Clinical features, risk of mass enlargement, and development of endocrine hyperfunction in patients with adrenal incidentalomas: a long-term follow-up study

Abstract Purpose To evaluate the risk of mass enlargement and endocrine function modification in patients with adrenal incidentaloma (AI). Methods In this retrospective study, we examined clinical and hormonal characteristics of 310 patients with AI (200 females and 110 males; age: 58.3 ± 12.9 years), followed up for a median (interquartile range) of 31.4 months (13.0–78.6) and evaluated for possible modification in adrenal mass size and hormonal function. The hormonal evaluation included morning serum cortisol and plasma ACTH at 8 a.m., aldosterone, plasma renin activity/direct renin concentration, and 24-h urine metanephrines/normetanephrines. One microgram overnight dexamethasone suppression test (DST) was performed. Autonomous cortisol secretion (ACS) was diagnosed in the presence of cortisol after 1 mg DST > 5 μg/dl (138 nmol/l) or >1.8 and ≤5 μg/dl (50–138 nmol/l) and at least one of the following: (i) low ACTH; (ii) increased 24-h urinary-free cortisol; (iii) absence of cortisol rhythm; and (iv) post-LDDST cortisol level > 1.8 μg/dl (50 nmol/l). When there was no biochemical evidence of adrenal hormonal hyperactivity, AIs were classified as nonfunctioning (NFAIs). The mass was considered significantly enlarged when the size increase was more than 20% and at least 5 mm compared to baseline. Results At diagnosis, NFAIs were found in 209 patients, while ACS and overt adrenal hyperfunction were diagnosed in 81 and 20 patients, respectively. During follow-up, 3.3% and 1.5% of patients with NFAI developed subtle and overt endocrine hyperfunction, respectively, while a significant mass enlargement was observed in 17.7% of all AIs. The risk of developing ACS was significantly higher in patients with adenoma >28 mm (hazard ratio [HR] 12.4; 95% confidence interval [CI], 2.33–66.52, P = 0.003), in those with bilateral adrenal tumors (HR: 5.36; 95% CI, 1.17–24.48, P = 0.030), and with low/suppressed ACTH values (HR: 11.2, 95% CI 2.06–60.77; P = 0.005). The risk of mass enlargement was lower for patients in the fourth quartile of body mass index than those in the first quartile (HR 0.33; 95% CI, 0.14–0.78; P = 0.012). Conclusions In patients with AI, the risk of developing hormonal hyperfunction and mass enlargement is overall low, although some tumor characteristics and anthropometric features might increase this risk. Taking account of all these aspects is important for planning a tailored follow-up in AI patients.

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Post-surgical hypocortisolism after removal of an adrenal incidentaloma: is it predictable by an accurate endocrinological work-up before surgery?

Acta Endocrinologica ◽

10.1530/eje-09-0775 ◽

2010 ◽

Vol 162 (1) ◽

pp. 91-99 ◽

Cited By ~ 47

Author(s):

Cristina Eller-Vainicher ◽

Valentina Morelli ◽

Antonio Stefano Salcuni ◽

Massimo Torlontano ◽

Francesca Coletti ◽

...

Keyword(s):

Hpa Axis ◽

Adrenal Incidentaloma ◽

Serum Cortisol ◽

Urinary Free Cortisol ◽

Tolerance Test ◽

Surgical Removal ◽

Acth Stimulation ◽

Unilateral Adrenalectomy ◽

Free Cortisol ◽

Few Data

ObjectiveFew data are available regarding the need of steroid substitutive therapy after unilateral adrenalectomy for adrenal incidentaloma (AI). It is unknown whether, before surgery, the hypothalamic–pituitary–adrenal (HPA) axis secretion parameters can predict post-surgical hypocortisolism.AimThis study aimed to evaluate whether, in AI patients undergoing unilateral adrenalectomy, post-surgical hypocortisolism could be predicted by the parameters of HPA axis function.DesignProspective, multicenter.MethodsA total of 60 patients underwent surgical removal of AI (surgical indication: 29 subclinical hypercortisolism (SH); 31 AI dimension). Before surgery, SH was diagnosed in patients presenting at least three criteria out of urinary free cortisol (UFC) levels>60 μg/24 h, cortisol after 1-mg dexamethasone suppression test (1 mg-DST)>3.0 μg/dl, ACTH levels<10 pg/ml, midnight serum cortisol (MSC)>5.4 μg/dl.Two months after surgery, HPA axis function was assessed by low dose ACTH stimulation test or insulin tolerance test when needed: 39 patients were affected (Group B) and 21 were not affected (Group A) with hypocortisolism. The accuracy in predicting hypocortisolism of pre-surgical HPA axis parameters or their combinations was evaluated.ResultsThe presence of >2 alterations among 1 mg-DST>5.0 μg/dl, ACTH<10 pg/ml, elevated UFC and MSC has the highest odds ratio (OR) for predicting post-surgical hypocortisolism (OR 10.45, 95% confidence interval, CI 2.54–42.95, P=0.001). Post-surgical hypocortisolism was predicted with 100% probability by elevated UFC plus MSC levels, but not ruled out even in the presence of the normality of all HPA axis parameters.ConclusionPost-surgical hypocortisolism cannot be pre-surgically ruled out. A steroid substitutive therapy is indicated after unilateral adrenalectomy for SH or size of the adenoma.

