An unusual case of Cushing’s syndrome due to bihormonal ACTH–prolactin secreting pituitary macroadenoma with rapid response to cabergoline

Posted on August 8, 2017 by MaryO
  1. Shalini Kunasegaran1,2,
  2. Michael S Croxson1,
  3. Ian Holdaway1,
  4. Rinki Murphy1

+Author Affiliations


  1. 1Department of Endocrinology, Auckland District Health Board, Auckland, New Zealand

  2. 2Department of Endocrinology, Waitemata District Health Board, Takapuna, New Zealand
  1. Correspondence to Dr Shalini Kunasegaran, shal84@gmail.com
  • Accepted 13 July 2017
  • Published 7 August 2017

Summary

A 23-year-old man presenting with florid Cushing’s syndrome was found to have high plasma ACTH and very high serum prolactin. Pituitary MRI showed a large invasive macroadenoma.

Low-dose cabergoline promptly suppressed both ACTH and prolactin levels within 2 weeks, with unexpected clinical and biochemical hypocortisolism requiring hydrocortisone replacement. Secondary hypogonadism was reversed. Clinical and biochemical remission of his Cushing’s syndrome together with significant shrinkage of his macroadenoma has been maintained for 1 year on cabergoline 0.5 mg twice weekly. Reduction in pituitary

Reduction in pituitary tumour volume and brisk fall in serum prolactin in response to low-dose cabergoline is regularly observed in patients with macroprolactinomas, but the concurrent fall in the plasma ACTH level and hypocortisolism was a pleasant surprise.

We assume that he most likely has a single bihormonal adenoma that is enriched with dopamine-2 receptors.

From http://casereports.bmj.com/content/2017/bcr-2017-219921.short?rss=1

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A Retrospective Review of 34 Cases of Pediatric Pituitary Adenoma

Posted on July 20, 2017 by MaryO

Abstract

Purpose

The purpose of this paper is to study invasiveness, tumor features and clinical symptoms of pediatric pituitary adenoma, and to discuss some inconclusive results in prior studies.

Methods

We retrospectively reviewed 34 cases of children (<20 year-old) who were pathologically diagnosed with pituitary adenoma and surgically treated from 2010 to 2017. Data of general information, clinical symptoms, invasive behaviors, surgery approaches, and tumor features were collected and analyzed.

Results

Sixteen boys and 18 girls aged from 12 to 19 years old were included. Prolactinoma was most suffered, followed by GH-, none- and ACTH-secreting pituitary adenoma. Invasive behaviors were observed frequently and suprasellar extensions were most found. Macroadenoma account 70% of all cases. Meanwhile, unlike prior studies, a significant raise of incidence on invasive tumor and pituitary adenoma apoplexy were observed. Craniotomy and transsphenoidal surgery were both applied with zero mortality. Nine cases occurred with transient hypopituitarism and diabetes insipidus. Three cases of tumor recurrence received secondary surgery or radiotherapy.

Conclusions

Invasive behaviors were more frequent than previous prediction. Craniotomy is worth considering for total tumor removal. Pituitary adenoma apoplexy needs further studies since its different features between children and adults in present study. Specialized care and teamwork of neurosurgeons, pediatricians, and endocrinologists are important.

Keywords

Pediatric pituitary adenoma Invasion Pituitary apoplexy Transsphenoidal surgery 

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Ectopic Cushing’s syndrome associated with thoracic tumors

Posted on July 3, 2017 by MaryO

Results of a retrospective review conducted in southern India demonstrate that ectopic Cushing’s syndrome occurred most commonly in association with thoracic tumors.

Researchers added that early control over hypercortisolemia was necessary to prevent metabolic complications and infections, both of which had the potential to be life-threatening.

“As compared to patients with pituitary-dependent Cushing’s syndrome, patients with [ectopic Cushing Syndrome] present with a rapid progression of symptoms,” Nihal Thomas, MD, MNAMS, DNB, FRACP, professor in the department of endocrinology, diabetes and metabolism at Christian Medical College, Vellore, India, and colleagues wrote. “It is also associated with typical features of proximal muscle weakness, severe hypokalaemic metabolic alkalosis, hyperpigmentation, edema, hypertension and glucose intolerance. Early diagnosis and localization of the ectopic source of [adrenocorticotrophic hormone] is crucial, because the treatment of choice in most of these patients is complete excision of the tumor. Localizing the source of excess ACTH continues to be a challenge in most patients.”

