Malignant phaeochromocytoma and hypercalcaemia.

We describe a case of hypercalcaemia secondary to recurrent malignant phaeochromocytoma. Parathyroid-related protein (PTHrp 1-86) immunoreactivity was identified in plasma and PTHrp was identified by immunocytochemistry in tumour tissue.     

Diabetic and endocrine emergencies

Endocrine emergencies constitute only a small percentage of the emergency workload of general doctors, comprising about 1.5% of all hospital admission in England in 2004-5. Most of these are diabetes related with the remaining conditions totalling a few hundred cases at most. Hence any individual doctor might not have sufficient exposure to be confident in their management. This review discusses the management of diabetic ketoacidosis, hyperosmolar hyperglycaemic state, hypoglycaemia, hypercalcaemia, thyroid storm, myxoedema coma, acute adrenal insufficiency, phaeochromocytoma hypertensive crisis and pituitary apoplexy in the adult population.     

Normotensive cardiomyopathy and malignant hypertension in phaeochromocytoma

A patient with two different presentations of phaeochromocytoma is described. She initially presented with normal blood pressure and heart failure following a prolonged feverish prodrome. A provisional diagnosis of myocarditis or early congestive cardiomyopathy was made and she improved with digoxin and diuretics. Eighteen months later, after a period of normotension free from heart failure, she developed malignant hypertension with recurrence of heart failure. A phaeochromocytoma was surgically removed, with return to normal of blood pressure and cardiac status. It would seem that the initial presentation of the phaeochromocytoma was a catecholamine-induced myocarditis without hypertension and this resolved with the subsequent development of malignant hypertension. The possible mechanisms responsible for this are discussed and it is concluded that phaeochromocytoma should be considered in patients who have heart failure and persistent features of myocarditis.     

Phaeochromocytoma unearthed by fluoxetine

Non-specific noradrenaline reuptake inhibition by high dose selective serotonin reuptake inhibitors, along with catecholamine release from phaeochromocytoma, may lead to a hypertensive paroxysm. This may unmask a clinically silent phaeochromocytoma. Hypertensive paroxysm induced by paroxetine leading to detection of phaeochromocytoma has been reported. The first patient in whom fluoxetine unmasked a phaeochromocytoma is reported.     

Hypercalcaemia in adult hospital population: comparison of inpatients of 1966 with those of 1976.

During 1976, inpatients with hypercalcaemia at The Royal Melbourne Hospital were identified from the worksheets of the Department of Biochemistry and compared with those discovered in a similar study in 1966. In 1966, the estimation of plasma calcium level had to be ordered specifically, whereas in 1976, for technical reasons, the measurement of plasma calcium level was frequently performed when not requested. Despite a six-fold increase in plasma calcium in the rate of detection of hypercalcaemia. In both studies, malignant disease was the most common casue of hypercalcaemia, but primary common cause of hypercalcaemia, but primary hyperparathyroidism was found slightly more frequently in 1976. This study suggests that screening inpatients for hypercalcaemia is of little value.     

Hypercalcaemia due to sarcoidosis corrects with bisphosphonate treatment

We report a case of sarcoid hypercalcaemia treated with the bisphosphonate, APD [(3-amino-1-hydroxypropylidene)-1,1-bisphosphonate]. Investigations showed that the hypercalcaemia was associated with a high plasma 1,25 dihydroxy vitamin D concentration. A low dietary intake of calcium partially corrected the hypercalcaemia but APD rapidly normalized plasma calcium without reducing the elevated 1,25 dihydroxy vitamin D concentration. The case demonstrates that hypercalcaemia in sarcoidosis results from the effects of 1,25 dihydroxy vitamin D on bone as well as on calcium absorption and that prolonged suppression of the effect on bone occurs with APD treatment.     

