A case of primary hyperparathyroidism that had been treated under a diagnosis of depression for 10 years

Abstract A 66 year old man who had been treated under a diagnosis of depression for 10 years was referred to the Kyoto Prefectural University of Medicine, Kyoto because of general fatigue and appetite loss. The patient was diagnosed as having primary hyperparathyroidism (PHPT) based on the increased parathyroid hormone (PTH) and serum calcium levels. Computed tomography revealed solitary adenoma of parathyroid gland. The resection of this solitary adenoma improved the PTH and serum calcium concentrations to normal ranges, which resulted in an improvement in his depressive state. This case suggests that ionic calcium levels contribute to the mental symptoms associated with PHPT. As PHPT is curable, the possibility of PHPT should be taken into account when patients have depressive symptoms.     

Tonic-clonic seizures in a patient with primary hypoparathyroidism: a case report.

Hypoparathyroidism, a life threatening disorder, occurs when insufficient parathyroid hormone is produced to maintain extracellular calcium levels within the normal range. The acute clinical signs and symptoms of hypoparathyroidism are the same as those of hypocalcemia, ranging from tingling to intractable generalized tonic-clonic seizures; therefore, it can be mistaken for epilepsy. We report the case of a 36-year-old man who presented two tonic-clonic seizures, characterized by sudden loss of consciousness with a fall and diffuse tonic contractions and clonic jerks. At first diagnosis of epilepsy was established and therapy with valproate was commenced. In the following days, the patient presented typical signs of hypocalcemia and the diagnosis of hypoparathyroidism was made. In the 4 months follow up, antiepileptic drug therapy was reduced until suspension and calcium supplementation was initiated. We briefly review the most recent reports in the literature.     

Hypoparathyroidism: A rare treatable cause of epilepsy – report of two cases

Hypoparathyroidism occurs due to insufficient production of parathyroid hormone to maintain extracellular calcium levels within the normal range. The acute clinical symptoms and signs of hypoparathyroidism are those of hypocalcaemia, ranging from tingling and numbness of limb extremities to intractable seizures. Often seizures are mistaken for epilepsy. Though hypoparathyroidism is not uncommon, the diagnosis is often missed due to its unusual clinical manifestation. This is the first documented report with vitamin D, Parathormone levels and urinary biochemical parameters from India. We present two cases of hypoparathyroidism who presented with seizures along with a short review of literature.     

Hypoparathyroidism and pseudotumor cerebri: an infrequent clinical association

We report a patient with chronic, untreated idiopathic hypoparathyroidism who presented with papilledema and progressive deterioration of visual function. The papilledema resolved with treatment of the hypocalcemia. Visual acuity progressively improved as the serum calcium rose during treatment with vitamin D and calcium supplements. Lumbar puncture may also have contributed to the normalization of cerebrospinal fluid pressure and recovery of vision in this patient. The association of hypoparathyroidism and pseudotumor cerebri is rare, and a retrospective review of 41 patients with hypoparathyroidism admitted to two local general hospitals revealed no other cases.     

Hypocalcemic myopathy without tetany due to idiopathic hypoparathyroidism: case report

Myopathy due to idiopathic hypoparathyroidism is very unusual. We report on a 30 years-old man referred with complaints of sporadic muscle pain and mild global weakness for 10 years. His physical examination showed normal strength in distal muscle and slightly weakness in the pelvic and scapular girdles with no atrophy. Deep muscle reflexes were slightly hypoactive. Trousseau's and Chvostek's signs were absent. He had bilateral cataract and complex partial seizures. His laboratory tests showed decreased ionised and total calcium and parathyroid hormone and increased muscle enzymes. EMG and muscle biopsy was compatible with metabolic myopathy. After treatment with calcium and vitamin D supplementation he showed clinical, neurophysiological and laboratorial improvement. In conclusion: patients with muscle symptoms, even when non-specific and with normal neurological examination, should have serum calcium checked, as myopathy due to idiopathic hypoparathyroidism, even being rare, is treatable and easy to diagnose.     

