Unilateral Adrenalectomy for Pediatric Cyclical Cushing Syndrome With Novel PRKAR1A Variant Associated Carney Complex

Posted on September 2, 2025 by MaryO

Abstract

Primary pigmented nodular adrenocortical disease is a rare cause of Cushing syndrome accounting for less than 1% of cases. We present a 9-year-old boy who presented at age 4 with cyclical Cushing syndrome and was eventually diagnosed with a novel, previously unreported, unpublished variant in PRKAR1A associated with Carney complex. He was treated with unilateral left adrenalectomy. At 1-year follow-up, he continues to be in remission of his symptoms of Cushing syndrome.

Introduction

Cushing syndrome is characterized by prolonged exposure to excess glucocorticoids and is broadly classified as either ACTH-dependent or ACTH-independent [1, 2]. Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTH-independent Cushing syndrome, characterized by bilateral adrenal hyperplasia with autonomous, hyperfunctioning nodules [1, 2]. Approximately 90% of PPNAD cases occur in the context of Carney complex, with isolated cases being exceedingly uncommon [1, 2].

PPNAD was first described in 1984 by Carney et al, who coined the term in a case series of 4 patients and a review of 24 previously reported cases [1]. In that series, patients presented with ACTH-independent Cushing syndrome and no radiographic evidence of adrenal tumors. All underwent bilateral adrenalectomy, with histopathology revealing bilateral pigmented nodules in otherwise small or normal-sized adrenal glands [1]. Histologically, the classic features of PPNAD include multiple small black or brown cortical nodules surrounded by an atrophic adrenal cortex—reflecting chronic ACTH suppression [1].

Clinically, PPNAD most often presents with cyclical Cushing syndrome, characterized by alternating periods of hypercortisolism and normocortisolemia [2]. This intermittent pattern poses a substantial diagnostic challenge, as biochemical confirmation requires detection of cortisol excess during active phases of the cycle.

Carney complex is a multiple neoplasia syndrome involving endocrine, cardiac, cutaneous, and neural tumors. First described by Carney et al in 1985, it is typically inherited in an autosomal dominant fashion. Approximately 70% of cases occur in familial settings, while the remaining 30% arise from de novo pathogenic variants [3, 4]. Over half of affected individuals harbor pathogenic variants in the PRKAR1A tumor suppressor gene on chromosome 17q24.2, while approximately 20% of cases are linked to alternate loci such as 2p16 [2, 4].

Diagnostic criteria for Carney complex include either 2 clinical manifestations or 1 clinical manifestation in combination with a pathogenic PRKAR1A variant or an affected first-degree relative [2]. The most common endocrine manifestation is PPNAD, reported in approximately 25% of patients with Carney complex, though this likely underestimates the true prevalence, as autopsy studies reveal histologic evidence of PPNAD in nearly all affected individuals [2].

The Endocrine Society clinical practice guidelines recommend bilateral adrenalectomy as the definitive treatment for PPNAD, effectively curing hypercortisolism but necessitating lifelong glucocorticoid and mineralocorticoid replacement therapy due to resultant adrenal insufficiency [5]. Unilateral adrenalectomy has emerged as an alternative approach, particularly in pediatric patients, with the potential to preserve endogenous adrenal function.

Herein, we present the case of a 9-year-old boy with Carney complex and cyclical Cushing syndrome due to PPNAD, successfully managed with unilateral adrenalectomy.

Case Presentation

A 4-year-old boy presented with a week-long history of facial swelling, hyperphagia, weight gain, and scrotal swelling. At presentation, his weight was 22 kg (99th percentile) and body mass index (BMI) was 18 kg/m² (96th percentile). Initial workup revealed normal 24-hour urinary free cortisol <0.0913 µg/day (SI: 274 nmol/day) with low urinary creatinine 215 mg/day (SI: 1.9 mmol/day) (normal reference range 973-2195 mg/day; SI: 8.6-19.4 mmol/day) suggesting an incomplete sample. A repeat collection produced similar results. A 1 mg dexamethasone suppression test demonstrated nonsuppressed cortisol (27.9 µg/dL; SI: 772 nmol/L), suggestive of Cushing syndrome.

Over 5 years, the patient experienced 2 to 3 episodes per year of rapid weight gain (20-50 lbs), facial flushing, abdominal distention, and mood changes. Despite persistent obesity (>97th percentile), linear growth remained normal.

