Longitudinal studies of mild primary hyperparathyroidism.

In 1969, a health survey was offered to all inhabitants of a town district in Sweden. A clinical examination was carried out, and among other variables, a measurement was made of serum calcium. The same procedure was repeated in 1971. From these two investigations a cohort of 176 individuals (1.1%) with sustained hypercalcemia was identified who could be followed during the subsequent 15 years. Comparisons were made with an age- and sex-matched control group from the same health survey. Survival was significantly lower in the hypercalcemic cohort than in the control group. This reduction was related to the degree of hypercalcemia and apparently mainly due to diseases of the circulatory organs. There was no marked deterioration of renal function, and although there was in some patients a moderate progression of the hypercalcemia, none developed a hypercalcemic crisis during 15 years of follow-up. In consecutively referred patients with primary hyperparathyroidism, psychiatric disturbances of mainly a depressive character were found upon detailed analysis within a majority of the patients, and parathyroid surgery resulted in a clear improvement in mental health.

Psychiatric symptoms and cerebrospinal fluid monoamine metabolites in primary hyperparathyroidism.

This prospective study included 32 patients with primary hyperparathyroidism (HPT). As compared with a healthy reference group, the patients had pronounced psychiatric symptomatology [CPRS score 17.2 +/- 9.0 (SD) versus 4.4 +/- 2.0], which was mainly affective in character. The severity of symptoms was not related to the serum calcium or parathyroid hormone concentrations. The majority of the patients had low CSF concentrations of monoamine metabolites (5-HIAA, HVA, and MHPG) and, in particular, those with the most severe psychiatric symptoms had low values for 5-HIAA. At follow-up, 1 year after parathyroid surgery, the patients displayed a clear improvement in mental health (CPRS score 4.4 +/- 3.0) together with an increase in CSF concentrations of 5-HIAA and HVA. The study demonstrates that significant psychiatric disturbances, which can be improved/normalized by surgery, are common in patients with HPT and are possibly related to changes in the central nervous system turnover of monoamines.

Cerebrospinal fluid calcium, parathyroid hormone, and monoamine and purine metabolites and the blood-brain barrier function in primary hyperparathyroidism.

Psychiatric disturbances are common in primary hyperparathyroidism (HPT), but their pathogenesis is essentially unknown. This study deals with cerebrospinal fluid (CSF) calcium homeostasis and its connection with parathyroid hormone (PTH), blood-brain barrier (BBB) function, and central monoamine and purine metabolites in patients with primary HPT. In 22 patients with primary HPT (serum calcium 2.85 +/- 0.21 mmol/l), the CSF concentrations of total and ionized calcium were higher (1.21 +/- 0.08 mmol/l, p less than 0.01, and 1.09 +/- 0.05 mmol/l, p less than 0.001, respectively) than in 11 normocalcemic reference subjects. The values correlated with serum calcium concentration (p less than 0.001) and CSF/serum albumin ratio, a measure of BBB permeability. The latter ratio was elevated in one-third of the patients with HPT, indicating BBB damage. CSF immunoreactive intact PTH was higher in the HPT patients than in the reference group (p less than 0.05), and serum and CSF PTH were positively correlated (p less than 0.05). The CSF levels of the monoamine metabolites 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) were lower, and the level of urate in CSF was higher, in the HPT patients than in the reference subjects, while there were no consistent differences in CSF hypoxanthine or xanthine. CSF 5HIAA correlated inversely with CSF ionized calcium (r = -0.42, p = 0.02). After parathyroid surgery, CSF calcium and urate decreased significantly and CSF monoamine metabolites increased slightly. The decrease in CSF ionized calcium correlated with the alleviation of psychiatric symptoms. The results indicate the importance of increased CSF calcium concentrations in patients with primary HPT and suggest a relation between central calcium regulation and central turnover of monoamines.

Self-rated psychiatric symptoms in patients operated on because of primary hyperparathyroidism and in patients with long-standing mild hypercalcemia.

