The Hypothalamic-Pituitary-Thyroid Axis in Cushing Syndrome Before and After Curative Surgery

Shekhar, Skand; McGlotten, Raven; Auh, Sunyoung; Rother, Kristina I.; Nieman, Lynnette K.

doi:10.1210/clinem/dgaa858

Cited by 16 publications

(15 citation statements)

References 34 publications

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“…The decreased T3:T4 often reported can be due to GC-mediated inhibition of peripheral deiodination [ 26 ]. Consistent with this, after curative surgery, T3 levels increased disproportionately to T4 and FT4, reflecting the possible recovery of the type 1 and type 2 deiodinase activity, which converts T4 to T3, after the resolution of hypercortisolism [ 27 ]. Moreover, hypercortisolism is associated to a reduction in thyroxin biding globulin (TBG) [ 24 ], which contributes to the reduced T3 and T4 concentration.…”

Section: Effects Of Glucocorticoids On Hypothalamus–pituitary–thyrmentioning

confidence: 79%

“…A recent study retrospectively evaluated the thyroid function in two groups of patients affected by CS (cohort 1, 68 patients and cohort 2, 55 patients, who performed follow-up in different years), before and after successful surgery [ 27 ]. Data demonstrated that 53% of patients in cohort 1 had central hypothyroidism (low FT4 levels with inappropriately low TSH), while in cohort 2, the nocturnal secretion of TSH was subnormal before surgery.…”

Section: Thyroid Function Dynamic Changes In Cushing’s Syndromementioning

confidence: 99%

“…Data demonstrated that 53% of patients in cohort 1 had central hypothyroidism (low FT4 levels with inappropriately low TSH), while in cohort 2, the nocturnal secretion of TSH was subnormal before surgery. The alteration in thyroid function was reversible after the remission of hypercortisolism (mean time of recovery: 8 months), and the degree of central hypothyroidism was related to the duration of symptoms, morning and midnight serum cortisol, and urinary-free cortisol [ 27 ]. Interestingly, the HPT axis recovery time seemed to be inversely related to the severity of hypercortisolism, in which elevated urinary-free cortisol levels (≥1000 mcg/day) are a prognostic marker of longer recovery time.…”

Section: Thyroid Function Dynamic Changes In Cushing’s Syndromementioning

confidence: 99%

“…Interestingly, the HPT axis recovery time seemed to be inversely related to the severity of hypercortisolism, in which elevated urinary-free cortisol levels (≥1000 mcg/day) are a prognostic marker of longer recovery time. In addition, secondary hypogonadism was more frequent in CS patients affected by hypothyroidism [ 27 ]. This can be explained by an additional effect of hypercortisolemia on other hypothalamic–pituitary axes and by the fact that a normal hypothalamic–pituitary–gonadal axis function requires an intact HPT axis [ 27 , 32 ].…”

Section: Thyroid Function Dynamic Changes In Cushing’s Syndromementioning

confidence: 99%

“…In addition, secondary hypogonadism was more frequent in CS patients affected by hypothyroidism [ 27 ]. This can be explained by an additional effect of hypercortisolemia on other hypothalamic–pituitary axes and by the fact that a normal hypothalamic–pituitary–gonadal axis function requires an intact HPT axis [ 27 , 32 ]. Cai et al focused their retrospective evaluation only on ACTH-independent CS, studying a group of 94 patients affected by cortisol-secreting monolateral adrenal adenoma [ 33 ] and comparing them with a control group of patients with non-functioning adrenal incidentalomas.…”

Section: Thyroid Function Dynamic Changes In Cushing’s Syndromementioning

confidence: 99%

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Cushing’s Syndrome Effects on the Thyroid

Paragliola

Corsello

Papi

et al. 2021

IJMS

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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.

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Section: Effects Of Glucocorticoids On Hypothalamus–pituitary–thyrmentioning