Hypocalcemia, hypoparathyroidism, and organic anxiety syndrome

The author describes a case of functional hypoparathyroidism with hypocalcemia that developed in a patient after ablation of a parathyroid adenoma. The patient's clinical presentation was characterized by a severe anxiety state. The literature on the neuropsychiatric manifestations of hypoparathyroidism indicates that anxiety states are not uncommon in this condition and suggests that hypoparathyroidism should be considered in the differential diagnosis of organic anxiety syndrome.     

Differential subtyping of depression

We studied a group of patients with depression divided into subtypes of non-chronic major depression, chronic major depression, and pure dysthymia. The purpose of this study was to determine if clinical and family history factors separated these types of depression. We reviewed records from semi-structured clinical interviews and abstracted data regarding factors that might differentiate these three depressive subtypes. In general we found what might be predicted from the definitions of dysthymia versus major depression, that is, ratings for severity of depression were lower for dysthymic patients as compared to patients with non-chronic or chronic major depression. We also found lower ratings for social functioning (GASF) for dysthymic patients as compared to the other depressive subtypes. Our study does not provide data to sufficiently separate these three subtypes. However, in the course of reviewing the literature on this topic, very few studies have separated patients into these distinct depressive subtypes. Further studies are needed to indicate if these subtypes can be meaningfully separated.     

Secondary cervical dystonia in iatrogenic hypoparathyroidism associated with extensive brain calcifications

Cervical dystonia (CD) is usually idiopathic, without a known aetiology. Hypoparathyroidism, both primary and secondary, can be associated with brain calcifications and various clinical neurological features. Anecdotal evidence suggests that patients affected by hypoparathyroidism show a rapid-onset oral dyskinesia after use of neuroleptic drugs. We report the case of a 60-year-old woman with CD, iatrogenic hypoparathyroidism and extensive brain calcifications. On the basis of the clinical features and the localization of the brain calcifications we suppose that they may have played a role in the development of this CD. This case may prove to be, after a review of literature, the first report of CD secondary to iatrogenic hypoparathyroidism in a patient with extensive brain calcifications.     

Major depression and depressive symptomatology among the physically disabled. Assessing the role of chronic stress

Although it is generally agreed that life stress represents a risk factor for depressive symptomatology, there is less agreement on the significance of such stress for the occurrence of major depression. Indeed, it has been suggested that stress factors of importance for depressive symptoms may be irrelevant for major depression. We report results based on a large sample of physically disabled and nondisabled adults that contradict this suggestion. The physically disabled show seriously elevated rates of both depressive symptomatology and major depressive disorder. Subgroup analyses confirmed the finding on depressive symptomatology within all age-gender groupings and the finding on major depression for young and middle-aged men and women but not for the aged. It is argued that these findings can be attributed to differences in chronic stress associated with disability status. We conclude that chronic stress represents a significant risk factor with respect to both depressive symptomatology and major depressive disorder.     

Serum antibodies to Epstein-Barr virus in patients with major depressive disorder

To determine whether major depressive disorder might be associated with serologic evidence for a chronic active Epstein-Barr virus infection, viral-specific antibodies were measured in two separate groups of depressed patients (N=43) and in 46 appropriately matched healthy volunteers. No evidence that depression affects cellular immunity to the point that a persistent Epstein-Barr virus carrier state becomes activated was found. There was also no evidence that depression results from an unrecognized chronic active Epstein-Barr virus infection. The authors conclude that the routine clinical determination of expensive commercial Epstein-Barr virus antibody profiles is not indicated in most patients with major depressive disorder in the absence of other signs of chronic active Epstein-Barr viral infection.     