Thomas and colleagues reviewed the records of 21 patients treated at a tertiary care center in southern India from 2006 to 2015. The researchers documented patients’ clinical features, history and images from radiological findings and PET scans, as well as details of management, follow-up and outcomes. They also compared those with ectopic Cushing’s syndrome with 20 patients who had Cushing’s disease.

Median age was 34 years. Thomas and colleagues reported that one patient demonstrated “an occult source of ACTH.” The rest had a variety of tumors: bronchial carcinoid (n = 7), thymic carcinoid (n = 7), lung malignancies (n = 3), medullary thyroid carcinoma (n = 2) and pancreatic neuroendocrine tumor (n = 1).

At presentation, muscle weakness was the most common clinical feature (95%), followed by hyperpigmentation (90%), facial puffiness (76%), easy bruising (61%), edema (57%) and striae (52%). Slightly less than half (43%) showed extensive acne. Central obesity in ectopic Cushing’s syndrome was uncommon and occurred in 14% of patients (n = 3), according to Thomas and colleagues; however, it was more prevalent (n = 18) in those with Cushing’s disease.

Median cortisol at 8 a.m. was 55.5 mcg/dL, the researchers wrote, while median 8 a.m. ACTH was 207 pg/mL. The median 24-hour urinary free cortisol level was 2,484 mcg.

Compared with patients with Cushing’s disease, those with ectopic Cushing’s syndrome had “markedly higher” midnight cortisol and ACTH, as well as basal cortisol and ACTH.

During follow-up, more than half of patients (12 of 21) with ectopic Cushing’s syndrome developed life-threatening infections. Although nine patients received surgery for their tumors, only one patient achieved a complete cure during the study period, the researchers wrote.

“In our series, patients with [ectopic Cushing’s syndrome] have more profound hypokalemia, and hypercortisolemia with higher levels of ACTH,” Thomas and colleagues wrote. “The prognosis of patients with [ectopic Cushing’s syndrome] was dependent on tumor histology. The role of a timely adrenalectomy needs to be considered in patients with hypercortisolemia unresponsive to medical management, and in patients with metastatic or recurrent disease.” – by Andy Polhamus

Disclosure: Endocrine Today was unable to confirm any relevant financial disclosures.

From https://www.healio.com/endocrinology/adrenal/news/in-the-journals/%7Be42c81a5-fd5b-4313-9b2b-9bcbdec7f8ce%7D/ectopic-cushings-syndrome-associated-with-thoracic-tumors

Filed under: Cushing's, symptoms | Tagged: , , , , , , , , | Leave a comment »

Cushing’s Syndrome, Cortisol, and Cognitive Competency: A Case Report

Posted on July 2, 2017 by MaryO
Published online 2017 Apr 6. doi:  10.1159/000470833
PMCID: PMC5422746
Neil Oronsky,a Bennett Thilagar,b,* Carolyn M. Ray,c Scott Caroen,b Michelle M.C. Lybeck,b Lindsey Ferry,b Ronald A. Voves,b and Bryan Oronskyb
Author information ► Article notes ► Copyright and License information ►

Abstract

Glucocorticoids are associated with immunosuppression and neuropsychiatric complications. We describe the case of a carcinoid patient with Cushing’s syndrome (CS) and neurocognitive impairment due to ectopic ACTH production who developed sepsis and died because of his family’s decision to withdraw antibiotic treatment. This report is presented to illustrate the importance of advanced-care planning in patients with CS.

Key Words: Cushing’s syndrome, Carcinoid patient, Glucocorticoids, ACTH, Immunosuppression, Neurocognitive impairment, Advanced directives

Introduction

Cushing’s syndrome (CS) is a general term for a cluster of endocrine abnormalities characterized by chronic cortisol overproduction. Characteristic clinical comorbidities include metabolic complications (e.g., visceral obesity, diabetes mellitus, and dyslipidemia), cardiovascular complications (e.g., systemic arterial hypertension, atherosclerosis, and thromboembolism), bone complications (e.g., osteoporosis and osteoarthritis) infective complications, and neuropsychiatric disorders (e.g., major depression, mania, anxiety, and cognitive impairment) [1]. CS may be exogenous and iatrogenic due to corticosteroid administration or endogenous due to excessive ACTH secretion, most commonly from a pituitary adenoma, referred to, somewhat confusingly, as Cushing’s disease, or less commonly from a nonpituitary tumor (ectopic CS) and primary adrenal neoplasms [2]. Several studies link untreated CS to fatal infectious complications [3]. This report describes the case of a 60-year-old carcinoid patient with cognitive impairment due to hypercortisolism from CS who developed bacteremia; his condition deteriorated, and he died after a decision was made to withdraw care.

