The role of vasopressin in the impaired water excretion of myxedema.

The plasma vasopressin response to acute water ingestion was evaluated in 20 patients with myxedema prior to definitive treatment and in eight of these same patients following therapy of their hypothyroidism. Vasopressin levels were elevated and failed to completely suppress following water ingestion in 15 subjects (75 per cent). Two hypothyroid patients with elevated plasma vasopressin levels (10 per cent) had a normal renal response to the water challenge suggesting partial end organ hormonal unresponsiveness. In three (15 per cent) of the five patients with suppressible vasopressin, water excretion was impaired indicating a nonvasopressin-mediated renal defect. In eight patients restudied after achievement of a euthyroid state, vasopressin inhibition and urinary excretion were normal following the oral water load. Although intrinsic renal changes in the hypothyroid state may contribute to the observed defect in water diuresis, the present study suggests a role of endogenous vasopressin in this disorder.

[Study on urinary function and metabolism of water and electrolytes in primary hypothyroidism].

Water excretion in 16 patients with primary hypothyroidism was lower in amount and more delayed (P less than 0.05) than that in 5 normal controls after acute water ingestion. The mean plasma osmolality of the patients was lower than that of normal controls both before and after water loading. However, the mean urine osmolality was not decreased but rather elevated. The clearance of free water in the patients was lower than that in normal controls before loading, Although the clearance of osmolality in the patients was higher than that in the controls, the difference was insignificant. These two clearance rates were lower than those in the controls after loading. The fractional excretion of sodium (P less than 0.05) and chloride (P less than 0.01) in the patients was significantly higher than that in the controls before loading and both of them remained elevated after loading. Most of the parameters mentioned above improved in 9 patients after treatment with desiccated thyroid.

Urinary glycosaminoglycans excretion in Graves' disease.

Urinary excretion of glycosaminoglycans was measured in 10 patients with pretibial myxoedema, 7 of whom also had thyroid-associated ophthalmopathy, and in 3 additional patients with ophthalmopathy but no skin changes. Total uronic acid excretion was raised above control levels in only 2 patients, who had both eye and skin disease of recent onset. In these patients excretion was initially three times the control level but declined sharply in subsequent months. This decline was in the absence of effective treatment or spontaneous improvement and would appear to reflect the natural history of the disease. These data show that although glycosaminoglycans excretion may be disturbed in Graves' disease, it provides an unreliable reflection of clinical status and of the effectiveness of treatment.

Urinary excretion of catechol metabolites particularly MHPG in children. Relation to age, body mass indices and thyroid function.

Determinations of noradrenaline (NA), adrenaline (A), vanillylmandelic acid (VMA), metanephrines (MN), homovanillic acid (HVA) and 3-methoxy-4-hydroxy-phenylglycol (MHPG) were performed in 24 h urine samples of three groups of children: 26 normal children, 7 cases of congenital myxedema (not treated for at least one month) and 8 obese children to whom a short (9-14 days) course of thyroid extract was administered. No sex difference was noted in any group. The results in the control group (mean +/- SE) were as follows: NA 23.8 +/- 2.18 micrograms, A 6.2 +/- 0.35 micrograms, VMA 1.58 +/- 0.22 mg, NM 0.526 +/- 0.079 mg, HVA 1.24 +/- 0.142 mg, MHPG, 1.60 +/- 0.232 mg. The excretion of MHPG was significantly (cor)related to NA (p less than .05) and completely unrelated to the other derivatives. Significant equations and curves were obtained from linear regression analysis of MHPG excretion to age (p less than .025), weight (p less than .025), body surface (p less than .05), and creatinine excretion (p less than .05) but not to height and Quetelet index. No significant change was encountered in both myxedema or thyroid extract-treated obese group in any urinary metabolite determined. It was concluded that in children the urinary MHPG excretion is closely correlated to NA excretion and is linearly dependent on age, weight and creatinine extraction. Thyroid activity seems to have no evident effect on urinary excretion of various catechol metabolites. Suggestion is made that the MHPG (cor)relation(s) found originate(s) in corresponding change(s) of noradrenergic receptor sensitivity within the brain.

Impaired renal tubular reabsorption of sodium in hypothyroid man.

The renal response to acute salt loading and to stimuli for rapid sodium conservation was studied in 14 patients with untreated myxedema and in 13 euthyroid control subjects in balance on a 155 mEq. sodium intake. The salt-loading studies reveal urinary excretion of sodium in the myxedema patients within the range of controls despite reductions of 34 per cent in glomerular filtration (p less than 0.001) and 37 per cent in filtered load of sodium (p less than 0.001) in the former group. The capacity to conserve sodium in response to stimuli for rapid sodium conservation [postural change and administration of a supramaximal dose of 9alpha-fluorohydrocortisone (9alpha-F)] was impaired in patients with myxedema. The per cent decrease in sodium excretion during the upright posture in the hypothyroid patients was 28 per cent, less than half that observed in the control subjects, 62 per cent (p less than 0.005). Following administration of 2 mg. of 9 alpha-F the per cent decrease in sodium excretion was less (p less than 0.05) in the hypothyroid patients (50 per cent) than in control subjects (72 per cent). In all studies, baseline sodium excretion was comparable in both groups. Fractional excretion of sodium was significantly increased in the hypothyroid patients prior to (p less than 0.005) and during saline loading (p less than 0.05) and at the time of the subnormal responses to stimuli for acute sodium conservation (p less than 0.05 less than 0.005). Potassium excretion was reduced in the hypothyroid patients, even after 9alpha-F. These observations indicate decreased tubular reabsorption of sodium in myxedema under the experimental conditions described. The findings are most consistent with a role for thyroid hormone in normal sodium reabsorption. That this is not related to mineralocorticoid deficiency is suggested by the impaired sodium reabsorptive response to 9alpha-F.

Clinical usefulness of urinary 3-methylhistidine excretion in indicating muscle protein breakdown.

Urinary excretion of the post-translationally modified amino-acid 3-methylhistidine, derived from the contractile proteins actin and myosin, was measured in patients with conditions associated with nitrogen loss. The ratio of 3-methylhistidine:creatinine excretion, a measure of the fractional catabolic rate of myofibrillar protein was increased in severe injury, thyrotoxicosis, neoplastic disease, prednisolone administration, and sometimes Duchenne muscular dystrophy. In myxoedema, osteomalacia, and hypothermia the ratio was decreased; and starvation, elective operations, and rheumatoid arthritis had little effect. Provided that the diet is meat free, measurement of urinary 3-methylhistidine may provide useful information on the cause of protein loss.