SAT-142 Periodic Cushing Syndrome in a Patient with an Intestinal Neuroendocrine Tumor (NET). A Novel Case Report

Abstract Introduction A major diagnostic enigma regarding ACTH-dependent Cushing syndrome is the distinction between the source of ACTH, which may have either a pituitary or ectopic origin. We present the first described patient with cyclic Cushing syndrome caused by an intestinal neuroendocrine tumour (NET) detected by 68GA-DOTATATE PET-CT, despite functional tests that were indicative of pituitary Cushing disease. Clinical Case A 53-year old man was admitted to outpatient clinic because of muscle weakness. His phenotype and clinical findings (progressively worsening upper and lower limb weakness, emotional disturbances, easy bruising, a Buffalo hump, prediabetes and leucocytosis) led to the diagnosis of Cushing syndrome. Initial laboratory tests established the diagnosis with an abnormal diurnal cortisol and ACTH secretion (night cortisol F: 22.1μg / dl), absence of suppression with dexamethasone 1mg and increased free urinary free cortisol 24h (243.5μg /24h). Abdominal CT scanning revealed a left-sided adrenal adrenocortical adenoma 1.5 mm in max diameter. Pituitary MRI and somatostatin scintigraphy were normal. Low dexamethasone suppression test was indicative of Cushing (F: 14μg / dl) followed by a combined CRH stimulation test during bilateral inferior petrosal sinus sampling. Pituitary / peripheral ACTH ratio pre-infusion of CRH and 3 min after CRH infusion was compatible with right-sided pituitary origin of ACTH hypersecretion. Pending the results of the laboratory, the patient showed a remission of his symptoms along with a laboratory-confirmed recession of active hypercortisolaemia (LDDST test), and this led to the suspicion of periodic Cushing syndrome. The patient was followed with clinical and laboratory examinations weekly, with recurrence of symptoms 2 months later followed by a new remission 3 months later. A PETGA CT SCAN with 68GA-HA-DOTATATE was performed, which showed an increased uptake of the radioisotope in the small intestine. A surgical excision of the affected small bowel region was performed according to the guidelines for intestinal NETs. Histology confirmed the existence of a well-differentiated neuroendocrine neoplasm of the small intestine of 1.1 cm diameter, grade 1 (WHO 2010). Immunophenotype was positive for serotonin and ACTH. Postoperatively, the patient showed a complete remission of symptomatology and regression of hypercortisolaemia over a 18-month period. Follow-up abdominal MRI and 68GA-HA-DOTATATE revealed no pathological findings. Conclusion: Our patient is the first case of ectopic Cushing disease caused by intestinal NET. The differential diagnosis between pituitary and ectopic Cushing syndrome due to ACTH or CRH hypersecretion is not easy and frequently complicated by the periodicity of the disease. In patients with no visible pituitary lesions on MRI we suggest further investigation for ectopic ACTH- driven Cushing syndrome.

Download Full-text

CLINICAL HETEROGENEITY OF ECTOPIC ACTH SYNDROME: A LONG-TERM FOLLOW-UP STUDY

Endocrine Practice ◽

10.4158/ep-2020-0368 ◽

2020 ◽

Vol 26 (12) ◽

pp. 1435-1441

Author(s):

Ana Laura Espinosa-de-los-Monteros ◽

Claudia Ramírez-Rentería ◽

Moisés Mercado

Keyword(s):

