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TRIIODOTHYRONINE INTOXICATION
700 TRIIODOTHYRONINE INTOXICATION
SIR,-A few reports on severe intoxication with desiccated thyroid or thyroxine have been published.I-3 In one of these cases a
hyperthyroid
state
resembling thyroid
storm
developed
several days after ingestion.’ The lag period reflects the long half-life of thyroxine and its metabolism to the active derivative triiodothyronine. In clinical tests of thyroid suppression triiodothyronine (50 g, twice daily for a week) has been found to cause adverse reactions much more frequently than correspondingly suppressive doses of thyroxine.4 The rapid and potent action of triiodothyronine suggests that it could be a greater hazard than thyroxine. We know of no case-reports of severe triiodothyronine overdose. We report here the outcome of a patient who ingested 1600 g triiodothyronine. A 30-year-old woman taking clomipramine because of mental depression ingested 80 20 g tablets of triiodothyronine in a suicidal attempt together with 40 tablets of the antihistamine LABORATORY FINDINGS AFTER POISONING WITH
1600 g
TRIIODOTHYRONINE
cular compartment. Thyroxine has a higher degree of protein binding,5 and overdosage of this hormone may produce protracted and severe intoxications.1-3 In situations with reduced T3 turnover (e.g., if circulating T3-binding antibodies6-7 are present or if glomerular filtration is reduced) overdosage of T3 may give rise to prolonged adverse reactions, which could need active therapeutic measures, such as beta-adrenergic blocking agents. In general, because of the rapid clearance of T3, ingestion of doses of the hormone leading to circulating levels even 50 times normal may follow a benign course. of Internal Medicine and Clinical Chemistry,
Departments
University Hospital, S-750 14 Uppsala, Sweden
P. A. DAHLBERG F. A. KARLSSON L. WIDE
RENAL-BIOPSY FINDINGS IN LITHIUM AND PRELITHIUM PATIENTS
SiR,-We have previously described’ a unique specific tubular lesion caused by lithium. We wish to publish some additional data about this lesion, and to give the results of a comparative histological survey of renal-biopsy material from age-matched lithium, prelithium, and donor kidneys used for cadaver transplantation. The specific tubular lesion is found in the cortical and medullary collecting ducts and distal convoluted tubules. It develops very soon after lithium is started and is absent in kidney sampled a year after lithium has been stopped. The site of the lesion is where the vasopressin receptors are thought to be, and hence this lesion may be the pathological basis of the vasopressin-resistant diabetes-insipidus-like syndrome seen in some patients taking lithium regularly.
brompheniramine (total dose 480 mg), and 20 tablets of clomipramine (total dose 200 mg). An hour later, when the patient arrived at the hospital, she was mentally confused but with no other signs of intoxication. After gastric lavage the patient was transferred to the intensive-care unit. After 4-6 h tachycardia developed (sinus rhythm, 110 beats/min); the patient started sweating but retained normal body temperature. Over the next 12 h these symptoms disappeared, the patient became mentally oriented, and could be referred to her psychiatrist for further care. The simultaneous intake of brompheniramine and clomipramine may have affected the patient mentally but reduced the thyrotoxic symptoms. Results of thyroid-hormone analyses shown in the table. On admission the circulating level of T3 was 80 nmol/1 and values of rT3, free and total T4, T3-resin uptake, and TSH were normal. A week later the T3 was normal, rT3 reduced to about half the initial value, and free and total T4 also reduced by a factor of two. The TSH value had fallen below normal. These changes illustrate the effective and suppressive action of T3 on TSH secretion from the pituitary, with consequent reduction of thyroxine release from the thyroid resulting in a reduced peripheral production of rT3. The T3-resin uptake value remained unchanged, probably as a result of a reduced synthesis of thyroxine-binding globulin.5 After another 11 days the laboratory findings were all normal. Despite the pronounced metabolic effects of the T3 overdose on thyroid hormone homceostasis, the patient had only moderate clinical signs of thyrotoxicosis. The short transitory clinical effects are explained by a rapid-elimination of T3 from the vasare
1. Schottstaedt ES, Smoller M. "Thyroid storm" produced by acute thyroid hormone poisoning. Ann Intern Med 1966; 64: 847-49. 2. Funderburk SJ, Spaulding JS. Sodium levothyroxine intoxication in a child. Pediatrics 1970; 45: 298-301. 3. Von Hofe SE, Young RL. Thyrotoxicosis after a single ingestion levothyroxine. JAMA 1977; 237: 1361. 4. Wenzel KW, Meinhold H. Evidence of lower dose: comparison to the classical L-triiodothyronine test for thyroid suppressibility. J Clin Endocrinol Metab 1974, 38: 902-05. 5. Robbms J, Cheng S-Y, Gershengorn MC, et al. Thyroxine transport proteins of plasma. Molecular properties and biosynthesis. Rec Progr Horm Res
1978; 34: 477-517.
