Laurence Kennedy

Growth hormone treatment of adults with growth hormone deficiency: results of a 13-month placebo controlled cross-over study.

objective We aimed to study the effect of biosynthetlc growth hormone (GH) replacement In growth hormone deficient adults.

Assessment of endocrine function after transsphenoidal surgery for Cushing's disease

OBJECTIVE We assessed the endocrine outcome after transsphenoidal surgery for Cushings disease.

Non-enzymatically glycosylated serum protein in diabetes mellitus: An index of short-term glycaemia

SummaryWe measured non-enzymatically-glycosylated serum protein by a colorimetric assay in 107 diabetic and 82 control subjects. The mean level in diabetics was more than twice that in controls. Cross sectional and longitudinal studies in diabetic patients showed that glycosylated serum protein levels correlated with both fasting serum glucose and glycosylated haemoglobin levels. The correlation between glycosylated serum protein and fasting serum glucose was closer in Type 2 than in Type 1 diabetes. Treatment aimed at improving control in eight poorly controlled diabetic patients resulted in a 37% mean fall in glycosylated serum protein within one week, whereas glycosylated haemoglobin decreased only 8%. These studies confirm that non-enzymatic glycosylation of serum proteins is enhanced in diabetes. Measurement of glycosylated serum protein appears to provide an index of glycaemia over the preceding several days. It has the advantage of detecting improvements in glycaemic control much sooner than does glycosylated haemoglobin measurement.

Bilateral adrenalectomy: low mortality and morbidity in Cushing's disease

OBJECTIVE We assessed the current role of bilateral adrenalectomy in the overall management strategy of hypercortisolism.

CLINICAL EXPERIENCE WITH KETOCONAZOLE AS A THERAPY FOR PATIENTS WITH CUSHING'S SYNDROME

Six consecutive patients with Cushings disease were treated with the broad spectrum antifungal drug ketoconazole. Urinary Cortisol levels rapidly fell to within the normal range in five of the six patients. Acute hypoadrenalism occurred in one patient, and nausea and pyrexia in three. Our experience with hepatotoxicity was different from that reported by others in that reversible hepatotoxicity was demonstrated in three patients within 7 to 12 days of treatment. Further work is required before ketoconazole can be recommended as a standard primary therapy for patients with Cushings syndrome. Continuing vigilance for both hypoadrenalism and hepatotoxicity is essential in any patient being treated with this drug either for hypercortisolism or for other reasons.

BILATERAL INFERIOR PETROSAL SINUS SAMPLING AS A ROUTINE PROCEDURE IN ACTH‐DEPENDENT CUSHING'S SYNDROME

Bilateral inferior petrosal sinus sampling was successfully performed in 12 of 13 consecutive patients with ACTH‐dependent Cushings syndrome. Ten of the patients subsequently had transsphenoidal pituitary microsurgery. Eight patients in whom the inferior petrosal sinus to peripheral vein ACTH level ratio was 1.5 or greater were found to have a pituitary adenoma. One of the remaining two patients who had ratios < 1.5 had pituitary hyperplasia while the other had no identified abnormality. In five of the patients with pituitary tumour a ratio above 1.5 was present on only one side. Bilateral petrosal sampling is therefore always necessary. Tumour localization within the pituitary was only poorly predicted by either petrosal sinus sampling (four of eight) or computed tomography scanning (three of eight). If petrosal sinus sampling is used early in the differential diagnosis of ACTH‐dependent hypercortisolism, then the use of other differential diagnostic tests may not always be necessary.

Lipodystrophy in Patients with Acromegaly Receiving Pegvisomant

CONTEXT Pegvisomant, a GH receptor antagonist, suppresses serum IGF-I levels into the normal range in more than 95% of patients with acromegaly. Documented side effects in the initial registration studies included headache, injection-site reactions, flu-like syndrome, and reversible elevation of hepatic enzymes. OBJECTIVE We report seven patients with acromegaly treated with pegvisomant who developed lipodystrophy at the site of injection (anterior abdominal wall, thigh, buttock, and upper arm). This side effect resulted in discontinuation of pegvisomant in four patients, with subsequent regression of lipohypertrophy. SUBJECTS Six female and one male patient with acromegaly, aged 24-59 yr, are reported. All patients had undergone prior transsphenoidal surgery, and four received subsequent radiotherapy. Four patients had been treated with maximal doses of somatostatin analogs with partial suppression of IGF-I levels before initiation of pegvisomant therapy. Pegvisomant suppressed IGF-I levels into the normal range in five of seven subjects, before discontinuation of the drug. Two of seven patients received pegvisomant as first-line medical therapy, without prior somatostatin analog treatment, and one received combination therapy with a long-acting somatostatin analog and weekly pegvisomant injections. One patient experienced an erythematous superficial injection-site reaction that responded to application of steroid cream before the onset of lipohypertrophy. CONCLUSIONS We report seven patients with acromegaly who developed lipohypertrophy at the pegvisomant injection site. Pegvisomant was discontinued due to dissatisfaction with lipohypertrophy by four patients. Lipohypertrophy regressed in all patients when the medication was discontinued. Lipohypertrophy recurred when two patients were rechallenged with pegvisomant. Patients receiving pegvisomant should undergo frequent examination of injection sites for lipohypertrophy.

Nonenzymatic Glycosylation of Serum and Plasma Proteins

Albumin and other serum and plasma proteins may be nonenzymatically glycosylated in vitro and in vivo. Chromatographie and colorimetrie measurement of these nonenzymatically glycosylated proteins shows that levels are approximately two to three times higher in diabetic than nondiabetic subjects. In diabetic patients levels appear to reflect glycemia in the preceding several days and correlate with other established parameters of glycemia such as fasting serum glucose, mean of several capillary blood glucose measurements, and glycosylated hemoglobin. Because serum and plasma proteins have shorter half-lives than hemoglobin, nonenzymatically glycosylated proteins are altered more rapidly than glycosylated hemoglobin in response to prolonged decreases or increases in blood glucose levels. Acetylsalicylic acid significantly inhibits in vitro glycosylation of albumin and other serum proteins incubated for up to 7 days in glucose. It is not known whether such inhibition occurs in vivo. Glycosylation of albumin appears to reduce its solubility, and glycosylation of low-density lipoprotein may increase its catabolism. Whether nonenzymatic glycosylation of other serum proteins alters their functions or may contribute to some of the long-term complications of diabetes is unknown at present.

Cyclical Cushing's syndrome first diagnosed after pituitary surgery : a trap for the unwary

Three patients were studied after transsphenoldal microsurgery for Cushings disease because their symptoms and signs were slow to settle and/or because they had variable endocrine results. All were established as having cyclical Cushings syndrome, first diagnosed post‐operatively. This may be a much more common finding than previously realized and emphasizes the need for detailed and ongoing endocrlnologlcal Investigation after transsphenoldal surgery for Cushings disease

Limited joint mobility in Type I diabetes mellitus.

Forty-two of 115 patients with Type I (insulin dependent) diabetes were found to have limited joint mobility affecting mainly the small joints of the hands. The presence of joint abnormalities was related to duration of diabetes. Patients with limited joint mobility had a significantly higher incidence of proliferative retinopathy than patients with normal joint mobility and a similar duration of diabetes (P<0·001). Limited joint mobility appears to be an early marker for the development of microvascular complications in diabetes.