Comparative assessment of ACTH and lipotropin plasma levels in the diagnosis and follow-up of patients with Cushing's syndrome: A study of 210 cases

Kuhn, Jean Marc; Proeschel, Marie François; Seurin, Danielle; Bertagna, Xavier; Luton, J. P.; Girard, François

doi:10.1016/0002-9343(89)90443-9

Cited by 58 publications

(33 citation statements)

References 30 publications

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“…Corticotroph macroadenomas have previously been considered to be associated with a more indolent disease (13), although to date this has not been systematically investigated, but other data from six previously published series (5,6,(16)(17)(18)(19) confirm our present observations (Table 5). Our results also suggest that corticotroph macroadenomas are less responsive to suppression by high-dose dexamethasone.…”

Section: Discussionsupporting

confidence: 83%

Cushing's disease: a comparison of pituitary corticotroph microadenomas and macroadenomas

Selvais

Donckier

Buysschaert

et al. 1998

European Journal of Endocrinology

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Cushing's disease appears as a functionally heterogeneous disease, but criteria that are able to distinguish between different clinical forms remain elusive. We compared two subgroups of patients with proven Cushing's disease according to the size of the pituitary adenoma, evaluated by computed tomography or magnetic resonance imaging. Our series comprised 11 patients with a microadenoma and 10 with a macroadenoma (median volumes (range): 173 (13-270) and 3022 (500-10312) mm 3 respectively; P < 0:0001). The clinical presentation was similar in the two groups, but the time elapsed before diagnosis was longer, and visual impairment was less frequent in the patients with a microadenoma (1:5 Ϯ 0:8 years and 0%) than in those with a macroadenoma (0:7 Ϯ 0:6 years and 40%; P < 0:05). Morning and evening peripheral concentrations of ACTH were greater in patients with macroadenoma (134 Ϯ 78 and 130 Ϯ 7 ng/l respectively) than in those with microadenoma (52 Ϯ 28 and 56 Ϯ 19 ng/l, P < 0:05). Hypokalaemia and lymphopenia were also more pronounced in patients with macroadenoma (3:4 Ϯ 0:3 mmol/l and 1273 Ϯ 401 lymphocytes/mm 3 ) than in those with microadenoma (3:8 Ϯ 0:3 mmol/l and 1852Ϯ668 lymphocytes/mm 3 ; P < 0:05), although morning and evening plasma cortisol concentrations were similar in both groups. In patients with macroadenoma, there was less relative nycthemeral variation of ACTH concentrations (28 Ϯ 24%, compared with 62 Ϯ 39% in those with microadenoma; P < 0:05), less suppression of plasma cortisol by high doses of dexamethasone (¹30 Ϯ 14%, compared with ¹61 Ϯ 25%; P < 0:05), and a reduced concentration ratio of mean basal cortisol to ACTH (7 Ϯ 3, compared with 12 Ϯ 5; P < 0:05). Plasma IGF-I concentration and the TSH peak response to TRH were significantly lower in patients with macroadenoma than in those with microadenoma (0:4 Ϯ 0:2 × 10 3 IU/l and 2:3 Ϯ 1:8 mIU/l, compared with 1:8 Ϯ 0:6 × 10 3 IU/l and 5:2 Ϯ 1:6 mUI/l; P < 0:05). Thus, in comparison with microadenomas, corticotroph macroadenomas are characterized by a greater and more autonomous ACTH secretion, inducing more pronounced biological signs of hypercorticism, and are more often accompanied by visual field defects and impairment of other pituitary hormonal secretions. European Journal of Endocrinology 138 153-159

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Section: Discussionsupporting

confidence: 83%

Cushing's disease: a comparison of pituitary corticotroph microadenomas and macroadenomas

Selvais

Donckier

Buysschaert

et al. 1998

European Journal of Endocrinology

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“…With regard to ACTH levels, no cut-off limit has been defined to distinguish patients with EAS and Cushing's disease with complete accuracy [2,13,16,40]. In 50-64% of patients with EAS ACTH levels were greater than 200 ng/L, but with considerable overlap between both patients groups [7,17,25,28]; 24% to 32% of patients with EAS had levels within the 'normal range' [13,14].…”

Section: ≤5mentioning

confidence: 99%

The ectopic ACTH syndrome

Alexandraki

Grossman

2010

Rev Endocr Metab Disord

185

131

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Ectopic Cushing's syndrome usually relates to the ectopic ACTH syndrome (EAS) and represents ∼20% of ACTH-dependent and ∼10% of all types of Cushing's syndrome (CS). Nearly any neuroendocrine or non-endocrine tumours may be associated with EAS, but the more prevalent tumours are bronchial carcinoids, small cell lung carcinomas, pancreatic carcinoids, thymic carcinoids, medullary carcinomas of the thyroid, and phaeochromocytomas. Occult tumours are highly represented in all the series (12-38%) and constitute the more challenging cases of EAS, requiring long term follow-up. The lack of any completely reliable diagnostic test procedure and imaging to clearly reveal the source of EAS suggests that we should adopt a step-by-step multidisciplinary approach for their diagnosis and therapeutic management. Clinical features are often similar in ACTH-dependent CS, but the rapid onset and progress may suggest an ectopic source. A combination of biochemical tests and imaging studies seems the most appropriate approach for the prompt identification of EAS, even if there are several pitfalls to be avoided along the way. The most appropriate management for cure of EAS, when its source is identified, is surgical excision after controlling the hypercortisolaemia by inhibitors of cortisol secretion and other newer modalities alone or in combination; bilateral adrenalectomy remains an alternative option. Tumour histology, the presence of metastases and the effective control of hypercortisolaemia affect mortality and morbidity. If a source repeatedly fails to be found, the prognosis is often favourable but the identification of a malignant tumour should still be sought during life-long follow-up to avoid the calamity of misdiagnosis.

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“…This adrenocorticotropic substance may be ACTH [5], which can also act physiologically, hence the name of ectopic ACTH syndrome [6]. When ACTH levels are normal [5], as in our patient, hypercortisolism may be explained by the predominance of other adrenocorticotropic substances. ACTH results from the cleavage in the pituitary of proopiomelanocortin (POMC).…”

Section: Discussionmentioning

confidence: 56%