Hormone Deficient Patients Research Articles

Mortality, cardiovascular events and risk factors in hypopituitarism

The issue of whether hypopituitarism is a risk factor for increased mortality from all causes, and particularly from vascular disease, has been evaluated in four retrospective analyses. In all studies, all-cause mortality was significantly increased by 1.3-2.2-fold compared to age- and sex-matched cohorts. The increase in vascular mortality was significant in the two studies from Sweden (1.8-1.9-fold) but not in the two from the UK (0.8-1.4-fold). The total number of deaths relating to all-cause and vascular mortality was relatively small, and the 95% confidence intervals on the observed to expected (O/E) mortality ratios were wide, in some instances crossing the unity line. As retrospective epidemiological studies, these trials suffer from several drawbacks. They included small numbers of patients and events (i.e. deaths), and determination of the number of deaths and their causes may be incomplete, with small additions or subtractions impacting on O/E mortality ratios. A precise diagnosis of pituitary hormone deficiency in patients recruited in the earlier years of the studies (pre-1965) often relied on historical details and not on firm biochemical values. None of the studies provided any measurement of growth hormone status for the cohorts, and in only one study was there any relationship between a particular axis deficiency and all-cause mortality. This finding suggested that hypogonadal subjects were relatively protected compared with eugonadal counterparts. However, this must be regarded as a preliminary conclusion. These retrospective studies indicate that there are no data to support a relationship between vascular or all-cause mortality in hypopituitarism and growth hormone deficiency. Nevertheless, they do provide preliminary evidence to suggest that it would be worthwhile to conduct a large, multicentre, prospective study of well-characterized and documented patients with a sufficient number of events, in order to establish definitively the relationship between various axis deficiencies and mortality.

Hypopituitarism Following External Radiotherapy for Pituitary Tumours in Adults

The development of anterior pituitary hormone deficiencies has been studied in a group of 165 patients who underwent external radiotherapy for tumours of the pituitary or closely related anatomical sites, and who have been observed for up to 10 years. One hundred and forty had undergone pituitary surgery before radiotherapy. All patients received external radiotherapy by a three-field technique, giving 3750-4250 cGy in 15 or 16 fractions over 20-22 days. A combined test of anterior pituitary function using insulin hypoglycaemia or glucagon stimulation in conjunction with thyrotrophin and gonadotrophin releasing hormone tests and basal estimations of prolactin, thyroid hormones and testosterone or oestradiol was performed before radiotherapy. This was repeated six and 12 months later and subsequently annually. Before radiotherapy, 18 per cent of patients had normal growth hormone secretion, 21 per cent had normal gonadotrophin secretion, 57 per cent had normal corticotrophin reserve and 80 per cent had normal thyrotrophin secretion. Life table analysis demonstrated increasing incidences of all anterior pituitary hormone deficiencies with time: by five years all patients were growth hormone deficient, 91 per cent were gonadotrophin deficient, 77 per cent were corticotrophin deficient and 42 per cent were thyrotrophin deficient. At eight years, respective incidences of deficiencies were 100, 96, 84 and 49 per cent. Radiation-induced hyperprolactinaemia was seen in 73 patients; mean serum prolactin concentration rose from 227 +/- 11 mU/l to a peak of 369 +/- 60 mU/l at two years and subsequently declined towards the basal value. The primary diagnosis, patient age, sex, irradiated tissue volume and previous surgery were examined as variables that might influence the rate of development of anterior pituitary hormone deficiencies, but none of these factors had a significant effect. The radiation induced hyperprolactinaemia was however more marked in female patients. Although anterior pituitary hormone deficiencies most commonly developed in the order growth hormone, gonadotrophin, corticotrophin, thyrotrophin (61 per cent of patients), other sequences were evident. Most notably corticotrophin deficiency occurred before gonadotrophin deficiency. There is a high incidence of anterior pituitary hormone deficiencies in patients treated surgically for pituitary tumours and the incidence increases after external radiotherapy. Deficiencies may occur in an unpredictable sequence and endocrine testing is recommended on an annual basis.

Growth Hormone Deficiency in Patients With Idiopathic Adrenocorticotropin Deficiency Resolves During Glucocorticoid Replacement

Glucocorticoids (GC) have stimulatory effects on GH secretion in vitro and suppressive effects when administered in pharmacological amounts in vivo. We studied six patients with ACTH deficiency and severely impaired serum GH responses to insulin tolerance tests and arginine infusion tests. All patients underwent the same tests during GC replacement while receiving cortisone acetate in doses ranging from 12.5-25 mg/day. The three patients with idiopathic ACTH deficiency and no evidence of pituitary mass lesions had impaired GH secretion, which returned to normal during GC replacement. In contrast, the three patients with ACTH deficiency and hypothalamo-pituitary mass lesions detected by a computed tomography scan had impaired GH secretion during GC replacement therapy. Our data indicate that in patients with idiopathic ACTH deficiency, an impaired GH response to stimuli reversible during GC replacement therapy may be the functional consequence of the low levels of circulating cortisol. We conclude that physiological serum cortisol levels are necessary for normal serum GH responses to provocative stimuli in man.

Growth hormone deficiency in patients with histiocytosis X

Twenty-two patients with biopsy proved histiocytosis X, aged 10 months to 14 years (median 2 years) at the time of diagnosis, were observed for 6 months to 13 years (median 4 years). One patient who had received 3000 rads irradiation directly to the hypothalamic-pituitary area had clinical and biochemical evidence of growth hormone deficiency and responded to GH therapy. Thirteen patients had normal stature, normal growth velocity, and no diabetes insipidus. The GH response to insulin-induced hypoglycemia was studied in three of these 13 patients (group 1), in three children with short stature and no diabetes insipidus (group 2), and in five patients with diabetes insipidus but normal stature and growth velocity (group 3). Peak GH responses were normal (greater than 5 micrograms/L) in all patients in groups 1 and 2, but three of the five patients in group 3 had subnormal GH responses to insulin-induced hypoglycemia and to arginine, L-DOPA/propranolol, and exercise. Their growth rates continue to be normal over 6 to 14 years follow-up. Thus, although impaired GH responses were observed in four of the 12 patients tested, true growth failure occurred only in association with direct hypothalamic-pituitary irradiation. This experience and the observation that GH deficiency was diagnosed in fewer than 1% of children with histiocytosis in Canada during a 15-year period (accounting for less than 1% of all children with GH deficiency) suggest that classic GH deficiency is not a common complication of histiocytosis unless direct hypothalamic-pituitary irradiation has been given.