Hyperparathyroidism with Coexisting Hyperthyroidism Norman 8. Ackerman, MD, PhD,’ Kansas City, Missouri R. F. Arribas, MD, Kansas City, Missouri
Hypercalcemia may be caused by a variety of conditions other than those arising directly from the parathyroid glands. With the advent of better diagnostic aids and a high index of suspicion among clinicians, differentiation between primary hyperparathyroidism and hypercalcemia from other causes is becoming less of a problem. However, a difficulty arises when primary hyperparathyroidism occurs concomitantly with other potential calcium-producing conditions. One uncommon but challenging situation is hyperparathyroidism with coexisting hyperthyroidism. Hyperthyroidism may cause an increase in the serum calcium, possibly due to an increased resorption of bone or to alterations in calcitonin secretion. Hypercalcemia in patients with concurrent hyperthyroidism and primary hyperparathyroidism is rare, with only eighteen reported cases. The present report describes an additional patient and reviews the approach to management. Case Report The patient, a thirty year old female, was first seen a year prior to her admission to the hospital in the Endocrine Clinic, where she was evaluated for complaints of frequent palpitations and extreme nervousness. This was two months after she delivered her second child, who was born with congenital hypoparathyroidism. On physical examination, the patient was found to have high blood pressure, exaggerated tremors of both hands and an enlarged, multinodular thyroid gland. Her laboratory results included elevated thyroxine and increased iodine 131 uptake. Results on serum auto-analyzer (SMA-12) showed serum calcium level within normal limits with low inorganic phosphate and an increased alkaline phosphatase level. Thyroid scan with radioiodine revealed diffuse enlargement of the thyroid gland, especially the right lobe. Chest x-ray examination showed demineralization of the distal portions of the clavicles, and additional x-ray examinations showed demineralization of the calvarium and lytic areas in the greater trochanter of the right
From the Department of Surgery, The University of Missouri-Kansas City, Menorah Medical Center. Kansas City, Misswi. ’ Present address and reprint requests: Department of Surgery, State University of New York, Upstate Medical Center. Syracuse, New York 13210.
660
femur. A possible concurrent diagnosis of hyperparathyroidism was considered because of these findings. X-ray examination of both hands showed nothing abnormal. The patient was given propylthiouracil, 100 mg four times a day. After one month of treatment her symptoms improved and she became euthyroid. At this time, her serum calcium level was found to be elevated (11.8 mg/lOO ml). On serial examinations thereafter, the serum calcium levels fluctuated from normal to elevated levels. After two months of antithyroid treatment, she discontinued her clinic visits and was not seen again until eight months later, when she presented herself to the clinic with overt symptoms of hyperthyroidism. When interviewed, it was learned that she had not been taking her medications regularly. She complained of irregular menses, intermittent pedal edema, generalized body weakness, joint pains, particularly of the shoulders, and frequent dysuria. At this time, her serum calcium level remained persistently elevated, ranging from 11.0 to 11.8 mg/lOO ml. Repeat x-ray examinations of both hands showed thinning of the cortex of the proximal and middle phalanges bilaterally. Propranolol, 40 mg daily, was substituted for propylthiouracil, and after three weeks of treatment she became clinically euthyroid. She was subsequently admitted to the hospital with a serum calcium level of 11.2 mg/lOO ml. Subtotal thyroidectomy was performed and exploration of the neck yielded a 2.1 gm parathyroid adenoma at the right lower pole of the thyroid gland. Her postoperative course was uneventful. Serum calcium level decreased to 9.8 mg/109 ml on the first postoperative day and remained within normal limits until her discharge from the hospital and on subsequent clinic follow-ups. She also has remained euthyroid. Comments
The frequency of hypercalcemia in patients with hyperthyroidism is not known, but it is not believed to be rare. In patients with hypercalcemia, the differentiation between hyperthyroidism and primary parathyroid disease may be difficult. As pointed out by Torsti and Lamberg [I], many of the clinical symptoms associated with elevated serum calcium levels are nonspecific and can occur in patients with hyperthyroidism. There are no tests that can distinguish between these two conditions, with the probable exception of parathyroid hormone radioimmunoassay. Patients with hyperthyroidism had parathyroid hormone levels less than those of normal
TheAnwkan
Journal 04 Surgery
Hyperparathyroidism
