Time to recovery of adrenal function after curative surgery for Cushing's syndrome depends on etiology

ContextCushing’s syndrome (CS) is a rare disease of endogenous hypercortisolism associated with high morbidity and mortality. Diagnosis and classification of CS is still challenging.ObjectiveCirculating microRNAs (miRNAs) are minimally invasive diagnostic markers. Our aim was to characterize the circulating miRNA profiles of CS patients and to identify distinct profiles between the two major CS subtypes.MethodsWe included three groups of patients from the German Cushing’s registry: ACTH-independent CS (Cortisol-Producing-Adenoma; CPA), ACTH-dependent pituitary CS (Cushing’s Disease; CD), and patients in whom CS had been ruled out (controls). Profiling of miRNAs was performed by next-generation-sequencing (NGS) in serum samples of 15 CS patients (each before and after curative surgery) and 10 controls. Significant miRNAs were first validated by qPCR in the discovery cohort and then in an independent validation cohort of 20 CS patients and 11 controls.ResultsNGS identified 411 circulating miRNAs. Differential expression of 14 miRNAs were found in the pre- and postoperative groups. qPCR in the discovery cohort validated 5 of the significant miRNAs from the preoperative group analyses. Only, miR-182-5p was found to be significantly upregulated in the CD group of the validation cohort. Comparing all CS samples as a group with the controls did not reveal any significant differences in expression.OutcomeIn conclusion, our study identified miR-182-5p as a possible biomarker for CD, which has to be validated in a prospective cohort. Furthermore, our results suggest that presence or absence of ACTH might be at least as relevant for miRNA expression as hypercortisolism itself.

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Neurocognitive functions and brain volume in patients with endogenous cushing's syndrome before and after curative surgery

Indian Journal of Endocrinology and Metabolism ◽

10.4103/ijem.ijem_162_20 ◽

2020 ◽

Vol 24 (5) ◽

pp. 396

Author(s):

Rama Walia ◽

Nachimuthu Kumar ◽

KushD S. Jarial ◽

Anil Bhansali ◽

Ritu Nehra ◽

...

Keyword(s):

Cushing’S Syndrome ◽

Brain Volume ◽

Cushing's Syndrome ◽

Curative Surgery ◽

Neurocognitive Functions ◽

Before And After

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The Hypothalamic-Pituitary-Thyroid Axis in Cushing Syndrome before and after Curative Surgery

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa858 ◽

2020 ◽

Author(s):

Skand Shekhar ◽

Raven McGlotten ◽

Sunyoung Auh ◽

Kristina I Rother ◽

Lynnette K Nieman

Keyword(s):

Thyroid Function ◽

Cushing’S Syndrome ◽

Cushing Syndrome ◽

Cushing's Syndrome ◽

Curative Surgery ◽

Central Hypothyroidism ◽

Duration Of Symptoms ◽

Before And After ◽

Pituitary Thyroid Axis ◽

Thyroid Axis

Abstract Background We do not fully understand how hypercortisolism causes central hypothyroidism or what factors influence recovery of the hypothalamic-pituitary-thyroid axis. We evaluated thyroid function during and after cure of Cushing’s syndrome (CS). Methods We performed a retrospective cohort study of adult patients with CS seen from 2005 – 2018 (cohort 1, c1, n=68) or 1985 – 1994 (cohort 2, c2, n=55) at a clinical research center. Urine (UFC) and diurnal serum cortisol (F: ~8AM and ~midnight (PM)), morning triiodothyronine (T3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) (c1) or hourly TSH from 1500-1900h (day) and 2400-04000h (night) (c2), were measured before and after curative surgery. Results While hypercortisolemic, 53% of c1 had central hypothyroidism (low/low normal fT4 + unelevated TSH). Of those followed long-term, 31% and 44% had initially subnormal FT4 and T3, respectively, which normalized 6—12 months after cure. Hypogonadism was more frequent in hypothyroid (69%) compared to euthyroid (13%) patients. Duration of symptoms, AM and PM F, ACTH, and UFC were inversely related to TSH, FT4 and/or T3 levels (r -0.24 to -0.52, P <0.0001 to 0.02). In c2, the nocturnal surge of TSH (mIU/L) was subnormal before (day 1.00±0.04 vs night 1.08±0.05, p=0.3) and normal at a mean of 8 months after cure (day 1.30±0.14 vs night 2.17±0.27, p=0.01). UFC >1000 μg /day was an independent adverse prognostic marker of time to thyroid hormone recovery. Conclusions Abnormal thyroid function, likely mediated by subnormal nocturnal TSH, is prevalent in Cushing’s syndrome and is reversible after cure.

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A study of hypothalamic-pituitary-adrenal suppression following curative surgery for Cushing's syndrome due to adrenal adenoma

Acta Endocrinologica ◽

10.1530/acta.0.1140166 ◽

1987 ◽

Vol 114 (2) ◽

pp. 166-170 ◽

Cited By ~ 7

Author(s):

D. Gordon ◽

C. G. Semple ◽

G. H. Beastall ◽

J. A. Thomson

Keyword(s):