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Accuracy of several parameters of hypothalamic–pituitary–adrenal axis activity in predicting before surgery the metabolic effects of the removal of an adrenal incidentaloma

Acta Endocrinologica ◽

10.1530/eje-10-0602 ◽

2010 ◽

Vol 163 (6) ◽

pp. 925-935 ◽

Cited By ~ 45

Author(s):

Cristina Eller-Vainicher ◽

Valentina Morelli ◽

Antonio Stefano Salcuni ◽

Claudia Battista ◽

Massimo Torlontano ◽

...

Keyword(s):

Adrenal Incidentaloma ◽

Serum Cortisol ◽

Urinary Free Cortisol ◽

Hypothalamic Pituitary Adrenal Axis ◽

Metabolic Effects ◽

Hypothalamic Pituitary Adrenal ◽

Adrenal Axis ◽

Free Cortisol ◽

Metabolic Outcome ◽

Pituitary Adrenal Axis

ContextIt is unknown whether the metabolic effects of the removal of an adrenal incidentaloma (AI) can be predicted by the assessment of cortisol hypersecretion before surgery.ObjectiveTo evaluate the accuracy of several criteria of hypothalamic–pituitary–adrenal axis activity in predicting the metabolic outcome after adrenalectomy.DesignRetrospective longitudinal study.PatientsIn 55 surgically treated AI patients (Group 1) before surgery and in 53 nontreated AI patients (Group 2) at the baseline, urinary free cortisol (UFC), cortisol after 1 mg overnight dexamethasone-suppression test (1 mg-DST), ACTH, and midnight serum cortisol (MSC) were measured. In Groups 1 and 2, metabolic parameters were evaluated before and 29.6±13.8 months after surgery and at the baseline and after 35.2±10.9 months respectively.Main outcome measuresThe improvement/worsening of weight, blood pressure, glucose, and cholesterol levels (endpoints) was defined by the presence of a >5% weight decrease/increase and following the European Society of Cardiology or the ATP III criteria respectively. The accuracy of UFC, 1 mg-DST, ACTH, and MSC, singularly taken or in combination, in predicting the improvement/worsening of ≥2 endpoints was calculated.ResultsThe presence of ≥2 among UFC>70 μg/24 h (193 nmol/l), ACTH<10 pg/ml (2.2 pmol/l), 1 mg-DST>3.0 μg/dl (83 nmol/l) (UFC–ACTH–DST criterion) had the best accuracy in predicting the endpoints' improvement (sensitivity (SN) 65.2%, specificity (SP) 68.8%) after surgery. In the nontreated AI patients, this criterion predicted the worsening of ≥2 endpoints (SN 55.6%, SP 82.9%).ConclusionsThe UFC–ACTH–DST criterion seems to be the best for predicting the metabolic outcome in surgically treated AI patients.

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Five years follow up of patients with Сushing’s disease with and without visualized pituitary adenoma on MRI, who underwent transsphenoidal adenomectomy

Problems of Endocrinology ◽

10.14341/probl2017635276-281 ◽

2017 ◽

Vol 63 (5) ◽

pp. 276-281

Author(s):

Patimat M. Khandaeva ◽

Zhanna E. Belaya ◽

Lyudmila Ya. Rozhinskaya ◽

Aleksandr V. Vorontsov ◽

Andrey Yu. Grigoriev ◽

...

