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

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.

scholarly journals Cushing’s Syndrome Effects on the Thyroid

2021 ◽  
Vol 22 (6) ◽  
pp. 3131
Author(s):  
Rosa Maria Paragliola ◽  
Andrea Corsello ◽  
Giampaolo Papi ◽  
Alfredo Pontecorvi ◽  
Salvatore Maria Corsello
Keyword(s):  
Thyroid Function ◽  
Cushing’S Syndrome ◽  
Immunological Tolerance ◽  
Cushing's Syndrome ◽  
Autoimmune Thyroid Diseases ◽  
Central Hypothyroidism ◽  
Immunological Mechanism ◽  
Autoimmune Thyroid ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis

The most known effects of endogenous Cushing’s syndrome are the phenotypic changes and metabolic consequences. However, hypercortisolism can exert important effects on other endocrine axes. The hypothalamus–pituitary–thyroid axis activity can be impaired by the inappropriate cortisol secretion, which determinates the clinical and biochemical features of the “central hypothyroidism”. These findings have been confirmed by several clinical studies, which also showed that the cure of hypercortisolism can determine the recovery of normal hypothalamus–pituitary–thyroid axis activity. During active Cushing’s syndrome, the “immunological tolerance” guaranteed by the hypercortisolism can mask, in predisposed patients, the development of autoimmune thyroid diseases, which increases in prevalence after the resolution of hypercortisolism. However, the immunological mechanism is not the only factor that contributes to this phenomenon, which probably includes also deiodinase-impaired activity. Cushing’s syndrome can also have an indirect impact on thyroid function, considering that some drugs used for the medical control of hypercortisolism are associated with alterations in the thyroid function test. These considerations suggest the utility to check the thyroid function in Cushing’s syndrome patients, both during the active disease and after its remission.

scholarly journals Circulating microRNA Expression in Cushing’s Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Sharmilee Vetrivel ◽  
Ru Zhang ◽  
Mareen Engel ◽  
Barbara Altieri ◽  
Leah Braun ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Validation Cohort ◽  
Cushing's Syndrome ◽  
Circulating Microrna ◽  
High Morbidity ◽  
Discovery Cohort ◽  
Serum Samples ◽  
Curative Surgery ◽  
Before And After ◽  
Diagnosis And Classification

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.

scholarly journals SAT-449 Factors Associated with Reduced Thyroid Hormones in Cushing Syndrome Patients Before and After Surgical Cure

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Skand Shekhar ◽  
Raven McGlotten ◽  
Lynnette K Nieman
Keyword(s):  
Thyroid Hormones ◽  
Thyroid Function ◽  
Cushing Syndrome ◽  
Hormone Secretion ◽  
Free T4 ◽  
Curative Surgery ◽  
Duration Of Symptoms ◽  
Free Cortisol ◽  
Hpt Axis ◽  
Pearson Correlations

Abstract Background: Hypercortisolemia adversely affects thyroid hormone secretion. We previously described the temporal pattern of thyroid function recovery in 23 patients (1). However, the factors leading to suppression and recovery of the hypothalamic-pituitary-thyroid (HPT) axis in Cushing’s syndrome (CS) are not fully understood. We performed two separate studies to investigate these factors. Methods: In study 1, we examined patients (pts, n=62) with CS who underwent curative surgery and recorded their serum morning and evening cortisol, ACTH, tumor volume and duration of symptoms and 24-hour urine free cortisol (UFC) at baseline and the morning serum free T4, TSH and T3 at six-month intervals after cure. Data were log-transformed and Pearson correlations were performed. Linear mixed models were used to study factors that predict recovery of thyroid function. In study 2, we examined the diurnal variation of TSH by performing hourly TSH measurement between 3—7 PM and 12—4 AM on a cohort of pts (n=45) before surgery. Wilcoxon Signed-Rank method was used for comparisons of mean TSH across time and Pearson correlations were performed on log-transformed data. P values <.05 were considered significant. Results: Study 1: In this larger cohort, we confirmed previous findings of suppressed or low normal fT4 and TSH values with active hypercortisolism, with normalization after cure that reflected changes in the T3:TSH, fT4:TSH and T3:fT4 ratios. There were inverse linear correlations between log10 UFC, serum AM and PM cortisol; and log10 TT3, fT4 and TSH before surgery. Independent negative prognosticators of circulating fT4 recovery included UFC greater than 1000mcg/day (nl: 3.5—45mcg/day), duration of symptoms of less than one year, and ACTH levels greater than 60pg/mL(nl: 5—45pg/mL) Study 2: The nocturnal (12 - 4AM) TSH surge was reduced, so that the difference in day and night TSH values was not statistically significant; this contrasts with the 30—50% nocturnal TSH increase above daytime values seen in healthy subjects. There was an inverse relationship between UFC and nocturnal TSH, daytime TSH and TBG values, but there was no direct relationship between UFC and percent changes in nocturnal TSH values. Conclusions: Our findings suggest that a deficit in TSH stimulation of the thyroid gland may explain the reduction in T3 and T4 levels. There is a dose-response relationship between various measures of hypercortisolemia and both thyroid hormones and the pattern of TSH secretion. Finally, the severity of hypercortisolism correlates with a longer time to recovery of the HPT axis in pts with CS after curative surgery. 1. Shekhar S et al. HPG and HPT Axes in Cushing Syndrome. J Endocr Soc, 3 S1, April May 2019