Diagnostic Assessment

At age 7, midnight salivary cortisol was markedly elevated at 3.7 µg/dL (SI: 103 nmol/L) (normal reference range < 0.4 µg/dL; SI: < 11.3 nmol/L), raising suspicion for cyclical Cushing syndrome. Magnetic resonance imaging of the abdomen was negative for adrenal lesions. At age 8, during an active episode, 2 elevated salivary cortisol samples, 2.0 µg/dL (SI: 55.1 nmol/L) and 2.2 µg/dL (SI: 61.9 nmol/L) (normal reference range < 0.4 µg/dL; SI: < 11.3 nmol/L), were obtained. A high-dose dexamethasone suppression test yielded a low baseline cortisol 3.2 µg/dL (SI: 89 nmol/L) and nonsuppressed cortisol post-dexamethasone 3.0 µg/dL (SI: 83 nmol/L). Baseline ACTH was 7.7 pg/mL (SI: 1.7 pmol/L), suppressed to <3.2 pg/mL (SI: < 0.7 pmol/L) post-dexamethasone—consistent with ACTH-independent cortisol excess.

At age 9, the patient underwent the gold standard diagnostic testing for cyclical Cushing, the Liddle test. The test involves 6 days of urine collection: days 1 to 2 establish baseline urinary cortisol levels, days 3 to 4 assess response to low-dose dexamethasone, and days 5 to 6 evaluate response to high-dose dexamethasone. The patient’s cortisol increased paradoxically from 118.5 µg/day (SI: 327 nmol/day) to 402.0 µg/day (SI: 1109 nmol/day) over 6 days, consistent with PPNAD physiology. Genetic testing was performed with the following report: “A heterozygous variant, NM_002734.4(PRKAR1A):c.550-2_553delinsG, p.(Val184_Tyr185delinsAsp), was detected in exon 7 of this gene. This variant does not appear to have been reported in population (gnomAD, ESP, dbSNP) and clinical databases (ClinVar), or in the literature. The impact of this variant on RNA splicing as assessed by multiple algorithms (Alamut Suite) is: abolishment of canonical acceptor splice site. Based on the current evidence, this variant was classified as likely pathogenic, American College for Medical Genetics category 2”. Family testing revealed this to be a de novo pathogenic variant.

Further workup included echocardiogram and thyroid ultrasound, both of which were normal. During workup for scrotal swelling at initial presentation, the patient was found to have bilateral testicular masses with negative testicular cancer tumor markers: α-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase. The family declined invasive biopsy of these lesions. He was followed by pediatric urology with yearly serial ultrasound, and these were felt to be benign testicular tumors, presumed noncalcifying Sertoli cell tumors, associated with Carney complex (Fig. 1).

 

Ultrasound of bilateral testicular lesions. A) Left testicle. B) Right testicle.

Figure 1.

Ultrasound of bilateral testicular lesions. A) Left testicle. B) Right testicle.

Based on the presence of 2 major diagnostic criteria in combination with the molecular diagnosis of a likely pathogenic variant of PRKAR1A, the diagnosis of Carney complex was established.

Treatment

The patient was referred for surgical evaluation for consideration of adrenalectomy. A comprehensive discussion was conducted regarding the potential benefits and risks of unilateral vs bilateral adrenalectomy. The family was counseled that unilateral adrenalectomy might not fully resolve the hypercortisolemia and that a subsequent contralateral adrenalectomy could be necessary. In contrast, bilateral adrenalectomy would definitively address cortisol excess but result in permanent adrenal insufficiency requiring lifelong glucocorticoid and mineralocorticoid replacement. After multidisciplinary consultation with endocrinology and surgery, the decision was made to proceed with unilateral adrenalectomy.

Preoperative IV contrast-enhanced computed tomography (CT), reviewed by a physician experienced in PPNAD, demonstrated greater nodularity in the left adrenal gland compared to the right. Therefore, a laparoscopic left adrenalectomy was performed electively without intraoperative complications. The patient was discharged on postoperative day 1. At the time of surgery (age 9), his weight was 70 kg (100th percentile), and BMI was 31.6 kg/m² (99th percentile). The resected left adrenal gland was submitted for histopathologic evaluation. Gross examination revealed no overt nodularity (Fig. 2); however, microscopic analysis identified multiple pigmented cortical nodules consistent with PPNAD (Fig. 3).

