Urinary Steroid Excretion Rates in Acromegaly

Vierhapper, H.; Nowotny, Peter; Waldhäusl, W.

doi:10.1159/000085840

Cited by 5 publications

(7 citation statements)

References 42 publications

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“…The low urine androsterone/etiocholanolone ratio identified in men with acromegaly demonstrated a decreased hepatic 5 α-reductase activity. 46 The inhibitory effect of GH on 11β-HSD1 was also observed by other researchers. 59,60…”

Section: Discussionsupporting

confidence: 70%

“…Women with active acromegaly had low urinary glucocorticoids concentrations vs healthy women (p<0.001). 46 Men with active acromegaly had a decreased urinary androsterone/etiocholanolone ratio and an increased urinary tetrahydrocortisone/tetrahydrocortisol ratio vs healthy men (Table 1). 46 The androsterone/etiocholanolone ratio negatively correlated with IGF-1 (r = −0.4, p < 0.05).…”

Section: Resultsmentioning

confidence: 99%

“…Both the tetrahydrocortisone/tetrahydrocortisol ratio and tetrahydrocortisone/(tetrahydrocortisol + allotetrahydrocortisol) ratio positively correlated with post-glucose GH (r > 47, p < 0.01). 46…”

Section: Resultsmentioning

confidence: 99%

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Metabolomics in acromegaly: a systematic review

Pînzariu

Georgescu

2023

Journal of Investigative Medicine

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The therapeutic response heterogeneity in acromegaly persists, despite the medical–surgical advances of recent years. Thus, personalized medicine implementation, which focuses on each patient, is justified. Metabolomics would decipher the molecular mechanisms underlying the therapeutic response heterogeneity. Identification of altered metabolic pathways would open new horizons in the therapeutic management of acromegaly. This research aimed to evaluate the metabolomic profile in acromegaly and metabolomics’ contributions to understanding disease pathogenesis. A systematic review was carried out by querying four electronic databases and evaluating patients with acromegaly through metabolomic techniques. In all, 21 studies containing 362 patients were eligible. Choline, the ubiquitous metabolite identified in growth hormone (GH)-secreting pituitary adenomas (Pas) by in vivo magnetic resonance spectroscopy (MRS), negatively correlated with somatostatin receptors type 2 expression and positively correlated with magnetic resonance imaging T2 signal and Ki-67 index. Moreover, elevated choline and choline/creatine ratio differentiated between sparsely and densely granulated GH-secreting PAs. MRS detected low hepatic lipid content in active acromegaly, which increased after disease control. The panel of metabolites of acromegaly deciphered by mass spectrometry (MS)-based techniques mainly included amino acids (especially branched-chain amino acids and taurine), glyceric acid, and lipids. The most altered pathways in acromegaly were the metabolism of glucose (particularly the downregulation of the pentose phosphate pathway), linoleic acid, sphingolipids, glycerophospholipids, arginine/proline, and taurine/hypotaurine. Matrix-assisted laser desorption/ionization coupled with MS imaging confirmed the functional nature of GH-secreting PAs and accurately discriminated PAs from healthy pituitary tissue.

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Section: Discussionsupporting

confidence: 70%

Section: Resultsmentioning

confidence: 99%

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Metabolomics in acromegaly: a systematic review

Pînzariu

Georgescu

2023

Journal of Investigative Medicine

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“…11βHSD-1 activity has been shown to be inhibited by GH excess, resulting in the reduced tissue exposure to glucocorticoids [15,18]. In fact, it has been reported that the ratio of urinary tetrahydrocortisol (THF)+allo-THF to tetrahydrocortisone (THE) was reduced in acromegalic patients, suggesting the increased metabolic clearance of cortisol [19]. In addition, a rare case of Cushing's disease without the classical phenotype has been reported due to a partial defect in the 11βHSD-1 activity protective against cortisol excess [20].…”

