Subacute Thyroiditis with Increased Serum Alkaline Phosphatase JOSEPH R. DALOVISIO, M.D.; LAWRENCE BLONDE, M.D.; LAURENCE M. CORTEZ, M.D.; and GEORGE A. PANKEY, M.D., F.A.C.P.; New Orleans, Louisiana
Three patients had subacute thyroiditis and elevated serum alkaline phosphatase, presumably related to the thyroiditis. Concomitant elevation of the serum gamma-glutamyl transferase suggested that the alkaline phosphatase was of hepatic origin. The elevation of the serum alkaline phosphatase could not be definitely related to the degree or duration of elevation of the serum thyroxine. The combination of elevated serum alkaline phosphatase with the systemic symptoms of subacute thyroiditis may obscure the diagnosis, especially if patients have little or no neck pain.
S U B A C U T E (de Quervain) thyroiditis, a well-characterized clinical e n t i t y , h a s b e e n t h e subject of m a n y r e v i e w s (1-5). W e h a v e seen t h r e e p a t i e n t s w i t h s u b a c u t e t h y r o i d i tis w h o h a d m a r k e d a n d u n e x p l a i n e d e l e v a t i o n of t h e serum alkaline phosphatase, which declined toward norm a l in p a r a l l e l w i t h clinical a n d l a b o r a t o r y e v i d e n c e of t h e p a t i e n t s ' r e c o v e r y . A l i t e r a t u r e review f o u n d n o rep o r t s of a b n o r m a l i t i e s of t h e s e r u m a l k a l i n e p h o s p h a t a s e associated with subacute thyroiditis and, thus, p r o m p t e d this c o m m u n i c a t i o n .
Materials and Methods The charts of all patients seen at the Ochsner Medical Institutions between 1973 and 1977 who had been coded with a diagnosis of subacute thyroiditis were reviewed. We were able to retrieve the records of 20 patients with subacute thyroiditis. In 10, serum alkaline phosphatase measurements had been made during their clinical thyroiditis. The method of serum alkaline phosphatase measurement was either the Technicon Sequential Multiple Analyzer (SMA 12/60) method (Technicon Instrument Corporation, Tarrytown, New York) which is based on the work of Morgenstern and associates (6), or the CentrifiChem® test (Union Carbide Corporation, Rye, New York), a modification of the Bessey-Lowry-Brock method (7).
Results O f t h e 10 p a t i e n t s w h o s e s e r u m a l k a l i n e p h o s p h a t a s e w a s m e a s u r e d d u r i n g t h e c o u r s e of clinical t h y r o i d i t i s , t h r e e h a d e l e v a t e d levels w i t h o u t a p p a r e n t b o n e o r liver disease. I n all t h r e e p a t i e n t s t h e e l e v a t i o n s b e c a m e n o r m a l w i t h r e s o l u t i o n of t h e t h y r o i d i t i s . T h e i r case r e p o r t s follow. N i n e of t h e 10 p a t i e n t s for w h o m s e r u m a l k a l i n e • From the Department of Internal Medicine, Section on Infectious Disease and Section on Endocrinology and Metabolic Diseases, Ochsner Medical Institutions; New Orleans, Louisiana. Annals of Internal Medicine 8 8 : 5 0 5 - 5 0 7 , 1 9 7 8
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p h o s p h a t a s e m e a s u r e m e n t s w e r e d o n e h a d e l e v a t e d ser u m thyroxine (T-4) values.