Cushing’S Syndrome ◽

Adrenal Adenoma ◽

Cushing's Syndrome ◽

Hypothalamic Pituitary Adrenal Axis ◽

Curative Surgery ◽

Unilateral Adrenalectomy ◽

Hypothalamic Pituitary Adrenal ◽

Adrenal Axis ◽

Cortisol Responses ◽

Pituitary Adrenal Axis

Abstract. The hypothalamic-pituitary-adrenal axis was investigated in all six patients requiring glucocorticoid replacement 2.5–11 years after unilateral adrenalectomy for adrenal adenomas causing Cushing's syndrome. The hypothalamic-pituitary-adrenal axis was assessed by insulin induced hypoglycaemia and CRF testing in each patient. Two patients showed normal cortisol and ACTH responses to hypoglycaemia. Two patients showed subnormal cortisol responses to hypoglycaemia in the presence of high or normal basal ACTH concentrations. ACTH concentrations increased with both hypoglycaemia and CRF. Two patients showed subnormal cortisol responses to hypoglycaemia and CRF. One of these patients showed an ACTH rise following hypoglycaemia but not CRF. Defects at either hypothalamic-pituitary or adrenal levels were demonstrated and recovery of the axis appears to commence at the hypothalamic-pituitary level.

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Effects of Aminoglutethimide Upon Adrenal Function and Cortisol Metabolism in Cushing's Syndrome

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem-27-12-1657 ◽

1967 ◽

Vol 27 (12) ◽

pp. 1657-1666 ◽

Cited By ~ 40

Author(s):

D. E. SCHTEINGART ◽

J. W. CONN

Keyword(s):

Cushing’S Syndrome ◽

Cushing's Syndrome ◽

Adrenal Function ◽

Cortisol Metabolism

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HYPOTHALAMO-PITUITARY-ADRENAL FUNCTION IN HYPERCORTICOSTEROID STATES

Acta Endocrinologica ◽

10.1530/acta.0.0580497 ◽

1968 ◽

Vol 58 (3) ◽

pp. 497-501 ◽

Cited By ~ 1

Author(s):

T. Livanou ◽

David Ferriman ◽

Michael Corns

Keyword(s):

Cushing’S Syndrome ◽

Cushing's Syndrome ◽

Adrenal Function ◽

Stress Tests ◽

Function Tests ◽

Response To Stress

ABSTRACT Results from hypothalamo-pituitary-adrenal function tests are reported in four patients with Cushing's syndrome. The results of the metyrapone and stress tests are compared with those in other corticosteroid states. It is tentatively concluded that the hypothalamic centres concerned in the response to stress are more sensitive to high levels of circulating steroids, than those subserving the feed-back mechanism.

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Predictive Accuracy of Delta Cortisol on Recovery of Adrenal Function in Patients With Drug Induced Cushing’s Syndrome With Secondary Adrenal Insufficiency

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.182 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A91-A91

Author(s):

Bo Bo San

Keyword(s):

Cushing’S Syndrome ◽

Cushing Syndrome ◽

Serum Cortisol ◽

Cushing's Syndrome ◽

Adrenal Function ◽

Drug Induced ◽

Basal Serum ◽

Synacthen Test ◽

Short Synacthen Test

Abstract There is a growing concern upon the finding of many drug induced Cushing’s syndrome because of inadvertent use of glucocorticoids (GC) either prescribed or as alternative medicine in Myanmar. These patients are presenting with diversity of clinical problems ranging from hypertension, diabetes to acute adrenal crisis due to hypothalamic-pituitary-adrenal (HPA) axis suppression and secondary adrenal insufficiency (AI). The present study aimed to assess the delta cortisol (the degree of cortisol increments) during the first short Synacthen test (SST) as a factor predictive of adrenal function recovery in patients with drug induced Cushing’ syndrome with secondary AI and to determine the proportion of patients who recovered from AI within six-month follow-up. This was a hospital based prospective analytical study that enrolled a total of 52 patients with drug induced Cushing’s syndrome with secondary AI from January 2018 to June 2019. Secondary AI is defined by morning basal serum cortisol ≤ 400 nmol/L with Synacthen stimulated peak cortisol level ≤ 550 nmol/L and serum ACTH < 60 pg/ml. The follow-up SSTs were performed at three-month and six-month after first SST, and the patients with morning basal serum cortisol > 400 nmol/L (or) Synacthen stimulated peak serum cortisol > 550 nmol/L during follow-up SSTs are defined as recovered adrenal function group. In this study, a total of 52 patients were treated with modified regimen of physiological dose of prednisolone with tapering schedule or stress dose GC based on the basal serum cortisol levels up to six months. Among them, nearly half (n=25 / 48.1%) of the patients with drug induced Cushing’s syndrome with secondary AI achieved normal adrenal function within six-month follow-up. It was found that mean values for delta cortisol were not statistically significant between recovered and non-recovered groups, 118.6 nmol/L (SD 72.3) and 97.2 nmol/L (SD 64.2) respectively. The delta cortisol during the first SST could not predict strongly (AUC - 0.6, 95% CI - 0.44 to 0.76, P = 0.2) the recovery of adrenal function in patients with drug induced Cushing’s syndrome with secondary AI and it was inconsistent with previous studies. The older age of the patients, oral route of administration of drugs causing Cushing’s syndrome and comorbid hypertension were found to be more significant in the non-recovered group. In conclusion, the present study did not support the evidence that the delta cortisol during the first SST could predict adrenal function recovery in patients with drug induced Cushing’ syndrome with secondary AI. Reference: (1) Baek et al., 2016; Recovery of Adrenal Function in Patients with Glucocorticoids Induced Secondary AI. Endocrinol Metab.31, pp. 153–160. (2) Pofi et al., 2018; The Short Synacthen Test Can Be Used to Predict Recovery of HPA Axis Function. J Clin Endocrinol Metab.103(8), pp. 3050–3059.

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