The Diuretic Response to Administered Water in Patients With Primary Myxedema

Bleifer, Kenneth H.; Belsky, Joseph L.; L, Saxon; Papper, Solomon

doi:10.1210/jcem-20-3-409

Cited by 17 publications

(4 citation statements)

References 4 publications

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“…Advanced hypothyroidism to the clinical stage of myxedema is associated with hyponatremia involving both the nonosmotic release of AVP and diminished GFR (1,(13)(14)(15). These events, which impair urinary dilution in advanced hypothyroidism, override the defect in urinary concentrating capacity, which also has been observed with hypothyroidism (1,2).…”

Section: Discussionmentioning

confidence: 99%

Urinary Concentrating Defect in Hypothyroid Rats

Cadnapaphornchai¹,

Kim²,

Gurevich³

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Hypothyroidism is associated with impaired urinary concentrating ability in humans and animals. The purpose of this study was to examine protein expression of renal sodium chloride and urea transporters and aquaporins in hypothyroid rats (HT) with diminished urinary concentration as compared with euthyroid controls (CTL) and hypothyroid rats replaced with L-thyroxine (HTϩT). Hypothyroidism was induced by aminotriazole administration. Body weight, water intake, urine output, solute and urea excretion, serum and urine osmolality, serum creatinine, 24-h creatinine clearance, and fractional excretion of sodium were comparable among the three groups. However, with 36 h of water deprivation, HT rats demonstrated significantly greater urine flow rates and decreased urine and medullary osmolality as compared with CTL and HTϩT rats at comparable plasma vasopressin concentrations. Western blot analyses revealed decreased renal protein abundance of transporters, including Na-K-2Cl, Na-K-ATPase, and NHE3, in HT rats as compared with CTL and HTϩT rats. Protein abundance of renal AQP1 and urea transporters UTA 1 and UTA 2 did not differ significantly among study groups. There was however a significant decrease in protein abundance of AQP2, AQP3, and AQP4 in HT rats as compared with CTL and HTϩT rats. These findings demonstrate a decrease in the medullary osmotic gradient secondary to impaired countercurrent multiplication and downregulation of aquaporins 2, 3, and 4 as contributors to the urinary concentrating defect in the hypothyroid rat.Hypothyroidism is a very common clinical disorder that is associated with abnormalities in many organs, including the kidney. The ability to conserve water during periods of fluid deprivation is an important function of the kidney. Hypothyroidism has been associated with an impaired urinary concentrating capacity (1,2). However, the mechanisms of this defect at the cellular and molecular level have not been defined.In the present study, the effect of hypothyroidism in rats on the pivotal components of the urinary concentrating mechanism have been examined and compared with euthyroid animals. These components during fluid deprivation include release of the antidiuretic hormone, arginine vasopressin (AVP), and upregulation of the abundance of aquaporin-2 (AQP2) water channels in the principal cells of the collecting duct. Activation of the countercurrent concentrating mechanism, which is initiated by increased sodium-potassium-2 chloride (Na-K-2Cl) co-transporter in the water impermeable ascending limb, creates the osmotic driving force for passive water reabsorption across the collecting duct. There are also roles for other water channels, including aquaporins 1, 3, and 4, and for urea transporters in urinary concentration. The present study was undertaken to define the effect of hypothyroidism on these various molecular events during fluid deprivation in the rat. Materials and Methods Animal ModelThe study protocol was approved by the University of Colorado Institutional Animal Ca...

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Section: Discussionmentioning

confidence: 99%

Urinary Concentrating Defect in Hypothyroid Rats

Cadnapaphornchai¹,

Kim²,

Gurevich³

et al. 2003

Journal of the American Society of Nephrology

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“…Hypothyroid patients frequently ex hibit a delayed diuretic response to a water load [32,72,138], although this was not a constant finding in older studies [13,100]. Nevertheless, even when water excretion in thyroid-deficient subjects appeared to be normal, peak urine flow was higher and urine osmolality lower when the patients were restudied after thyroid hormone replacement [13]. Since the diuretic response is impaired both after water loading and intravenous dextrose [32], this defect cannot be attributed to decreased intestinal absorption of water.…”

Section: Renal Functionmentioning

confidence: 99%

“…This ex planation is strongly supported by the fact that glomerular filtration is in variably reduced in hypothyroidism, and the improved water excretion after thyroid hormone therapy is consistently associated with increased GFR [13,36,39]. In addition, urine flow and free water formation increase when filtrate delivery to the distal diluting segment is enhanced by inhibiting proximal re absorption [36], In order to evaluate the nature of the defect in water excretion we studied the diluting mechanism in hypothyroid rats [42].…”

Section: Renal Functionmentioning

confidence: 99%

Thyroid Hormone and the Kidney

Katz

Emmanouel

Lindheimer

1975

Nephron

174

127

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Thyroid hormones affect both renal morphology and function. They are required for kidney growth and development, and thyroid deficiency results in decreased renal plasma flow and glomerular filtration rate and in impaired urinary concentration and dilution. Thyroid hormones also influence membrane transport and electrolyte metabolism, and alterations in mineral metabolism in hyperthyroidism frequently cause calcium nephropathy which affects renal function adversely. The kidney plays an important role in the peripheral metabolism of iodine and thyroid hormones, and thyroid function is altered in certain kidney diseases, particularly chronic renal failure. The pathogenesis of these alterations is currently under active investigation.

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“…The myxedema patients had a modest reduction in maximal urine osmolality (p<0.04), which was entirely attributable to the lower values observed in younger patients. The results may be explained best by decreased sodium chloride reabsorption in the ascending limb of Henle's loop and/or diminished permeability of the distal nephron in myxedema.There is much evidence suggesting abnormal sodium and water handling in myxedema: decreased glomerular filtration rate (GRF) [1][2][3][4], impaired diuretic response to administered water [5][6][7], and decreased tubular reab sorption of sodium following acute salt loading as well as after stimuli for acute sodium conservation [4], In addition, patients with severe myxedema are unable to achieve sodium balance or do so very slowly when challenged with a low sodium intake [3]. The present study of renal concentrating ability, undertaken to define further the characteristics of renal sodium and water handling in human hypothyroidism, demonstrates decreased maximum uri nary osmolality (Uosm max) and solute-free water reabsorption (T0H 2O) in hypothyroid patients.…”

mentioning

confidence: 99%

Impaired Renal Concentrating Ability in Hypothyroid Man

Vaamonde¹,

Michael²,

Oster³

et al. 1976

Nephron

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The renal concentrating ability was studied in ten patients with hypothyroidism and in 15 euthyroid controls. Solute-free water reabsorption was reduced in the patients with myxedema (4.2 ± 0.3 ml/min: controls 5.8 ± 0.6 ml/min; p < 0.01). This defect was apparent at high rates of solute excretion, and was associated with enhanced excretion of sodium (p < 0.01) despite a decreased filtered load (p < 0.005). The myxedema patients had a modest reduction in maximal urine osmolality (p < 0.04), which was entirely attributable to the lower values observed in younger patients. The results may be explained best by decreased sodium chloride reabsorption in the ascending limb of Henle’s loop and/or diminished permeability of the distal nephron in myxedema.

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The Diuretic Response to Administered Water in Patients With Primary Myxedema

Cited by 17 publications

References 4 publications

Urinary Concentrating Defect in Hypothyroid Rats

Urinary Concentrating Defect in Hypothyroid Rats

Thyroid Hormone and the Kidney

Impaired Renal Concentrating Ability in Hypothyroid Man

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