The curative therapy of primary hyperparathyroidism by percutaneous ethanol injections

HISTORY AND CLINICAL FINDINGS: An 86-year-old woman was admitted because of acute nonspecific upper abdominal symptoms and vomiting. She was occasionally disoriented, generally slower in movement and reaction, apathetic and mainly bed-ridden. She was a known insulin-dependent diabetic who had sustained a posterior wall myocardial infarction and cerebrovascular accident and had undergone a cholecystectomy. On physical examination her upper abdomen was painful to pressure, blood pressure was 180/95 mm Hg, but there were no other findings. INVESTIGATIONS: Sonography demonstrated bile-duct dilatation, confirmed at endoscopic retrograde cholangiopancreatography, and a prepapillary choledochal concrement of about 10 mm. Sonography also revealed an echo-poor tumour of the right caudal parathyroid. The calcium concentration was raised to 2.94-3.16 mmol/l and the parathormone level was also increased (99.5 pmol/l, normal 1.2-5.7 pmol/l), as were amylase (375.6 U/l) and lipase (1038-5394 U/l). TREATMENT AND COURSE: After papillotomy and extraction of the choledochal concrement the acute biliary pancreatitis quickly improved. Operation on the parathyroid tumour was not undertaken because of the patient's various illnesses. Instead, 95% alcohol was instilled, 3.5 and 4.5 ml respectively, into the tumour, under sonographic control in two sessions, 3 days apart. Her clinical condition clearly improved and serum calcium became normal and the parathormone level fell significantly. CONCLUSION: Percutaneous ethanol injection of a parathyroid tumour can be a curative and sparing alternative to operation in patients with hyperparathyroidism seemed too ill for surgery.     

Carcinoma of the pancreas with amyloid stroma and calcitonin secretion : ultrastructural study (author''s transl)

The authors report a case of anaplastic carcinoma with amyloid stroma, accompanied by the secretion of calcitonin, detected in a cervical lymph node and initially interpreted as being a metastasis from a medullary carcinoma of the thyroid. The actual pancreatic origin of the malignant tumour was proved only during the advanced stages. Ultrastructural study confirmed the endocrine nature of the tumour (neurosecretory granules). Despite its exceptional character, the existence of such a tumour is not surprising, if one accepts the concept of a diffuse endocrine system.     

An assessment of test criteria for evaluating the performance and integrity of sterilizing filters

Measurements of serum calcitonin (iCT) were performed in 300 relatives of 43 Norwegian patients with medullary thyroid carcinoma (MCT). Prior to the screening, familial occurrence of the disease was known in only one of the families. Persistant hypercalcitoninemia (serum levels greater than 0.50 ng/ml) was demonstrated in 2 healthy persons from this family and in 3 first degree relatives of 2 patients with apparently sporadic disease. Additional 7 relatives of 5 other "sporadic" cases showed elevation of serum iCT on one occasion, while later controls revealed normal values. Twenty persons had high normal serum levels (0.35 ng/ml less than or equal to iCT less than 0.50 ng/ml). The significance of transitory hypercalcitoninemia and high normal values are at the present unknown, but these persons will have further tests. Stimulation tests for iCT secretion were found to be of limited value in distinguishing between normal and pathological serum iCT. All individuals found to have chronic hypercalcitoninemia belonged to families in which the probands showed one or several of the following "high risk" factors: A positive history of thyroid disease, early age of onset, bilateral presence of the thyroid tumour, association with other endocrine or peripheral neurogenic tumours, and marphanoid habitus. The iCT screening was however negative in the relatives of the two probands revealing 4 and 5 of these factors. Since neither the family history nor the presence or absence of "high risk" factors distinguished between sporadic and familial cases, it is concluded that serum iCT measurements should be carried out in primary relatives of all patients with MCT.     

