| Abstract|| |
A 43- year- old woman on treatment for primary hypothyroidism presented with 1- day progressive weakness of all her limbs and history of similar episodes in the past. Clinical examination revealed grade 2 hyporeflexive weakness. Investigations revealed features of hypokalemia, metabolic acidosis, alkaline urine, and a fractional bicarbonate excretion of 3.5%, consistent with distal renal tubular acidosis. Antithyroid peroxidase and antithroglobulin antibodies were positive, suggesting an autoimmune basis for the pathogenesis of the functional tubular defect. Bicarbonate therapy resulted in a sustained clinical recovery.
|How to cite this article:|
Koul PA, Wahid A. Distal renal tubular acidosis and hypokalemic paralysis in a patient with hypothyroidism. Saudi J Kidney Dis Transpl 2011;22:1014-6
|How to cite this URL:|
Koul PA, Wahid A. Distal renal tubular acidosis and hypokalemic paralysis in a patient with hypothyroidism. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2016 Dec 9];22:1014-6. Available from: http://www.sjkdt.org/text.asp?2011/22/5/1014/84524
| Introduction|| |
Hypokalemic periodic paralysis classically presents in its familial form, but occasionally presents as a result of excessive gastrointestinal and/or urinary loss of potassium. Distal renal tubular acidosis (dRTA) is a disorder associated with an inappropriately high potassium excretion and symptomatic hypokalemia. The disorder has been found to be endemic in Thailand,  but has been reported from many other countries in a sporadic,  and/or hereditary form with variable modes of genetic transmission. , Classical dRTA is characterized by hyperchloremic metabolic acidosis and a defect in urinary acidification, which may be associated with hypercalciuria, hypocitraturia, nephrolithiasis, nephrocalcinosis, hypokalemia, progressive renal failure and growth retardation.  Hypokalemic muscular weakness is one of the manifestations of dRTA and it typically presents as hyporeflexive limb weakness, although involvement of the extraocular muscles, sphincters and cranial nerves has been reported. 
We herewith present a case of hypothyroidism that presented with hypokalemic paralysis as the initial manifestation of dRTA.
| Case Report|| |
A 43- year- old woman presented to the emergency room with history of gradually progressive weakness of all her limbs. There was no preceding viral illness, drug intake, or diarrhea. Seven months earlier, she was diagnosed as a case of hypothyroidism and was on supplemental thyroxin (200 μg daily). The patient experienced a similar episode of weakness in her lower limbs about four months earlier and was diagnosed as hypokalemic paralysis at a different hospital, and she was treated with potassium chloride which resulted in a total recovery over a period of 48 hours. She was not investigated further.
Clinical examination revealed hypotonic grade 2 quadriparesis with diminished reflexes. The rest of the physical and systemic examination was unremarkable. Preliminary investigations were within normal limits except a serum potassium level of 2.1 mmol/L, arterial pH of 7.29, pCO 2 32.7 torr, pO 2 89.1 torr, and bicarbonate level of 15.6 mmol/L (normal 22-28 mmol/L). The patient was started on 200 mEq of potassium chloride and the weakness recovered over the next 24 hours. Subsequent investigations revealed that the hemogram was normal. Serum urea was 19 mg/dL, creatinine level 0.9 mg/dL, glucose 99 mg/dL, calcium 10.8 mg/dL, phosphate 4.2 mg/dL, and uric acid 3.8 mg/dL. Serum levels of bilirubin, creatine kinase (CK), lactate dehydrogenase (LDH), calcium, phosphate, proteins, albumin, aspartate and alanine aminotransferases were normal. Serum sodium was 149 mmol/L, potassium 2.7 mmol/L, and chloride 108 mmol/L. Serum levels of T 3 , T 4 and thyroid stimulating hormone (TSH) were normal. Serum level of anti- thyroid peroxidase antibodies was 39.86 IU/mL (normal 0-18 IU/ mL) and that of anti- thyroglobulin anti- bodies was 206.21 IU/mL (normal 0-70 IU/mL). Antibodies to nuclear antigen, latex agglutination test, antimitochondrial antibodies, and antiparietal cell and smooth muscle antibodies were negative. Anti- dsDNA, anti- Sm, anti- RNP, anti- Ro and anti- La were negative. Levels of serum immunoglobulin complements, C 3 and C 4 , were normal. Schirmer test for lacrimation was normal. Ultrasound examination of abdomen was normal. Radiograph of the chest and electrocardiogram were normal. Urine was negative for glucose, protein, or blood, and the microscopy was normal. Urine pH was 7.0 at a correspond ding blood pH of 7.27. Urinary excretion of calcium, creatinine, uric acid, phosphates was normal. No amino acids were detected in the urine. Bicarbonate infusion test revealed a U- P CO 2 of 11.3 mmol/L and a fractional excretion of 3.5%. Nerve conduction and electromyographic studies were normal. The patient was discharged on oral sodium bicarbonate and has been weakness free over a follow- up period exceeding 2 years.