cytoplasm in renal tubular cell ot patient on iitnium N=nucleus; M=mitochondrion. (Reduced to 3/8 of x 10 000).
swelling
ot
Ultrastructural studies show distortion of the renal tubular cells due to an apparent swelling of the cytoplasm due to an increase in cell water (see figure). Mitochondria and other intracellular organelles tend to be distributed at the periphery of the cells giving rise to the periodic-acid/Schiff positive granular appearance described on light microscopy.’ No evidence has yet been found of actual cell necrosis on electronmicrographs, although this has been described in rats given high doses of lithium.2 V, Vallotton MB, Burger A. Detection of human anti-thyroxine and antibodies in different clinical conditions. J Clin Endocrinol Metab 1975; 41: 669-75. 7. Karlsson FA, Wibell L, Wide L. Hypothyroidism due to thyroid-hormone-
6. Staeheli
anti-triiodothyronine
binding antibodies. N Engl J Med 1977, 296: 1146-48. 1. Burrows GD, Davies B, Kincaid-Smith P. Unique tubular lesion after lithium. Lancet 1978; i: 1310. 2. Evan AP, Ollerick DA. The effect of lithium carbonate on the structure of the rat kidney. Am J Anat 1972; 134: 97-106.
SIR,-A few reports on severe intoxication with desiccated thyroid or thyroxine have been published.I-3 In one of these cases a
hyperthyroid
state
resembling thyroid
storm
developed
several days after ingestion.’ The lag period reflects the long half-life of thyroxine and its metabolism to the active derivative triiodothyronine. In clinical tests of thyroid suppression triiodothyronine (50 g, twice daily for a week) has been found to cause adverse reactions much more frequently than correspondingly suppressive doses of thyroxine.4 The rapid and potent action of triiodothyronine suggests that it could be a greater hazard than thyroxine. We know of no case-reports of severe triiodothyronine overdose. We report here the outcome of a patient who ingested 1600 g triiodothyronine. A 30-year-old woman taking clomipramine because of mental depression ingested 80 20 g tablets of triiodothyronine in a suicidal attempt together with 40 tablets of the antihistamine LABORATORY FINDINGS AFTER POISONING WITH
1600 g
TRIIODOTHYRONINE
cular compartment. Thyroxine has a higher degree of protein binding,5 and overdosage of this hormone may produce protracted and severe intoxications.1-3 In situations with reduced T3 turnover (e.g., if circulating T3-binding antibodies6-7 are present or if glomerular filtration is reduced) overdosage of T3 may give rise to prolonged adverse reactions, which could need active therapeutic measures, such as beta-adrenergic blocking agents. In general, because of the rapid clearance of T3, ingestion of doses of the hormone leading to circulating levels even 50 times normal may follow a benign course. of Internal Medicine and Clinical Chemistry,
Departments
University Hospital, S-750 14 Uppsala, Sweden
P. A. DAHLBERG F. A. KARLSSON L. WIDE
RENAL-BIOPSY FINDINGS IN LITHIUM AND PRELITHIUM PATIENTS
SiR,-We have previously described’ a unique specific tubular lesion caused by lithium. We wish to publish some additional data about this lesion, and to give the results of a comparative histological survey of renal-biopsy material from age-matched lithium, prelithium, and donor kidneys used for cadaver transplantation. The specific tubular lesion is found in the cortical and medullary collecting ducts and distal convoluted tubules. It develops very soon after lithium is started and is absent in kidney sampled a year after lithium has been stopped. The site of the lesion is where the vasopressin receptors are thought to be, and hence this lesion may be the pathological basis of the vasopressin-resistant diabetes-insipidus-like syndrome seen in some patients taking lithium regularly.
