Cushing's syndrome in women with polycystic ovaries and hyperandrogenism.

BACKGROUND: A 41-year-old woman presented to an endocrinology-gynecology clinic having been diagnosed 7 years earlier with polycystic ovarian syndrome on account of hirsutism, subfertility, greasy skin, acne and multiple ovarian cysts. Ovulation induction had led to a successful pregnancy. Subfertility recurred, however, and persisted alongside a new diagnosis of hypertension and progressive weight gain. Upon examination, the patient was hypertensive with facial plethora, rounded facies and violaceous abdominal striae. INVESTIGATIONS: Low-dose dexamethasone test, bedtime salivary and 24-h urinary free cortisol estimations, CT scan of the abdomen, and serum hormone and gonadotropin analyses. DIAGNOSIS: Cushing's syndrome due to a right adrenocortical adenoma. MANAGEMENT: The patient underwent laparoscopic right adrenalectomy, which led to resolution of all symptoms, signs and biochemical abnormalities.

Percentage of body fat and plasma glucose predict plasma sialic acid concentration in type 2 diabetes mellitus.

Circulating sialic acid is an independent risk factor for cardiovascular disease and is higher in people with type 2 diabetes mellitus. Sialic acid is associated with body mass index, but it is uncertain whether body fat contributes to the higher levels of sialic acid in type 2 diabetes mellitus. Therefore, we have investigated whether the higher levels of sialic acid observed in type 2 diabetes mellitus persist when controlling for fatness. Fasting plasma samples were collected from 24 individuals with type 2 diabetes mellitus and 24 controls. Percentage of body fat was measured by bioelectrical impedance. Plasma sialic acid was quantified by an enzymatic method. Plasma sialic acid was higher in the group with type 2 diabetes mellitus than controls (602 +/- 14 vs 545 +/- 14 mg/L, P = .007). Percentage of body fat was associated with plasma sialic acid concentration in both the control group (r = 0.481, P = .020) and the group with type 2 diabetes mellitus (r = 0.527, P = .007). Fasting glucose was also associated with plasma sialic acid in the group with type 2 diabetes mellitus (r = 0.700, P < .001). Adjustment for percentage of body fat accounted for the higher levels of sialic acid in type 2 diabetes mellitus. Using linear regression, 54.3% of the variation of plasma sialic acid was explained by percentage of body fat and glucose concentrations in the whole group. Seventy-four percent of sialic acid variation was explained by the same model in type 2 diabetes mellitus. In conclusion, this is the first study to show that percentage of body fat predicts plasma sialic acid concentration and contributes toward higher levels of sialic acid in type 2 diabetes mellitus.

Premenopausal advantages in postprandial lipid metabolism are lost in women with type 2 diabetes.

OBJECTIVE: Women with type 2 diabetes appear to lose the protection against cardiovascular disease afforded by estrogens. We examined the effects of menopausal status on postprandial clearance of dietary fat in healthy and diabetic women. RESEARCH DESIGN AND METHODS: Fasting subjects (premenopausal and postmenopausal control subjects, premenopausal and postmenopausal diabetic women, all n = 8) were given a meal containing the stable isotope 1,1,1-(13)C-tripalmitin, with blood and breath sampled for 6 and 24 h, respectively, in the postprandial period. Lower levels of (13)C-palmitic acid ((13)C-PA) in the triglyceride fraction implies more efficient chylomicron clearance, lower levels of (13)C-PA in the nonesterified fatty acid (NEFA) fraction implies improved dietary NEFA entrapment, and higher levels of (13)CO(2) in the breath denote more efficient of oxidation of dietary-derived lipid. RESULTS: In diabetic women, there were no differences between the pre- and postmenopausal groups for any of these parameters. In contrast, premenopausal control subjects, compared with postmenopausal control subjects, had lower (13)C-PA in the triglyceride fraction area under the curve (AUC) (premenopausal median [range] 25.2 [12.1-49.4 mmol/l] per 6 h, postmenopausal 48.5 [15.5-77.2 mmol/l] per 6 h; P < 0.01) and higher (13)CO(2) levels in the breath AUC (premenopausal 22.5 [18.0-31.5%] of administered dose, postmenopausal 17.2 [11.2-31.5%] of administered dose; P < 0.01) with no difference between groups in levels of (13)C-PA in the NEFA fraction AUC. CONCLUSIONS: The premenopausal advantage in clearance of dietary lipid is not seen in premenopausal diabetic women. This is likely to promote an atherogenic lipoprotein profile and may contribute to the loss of cardiovascular disease protection seen in diabetic women.

Pasireotide therapy in a rare and unusual case of plurihormonal pituitary macroadenoma.

UNLABELLED: We report the use of pasireotide in a rare and unusual case of pituitary macroadenoma co-secreting GH, prolactin and ACTH. A 62-year-old Caucasian man presented with impotence. Clinically, he appeared acromegalic and subsequent investigations confirmed GH excess and hyperprolactinaemia. Magnetic resonance imaging (MRI) of pituitary revealed a large pituitary macroadenoma. He underwent trans-sphenoidal surgery and histology confirmed an adenoma with immunohistochemistry positive for ACTH, GH and prolactin. Acromegaly was not cured following surgery and inadequately controlled despite subsequent octreotide therapy. He underwent further debulking pituitary surgery, following which IGF1 levels improved but still high. This time adenoma cells showed immunohistochemistry positivity for ACTH only, following which subsequent investigations confirmed intermittent hypercortisolaemia compatible with pituitary Cushing's disease. We recommended radiotherapy, but in view of the pluripotential nature of the tumour, we proceeded with a trial of s.c. pasireotide therapy on the basis that it may control both his acromegaly and Cushing's disease. After 3 months of pasireotide therapy, his mean GH and IGF1 levels improved significantly, with improvement in his symptoms but intermittent hypercortisolaemia persists. His glycaemic control deteriorated requiring addition of new anti-diabetic medication. MRI imaging showed loss of contrast uptake within the tumour following pasireotide therapy but no change in size. We conclude that our patient has had a partial response to pasireotide therapy. Long-term follow-up studies are needed to establish its safety and efficacy in patients with acromegaly and/or Cushing's disease. LEARNING POINTS: Plurihormonal pituitary adenomas are rare and unusual.Patients with pituitary adenomas co-secreting ACTH and GH are more likely to present with acromegaly because GH excess can mask hypercortisolaemia.Pasireotide holds potential where conventional somatostatin analogues are not effective in acromegaly due to higher affinity for somatostatin receptor subtypes 1, 2, 3 and 5.Significant deterioration in glycaemic control remains a concern in the use of pasireotide.Currently, long-term safety and efficacy of pasireotide in patients with acromegaly and/or Cushing's disease are not fully clear.