations revealed microcytic hypochromic anemia (Hb
7.8gm/dL), with sodium 135 mEq/L, potassium 3.4 meq/L, magnesium 1.6 mg/dL,
calcium 8.3 mg/dL, phosphates 2.92 mg/dL, and uric acid 4.4 mg/dL. The
estimated GFR by Schwartz formula was 46.4 mL/min/1.73m² (creatinine 0.89
mg/dL). Free triiodothyronine was 1.3 pg/mL with free thyroxine 0.10 µgm/dL
and thyroid stimulating hormone (TSH) 150 µIU /mL. Venous blood gas showed
pH 7.39, bicarbonate 22 mEq/L and base excess 1.4 mEq/L. Radiographs of
limbs, pelvis, and skull showed thickened dense calvaria, retarded bone
ossification, presence of wormian bones, and presence of epiphyseal
dysgenesis in long bones. Radiography showed bone age <1 year and dense
calcifications in the renal areas of pelvic film. Ultrasonography of
abdomen revealed right kidney 5.2×3.4 cm in size; left kidney 5.0×2.8 cm
with bilateral dense medullary nephrocalcinosis. The 24-hours urinary
calcium excretion was 5 mg/kg (spot calcium/creatinine ratio 0.6 mg/mg),
indicating hypercalciuria. A diagnosis of congenital hypothyroidism with
bilateral nephro-calcinosis was made.
The association of congenital hypothyroidism with
nephrocalcinosis has been reported previously(2,3). Newman(4) in 1973
reviewed the entity and found that 23 cases were reported in world
literature. The mechanism of nephrocalcinosis postulated was that intact
mitochondria can accumulate calcium against concentration gradient as an
active process using oxidative phosphorylation in proximal or distal renal
tubular cells. This mechanism is altered in hypothyroidism, leading to
high intracytoplasmic calcium concentrations predisposing to
nephrocalcinosis. Studies have shown that supplementation of thyroxine
increases serum calcium and 1,25-dihydroxyvitmin D levels. Serum
parathormone levels have also been reported to be elevated in adult
hypothyroid patients on treatment with thyroxine. This further predisposes
to nephrolithiasis.
Thus, apart from impaired renal growth, children with
congenital hypothyroidism are also predisposed to nephrolithiasis. Care
should be taken to avoid large supplements of calcium or vitamin D during
initial treatment of hypothyroidism with thyroxine, as this may exacerbate
hypercalciuria and cause nephrocalcinosis.
References
1. Bulbul M, Cetinkaya S, Eksioglu S, Ozkasap S, Ginis
T. Kidney growth in children with congenital hypothyroidism. Pediatr
Nephrol 2009; 24: 333-340.
2. Bateson EM, Chandler S. Nephrocalcinosis in
cretinism. Br J Radiol 1965; 38: 581-584.
3. Naylor JM. A case of hypothyroidism with
nephrocalcinosis. Arch Dis Child 1955; 165-168.
4. Newman RJ. The effects of thyroid hormone on vitamin-D induced
nephrocalcinosis. J Path 1973: 13-21.