title: Thyroxine treatment induces upregulation of renin-angiotensin-aldosterone system due to decreasing effective plasma volume in patients with primary myxoedema.
abstract: BACKGROUND
  In experimental animals and humans, hypothyroidism is associated with fluid retention and generalized oedema, increased antidiuretic hormone (ADH), decreased atrial natriuretic hormone (ANH), and decreased renin-angiotensin-aldosterone system (RAAS), which subsequently can be corrected by thyroid hormone replacement. The purpose of this study was to determine the effect of thyroxine therapy on RAAS and neurohormones affecting water and electrolyte metabolism and the reason for these changes in patients with primary myxoedema.
  
  
  METHODS
  We measured changes in the plasma renin activity (PRA), serum aldosterone (Aldo), ADH, ANH levels, serum and 24 h urinary electrolytes and osmolalities, and cardiac function in 22 female patients with primary myxoedema before and after correction of hypothyroidism. We also evaluated age-, sex-, and BMI-matched 15 healthy control subjects (Cont).
  
  
  RESULTS
  It took an average of 4.3 months (range, 3-9 months) to normalize thyroid function. The mean reductions of body weight and estimated plasma volume were 1.8+/-1.0 kg (P=0.002) and 8.5% (P<0.001), respectively. In addition, serum Na+ and osmolality and the haematocrit were significantly elevated after correction of hypothyroidism (P<0.01 and P<0.001, respectively). Increased F(E)Na and C(OSM) (P<0.05) levels in patients with hypothyroidism (Ho) compared with those in Cont did not change after thyroxine therapy (Eu). However, C(H(2)O), U(E)K, F(E)K, and TTKG levels as well as creatinine clearance (Ccr) were markedly increased in Eu compared with Ho and Cont (P<0.01, respectively). Increased plasma ADH concentration and decreased plasma ANH concentration were normalized compared to Cont after thyroxine therapy (P<0.001 and P<0.01, respectively). Low PRA and serum Aldo concentration in Ho were significantly increased in Eu (P<0.001 and P<0.01, respectively). In addition, increased left ventricular mass index and decreased cardiac output in Ho were normalized compared to Cont after thyroxine therapy (P<0.01, respectively)
  
  
  CONCLUSIONS
  These findings suggest that the exaggerated upregulation of RAAS after correction of hypothyroidism in patients with primary myxoedema is associated with an increase in Ccr and a decrease in plasma volume resulting from water diuresis, natriuresis, osmotic diuresis and inappropriate changes in plasma ADH and ANH levels. The improved renal function coincided with an amelioration of cardiac function. These changes seem to be an adaptive response for preventing excessive plasma volume and weight loss after thyroxine therapy.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, #62 Yoido-Dong, Youngdungpo-Ku, Seoul 150-713, Korea.
authors.forename: C W
authors.initials: CW
authors.lastname: Park
authors.forename: Y S
authors.initials: YS
authors.lastname: Shin
authors.forename: S J
authors.initials: SJ
authors.lastname: Ahn
authors.forename: S Y
authors.initials: SY
authors.lastname: Kim
authors.forename: E J
authors.initials: EJ
authors.lastname: Choi
authors.forename: Y S
authors.initials: YS
authors.lastname: Chang
authors.forename: B K
authors.initials: BK
authors.lastname: Bang
mesh_terms: D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D009230:Myxedema / Q000188:drug therapy* / Q000503:physiopathology*; D018377:Neurotransmitter Agents / Q000097:blood; D010953:Plasma Volume; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013963:Thyroid Hormones / Q000097:blood; D013974:Thyroxine / Q000627:therapeutic use*; D015854:Up-Regulation
chemical_list: D018377:Neurotransmitter Agents; D013963:Thyroid Hormones; D013974:Thyroxine