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G. Forsbach, J. Contreras, R. de Hoyos and A. Martinez-Campos

Abstract. Only partial studies evaluating the endocrine profile in molar pregnancy have been performed. In order to characterize the neuro-endocrine pattern during and after molar pregnancy, we studied the basal hormonal levels of hCG, human placental lactogen (hPL), FSH, GH, TSH, free thyroxine index (FTI), oestradiol-17β (E2), and progesterone (PG), as well as the anterior pituitary response to TRH, GnRH, and hypoglycaemia induced by insulin in 7 patients during molar pregnancy and one week after molar abortion. hCG showed significantly higher serum levels during rather than after molar pregnancy and hPL was detectable in only 4 patients during, but in none after molar pregnancy. FSH values were in the follicular phase range before and after molar abortion (12.7 ± 0.8 and 12.7 ± 3.5 IU/l). PRL had elevated basal levels before and after molar abortion; 103.0 ± 16.5 and 43 ± 10.6 μg/l, respectively (P < 0.05). GH levels were distinctly elevated in 3 patients during molar pregnancy; after molar abortion, the basal GH values were normal in all patients < 10 μg/l. Basal cortisol and TSH levels were in the normal range before and after molar abortion. The FTI was above the normal range in 3 patients during molar pregnancy, whereas after molar abortion the values were normalized. E2 levels were elevated before and after molar abortion, 1881 ± 477 and 96.5 ± 39.2 ng/l, respectively (P < 0.01). PG levels before and after molar abortion were 30.9 ± 5.4 and 10 ± 6.7 μg/l, respectively (P < 0.05). Comparison of women with molar pregnancy vs women with normal pregnancy showed a significant difference only as to β hCG (P < 0.05), whereas comparison of women in molar puerperium vs women in normal puerperium after term pregnancy showed a significant difference in β hCG (P < 0.01), PRL (P < 0.01), and PG (P < 0.01). Six of the 7 patients had a PRL increase of over 100% of the basal level in the first 15 min after TRH administration; one week after molar abortion, all patients had a normal PRL response to TRH. During molar pregnancy, only 3 patients showed a normal TSH response to TRH, 4 patients did not respond; 3 of them had an FTI above normal range. During the second challenge one week after molar abortion, 5 patients showed a normal TSH response to TRH. The hypoglycaemia stimulus induced a normal cortisol and GH response in 6 and in 5 patients, respectively, during molar pregnancy; after molar abortion, all patients had a normal cortisol and GH response to hypoglycaemia. FSH had no response to GnRH during or after molar pregnancy. These results establish the neuro-endocrine pattern in patients with molar pregnancy showing a clear disturbance in the neuro-endocrine regulation of the thyroid axis as well as in the GH release.

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E. E. Müller, F. Cavagnini, A. Martinez-Campos, C. Maraschini, P. Giovannini, A. Novelli and V. De Leo

Abstract. Prolactin (Prl) and growth hormone (GH) responses to different pharmacologic probes acting at the central nervous system (CNS) or the anterior pituitary (AP) level were evaluated in patients with distinct neuroendocrine disorders. Thirteen patients with Prl-secreting tumours (PST), 10 acromegalics (A) and 8 patients with hypothalamic lesions (HL), as assessed on clinical, radiological and surgical grounds, underwent on separate occasions acute testing with the opioid peptide FK 33-824 (0.5 mg iv), the indirect dopamine (DA) agonist nomifensine (NOM, 200 mg po), the DA receptor antagonist domperidone (DOM, 10 mg iv), TRH (200 μg iv) and insulin (ITT, 0.10-0.15 IU/kg iv). All patients were evaluated pre-surgery and 4 of them also post-surgery. Prl and GH were evaluated by RIA at different time intervals following treatments.

Peculiar features of Prl and GH response could be evidenced in the patients as follows: Prl: PST patients did not respond either to stimulation by FK 33-824 (12/13) or to inhibition by NOM, (9/10), but 2/8 and 4/12 of them did respond to DOM or TRH stimulation, respectively; 8/10 A and all of the HL patients did not suppress plasma Prl following NOM, but many of them did respond to FK 33-824 (6/10 A, 5/8 HL) and TRH (9/10 A, 6/8 HL); as for GH, PST patients could be divided into FK 33-824 responders (8/12) and non-responders, whereas in only one of the A and in none of the HL patients a consistent response to the peptide was present; a major difference between A and HL patients was the ability of TRH to elicit a GH rise in the former (8/10) but not the latter (0/6). In conclusion, concomitant application of different CNS- or AP-acting stimuli seems to enable better functional connotation of individual disorders, and hence, provide information of value for the underlying pathophysiology.