confidence: 79%

Section: Thyroid Function Dynamic Changes In Cushing’s Syndromementioning

confidence: 99%

Section: Thyroid Function Dynamic Changes In Cushing’s Syndromementioning

confidence: 99%

Section: Thyroid Function Dynamic Changes In Cushing’s Syndromementioning

confidence: 99%

Section: Thyroid Function Dynamic Changes In Cushing’s Syndromementioning

confidence: 99%

See 3 more Smart Citations

Cushing’s Syndrome Effects on the Thyroid

Paragliola

Corsello

Papi

et al. 2021

IJMS

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Cushing Syndrome

Reincke

Fleseriu

2023

JAMA

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ImportanceCushing syndrome is defined as a prolonged increase in plasma cortisol levels that is not due to a physiological etiology. Although the most frequent cause of Cushing syndrome is exogenous steroid use, the estimated incidence of Cushing syndrome due to endogenous overproduction of cortisol ranges from 2 to 8 per million people annually. Cushing syndrome is associated with hyperglycemia, protein catabolism, immunosuppression, hypertension, weight gain, neurocognitive changes, and mood disorders.ObservationsCushing syndrome characteristically presents with skin changes such as facial plethora, easy bruising, and purple striae and with metabolic manifestations such as hyperglycemia, hypertension, and excess fat deposition in the face, back of the neck, and visceral organs. Cushing disease, in which corticotropin excess is produced by a benign pituitary tumor, occurs in approximately 60% to 70% of patients with Cushing syndrome due to endogenous cortisol production. Evaluation of patients with possible Cushing syndrome begins with ruling out exogenous steroid use. Screening for elevated cortisol is performed with a 24-hour urinary free cortisol test or late-night salivary cortisol test or by evaluating whether cortisol is suppressed the morning after an evening dexamethasone dose. Plasma corticotropin levels can help distinguish between adrenal causes of hypercortisolism (suppressed corticotropin) and corticotropin-dependent forms of hypercortisolism (midnormal to elevated corticotropin levels). Pituitary magnetic resonance imaging, bilateral inferior petrosal sinus sampling, and adrenal or whole-body imaging can help identify tumor sources of hypercortisolism. Management of Cushing syndrome begins with surgery to remove the source of excess endogenous cortisol production followed by medication that includes adrenal steroidogenesis inhibitors, pituitary-targeted drugs, or glucocorticoid receptor blockers. For patients not responsive to surgery and medication, radiation therapy and bilateral adrenalectomy may be appropriate.Conclusions and RelevanceThe incidence of Cushing syndrome due to endogenous overproduction of cortisol is 2 to 8 people per million annually. First-line therapy for Cushing syndrome due to endogenous overproduction of cortisol is surgery to remove the causative tumor. Many patients will require additional treatment with medications, radiation, or bilateral adrenalectomy.

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Evaluation of non-thyroidal illness syndrome in shock patients admitted to pediatric intensive care unit in a developing country

El-Nawawy,

Elwafa,

Khalil Abouahmed

et al. 2023

Eur J Pediatr

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During critical illness, children my experience various changes in their thyroid hormone levels. Such changes are termed non-thyroidal illness syndrome (NTI). The extent of change correlates with the severity of the illness and its outcomes in critically ill patients. This study aimed to investigate the correlation between the severity of shock and thyroid hormone derangement. This prospective observational study included forty patients aged one month to five years who were admitted to the pediatric intensive care unit (PICU) with shock. Thyroid function tests were conducted on admission, after shock reversal, and five days later. NTI patterns were observed in 70% of patients. The PIM2 score showed a significant negative correlation with T3 (r = − 0.353, p = 0.026) and FT3 levels on admission (r = − 0.417, p = 0.007). Furthermore, after shock reversal, the PIM2 score continued to exhibit significant negative correlations with T4 (r = − 0.444, p = 0.004), T3 (r = − 0.329, p = 0.038), FT3 (r = − 0.355, p = 0.025), and FT4 levels (r = − 0.379, p = 0.016). Conclusion: This study underscores the high prevalence of NTI in PICU shock patients and suggests monitoring thyroid hormone levels for outcome prediction and treatment guidance. Further research is needed to optimize NTI management in critically ill children. What is Known:• Non-thyroidal illness syndrome (NTIS) is a condition observed in critically ill patients.• There has been limited research on NTI in children, and existing studies have generated conflicting results regarding the relationship between thyroid hormones and clinical outcomes in cases of sepsis and septic shock. What is New:• The study has revealed dynamic changes in free triiodothyronine (FT3) levels during the process of shock reversal and recovery in children who experienced shock.• A significant negative correlation was found between the Pediatric Index of Mortality 2 (PIM2) score and several thyroid hormone levels, including FT3 on admission and T4, FT3, and FT4 on shock reversal.

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The Hypothalamic-Pituitary-Thyroid Axis in Cushing Syndrome Before and After Curative Surgery

Cited by 16 publications

References 34 publications

Cushing’s Syndrome Effects on the Thyroid

Cushing’s Syndrome Effects on the Thyroid

Cushing Syndrome

Evaluation of non-thyroidal illness syndrome in shock patients admitted to pediatric intensive care unit in a developing country

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