| |
|
|
| Year : 2012 | Volume
: 23
| Issue : 4 | Page : 846-849 |
|
| Distal renal tubular acidosis associated with non-autoimmune hypothyroidism |
|
|
Bashir Ahmad Laway1, Imran Ali1, Mir Iftikhar Bashir1, Shahnaz Ahmad Mir1, Mohd. Ashraf Ganie1, Imtiyaz Ahmad Wani2
1 Department of Endocrinology, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, India
2 Department of Nephrology, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, India
Click here for correspondence address and email
| Date of Web Publication | 9-Jul-2012 |
|
|
 |
|
How to cite this article:
Laway BA, Ali I, Bashir MI, Mir SA, Ganie M, Wani IA. Distal renal tubular acidosis associated with non-autoimmune hypothyroidism. Saudi J Kidney Dis Transpl 2012;23:846-9 |
How to cite this URL:
Laway BA, Ali I, Bashir MI, Mir SA, Ganie M, Wani IA. Distal renal tubular acidosis associated with non-autoimmune hypothyroidism. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2013 May 18];23:846-9. Available from: http://www.sjkdt.org/text.asp?2012/23/4/846/98185 |
To the Editor,
Defects in acidification of urine, particularly distal renal tubular acidosis (dRTA), have been described in patients with hypothyroidism of autoimmune etiology. In children, dRTA usually presents with growth failure and bone disease like rickets while in adults, hypokalemia and muscle weakness are the predominant presentation. [1],[2],[3],[4] The common causes in adults are autoimmune disorders like Sjogren's syndrome, Systemic lupus erythematosus and hyperglobulinemia and, rarely, hypothyroidism. [5] In the literature, most of the cases of dRTA associated with thyroid dysfunction are reported to be of autoimmune etiology. [6] There are only a few case reports of non-autoimmune hypothyroidism and dRTA in the literature, but these are limited to single patient reports. [7] Here, we report two patients with non-autoimmune hypothyroidism associated with dRTA.
Case 1
A 20-year-old female had been detected to have primary hypothyroidism two months before; thyroid function tests at diagnosis revealed T3 of 1.2 ng/mL,T4 of 5.96 μg/dL, TSH of 13.15 μIU/mL and anti-thyroid peroxidase (TPO) antibody negative (<35 IU/L). She was taking L-thyroxine 25 μg/day and was clinically and biochemically euthyroid. The patient was admitted for evaluation of recent-onset polyuria (24-h urine volume of more than 6 L on multiple occasions). Physical examination revealed body weight of 35 kg and height of 146 cm. Blood pressure was 110/70 mmHg and there was no postural drop. Thyroid gland was not enlarged and she was found to have proximal muscle weakness. Rest of the systemic examination was normal. Laboratory studies revealed urea 25 mg/dL, creatinine 0.90 mg/dL, sodium 135 mmol/L and potassium 2.6 mmol/L. Fasting blood glucose, serum proteins, calcium, phosphorus and alkaline phosphatase were all normal. Arterial blood gas analysis revealed normal anion gap metabolic acidosis with hypokalemia [Table 1]; simultaneously collected urine was alkaline. Routine urine analysis was normal and there was no proteinuria or glycosuria; urine osmolality was 199 mosmol/L and serum osmolality was 294 mosmol/L. Anti-nuclear antibody (ANA) and antibody against double stranded DNA (dsDNA) were negative. Renal sonography was normal. A diagnosis of distal (type 1) RTA (dRTA) was made in view of metabolic acidosis, alkaline urine and hypokalemia. There was no evidence of proximal RTA in view of absence of urinary glucose, amino acids and phosphate with normal serum phosphate concentration. The patient was treated with oral potassium citrate 60 mmol/day and elemental calcium 1 g/day in addition to continuing her on L-thyroxine 25 μg/day. When the patient was again seen two months later, the polyuria had disappeared and repeat metabolic parameters meters revealed partial reversal of acidosis and correction of hypokalemia. | Table 1: Clinical characters and laboratory features in two cases before starting treatment.