| Discussion|| |
Hypokalemic paralysis is a common manifestation of RTA in some parts of the world. RTA is defined as an inability of the renal tubule to acidify urine, which is out of proportion to any reduction in the glomerular filtration rate. The disorder can occur as a primary disorder or can be associated with a variety of systemic disorders such as Sjogren's syndrome and chronic active hepatitis. Of the endocrine disorders, RTA has rarely been reported in patients with thyroid dysfunction including hyperthyroidism, Hashimoto's thyroiditis, and hypothyroidism. A defect in the renal acidification was observed in hypothyroid rats when compared to controls.  After having been fed with ammonium chloride, two of five patients with hypothyroidism were unable to acidify urine, suggesting an incomplete form of RTA.  The acidification defect has been described to be mild and presumably related to thyroxine deficiency. ,
An autoimmune mechanism has also been suggested to cause RTA in hypothyroidism disorder. , High titers of antithyroglobulin antibodies in our patient would also point to an auto- immune underlying defect as suggested by others too. , Moreover, dRTA was also reported with a non- autoimmune hypothyroidism. 
The improvement of the acidification defect in a patient after replacement therapy with thyroxine argues in favor of thyroid deficiency as an underlying cause of the functional tubular defect.  However, the hypothesis is not supported in our patient because despite being on thyroxine therapy sufficient to give biochemical and clinical euthyroid status, she developed features of dRTA. In a recent study in rats with induced hypothyroidism, the investigators demonstrated a reduced expression of Na + /H + exchanger NHE3, the Na + - phosphate co- transporter NaPi- IIa, and the B2 sub- unit of the vacuolar H + - ATPase in the brush- border membrane of the proximal tubule, paralleled by a lower abundance of the Na + /HCO3 - co- transporter NBCe1 and a higher expression of the acid- secretory type A intercalated cell- specific Cl - /HCO3 - exchanger AE1.  The study concluded that thyroid hormones modulate the response to an acid challenge and alter the expression of several key acid-base transporters, with mild hypothyroiddism being associated with a mild defect in renal handling and one that is compensated by the distal nephron. The data of our patient argue for an association of an autoimmune cause that influences the renal acidification mechanisms through dysfunction of various transporters and co- transporters involved in the acidification in the renal tubular system.
| References|| |
|1.||Nilwarangkur S, Nimmannit S, Chaovakul V, et al. Endemic primary distal renal tubular acidosis in Thailand. Q J Med 1990;74:289- 301. |
|2.||Koul PA, Saleem SM, Bhat D. Sporadic renal tubular acidosis presenting as periodic hypokalaemic paralysis in Kashmir. J Intern Med 1993; 233(6):463- 6. |
|3.||Koul PA, Bhat D. Distal renal tubular acidosis and hypokalemic paralysis- genetic and precipitating factors. J Assoc Physicians India 1996;44(10):752- 3. |
|4.||Morris RC Jr, Sebastian A. Renal tubular acidosis and Fanconi Syndrome. In: Stanbury JC, Wyngaarden JB, Fredrickson DS, Brown HS, eds. The Metabolic Basis of Renal Disease. New York: McGraw Hill;1983 .p. 1808- 43. |
|5.||Michael UF, Chavez R, Cookson SL, Vaamonde CA. Impaired urinary acidification in the hypothyroid rat. Pflugers Arch 1976;24;361(3):215- 20. |
|6.||Oster Jr, Micheal UF, Perez GO, Sonneborn RE, Vaamonde CA. Renal acidification in hypothyroid man. Clin Nephrol 1976;6;398- 403. |
|7.||Drukker A, Dolberg M, 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(3):205- 9. |
|8.||Mason AM, Golding PL. Renal tubular acidosis and autoimmune thyroid disease. Lancet 1970; 2(7683):1104- 7. |
|9.||Maeng M, Pedersen KM. A young woman with metabolic acidosis and recently detected IDDM without ketonuria. A rare autoimmune (?) combination of hypothyroidism, diabetes mellitus and distal renal tubular acidosis. Ugeskr Laeger 1998;160:5663- 4. |
|10.||Fang JT, Huang CC. Distal renal tubular acidosis associated with non- autoimmune hypothyroidism. Nephrol Dial Transplant 1996;11(6): 1146- 7. |
|11.||Mohebbi N, Kovacikova J, Nowik M, Wagner CA. Thyroid hormone deficiency alters expression of acid- base transporters in rat kidney. Am J Physiol Renal Physiol 2007;293(1):F416- 27. |
Parvaiz Ahmad Koul
Professor and Head, Department of Internal and Pulmonary Medicine, Sheri Kashmir Institute of Medical Sciences, Soura, Srinagar 190011, Kashmir