Search

Summary: Glucocorticoids (GCs) are steroid hormones, which are essential for life. They are secreted by the adrenal cortex under the control of the hypothalamic‐pituitary‐adrenal (HPA) axis. Glucocorticoids are essential for the normal function of most organ systems and, in both, excess and deficiency can lead to significant adverse consequences. Adrenal insufficiency (AI) is a rare, life‐threatening disorder characterized by insufficient production of corticosteroid hormones. Primary AI is defined by the inability of the adrenal cortex to produce sufficient amounts of glucocorticoids and/or mineralocorticoids despite normal or increased adrenocorticotropin hormone (ACTH). Secondary AI is adrenal hypofunction due to insufficient amount of ACTH produced by the pituitary gland. Conventional treatment of both primary and secondary adrenal insufficiencies involves lifelong glucocorticoid replacement therapy. The role of cortisol deficiency and the impact of hydrocortisone replacement on morbidity and mortality in this patient group are under increasing scrutiny. Established glucocorticoid replacement regimens do not completely mirror endogenous hormonal production, and their monitoring to ensure optimum therapy is hampered by the lack of reliable biomarkers of hormone sufficiency. A further confounding issue is the tissue‐specific regulation of glucocorticoid through the two isozymes of 11β‐hydroxysteroid dehydrogenase (11β‐HSD) with research focusing on the role of this prereceptor regulation in the development of adverse metabolic features in patients. This review defines the factors influencing glucocorticoid action in patients with adrenal insufficiency receiving glucocorticoid therapy. [ABSTRACT FROM AUTHOR]

Somatostatin analogues have been used as an adjunct to surgery and radiotherapy in the treatment of acromegaly for over 15 years, but debate surrounds their use as primary therapy. Newman suggested that octreotide was equally effective as primary or adjuvant therapy, but the effects of previous surgery/radiotherapy may have led to a preselection bias. In an attempt to eliminate this bias, the efficacy of the depot somatostatin analogue Sandostatin® LAR® as primary and adjuvant therapy has been assessed using GH and IGF-I levels at diagnosis as baseline values. We retrospectively analysed the GH and IGF-I data from a large multicentre study in which patients’ biochemical response to treatment with the depot somatostatin analogue Sandostatin LAR as primary and adjuvant therapy was assessed. We used GH and IGF-I levels at diagnosis as baseline values to eliminate any preselection bias. In 91 patients (42 male) studied, mean serum GH fell from 36·2 ± 3·3 µg/l (SEM) at diagnosis to 2·2 ± 0·2 µg/l after 48 weeks of treatment ( P < 0·0001). In the primary ( n = 34) and adjuvant ( n = 57) therapy groups, mean GH fell from 30·7 ± 5·7 to 2·6 ± 0·4 µg/l ( P < 0·0001) and from 39·5 ± 4·1 to 2·0 ± 0·2 µg/l ( P < 0·0001), respectively. Sixty-two percent of patients in the primary therapy group and 70% in the adjuvant therapy group achieved GH < 2 µg/l. Serum IGF-I levels were available in 67 patients (34 male). In the primary therapy group ( n = 25) mean IGF-I fell from 764 ± 68 to 414 ± 31 µg/l ( P < 0·0001) at 48 weeks. In the adjuvant therapy group ( n = 42) mean IGF-I was 666 ± 50 µg/l, falling to 384 ± 30 µg/l ( P < 0·0001) at 48 weeks. 72% of patients achieved normal age-related IGF-I-values. There were no statistically significant differences in GH or IGF-I levels between the primary and adjuvant therapy groups at diagnosis, pre Sandostatin LAR or after 48 weeks of treatment. This retrospective study demonstrates that in a group of patients with similar diagnostic GH and IGF-I levels, Sandostatin LAR was equally effective as primary therapy in acromegalic patients as in patients previously treated with surgery and/or radiotherapy. [ABSTRACT FROM AUTHOR]

OBJECTIVESTo evaluate the efficacy and safety of a long-acting preparation of the somatostatin analogue octreotide, Sandostatin-LAR® (SMS-LAR) for the treatment of acromegaly. DESIGN AND PATIENTSThirteen patients with acromegaly received intramuscular injections of SMS-LAR 20–40 mg at 4–6-week intervals for a period of up to 3 years. MEASUREMENTSSerial measurement of serum GH and IGF-1 concentrations were obtained. Symptoms related to acromegaly were scored by patients at baseline and following each injection. Serial gallbladder ultrasound and pituitary imaging was performed throughout the study. RESULTSOne patient was withdrawn from the study after 6 months because of continued gastrointestinal side effects; 4 patients were treated with monthly injections for 12 months and 8 patients with injections at either 1 month or 6-week intervals for 36 months; hence data is presented for n = 12 for up to 12 months and thereafter n = 8. SMS-LAR significantly reduced serum GH and IGF-1 values: for the whole group GH concentrations fell from 24.8 ± 4.2 mU/l (mean ± SE) at baseline to 5.2 ± 0.8 mU/l at 12 months (P < 0.01, n = 12). In the 8 patients treated for 3 years GH fell from 27.8 ± 6.1 mU/l at baseline to 4.2 ± 0.8 mU/l at the end of 3 years (P < 0.01, n = 8). GH fell to <10 mU/l in all subjects and was <5 mU/l in 50% after both 1 and 3 years. IGF-1 concentrations fell from 95 ± 13 nmol/l at baseline to 63 ± 13 nmol/l after 1 year (P < 0.01, n = 12; reference range <65 nmol/l). In the 8 patients treated for 3 years IGF-1 concentrations fell from 119 ± 14 nmol/l at baseline to 60 ± 13 nmol/l after 3 years (P < 0.001, n = 8). IGF-1 was <65 nmol/l in 60% of patients after 1 year and 75% after 3 years. Treatment resulted in trends towards improvement in symptoms of acromegaly and statistically significant improvement in sweating. There was no evidence of tachyphylaxis or evidence to suggest... [ABSTRACT FROM AUTHOR]