Case Reports PATIENT 1
A 47-year-old white man had a 3-week history of fever, malaise, and a 5-kg weight loss. A "sore-throat" resolved after the first few days of his illness. A throat culture was negative for beta hemolytic streptococci. He was admitted to another hospital where he continued to have daily temperature elevations to 39 °C. The result of serum alkaline phosphatase measurement exceeded the assay's maximal measurable value. There was no history of drug ingestion, hepatitis, or hepatotoxin exposure. He was transferred to Ochsner Foundation Hospital. Results of admission physical examination were unremarkable except for a mildly enlarged, nontender, non-nodular thyroid gland. Initial laboratory evaluation showed an erythrocyte sedimentation rate of 106 m m / h (Westergren) (Figure 1). The SMA 12/ 60 analysis showed a serum alkaline phosphatase of greater than 350 U/litre (normal, 30 to 100 U/litre) and a serum glutamic-oxalacetic transaminase (SGOT) of 58 U/litre (normal, 7 to 50 U/litre). Serum alkaline phosphatase done by the CentrifiChem method showed a value of 231 U/litre (normal, 25 to 80 U/litre). Serum gamma-glutamyl transferase (SGGT) was 252 U/litre (normal, 7 to 45 U/litre). Mono-test® (Wampole Laboratories, Cranbury, New Jersey) was negative. Hepatitis-B surface antigen measurement was not done. Other routine examinations yielded normal results. Results of technetium-99 sulphur colloid liver scan and technetium-99 pyrophosphate bone scan, obtained because of suspicion of neoplastic or infectious cause of serum alkaline phosphatase elevation, were normal. Results of ultrasound examination of the abdomen and a roentgenographic survey of the skeleton were normal. A gallium-67 citrate scan showed increased tracer localization in the region of the thyroid gland, more in the left thyroid lobe than the right (Figure 2). Serum T-4 by radioimmunoassay was 14.1 jug/dl (normal, 4.5 to 11.5 jixg/dl), T-3 uptake was 47.4% (normal, 35 to 4 5 % ) . A 24-h radioactive 131 I uptake was less than 1%. The clinical picture, in conjunction with the elevated T-4 and low radioactive m I uptake, appeared to confirm the diagnosis of subacute thyroiditis. Lack of thyroid pain and high serum alkaline phosphatase values initially obscured the diagnosis of subacute thyroiditis. The patient was seen 10 days after hospital discharge and his symptoms had resolved. Erythrocyte sedimentation rate (Westergren) was 53 m m / h . Serum alkaline phosphatase (CentrifiChem method) was 129 U/litre. The SGOT, serum T-4, and T3 uptake were normal. The patient was not receiving salicylates or adrenal steroids. Nine weeks after the patient's initial symptoms, erythrocyte sedimentation rate, and serum alkaline phosphatase, SGOT, T-4 and T-3 uptake were all normal. PATIENT 2
A 36-year-old white man had a 5-week history of severe fa© 1 9 7 8 American College of Physicians
505
Two weeks after onset of this illness, the patient was evaluated at the Ochsner Clinic. He reported taking cimetidine for 25 days for peptic ulcer disease. The medication had been withdrawn 1 week after onset of the fever and neck pain. Examination showed a nodular, firm, nontender thyroid gland that was twice normal size. N o other abnormalities were found. Laboratory studies showed an erythrocyte sedimentation rate (Westergren) of 87 m l / h and a serum alkaline phosphatase (SMA 12/60 method) of 272 U/litre. The remainder of the SMA 12/60 results were normal. An S G O T measurement done manually was 27 U/litre (normal, 4 to 20 U/litre). Repeat serum alkaline phosphatase measurement (CentrinChem method) was 175 U/litre. Serum T-4 was 17.5 jutg/dl, and T-3 uptake was 53.8%. Hepatitis-B surface antigen determination was not done. Twenty-four-hour radioactive m I uptake was less than 1%. These laboratory studies strongly suggested the diagnosis of subacute thyroiditis. In 6 weeks all symptoms had resolved. Repeat erythrocyte sedimentation rate, serum alkaline phosphatase, SGOT, T-3 uptake, and T-4 measurements were within normal limits. Discussion
Figure 1 . Temporal progression of laboratory values of Patients 1, 2, and 3. ESR = erythrocyte sedimentation rate.