brompheniramine (total dose 480 mg), and 20 tablets of clomipramine (total dose 200 mg). An hour later, when the patient arrived at the hospital, she was mentally confused but with no other signs of intoxication. After gastric lavage the patient was transferred to the intensive-care unit. After 4-6 h tachycardia developed (sinus rhythm, 110 beats/min); the patient started sweating but retained normal body temperature. Over the next 12 h these symptoms disappeared, the patient became mentally oriented, and could be referred to her psychiatrist for further care. The simultaneous intake of brompheniramine and clomipramine may have affected the patient mentally but reduced the thyrotoxic symptoms. Results of thyroid-hormone analyses shown in the table. On admission the circulating level of T3 was 80 nmol/1 and values of rT3, free and total T4, T3-resin uptake, and TSH were normal. A week later the T3 was normal, rT3 reduced to about half the initial value, and free and total T4 also reduced by a factor of two. The TSH value had fallen below normal. These changes illustrate the effective and suppressive action of T3 on TSH secretion from the pituitary, with consequent reduction of thyroxine release from the thyroid resulting in a reduced peripheral production of rT3. The T3-resin uptake value remained unchanged, probably as a result of a reduced synthesis of thyroxine-binding globulin.5 After another 11 days the laboratory findings were all normal. Despite the pronounced metabolic effects of the T3 overdose on thyroid hormone homceostasis, the patient had only moderate clinical signs of thyrotoxicosis. The short transitory clinical effects are explained by a rapid-elimination of T3 from the vasare
1. Schottstaedt ES, Smoller M. "Thyroid storm" produced by acute thyroid hormone poisoning. Ann Intern Med 1966; 64: 847-49. 2. Funderburk SJ, Spaulding JS. Sodium levothyroxine intoxication in a child. Pediatrics 1970; 45: 298-301. 3. Von Hofe SE, Young RL. Thyrotoxicosis after a single ingestion levothyroxine. JAMA 1977; 237: 1361. 4. Wenzel KW, Meinhold H. Evidence of lower dose: comparison to the classical L-triiodothyronine test for thyroid suppressibility. J Clin Endocrinol Metab 1974, 38: 902-05. 5. Robbms J, Cheng S-Y, Gershengorn MC, et al. Thyroxine transport proteins of plasma. Molecular properties and biosynthesis. Rec Progr Horm Res
1978; 34: 477-517.
cytoplasm in renal tubular cell ot patient on iitnium N=nucleus; M=mitochondrion. (Reduced to 3/8 of x 10 000).
swelling
ot
Ultrastructural studies show distortion of the renal tubular cells due to an apparent swelling of the cytoplasm due to an increase in cell water (see figure). Mitochondria and other intracellular organelles tend to be distributed at the periphery of the cells giving rise to the periodic-acid/Schiff positive granular appearance described on light microscopy.’ No evidence has yet been found of actual cell necrosis on electronmicrographs, although this has been described in rats given high doses of lithium.2 V, Vallotton MB, Burger A. Detection of human anti-thyroxine and antibodies in different clinical conditions. J Clin Endocrinol Metab 1975; 41: 669-75. 7. Karlsson FA, Wibell L, Wide L. Hypothyroidism due to thyroid-hormone-
6. Staeheli
anti-triiodothyronine
binding antibodies. N Engl J Med 1977, 296: 1146-48. 1. Burrows GD, Davies B, Kincaid-Smith P. Unique tubular lesion after lithium. Lancet 1978; i: 1310. 2. Evan AP, Ollerick DA. The effect of lithium carbonate on the structure of the rat kidney. Am J Anat 1972; 134: 97-106.