Medullary carcinoma of the thyroid in Norway. Clinical course and endocrinological aspects

A study of the clinical, biochemical and histological findings of 57 patients with medullary thyroid carcinoma (MCT) in Norway, is presented. The diagnosis was established by light and electron microscopy and by measurements of immunoreactive calcitonin (iCT) in serum. The major factor influencing the prognosis was the extension of the disease at presentation. None of the 24 patients with tumour confined to the thyroid gland have died of the disease, and serum iCT was normal in 15 patients. Of 19 patients with regional lymph node metastes only 11 are alive 1 to 14 years after treatment, and of these 9 had increased serum iCt. 14 patients technically inoperable and/or with distant metastases, 12 have died of MCT, 1 are alive with elevated serum iCT. Of 14 patients with raised serum iCT, 8 have no clinical recurrence of the disease from 1 to 15 years after the operation. MCT-associated diseases were found in 8 patients, chronic thyroiditis in 10. Serum iCT was measured in 249 relatives of 42 patients, and abnormal elevations were found in 11 members of 6 families.     

The bioregulatory system L-arginine--nitric oxide

BACKGROUND: Patients operated on for medullary thyroid carcinoma (MTC) frequently have persistent elevated plasma calcitonin concentrations after operation, indicating remaining tumor. The plasma calcitonin concentration in a patient with MTC roughly reflects the endogenous tumor burden. The only effective treatment for MTC is surgical. The decision about whether a patient with persistent MTC should have a repeat operation would be influenced by knowledge of the natural course of the disease. METHODS: Forty patients with persistently elevated peak plasma calcitonin concentrations after thyroidectomy for MTC were monitored for a mean of 6 years. Serial determinations of plasma calcitonin levels were obtained before and after intravenous injection of calcium and pentagastrin. RESULTS: At the first postoperative test 63% of the patients had undetectable basal calcitonin values, although their stimulated plasma calcitonin concentrations were elevated. The mean annual increase in stimulated plasma calcitonin concentrations was 117%, but plasma calcitonin concentrations were stable in three patients and decreased in one patient. Five patients are known to have experienced distant metastases. CONCLUSIONS: MTC is a progressive disease in most patients with persistent hypercalcitoninemia after thyroidectomy. Stimulated peak plasma calcitonin levels are more meaningful than basal levels in the serial postoperative evaluation of patients with persistent hypercalcitoninemia after thyroidectomy for MTC.     

Phosphate deficiency as a rare cause of osteomalacia--case report of several years of enteral feeding and antacid therapy

HISTORY AND CLINICAL FINDINGS: Floor-of-the-mouth cancer had been diagnosed and surgically treated in a 55-year-old man 4 years before the latest admission. For the last 3 years he had been fed through a percutaneous endoscopic gastrostomy (PEG). Since then he had experienced reflux oesophagitis which was being treated with aluminium-containing antacids. He was hospitalized for the surgical treatment of bilateral fractures of the neck of the femur. A surgical biopsy revealed osteomalacia but no metastasis. INVESTIGATIONS: The serum phosphate level was significantly reduced (0.21 mmol/l) and there was no detectable phosphate excretion in the 24-hour urine. Serum calcium concentration was unremarkable, but there was hypercalciuria (34.4 mmol/d). Alkaline phosphate activity was significantly raised (393 U/l) and parathormone level reduced (7 ng/l). Vitamin D concentration was unremarkable. TREATMENT AND COURSE: The phosphate content in the parenteral feed was at first increased and additional phosphate was given by mouth. The calcium and phosphate levels slowly became normal only after medication had been changed from antacids to H2-blockers. CONCLUSIONS: In this case osteomalacia was caused not by vitamin D deficiency but by a lack of phosphate. The reduced intestinal phosphate absorption by the antacids only partially explains the pronounced clinical signs. If antacids are taken over long periods the phosphate balance should be carefully monitored to avoid osteomalacia.     