tigue, recurrent nightly temperature to 38 °C, anorexia, a 6-kg weight loss, dysphagia, and posterior cervical pain. Past history was unremarkable. Heart rate was 110/min, and the thyroid gland was three times normal size, extremely firm, and mildly tender. The remainder of the physical examination was normal. Initial laboratory work showed an erythrocyte sedimentation rate (Westergren) of 71 m m / h . Results from SMA 12/60 analysis were normal with the exception of a serum calcium level of 10.7 m g / d l (normal, 8.5 to 10.3 mg/dl), S G O T of 67 U/litre, and serum alkaline phosphatase greater than 350 U/litre. Serum glutamic pyruvic transaminase (SGPT) was 57 U/litre (normal, 4 to 20 U/litre). Serum alkaline phosphatase (CentrifiChem method) was 226 U/litre. Sodium sulfobromophthalein excretion was 1 3 % (normal, 0 to 6%). The S G G T level was 163 U/litre. Hepatitis-B surface antigen was negative. Serum T-4 was 12.9 jag/dl, T-3 uptake was 4 6 . 1 % , and serum triiodothyronine (T-3) by radioimmunoassay was 307 ng/dl (normal, 70 to 210 ng/dl). Radioactive m I uptake at 24 h was less than 1%. A provisional diagnosis of subacute thyroiditis was made and the patient was given aspirin as needed for pain. When he was seen again 6 weeks later, the erythrocyte sedimentation rate, serum T-4, and T-3 uptake were normal. Results from S M A 12/60 analysis, including calcium and SGOT, were normal with the exception of a mildly elevated serum alkaline phosphatase of 120 U/litre. The patient's pulse rate was 80 beats/min. He was asymptomatic. Subsequent follow-up has indicated no evidence of thyroid or hepatic dysfunction, and the thyroid enlargement has abated. A repeat serum alkaline phosphatase done 14 weeks after the patient's onset of symptoms was normal.
Patients with thyrotoxicosis have been reported to h a v e e l e v a t i o n of t h e s e r u m a l k a l i n e p h o s p h a t a s e , b u t t h e r e h a s b e e n n o c o n c l u s i v e d e t e r m i n a t i o n of t h e s o u r c e tissue (8-10). T h e effects of h y p e r t h y r o i d i s m o n b o n e m e t a b o l i s m a r e c o m p l e x a n d n o t c o m p l e t e l y u n d e r s t o o d (9, 11, 12). M i l d , nonspecific a b n o r m a l i t i e s of liver e n z y m e s , s e r u m bilirubin, a n d liver h i s t o l o g y h a v e also b e e n d e s c r i b e d in p a t i e n t s w i t h h y p e r t h y r o i d i s m a n d a r e s i m i l a r ly u n e x p l a i n e d (8, 10, 13, 14). T e n p a t i e n t s in o u r s t u d y h a d c o n c o m i t a n t m e a s u r e m e n t s of t h e s e r u m T - 4 a n d ser u m a l k a l i n e p h o s p h a t a s e . N i n e of 10 h a d significant elev a t i o n of t h e s e r u m T-4, yet o n l y t h r e e h a d e l e v a t i o n s of t h e s e r u m a l k a l i n e p h o s p h a t a s e . T h e p a t h o p h y s i o l o g y of t h e elevated s e r u m a l k a l i n e p h o s p h a t a s e in t h e s e p a t i e n t s is u n k n o w n . It c a n n o t b e definitely r e l a t e d t o t h e d e g r e e of T - 4 e l e v a t i o n b e c a u s e [1] t h e p a t i e n t w i t h s u b a c u t e t h y r o i d i t i s w i t h t h e h i g h e s t T - 4 v a l u e h a d a n o r m a l ser u m a l k a l i n e p h o s p h a t a s e , a n d [2] in P a t i e n t s 1 a n d 2 t h e s e r u m T - 4 n o r m a l i z e d l o n g before t h e s e r u m a l k a l i n e p h o s p h a t a s e . D a m a g e t o t h e liver f r o m t h e as yet u n i d e n tified etiologic a g e n t (2, 5) of s u b a c u t e t h y r o i d i t i s c o u l d
PATIENT 3
A 47-year-old white man from Mexico had fever and diarrhea, diagnosed as shigellosis, and was treated with ampicillin and furazolidone. His symptoms resolved, but 1 week later he began to have a low-grade fever and mild anterior neck pain. An upper gastrointestinal series and liver scan were reportedly normal. c/\g
April 1978 • Annals of Internal Medicine • Volume 88 • Number 4
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Figure 2A. Anterior view of gallium-67 citrate scan showing increased uptake in thyroid gland. B. Posterior view.
