Syndrome of resistance to thyroid hormone and thyrotropin-secreting pituitary adenoma: Case series study / 中华内分泌代谢杂志

Objective:To outline clinical features in syndrome of resistance to thyroid hormone(RTH) and thyrotropin-secreting pituitary adenoma(TSH adenoma) based on a case series, and to assess the value of octreotide suppression test and high-dose dexamethasone suppression test(HDDST) in differentiating the two diseases.Methods:A total of 22 cases with RTH and TSH adenoma clinically diagnosed in Xiangya Hospital of Central South University from October 2010 to December 2021 were retrieved. The clinical characteristics of the two diseases and results to different tests were analyzed and summarized.Results:(1) The tumors in TSH adenoma patients were larger than those with RTH complicated with pituitary mass, which presented chiasmatic compression on images( P<0.05). (2) In octreotide suppression test, thyrotropin(TSH) inhibition rate in RTH patients was lower than that in TSH adenoma patients( P<0.05). In HDDST, TSH inhibition rate was higher in patients with RTH than in patients with TSH adenoma( P<0.05). (3) The TSH inhibition rate was calculated by receiver operating characteristic(ROC) curve. The sensitivity and specificity of octreotide suppression test were 91.9% and 55.6%, respectively, and the threshold value of TSH inhibition rate was 64.24%. The sensitivity and specificity of HDDST were 54.4% and 89.0%, respectively, and the threshold value of TSH inhibition rate was 65.73%.The combined sensitivity and specificity of the two tests were 77.8% and 90.9%, indicating better diagnostic value( P<0.05). Conclusions:The combination of octreotide suppression test and HDDST is of clinical value in differentiating RTH from TSH adenoma. TSH adenoma is more aggressive than that of pituitary adenoma with RTH.

Validation of salivary cortisol among Filipino adults suspected with Cushing's syndrome

BACKGROUND: Cushing's syndrome is a state of hypercortisolism manifesting non-specific clinical; features where its diagnosis entails biochemical confirmation of cortisol excess. this study aims to validate the efficacy of midnight salivary cortisol as a screening test for Filipino suspected with Cushing's syndrome and determine the cut-off value applicable in the local setting. METHODS: This is a cross-sectional study of Filipinos suspected with endogenous Cushing's syndrome seen at a tertiary hospital. Modification of plasma cortisol measured by RIA was used to measure salivary cortisol. The sensitivity, specificity, positive predictive curve, negative predictive curve and area under the screening tests were estimated and compared using 48 hour low dose dexamethasone suppression test (LDDST) as the reference standard. RESULTS: The determine cut-off value (? 7.0 nmol/L) for salivary cortisol showed a relatively high sensitivity (91.3%) and specificity (89.5%) in detecting cases suspected of Cushing's syndrome. One milligram (1mg) dexamethasone suppression test had the highest sensitivity (100%) but had the lowest specificity (68.4%) as a screening test. The area under the curve of the three diagnostic test appeared to be similar when compared with the low dose dexamethasone suppression test. CONCLUSIONS: Using a cut-off value of 7nmol/L, local utility if late-night salivary cortisol has a high sensitivity and specificity in detecting Cushing's syndrome. It has a similar efficiency with 24-hour urine free cortisol and 1mg dexamethasone suppression test as a screening test for Cushing's syndrome. Salivary cortisol may be considered as a valid initial screening test for Filipinos suspected of cushing's syndrome.

Limited Diagnostic Utility of Plasma Adrenocorticotropic Hormone for Differentiation between Adrenal Cushing Syndrome and Cushing Disease