Self-rated psychiatric symptoms were investigated in 30 patients referred for surgery because of primary hyperparathyroidism (HPT) (serum calcium, 2.87 +/- 0.21 mmol/L) in 38 subjects detected in a health screening, with 15 years of mild hypercalcemia and probable HPT (serum calcium, 2.66 +/- 0.09 mmol/L), and in 38 normocalcemic control subjects. The psychiatric symptomatology was evaluated by use of the Hopkins Symptom Checklist (HSCL-56), a self-rating symptom scale. The patients with verified HPT had the highest mean HSCL score, 89.1 +/- 20.1 before surgery, compared with 76.6 +/- 17.0 (p less than 0.01) in the health survey hypercalcemic patients and 73.8 +/- 16.0 (p less than 0.001) in the controls. The factors for anxiety, depression, and cognitive symptoms were the most pronounced in the HPT patients and were also increased among the mildly hypercalcemic persons of the health survey, compared with the controls. Somatic symptoms such as headache, back pain, chest pain, and weakness were equally common in HPT and in the controls, and measurements of isometric muscle strength of knee extension did not demonstrate reduction of muscle strength in the health survey hypercalcemic patients. Follow-up of the HPT patients 1 year after parathyroid surgery revealed a marked improvement in mental health (HSCL score 73.2 +/- 13.7, p less than 0.001). In the health survey hypercalcemic patients, neither the psychiatric symptomatology nor the muscle strength were influenced by 6 months of oral vitamin D therapy (alphacalcidol). The results demonstrate that psychiatric symptoms are experienced frequently by patients with HPT and minimum to moderate increases in the serum calcium level and that these disturbances are reversed by parathyroid surgery.

Psychiatric symptomatology in patients with primary hyperparathyroidism.

A retrospective investigation was made of the occurrence of psychiatric symptoms among 441 patients operated on for primary hyperparathyroidism in Uppsala in 1956-79, and of the relationship between such symptoms and age, sex and degree of hypercalcaemia. A follow-up, using a mailed questionnaire, was carried out 4-27 years postoperatively. Psychiatric symptoms were found in 23% of the patients (102/441). The patients with these symptoms had the same sex distribution and serum calcium levels as the other patients, but were significantly older. Severe symptoms occurred more frequently in older patients. Such symptoms were noted not only in patients with very high serum calcium values but also in association with mild or moderate hypercalcaemia. The most common symptoms were depressive and anxiety states, which occurred in 78 patients. Psychosis with hallucinations and paranoid ideas was found in four patients. Eight patients had an organic brain syndrome and a further 12 patients had minor cerebral impairment. At the follow-up half of the patients reported an improvement after the first postoperative year. Most of them considered that this improvement was sustained at the time of follow-up. This study indicates that psychiatric symptoms are common among patients with hyperparathyroidism and can occur even with moderate hypercalcaemia. Elderly patients seem to be more vulnerable and more often develop severe symptoms such as psychosis or organic brain syndrome.

[Primary hyperparathyroidism--a frequently overlooked cause of psychological symptoms]. / Primär hyperparatyreoidism--en ofta förbisedd orsak till psykiska besvär.

Studies in recent years have demonstrated that nervous symptoms are common in hyperparathyroidism but that they are often overlooked even in very serious cases. The mechanisms behind the symptoms have to some extent been surveyed and show that operation, which normalizes the parathyroid function, also leads as a rule to considerable improvement of the patient's nervous symptoms.

Maximal isokinetic muscle strength in patients with primary hyperparathyroidism before and after parathyroid surgery.