scholarly journals Diminished and irregular TSH secretion with delayed acrophase in patients with Cushing's syndrome

2009 ◽  
Vol 161 (5) ◽  
pp. 695-703 ◽  
Author(s):  
Ferdinand Roelfsema ◽  
Alberto M Pereira ◽  
Nienke R Biermasz ◽  
Marijke Frolich ◽  
Daniel M Keenan ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Approximate Entropy ◽  
Pituitary Surgery ◽  
Pulse Frequency ◽  
Cushing's Syndrome ◽  
Pituitary Thyroid Axis ◽  
Tsh Secretion ◽  
Thyroid Axis ◽  
Serum Tsh ◽  
Active Disease

ContextThe hypothalamus–pituitary–thyroid axis in Cushing's syndrome may be altered. Previous reports have shown diminished serum TSH concentration and decreased response to TRH.ObjectiveWe analyzed serum TSH profiles in relation to cortisol profiles in patients with hypercortisolism of pituitary (n=16) or primary-adrenal origin (n=11) and after remission by pituitary surgery (n=7) in order to delineate aberrations in the hypothalamus–pituitary–thyroid system.InterventionPatients and controls (n=27) underwent a 24-h blood sampling study. Serum TSH and cortisol were measured with precise methods, and data were analyzed with a deconvolution program, approximate entropy (ApEn), and cosinor regression.ResultsPulsatile TSH secretion and mean TSH pulse mass were diminished during hypercortisolism, independently of etiology (P<0.001). TSH secretion was increased in patients in remission only during daytime due to increased basal secretion (P<0.01). Pulse frequency and half life of TSH were similar in patients and controls. TSH ApEn (irregularity) was increased in patients with hypercortisolism (P<0.01), but was normal in cured patients. Cross-ApEn between TSH and cortisol, a measure of pattern synchrony loss, was increased in active disease, indicating (partial) loss of secretory synchrony. The TSH rhythm was phase delayed in hypercortisolemic patients, but normal in cured patients (P<0.01). Free thyroxine levels were decreased only in pituitary-dependent hypercortisolism compared with controls (P=0.003). Total 24-h TSH correlated negatively and linearly with log-transformed cortisol secretion (R=0.43, P=0.001).ConclusionCortisol excess decreases TSH secretion by diminishing pulsatile release, whereas surgically cured patients have elevated nonpulsatile TSH release. Diminished TSH secretory regularity in active disease suggests glucocorticoid-induced dysregulation of TRH or somatostatinergic/annexin-1 control.