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H Sourij, I Schmoelzer, A de Campo, N J Tripolt, T Stojakovic, H Scharnagl, E Kettler-Schmut, T Forst and T C Wascher

Objective

To control postprandial hyperglycemia in insulin-treated type 2 diabetic patients, prandial therapy with regular human insulin (HI) or fast acting insulin analogs is used. Postprandial hyperglycemia seems to be reduced more effectively with insulin analogs than with normal insulin, but there are no data concerning the effect on lipolysis or pancreatic insulin and proinsulin secretion of normal insulin in comparison to insulin analogs.

Design and methods

We included 13 patients with type 2 diabetes mellitus (age 62.2±10.3 years) with preexisting insulin therapy in this crossover, prospective, open-labeled, randomized trial comparing regular HI with insulin aspart (IA) in the setting of a standardized breakfast and a standardized lunch 4 h later. Blood samples for determination of glucose, free fatty acids (FFA), triglycerides, C-peptide, and intact proinsulin were drawn during fasting and every 30 min until 4 h after the second test meal. Statistical analysis was performed with ANOVA for repeated measurements and paired Student's t-test.

Results

The mean increase in blood glucose was significantly lower after IA (24.18±16.33 vs 34.92±29.07 mg/dl, P=0.02) compared with HI. Both therapies reduced FFA; however, the mean reduction was significantly higher after IA than after HI (−0.47±0.16 vs −0.35±0.15 μmol/l, P<0.001). The mean increase in intact proinsulin was significantly lower after IA than after HI (10.53±5 vs 15.20±6.83 pmol/l, P<0.001). No differences were observed in the C-peptide levels between the two groups.

Conclusion

In the setting of two consecutive meals, IA reduces lipolysis and proinsulin secretion more effectively than HI.

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Jose de Jesus Garduño-Garcia, Ulices Alvirde-Garcia, Guadalupe López-Carrasco, Ma Elena Padilla Mendoza, Roopa Mehta, Olimpia Arellano-Campos, Ricardo Choza, Leobardo Sauque, Maria Eugenia Garay-Sevilla, Juan Manuel Malacara, Francisco J Gomez-Perez and Carlos A Aguilar-Salinas

Objective

To examine the association between thyroid function and the components of the metabolic syndrome and insulin resistance in an Hispanic population.

Design

Cross-sectional study.

Methods

Subjects with no history of thyroid disease or diabetes were included. Thyroid function was stratified as euthyroid or subclinical hypothyroidism (SCH) status and subsequently by free thyroxine (FT4) and TSH tertiles. The association of the metabolic syndrome components (defined by 2004 Adult Treatment Panel III criteria) and insulin resistance with thyroid status, TSH, and FT4 were examined.

Results

A total of 3148 subjects were analyzed. The prevalence of SCH was 8.3%. The prevalence of the metabolic syndrome was similar in euthyroid and SCH patients (31.6 vs 32.06%, P=0.89). Total cholesterol was higher in patients with SCH (5.51±1.19 vs 5.34±1.05 mmol/l, P<0.032). Serum TSH values showed a positive correlation (adjusted for age and sex) with total cholesterol, triglycerides, and waist circumference. In contrast, FT4 showed a positive correlation with high-density lipoprotein cholesterol, and an inverse correlation with waist circumference, insulin, and HOMA-IR.

Conclusion

SCH is not associated with an increased risk for the metabolic syndrome (as conceived as a diagnostic category defined by the National Cholesterol, Education Program, Adult Treatment Panel III criteria). Despite this, low thyroid function (even in the euthyroid state) predisposes to higher cholesterol, glucose, insulin, and HOMA-IR levels. The combined use of TSH and FT4, compared with the assessment based on only FT4, is a more convenient approach to evaluate the association between thyroid function and metabolic variables.