Adrenocorticotropic Hormone ◽

Cushing Syndrome ◽

Neuroendocrine Neoplasm ◽

Ectopic Acth Syndrome ◽

Tumor Type ◽

Ectopic Acth ◽

Long Term Outcome ◽

Free Cortisol

Objective: Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a heterogeneous condition caused by neuroendocrine neoplasms (NENs) located in the lungs, thymus, or pancreas. Our purpose was to evaluate the long-term outcome of these patients. Methods: Retrospective study at a referral center. The charts of 164 patients with Cushing syndrome, followed at our center from 1993 to 2019, were analyzed. Results: EAS was found in 16 patients (9.75%, 9 women, mean age 36.01 years) who had been followed for a median of 72 months. The source of EAS was a NEN in 10 patients (8 bronchial and 2 thymic carcinoid tumors) and a mixed corticomedullary tumor, consisting of a pheochromocytoma and an adrenocortical carcinoma in 1 patient. In 2 of the 6 patients initially considered to have occult EAS, the source of the ACTH excess became apparent after adrenalectomy, whereas in the remaining 4 (25%) patients, it has remained occult. Of the 11 patients in whom resection of the NEN was attempted, 10 patients achieved an early remission (91%), but 4 (25%) of these patients had a recurrence during follow-up (biochemically and clinically silent in 2 patients). Three patients died (18.75%): the young woman with the mixed corticomedullary tumor, a man with a thymic NEN that evolved into a neuroendocrine (NE) carcinoma after 11 years of follow-up, and a woman with a bronchial NEN. Conclusion: The course of EAS varies according to tumor type and grade. Some patients have a protracted course, whereas others may evolve into neuroendocrine carcinomas. Abbreviations: ACTH = adrenocorticotropic hormone; CS = Cushing syndrome; CT = computed tomography; CV = coefficient of variation; EAS = ectopic ACTH syndrome; IQR = interquartile range; NEN = neuroendocrine neoplasm; SCCL = small cell carcinoma of the lung; TSS = transsphenoidal surgery; UFC = urinary free cortisol

Download Full-text

Diagnostic approach to Cushing disease

Neurosurgical FOCUS ◽

10.3171/foc.2007.23.3.2 ◽

2007 ◽

Vol 23 (3) ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Bradley A. Gross ◽

Stefan A. Mindea ◽

Anthony J. Pick ◽

James P. Chandler ◽

H. Hunt Batjer

Keyword(s):

Mr Imaging ◽

Low Dose ◽

Cushing Syndrome ◽

Diagnostic Approach ◽

Ectopic Acth Syndrome ◽

Cushing Disease ◽

Ectopic Acth ◽

Imaging Results ◽

Free Cortisol ◽

Dexamethasone Suppression

✓ In Cushing disease, a pituitary corticotroph neoplasm causes secondary adrenal hypercortisolism. This condition has known morbidity and mortality, underscoring the need for an efficient and accurate diagnostic approach. An 11 p.m. salivary cortisol level is a modern, simple initial screening tool for the diagnosis of Cushing syndrome. Confirmation with a 24-hour urinary free cortisol test and/or a low-dose dexamethasone suppression test may subsequently be performed. Patients with repeatedly equivocal results should be reevaluated after several months or undergo a corticotropin-releasing hormone (CRH) stimulation test following low-dose dexamethasone suppression to help rule out pseudo-Cushing states. The presence of low morning serum adrenocorticotropic hormone (ACTH) levels then distinguishes primary adrenal hypercortisolism from Cushing disease and the ectopic ACTH syndrome. Patients with moderate ACTH levels can undergo CRH stimulation testing to clarify the underlying disease because those with an ACTH-independent disorder have blunted subsequent ACTH levels. Once ACTH-dependent hypercortisolemia is detected, magnetic resonance (MR) imaging of the pituitary gland can be performed to detect a pituitary neoplasm. Normal or equivocal MR imaging results revealing small pituitary lesions should be followed up with inferior petrosal sinus sampling, a highly specific measure for the diagnosis of Cushing disease in experienced hands. If necessary, body imaging may be used in turn to detect sources of ectopic ACTH.