Case Presentation

A 60-year-old male with metastatic bronchopulmonary neuroendocrine tumor treated on a clinical trial for over 5 months was admitted to the hospital with complaints of fever, agitation, and weakness. His medical history was significant for newly diagnosed CS secondary to ACTH secretion; he had been hospitalized 2 weeks earlier for CS-induced hyperglycemic crisis. On admission, the patient presented with classic cushingoid habitus of facial plethora, moon facies, muscle atrophy, abdominal striae, and truncal obesity. His physical examination was significant for bilateral crackles and agitation consistent with corticosteroid psychosis. The arterial blood gas analysis on room air was pH 7.497, PaCO2 29 mm Hg, PaO2 71 mm Hg, and oxygen saturation 95%.

Laboratory data were significant for hyperglycemia, hypokalemia, and leukocytosis with bandemia. The chest CT scan showed no definite evidence of pulmonary thromboembolism.

As respiratory failure was imminent, he was transferred to the intensive care unit and mechanically ventilated. The highest positive end-expiratory pressure and FiO2 required to maintain oxygenation were 5 cm H2O and 50%, respectively. Cultures were taken from bronchial secretions directly after endotracheal intubation and from urine and blood. The patient was diagnosed with Staphylococcus aureus bacteremia, and based on susceptibility testing, he was started on vancomycin and Zosyn. In addition to antibiotics, the patient received lisinopril for CS-induced hypertension and insulin sliding scale to control hyperglycemia.

Since high circulating levels of glucocorticoids due to ectopic ACTH secretion predispose to infection and impair immune function and clearance of bacteria, the immediate plan was to start him on mifepristone (600 mg daily) as a glucocorticoid receptor antagonist to counteract the immunosuppressive and cognitive effects of the endogenous hypercortisolism. As soon as the patient’s condition improved (which would have been expected given the known reversibility of hypercortisolism), cytoreductive chemotherapy would have been restarted to reduce the paraneoplastic stimulus. However, the patient’s family with medical power of attorney refused consent and withdrew him from the ventilator. The patient died shortly thereafter.

Discussion

Advance directives are written to guarantee autonomy in the event that individual decision-making capacity is lost due to disease severity or treatment [4]. However, as a blanket statement that may contain overly broad (or overly specific) prewritten blocks of text, especially for cancer patients, the content of advance directives may or may not necessarily apply to and/or the patient’s wishes may or may not be correctly interpreted during acute, temporary and potentially reversible conditions that occur during cancer treatment such as infection due to ectopic CS.

Given the potential for cognitive impairment and other acute sequelae such as difficult-to-treat infections from the development of ectopic CS, this case illustrates the importance of revisiting the advance directive when a medical diagnosis associated with temporary cognitive impairment such as CS is made.

Statement of Ethics

The authors have no ethical conflicts to disclose.

Disclosure Statement

The authors have no conflicts of interest to declare.

References

1. Pivonello R, Simeoli C, De Martino MC, Cozzolino A, De Leo M, Iacuaniello D, Pivonello C, et al. Neuropsychiatric disorders in Cushing’s syndrome. Front Neurosci. 2015;9:129. [PMC free article][PubMed]
2. Tsigos C, Chrousos GP. Differential diagnosis and management of Cushing’s syndrome. Annu Rev Med. 1996;47:443–461. [PubMed]
3. Bakker RC, Gallas PR, Romijn JA, Wiersinga WM. Cushing’s syndrome complicated by multiple opportunistic infections. J Endocrinol Invest. 1998;21:329–333. [PubMed]
4. Halpern NA, Pastores SM, Chou JF, Chawla S, Thaler HT. Advance directives in an oncologic intensive care unit: a contemporary analysis of their frequency, type, and impact. J Palliat Med. 2011;14:483–489.[PMC free article] [PubMed]
Articles from Case Reports in Oncology are provided here courtesy of Karger Publishers

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Cushing’s Testing at NIH

Posted on May 21, 2017 by MaryO
Rank Status Study
1 Recruiting Study to Evaluate CORT125134 in Patients With Cushing’s Syndrome

Condition: Cushing’s Syndrome
Intervention: Drug: CORT125134
2 Recruiting Cushing’s Disease Complications

Condition: Cushing’s Disease
Intervention: Other: Exams and questionnaires
3 Recruiting The Accuracy of Late Night Urinary Free Cortisol/Creatinine and Hair Cortisol in Cushing’s Syndrome Diagnosis

Condition: Cushing Syndrome
Intervention:
4 Recruiting Treatment for Endogenous Cushing’s Syndrome

Condition: Endogenous Cushing’s Syndrome
Intervention: Drug: COR-003
5 Recruiting Saliva Cortisol Measurement as a Screening Test for Suspicious Cushings Syndrome in Children.