Keyword(s):

Pituitary Adenoma ◽

Cushing’S Disease ◽

Remission Rate ◽

Serum Cortisol ◽

Urinary Free Cortisol ◽

Cushing's Disease ◽

Surgery Complications ◽

Free Cortisol ◽

Transsphenoidal Adenomectomy

The remission rate of Cushing’s disease in patients after neurosurgery varies from 59 to 94%, while the recurrence rate is 3 to 46%. Aim — to evaluate the five-year outcome in neurosurgery patients with Cushing’s disease (CD), depending on preoperative MRI-based identification of pituitary adenoma. Material and methods. The study included 105 neurosurgery patients with histologically confirmed CD. CD remission was confirmed by the development of adrenal insufficiency and/or normalization of serum cortisol and 24-hour urinary free cortisol (24h UFC) levels, as well as by clinical remission. Results. Pituitary adenoma was not visualized by gadolinium MRI in 35 cases. The size of visualized pituitary adenoma varied from 0.3 to 29 mm. After first neurosurgery, remission was achieved in 87 (82.8%) patients. After second neurosurgery, remission occurred in 12 patients. Radiation therapy was conducted in 24 patients. Six patients had bilateral adrenalectomy. Two patients died during remission: one patient died from stroke two years after neurosurgery, and the other patient died due to surgery complications. During five-year follow-up after neurosurgery, remission continued in 76 (72.8%) patients, including 27 (77%) of 35 patients without MRI-detected adenoma and 49 (70%) of 70 patients with MRI-detected pituitary adenoma, p=0.15. Sixty-six patients developed recurrence, and 14 patients had active hypercortisolism. Conclusion. There was no correlation between the rate of preoperative MRI-based detection of pituitary adenoma and the rate of remission in neurosurgery patients with Cushing’s disease during the five year follow-up. The size of pituitary adenoma was a risk factor for adenoma recurrence.

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The Occurrence of Subclinical Hypercortisolism and Osteoporosis in Patients with Incidentally Discovered Unilateral and Bilateral Adrenal Tumors

Journal of Medical Biochemistry ◽

10.1515/jomb-2016-0020 ◽

2016 ◽

Vol 35 (4) ◽

pp. 401-409

Author(s):

Sanja Ognjanović ◽

Djuro Macut ◽

Milan Petakov ◽

Valentina Elezović Kovačević ◽

Tatjana Isailović ◽

...

Keyword(s):

Serum Cortisol ◽

Urinary Free Cortisol ◽

Adrenal Tumors ◽

Mineral Density ◽

Subclinical Hypercortisolism ◽

Similar Frequency ◽

Free Cortisol ◽

Adrenal Masses ◽

Suppression Test ◽

Cortisol Levels

SummaryBackground:Adrenal incidentalomas (AI) are clinically silent adrenal masses that are detected incidentally during imaging procedures performed for unrelated diseases. The aim of this study was to investigate the prevalence of subclinical hypercortisolism (SH) and associated co-morbidities in patients with unilateral AI (UAI) and bilateral AI (BAI).Methods:We evaluated 152 patients, 105 (69.1%) with UAI and 47 (30.9%) with BAI. SH was diagnosed in the presence of serum cortisol levels after 1 mg dexamethasone suppression test (DST) or after 2-day low-dose DST (LDDST) > 50 nmol/L with at least one of the following parameters: midnight serum cortisol > 208 nmol/L, 24-h urinary free cortisol > 245 nmol/24 h, or ACTH < 10 ng/L. Bone mineral density (BMD) was measured at lumbar spine (LS) and femoral neck (FN).Results:Age, BMI, and waist circumference were comparable, and diabetes, hypertension and dyslipidemia occurred with similar frequency in both groups. The overall prevalence of SH was 20.5% based on post-1 mg DST, and 20.0% based on post-LDDST cortisol levels, and it was more prevalent in BAI than UAI patients (31.1%vs15.2%, respectively, p=0.026). LS BMD was lower in BAI than in UAI patients (0.96±0.14vs0.87±0.15, p=0.002). There were no differences in FN BMD. The prevalence of osteoporosis was higher in BAI compared to UAI patients (37.1%vs15.9%, respectively, p=0.011).Conclusions:Patients with BAI had higher prevalence of SH and osteoporosis than those with UAI. Frequency of other co-morbidities was similar. This may be due to the higher degree of autonomous cortisol secretion or different tissue-specific sensitivity to glucocorticoids.

