Postmenopausal women with vasomotor symptoms have increased urinary excretion of calcitonin gene-related peptide.

OBJECTIVES: To establish whether 24 h urinary excretion of the potent vasodilator calcitonin gene-related peptide (CGRP) was higher in postmenopausal women with vasomotor symptoms compared to the level in women without symptoms. We also wanted to establish whether urinary excretion of CGRP changed during the menstrual cycle in women of fertile age. MATERIAL AND METHODS: Thirteen postmenopausal women with and 13 women without vasomotor symptoms were included. Urine was collected over 24 h and CGRP excretion was measured utilizing radio-immunoassay technique. Twenty-four hour CGRP excretion was also measured in ten fertile women with regular cycles in early follicular, preovulatory and midluteal phase. RESULTS: Twenty-four hour urinary excretion of CGRP was significantly higher in women with vasomotor symptoms compared to non-flushing women (median 7.16 vs 5.15 pmol/24 h; P = 0.028). CGRP concentrations were stable throughout the ovulatory cycles. CONCLUSION: The 24 h urinary excretion of CGRP is higher in women with vasomotor symptoms than in women without these symptoms. CGRP may be the mediator of vasodilator signals originating from the thermoregulatory center.

Pseudocarcinoid syndrome associated with hypogonadism and response to testosterone therapy.

OBJECTIVE: To characterize a disorder of episodes of flushing and increased levels of 5-hydroxyindoleacetic acid (5-HIAA) in men with secondary hypogonadism who respond to testosterone therapy. MATERIAL AND METHODS: We present detailed case reports of three male patients who had flushing, secondary hypogonadism, and increased urinary 5-HIAA levels and describe their clinical and laboratory features before and after treatment with testosterone. In addition, six male patients with hypogonadism (three with primary and three with secondary hypogonadism) without flushing were assessed. RESULTS: The three patients with flushing and secondary hypogonadism (serum total testosterone 5.45 +/- 0.63 nmol/L, free testosterone 89.3 +/- 7.0 pmol/L, follicle-stimulating hormone 3.85 +/- 0.58 IU/L, and luteinizing hormone 4.41 +/- 0.98 IU/L) had increased urinary 5-HIAA levels (98.5 +/- 12.2 micromol/24 h) but normal blood serotonin levels (9.66 +/- 1.58 micromol/L). During a pentagastrin-calcium stimulation test, serum calcitonin and blood serotonin values were normal in patients with secondary hypogonadism and flushing. Detailed investigation showed no evidence of a carcinoid tumor. Urinary 5-HIAA levels became normal (16.6 +/- 1.73 micromol/24 h) after treatment with testosterone. When testosterone therapy was discontinued in two patients, flushing and increased urinary 5-HIAA levels recurred. Furthermore, flushing and the elevated urinary 5-HIAA values resolved when testosterone treatment was reinitiated. The six patients with hypogonadism without flushing had normal urinary 5-HIAA levels (14.9 +/- 3.31 micromol/24 h). CONCLUSION: Male patients with flushing and increased urinary 5-HIAA levels should undergo assessment for hypogonadism after screening for carcinoid tumor. If hypogonadism is diagnosed, resolution of flushing and normalization of 5-HIAA may be achieved with testosterone treatment. We suggest that pseudocarcinoid syndrome associated with hypogonadism be the descriptive label used for this combination of clinical features.

The clinical and laboratory correlates of an increased urinary 5-hydroxyindoleacetic acid.

Over a five-and-a-half-year period, there were 298 laboratory requests for urinary 5-hydroxyindoleacetic acid (5-HIAA). The clinical and laboratory associations of the 24 patients in which there were 43 urinary 5-HIAA 24-h collection results greater than the laboratory upper reference limit are detailed. Four were confirmed carcinoid tumours and two were phaeochromocytomas. Flushing was a prominent symptom in 46% and diarrhoea or altered bowel habit in 37%. Associated with the raised urinary 5-HIAA values were increased levels of 4-hydroxy-3-methoxymandelic acid and homovanillic acid in 14.3% and 21%, respectively, of those collections where the metabolites were requested. Diagnostic imaging was performed in 57%. While the specificity was 88%, 5-HIAA is relatively insensitive in the diagnosis of carcinoid tumours and a more widespread use of diagnostic imaging including isotope scanning with labelled metaiodo-benzylguanidine, vasoactive intestinal peptide and octreotide is suggested.