be postulated. All three of these patients had concomitant elevation of the SGOT and SGGT, which suggests, but does not prove, that the serum alkaline phosphatase elevation was of hepatic rather than osseous origin (15). Several other aspects of these case reports deserve comment. The temporal correlation of the serum alkaline phosphatase elevation with the clinical picture of subacute thyroiditis in Patients 1 and 2 and the absence of other demonstrable causes for the serum alkaline phosphatase abnormality suggests that these two processes are in some way related. In the third case, the increase in the serum alkaline phosphatase and SGOT could be related to the patient's ingestion of cimetidine, although cimetidine has not been conclusively shown to be hepatotoxic (16). It is interesting that the gallium scan in Patient 1 showed increased tracer localization in the area of the thyroid gland. We are unaware of any other reports of gallium scans in subacute thyroiditis. The transient hypercalcemia noted in Patient 2 may be a reflection of the effect of the elevated levels of thyroid hormone analogous to the hypercalcemia seen with hyperthyroidism from other causes. These cases show that subacute thyroiditis may mimic much more serious illnesses. The presence of elevated serum alkaline phosphatase and erythrocyte sedimentation rate, prolonged fever, and weight loss, especially when neck pain is minimal or absent (17), may suggest the diagnosis of liver abscess, granulomatous hepatic disease, or malignant neoplasm rather than subacute thyroiditis. In patients who have serum alkaline phosphatase elevation without an apparent source, thyroid function should be evaluated because subacute thyroiditis, as well as thyrotoxicosis, can be associated with elevation of the serum alkaline phosphatase. ACKNOWLEDGMENTS: Received 29 August 1977; revision accepted 7 December 1977.
• Requests for reprints should be addressed to Joseph R. Dalovisio, M.D.; Ochsner Clinic; 1514 Jefferson Highway; New Orleans, LA 70121.
References
1. VOLPE R, JOHNSTON MW: Subacute thyroiditis: a disease commonly mistaken for pharyngitis. Can Med Assoc J 77:297-307, 1957 2. STEINBERG FU: Subacute granulomatous thyroiditis. A review. Ann Intern Med 52:1014-1025, 1960 3. VANDERLINDE RJ, M I L N E J: Subacute thyroiditis, with special emphasis on the problem of early recognition. JAMA 173:1799-1802, 1960 4. SCHULTZ AL: Subacute diffuse thyroiditis. Clinical and laboratory findings in 24 patients and the effect of treatment with adrenal corticoids. Postgrad Med 29:76-85, 1961 5. G R E E N E JN: Subacute thyroiditis. Am J Med 51:97-108, 1971 6. M O R G E N S T E R N S, K E S S L E R G, A U E R B A C H J, F L O R RV, K L E I N B: An
automated p-nitrophenylphosphate serum alkaline phosphatase procedure for the Autoanalyzer. Clin Chem 11:876-888, 1965 7. BESSEY OA, LOWRY OH, BROCK MJ: A method for the rapid determination of alkaline phosphatase with five cubic millimeters of serum. / Biol Chem 164:321-329, 1946 8. PIPER J, POULSEN E: Liver biopsy in thyrotoxicosis. Acta Med Scand 127:439-447, 1947 9. BAXTER JD, BONDY PK: Hypercalcemia of thyrotoxicosis. Ann Intern Med 65:429-442, 1966 10. D O O N E R HP, P A R A D A J, A L I A G A C, H O Y L C: The liver in thyrotoxico-