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Usefulness of adrenal scintigraphy in the follow-up of adrenocortical incidentalomas: a prospective multicenter study

Acta Endocrinologica ◽

10.1530/eje-08-0299 ◽

2009 ◽

Vol 160 (2) ◽

pp. 257-264 ◽

Cited By ~ 34

Author(s):

Cédric Fagour ◽

Stéphane Bardet ◽

Vincent Rohmer ◽

Yannick Arimone ◽

Pierre Lecomte ◽

...

Keyword(s):

Tumor Size ◽

Rare Event ◽

Urinary Free Cortisol ◽

Adrenocortical Adenomas ◽

Free Cortisol ◽

Clinical Consequences ◽

Hormonal Evaluation ◽

The Relationship ◽

Adrenal Hyperfunction

ObjectivesPrognostic factors for progression of benign adrenocortical adenomas (AI) remain poorly known. We assessed the usefulness of 131I-6-β-iodomethylnorcholesterol scintigraphy (IMS) to predict the occurrence of adrenal hyperfunction or mass enlargement.DesignFifty-one consecutive inpatients with unilateral AI and normal 24-h urinary free cortisol (UFC) were enrolled in a multicenter observational prospective study to investigate the relationship between the scintigraphic pattern and the progression of biological abnormalities of the hypothalamo-pituitary–adrenal axis or tumor size.ResultsBiochemically defined ‘subclinical’ Cushing's syndrome (SCS) was found at baseline in 47% of patients. Unilateral uptake (UU) was significantly associated with SCS (P<0.05). During the follow-up (4.3±1.6-year): 53% of patients showed unchanged hormonal evaluation, 29% displayed intermittent SCS and 18% showed definitive hormonal progression of SCS but without overt biochemical hypercortisolism. UU was associated with persistence of SCS and hormonal progression (P<0.01). In multivariate analysis, UU and impaired 1 mg dexamethasone suppression were independently associated with hormonal progression. Three patients with UU developed clinical CS despite persistently normal UFC. Tumor size increased in 10% patients and was not associated with any scintigraphic pattern.ConclusionEvolution of SCS toward overt biochemical CS in patients with AI is a rare event during a 4-year follow-up. UU is predictive for the occurrence of SCS, its persistence and progression within the spectrum of SCS. Further studies aiming to establish the clinical consequences of SCS are needed to recommend IMS as a complementary evaluation in patients with AI and biochemical SCS.

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The role of imaging in congenital adrenal hyperplasia

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/0004-2730000003371 ◽

2014 ◽

Vol 58 (7) ◽

pp. 701-708 ◽

Cited By ~ 6

Author(s):

Sara Reis Teixeira ◽

Paula Condé Lamparelli Elias ◽

Marco Túlio Soares Andrade ◽

Andrea Farias Melo ◽

Jorge Elias Junior

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Adrenal Tumors ◽

Adrenal Hyperplasia ◽

Salt Wasting ◽

Testicular Adrenal Rest Tumors ◽

High Incidence ◽

Adrenal Rest ◽

Hormonal Evaluation

Congenital adrenal hyperplasia (CAH) is an autossomic recessive disorder caused by impaired steroidogenesis. Patients with CAH may present adrenal insufficiency with or without salt-wasting, as well as various degrees of virilization and fertility impairment, carrying a high incidence of testicular adrenal rest tumors and increased incidence of adrenal tumors. The diagnosis of CAH is made based on the adrenocortical profile hormonal evaluation and genotyping, in selected cases. Follow-up is mainly based on hormonal and clinical evaluation. Utility of imaging in this clinical setting may be helpful for the diagnosis, management, and follow-up of the patients, although recommendations according to most guidelines are weak when present. Thus, the authors aimed to conduct a narrative synthesis of how imaging can help in the management of patients with CAH, especially focused on genitography, ultrasonography, computed tomography, and magnetic resonance imaging.

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Spontaneous remission of hypercortisolism presumed due to asymptomatic tumor apoplexy in ACTH-producing pituitary macroadenoma

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302013000600012 ◽

2013 ◽

Vol 57 (6) ◽

pp. 486-489 ◽

Cited By ~ 4

Author(s):

Marcio Carlos Machado ◽

Patricia Sampaio Gadelha ◽

Marcello Delano Bronstein ◽

Maria Candida Barisson Vilares Fragoso

Keyword(s):