control patients in a recent preliminary study by Bouillon and DeMoor [2]. Bortz et al [3] considered measurement of the renal tubular reabsorption of phosphate useful in differentiating between thyroid and parathyroid causes of hypercalcemia, but these findings were not confirmed by Breuer and McPherson [4]. Radiologic examination of the bones in both conditions may indicate demineralization, but the patterns are usually different. Bone cysts, absent lamina dura, and phalangeal reabsorption are more commonly found in parathyroid disease. The best clinical test in patients with known hyperthyroidism suggesting the possibility of coexisting hyperparathyroidism is the response of the serum calcium level to the antithyroid medication. As mentioned by Bortz et al [3] and Rao [5], elevated serum calcium level should return to normal limits when the thyrotoxicosis comes under control by appropriate drug therapy, if the hypercalcemia is due to hyperthyroidism. The diagnosis in the present case, which is the nineteenth to be reported, was initially suggested by the radiologic findings and strongly confirmed by the persistence of hypercalcemia when the patient became euthyroid on propylthiouracil medication. Combined operation for these two conditions is relatively easy; the search for a parathyroid tumor as well as identification of normal parathyroid glands is facilitated by subtotal thyroidectomy. Of added interest in this case is the fact that shortly before the patient was first seen for her endocrine complaints, she delivered a child who was born with congenital hypoparathyroidism. This is a similar situation to that recently described by Better et al [6] in which the neonatal hypoparathyroidism was secondary to asymptomatic maternal hyper-
Vnhwna 182. November
1976
with Hyperthyroidism
parathyroidism. It is believed that the suppression of the fetal parathyroid glands is due to the maternal and fetal hypercalcemia rather than placental crossover of increased circulating parathyroid hormone. Suspicion of hyperparathyroid disease should be directed towards the mother when infants are born with hypoparathyroidism. Summary
Diagnosis of parathyroid disease in patients with hyperthyroidism may be difficult on clinical findings alone. Radiologic examination of the bones suggested the possibility of parathyroid disease in this patient. Confirmation of the diagnosis was made when serum calcium levels remained elevated in spite of adequate antithyroid medication. Measurement of serum parathyroid hormone levels may prove to be of greatest value. Of additional interest is the fact that the patient, before her symptoms became apparent, delivered an infant with congenital hypoparathyroidism. References 1. Torsti P, Lamberg BA: Coexisting hyperthyroidism and hyperparathyroidism. Acta Med Stand 174: 115, 1963. 2. Bouillon R, DeMoor P: Parathyroid function in patients with hyperor hypothyroidism. J C/in Endocrinol38: 999, 1974. 3. Bortz W, Eisenberg E, Bowers CY, Pont M: Differentiation between thyroid and parathyroid causes of hypercalcemia. Ann Intern Med54: 610. 1961. 4. Breuer RI, McPherson HT: Hypercalcemia in concurrent hyperthyroidism and hyperparathyroidism. Arch intern Med 118: 310, 1966. 5. Rao KM: Concurrent hyperthyroidism and hyperparathyroidism. Sr J Surg 57: 868, 1970. 6. Better OS, Levi J, Greif E, Tuma S, Gellei B, Erlik D: Prolonged neonatal parathyroid suppression. A sequel to asymptomatic maternal hyperparathyroidism. Arch Surg 106: 722, 1973.
661
Hypercalcemia may be caused by a variety of conditions other than those arising directly from the parathyroid glands. With the advent of better diagnostic aids and a high index of suspicion among clinicians, differentiation between primary hyperparathyroidism and hypercalcemia from other causes is becoming less of a problem. However, a difficulty arises when primary hyperparathyroidism occurs concomitantly with other potential calcium-producing conditions. One uncommon but challenging situation is hyperparathyroidism with coexisting hyperthyroidism. Hyperthyroidism may cause an increase in the serum calcium, possibly due to an increased resorption of bone or to alterations in calcitonin secretion. Hypercalcemia in patients with concurrent hyperthyroidism and primary hyperparathyroidism is rare, with only eighteen reported cases. The present report describes an additional patient and reviews the approach to management. Case Report The patient, a thirty year old female, was first seen a year prior to her admission to the hospital in the Endocrine Clinic, where she was evaluated for complaints of frequent palpitations and extreme nervousness. This was two months after she delivered her second child, who was born with congenital hypoparathyroidism. On physical examination, the patient was found to have high blood pressure, exaggerated tremors of both hands and an enlarged, multinodular thyroid gland. Her laboratory results included elevated thyroxine and increased iodine 131 uptake. Results on serum auto-analyzer (SMA-12) showed serum calcium level within normal limits with low inorganic phosphate and an increased alkaline phosphatase level. Thyroid scan with radioiodine revealed diffuse enlargement of the thyroid gland, especially the right lobe. Chest x-ray examination showed demineralization of the distal portions of the clavicles, and additional x-ray examinations showed demineralization of the calvarium and lytic areas in the greater trochanter of the right
From the Department of Surgery, The University of Missouri-Kansas City, Menorah Medical Center. Kansas City, Misswi. ’ Present address and reprint requests: Department of Surgery, State University of New York, Upstate Medical Center. Syracuse, New York 13210.