Condition: Cushings Syndrome
Intervention: Other: Children refered to the obesity clinic
6 Recruiting Safety and Efficacy of LCI699 for the Treatment of Patients With Cushing’s Disease

Condition: Cushing’s Disease
Intervention: Drug: LCI699
7 Recruiting Treatment of Cushing’s Disease With R-roscovitine

Condition: Cushings Disease
Intervention: Drug: R-roscovitine
8 Recruiting A Study of ATR-101 for the Treatment of Endogenous Cushing’s Syndrome

Condition: Cushing Syndrome
Interventions: Drug: ATR-101;   Drug: Placebos
9 Recruiting Evaluation of 68Ga-DOTATATE PET/CT, Octreotide and F-DOPA PET Imaging in Patients With Ectopic Cushing Syndrome

Condition: Cushing Syndrome
Interventions: Drug: F-DOPA PET Scan;   Drug: Mifepristone;   Drug: Ga-DOTATATE;   Drug: Octreoscan;   Other: CT, MRI
10 Not yet recruiting Endocrine Cardiomyopathy in Cushing Syndrome: Response to Cyclic GMP PDE5 inhibitOrs

Condition: Cushing’s Syndrome Cardiomyopathy
Intervention: Drug: Tadalafil
11 Recruiting Long-term Beneficial Metabolic Effects of Adrenalectomy in Subclinical Cushing’s Syndrome of Adrenal Incidentaloma

Condition: Cushing Syndrome
Intervention: Procedure: surgery
12 Recruiting Long Term Safety and Efficacy of Pasireotide s.c. in Patients With Cushing’s Disease

Condition: Cushings Disease
Intervention: Drug: SOM230
13 Recruiting New Imaging Techniques in the Evaluation of Patients With Ectopic Cushing Syndrome

Condition: Cushing Syndrome
Interventions: Drug: Pentetreotide;   Drug: 18-F-fluorodeoxyglucose;   Drug: (18F)-L-3,4-dihydroxyophenylalanine (18F-DOPA)
14 Not yet recruiting Targeting Iatrogenic Cushing’s Syndrome With 11β-hydroxysteroid Dehydrogenase Type 1 Inhibition

Condition: Iatrogenic Cushing’s Disease
Interventions: Drug: AZD4017 and prednisolone;   Drug: Placebo Oral Tablet and prednisolone
15 Not yet recruiting Assessment of Persistent Cognitive Impairment After Cure of Cushing’s Disease

Condition: Cushing’s Disease
Intervention: Device: Virtual radial task in 3D
16 Recruiting Biomarker Expression in Patients With ACTH-Dependent Cushing’s Syndrome Before and After Surgery

Condition: Cushing’s Syndrome
Intervention:
17 Recruiting Efficacy and Safety Evaluation of Osilodrostat in Cushing’s Disease

Condition: Cushing’s Disease
Interventions: Drug: osilodrostat;   Drug: osilodrostat Placebo
18 Recruiting Effects of Metyrapone in Patients With Endogenous Cushing’s Syndrome

Condition: Cushing’s Syndrome
Intervention: Drug: metyrapone
19 Recruiting Adrenal Venous Sampling in Patients With Overt or Subclinical Cushings Syndrome, and Bilateral Adrenal Tumors

Condition: Cushing Syndrome
Intervention: Radiation: Adrenal venous sampling
20 Recruiting Glycemic Fluctuations in Newly Diagnosed Growth Hormone-Secreting Pituitary Adenoma and Cushing Syndrome Subjects

Condition: Pituitary Adenoma
Intervention: Device: continuous glucose monitoring
Rank Status Study
21 Recruiting Targeted Therapy With Gefitinib in Patients With USP8-mutated Cushing’s Disease

Conditions: Cushing’s Disease;   Corticotrophin Adenoma
Intervention: Drug: Gefitinib
22 Recruiting Cardiac Steatosis in Cushing’s Syndrome

Conditions: Endocrine System Disease;   Cardiovascular Imaging
Intervention: Other: 1H magnetic resonance spectroscopy and CMRI
23 Recruiting Study of Management of Pasireotide-induced Hyperglycemia in Adult Patients With Cushing’s Disease or Acromegaly

