title: Clinical endocrine and metabolic studies in medical conditions characterised by hypoxia
Creators: name: Semple, Peter d'Almaine
Publisher: name: University of Glasgow
Year: 1984

description: The thesis embraces fourteen related projects carried out along with various willing colleagues in several Scottish hospitals over nine years and most of the findings have been published (reprints enclosed). In the first clinical and illustrated autopsy studies of Scottish patients with severe emphysema associated with alpha-1-antitrypsin deficiency, we found weight loss to be a frequent accompaniment of the panacinar emphysema. Though decreased calorie intake had been claimed to be a cause of weight loss in emphysema scrutiny of the evidence suggested other factors to be involved. My early research endeavoured to cast light on reasons other than genetic for such weight loss and for the contrast in body habitus between emphysematous 'pink puffers' and bronchitic 'blue bloaters'. The early results provided more questions than answers and set the stage for the further work described in the thesis. In our pilot studies searching for metabolic abnormalities, low total body potassium values, believed to indicate lean tissue loss, were found in both 'pink puffers' and 'blue bloaters'. Though the latter group were considerably heavier they showed no difference in calorie intake or dietary absorption. Anabolic steroid studies showed major changes including low levels of serum testosterone especially in blue bloaters while the pink puffers in addition had high levels of the adrenal androgen dehydroepiandrosterone. We felt these endocrine patterns might to some extent be effecting physical characteristics in the two groups. A further study of similar patients confirmed a correlation between the level of hypoxia, but not of hypercapnia, and the degree of testosterone reduction and indeed eighty per cent of patients with a PaO2 below 6.6kPa (50mmHg) had low serum testosterone levels. The association which to us strongly suggested a causal relationship had never previously been described. Combined pituitary stress tests in these patients indicated suppression of the hypothalamo-pituitary-testicular axis while other aspects of hypothalamic and pituitary function were comparatively well preserved. Evidence was found that the hypothalamus rather than the pituitary was responsible for the deficient steroidogenesis. Similar but not identical endocrine abnormalities were found in patients with hypoxic restrictive. lung disease (pulmonary fibrosis) and here in some cases pituitary rather than hypothalamic suppression seemed responsible for the low testosterone levels. Individuals with cyanotic congenital heart disease, similarly hypoxic, had normal testosterone values perhaps because they have tolerance to hypoxia from birth. A parallel may be drawn between visitors at high altitudes who develop low testosterone production and high altitude natives who, though similarly hypoxic, retain normal levels. As an appendix we have reported a case of obstructive sleep apnoea (Pickwickian) syndrome. Rapid weight gain following cessation of smoking was accompanied by onset of sexual impotence and bouts of somnolence. Frankly low serum testosterone levels were found but after weight reduction, which improved respiratory function and oxygenation, testosterone levels became normal and sexual potency returned. Although sexual impotence had been noted previously in this rare syndrome, the hormone changes had never been described. A study of patients in acute phase cor pulmonale confirmed low levels of serum testosterone, luteinising hormone, follicle stimulating hormone and dehydroepiandrosterone. They had all risen on recovery three months later along with improvement in arterial oxygen tensions thus offering further evidence of hypoxic suppression of the hypothalamus and/or pituitary and also illustrating that such suppression is reversible. Possible consequences of low testosterone production were investigated. Hypoxic respiratory patients were found to have diminished libido and evidence of organic sexual impotence which varied with disease severity, arterial oxygenation and testosterone values. This contrasted with normal sexual function in men with cyanotic congenital heart disease and comparable hypoxia.