THE PITUITARY-THYROID AXIS IN KLINEFELTER's SYNDROME

1977 ◽  
Vol 84 (1) ◽  
pp. 72-79 ◽  
Author(s):  
A. G. H. Smals ◽  
P. W. C. Kloppenborg ◽  
R. L. Lequin ◽  
L. Beex ◽  
A. Ross ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Preliminary Data ◽  
Klinefelter’S Syndrome ◽  
Klinefelter's Syndrome ◽  
Testosterone Treatment ◽  
Before And After ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Per Se

ABSTRACT Conventional thyroid function indices (serum T4, T3, TSH and thyroidal RAIU before and after TSH) appeared to be normal in most of 25 clinically euthyroid patients with chromatine positive Klinefelter's syndrome. Administration of TRH, however, revealed a decreased TSH reserve in the Klinefelter patients, both off or on testosterone treatment, in comparison to euthyroidal eugonadal male controls. Preliminary data suggest that this blunted TSH response to TRH is not a characteristic of Klinefelter's syndrome per se but might be caused by the concurrent hypergonadotrophism. Despite the blunted TSH response, the TRH mediated T3 response in the Klinefelter patients was about equal to that in the male controls.

scholarly journals Chronothyroidology: Chronobiological Aspects in Thyroid Function and Diseases

Life ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 426
Author(s):  
Giuseppe Bellastella ◽  
Maria Ida Maiorino ◽  
Lorenzo Scappaticcio ◽  
Annamaria De Bellis ◽  
Silvia Mercadante ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Biological Rhythms ◽  
Cellular Level ◽  
Scientific Discipline ◽  
Biological Phenomena ◽  
Pituitary Thyroid Axis ◽  
Circadian Organization ◽  
Thyroid Axis ◽  
Central Clock ◽  
Thyroid Dysfunctions

Chronobiology is the scientific discipline which considers biological phenomena in relation to time, which assumes itself biological identity. Many physiological processes are cyclically regulated by intrinsic clocks and many pathological events show a circadian time-related occurrence. Even the pituitary–thyroid axis is under the control of a central clock, and the hormones of the pituitary–thyroid axis exhibit circadian, ultradian and circannual rhythmicity. This review, after describing briefly the essential principles of chronobiology, will be focused on the results of personal experiences and of other studies on this issue, paying particular attention to those regarding the thyroid implications, appearing in the literature as reviews, metanalyses, original and observational studies until 28 February 2021 and acquired from two databases (Scopus and PubMed). The first input to biological rhythms is given by a central clock located in the suprachiasmatic nucleus (SCN), which dictates the timing from its hypothalamic site to satellite clocks that contribute in a hierarchical way to regulate the physiological rhythmicity. Disruption of the rhythmic organization can favor the onset of important disorders, including thyroid diseases. Several studies on the interrelationship between thyroid function and circadian rhythmicity demonstrated that thyroid dysfunctions may affect negatively circadian organization, disrupting TSH rhythm. Conversely, alterations of clock machinery may cause important perturbations at the cellular level, which may favor thyroid dysfunctions and also cancer.

scholarly journals The role of bilateral inferior petrosal sinus sampling in the diagnosis of Cushing's syndrome

2007 ◽  
Vol 51 (8) ◽  
pp. 1329-1338 ◽  
Author(s):  
Andrea Utz ◽  
Beverly M.K. Biller
Keyword(s):  
Cushing’S Syndrome ◽  
Venous Drainage ◽  
Cushing's Syndrome ◽  
Blood Levels ◽  
Inferior Petrosal Sinus ◽  
Ectopic Acth ◽  
Inferior Petrosal Sinus Sampling ◽  
Neoplastic Lesion ◽  
Before And After ◽  
Acth Secreting

Adrenocorticotropin hormone (ACTH)-dependent Cushing's syndrome is most often due to a pituitary corticotroph adenoma, with ectopic ACTH-secreting tumors representing approximately 15% of cases. Biochemical and radiological techniques have been established to help distinguish between these two entities, and thus aid in the localization of the neoplastic lesion for surgical resection. The test that offers the highest sensitivity and specificity is bilateral inferior petrosal sinus sampling (BIPSS). BIPSS is an interventional radiology procedure in which ACTH levels obtained from venous drainage very near the pituitary gland are compared to peripheral blood levels before and after corticotropin hormone (CRH) stimulation. A gradient between these two locations indicates pituitary Cushing's, whereas the absence of a gradient suggests ectopic Cushing's. Accurate BIPSS results require hypercortisolemia to suppress normal corticotroph ACTH production and hypercortisolemia at the time of the BIPSS to assure excessive ACTH secretion. In some cases, intrapituitary gradients from side-to-side can be helpful to localize small corticotroph adenomas within the sella. BIPSS has rare complications and is considered safe when performed at centers with experience in this specialized technique.