"Double depression": two-year follow-up

Of 316 patients with a major depressive disorder who were followed for between 6 months and 2 years, 80 (25%) had a preexisting chronic minor depression of at least 2 years' duration. The chronic minor depression reduced the apparent effect of the known predictors of recovery and relapse from the major depressive disorder and predicted a very pernicious course for the chronic depression. Furthermore, the longer the patient continued to suffer from a chronic minor depression after recovering from the major depression, the greater the probability that relapse into another major depression would preempt recovery from the chronic depression.     

Blockade of 2‐arachidonoylglycerol hydrolysis produces antidepressant‐like effects and enhances adult hippocampal neurogenesis and synaptic plasticity

The endocannabinoid ligand 2‐arachidonoylglycerol (2‐AG) is inactivated primarily by monoacylglycerol lipase (MAGL). We have shown recently that chronic treatments with MAGL inhibitor JZL184 produce antidepressant‐ and anxiolytic‐like effects in a chronic unpredictable stress (CUS) model of depression in mice. However, the underlying mechanisms remain poorly understood. Adult hippocampal neurogenesis has been implicated in animal models of anxiety and depression and behavioral effects of antidepressants. We tested whether CUS and chronic JZL184 treatments affected adult neurogenesis and synaptic plasticity in the dentate gyrus (DG) of mouse hippocampus. We report that CUS induced depressive‐like behaviors and decreased the number of bromodeoxyuridine‐labeled neural progenitor cells and doublecortin‐positive immature neurons in the DG, while chronic JZL184 treatments prevented these behavioral and cellular deficits. We also investigated the effects of CUS and chronic JZL184 on a form long‐term potentiation (LTP) in the DG known to be neurogenesis‐dependent. CUS impaired LTP induction, whereas chronic JZL184 treatments restored LTP in CUS‐exposed mice. These results suggest that enhanced adult neurogenesis and long‐term synaptic plasticity in the DG of the hippocampus might contribute to antidepressant‐ and anxiolytic‐like behavioral effects of JZL184. © 2014 Wiley Periodicals, Inc.     

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.     

Depressive symptoms in chronically ill elderly people in residential homes

Physical ill health is known to be a risk factor for depression. However, little is known about the relationship between chronic illness and depression in older people living in residential homes. This study looked at the differences in the level of depressive symptoms between patients with different types of chronic illness, and the relationship between chronic illness and depression when other risk factors of depression were controlled for. Four hundred and twenty-four people living in residential homes in the Netherlands were included in the study. Residents with cognitive impairment were excluded. The degree of depression was assessed with the Geriatric Depression Scale (GDS) and psychological distress was measured with the MOS-SF-20 mental health sub-scale. Other risk factors included functional impairment, earlier depression, degree of pain, life events and social support. Few residents had no chronic illness and almost half of them had more than one illness. There was only modest evidence to suggest that chronic illnesses were related to depressive symptomatology or psychological distress. However, other risk factors were found to be much stronger predictors of depression and psychological distress. The results should be treated with caution because of the limitations of the study. Nevertheless, the results suggest that chronic illness is not the best predictor of depression in people living in residential care homes.     

Changes in hypothalamic-pituitary-adrenal axis measures after vagus nerve stimulation therapy in chronic depression.

BACKGROUND: Little is known about the hypothalamic-pituitary-adrenal (HPA) axis stress system in chronic depression. This study examined the corticotropin-releasing hormone (CRH) challenge test in a group of patients with chronic depression, before and after 3 months of treatment with vagus nerve stimulation (VNS) therapy, and a matched group of healthy control subjects. METHODS: Key inclusion criteria were DSM-IV-defined major depressive disorder, a history of a current episode lasting for at least 2 years, and unresponsiveness to at least two classes of antidepressant medications. Eleven test subjects and 11 matched control subjects underwent a CRH challenge. RESULTS: There were significant reductions in depression scores over the study period. The CRH/ACTH (adrenocorticotropic hormone) responses in the depressed group before VNS implantation were significantly higher than in the healthy group and were reduced to normal values after VNS treatment. Some measures of cortisol response were elevated before treatment and were reduced to normal over the study period. The only clinical measure correlated with HPA axis alterations was reduction in atypical depressive symptom scores. CONCLUSIONS: These preliminary results suggest that chronic depression, in contrast to acute melancholic depression, might be characterized by increased ACTH response to CRH challenge. Short-term treatment with VNS therapy was associated with normalization of this response.     

