Characteristic changes in psychiatric symptoms, cortisol and melatonin but not prolactin in primary hyperparathyroidism

Psychiatric symptoms in primary hyperparathyroidism (PHPT) are usually characterized as depressive. In this study 13 patients with PHPT and six control patients with atoxic nodular goiter underwent psychiatric ratings with the comprehensive psychopathological rating scale (CPRS) the day before surgery. The 21 items in this scale were grouped into clusters. The ratings were repeated after successful removal of a parathyroid adenoma. Diurnal serum concentrations of cortisol, melatonin and prolactin were studied pre- and postoperatively in eight of the patients. Patients with PHPT had significantly higher CPRS total scores, 8.5 +/- 1.3, compared with goiter controls, 1.9 +/- 0.8, and showed a significant improvement of psychiatric symptoms after excision of the parathyroid adenoma, to 3.3 +/- 0.9. The preoperative diurnal and peak levels of cortisol and melatonin were higher (P less than 0.05) than after surgery. Serum melatonin fell to levels lower than those in healthy controls. Correlations were found between some clusters or items and cortisol or melatonin. Serum prolactin levels were normal and unaltered by parathyroid surgery. It is concluded that patients with PHPT show well defined psychiatric symptoms many of which are correlated to alterations in serum cortisol and melatonin accompanying PHPT. The improvement of symptoms seen after successful surgery further suggests that PHPT is associated with a specific psychiatric disorder similar to but distinguishable from major depressive disorder.     

Psychosis resulting in suicide in a patient with primary hyperparathyroidism

A case is reported of a patient presenting to the psychiatric unit of our hospital with symptoms of depression and found to have an organic psychosis. On routine SMA-12 investigation (12 channel auto analyzer), elevated serum calcium was detected on admission leading to the diagnosis of primary hyperparathyroidism (PHPT). The surgical removal of a parathyroid adenoma was followed by a rapid return of biochemical abnormalities to normal ranges. In spite of appropriate psychiatric management and fluctuations in the patient's clinical condition, the organic psychosis was unaltered and culminated in suicide 4 months after admission.     

Depression as a manifestation of latent chronic hypoparathyroidism.

The exact cause of depression in cases of hypoparathyroidism is not known. We report the first case of an elderly patient with a long history of major depression as a complication of an undiagnosed chronic hypoparathyroidism following surgery on a parathyroid adenoma. Her depression was completely eliminated by calcium supplementation therapy to restore the calcium homeostasis in serum. As it is well known that disturbances in the endocrine hypothalamus-pituitary-thyroid system might be consistent findings of depressive disorders concerning neuroendocrinological alterations, this case report and review of literature strongly supports our claim that also parathyroid diseases like chronic hypoparathyroidism, even in its latent form, might be a relevant factor in the development of depressive symptoms.     

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.     

Dementia as presenting symptom of primary hyperparathyroidism: favourable outcome after surgery

The case of a 76-year-old female patient is presented with a two-year history of progressive dementia, apathy and gait impairment. Initially, Alzheimer's disease was diagnosed and she was given donepezil for one year with no significant improvement. An extensive blood and biochemical control revealed high serum calcium and parathormone levels, and normal thyroid hormones and anti-thyroid antibodies. Ultrasound of thyroid and parathyroid glands revealed an adenoma of the right parathyroid. The detailed investigation for causes of secondary hyperparathyroidism was negative. Due to the absence of clinical hyperparathyroidism she was initially treated conservatively. At referral, the neurological picture consisted of: mild signs of parkinsonism, moderate dementia (MMSE=15) and severe behavioural disturbances. Because of the continuous aggravation of the cognitive deficit, parathyroidectomy was decided although there were no clinical or laboratory signs of involvement from other organs. Three weeks after the operation the neurological picture showed dramatical improvement. Parkinsonism and behavioural disorders were remarkably reduced and the MMSE score raised to 25. In summary we report an exceptional case of primary hyperparathyroidism (PHPT) presenting as dementia and treated successfully by parathyroidectomy.     