sis. Arch Intern Med 120:25-32, 1967 11. K R A N E SM: Skeletal system; neuromuscular system; emotions and mentation, in The Thyroid: A Fundamental and Clinical Text. 3rd ed., edited by W E R N E R SC, INGBAR SH. New York, Harper & Row, 1971, pp. 598-615 12. EPSTEIN FH: Bone and mineral metabolism in hyperthyroidism. Ann Intern Med 68:490-491, 1968 13. G R E E N B E R G E R NJ, M I L L I G A N F D , D E G R O O T LJ, ISSELBACHER KJ:
Jaundice and thyrotoxicosis in the absence of congestive heart failure. A study of four cases. Am J Med 36:840-846, 1964 14. KIMBERG DV: Liver. See Reference 11, pp. 569-573. 15. BOONE DJ, R O U T H JI, S C H R A N T Z R: Gamma-glutamyl transpeptidase
and 5'nucleotidase. Comparison as diagnostics for hepatic disease. Am J Clin Pathol 61:321-327, 1974 16. SHARPE PC, H A W K I N S BW: Efficacy and safety of cimetidine. Longterm treatment with cimetidine, in Proceedings of the Second International Symposium on Histamine H-2 Receptor Antagonists, edited by BURLAND WL, SIMKINS MA. Amsterdam, Oxford, Excerpta Medica, 1977 pp. 358-366. 17. BLONDE L, W I T K I N M, HARRIS R: Painless subacute thyroiditis similating Graves' disease. West J Med 125:75-78, 1976
Dalovisio et al. • Thyroiditis and Phosphatase
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Three patients had subacute thyroiditis and elevated serum alkaline phosphatase, presumably related to the thyroiditis. Concomitant elevation of the serum gamma-glutamyl transferase suggested that the alkaline phosphatase was of hepatic origin. The elevation of the serum alkaline phosphatase could not be definitely related to the degree or duration of elevation of the serum thyroxine. The combination of elevated serum alkaline phosphatase with the systemic symptoms of subacute thyroiditis may obscure the diagnosis, especially if patients have little or no neck pain.
S U B A C U T E (de Quervain) thyroiditis, a well-characterized clinical e n t i t y , h a s b e e n t h e subject of m a n y r e v i e w s (1-5). W e h a v e seen t h r e e p a t i e n t s w i t h s u b a c u t e t h y r o i d i tis w h o h a d m a r k e d a n d u n e x p l a i n e d e l e v a t i o n of t h e serum alkaline phosphatase, which declined toward norm a l in p a r a l l e l w i t h clinical a n d l a b o r a t o r y e v i d e n c e of t h e p a t i e n t s ' r e c o v e r y . A l i t e r a t u r e review f o u n d n o rep o r t s of a b n o r m a l i t i e s of t h e s e r u m a l k a l i n e p h o s p h a t a s e associated with subacute thyroiditis and, thus, p r o m p t e d this c o m m u n i c a t i o n .
Materials and Methods The charts of all patients seen at the Ochsner Medical Institutions between 1973 and 1977 who had been coded with a diagnosis of subacute thyroiditis were reviewed. We were able to retrieve the records of 20 patients with subacute thyroiditis. In 10, serum alkaline phosphatase measurements had been made during their clinical thyroiditis. The method of serum alkaline phosphatase measurement was either the Technicon Sequential Multiple Analyzer (SMA 12/60) method (Technicon Instrument Corporation, Tarrytown, New York) which is based on the work of Morgenstern and associates (6), or the CentrifiChem® test (Union Carbide Corporation, Rye, New York), a modification of the Bessey-Lowry-Brock method (7).