Salivary Cortisol ◽

Signs And Symptoms ◽

Spontaneous Remission ◽

Pituitary Surgery ◽

Serum Cortisol ◽

Urinary Free Cortisol ◽

High Plasma ◽

Imaging Data ◽

Cystic Component ◽

Free Cortisol

Cushing's disease (CD) is usually caused by secretion of ACTH by a pituitary corticotroph microadenoma. Nevertheless, 7%-20% of patients present with ACTH-secreting macroadenomas. Our aim is to report a 36-year-old female patient with CD due to solid-cystic ACTH-macroadenoma followed up during 34 months. The patient presented spontaneous remission due to presumed asymptomatic tumor apoplexy. She showed typical signs and symptoms of Cushing's syndrome (CS). Initial tests were consistent with ACTH-dependent CS: elevated urinary free cortisol, abnormal serum cortisol after low dose dexamethasone suppression test, and elevated midnight salivary cortisol, associated with high plasma ACTH levels. Pituitary magnetic resonance imaging (MRI) showed a sellar mass of 1.2 x 0.8 x 0.8 cm of diameter with supra-sellar extension leading to slight chiasmatic impingement, and showing hyperintensity on T2-weighted imaging, suggesting a cystic component. She had no visual impairment. After two months, while waiting for pituitary surgery, she presented spontaneous resolution of CS. Tests were consistent with remission of hypercortisolism: normal 24-h total urinary cortisol and normal midnight salivary cortisol. Pituitary MRI showed shrinkage of the tumor with disappearance of the chiasmatic compression. She has been free from the disease for 28 months (without hypercortisolism or hypopituitarism). The hormonal and imaging data suggested that silent apoplexy of pituitary tumor led to spontaneous remission of CS. However, recurrence of CS was described in cases following pituitary apoplexy. Therefore, careful long-term follow-up is required.

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Clozapine Use Presenting with Pseudopheochromocytoma in a Schizophrenic Patient: A Case Report

Case Reports in Endocrinology ◽

10.1155/2013/194927 ◽

2013 ◽

Vol 2013 ◽

pp. 1-3 ◽

Cited By ~ 2

Author(s):

Jaskanwal Sara ◽

Matt Jenkins ◽

Tanveer Chohan ◽

Karan Jolly ◽

Lisa Shepherd ◽

...

Keyword(s):

Blood Pressure ◽

Adrenal Glands ◽

Serum Cortisol ◽

Serum Levels ◽

Urinary Free Cortisol ◽

Free Cortisol ◽

History Of ◽

Caucasian Female ◽

Abnormal Uptake ◽

Noradrenaline Levels

Introduction. There have been six previous cases that reported pseudopheochromocytoma in patients taking clozapine. Our case showed the direct link of clozapine to serum levels of certain markers.Case. This is a case of a 49-year-old obese Caucasian female who was referred to endocrinology for investigation of Cushing’s syndrome, based on raised blood pressure and Cushingoid facies. The patient had underlying schizophrenia and was stable on clozapine. Her blood pressure was 150/99 mmHg on bendroflumethiazide and candesartan. We measured her 24-hour urinary-free cortisol, which was normal but 24-hour urinary-free noradrenaline was elevated at 835 nmol (76–561) with normal adrenaline 36 nmol (7–82) and dopamine 2679 nmol (366–2879), as the patient had history of palpitations and sweating. Two sets of 24-hour urinary-free cortisol measurements were normal and serum cortisol suppressed to <50 nmol/l after a 1 mg overnight dexamethasone. Two further 24-hour urinary-free catecholamines showed a raised level of noradrenaline. MRI demonstrated normal adrenals and MIBG scan did not show any abnormal uptake at adrenal glands.Conclusion. Pseudopheochromocytoma has been reported in patients taking clozapine. A number of different mechanisms for raised plasma noradrenaline levels with clozapine have been postulated. The above case highlights an unusual but known side effect of clozapine.

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SUN-154 Resistant Hypertension After Shockwave Lithotripsy: The Rude Awakening of an Adrenal Incidentaloma

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.046 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Ramon B Larrazabal

Keyword(s):

