The Development of a Direct Homologous Radioimmunoassay for Serum Cortisol

Peer Reviewe

Advances in understanding pituitary tumors.

Pituitary tumors are common in the general population. Since neuroimaging techniques have improved, pituitary tumors are more often diagnosed incidentally. About 16.7% of the general population show changes in the pituitary gland. Predominantly, pituitary tumors are benign pituitary adenomas. Pituitary carcinomas or aggressive pituitary tumors are extremely rare. They might develop from benign adenomas. New genetic and epigenetic abnormalities help us to understand pituitary tumorigenesis and might lead to therapeutical targeting drugs in the future. Macroadenomas (>1 cm) can lead to visual field disturbances, compression of cranial nerves, hypopituitarism, and infiltration of the cavernous sinuses. The functional status of the pituitary tumor is important. About half to one third of all pituitary tumors are non-functioning pituitary adenomas. The other pituitary tumors show a specific pattern of hormone secretion. About 25% to 41% of all pituitary tumors are prolactinomas, acromegaly with production of growth hormone represents 10% to 15% of adenomas, Cushing's disease with production of adrenocorticotropic hormone accounts for 10%, and other hormonal characteristics are less common. Transsphenoidal resection and total adenomectomy are desirable. Radiosurgery has enriched the surgical treatment options. Surgical treatment is the intervention of choice except for prolactinomas, where pharmaceutical treatment is recommended. Pharmaceutical treatment consists of dopamine agonists such as cabergoline and somatostatin analogues that include octreotide and pasireotide; retinoic acid is of theoretical interest while peroxisome proliferator-activated receptor-gamma-ligands are not clinically useful. In acromegaly, pegvisomant is a further treatment option. Temozolomide should be considered in aggressive pituitary tumors. In general, pharmaceutical options developed recently have extended the repertoire of treatment possibilities of pituitary tumors

A Rapid and Specific Method for Separation of Bound and Free Antigen in Radioimmunoassay Systems

Peer Reviewe

Growth Hormone (GH)-Releasing Peptide Stimulation of GH Release from Human Somatotroph Adenoma Cells: Interaction with GH-Releasing Hormone, Thyrotropin- Releasing Hormone, and Octreotide.

The synthetic hexapeptide GH-releasing peptide (GHRP; His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) specifically stimulates GH secretion in humans in vivo and in animals in vitro and in vivo via a still unknown receptor and mechanism. To determine the effect of GHRP on human somatotroph cells in vitro, we stimulated cell cultures derived from 12 different human somatotroph adenomas with GHRP alone and in combination with GH-releasing hormone (GHRH), TRH, and the somatostatin analog octreotide. GH secretion of all 12 adenoma cultures could be stimulated with GHRP, whereas GHRH was active only in 6 adenoma cultures. In GHRH-responsive cell cultures, simultaneous application of GHRH and GHRP had an additive effect on GH secretion. TRH stimulated GH release in 4 of 7 adenoma cultures; in TRH-responsive cell cultures there was also an additive effect of GHRP and TRH on GH secretion. In 5 of 9 adenoma cultures investigated, octreotide inhibited basal GH secretion. In these cell cultures, GHRP-induced GH release was suppressed by octreotide. In 5 of 5 cases, the protein kinase-C inhibitor phloretin partly inhibited GHRP-stimulated GH release, but not basal GH secretion. In summary, GH secretion was stimulated by GHRP in all somatotroph adenomas investigated, indicating that its unknown receptor and signaling pathway are expressed more consistently in somatotroph adenoma cells than those for GHRH, TRH, and somatostatin. Our data give further evidence that GHRP-stimulated GH secretion is mediated by a receptor different from that for GHRH or TRH, respectively, and that protein kinase-C is involved in the signal transduction pathway. Because human somatotroph adenoma cell cultures respond differently to various neuropeptides (GHRH, TRH, somatostatin, and others), they provide a model for further investigation of the mechanism of action of GHRP-induced GH secretion

Transgender Transitioning and Change of Self-Reported Sexual Orientation

Objective: Sexual orientation is usually considered to be determined in early life and stable in the course of adulthood. In contrast, some transgender individuals report a change in sexual orientation. A common reason for this phenomenon is not known. Methods: We included 115 transsexual persons (70 male-to-female "MtF" and 45 female-to-male "FtM") patients from our endocrine outpatient clinic, who completed a questionnaire, retrospectively evaluating the history of their gender transition phase. The questionnaire focused on sexual orientation and recalled time points of changes in sexual orientation in the context of transition. Participants were further asked to provide a personal concept for a potential change in sexual orientation. Results: In total, 32.9% (n = 23) MtF reported a change in sexual orientation in contrast to 22.2% (n = 10) FtM transsexual persons (p = 0.132). Out of these patients, 39.1% (MtF) and 60% (FtM) reported a change in sexual orientation before having undergone any sex reassignment surgery. FtM that had initially been sexually oriented towards males (= androphilic), were significantly more likely to report on a change in sexual orientation than gynephilic, analloerotic or bisexual FtM (p = 0.012). Similarly, gynephilic MtF reported a change in sexual orientation more frequently than androphilic, analloerotic or bisexual MtF transsexual persons (p = 0.05). Conclusion: In line with earlier reports, we reveal that a change in self-reported sexual orientation is frequent and does not solely occur in the context of particular transition events. Transsexual persons that are attracted by individuals of the opposite biological sex are more likely to change sexual orientation. Qualitative reports suggest that the individual's biography, autogynephilic and autoandrophilic sexual arousal, confusion before and after transitioning, social and self-acceptance, as well as concept of sexual orientation itself may explain this phenomenon

Obstructive Sleep Apnea Syndrome Is Less Frequent in Patients With Well-Controlled Acromegaly Treated With Somatostatin Analogues, Pegvisomant or in Combination

Background: Obstructive sleep apnea (OSA) often occurs in patients with active acromegaly and improves after treatment. Less is known about the development of OSA in patients after a longer period of control treated with somatostatin analogues (SSA) and pegvisomant. Methods: Seventy-nine patients (12 females, 17 males; age 49 +/- 14 years; body mass index 29.9 +/- 5.4 kg/m(2); IGF-1 184 +/- 73 mu g/L; disease duration 13 +/- 8 years (mean +/- standard deviation)) with wellcontrolled acromegaly treated with SSA (38%), pegvisomant (38%) or in combination (24%) who underwent ambulatory polygraphy were included in a prospective multicenter cross-sectional study. Results: Fourteen percent had OSA (range of apnea-hypopnea index (AHI) 5 -15). Patients with OSA (AHI >= 5 vs. < 5) had a longer disease duration (16 +/- 1 vs. 12 +/- 8 years; P = 0.01) and were older (61 +/- 9 vs. 47 +/- 13 years; P = 0.037). The AHI of all patients correlated with age (P = 0.01; r = 0.44). No differences were seen in terms of BMI and Epworth sleepiness scale score. Previous transsphenoidal surgery and radiation had no impact of the detection of OSA. The duration of well-controlled acromegaly was 7 +/- 3 years. Conclusion: OSA in patients with well-controlled acromegaly treated with SSA, pegvisomant or in combination is less frequent (14%) than previously described. Early treatment to reduce the active disease period should be aimed to prevent OSA