A rare case of a primary intrabronchial neurofibroma

HISTORY AND CLINICAL FINDINGS: A 42-year-old woman, a smoker for many years, had suffered from dry cough for some time. She was admitted because of haemoptyses, the first one month previously. Physical examination was unremarkable. INVESTIGATIONS: Chest radiography in two planes showed no abnormality. Computed tomography revealed a space-occupying lesion adjacent to the right main bronchus, strongly suspicious of a central bronchial carcinoma. Bronchoscopy showed a smoothly circumscribed tumour in the upper lobe bronchus which almost occluded its lumen. Multiple biopsies failed to establish the benignity/malignity of the tumour. TREATMENT AND COURSE: The tumour was removed by upper lobe resection. There was no macroscopic intraoperative evidence of infiltration. Histology provided the surprising diagnosis of a benign neurofibroma. CONCLUSION: Thoracotomy should, if at all possible, be performed whenever biopsy of a pulmonary mass fails to establish its benignity. Intrapulmonary neurofibroma is very rare, unless it is part of v. Recklinghausen's disease.     

Eggshell thickness in mallards fed methylmercury

Immunoperoxidase studies have been utilized to investigate further the previously reported presence of immunoassayable calcitonin in pheochromocytoma tissue from some patients with MEN II syndromes. We have been able to demonstrate calcitonin in pheochromocytoma tissue only in two patients with MEN II syndromes in whom the pheochromocytomas contained metastatic medullary thyroid carcinoma. In both cases, the calcitonin was present only in the medullary carcinoma. We have not been able to demonstrate immunoreactive calcitonin in normal adrenal glands or in pheochromocytomas of other patients with and without MEN syndromes. Adrenal medullary cells and thyroid C cells are both of neural crest origin and both possess APUD characteristics. The presence of calcitonin in medullary thyroid carcinoma cells and not in pheochromocytes has important implications with regard to cellular differentiation and peptide hormone production.     

Pyostomatitis vegetans and Crohn's disease. A specific association of 2 diseases

HISTORY AND CLINICAL FINDINGS: A 27-year-old man was referred to the dermatological out-patient clinic because of inflammatory changes in the oral mucosa of unknown cause. 5 months earlier he had been diagnosed as having Crohn's disease of the terminal ileum. On both sides of the buccal mucosa there were rough erythematous vegetations and disseminated miliary abscesses, which extended to the labial gingiva and the soft palate. Further physical examination was unremarkable. INVESTIGATIONS: Several inflammatory parameters were increased: C-reactive protein 100 mg/l, erythrocyte sedimentation rate 55/88 mm, eosinophilic cationic protein 35.8 ng/ml (normal range 2.3-16 ng/ml). White cell count was normal (7,25/nl), with a lymphocytopenia of 11.9%. There was no eosinophilia. Haemoglobin was reduced to 11.6 g/dl and the platelets raised to 526/nl. Smears of the oral mucosa showed no fungal, viral or bacterial infection. Biopsy revealed leucocytic microabscesses in the epithelium, granulation tissue and flat ulcerations with adjoining superficial necrotic zones. DIAGNOSIS, TREATMENT AND COURSE: The clinical and histological picture as well as the association with Crohn's disease (CD) suggested pyostomatitis vegetans (PV). The PV was treated with disinfectant mouth washes which improved the subjective findings. Budesonide was given for CD. CONCLUSION: PV is a rare and usually isolated condition, but it can also occur in association with a chronic gastrointestinal disease such as ulcerative colitis and Crohn's disease. The diagnosis of PV indicates a thorough gastroenterological investigation.     

Solitary metastasis of a clear cell renal cell carcinoma after a 20 year latency clinically simulating a vascular tumor