Click here to view |
Case 2
A 45-year-old multiparous female was admitted for evaluation of polyuria and polydipsia of two months duration. Twenty-four-hour urinary volume was more than 4.5 L on several occasions. The patient was diagnosed to have primary hypothyroidism one year earlier. Initial thyroid function tests revealed primary hypothyroidism with negative anti-thyroid peroxidase antibody [Table 1]. She was receiving L-thyroxine 50 μg/day; repeat TSH a month before was 1.07 μIU/mL. On physical examination, her body weight was 46 kg and height 149 cm, and blood pressure was 110/70 mmHg without any postural drop. Thyroid gland was not enlarged. Systemic examination was normal. Laboratory studies revealed urea 41 mg/dL, creatinine 1.1 mg/dL, sodium 138 mmol/L and potassium 2.47 mmol/L. Fasting blood glucose, serum calcium, phosphorus and serum proteins were all normal. Arterial blood gas and urine results revealed normal anion gap metabolic acidosis with alkaline urine [Table 1]. Urinary calcium excretion was normal. Renal sonography did not reveal any evidence of nephrolithiasis or nephrocalcinosis. She also was diagnosed as a case of dRTA on the basis of hypokalemia, normal anion gap metabolic acidosis and alkaline urine. The diagnosis of proximal RTA was not considered in view of absence of hypophosphatemia, phosphaturia and absence of features of Fanconi's syndrome. The patient was put on oral potassium citrate. On follow-up after two months, polyuria, acidosis and hypokalemia had partially corrected. The patient is on regular follow-up. dRTA refers to the state of normal anion gap metabolic acidosis with inability to acidify urine, which is out of proportion to the degree of fall in the glomerular filtration rate. The disorder has a varied clinical presentation depending on age. [2],[3] Many conditions are associated with dRTA in adults, including Wilson's disease, nephrocalcinosis, sickle cell disease, drugs, toxins and autoimmune disorders. [8] The combination of thyroid dysfunction and dRTA has been described in the literature and a number of changes in structure and function have been documented in experimental and clinical hypothyroid state. Kidney weight has been found to be decreased mainly because of a decrease in cortical volume. A reduction in the peritubular diameter in proximal and thick ascending limb (TAL) and decrease in cell height in TAL has been documented. [9] A regulatory role of thyroid hormone on membrane proliferation and cell growth has been postulated to be the mechanism for other kidney changes like decrease in cross-sectional area of medullary TAL of outer and inner strip of outer medulla. There is a significant decrease in surface area of the apical and basolateral plasma membrane of TAL. [10] The functional implications of these changes are transformed into decrease in Na-K-ATPase activity in renal cortex and proximal tubules. Thyroid hormones have a stimulatory effect on the Na-K-ATPase activity in TAL of the outer medulla. [11] The association of autoimmune thyroid disease and dRTA has also been previously described. [12] Both auto-immune thyroid disease and dRTA have been thought to be of autoimmune etiology but with a difference; the thyroid disease being associated with organ-specific antibodies such as in Addison's disease and dRTA being associated with non-organ-specific diseases such as Sjogren's syndrome. [6] RTA has been described in patients with autoimmune thyroid disease including Hashimoto's thyroiditis and myxedema. [13] However, in most of the cases, either organ-specific autoantibodies or non-organ-specific antibodies have been described, and a close association between the two disorders has also been reported. [14] Functionally, hypothyroidism is associated with impaired renal bicarbonate reabsorption after bicarbonate loading, reduced hydrogen secretion in the distal nephron, a decreased urinary-blood PCO 2 gradient typical of distal renal tubular acidosis and the impaired ability to acidify urine and excrete ammonium after an acute ammonium chloride load. [13],[15],[16] Subtle abnormalities in acidification in the form of incomplete dRTA have been described in patients with over thypothyroidism. [17],[18] The association of non-autoimmune thyroid disease and dRTA has been described, but is extremely rare. Coexistence of these two disorders was described for the first time in 1996 by Fang et al in a 68-year-old man with severe post-radioiodine ablation hypothyroidism. The patient presented with hyperkalemic dRTA; a voltage-dependent defect was presumed to be the possible mechanism responsible. The patient was put on L-thyroxine and follow-up metabolic studies documented complete reversal of metabolic acidosis and normalization of serum potassium. [7] Whether RTA in our patients was because of hypothyroidism as such or the two disorders are incidentally together is not clear; however, partial recurrence of hypokalemia and other metabolic abnormalities after stopping thyroxine point toward unrelated disorders. Whether the abnormalities in acidification were exacerbated with overt hypothyroidism cannot be ruled out. Also, the possibility of an auto-immune disorder getting unfolded on long-term follow-up also cannot be ruled out.