Immobilization hypercalcaemia due to low bone formation and responding to intravenous sodium sulphate

A young man developed acute renal failure and hypercalcaemia following severe burns. The hypercalcaemia was initially controlled by haemodialysis, but it persisted after return of renal function. Plasma PTH was inappropriately elevated, but the nephrogenous cyclic adenosine monophosphate level was low; thus the PTH was probably not biologically active, and may have been artefactually elevated by the moderate renal impairment. Bone histology, showed a normal resorbing surface, but a zero forming surface, implying that the bone dissolution leading to hypercalcaemia resulted from a failure of bone formation. Because of widespread infection and impaired renal function, the hypercalcaemia could not be treated by corticosteroid drugs, mithramycin or phosphate, and there was no response to salmon calcitonin. He was therefore treated with intravenous sodium sulphate, which increased urinary calcium excretion and reduced the plasma calcium. Sodium sulphate still has a role in the treatment of patients with hypercalcaemia.     

Survival in hypercalcaemic patients with cancer and co-existing primary hyperparathyroidism.

Hypercalcaemia associated with malignancy is generally thought to carry a poor prognosis. Of 47 consecutive patients with hypercalcaemia and malignancy, serum parathyroid hormone (PTH) was elevated in seven, consistent with co-existing hyperparathyroidism. Median survival from onset of hypercalcaemia in these seven patients was 817 days; compared to 33 days in the remaining 40 patients with hypercalcaemia of malignancy, in whom PTH was suppressed (p = 0.007). Among patients with hypercalcaemia of malignancy, plasma PTH-related protein (PTHrP) concentration showed no correlation with survival (r2 = 2.1%), but one patient with increased levels of both PTH and PTHrP survived only nine days after the onset of hypercalcaemia. A raised PTH had a positive predictive value of 86% for survival > 100 days, and of 71% for survival > 1 year. A raised plasma PTHrP predicted death within 100 days with a positive predictive value of 69%. We conclude that measurement of serum PTH is indicated in patients with hypercalcaemia and malignancy to identify the 15% with hyperparathyroidism, since this is associated with prolonged survival. In patients with hyperparathyroidism, assay of plasma PTHrP may indicate concurrent hypercalcaemia of malignancy, with an associated poor prognosis.     

The impact of recent advances in diagnostic technology on the clinical presentation of phaeochromocytoma.

OBJECTIVE: To examine the impact of recent advances in diagnostic technology on the spectrum of clinical and biochemical features of patients presenting with a new diagnosis of phaeochromocytoma. DESIGN: A retrospective review of the clinical and biochemical features of patients diagnosed by our laboratory as having phaeochromocytoma within a 27-month period up to December, 1990. Noradrenaline, adrenaline and dihydroxyphenylglycol were assayed in 24-hour urine specimens (19 patients) or plasma (1 anuric patient) by gas chromatography/mass spectrometry. SETTING: A tertiary level chemical pathology department. PATIENTS: Twenty patients with a new diagnosis of phaeochromocytoma. RESULTS: The classic, episodic adrenergic symptoms traditionally associated with phaeochromocytoma were absent in 9 of the 20 patients (45%). "Atypical" phaeochromocytoma presented as a mass on computed tomography imaging (6 patients, 30%), "phaeochromocytoma crisis" (4 patients, 20%) or family screening (1 patient, 5%). Excessive adrenaline production was found in 11 patients (55%) and six (30%) had predominantly adrenaline-secreting tumours. The urinary noradrenaline:dihydroxyphenylglycol ratio was raised in all nine patients with predominantly noradrenaline-secreting tumours but was not raised in nine out of ten patients with adrenaline-secreting phaeochromocytoma. Adrenaline excretion was significantly correlated with tumour size (r = 0.8; P less than 0.05). CONCLUSIONS: Advances in diagnostic technology, particularly specific adrenaline assays and computed tomography, have made possible the early diagnosis of patients with phaeochromocytoma presenting in ways previously thought to be uncommon. All patients with adrenal masses noted incidentally on CT scan should be investigated for phaeochromocytoma. Adrenaline-secreting tumours are common and both noradrenaline and adrenaline should be assayed in all patients investigated for phaeochromocytoma.     