Neuropsychiatric disorders in primary hyperparathyroidism

This is a report of two middle-aged women whose diagnosis of PHPT was made on hypercalcemia during treatment of depression and paranoid state, leading to the surgical confirmation of parathyroid adenoma. After the operation, their mental symptoms disappeared as the blood level of calcium was depressed in both cases, and there has been no recurrence for 12 and 18 months, respectively. In Case, 1 antipsychotics were effective, though transiently, for the mental symptoms other than physical ones. In Case 2, levodopa and hypercalcemia might have acted synergistically. Abnormal metabolism of magnesium was not noted in either case. A preoperative EEG showed the presence of sporadic slow waves in Case 1 and low voltage activity in Case 2. After the operation, the EEG showed an improvement to regular hypersynchronous alpha activity in both cases. The mechanism involved in the appearance of mental symptoms and EEG findings in hypercalcemia were discussed.     

Calcium Homeostasis During Magnesium Treatment in Aneurysmal Subarachnoid Hemorrhage

Objective  Magnesium treatment in patients with subarachnoid hemorrhage (SAH) can result in hypocalcemia; this hypocalcemia increases the risk of delayed cerebral ischemia (DCI) and poor outcome. We assessed whether low serum levels of total calcium in patients with SAH treated with magnesium is mediated by parathyroid hormone (PTH) or calcitriol, and whether increased PTH or low serum levels of ionized calcium are associated with an increased risk of DCI and poor outcome. Patients and Methods  We studied 167 patients included in a randomized, placebo controlled trial on magnesium in SAH. Mean serum magnesium during treatment was related to mean serum levels of ionized calcium, PTH and calcitriol with linear regression. Hypocalcemia (Ca²⁺) and high serum PTH were related to the occurrence of DCI by means of the Cox proportional hazards model and to poor outcome by logistic regression. Results  Serum magnesium was inversely related to ionized calcium (B = −0.1; 95% CI −0.12 to −0.06), but not to PTH or calcitriol. Neither hypocalcemia nor high serum PTH was related to DCI. Hypocalcemia did not increased the risk for poor outcome (OR 1.2; 95% CI 0.6–2.3). In the subgroup of patients with known PTH (n = 67), high serum PTH increased the risk for poor outcome (OR 5.4; 1.6–18.9). Conclusions  Magnesium treatment in patients with SAH leads to hypocalcemia without effect on outcome. PTH is related to poor outcome, but this is independent of magnesium therapy.     

Calcium homeostasis in long-term lithium-treated women with bipolar affective disorder

The authors investigated the effect of long-term lithium administration on intracellular calcium mobilization. The subjects were 13 women with bipolar affective disorder stabilized on lithium and 12 matched healthy controls. Total and ionized serum calcium, intracellular calcium ion concentration, plasma parathyroid hormone (PTH) and tyrotropin (TSH), serum electrolytes and cyclic AMP (cAMP) activity in platelets were measured. The serum electrolytes sodium, potassium and creatinine and plasma PTH and TSH were all within normal ranges in patients and controls and no differences were found between the two groups. No difference was found in basal and prostaglandin E1 (PGE1)-stimulated cAMP generation in platelets between patients and controls. However, total serum calcium and ionized serum calcium levels were higher in patients than in controls and there was a significant correlation between these two measures. In the patient group, serum lithium concentration correlated positively with stimulated levels of intracellular calcium in platelets. In the present study, no distinct hyperparathyroidism was found in lithium-treated patients. However, our findings indicate that lithium administration affects calcium metabolism in patients with bipolar affective disorder inducing mild hypercalcemia and a dose-dependent normalized calcium mobilization. Furthermore, our results did not support the hypothesis that lithium's primary site of action in bipolar illness may be on signal transduction mechanisms.     