scholarly journals Frequency of Osteoporosis in Iatrogenic Cushing’s syndrome: Scenario of outpatient department in urban hospitals

2020 ◽  
Vol 31 (1) ◽  
pp. 18-21
Author(s):  
Tamanna Bahar ◽  
Shaila Rahman ◽  
Lilian Catherene Gomes ◽  
Mohammad Murad Hossain ◽  
Zulfia Zinat Chowdhury ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing Syndrome ◽  
Reference Population ◽  
Final Diagnosis ◽  
Cushing's Syndrome ◽  
Outpatient Department ◽  
Clinical Feature ◽  
Cross Sectional ◽  
Prevalence Of Osteoporosis ◽  
Iatrogenic Cushing’S Syndrome

Background: Cushing’s syndrome is caused by excessive activation of glucocorticoid receptor. Iatrogenic Cushing syndrome is the prevalent one world -wide .Patients with Cushing’s syndrome has a high prevalence of osteoporosis. Objective: To see the prevalence of osteoporosis in Iatrogenic Cushing’s syndrome patient. Method: This descriptive cross-sectional study included 211 diagnosed case of Cushing’s syndrome during the time period of December 2013 to December 2018 in outpatient department of Dhaka Medical College and Health and Hope Hospital. Final diagnosis was done on the basis of clinical feature, serum basal cortical level and BMD. We found male were prevalent one (56%).80.56% showed biochemical evidence of Cushing’s syndrome. BMD was done in 113 patients compared with a reference population by means of T score, 17.69% patient in osteoporotic range. Conclusion: The prevalence of osteoporosis and osteopenia is age and sex independent. Judicial use of steroid and co administration with calcium, bisphosphonate can prevent osteoporosis. Treatment with bisphosphonates should be considered in all patients (irrespective of age) with Cushing’s syndrome with a low BMD to reduce fracture. Bangladesh J Medicine Jan 2020; 31(1) : 18-21

A Novel GNAS Mutation Causing Isolated Infantile Cushing’s Syndrome

2019 ◽  
Vol 92 (3) ◽  
pp. 196-202
Author(s):  
Prapai Dejkhamron ◽  
Chupong Ittiwut ◽  
Hataitip TangNgam ◽  
Kanokkarn Sunkonkit ◽  
Rungrote Natesirinilkul ◽  
...  
Keyword(s):  
Fibrous Dysplasia ◽  
Precocious Puberty ◽  
Cushing’S Syndrome ◽  
De Novo ◽  
Cushing Syndrome ◽  
Skin Pigmentation ◽  
Cushing's Syndrome ◽  
Polyostotic Fibrous Dysplasia ◽  
Pneumocystis Jiroveci ◽  
Gnas Gene

Infantile Cushing’s syndrome is potentially found as part of McCune-Albright syndrome (MAS) which is caused by postzygotic somatic mutations of the GNAS gene. MAS is typically characterized by a triad of polyostotic fibrous dysplasia, café-au-lait skin pigmentation, and precocious puberty or other endocrine hyperfunction. Here, we describe a 2-month-old female infant with features of Cushing’s syndrome without café au lait spots, polyostotic fibrous dysplasia, and clinical evidence of other endocrine hyperfunction. Investigations demonstrated adrenocorticotropic hormone-independent Cushing’s syndrome with bilateral adrenal gland enlargement. Whole-exome sequencing of leukocytes identified a de novo heterozygous novel missense mutation (c.521G>A, p.Cys174Tyr) in the GNAS gene. The patient experienced clinical improvement of Cushing’s syndrome during ketoconazole treatment. Her clinical course was complicated by Pneumocystis jiroveci pneumonia. She also had shortened activated partial thromboplastin time indicating a hypercoagulable state and resulting in pulmonary embolism. She eventually manifested gonadotropin-independent precocious puberty at the age of 13 months after ketoco­nazole was discontinued. This patient demonstrated that Cushing syndrome can be the presenting sign of MAS in infancy. A high index of suspicion followed by genetic analysis is essential in order to establish a diagnosis.

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