Results O f t h e 10 p a t i e n t s w h o s e s e r u m a l k a l i n e p h o s p h a t a s e w a s m e a s u r e d d u r i n g t h e c o u r s e of clinical t h y r o i d i t i s , t h r e e h a d e l e v a t e d levels w i t h o u t a p p a r e n t b o n e o r liver disease. I n all t h r e e p a t i e n t s t h e e l e v a t i o n s b e c a m e n o r m a l w i t h r e s o l u t i o n of t h e t h y r o i d i t i s . T h e i r case r e p o r t s follow. N i n e of t h e 10 p a t i e n t s for w h o m s e r u m a l k a l i n e • From the Department of Internal Medicine, Section on Infectious Disease and Section on Endocrinology and Metabolic Diseases, Ochsner Medical Institutions; New Orleans, Louisiana. Annals of Internal Medicine 8 8 : 5 0 5 - 5 0 7 , 1 9 7 8
Downloaded from https://annals.org by Tulane University user on 01/13/2019
p h o s p h a t a s e m e a s u r e m e n t s w e r e d o n e h a d e l e v a t e d ser u m thyroxine (T-4) values.
Case Reports PATIENT 1
A 47-year-old white man had a 3-week history of fever, malaise, and a 5-kg weight loss. A "sore-throat" resolved after the first few days of his illness. A throat culture was negative for beta hemolytic streptococci. He was admitted to another hospital where he continued to have daily temperature elevations to 39 °C. The result of serum alkaline phosphatase measurement exceeded the assay's maximal measurable value. There was no history of drug ingestion, hepatitis, or hepatotoxin exposure. He was transferred to Ochsner Foundation Hospital. Results of admission physical examination were unremarkable except for a mildly enlarged, nontender, non-nodular thyroid gland. Initial laboratory evaluation showed an erythrocyte sedimentation rate of 106 m m / h (Westergren) (Figure 1). The SMA 12/ 60 analysis showed a serum alkaline phosphatase of greater than 350 U/litre (normal, 30 to 100 U/litre) and a serum glutamic-oxalacetic transaminase (SGOT) of 58 U/litre (normal, 7 to 50 U/litre). Serum alkaline phosphatase done by the CentrifiChem method showed a value of 231 U/litre (normal, 25 to 80 U/litre). Serum gamma-glutamyl transferase (SGGT) was 252 U/litre (normal, 7 to 45 U/litre). Mono-test® (Wampole Laboratories, Cranbury, New Jersey) was negative. Hepatitis-B surface antigen measurement was not done. Other routine examinations yielded normal results. Results of technetium-99 sulphur colloid liver scan and technetium-99 pyrophosphate bone scan, obtained because of suspicion of neoplastic or infectious cause of serum alkaline phosphatase elevation, were normal. Results of ultrasound examination of the abdomen and a roentgenographic survey of the skeleton were normal. A gallium-67 citrate scan showed increased tracer localization in the region of the thyroid gland, more in the left thyroid lobe than the right (Figure 2). Serum T-4 by radioimmunoassay was 14.1 jug/dl (normal, 4.5 to 11.5 jixg/dl), T-3 uptake was 47.4% (normal, 35 to 4 5 % ) . A 24-h radioactive 131 I uptake was less than 1%. The clinical picture, in conjunction with the elevated T-4 and low radioactive m I uptake, appeared to confirm the diagnosis of subacute thyroiditis. Lack of thyroid pain and high serum alkaline phosphatase values initially obscured the diagnosis of subacute thyroiditis. The patient was seen 10 days after hospital discharge and his symptoms had resolved. Erythrocyte sedimentation rate (Westergren) was 53 m m / h . Serum alkaline phosphatase (CentrifiChem method) was 129 U/litre. The SGOT, serum T-4, and T3 uptake were normal. The patient was not receiving salicylates or adrenal steroids. Nine weeks after the patient's initial symptoms, erythrocyte sedimentation rate, and serum alkaline phosphatase, SGOT, T-4 and T-3 uptake were all normal. PATIENT 2