Restless legs syndrome associated with primary hyperparathyroidism

Restless legs syndrome (RLS) is a poorly understood sleep-related movement disorder which can be primary or associated with other conditions, most commonly iron deficiency, uremia and peripheral nerve disease. We present a case of RLS with an unusual secondary cause: primary hyperparathyroidism with hypercalcemia. This patient experienced complete and sustained relief of RLS symptoms immediately after parathyroidectomy, with normalization of her serum parathyroid hormone (PTH) and calcium levels. Early recognition and treatment of this uncommonly detected underlying cause is important because it is potentially curative in this frequently disabling condition for which usually only symptomatic treatment is available.     

Severe neurological disease associated with hyperparathyroidism

Two patients, one with ataxia, internuclear ophthalmoplegia, muscle weakness, atrophy, fasciculations, and bilateral Babinski's signs, the other with dysarthria, dysphagia, muscle weakness, atrophy, fasciculations, and hyperreflexia, had elevated serum calcium and parathyroid hormone levels, establishing the diagnosis of primary hyperparathyroidism (HPT). Removal of a parathyroid adenoma in one patient and three hyperplastic parathyroid glands in the other resulted in remission of the hyperparathyroidism but left both patients with residual neurological damage. Postmortem examination of the second patient showed typical features of amyotrophic lateral sclerosis. The findings in these patients show that hyperparathyroidism may be associated with signs of severe central nervous system disease and that patients with unexplained neurological signs or symptoms should be checked for hyperparathyroidism.     

Abnormal bone and calcium metabolism in immobilized Parkinson's disease patients.

To elucidate the influence of immobilization-induced hypercalcemia on bone metabolism in Parkinson's disease (PD), we measured serum biochemical indexes and bone mineral density (BMD) in the second metacarpals of 142 elderly PD patients and 99 age-matched healthy controls. Serum concentrations of 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D (1,25-[OH](2)D), ionized calcium, intact parathyroid hormone (PTH), and intact bone Gla protein (BGP) were measured. Urinary deoxypyridinoline (D-Pyr) was also measured. Increased serum calcium levels (mean, 1.27 mmol/L) were observed in PD patients, and the levels correlated negatively with the Unified Parkinson's Disease Rating Scale III (UPDRS III), indicating the presence of immobilization-induced bone resorption with resultant hypercalcemia. Decreased serum concentrations of 1,25-[OH](2)D (mean, 88.7 pmol/L) and 25-OHD (mean, 29.7 nmol/L) were noted. Serum PTH was decreased (mean, 25.2 ng/L). Serum BGP was decreased while urinary D-Pyr concentration elevated. A negative correlation was observed between 1,25-[OH](2)D levels and serum calcium or UPDRS III (P < 0.0001). In disabled PD patients, immobilization-induced hypercalcemia may inhibit secretion of PTH, which in turn suppresses 1,25-[OH](2)D production. 25-OHD insufficiency may also contribute to decreased 1,25-[OH](2)D. These abnormalities may be corrected by the suppression of bone resorption with bisphoshonate, and supplementations of calcium and vitamin D should be avoided in these patients.     

High 1,25-Dihydroxyvitamin D and Low 25-Hydroxyvitamin D Concentrations in Plasma in Patients Receiving Antiepileptic Drugs

Abstract: Plasma 25-hydroxyvitamin D (25-OH D), 1,25-dihydroxy vitamin D (1,25-(OH)₂ D) and parathyroid hormone (PTH) concentrations were determined in 30 outpatients receiving various antiepileptic drugs (AED). None of the patients exhibited high plasma PTH levels. The plasma 1,25-(OH) ₂ D levels were normal or high, a'though in a third of the patients the 25-OH D levels were reduced. There was a corre'ation between the 25-OH D and serum calcium levels. These findings suggest that the low plasma concentrations of 25-OH D, not 1,25-(OH)₂ D, might play an important part in the occurrence of AED-induced disturbances of bone metabolism.     

Serial assessment of serum calcium correlates with mental state

Serial assessment of cognitive state using clinical and psychometric instruments correlated closely with serum calcium in an elderly woman with hyperparathyroidism. ‘Medical parathyroidectomy’ was associated with biochemical and clinical improvement but was not sustained. Following surgical removal of a parathyroid adenoma her serum calcium and her cognitive state returned to normal.     