Blood Pressure ◽

Adrenal Mass ◽

Adrenal Incidentaloma ◽

Adrenal Tumors ◽

Shockwave Lithotripsy ◽

Adrenocortical Adenoma ◽

Institutional Perspective ◽

Surgical Interventions ◽

First Case ◽

Free Cortisol

Abstract BACKGROUND The National Institutes of Health defines adrenal incidentalomas (AIs) as clinically inapparent adrenal masses discovered inadvertently in diagnostic testing or treatment for conditions not related to the adrenal glands. Non-functional adenoma remains the most frequent (60–85%) cause, while functional adenomas at 5–16%. CLINICAL CASE A previously healthy 41 year-old female consulted for a 2-month history of left flank pain. Computed tomography (CT) scan of the kidneys revealed left calculi and incidental right adrenal mass. She was asymptomatic at this time. She then underwent shockwave lithotripsy for the renal calculi. However, post-operatively, she had elevated blood pressure and was started on anti-hypertensives. She remained hypertensive despite being on four different medications. Pertinent physical examination findings: plethora of the face and extremities, Moon facies, Buffalo Hump, and pendulous abdomen with grayish striae. Further work-up revealed the AI to be cortisol-secreting. Pertinent laboratories: 1 mg dexamethasone suppression test - 800 nmol/L (<50 nmol/L), 24-hr urine free cortisol - 1014.86 ug/24 hr (20–90 ug/24 hr), Adrenocorticotropic Hormone (ACTH) - 5.0 pg/ml (9–52 pg/ml). She then underwent a right laparoscopic adrenalectomy. Post-operatively, her blood pressure normalized without her anti-hypertensive medications. Tissue biopsy of the mass was consistent with an adrenocortical adenoma. On her follow-up after one month, signs of Cushing’s Syndrome were clinically improving. CONCLUSION This is the first case that demonstrated shockwave lithotripsy converting a non-functioning adrenal incidentaloma into a functioning one. It also shows how internists and surgeons (i.e. Urologists) can manage various aspects of patient care through the facilitation of medical treatments, surgical interventions, and ensuring a proper multidisciplinary approach based on the endocrinology clinical guidelines. So as not to delay the delivery of proper management to the patient. REFERENCES (1) Grumbach M, Biller B, Braunstein G. et al. “Management of the clinically inapparent adrenal mass (“incidentaloma”).” Annals of internal medicine 2003; 138:424–4292 Herrera M, Grant C, van Heerden J. et al. “Incidentally discovered adrenal tumors: an institutional perspective.” Surgery 1991; 110:1014.

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Corticotrope hypersecretion coupled with cortisol hypo-responsiveness to stimuli is present in patients with autoimmune endocrine diseases: evidence for subclinical primary hypoadrenalism?

Acta Endocrinologica ◽

10.1530/eje.1.02222 ◽

2006 ◽

Vol 155 (3) ◽

pp. 421-428 ◽

Cited By ~ 10

Author(s):

Roberta Giordano ◽

Marcella Balbo ◽

Andreea Picu ◽

Lorenza Bonelli ◽

Rita Berardelli ◽

...

Keyword(s):

Plasma Renin ◽

Normal Subjects ◽

Urinary Free Cortisol ◽

Tolerance Test ◽

Activity Levels ◽

Autoimmune Polyglandular Syndrome ◽

Insulin Tolerance ◽

Free Cortisol ◽

Adrenal Secretion ◽

Symptoms And Signs

Objective: In autoimmune polyglandular syndrome types 1, 2, and 4 primary adrenal insufficiency is present, but its diagnosis is often late. We investigated the function of the hypothalamic–pituitary–adrenal axis in a group of patients with autoimmune diseases (AP) without any symptoms and signs of hypoadrenalism. Design: In 10 AP and 12 normal subjects (NS), we studied cortisol (F), aldosterone (A), and DHEA responses to 0.06 μg adrenocorticotropin (ACTH) (1–24) followed by 250 μg, ACTH and F responses to human corticotropin-releasing hormone (hCRH; 100 μg) and insulin tolerance test (ITT) (0.1 UI/kg). Results: Basal F, A, DHEA, as well as urinary free cortisol and plasma renin activity levels in AP and NS were similar, whereas ACTH levels in AP were higher (P<0.05) than in NS. NS showed F, A, and DHEA response to both consecutive ACTH doses. In AP, the F, A, and DHEA responses to 250 μg ACTH were similar to those in NS, whereas the 0.06 μg ACTH dose did not elicit any significant response. The ACTH responses to hCRH and ITT in AP were higher (P<0.05) than in NS. The F response to hCRH in AP was lower (P<0.05) than in NS, whereas the F response to ITT in AP did not significantly differ from NS. Conclusions: Enhancement of both basal and stimulated corticotrope secretion coupled with reduced adrenal sensitivity to low ACTH dose is present in AP patients without symptoms and signs of hypoadrenalism. This functional picture suggests that normal adrenal secretion is maintained due to corticotrope hyperfunction, suggesting the existence of some subclinical primary hypoadrenalism.

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