Thyroid Research and Practice

CASE REPORT
Year
: 2016  |  Volume : 13  |  Issue : 1  |  Page : 40--42

Congenital hypothyroidism due to thyroid dysgenesis associated with distal renal tubular acidosis and hypoplastic kidney, an unknown association


Raiz Ahmad Misgar1, Idrees Mubarik1, Naseer Ahmad Choh2, Arshad Iqbal Wani1,  
1 Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
2 Department of Radiodiagnosis, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India

Correspondence Address:
Raiz Ahmad Misgar
Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir
India

Abstract

Congenital hypothyroidism, the most common congenital endocrine disorder, is associated with increased risk of additional congenital malformations involving other organs. Distal renal tubular acidosis (dRTA) in children is usually a primary disorder of renal tubular acidification. Hypothyroidism, usually of autoimmune etiology and only occasionally of nonautoimmune etiology, has been reported to be associated with dRTA. The association has seldom been reported in children and to the best of our knowledge congenital hypothyroidism associated with dRTA has not been reported. Here, we report a child with congenital hypothyroidism associated with dRTA and hypoplastic kidney.



How to cite this article:
Misgar RA, Mubarik I, Choh NA, Wani AI. Congenital hypothyroidism due to thyroid dysgenesis associated with distal renal tubular acidosis and hypoplastic kidney, an unknown association.Thyroid Res Pract 2016;13:40-42


How to cite this URL:
Misgar RA, Mubarik I, Choh NA, Wani AI. Congenital hypothyroidism due to thyroid dysgenesis associated with distal renal tubular acidosis and hypoplastic kidney, an unknown association. Thyroid Res Pract [serial online] 2016 [cited 2020 Jun 5 ];13:40-42
Available from: http://www.thetrp.net/text.asp?2016/13/1/40/159526


Full Text

 Introduction



Thyroid hormones play an important role in growth, development, and physiology of the kidney.[1],[2] It is known that hypothyroidism reduces the kidney-to-body weight ratio.[3] On the other hand, children with congenital hypothyroidism have an increased prevalence of congenital renal anomalies. These observations support an important role of thyroid hormones during early embryogenesis.[4] There is evidence that thyroid hormones play a role in renal tubular acidification.[5]

In distal renal tubular acidosis (dRTA), kidneys are unable to acidify the urine to pH <5.5 in presence of systemic metabolic acidosis or after acid loading as a result of impaired hydrogen ion secretion or bicarbonate reabsorption in the distal nephron. In children, dRTA is most often a primary, hereditary condition and presents as hyperchloremic metabolic acidosis, hypokalemia, nephrocalcinosis/nephrolithiasis, polyuria, and rickets. dRTA associated with autoimmune thyroid dysfunction is well-known.[6] There are few case reports of nonautoimmune hypothyroidism and dRTA in the literature.[7] We present a 6½-year-old child with congenital hypothyroidism associated with dRTA.

 Case Report



A 6½-year-old female child was referred to the endocrine center at Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir for evaluation of polyuria of 6 weeks duration and failure to thrive. Her 24 h urine volume was 1500 ml. The child had been diagnosed to have primary hypothyroidism at the age of 3 years and was started on levothyroxine replacement by a general practitioner. The etiology of hypothyroidism was not evaluated. Unfortunately, the child was not following any physician and was on inadequate levothyroxine dose (12.5 μg/day) that too with poor compliance. On physical examination, the child had dry hair, coarse skin, and puffy face and hung up deep tendon reflexes. Thyroid was impalpable. Anthropometry revealed severe, disproportionate short stature (height 95 cm, height standard deviation (SD) score - 4.5, upper segment 52 cm and lower segment 43 cm. Her weight was 12 kg (−2.8 SD). She had clinical features of rickets in the form of genu valgum, frontal bossing and wrist widening. Investigations revealed a hyperchloremic metabolic acidosis (Serum pH 7.21 and serum anion gap 11), alkaline urine (pH = 7.0) and hypokalemia (serial serum K + =2.9, 2.2, 3.0 meq/l). Blood glucose and kidney function tests were normal. Serum 25-OH D levels were normal (37 ng/ml). 24 h urinary calcium and urine protein excretion were normal while routine urine examination did not reveal glycosuria. Thyroid function test revealed severe primary hypothyroidism (thyroid stimulating hormone = >100 µIU/ml, T4 = 3.16 µg/dl, T3 = 1.7 ng/dl). Serum anti thyroperoxidase antibody concentration was 22.72 IU/L (Ref. <60). Ultrasonography (USG) neck revealed a hypoplastic thyroid gland [Figure 1] and USG abdomen revealed a hypoplastic left kidney without nephrolithiasis/nephrocalcinosis [Figure 2]. Radiograph of left wrist revealed features of rickets and delayed bone age (Bone age was 4 years according to Greulich and Pyle Atlas).{Figure 1}{Figure 2}