HISTORY AND CLINICAL FINDINGS: A 72-year-old woman was referred because of progressive skin discoloration with venectasia and swelling in the left lower leg, the possible diagnosis being atypical varicose veins. 20 years before she had a right nephrectomy for "clear-cell" renal adenocarcinoma with subsequent tele-cobalt radiotherapy. On examination a pulsating swelling was palpated over the hyperpigmented area of the skin with venectasia. INVESTIGATIONS: She had hypercholesterolaemia (254 mg/dl) and hyperuricaemia (uric acid 6.2 mg/dl). Duplex sonography, angiography and computed tomography of the lower leg revealed a vascular tumour with infiltration of the right head of the gastrocnemius. DIAGNOSIS, TREATMENT AND COURSE: Because an arteriovenous fistula within a vascular soft-tissue tumour of unknown histology was suspected, a wide resection was performed. Histopathological examination revealed a metastasis of a clear-cell adenocarcinoma. Postoperative diagnostic tests discovered no other findings suspicious of malignancy. It is therefore to be assumed that the resected tumour was a solitary metastasis of the renal adenocarcinoma removed 20 years previously. CONCLUSION: Even rare causes should be considered in the differential diagnosis of vascular tumour, as this case of a solitary metastasis after a latency of 20 years demonstrates.     

The diagnosis of medullary carcinoma of the thyroid (author's transl)

The pentagastrin stimulation test was given to ten brothers and sisters of two patients who had previously undergone total thyroidectomy for medullary carcinoma of the thyroid. 5 microng pentagastrin/kg body-weight were injected as an intravenous bolus and calcitonin levels determined before and after. The test was positive in four members of the family and the presence of a medullary carcinoma was subsequently confirmed in them histologically.     

Churg-Strauss syndrome with right ventricular tumor

HISTORY AND CLINICAL FINDINGS: A 47-year-old woman was admitted because of diarrhoea (3-5 stools daily) for 9 days, weakness for 3 weeks and painful wrist swelling, arthralgia and hyperesthesia over the medial aspect of the right thigh for 6 weeks. For 6 years she had been treated for asthma. Two operation had been performed for chronic sinusitis. ADMISSION FINDINGS AND INVESTIGATIONS: There was marked eosinophilia (5889/microliter) and thrombocytopenia (96,000/microliter), markedly increased serological inflammatory parameters and a raised total IgE level (134 IU/ml). The chest radiogram showed pulmonary infiltrates and bone marrow biopsy indicated eosinophilia. Echocardiography revealed a mass, 3 x 8 cm, in the ventral wall of the right ventricle with extension into the outflow tract. DIAGNOSIS, TREATMENT AND COURSE: These findings met the criteria of the American College of Rheumatology for Churg-Strauss syndrome (CSS). On methylprednisolone (1 mg/kg daily) the eosinophil and platelet counts became normal within 5 days and erythrocyte sedimentation rate and the level of C-reactive protein fell. Under cardiopulmonary bypass the tumour was removed, the tricuspid valve replaced, and the right ventricle reconstructed. Histology of the mass revealed it to be an organized thrombus. CONCLUSION: The relationship between the thrombus formation and CSS is unclear. Hypercoagulability connected with the inflammatory process may have played a part in the pathogenesis.     

Prophylactic thyroidectomy for medullary thyroid carcinoma in gene carriers of MEN2 syndrome

BACKGROUND/PURPOSE: Although medullary thyroid carcinoma (MTC) can occur sporadically, in the pediatric population it is most often associated with the multiple endocrine neoplasia syndrome (MEN type 2). Traditional screening was based on evaluation of basal and stimulated serum calcitonin levels. The recent cloning of the MEN2 gene on the RET proto-oncogene of chromosome 10 now allows for testing of gene carrier status in individuals at risk who could benefit from prophylactic treatment. The current study was undertaken to determine the appropriate age for safe total prophylactic thyroidectomy. METHODS: Over a 16-year period, 12 patients with a family history of MEN2A and one with a MEN2B underwent total thyroidectomy and central neck dissection without parathyroid autotransplantation. Four patients (31%) were treated previously for Hirschsprung's disease. RESULTS: In seven patients (mean age, 11.8 years) undergoing biochemical screening for diagnosis, multifocal MTC and C cell hyperplasia (CCH) were found in all the resected specimens. Of six patients identified with genetic screening (mean age, 9.1 years), two had elevated stimulated calcitonin levels, one (age 14) had evidence of MTC, and one (age 6) had CCH. Four patients with normal calcitonin levels had no evidence of MTC (ages 6, 8, 10) but there was one occurrence of CCH (age 11). No permanent postoperative hypoparathyroidism or recurrent laryngeal nerve damage occurred in this series. With a mean follow-up of 4 years (range, 1 to 14 years), the overall disease-free survival is 100%. CONCLUSIONS: From this study the authors conclude that total thyroidectomy can be performed safely in children and should be the treatment of choice in patients with a family history of MEN2A carrying a germinal RET mutation even if the serum basal or stimulated serum calcitonin level is normal. Total thyroidectomy should be performed as early as 5 years of age before the occurrence of CCH or MTC.     