Trouble de l’humeur unipolaire dépressif. À propos d’un cas

The authors aimed to show how difficult the nosography seems to be between unipolar depression and paraphrenia, especially when treatments (even with ECT) were poorly effective. Mrs A. presented megalomania and persecution delusions and for years lived in a chronic delusional state. She suffered from delusions after three depressive relapses but she did not show any dissociation or cognitive impairment. The mechanisms were imaginative, intuitive, without hallucinations, but with little coherence, and delusions were constantly stable. This case brings to mind paraphrenia as an evolutionary state of a persistent major depressive period. It is as if a continuum exists between different kinds of psychosis. The report concerns paraphrenia as a secondary process with thymic disorders, discusses the place of chronic delusion in the nosography, and questions the concept of single psychosis.     

Overexpression of piccolo C2A domain induces depression-like behavior in mice

Piccolo is one of the components of the active zone at chemical synapses and regulates the transport of synaptic vesicles. The piccolo C2A domain is an important calcium sensor and binds with phosphatidylinositol or synaptotagmin-1. Recently, clinical studies suggested that a single nucleotide polymorphism in the piccolo C2A domain might be a causal risk factor for major depression. To clarify the association of piccolo with depression, we produced a transgenic mouse overexpressing the C2A domain of piccolo, and investigated the behavior of these mice. The mice exhibited depression-like behavior in both forced swim and tail suspension tests, suggesting that piccolo might regulate the depressive behavior.     

Obstructive sleep apnoea syndrome as the cause of atypical depression

Sleep apnoea is a common disorder presenting with somatic comorbidities and psychiatric symptoms. This case report describes a 43-year-old man with an organic depressive disorder due to obstructive sleep apnoea. Initially, an atypical depressive episode or schizophrenic residual syndrome had been considered likely diagnoses; subsequent polysomnography results, however, suggested obstructive sleep apnoea instead. Upon nasal continuous positive airway pressure (nCPAP), the respiratory distress symptoms improved. The case report highlights the association between sleep disturbances and depressive symptoms. In patients presenting with symptoms of atypical depression and excess body weight sleep apnoea should be considered.     

Platelet cytosolic calcium hyperresponsivity to serotonin in patients with hypertension and depressive symptoms.

BACKGROUND: Data from recent studies indicate that the presence of depression is an independent risk factor for cardiovascular and cerebrovascular events. The mechanism by which depression increases the morbidity and mortality risks in patients with comorbid vascular disease is currently the object of considerable research interest. Platelets may be involved in this pathological process. Although many investigators have extensively evaluated platelet biochemistry in depressed patients, there currently exists very little information regarding how the biochemical alterations might relate to an increased risk of cardiovascular events. In this study, we examined the responsivity of platelet cytosolic calcium concentrations ([Ca++]i) to serotonin stimulation in populations of hypertensive patients with or without comorbid depressive symptoms. METHODS: We utilized Fura-2 loaded platelets to compare changes in intracellular calcium levels (delta [Ca++]i) following serotonin stimulation among 48 patients with hypertension and varying degrees of depressive symptomatology. RESULTS: We found that those patients with higher scores on standardized depression rating scales showed significantly greater [Ca++]i (82.82 +/- 15.88 mmol/L) increase compared with [Ca++]i (60.10 +/- 22.65 mmol/L) patients with lower depression scores. CONCLUSIONS: The results of this study support the hypothesis that the enhanced platelet reactivity seen in patients with depressive symptoms may mediate the deleterious effects of depression on cardiovascular disease.