Digoxin, hypercalcaemia, and cardiac conduction

The cardiac effects of hypercalcaemia are usually manifest as a shortening of the QT-interval. Hypercalcaemia is infrequently associated with a clinically manifest arrhythmia. However, concomitant therapy with digoxin or underlying cardiac disease can potentiate the arrhythmogenic effects of hypercalcaemia, leading to a symptomatic rhythm disorder. We describe a symptomatic arrhythmia, which developed in a patient with hypercalcaemia secondary to squamous cell carcinoma of the bronchus. The patient was on digoxin therapy at the time. The arrhythmia did not recur after discontinuation of digoxin therapy and correction of the hypercalcaemia. Because of its effect on cardiac conduction, hypercalcaemia should be considered in the evaluation of any patient with an unexplained bradyarrhythmia. Conversely, patients with hypercalcaemia should discontinue digoxin therapy and be evaluated for the presence of rhythm disorders while receiving appropriate treatment for hypercalcaemia.     

Mechanism of malignant hypercalcaemia in carcinoma of the breast

To investigate the mechanisms of hypercalcaemia in carcinoma of the breast, 22 patients with hypercalcaemia due to metastatic carcinoma were studied and the findings compared with those obtained in normal subjects and patients with benign and malignant breast disease without hypercalcaemia. As expected, patients with metastases of bone showed biochemical evidence of increased bone resorption. Whereas all patients with hypercalcaemia had skeletal metastases, not all patients with skeletal metastases had hypercalcaemia despite considerable degrees of bone resorption. The presence of hypercalcaemia was associated with a significant increase in renal tubular reabsorption of calcium (p less than 0.001) and decreased reabsorption of phosphate (p less than 0.001) despite adequate rehydration of patients. These studies suggest that increased renal tubular reabsorption of calcium, possibly mediated by a humoral factor with activity similar to that of parathyroid hormone, contributes appreciably to the hypercalcaemia of malignant breast disease.     

Malignant phaeochromocytoma metastasising to the breast

Background Nearly one-quarter of metastatic tumours in the breast are from an occult extramammary tumour, usually a lung carcinoma. Aim To report on a patient with a history of metastatic malignant phaeochromocytoma and a breast mass. Result A 54-year-old female presented with a right breast mass. At the age of 32, she had presented with a phaeochromocytoma. The staining of the breast mass was comparable with that of her original adrenal tumour. Conclusion This is the first published case of a phaeochromocytoma metastasising to the breast, and demonstrates the challenge that extramammary tumours in the breast can pose for the pathologist.     

Hypercalcaemia in thyrotoxicosis with and without hyperparathyroidism

Two cases of thyrotoxicosis with hypercalcaemia are reported. The hypercalcaemia in one of the patients was a manifestation of hyperthyroidism and in the other was due to co-existent hyperparathyroidism.     

Parathyroid hormone-related protein as a tumour marker in humoral hypercalcaemia associated with occult malignancy.

The tumour-derived factor PTH-related protein (PTHRP) is the primary humoral factor responsible for hypercalcaemia in patients with solid tumours. In a woman presenting with anaemia and hypercalcaemia, the finding of raised plasma PTHRP and undetectable serum PTH concentrations led to further investigations and the subsequent identification of a uterine tumour. No evidence of tumour spread was found at operation, and removal of the tumour resulted in normalization of both serum calcium and plasma PTHRP. Expression of PTHRP by the tumour was shown by immunohistochemistry and in situ hybridization. We conclude that the identification of an occult tumour in a patient with hypercalcaemia and raised plasma PTHRP provides evidence of the diagnostic utility of PTHRP immunoassays in the investigation of patients with hypercalcaemia and suspected malignancy.     