BACKGROUND: Measurement of the plasma adrenocorticotropic hormone (ACTH) level has been recommended as the first diagnostic test for differentiating between ACTH-independent Cushing syndrome (CS) and ACTH-dependent CS. When plasma ACTH values are inconclusive, a differential diagnosis of CS can be made based upon measurement of the serum dehydroepiandrosterone sulfate (DHEA-S) level and results of the high-dose dexamethasone suppression test (HDST). The aim of this study was to assess the utility of plasma ACTH to differentiate adrenal CS from Cushing' disease (CD) and compare it with that of the HDST results and serum DHEA-S level. METHODS: We performed a retrospective, multicenter study from January 2000 to May 2012 involving 92 patients with endogenous CS. The levels of plasma ACTH, serum cortisol, 24-hour urine free cortisol (UFC) after the HDST, and serum DHEA-S were measured. RESULTS: Fifty-seven patients had adrenal CS and 35 patients had CD. The area under the curve of plasma ACTH, serum DHEA-S, percentage suppression of serum cortisol, and UFC after HDST were 0.954, 0.841, 0.950, and 0.997, respectively (all P<0.001). The cut-off values for plasma ACTH, percentage suppression of serum cortisol, and UFC after HDST were 5.3 pmol/L, 33.3%, and 61.6%, respectively. The sensitivity and specificity of plasma ACTH measurement were 84.2% and 94.3%, those of serum cortisol were 95.8% and 90.6%, and those of UFC after the HDST were 97.9% and 96.7%, respectively. CONCLUSION: Significant overlap in plasma ACTH levels was seen between patients with adrenal CS and those with CD. The HDST may be useful in differentiating between these forms of the disease, especially when the plasma ACTH level alone is not conclusive.

The value of bilateral inferior petrosal sinus sampling in the differential diagnosis of ACTH-dependent Cushing's syndrome / 中华内分泌代谢杂志

Objective To evaluate the values of bilateral inferior petrosal sinus sampling ( BIPSS),high dosage dexamethasone suppression test (HDDST) and pituitary image in the differential diagnosis of ACTH-dependent Cushing's syndrome. Methods Totally 87 patients with confirmed pathological diagnosis were recruited in the study.All received the procedure of BLPSS,HDDST,and pituitary MRI with dynamic enhancement.The diagnostic performances of three differential diagnosis methods in ACTH-dependent Cushing's syndrome were evaluated.Results Seventy-eight patients were diagnosed as cases of pituitary ACTH adenoma,and the remaining 9 were confirmed cases of ectopic ACTH syndrome due to the thymic carcinoid.The sensitivity and specificity of HDDST,pituitary MRI,and BIPSS for the diagnosis of ACTH-dependent Cushing's syndrome were 82.1％ and 100％,79.5％ and 44.4％,92.3％ and 100％,respectively.In Cushing's disease,the diagnostic accuracy was 83.9％ with HDDST,77.0％with pituitary MRI,and93.1％ with BIPSS.In those patients with Cushing's disease,the coincidence of lateralization was 83.9％ with BIPSS and 64.5％ with MRII.Conclusion BIPSS was better than the other two methods in differential diagnosis of ACTH-dependent Cushing's syndrome.Compared with the pituitary MRI,the concordant rate of BIPSS in lateralization of the tumor is higher,and it is more reliable.

Relationship between low- and high-dose dexamethasone suppression test in patients with Cushing syndrome / 中华内分泌代谢杂志

Objective To investigate the relationship between the degree of serum cortisol suppression by low-dose dexamethasone (1 mg) and full serum cortisol suppression (suppression rate > 50% ) by high-dose dexamethasone (8 mg) in patients with Cushing syndrome, and to evaluate these tests in Cushing disease. Methods Ninty-one patients with Cushing syndrome were studied retrospectively. The relationship of 20%, 30%, 40%, and 50% cortisol suppression by overnight 1mg dexamethasone with full serum cortisol suppression by overnight 8 mg dexamethasone was analyzed, and the sensitivity and specificity in the diagnosis of Cushing disease were evaluated. Results The degree of cortisel suppression during overnight 1 mg dexamethasone suppression test was correlated with that during overnight 8 mg dexamethasone suppression test (r=0. 649,P<0. 001 ). 30, 22, 13, and 9 patients had greater than 20%, 30%, 40%, and 50% serum cortisol suppression respectively during overnight 1 mg dexamethasone suppression test. Among them, 23 ( 76. 7% ), 20 (90. 9% ), 12 (92.3%), and 9 ( 100.0% )patients had full serum cortisol suppression during overnight 8 mg dexamethasone suppression test. The sensitivity of the cutoff of greater than 20%, 30%, 40%, and 50% serum cortisol suppression for the diagnosis of Cushing disease was 52.8%, 32.7%, 22.6%, and 15.7%, and the specificity was 94.7%, 94.7%, 97.4%, and 97.4% respectively. Conclusions In patients with Cushing syndrome, greater than 20% serum cortisol suppression during overnight 1 mg dexamethasone suppression test is usually associated with full serum cortisol suppression during overnight 8 mg dexamethasone suppression test, and most of them are finally diagnosed as Cushing disease.