On the basis of clinical profile and investigations, a diagnosis of congenital hypothyroidism associated with dRTA was made. She was started on potassium citrate (at 8 mg/kg in four divided doses), and dose of levothyroxine was increased to 100 μg/day. Treatment with potassium citrate resulted in correction of hypokalemia and systemic acidosis. Three months after achieving and maintaining euthyroidism, we documented persistence of hyperchloremic metabolic acidosis with alkaline urine (after stopping potassium citrate for few days) indicating irreversibility of dRTA after adequate control of hyphothyroid state.

 Discussion



Congenital hypothyroidism is the most common congenital endocrine disorder occurring in approximately 1 in 2000–4000 newborns. The most common cause of congenital hypothyroidism is thyroid dysgenesis (85% of cases).[8] Congenital hypothyroidism is associated with 4 times increased risk of additional congenital malformations like renal, cardiac, gastrointestinal, and skeletal.[4],[9] Children with congenital hypothyroidism have an increased prevalence of congenital renal and urological anomalies; hydronephrosis, ureteropelvic junction obstruction, renal dysplasia and renal agenesis are significantly increased in children with congenital hypothyroidism.[4] One explanation for the increased risk of congenital renal and urological malformations in children with congenital hypothyroidism is that some common genes are involved in both thyroid and renal organogenesis. Pax 8 is one of these common genes expressed in the developing central nervous system and kidney, including the ureteric bud, mesonephric ducts, and the main collecting ducts.[10] Another possible explanation for the multiple organ system malformations seen in children with congenital hypothyroidism could be that the thyroid hormones play an important role during early embryogenesis.

In children, dRTA is most often a primary hereditary condition; both autosomal recessive and autosomal dominant forms have been described. In autosomal recessive form, mutations involve subunits of the H – ATPase proton pump while autosomal dominant form results from mutations involving the chloride-bicarbonate exchanger. Thyroid dysfunction has been uncommonly associated with dRTA. The most common thyroid dysfunction associated with dRTA is autoimmune hypothyroidism.[6] There are only a few case reports of nonautoimmune hypothyroidism and dRTA in the literature.[7] Although the association of congenital hypothyroidism with congenital renal and urological malformations is well-known, there is no reported case of congenital hypothyroidism associated with dRTA in the literature

How thyroid dysfunction causes defect in renal tubule acidification? Hypothyroidism is associated with decrease in tubular mass. There is evidence from animal studies that thyroid hormones have a role in renal tubular acidification.[5] Functionally, hypothyroidism is associated with impaired renal bicarbonate reabsorption after bicarbonate loading, reduced hydrogen secretion in the distal nephron, a decreased urinary – blood PCO2 gradient typical of dRTA and the impaired ability to acidify urine and excrete ammonium after an acute ammonium chloride load.[5],[11]

Both hypothyroidism and renal tubular acidosis are important causes of short stature. Our patient had congenital hypothyroidism as hypoplastic thyroid was seen on thyroid ultrasound. She also had left hypoplastic kidney, which is an associated congenital malformation of congenital hypothyroidism. Both poorly treated congenital hypothyroidism and dRTA have contributed to severe short stature in our patient. The irreversibility of dRTA after achieving euthyroidism indicates that long-standing poorly treated hypothyroidism may cause permanent tubular dysfunction.

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