 References | |  |
| 1. | Caldas A, Broyer M, Bechaux M, Kleinknecht C. Primary distal tubular acidosis in childhood: Clinical study and long term follow-up of 28 patients. J Pediatr 1992;121:233-41. 
|
| 2. | Zargar AH, Laway BA, Masoodi SR, Wani AI, Salahuddin M. Etiological profile of short stature in Indian Subcontinent. J Pediatr Child health 1998;34:571-6.
[PUBMED] |
| 3. | Rao N, John M, Thomas N, Rajaratnam S, Seshadri MS. Aetiological, clinical and metabolic profile of hypokalaemic periodic paralysis in adults: A single- centre experience. Natl Med J India 2006:19:246-9.
|
| 4. | Koul PA, Saleem SM, Bhat D. Sporadic distal renal tubular acidosis and periodic hypokalemic paralysis in Kashmir. J Intern Med 1993; 233:463-6.
[PUBMED] |
| 5. | Lash J, Cowell G, Arruda JA. Calcium nephrolithiasis and renal tubular acidosis, In: Coe FL, Favus MJ (eds). Disorders of bone and mineral metabolism 2 nd edition, Philadephia: Lippincott Williams & Wilkins; 2002:717-40.
|
| 6. | Mason AM, Golding PL. Renal tubular acidosis and autoimmune thyroid disease. Lancet 1970;2:1104-6.
[PUBMED] |
| 7. | Fang JT, Huang CC. Distal renal tubular acidosis associated with non-autoimmune hypothyroidism. Nephrol Dial Transplant 1996;11: 1146-7.
[PUBMED] [FULLTEXT] |
| 8. | Carruana RJ, Buckalew VM Jr. The syndrome of distal (type 1) renal tubular acidosis. Clinical and laboratory findings in 58 cases. Medicine 1988;67:84-99.
|
| 9. | Davis RG, Madsen KM, Fregly MJ, Tisher CC. Kidney structure in hypothyroidism. Am J Pathol 1983;113:41-49.
[PUBMED] [FULLTEXT] |
| 10. | Bentley AG, Madsen KM, Davis RG, Tisher CC. Response of the medullary thick ascending limb to hypothyroidism in rats. Am J Pathol 1985;120:215-21.
[PUBMED] [FULLTEXT] |
| 11. | Garg LC, Mackies S, Tisher CC. Site of actions of thyroid hormones on Na-K-ATPase in rat nephron segments. Kidney Int 1982;21: 274.
|
| 12. | Drukker A, Dolberg U, Landau H. Renal tubular acidosis in a patient with hypothyroidism due to autoimmune thyroiditis - improvement with hormone replacement therapy. Int J Pediatr Nephrol 1982;3:205-9.
|
| 13. | Mohebbi N, Kovacikova J, Nowik M, Wagner CA. Thyroid hormone alters acid-base transporters. Am J Physiol Renal Physiol 2007; 293:416-27.
[PUBMED] [FULLTEXT] |
| 14. | Bloch KT, Buchanan WW, Wohi MJ, Bunim JJ. Sjogren's syndrome: a clinical, serological, pathological study of sixty-two cases. Medicine (Baltimore) 1965;44:187-231.
|
| 15. | Brungger M, Hulter HN, Krapf R. Effect of chronic metabolic acidosis on thyroid hormone homeostasis in humans. Am J Physiol Renal Physiol 1997;272:F648-53.
|
| 16. | Morales MM, Brucoli HC, Malnic G, Lopes AG. Role of thyroid hormones in renal tubule acidification. Mol Cell Biochem 1996;154:17-21.
|
| 17. | Oster JR, Michael UF, Parez GO, Sonneborn RE, Vaamonde CA. Renal acidification in hypothyroid man. Clin Nephrol 1976;6:398-403.
|
| 18. | Michael UF, Chavez R, Cookson SL, Vaamonde CA. Impaired urinary acidification in the hypothyroid rat. Pflugers Arch 1976;361:215-20.
[PUBMED] |
Correspondence Address:
Bashir Ahmad Laway
Department of Endocrinology, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar
India
DOI: 10.4103/1319-2442.98185
[Table 1] |
|
|
|
|
|
|
|
|
|
|
|
|
|
| Article Access Statistics | | | Viewed | 630 | | | Printed | 30 | | | Emailed | 0 | | | PDF Downloaded | 133 | | | Comments | [Add] | | |
|
|