Coexistence of papillary and medullary carcinoma of the thyroid gland-mixed or collision tumour? Clinicopathological analysis of three cases

We present three thyroid carcinomas displaying medullary and papillary components. In two cases the papillary component was characterized by typical papillae with a fibrovascular core; in one a follicular variant of papillary carcinoma was found. The papillary component was dominant in two and the medullary in one case. One tumour showed clear-cut borders between the two components, the others displayed an intermingled pattern. Both tumour components were seen in lymph node metastases with immunostaining with antibodies to calcitonin, chromogranin A, carcinoembryonic antigen, other neuroendocrine markers and thyroglobulin. At least two of our cases are true mixed carcinomas probably arising from a common stem cell.     

Congenital absence and aberrant course of the internal carotid artery

OBJECTIVE: To evaluate the extent of vascularization by assessing vascular surface density in renal cell carcinomas (RCCs) of different nuclear grades, and in normal renal cortex and medulla. MATERIALS AND METHODS: Specimens of 79 RCCs of different nuclear grades (16 of G1, 42 of G2 and 21 of G3) were immunostained with the lectin Ulex europaeus agglutinin-I (UEA I). The vascular surface density of tumour tissue was assessed stereologically using a test grid at x400 magnification and compared to the values obtained in normal renal tissue. RESULTS: G3 tumours had a lower vascular surface density than had G1 and G2 RCCs and normal renal tissue of the cortex and medulla (P < 0.001, respectively). G1 tumours had a significantly higher vessel density than had normal medullary parenchyma and G2 carcinomas (P < 0.001). Vessel density was not significantly different among G1 tumours and cortical parenchyma in controls and among normal medullary tissue and G2 tumours. Statistical analysis showed that the vascular surface density was independent of tumour stage and size and the age and sex of the patients. CONCLUSION: The degree of vascularization in RCCs decreased with their grade of differentiation, suggesting that the extent of neovascularization in tumour tissue reflects the relationship between tumour cell proliferation and vascular growth. The values of vascular surface density in normal renal tissue of the cortex and medulla partially overlapped with those obtained in tumour tissue.     

A 44-year-old patient with cardial carcinoma and paraneoplastic orbital disease

HISTORY AND CLINICAL FINDINGS: Bilateral orbital involvement with chemosis, protrusion and reduced vision developed in a 44-year-old man 12 weeks after carcinoma of the cardia with lymph node metastases and peritoneal carcinomatosis had been diagnosed and palliative chemotherapy with a cycle of leucovorin and 5-fluorouracil had been concluded. INVESTIGATIONS: Computed tomography excluded a retrobulbar metastasis. Thyroid hormone concentration was normal as was the thyroid autoantibody titre. There was also no evidence on sonography of endocrine orbital disease. These findings established the diagnosis of paraneoplastic orbital myositis. TREATMENT AND COURSE: The symptoms briefly regressed on initial treatment with systemically administered high doses of corticosteroids. Renewed marked eyeball protrusion with incipient visual loss was treated with conjunctival drainage and tarsorrhaphy, as well as radiotherapy to the retrobulbar space. This achieved significant improvement. Shortly thereafter the patients died of acute bleeding from the primary tumour. CONCLUSION: In patients with an underlying malignancy and symptoms of orbital myositis orbital involvement as part of a paraneoplastic syndrome should be diagnosed once other causes have been excluded.     