Influence of immobilization upon calcium metabolism in the week following hemiplegic stroke

Hip fractures on the paretic side are a serious post-stroke complication and may result from disuse hemiosteopenia, hypovitaminosis D, and an increasing risk of falls. To evaluate short-term immobilization effects, we assessed calcium metabolism in 89 patients 1 week after the hemiplegic stroke and in 36 controls. Patient activity was rated using the Barthel index (BI). Sera from stroke patients and control subjects were assayed for ionized calcium, parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OHD), 1, 25-dihydroxyvitamin D (1,25-(OH)(2)D), bone Gla protein (BGP; a bone formation marker) and pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP; a bone resorption marker). Patients' serum concentrations of ionized calcium and ICTP were higher than in controls and correlated negatively with BI; their BGP concentrations were low, correlating positively with BI. Concentrations of serum 25-OHD, 1,25-(OH)(2)D, and PTH also were low; serum 25-OHD was at a deficient level (<10 ng/ml) in nine patients (10%), an insufficient level (10-20 ng/ml) in 56 (63%), and a sufficient level (>20 ng/ml) in only 24 (27%). PTH correlated negatively with calcium and 1,25-(OH)(2)D. Hypovitaminosis D is common in acute stroke patients. Immobilization from acute hemiplegia can increase bone resorption and serum calcium, and inhibit PTH secretion and 1,25-(OH)(2)D production to add to the effects of hypovitaminosis D.     

Uremic neuropathy: correlations between electroneurographic parameters and serum levels of parathyroid hormone and aluminum

An electrophysiological investigation on 29 dialysis patients was performed with the aim of verifying whether serum parathyroid hormone (PTH) and aluminum (Al) levels may play a role in the pathogenesis of uremic neuropathy. All patients except 1 showed electrophysiological abnormalities. Both PTH and Al levels were found to be significantly correlated with the time on dialysis. On the contrary, the values of each single electroneurographic parameter did not show any correlation with the duration of dialysis, PTH levels and Al levels. The authors conclude that PTH and Al does not seem to play a role in the etiology of uremic neuropathy.     

Neuropsychological function in relation to serum parathyroid hormone and serum 25–hydroxyvitamin D levels

There are receptors for parathyroid hormone (PTH) and 1,25–dihydroxyvitamin D in the brain, and there are clinical and experimental data indicating that PTH and vitamin D may affect cerebral function. In the present study 21 subjects who both in the 5^th Tromsø study and at a follow–up examination fulfilled criteria for secondary hyperparathyroidism (SHPT) without renal failure (serum calcium < 2.40 mmol/L, serum PTH > 6.4 pmol/L, and normal serum creatinine) and 63 control subjects were compared with tests for cognitive and emotional function. Those in the SHPT group had significantly impaired performance in 3 of 14 cognitive tests (Digit span forward, Stroop test part 1 and 2, and Word association test (FAS)) as compared with the controls, and also had a significantly higher depression score at the Beck Depression Inventory (BDI) (items 1–13). In a multiple linear regression model, a high serum PTH level was significantly associated with low performance at the Digit span forward, Stroop test part 1 and 2, and Digit Symbol tests. A low level of serum 25–hydroxyvitamin D was significantly associated with a high depression score. In conclusion, a deranged calcium metabolism appears to be associated with impaired function in several tests of neuropsychological function.     

Basilar artery narrowing and hyperparathyroidism: illustrative case

A patient presenting with a pontine infarction caused by mid-basilar artery narrowing associated with hyperparathyroidism is described. The narrowing reversed with surgical removal of his parathyroid adenoma and normalization of his serum calcium. This patient's illness lends evidence to the role of calcium in cerebral vasoconstriction.     