Download Full-text

Fluconazole treatment in severe ectopic Cushing syndrome

Endocrinology Diabetes and Metabolism Case Reports ◽

10.1530/edm-19-0020 ◽

2019 ◽

Vol 2019 ◽

Cited By ~ 2

Author(s):

Teresa M Canteros ◽

Valeria De Miguel ◽

Patricia Fainstein-Day

Keyword(s):

Liver Metastases ◽

Alternative Treatment ◽

Cushing Syndrome ◽

Serum Cortisol ◽

Bilateral Adrenalectomy ◽

Ectopic Acth Syndrome ◽

List Type ◽

Ectopic Acth ◽

Free Cortisol ◽

Cortisol Levels

Summary Severe Cushing syndrome (SCS) is considered an emergency that requires immediate treatment to lower serum cortisol levels. Fluconazole may be considered an alternative treatment in Cushing syndrome when ketoconazole is not tolerated or unavailable. We report a 39-year-old woman with a history of partial pancreaticoduodenectomy due to a periampullary neuroendocrine tumor with locoregional extension. Three years after surgery, she developed liver metastases and was started on 120 mg of lanreotide/month, despite which, liver metastases progressed in the following 6 months. The patient showed extreme fatigue, muscle weakness, delirium, moon face, hirsutism and severe proximal weakness. Laboratory tests showed anemia, hyperglycemia and severe hypokalemia. 24-h urinary free cortisol: 2152 nmol/day (reference range (RR): <276), morning serum cortisol 4883.4 nmol/L (RR: 138–690), ACTH 127.3 pmol/L (RR: 2.2–10). She was diagnosed with ectopic ACTH syndrome (EAS). On admission, she presented with acute upper gastrointestinal tract bleeding and hemodynamic instability. Intravenous fluconazole 400 mg/day was started. After 48 h, her mental state improved and morning cortisol decreased by 25%. The dose was titrated to 600 mg/day which resulted in a 55% decrease in cortisol levels in 1 week, but then had to be decreased to 400 mg/day because transaminase levels increased over 3 times the upper normal level. After 18 days of treatment, hemodynamic stability, lower cortisol levels and better overall clinical status enabled successful bilateral adrenalectomy. This case report shows that intravenous fluconazole effectively decreased cortisol levels in SCS due to EAS. Learning points: Severe Cushing syndrome can be effectively treated with fluconazole to achieve a significant improvement of hypercortisolism prior to bilateral adrenalectomy. Intravenous fluconazole is an alternative treatment when ketoconazole is not tolerated and etomidate is not available. Fluconazole is well tolerated with mild side effects. Hepatotoxicity is usually mild and resolves after drug discontinuation.

Download Full-text

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.

Download Full-text

Presentation, Treatment, Histology, and Outcomes in Adrenal Medullary Hyperplasia Compared With Pheochromocytoma

Journal of the Endocrine Society ◽

10.1210/js.2019-00200 ◽

2019 ◽

Vol 3 (8) ◽

pp. 1518-1530 ◽

Cited By ~ 4

Author(s):

Henrik Falhammar ◽

Adam Stenman ◽

Jan Calissendorff ◽

Carl Christofer Juhlin

Keyword(s):

Blood Pressure ◽

Surgical Management ◽

Cushing Syndrome ◽

Adrenocortical Adenoma ◽

Cushing Disease ◽

Genetic Syndrome ◽

Alpha Blockers ◽

Adrenal Medullary Hyperplasia ◽

Symptoms And Signs

Abstract Context Information about adrenal medullary hyperplasia (AMH) is scarce. Objective To study a large cohort of AMHs. Design, Setting, and Participants Nineteen AMH cases were compared with 95 pheochromocytomas (PCCs) without AMH. AMH without (n = 7) and with PCC (n = 12) were analyzed separately. Results Of 936 adrenalectomies, 2.1% had AMH. Mean age was 47.2 ± 15.1 years. Only two (11%) AMHs had no concurrent PCC or adrenocortical adenoma. In AMHs, a genetic syndrome was present in 58% vs 4% in PCCs (P < 0.001). The noradrenaline/metanephrine levels were lower in AMHs, whereas suppression of dexamethasone was less than in PCCs. Cushing syndrome was found in 11% of AMHs. More AMHs were found during screening and less as incidentalomas. PCC symptoms were less prevalent in AMHs. Surgical management was similar; however, fewer of the AMHs were pretreated with alpha-blockers. Adrenalectomy improved blood pressure slightly less in AMHs. The disappearance of glycemic disturbances was similar to the PPCs. During a period of 11.2 ± 9.4 years, a new PCC developed in 32% of patients with AMH, 11% died, but no PCC metastasis occurred (PCCs: 4%, P < 0.001; 14% and 5%). AMHs without PCC had milder symptoms but more often Cushing disease than patients with PCC, whereas AMH with PCC more often displayed a familiar syndrome with more PCC recurrences. Conclusion A total of 2.1% of all adrenalectomies displayed AMH. AMH seemed to be a PCC precursor. The symptoms and signs were milder than PCCs. AMHs were mainly found due to screening. Outcomes seemed favorable, but new PCCs developed in many during follow-up.