Primary hyperparathyroidism (HPT) is associated with symptoms of generalized fatigue and muscle weakness. The purpose of this study was to investigate muscular function in HPT quantitatively and to evaluate the effect of parathyroid surgery in this respect. The maximal isokinetic muscle strength (peak torque) of knee extension and flexion was measured with a Cybex-II dynamometer in 16 patients with primary HPT (mean serum calcium 2.81 +/- 0.14 mmol/l), four of whom had subjective impairment of strength, and in nine control patients submitted to hemithyroidectomy due to atoxic thyroid adenoma. Before surgery there was no significant difference in muscle strength between the two groups, neither was there any consistent relationship between the subjective feeling of muscular weakness and the measured peak torque. Seven months after surgery the HPT patients had increased their muscle strength by 8 per cent (P less than 0.05). The improvement was correlated with the pre-operative serum calcium levels (r = 0.56, P = 0.02) and was particularly seen in patients with pre-operative subjective muscular weakness. Patients with only slightly raised calcium values and without subjective muscular symptoms did not benefit clearly from surgery, compared with the controls. The study demonstrates that HPT patients, especially those with neuromuscular symptoms, can improve their muscle strength after parathyroid surgery.

Muscle function in patients with primary hyperparathyroidism.

The muscle contraction of the anterior tibial muscle was investigated by measurements of electrically stimulated and computer-analyzed muscle twitches in 18 unselected patients with primary hyperparathyroidism (HPT) and in 20 healthy control persons. The HPT patients had a lower muscle twitch tension (TT) at single stimulation, compared with the control group [76 +/- 24 N (SD) and 99 +/- 33 N respectively, P less than 0.05]. At high-frequency stimulation the difference in muscle force increased, and at 20 Hz stimulation the force in the HPT patients was 73% of that in the controls (P less than 0.01). There were no differences between the HPT patients and the control persons in neither contraction time nor half relaxation time at single muscle twitch nor in twitch potentiation after 20 and 90 seconds maximal voluntary contraction. The results indicate that patients with primary HPT have an impaired muscle function of probable importance for their symptoms of weakness and generalized fatigue.

Primary hyperparathyroidism in patients with organic brain syndrome.

In a retrospective study of 552 patients operated on for primary hyperparathyroidism (HPT) the effects of parathyroid surgery were selectively investigated in 13 elderly patients with organic brain syndrome. With a few exceptions, these 13 patients had mild or moderate hypercalcaemia but severe mental impairment. Ten patients had a clinical diagnosis of senile dementia and 12 had been admitted from a mental hospital. Postoperatively, eight patients improved mentally and seven of them were able to return to their homes or could be transferred to somatic units. The eight patients who showed improvement, either temporary or more permanent, had a relatively short duration of mental symptoms preoperatively, all less than 2 years, while those who did not improve mentally after surgery had a longer history of mental illness. Screening for HPT was subsequently performed in a psychogeriatric clinic to investigate the prevalence of HPT in this population. Hypercalcaemia and probable HPT was found in five (5%) of 101 patients. The results indicate that parathyroidectomy may improve the mental state in patients with HPT and organic brain syndrome. As a substantial number of patients in a psychogeriatric population seem to have HPT, the disease should be searched for in patients with newly diagnosed organic brain syndrome.

Skeletal responsiveness to parathyroid hormone in healthy females: relationship to menopause and oestrogen replacement.

In order to directly evaluate the role of parathyroid hormone (PTH) and its interaction with oestrogens for postmenopausal bone loss, studies were performed where synthetic human (1-38) PTH was infused s.c. over 24 h in 15 healthy females. Measurements were made of serum electrolytes, PTH and biochemical indices of bone turnover: serum osteocalcin and alkaline phosphatase and fasting urinary hydroxyproline and calcium. During the infusion of PTH there were significant increases of serum calcium (15%), fasting urinary calcium (55%) and hydroxyproline (80%) but a reduction of the serum osteocalcin concentrations (15%). There were significant relations between the calcaemic response and the increases of urinary calcium and hydroxyproline and the two latter were also closely related. There was, however, no correlation between the responses to PTH for the formative vs the resorptive indices. Postmenopausal women displayed greater increases of serum calcium and fasting urinary hydroxyproline indicating greater skeletal sensitivity to exogenous PTH. Following treatment with oestrogens the indices of skeletal responsiveness were reversed towards the premenopausal values. The findings demonstrate that during short-term infusion of PTH there is a dissociation between bone resorption and formation and, furthermore, that the menopause is associated with an enhanced skeletal sensitivity for PTH.