Diarrhoea associated with medullary carcinoma of the thyroid

Abstract

SUMMARY Diarrhoea, which is present in roughly one third of cases of medullary carcinoma of the thyroid, was investigated in five cases.Excessive loss of water and electrolytes in the stools was the major factor. Steatorrhoea was mild or absent, and intestinal absorption of glucose and vitamin B12 was normal; the histological appearance of the small intestinal mucosa was normal or subnormal. Water and sodium diarrhoea seems to be linked to a sometimes considerable increase in the rate of transit through the small intestine and colon, and may be relieved by codeine or codethyline. The frequent increase in the maximum blood sugar level during an oral tolerance test should not be interpreted as evidence of a paradiabetic condition. In fact, the intravenous glucose tolerance test is usually normal and the excessive rise in blood sugar after oral administration seems to be the consequence of the increased rate of transit through the small intestine.The link between the tumour and the disordered motility seems definite in view of certain cases in which removal of the tumour caused the diarrhoea to disappear immediately. Production by the tumour of serotonin or other derivatives of tryptophan or of kallikrein, which activates bradykinin, is rare. With regard to prostaglandins, high concentrations have been observed in the tumours and in the venous blood draining the tumours, but their presence in systemic blood is inconstant. The only hormonal substance, concentration of which seems to be definitely increased in the systemic blood of patients with a medullary carcinoma of the thyroid, is thyrocalcitonin but this hormone does not seem to have any effect on the motor activity of the digestive tract.Since the first descriptions by Williams (1966) and Bemiel, Bouvry, Cattan, and Prost (1966) diarrhoea associated with medullary carcinoma of the thyroid has been reported on several occasions (Bemier,

Familial medullary thyroid carcinoma, pheochromocytoma, and parathyroid adenoma (Sipple's syndrome)Study of a kindred

“…All available evidence, however, indicates that they probably occur as a compensatory response to the hypocalcemic effect of chronically increased circulating thyrocalcitonin which is elaborated by medullary thyroid carcinoma.26~44 This tumor is the only tumor in which the production of thyrocalcitonin has been described, and it has been shown to occur in concentrations greater than two thousand times that in normal thyroid t i s s~e .~~, 4 4 Thyrocalcitonin is a hypocalcemic agent which probably acts by blocking resorption of bone,l7 and it is remarkable that hypocalcemia has been reported only once and then in a patient with large masses of metastatic medullary thyroid carcinoma who also had previously undergone thyroid surgery. 26 Presumably, this is because of the ability of the 3,21,37,64 Vol. 28 parathyroid glands to compensate adequately.…”

Chronic diarrhoea-all in the bowel?

“…14 Calcitonin-induced secretory diarrhoea may be an important mechanism 15 that may be independent of cyclic adenosine monophosphate. 16 Other potential mediators of diarrhoea include prostaglandins, 17 calcitonin gene-related peptide, 18 serotonin, 19 histaminase, 20 kallikrein 17 and dopa-decarboxylase. 21 The diarrhoea may be related to disordered intestinal motility, 19 but secretory mechanisms are clearly important.…”

Medullary Carcinoma of the Thyroid Gland

“…Less frequently diarrhoea may be the major presenting feature. The cause of the diarrhoea in such patients remains unknown although a number of suggestions have been put forward and attempts made to incriminate several different agents, including calcitonin itself, serotonin and the prostaglandins E2 and F2 C (Williams et al, 1968;Bernier et al, 1969;Steinfield et al, 1973). Diarrhoea seems to be more prevalent in those patients who have extensive local disease or disseminated tumour and would, therefore, appear to be related to tumour bulk (Williams, 1966).…”