Download Full-text

Ectopic ACTH syndrome in a dog with a mesenteric neuroendocrine tumour: a case report

Veterinární Medicína ◽

10.17221/7623-vetmed ◽

2014 ◽

Vol 59 (No. 7) ◽

pp. 352-358 ◽

Cited By ~ 4

Author(s):

VA Castillo ◽

PP Pessina ◽

JD Garcia ◽

P. Hall ◽

MF Gallelli ◽

...

Keyword(s):

Cushing Syndrome ◽

Neuroendocrine Tumour ◽

Clinical Signs ◽

Ectopic Acth Syndrome ◽

Histopathological Diagnosis ◽

Left Adrenal Gland ◽

Plasma Acth ◽

Hormone Activity ◽

Ectopic Acth ◽

Ectopic Acth Secretion

Ectopic ACTH secretion is provoked by extra-pituitary tumours that secrete ACTH, constituting an infrequent type of Cushing Syndrome in the dog. Neuroendocrine tumours (NET) are characterised by the synthesis of peptides with hormone activity. A dog with clinical diagnosis of Cushing’s syndrome and presenting an abdominal tumour located in the area of the left adrenal gland was sent to the hospital. Cortisol was not inhibited at four and eight hours after the application of low-dose dexamethasone and the cortisol/creatinine ratio was elevated (93 × 10<sup>-6</sup>, referencevalues < 10 × 10<sup>–6</sup>). Plasma ACTH measurements were high (28.6 pmol/l, reference values 5.5–14.3 pmol/l). On computed tomography, the tumour was found in the meso-epigastrium, with both adrenal glands hyperplasic and no alteration of the pituitary image. The tumour was located between the two layers of the meso-colon and was removed using laparoscopy. After surgery, ACTH concentrations became normal and clinical signs remitted. The histopathological diagnosis was NET, with positive ACTH immunostaining.

Download Full-text

A Challenging Case of an Ectopic Cushing Syndrome

Case Reports in Medicine ◽

10.1155/2014/413136 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Joana Menezes Nunes ◽

Elika Pinho ◽

Isabel Camões ◽

João Maciel ◽

Pedro Cabral Bastos ◽

...

Keyword(s):

Cushing Syndrome ◽

Lung Resection ◽

Signs And Symptoms ◽

Urinary Free Cortisol ◽

Community Acquired Pneumonia ◽

Interesting Case ◽

Ectopic Acth Syndrome ◽

Ectopic Acth ◽

Free Cortisol ◽

Fdg Pet Scan

Bronchopulmonary carcinoids are rare pulmonary neoplasms although they account for most cases of ectopic ACTH syndromes. When feasible, the mainstay treatment is surgical resection of the tumor. We report the case of a 52-year-old woman with signs and symptoms suggestive of hypercortisolism for 12 months, admitted to our department because of community acquired pneumonia. Blood hormone analysis showed increased levels of ACTH and urinary free cortisol and nonsuppressibility to high- and low-dose dexamethasone tests. Pituitary MRI showed no lesion and no central-to-peripheral ACTH gradient was present in bilateral inferior petrosal sinus sampling. CRH stimulation test suggested an ectopic ACTH source. Thoracic CT scan revealed a nodular region measuring 12 mm located in the inferior lingular lobule of the left superior lung with negative uptake by18-FDG-PET scan and negative SRS. The patient was successfully treated with an atypical lung resection and histology revealed an atypical bronchial carcinoid tumor with positive ACTH immunoreactivity. This was an interesting case because the patient was admitted due to pneumonia that may have been associated with her untreated and chronic hypercortisolism and a challenging case of ectopic ACTH syndrome due to conflicting results on the diagnostic exams.