Surgical treatment of endocrine hypertension experience in India

Between 1980 and 1994, 162 cases of endocrine based hypertension were diagnosed and treated surgically. Seventy-nine cases (48.7%) of phaeochromocytoma, 63 cases (38.8%) of Cushing's syndrome, and 20 cases (12.3%) of Conn's syndrome were diagnosed. In phaeochromocytoma 75% of the tumours arose from the adrenal glands and 25% arose from the extra-adrenal sites. Cushing's syndrome was caused by adenoma (45%), diffuse bilateral adrenal hyperplasia (36%), pigmented macronodular hyperplasia (9%), and adrenal carcinoma (10%). The most common cause of Conn's syndrome was adenoma (95%) which arose mainly from the left adrenal gland (60%). In the present series the success rate of surgical treatment was 100% for phaeochromocytoma, 90% for Cushing's syndrome and 96% for Conn's syndrome. Trucut biopsy of the kidneys of these patients showed hypertensive changes, the moderate hypertension could be due to renal damage.     

Phaeochromocytoma and acute cardiovascular death (with special reference to myocardial infarction)

The causes of death, as determined by autopsy, in 10 patients dying from the acute effects of phaeochromocytoma were myocardial infarction (five patients), left ventricular failure (two patients), cerebral haemorrhage (two patients) and circulatory collapse with malignant phaeochromocytoma (one patient). Most patients died shortly after admission during the course of a fulminant cardiovascular illness and the underlying tumour was unsuspected in eight instances. The clinical features and post-mortem cardiovascular findings are reviewed.     

Renal handling of calcium and sodium in metastatic and non-metastatic malignancy

Investigation of the renal handling of calcium and sodium in rehydrated patients with hypercalcaemia associated with malignancy showed enhanced reabsorption of calcium in most cases. This was a feature of both metastatic and non-metastatic malignancy, and in this respect the patients were indistinguishable from patients with primary hyperparathyroidism. As the increased calcium reabsorption was inversely correlated with the rate of excretion of sodium modest salt loading can be used to inhibit this process. This is an important practical aspect of the treatment of patients with this type of hypercalcaemia.     

Recurrence of asthma following removal of a noradrenaline-secreting phaeochromocytoma

A patient with asthma and a phaeochromocytoma is described. At about the time she was first noted to be hypertensive her asthma resolved spontaneously but bronchospasm returned with some severity when the tumour was removed. The phaeochromocytoma was of the noradrenaline secreting variety. Possible mechanisms through which this catecholamine might have produced the observed alleviation of asthma are considered.     

Lipid and lipoprotein metabolism in familial combined hyperlipidaemia during treatment of sporadic phaeochromocytoma: a case study.

Lipid metabolism was evaluated during management of phaeochromocytoma in a 41 year old non-obese post-menopausal women with familial combined hyperlipidaemia. The main effect of the excess catecholamine secretion on lipid metabolism was increased lipolytic activity, lower serum triglyceride and increased HDL cholesterol concentrations, compared with findings following removal of the tumour. Before removal of the tumour, the use of beta blockers alone led to marked deterioration of the hyperlipidaemic state, and combined alpha and beta blockade additionally led to a marked reduction in fat oxidation and lipoprotein lipase activity. Overactivity of the adrenergic system leads to changes in lipid metabolism in phaeochromocytoma. Treatment of the phaeochromocytoma may lead to worsening of hyperlipidaemia pre-existing in such individuals.     

Presentation of a PTHrP-secreting pancreatic neuroendocrine tumour,with hypercalcaemic crisis,pre-eclampsia,and renal failure

Severe hypercalcaemia during pregnancy is rare and most cases are secondary to hyperparathyroidism. This is the first report of a parathyroid hormone related protein (PTHrP) secreting neuroendocrine tumour of the pancreas manifesting with severe hypercalcaemia during pregnancy. Measurement of PTHrP was useful in both the diagnosis and follow up of our patient and should be considered in the diagnostic workup of patients with unexplained hypercalcaemia. A raised PTHrP concentration is a strong indicator of malignancy.