Simultaneous evaluation of in vivo glucocorticoid sensitivity and expression of glucocorticoid receptor alpha-isoform in rheumatoid arthritis patients / Avaliação concomitante da sensibilidade in vivo aos glicocorticóides e da expressão da isoforma alfa do receptor de glicocorticóide em pacientes com artrite reumatóide

OBJECTIVES: To analyze glucocorticoid (GC) sensitivity using intravenous very low dose dexamethasone suppression test (IV-VLD-DST) in patients with rheumatoid arthritis (RA) and its correlation with glucocorticoid receptor alpha-isoform (GRα) gene expression. METHODS: We evaluated 20 healthy controls and 32 RA patients with Health Assessment Questionnaire (HAQ) and Disease Activity Score 28 joints (DAS) scores and IV-VLD-DST and GRα expression in mononuclear cells. RESULTS: Basal cortisol and the percentage of cortisol reduction after IV-VLD-DST were lower in RA patients than in controls, whereas GRα expression was similar among groups. In the RA group there was an inverse correlation between GRα expression and the percentage of cortisol suppression that was not observed in controls. There was a direct relationship between DAS and GRα expression. CONCLUSIONS: Mechanisms involved in GC resistance observed in patients with RA are possibly not at the level of GRα gene expression, since it was similar among groups and GRα increased with disease activity.

OBJETIVOS: Determinar a sensibilidade aos glicocorticóides (GC) utilizando teste de supressão com dexametasona em doses muito baixas (IV-VLD-DST) em pacientes com artrite reumatóide (AR) e sua correlação com a expressão gênica da isoforma alfa do receptor glicocorticóide (GRα). MÉTODOS: Foram avaliados 20 controles saudáveis e 32 pacientes com AR com Health Assessment Questionnaire (HAQ) e Disease Activity Score 28 joints (DAS), IV-VLD-DST e expressão do GRα em células mononucleares. RESULTADOS: Cortisol basal e porcentagem de redução do cortisol após IV-VLD-DST foram menores no grupo AR do que nos controles, enquanto a expressão de GRα foi similar entre eles. No grupo com AR, ocorreu correlação negativa entre a expressão do GRα e a porcentagem de supressão do cortisol, enquanto nos controles não houve correlação. Ocorreu relação direta entre DAS e expressão de GRα . CONCLUSÕES: Sugerimos que os mecanismos envolvidos na resistência aos GC observada na AR não estejam ao nível da expressão gênica do GRα, já que esta é igual entre os grupos e aumenta com a gravidade da doença.

Screening and diagnosis of Cushing's syndrome: [review]

Cushing's syndrome (CS) results from sustained pathologic hypercortisolism. The clinical features are variable and the most specific features for CS include abnormal fat distribution, particularly in the supraclavicular and temporal fossae, proximal muscle weakness, wide purple striae, and decreased linear growth with continued weight gain in a child. Clinical presentation of CS can be florid and in this case the diagnosis is usually straightforward. However, the diagnosis can be difficult particularly in states of mild or cyclical or periodical hypercortisolism. Several tests based on the understanding of the physiologic characteristics of the hypothalamic-pituitary-adrenal axis have been used extensively to confirm the diagnosis of Cushing's syndrome, but none has proven fully capable of distinguishing all cases of CS from normal and/or pseudo-Cushing individuals. Three first-line diagnostic tests are currently used to screen for CS: measurement of free cortisol in 24-hour urine (UFC), cortisol suppressibility by low doses of dexamethasone (DST), and assessment of cortisol circadian rhythm using late-night serum and/or salivary cortisol. This paper discusses the effectiveness regarding best cut-off values, the sensitivity and the specificity of these tests to screen for CS. Late-night salivary cortisol appears to be the most useful screening test. UFC and DST should be performed to provide further confirmation of the diagnosis.