Download Full-text

Ectopic ACTH-Producing Pheochromocytoma as a Rare Cause for Rapid Progressing Cushing Syndrome: A Case Report

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.258 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A128-A128

Author(s):

Daniela Salazar ◽

Cláudia Fernandes Costa ◽

Joana Oliveira ◽

Liliana Violante ◽

Ana Luísa Cunha ◽

...

Keyword(s):

Adrenal Gland ◽

Cushing Syndrome ◽

Somatostatin Receptors ◽

Osteoporotic Fractures ◽

Urinary Free Cortisol ◽

Hand Tremor ◽

Ectopic Acth ◽

Late Night ◽

Free Cortisol ◽

The Right

Abstract Background: Cushing syndrome due to ectopic CRH or ACTH secretion can be rarely caused by pheochromocytoma, commonly as part of genetic conditions. Case: A 21 year-old male, previously healthy, with no usual medication, went to the physician assistant for hematuria. The kidney US revealed, besides lithiasis, a highly vascularized mass in the right adrenal gland with 10 cm. In his first evaluation the patient had no complaints or pheochromocitoma/hypercortisolism stigmata, other than hand tremor and slight rounding of the face. Blood pressure was 149/88 mmHg, and heart rate 86 bpm. There was no family history of endocrine disease. He rapidly developed increased appetite, insomnia, and severe myalgias, with filling of supraclavicular fossae, facial plethora, and cervical and truncal acne. Laboratory analysis showed abnormal overnight dexamethasone suppression test (57.4 µg/dL, N < 1.8), elevated ACTH 378 pg/mL (N 9.0–52.0), 24h-urinary free cortisol (UFC) (5334.0 µg/24h, N 4.3–176.0), and late-night salivar cortisol (1.44 µg/dL, N < 0.32), hypokalemia (2.8 mEq/L, N 3.8–5.0), and leukocytosis (22.4*109/L, N 4.0–11.0); DHEA-S 962 µg/dL (N 80–560), 4-androstenedione 380 ng/dL (N 70–360), 17-OH progesterone 4.5 ng/mL (N 0.59–3.44), cromogranine A 6063 ng/mL (N 0–100), and markedly elevated urinary amines (adrenaline 173 nmol/24h, N 0–109; noradrenaline 5033 nmol/24h, N 89–473; normetanephrine 334605 nmol/24h, N 480–2424; metanephrine 15998 nmol/24h, N 264–1729; dopamine 4808 nmol/24h, N 424–2612). Hypercalcemia with hypophosphatemia and supressed PTH level was also detected. 68Ga-DOTANOC PET revealed a mass of the right adrenal gland with overexpression of somatostatin receptors (likely pheochromocytoma), without evidence of other tumor lesions of neuroendocrine origin. Pituitary MRI showed normal pituitary gland. Potassium supplementation, alpha-blockade with phenoxybenzamine, and metyrapone were initiated. Due to severe back pain, a CT scan of the spine was performed detecting compressive osteoporotic fractures in the mid dorsal and low dorsal segments. The patient was submitted to right adrenalectomy. Histology revealed pheochromocytoma with 11.2*9mm, with capsular and vascular invasion, extra-adrenal extension, necrosis, and atypical mitosis, with Ki67 of 9.5% and PASS score of 16. Postoperative analysis showed ACTH 45.6 pg/mL (N 7.2-63,3), late-night salivar cortisol < 0,0544 µg/dL (N < 0,32) and free urinary cortisol 41.4 µg/24h (N 4.3–176.0). Discussion: Ectopic cushing syndrome caused by pheochromocytoma is a rarely described entity. In this young patient, it caused rapid clinical progression of hypercortisolism with important hydroelectrolytic disturbances and compressive vertebral fractures, requiring prompt surgical intervention for clinical remission and improvement.