660
femur. A possible concurrent diagnosis of hyperparathyroidism was considered because of these findings. X-ray examination of both hands showed nothing abnormal. The patient was given propylthiouracil, 100 mg four times a day. After one month of treatment her symptoms improved and she became euthyroid. At this time, her serum calcium level was found to be elevated (11.8 mg/lOO ml). On serial examinations thereafter, the serum calcium levels fluctuated from normal to elevated levels. After two months of antithyroid treatment, she discontinued her clinic visits and was not seen again until eight months later, when she presented herself to the clinic with overt symptoms of hyperthyroidism. When interviewed, it was learned that she had not been taking her medications regularly. She complained of irregular menses, intermittent pedal edema, generalized body weakness, joint pains, particularly of the shoulders, and frequent dysuria. At this time, her serum calcium level remained persistently elevated, ranging from 11.0 to 11.8 mg/lOO ml. Repeat x-ray examinations of both hands showed thinning of the cortex of the proximal and middle phalanges bilaterally. Propranolol, 40 mg daily, was substituted for propylthiouracil, and after three weeks of treatment she became clinically euthyroid. She was subsequently admitted to the hospital with a serum calcium level of 11.2 mg/lOO ml. Subtotal thyroidectomy was performed and exploration of the neck yielded a 2.1 gm parathyroid adenoma at the right lower pole of the thyroid gland. Her postoperative course was uneventful. Serum calcium level decreased to 9.8 mg/109 ml on the first postoperative day and remained within normal limits until her discharge from the hospital and on subsequent clinic follow-ups. She also has remained euthyroid. Comments
The frequency of hypercalcemia in patients with hyperthyroidism is not known, but it is not believed to be rare. In patients with hypercalcemia, the differentiation between hyperthyroidism and primary parathyroid disease may be difficult. As pointed out by Torsti and Lamberg [I], many of the clinical symptoms associated with elevated serum calcium levels are nonspecific and can occur in patients with hyperthyroidism. There are no tests that can distinguish between these two conditions, with the probable exception of parathyroid hormone radioimmunoassay. Patients with hyperthyroidism had parathyroid hormone levels less than those of normal
TheAnwkan
Journal 04 Surgery
Hyperparathyroidism
control patients in a recent preliminary study by Bouillon and DeMoor [2]. Bortz et al [3] considered measurement of the renal tubular reabsorption of phosphate useful in differentiating between thyroid and parathyroid causes of hypercalcemia, but these findings were not confirmed by Breuer and McPherson [4]. Radiologic examination of the bones in both conditions may indicate demineralization, but the patterns are usually different. Bone cysts, absent lamina dura, and phalangeal reabsorption are more commonly found in parathyroid disease. The best clinical test in patients with known hyperthyroidism suggesting the possibility of coexisting hyperparathyroidism is the response of the serum calcium level to the antithyroid medication. As mentioned by Bortz et al [3] and Rao [5], elevated serum calcium level should return to normal limits when the thyrotoxicosis comes under control by appropriate drug therapy, if the hypercalcemia is due to hyperthyroidism. The diagnosis in the present case, which is the nineteenth to be reported, was initially suggested by the radiologic findings and strongly confirmed by the persistence of hypercalcemia when the patient became euthyroid on propylthiouracil medication. Combined operation for these two conditions is relatively easy; the search for a parathyroid tumor as well as identification of normal parathyroid glands is facilitated by subtotal thyroidectomy. Of added interest in this case is the fact that shortly before the patient was first seen for her endocrine complaints, she delivered a child who was born with congenital hypoparathyroidism. This is a similar situation to that recently described by Better et al [6] in which the neonatal hypoparathyroidism was secondary to asymptomatic maternal hyper-
Vnhwna 182. November
1976
with Hyperthyroidism
parathyroidism. It is believed that the suppression of the fetal parathyroid glands is due to the maternal and fetal hypercalcemia rather than placental crossover of increased circulating parathyroid hormone. Suspicion of hyperparathyroid disease should be directed towards the mother when infants are born with hypoparathyroidism. Summary
Diagnosis of parathyroid disease in patients with hyperthyroidism may be difficult on clinical findings alone. Radiologic examination of the bones suggested the possibility of parathyroid disease in this patient. Confirmation of the diagnosis was made when serum calcium levels remained elevated in spite of adequate antithyroid medication. Measurement of serum parathyroid hormone levels may prove to be of greatest value. Of additional interest is the fact that the patient, before her symptoms became apparent, delivered an infant with congenital hypoparathyroidism. References 1. Torsti P, Lamberg BA: Coexisting hyperthyroidism and hyperparathyroidism. Acta Med Stand 174: 115, 1963. 2. Bouillon R, DeMoor P: Parathyroid function in patients with hyperor hypothyroidism. J C/in Endocrinol38: 999, 1974. 3. Bortz W, Eisenberg E, Bowers CY, Pont M: Differentiation between thyroid and parathyroid causes of hypercalcemia. Ann Intern Med54: 610. 1961. 4. Breuer RI, McPherson HT: Hypercalcemia in concurrent hyperthyroidism and hyperparathyroidism. Arch intern Med 118: 310, 1966. 5. Rao KM: Concurrent hyperthyroidism and hyperparathyroidism. Sr J Surg 57: 868, 1970. 6. Better OS, Levi J, Greif E, Tuma S, Gellei B, Erlik D: Prolonged neonatal parathyroid suppression. A sequel to asymptomatic maternal hyperparathyroidism. Arch Surg 106: 722, 1973.
661