A síndrome de Cushing (SC) resulta de um hipercortisolismo patológico mantido. As manifestações clínicas são variáveis e os achados mais específicos para a SC incluem distribuição anormal de gordura, particularmente nas fossas supraclaviculares e temporais, fraqueza muscular proximal, estrias purpúreas largas e interrupção do crescimento linear com ganho contínuo de peso na criança. A apresentação clínica da SC pode ser florida e, neste caso, o diagnóstico é usualmente direto. Entretanto, o diagnóstico pode ser dificultado particularmente em estados de hipercortisolismo leve ou cíclico/periódico. Vários testes baseados na compreensão das características fisiológicas do eixo hipotálamo-hipófise-adrenal têm sido usados extensivamente para confirmar o diagnóstico da SC, mas nenhum deles mostrou-se totalmente capaz de distinguir todos os casos de SC dos indivíduos normais e/ou portadores de pseudo-Cushing. Três testes diagnósticos de primeira linha são atualmente empregados para rastrear SC: a medida do cortisol livre em urina de 24-horas (CLU), a supressão do cortisol por doses baixas de dexametasona (TSD) e a avaliação do ritmo circadiano do cortisol usando a dosagem do cortisol sérico ou salivar às 23-24 hs. Este artigo discute a efetividade com relação aos melhores valores de corte e a sensibilidade e especificidade destes testes no rastreamento da SC. O cortisol salivar às 23-24 hs parece ser o teste mais útil de rastreamento. O CLU e o TSD devem ser realizados na tentativa de fornecer confirmação adicional ao diagnóstico.

Pitfalls in the diagnosis of Cushing's syndrome: [review]

Among endocrine disorders, Cushing's syndrome (CS) is certainly one of the most challenging to endocrinologists due to the difficulties that often appear during investigation. The diagnosis of CS involves two steps: confirmation of hypercortisolism and determination of its etiology. Biochemical confirmation of the hypercortisolaemic state must be established before any attempt at differential diagnosis. Failure to do so will result in misdiagnosis, inappropriate treatment, and poor management. It should also be kept in mind that hypercortisolism may occur in some patients with depression, alcoholism, anorexia nervosa, generalized resistance to glucocorticoids, and in late pregnancy. Moreover, exogenous or iatrogenic hypercortisolism should always be excluded. The three most useful tests to confirm hypercortisolism are the measurement of 24-h urinary free cortisol levels, low-dose dexamethasone-suppression tests, and determination of midnight serum cortisol or late-night salivary cortisol. However, none of these tests is perfect, each one has different sensitivities and specificities, and several are usually needed to provide a better diagnostic accuracy. The greatest challenge in the investigation of CS involves the differentiation between Cushing's disease and ectopic ACTH syndrome. This task requires the measurement of plasma ACTH levels, non-invasive dynamic tests (high-dose dexamethasone suppression test and stimulation tests with CRH or desmopressin), and imaging studies. None of these tests had 100 percent specificity and their use in combination is usually necessary. Bilateral inferior petrosal sinus sampling is mainly indicated when non-invasive tests do not allow a diagnostic definition. In the present paper, the most important pitfalls in the investigation of CS are reviewed.