Section: Discussionmentioning

confidence: 99%

A Case of Acromegaly Associated with Subclinical Cushing's Disease

et al. 2006

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Abstract.A 54-year-old man with type 2 diabetes was referred to our hospital for endocrine evaluation of acromegaly. Physical examination showed typical acromegalic features without Cushingoid features. Magnetic resonance imaging of the brain revealed the presence of a pituitary macroadenoma. Basal plasma levels of GH and insulin-like growth factor-I under fasting hyperglycemia (202 mg/dl) were markedly elevated. Plasma GH levels paradoxically increased after stimulation with TRH and LH-RH, and decreased after bromocriptine and octreotide administration. Endocrine examination of the hypothalamo-pituitary-adrenal (HPA) axis showed a lack of circadian rhythm of ACTH and cortisol, non-suppressibility to low-dose (1 mg), but suppressibility to high-dose (8 mg) dexamethasone, and normal response to CRH stimulation. The tumor resected by transsphenoidal surgery was histopathologically consistent with the diagnosis of eosinophilic adenoma: positive immunoreactivities of GH, PRL and ACTH were demonstrated, but negative immunoreactivities of prohormone convertase (PC) 1/3 by immunohistochemical method. After surgery, plasma GH and IGF-I levels decreased along with normalization of HPA axis. Metabolic co-morbidities such as diabetes and hypertension disappeared after removal of the pituitary tumor. This is a very rare case of GH-producing pituitary adenoma causing typical acromegaly with concomitant production of ACTH causing subclinical Cushing's disease.

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“…Female rodents have lower hepatic 11βHSD1 enzyme activity than male animals (5). This putative gender difference in glucocorticoid metabolism may be influenced by sex hormones, growth hormones, and “adipokines,” i.e., fat‐derived hormones, including leptin and tumor necrosis factor‐alpha (TNF‐α), with a possible fat‐liver cross‐talk (6, 7, 8). However, little is known about potential influences of gender and adipokines on hepatic 11β reduction of cortisone in humans.…”

Section: Introductionmentioning

confidence: 99%

Gender‐specific Links Between Hepatic 11β Reduction of Cortisone and Adipokines

Mattsson

Rask

Carlström

et al. 2007

Obesity

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Objective: Reduction of cortisone to cortisol is mediated by 11␤-hydroxysteroid dehydrogenase type 1 (11␤HSD1), a putative key enzyme in obesity-related complications. Experimental studies suggest that adipokines, notably leptin and tumor necrosis factor-␣ (TNF-␣), are of importance for 11␤HSD1 activity. We hypothesized that the regulation of hepatic preceptor glucocorticoid metabolism is gender-specific and associated with circulating levels of leptin and TNF-␣ receptors and/or sex hormones. Research Methods and Procedures: A total of 34 males and 38 women (14 premenopausal and 22 postmenopausal) underwent physical examination and fasting blood sampling. Insulin sensitivity was tested by euglycemic hyperinsulinemic clamps, and hepatic 11␤HSD1 enzyme activity was estimated by the conversion of orally-ingested cortisone to cortisol. Results: Hepatic 11␤HSD1 activity was negatively associated with leptin and soluble TNF (sTNF) r1 and sTNFr2 in males. These correlations remained significant after adjustment for age and insulin sensitivity, and for sTNF-␣ receptors also after adjustment of BMI and waist circumference.In contrast, 11␤ reduction of cortisone was positively associated to leptin in females after adjustment for BMI and waist circumference. Discussion: Hepatic 11␤ reduction shows different links to circulating adipocyte-derived hormones in males and females. This emphasizes the need for further studies on tissue-specific regulation of 11␤HSD1 in both genders.

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Urinary Steroid Excretion Rates in Acromegaly

Cited by 5 publications

References 42 publications

Metabolomics in acromegaly: a systematic review

Metabolomics in acromegaly: a systematic review

A Case of Acromegaly Associated with Subclinical Cushing's Disease

Gender‐specific Links Between Hepatic 11β Reduction of Cortisone and Adipokines

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