Download Full-text

Stereotactic radiosurgery for Cushing disease

Neurosurgical FOCUS ◽

10.3171/foc.2004.16.4.6 ◽

2004 ◽

Vol 16 (4) ◽

pp. 1-7 ◽

Cited By ~ 12

Author(s):

Stephen J. Hentschel ◽

Ian E. McCutcheon

Keyword(s):

Stereotactic Radiosurgery ◽

Cortisol Level ◽

Cushing Syndrome ◽

Latency Period ◽

Serum Cortisol ◽

Serum Cortisol Level ◽

Cushing Disease ◽

Fractionated Radiotherapy ◽

Free Cortisol ◽

Microsurgical Resection

The most common cause of Cushing syndrome is Cushing disease, in which hypercortisolism is produced by a functional adrenocorticotropic hormone–producing adenoma of the anterior pituitary gland. The common therapies available include microsurgical resection, conventional fractionated radiotherapy, and stereotactic radiosurgery (SRS). In this article the authors review the indications, results, and complications associated with SRS in the treatment of Cushing disease. In as many as 90% of patients SRS results in disease remission, which is defined as a normal 24-hour urinary free cortisol level and a normal or subnormal morning serum cortisol level. Although in most patients who are subsequently cured a marked decrease in the serum cortisol level is demonstrated within 3 months after treatment, a biochemical cure may be delayed up to 3 years in some cases. Complications following SRS for pituitary adenomas are uncommon, particularly in patients with microadenomas, which are most commonly seen in Cushing disease. The most common complication is hypopituitarism, which occurs in up to 50% of patients with a mean latency period of 5 years. Radiation-induced optic neuropathy has been reported in less than 2% of cases and induction of a secondary neoplasm in less than 1% of cases. For patients with Cushing disease, the rate of endocrinological cure following SRS appears to be similar to that attained using microsurgical resection. In contrast to surgery, SRS has the benefit of being noninvasive and associated with a very low incidence of diabetes insipidus, although hypopituitarism may be more common with SRS. With continued follow-up patient reviews and additional experience with SRS, it may become possible to make more definitive statements regarding SRS as the initial treatment for patients with Cushing disease.

Download Full-text

PRKAR1A mutation causing pituitary-dependent Cushing disease in a patient with Carney complex

Acta Endocrinologica ◽

10.1530/eje-17-0227 ◽

2017 ◽

Vol 177 (2) ◽

pp. K7-K12 ◽

Cited By ~ 15

Author(s):

Florian W Kiefer ◽

Yvonne Winhofer ◽

Donato Iacovazzo ◽

Márta Korbonits ◽

Stefan Wolfsberger ◽

...

Keyword(s):

Cushing Syndrome ◽

Pituitary Tumour ◽

Carney Complex ◽

Regulatory Subunit ◽

Loss Of Function ◽

Cushing Disease ◽

First Case ◽

Acth Secreting ◽

Inactivating Mutation

Context Carney complex (CNC) is an autosomal dominant condition caused, in most cases, by an inactivating mutation of the PRKAR1A gene, which encodes for the type 1 alpha regulatory subunit of protein kinase A. CNC is characterized by the occurrence of endocrine overactivity, myxomas and typical skin manifestations. Cushing syndrome due to primary pigmented nodular adrenocortical disease (PPNAD) is the most frequent endocrine disease observed in CNC. Case description Here, we describe the first case of a patient with CNC and adrenocorticotropic hormone (ACTH)-dependent Cushing disease due to a pituitary corticotroph adenoma. Loss-of-heterozygosity analysis of the pituitary tumour revealed loss of the wild-type copy of PRKAR1A, suggesting a role of this gene in the pituitary adenoma development. Conclusion PRKAR1A loss-of-function mutations can rarely lead to ACTH-secreting pituitary adenomas in CNC patients. Pituitary-dependent disease should be considered in the differential diagnosis of Cushing syndrome in CNC patients.

Download Full-text