Entre as doenças endócrinas, a síndrome de Cushing (SC) é certamente uma das mais desafiadoras para o endocrinologista, devido às dificuldades que comumente surgem durante a investigação. O diagnóstico de SC envolve dois passos: a confirmação do hipercortisolismo e a determinação de sua etiologia. A confirmação bioquímica do excesso de cortisol precisa ser estabelecida antes de qualquer tentativa de diagnóstico diferencial; caso contrário, poderá resultar em diagnóstico incorreto, tratamento impróprio e manejo insuficiente. Deve também ser lembrado que hipercortisolismo pode ocorrer em certos pacientes com depressão, alcoolismo, anorexia nervosa, resistência generalizada aos glicocorticóides e no final da gravidez. Além disso, hipercortisolismo exógeno ou iatrogênico deverá ser sempre excluído. Os três testes mais úteis para a confirmação do hipercortisolismo são: a medida do cortisol livre em urina de 24 h, os testes de supressão com dexametasona (TSD) em doses baixas e a determinação do cortisol sérico à meia-noite ou do cortisol salivar no final da noite. Contudo, nenhum deles é perfeito, cada um com sua sensibilidade e especificidade, sendo vários deles usualmente necessários para fornecer uma melhor acurácia diagnóstica. O maior desafio na investigação da SC envolve a diferenciação entre a doença de Cushing e a síndrome do ACTH ectópico. Esta tarefa requer a medida dos níveis plasmáticos de ACTH, testes dinâmicos não-invasivos (TSD com doses altas e testes de estímulo com CRH ou desmopressina) e estudos de imagem. Nenhum desses testes tem 100 por cento de especificidade e muitas vezes é necessário seu uso combinado. Amostragem venosa do seio petroso inferior está indicada principalmente quando os testes não-invasivos não permitem uma definição diagnóstica. Neste artigo, revisaremos as mais importantes armadilhas na investigação da SC.

Comparison of effects between the combined and classic dexamethasone suppression test on diagnosis of Cushing's syndrome / 中国实用内科杂志

Objective To evaluate effects of the combined and classic dexamethasone suppression test(DST)on the diagnosis of Cushing's syndrome.Methods Retrospective analysis was made about the results of DST from 152 patients of Cushing syndrome with surgically confirmed causes in recent 10 years.Results The diagnosis accuracy of overnight low dose DST,classic low dose DST and of combined low dose DST was 97.5%,96.1%and 97.6% respectively for determining diagnosis of Cushing's syndrome.No obvious difference was found in three groups(P=0.86).The diagnosis accuracy of 31 cases of classic and 17 cases of combined high dose DST was 80.6%(25/31)and 76.4% respectively without obvious difference(P =0.73)for locating diagnosis of Cushing's disease.The diagnosis accuracy of classic and combined high dose DST was 94.2% and 95.5% respectively without obvious difference(P =0.83)for locating diagnosis of ACTH independent Cushing's syndrome.Sensitivity and specificity for Cushing's disease were 81.5% and 92.5% in classic low dose and high dose DST and 77.8% and 95.5% in combined low dose and high dose DST.Conclusion Compared to the classic DST,combined DST has the advantages of double controls,simplicity and saving time.Because diagnosis accuracy of combined DST is in accordance with the classic DST,it is recommended to be a routine for diagnosing Cushing's syndrome.

A Case of Bilateral Macronodular Adrenal Hyperplasia with Cushing's Syndrome Treated by Unilateral Adrenalectomy / 대한내분비학회지

In order to differentiate the causes of Cushing's syndrome; whether it is pituitary or adrenal-dependent, a high dose dexamethasone suppression test is usually performed but this does not always correlated with the imaging diagnosis. We report a case of bilateral macronodular adrenal hyperplasia, which was thought to be independent to adrenocorticotrophin (ACTH) stimulation. At first we thought it was pituitary-dependent Cushing's syndrome, due to its suppression by high dose dexamethasone. However, we found no abnormal findings on the brain sella magnetic resonance image (MRI). A significant finding, however, we found bilateral adrenal masses on the abdominal computed tomography (CT). We performed percutaneous selective adrenal venous sampling (PSAVS), and confirmed hypercortisolism of the left adrenal mass only. Therefore, we decided to remove the left adrenal gland to preserve the residual function of the right adrenal gland. After the left adrenalectomy, the patient became normotensive, and their buffalo hump disappeared, and her 24 hour urinary free cortisol level returned to normal.

The Understanding of Depression Subtypes

The debate about whether depressive disorders should be divided into categories or arrayed along a continuum has gone for decade, without resolution. In our review, there is more evidence consistent with the spectrum concept than there is with the idea that depressive disorders constitute discrete clusters marked by relatively discontinuous boundaries. First, "depression spectrum", "is there a common genetic factors in bipolar and unipolar affective disorder", "threshold model of depression" and "bipolar spectrum disorder" are reviewed. And, a new subtype of depression is so called SeCA depression that is a stressor-precipitated, cortisol-induced, serotonin-related, anxiety/aggression-driven depression. SeCA depression is discussed. But, there is with the idea that depressive disorders constitute discrete subtypes marked by relatively discontinuous boundaries. This subtypes of depressive disorder were reviewed from a variety of theoretical frames of reference. The following issues are discussed ; Dexamethasone suppression test(DST), TRH stimulation test, MHPG, Temperament Character Inventory(TCI), and heart rate variability(HRV).