Usefulness of the genetic study in the diagnosis of medullary carcinoma of the thyroid

Germ-line mutations in the RET proto-oncogene are associated with multiple endocrine neoplasia type 2A (MEN 2A) and with familial medullary thyroid carcinoma (FMTC). Detection of these mutations allows the identification of the affected kindred members, who will develop medullary thyroid carcinoma (MTC) in 100% of cases. We studied 24 patients of two kindreds (MEN 2A and FMTC). Basal calcitonin levels and pentagastrin-stimulated calcitonin were measured in all patients. The RET mutations were detected by DNA analysis. The RET mutations were identified in 14 patients. Two of them had been operated in the past, 2 refused operation and 4 were living abroad. In the 6 remaining, only one showed a thyroid mass, basal calcitonin was normal in all patients except one, and pentagastrin-stimulated calcitonin was negative in 2 patients. Total thyroidectomy was performed in all cases. Histology showed C-cell hyperplasia in all patients and MTC in 5 of them. In MEN 2A and FMTC DNA analysis allows the identification of RET mutation carriers, in which presymptomatic thyroidectomy allows and improvement in survival.     

Syncope in 3rd degree atrioventricular block. Detection of virus genome in the myocardium

HISTORY AND CLINICAL FINDINGS: A 28-year-old woman was admitted after syncope which had been preceded by several flulike episodes. There was no history of any other serious disease. Physical examination was unremarkable. Heart sounds were regular and normal, there were no murmurs. INVESTIGATIONS: White cell count was 9400/microliter, with a normal differential count. Erythrocyte sedimentation rate and C-reactive protein were also normal. Virus serology revealed no abnormality. The electrocardiogram (ECG) showed complete (third degree) atrioventricular (AV) block with an idioventricular rhythm of 38 beats/min and right bundle branch block pattern. TREATMENT AND COURSE: A temporary transvenous pacemaker was inserted on the first hospital day. As myocarditis was suspected a right ventricular endomyocardial biopsy was obtained. Histological and immunohistological examinations demonstrated no unequivocal findings. But molecular-biological tests revealed. Coxsackie-B3 virus genome. The pacemaker was removed on the 6th day, when the ECG had shown intermittent second degree AV block. Regular sinus rhythm with a PR interval of 0.18 s was recorded on day 12, and 24-hour ECG monitoring for several days until her discharge on the 18th day confirmed this rhythm throughout. CONCLUSION: In aetiologically undetermined disease molecular-biological techniques can be indispensable for the exact diagnosis and may be decisive for administering specific treatment.     

Social medicine and public health]

A case of Sipple's syndrome is reported, in which the full phenotype was expressed. The patient had the typical marfanoid habitus, with thickened lips and alae nasi, neuromas on lips and tongue, medullary carcinoma of the thyroid gland, phaeochromocytomas, and medullated corneal nerve fibres. The plasma calcitonin level was initially elevated, rose on calcium infusion before thyroidectomy, and was undetectably after thyroidectomy. The urinary catecholamine excretion was elevated. The plasma parathyroid hormone, adrenocorticotrophin and growth hormone levels and the serum calcium level were normal.     

Intestinal ganglioneuromatosis--a rare cause of chronic diarrhea

A case of intestinal ganglioneuromatosis is reported. The symptoms were watery diarrhoea and abdominal pain of several months duration. Endoscopic examination of the oesophagus, ventricle, duodenum, colon and rectum was normal. Mucosal biopsies from colon and rectum revealed ganglia cells and thin nerve fibres in the lamina mucosa, giving the diagnosis ganglioneuromatosis. As a consequence of the diagnosis thyroid scintigraphy, CT-scanning of the thyroid and adrenal glands and measurement of serum calcitonin and gastrin were performed. The tests revealed an intrathoracic nodular struma, and beyond this no abnormalities. The relation of intestinal ganglioneuromatosis to Multiple Endocrine Neoplasia type II b is discussed and the necessity of performing mucosal-biopsy from endoscopically normal colonic mucosa in cases of chronic diarrhoea is emphasised.