A 36-year-old white man had a 5-week history of severe fa© 1 9 7 8 American College of Physicians
505
Two weeks after onset of this illness, the patient was evaluated at the Ochsner Clinic. He reported taking cimetidine for 25 days for peptic ulcer disease. The medication had been withdrawn 1 week after onset of the fever and neck pain. Examination showed a nodular, firm, nontender thyroid gland that was twice normal size. N o other abnormalities were found. Laboratory studies showed an erythrocyte sedimentation rate (Westergren) of 87 m l / h and a serum alkaline phosphatase (SMA 12/60 method) of 272 U/litre. The remainder of the SMA 12/60 results were normal. An S G O T measurement done manually was 27 U/litre (normal, 4 to 20 U/litre). Repeat serum alkaline phosphatase measurement (CentrinChem method) was 175 U/litre. Serum T-4 was 17.5 jutg/dl, and T-3 uptake was 53.8%. Hepatitis-B surface antigen determination was not done. Twenty-four-hour radioactive m I uptake was less than 1%. These laboratory studies strongly suggested the diagnosis of subacute thyroiditis. In 6 weeks all symptoms had resolved. Repeat erythrocyte sedimentation rate, serum alkaline phosphatase, SGOT, T-3 uptake, and T-4 measurements were within normal limits. Discussion
Figure 1 . Temporal progression of laboratory values of Patients 1, 2, and 3. ESR = erythrocyte sedimentation rate.
tigue, recurrent nightly temperature to 38 °C, anorexia, a 6-kg weight loss, dysphagia, and posterior cervical pain. Past history was unremarkable. Heart rate was 110/min, and the thyroid gland was three times normal size, extremely firm, and mildly tender. The remainder of the physical examination was normal. Initial laboratory work showed an erythrocyte sedimentation rate (Westergren) of 71 m m / h . Results from SMA 12/60 analysis were normal with the exception of a serum calcium level of 10.7 m g / d l (normal, 8.5 to 10.3 mg/dl), S G O T of 67 U/litre, and serum alkaline phosphatase greater than 350 U/litre. Serum glutamic pyruvic transaminase (SGPT) was 57 U/litre (normal, 4 to 20 U/litre). Serum alkaline phosphatase (CentrifiChem method) was 226 U/litre. Sodium sulfobromophthalein excretion was 1 3 % (normal, 0 to 6%). The S G G T level was 163 U/litre. Hepatitis-B surface antigen was negative. Serum T-4 was 12.9 jag/dl, T-3 uptake was 4 6 . 1 % , and serum triiodothyronine (T-3) by radioimmunoassay was 307 ng/dl (normal, 70 to 210 ng/dl). Radioactive m I uptake at 24 h was less than 1%. A provisional diagnosis of subacute thyroiditis was made and the patient was given aspirin as needed for pain. When he was seen again 6 weeks later, the erythrocyte sedimentation rate, serum T-4, and T-3 uptake were normal. Results from S M A 12/60 analysis, including calcium and SGOT, were normal with the exception of a mildly elevated serum alkaline phosphatase of 120 U/litre. The patient's pulse rate was 80 beats/min. He was asymptomatic. Subsequent follow-up has indicated no evidence of thyroid or hepatic dysfunction, and the thyroid enlargement has abated. A repeat serum alkaline phosphatase done 14 weeks after the patient's onset of symptoms was normal.