Conditions: Cushing’s Disease;   Acromegaly
Interventions: Drug: Pasireotide s.c.;   Drug: Sitagliptin;   Drug: Liraglutide;   Drug: Insulin;   Drug: Pasireotide LAR;   Drug: Metformin
24 Recruiting Study of Efficacy and Safety of Osilodrostat in Cushing’s Syndrome

Conditions: Cushing’s Syndrome;   Ectopic Corticotropin Syndrome;   Adrenal Adenoma;   Adrenal Carcinoma;   AIMAH;   PPNAD
Intervention: Drug: Osilodrostat
25 Recruiting Effects of Hormone Stimulation on Brain Scans for Cushing s Disease

Condition: Pituitary Neoplasm
Intervention: Drug: Acthrel
26 Recruiting Does Serum-DXM Increase Diagnostic Accuracy of the Overnight DXM Suppression Test in the Work-up of Cushing’s Syndrome?

Conditions: Cushing’s Syndrome;   Adrenal Incidentalomas;   Alcoholism;   Obesity
Intervention:
27 Recruiting Adrenalectomy Versus Follow-up in Patients With Subclinical Cushings Syndrome

Condition: Adrenal Tumour With Mild Hypercortisolism
Intervention: Procedure: Adrenalectomy
28 Recruiting Study of Adrenalectomy Versus Observation for Subclinical Hypercortisolism

Conditions: Hypercortisolism;   Cushing Syndrome
Interventions: Procedure: Adrenalectomy;   Other: Observation
29 Not yet recruiting Dynamic Hormone Diagnostics in Endocrine Disease

Conditions: Adrenal Insufficiency;   Congenital Adrenal Hyperplasia;   Cushing Syndrome;   Growth Hormone Deficiency;   Acromegaly;   Primary Hyperaldosteronism
Intervention: Other: 27 hour subcutaneous fluid sampling
30 Recruiting An Investigation of Pituitary Tumors and Related Hypothalmic Disorders

Conditions: Abnormalities;   Craniopharyngioma;   Cushing’s Syndrome;   Endocrine Disease;   Pituitary Neoplasm
Intervention:
31 Recruiting Ga-68-DOTATOC -PET in the Management of Pituitary Tumours

Condition: Pituitary Tumours
Intervention: Procedure: Gallium-68 DOTATOC PET
32 Recruiting Efficacy of Mifepristone in Males With Type 2 Diabetes Mellitus

Conditions: Type 2 Diabetes Mellitus;   Insulin Resistance
Interventions: Drug: Mifepristone 600 mg daily;   Drug: Placebo
33 Recruiting Targeted Therapy With Lapatinib in Patients With Recurrent Pituitary Tumors Resistant to Standard Therapy

Conditions: Pituitary Adenomas;   Prolactinomas
Intervention: Drug: Lapatinib
34 Recruiting Mutations of Glucocorticoid Receptor in Bilateral Adrenal Hyperplasia

Condition: General Glucocorticoid Resistance
Intervention: Genetic: blood collection for mutation characterization
35 Recruiting Defining the Genetic Basis for the Development of Primary Pigmented Nodular Adrenocortical Disease (PPNAD) and the Carney Complex

Conditions: Cushing’s Syndrome;   Hereditary Neoplastic Syndrome;   Lentigo;   Neoplasm;   Testicular Neoplasm
Intervention:
36 Not yet recruiting Reduction by Pasireotide of the Effluent Volume in High-output Enterostomy in Patients Refractory to Usual Medical Treatment

Condition: Enterostomy
Interventions: Drug: Pasireotide;   Drug: Placebo
37 Recruiting Mifepristone for Breast Cancer Patients With Higher Levels of Progesterone Receptor Isoform A Than Isoform B.

Condition: Breast Cancer
Intervention: Drug: Mifepristone
38 Recruiting SOM230 Ectopic ACTH-producing Tumors

Condition: Ectopic ACTH Syndrome
Intervention: Drug: Pasireotide
39 Recruiting Decreasing Rates of Intraurethral Catheterization Postoperatively in Spine Surgery

Condition: Post-operative Urinary Retention
Interventions: Drug: Tamsulosin;   Drug: Placebo
40 Recruiting Adrenal Tumors – Pathogenesis and Therapy

Conditions: Adrenal Tumors;   Adrenocortical Carcinoma;   Cushing Syndrome;   Conn Syndrome;   Pheochromocytoma
Intervention:

Filed under: adrenal, Clinical trials, Cushing's, Diagnostic Testing, pituitary, Rare Diseases, Treatments | Tagged: , , , , , , , , , , , , , , , , , , , , , , , , | Leave a comment »

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