Comparison of various assays in diagnosing Cushing′s syndrome / 中华内分泌代谢杂志

Objective To evaluate the sensitivity and specificity of various assays in diagnosing Cushing′s syndrome. Methods The plasma cortisol, urinary free cortisol (UFC), circadian rhythm in cortisol secretion and dexamethasone suppression test were assessed in 173 patients clinically diagnosed Cushing′s syndrome. The data were compared with the postoperative pathologic diagnosis. Results The normal diurnal rhythm of cortisol secretion was lost in 92.9% patients with Cushing′s syndrome. The loss of normal diurnal rhythm of cortisol secretion of 2 time points occurred in 85.1% (8:00, 16:00) and 91.8% (8:00, 24:00), and that of 3 time points (8:00, 16:00, 24:00) in 94.7% of the cases. The excretion of UFC was increased in 91.7% of patients with Cushing′s syndrome. Low-dosedexamethasonedidnotsuppressthe excessive secretion of glucocorticoid in 79.7% (1 mg) and 84.3% (2 mg) patients with Cushing′s syndrome. The basal level of plasma cortisol was raised in 75.6% patients. The sensitivity of 8 mg dexamethasone suppression test was 50%-70% as the standard was set at 50% suppression, and specificity was more than 95%. Conclusion The most sensitive tests for Cushing′s syndrome are the loss of normal circadian rhythm of cortisol secretion and increased UFC. The method of 3 time points is more sensitive than that of 2 time points in the assessment of circadian rhythm. The 8 mg dexamethasone suppression test is the most useful method in differentiating Cushing′s disease from adrenal adenoma.

Re-evaluation of overnight low-dose dexamethasone suppression test in the diagnosis of Cushing syndrome / 中华内分泌代谢杂志

Objective To reinvestigate the value of overnight low-dose dexamethasone suppression test in the diagnosis of Cushing syndrome.Methods Fifty-two patients with Cushing syndrome and 153 patients with simple obesity or essential hypertension in whom Cushing syndrome was excluded were studied retrospectively in order to compare the sensitivity and specificity of different serum cortisol cut-off levels in overnight 1 mg dexamethasone suppression test in the diagnosis of Cushing syndrome.Results The sensitivity of 50% of basal serum cortisol level at 8:00 and of the serum cortisol cut-off levels of 275,200,138,50 nmoL/L at 8:00 after the overnight 1 mg dexamethasone suppression test was 92.3%,92.3%,92.3%,92.3% and 100.0% respectively, and the specificity was 90.8%,98.7%,96.1%,91.5% and 78.4%,respectively.Conclusion The serum cortisol cut-off level of 50 nmol/L in the overnight 1 mg dexamethasone suppression test has very high sensitivity and can be used as a screening test for Cushing syndrome.

High-dose dexamethasone suppression test-related differences in the clinical and biochemical features of Cushing's disease / 中华内分泌代谢杂志

Objective To analyse the high-dose dexamethasone suppression test(HDDST)-related differences in the clinical and biochemical features of the patients with Cushing's disease Methods Cases were drawn from 60 consecutive patients with Cushing's disease,who were then divided into two groups according to the response to the HDDST.The clinical and biochemical features between two groups were compared.Results(1) Of the 60 patients with Cushing's disease,23.3%(14/60)of patients(group A)did not yield results of suppression with the HDDST,and the others(group B)did.No difference was found in the age[(33.8?10.4 vs 36.2?11.2)years]and duration of illness[(2.1?1.6 vs 3.9?3.1)years]between two groups.(2)In clinical features,the patients in group A were more likely to have edema of lower limbs(64.3% vs 32.6%),hypokalemia (71.4% vs 28.3%),secondary diabetes(57.1% vs 26.1%)and purple striae(85.7% vs 54.3%,all P