Patients with thyrotoxicosis have been reported to h a v e e l e v a t i o n of t h e s e r u m a l k a l i n e p h o s p h a t a s e , b u t t h e r e h a s b e e n n o c o n c l u s i v e d e t e r m i n a t i o n of t h e s o u r c e tissue (8-10). T h e effects of h y p e r t h y r o i d i s m o n b o n e m e t a b o l i s m a r e c o m p l e x a n d n o t c o m p l e t e l y u n d e r s t o o d (9, 11, 12). M i l d , nonspecific a b n o r m a l i t i e s of liver e n z y m e s , s e r u m bilirubin, a n d liver h i s t o l o g y h a v e also b e e n d e s c r i b e d in p a t i e n t s w i t h h y p e r t h y r o i d i s m a n d a r e s i m i l a r ly u n e x p l a i n e d (8, 10, 13, 14). T e n p a t i e n t s in o u r s t u d y h a d c o n c o m i t a n t m e a s u r e m e n t s of t h e s e r u m T - 4 a n d ser u m a l k a l i n e p h o s p h a t a s e . N i n e of 10 h a d significant elev a t i o n of t h e s e r u m T-4, yet o n l y t h r e e h a d e l e v a t i o n s of t h e s e r u m a l k a l i n e p h o s p h a t a s e . T h e p a t h o p h y s i o l o g y of t h e elevated s e r u m a l k a l i n e p h o s p h a t a s e in t h e s e p a t i e n t s is u n k n o w n . It c a n n o t b e definitely r e l a t e d t o t h e d e g r e e of T - 4 e l e v a t i o n b e c a u s e [1] t h e p a t i e n t w i t h s u b a c u t e t h y r o i d i t i s w i t h t h e h i g h e s t T - 4 v a l u e h a d a n o r m a l ser u m a l k a l i n e p h o s p h a t a s e , a n d [2] in P a t i e n t s 1 a n d 2 t h e s e r u m T - 4 n o r m a l i z e d l o n g before t h e s e r u m a l k a l i n e p h o s p h a t a s e . D a m a g e t o t h e liver f r o m t h e as yet u n i d e n tified etiologic a g e n t (2, 5) of s u b a c u t e t h y r o i d i t i s c o u l d
PATIENT 3
A 47-year-old white man from Mexico had fever and diarrhea, diagnosed as shigellosis, and was treated with ampicillin and furazolidone. His symptoms resolved, but 1 week later he began to have a low-grade fever and mild anterior neck pain. An upper gastrointestinal series and liver scan were reportedly normal. c/\g
April 1978 • Annals of Internal Medicine • Volume 88 • Number 4
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Figure 2A. Anterior view of gallium-67 citrate scan showing increased uptake in thyroid gland. B. Posterior view.
be postulated. All three of these patients had concomitant elevation of the SGOT and SGGT, which suggests, but does not prove, that the serum alkaline phosphatase elevation was of hepatic rather than osseous origin (15). Several other aspects of these case reports deserve comment. The temporal correlation of the serum alkaline phosphatase elevation with the clinical picture of subacute thyroiditis in Patients 1 and 2 and the absence of other demonstrable causes for the serum alkaline phosphatase abnormality suggests that these two processes are in some way related. In the third case, the increase in the serum alkaline phosphatase and SGOT could be related to the patient's ingestion of cimetidine, although cimetidine has not been conclusively shown to be hepatotoxic (16). It is interesting that the gallium scan in Patient 1 showed increased tracer localization in the area of the thyroid gland. We are unaware of any other reports of gallium scans in subacute thyroiditis. The transient hypercalcemia noted in Patient 2 may be a reflection of the effect of the elevated levels of thyroid hormone analogous to the hypercalcemia seen with hyperthyroidism from other causes. These cases show that subacute thyroiditis may mimic much more serious illnesses. The presence of elevated serum alkaline phosphatase and erythrocyte sedimentation rate, prolonged fever, and weight loss, especially when neck pain is minimal or absent (17), may suggest the diagnosis of liver abscess, granulomatous hepatic disease, or malignant neoplasm rather than subacute thyroiditis. In patients who have serum alkaline phosphatase elevation without an apparent source, thyroid function should be evaluated because subacute thyroiditis, as well as thyrotoxicosis, can be associated with elevation of the serum alkaline phosphatase. ACKNOWLEDGMENTS: Received 29 August 1977; revision accepted 7 December 1977.
• Requests for reprints should be addressed to Joseph R. Dalovisio, M.D.; Ochsner Clinic; 1514 Jefferson Highway; New Orleans, LA 70121.
References
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