Depression is associated with low levels of 25-hydroxyvitamin D among Jordanian adults: results from a national population survey

Although low serum 25-hydroxyvitamin D (25(OH)D) and elevated serum parathyroid hormone (PTH) have been associated with depression in clinical settings, this link in community-dwelling individuals is inconclusive. The present study aimed at examining the association between serum 25(OH)D and PTH levels and the presence of depression in a national population-based household sample of 4,002 Jordanian participants aged ≥25 years. The DASS21 depression scale was used to screen for depression, and serum concentrations of 25(OH)D and PTH were measured by radioimmunoassay. Multiple logistic regression models were used to explore the association between serum 25(OH)D and PTH levels and depression. The unadjusted odds ratio (OR) decreased linearly with increasing quartiles of serum 25(OH)D (P(trend) = 0.00). The OR for having depression was significantly higher among individuals in the first and second quartiles (OR = 1.4, 1.23, respectively) than among those in the fourth quartile (P values = 0.00 and 0.03, respectively). This relationship remained significant after adjusting for age, sex, marital status, education, BMI, serum creatinine, number of chronic diseases (OR = 1.39 and 1.21 and P values = 0.00 and 0.05, respectively) and after further adjustment for exercise, altitude, and smoking (OR = 1.48 and 1.24, respectively, and P values = 0.00 and 0.03, respectively). No significant association was found between serum PTH levels and depression. The decrease in risk of depression among participants started to be significant with serum 25(OH) D levels higher than 42.3 ng/ml (lower limit of the range of the third quartile). This value may help pinpoint the desirable level of serum 25(OH)D to be attained to help aid the prevention and treatment of depression.     

The effect of anti epileptic drug therapy on serum 25-hydroxyvitamin D and parameters of calcium and bone metabolism—A longitudinal study

BackgroundChronic antiepileptic drug use is associated with bone loss. We sought to assess the longitudinal effect of antiepileptic drug on serum 25-hydroxyvitamin D [25(OH)D] levels and bone mineral metabolism markers.MethodsPatients in the emergency services or those in neurology outpatient department with history of seizure were characterized and included in the study prospectively. Daily dietary intake of calories, calcium, phosphorus and phytates were characterized by dietary recall method. Base line bone mineral parameters – serum calcium, phosphorus, alkaline phosphatase (SAP), tartrate resistant acid phosphatase (TRACP), 25(OH)D levels, parathyroid hormone (PTH) and urinary calcium creatinine ratio (Ca.Cr), urinary calcium/kg/bodyweight (BW) and phosphate excretion index (PEI) were determined. Patients on AED therapy with normal 25(OH)D levels were followed up and were re-evaluated at the end of 6 months.ResultsThe daily dietary calcium intake of the subjects was lower than the RDA (Recommended Dietary Allowance) by ICMR (Indian Council of Medical Research). The diet was high in phytates. Two-thirds of the recruited subjects were vitamin D deficient. Subjects with normal 25(OH)D levels at base line showed a significant fall of 25(OH)D levels, urinary calcium, urinary calcium/kg/BW and TRACP levels at the end of 6 months irrespective of the AED used or the plasma level of AED.ConclusionsHypovitaminosis D is common in our population. Subjects with normal 25(OH)D levels, irrespective of the type of antiepileptic medications even at sub-therapeutic serum levels of the drug, went into 25(OH)D deficiency and insufficiency states. Theoretically it can be worthwhile to supplement calcium and vitamin D even before initiation of antiepileptic therapy.     

抑郁症患者血清同型半胱氨酸水平的研究

目的探讨抑郁症患者血清同型半胱氨酸水平与抑郁症发病的相关性。方法将94例抑郁症患者作为研究组,选取98例身心健康正常人为对照组,应用荧光偏振免疫法检测血清同型半胱氨酸水平。结果研究组患者血清同型半胱氨酸水平显著高于对照组(16.72±3.94)μmol/L,(10.99±3.51)μmol/L,P<0.05,研究组高同型半胱氨酸血症发生率显著高于对照组(41.5%,14.3%)(χ2=14.89,P<0.05)。结论血清同型半胱氨酸水平升高可能是抑郁症发病的重要危险因素之一,血清同型半胱氨酸水平对抑郁症严重程度有一定的影响。