 

Left adrenal gland gross morphology. No macroscopic nodularity appreciable.

Figure 2.

Left adrenal gland gross morphology. No macroscopic nodularity appreciable.

 

Hematoxylin and Eosin staining on microscopy of left adrenal gland demonstrating hyperpigmented nodule.

Figure 3.

Hematoxylin and Eosin staining on microscopy of left adrenal gland demonstrating hyperpigmented nodule.

Outcome and Follow-up

The patient was followed closely in the postoperative period and was last evaluated 11 months after adrenalectomy. He remained clinically well, with complete resolution of Cushingoid features and no evidence of recurrence. Since surgery, he had experienced significant weight loss of 11.4 kg, with a current weight of 58.6 kg and a BMI of 25 kg/m² (97th percentile).

In summary, this case describes a 9-year-old boy with ACTH-independent, cyclical Cushing syndrome secondary to PPNAD, associated with a de novo likely pathogenic variant in the PRKAR1A gene, consistent with Carney complex. Histopathologic analysis of the resected adrenal gland confirmed the diagnosis of PPNAD. At nearly 1 year post-unilateral adrenalectomy, the patient remains asymptomatic with no biochemical or clinical signs of disease recurrence.

Discussion

Diagnosis of cyclical Cushing is challenging due to the cyclical nature of the disease and the challenges with current available testing modalities. Late-night salivary cortisol testing was a more reliable screening tool in this case as the 24-hour urinary cortisol were affected by inaccurate collection. The cyclical nature of the disease, coupled with the necessity for appropriately timed testing, contributed to a prolonged interval before definitive diagnosis and treatment. Additionally, initial imaging was interpreted as normal, and it was only upon review by a clinician with expertise in PPNAD that subtle adrenal nodularity was identified on CT. Ultimately, the Liddle test and genetic testing were the highest yield for confirmation of disease. This test measures the suppressibility of endogenous cortisol following exogenous dexamethasone administration. In patients with PPNAD, a paradoxical increase in cortisol excretion may occur, attributed to glucocorticoid receptor–mediated activation of protein kinase A catalytic subunits [6]. The likely pathogenic variant found in this case is a novel, previously unreported, variant in the PRKAR1A gene. This rare variant impact both the canonical acceptor splice site in intron 6 as well as results in an in-frame protein change in exon 7 (Val184_Tyr185delinsAsp).

The treatment of PPNAD in the context of Carney complex is typically with bilateral adrenalectomy, as per Endocrine Society guidelines [5]. The drawback of bilateral adrenalectomy is the resultant adrenal insufficiency resulting in lifelong adrenal replacement. Unilateral adrenalectomy is an attractive option for the treatment of PPNAD given the ability to avoid adrenal insufficiency brought upon by bilateral adrenalectomy. Case reports and case series in adult patients have demonstrated variable success in unilateral treatment. In a case series of 17 patients with classic cyclical Cushing, 3 patients had recurrence of Cushing syndrome after unilateral adrenalectomy and were cured with contralateral adrenalectomy [7]. One patient had subtotal (<90%) left adrenalectomy and did not have recurrence with 66 years of follow-up [7].

A case series by Xu et al 2013 described 12 out of 13 patients with PPNAD successfully cured with unilateral adrenalectomy at median 47 months follow-up [8]. The side of adrenalectomy was selected based on CT/magnetic resonance imaging in 3 patients and adrenal iodine131-norcholesterol scintigraphy in the remaining. At our center, the iodine131-norcholesterol scintigraphy was not available so CT was the chosen imaging modality.

Ultimately, the efficacy and morbidity of unilateral adrenalectomy remains unclear. Furthermore, due to the rarity of PPNAD, the criteria for selection of patients who are candidates for unliteral adrenalectomy is challenging to establish. This case reports adds to the existing literature the clinical characteristics of one patient treated successfully by unilateral adrenalectomy.

Learning Points

  • Diagnosis of cyclical Cushing can be very challenging. Late-night salivary cortisol is more reliable than 24-hour urinary cortisol.
  • The paradoxical rise in cortisol in the Liddle test is confirmatory for cyclical Cushing, hence the testing should be considered early in affected patients.
  • Genetic testing assessing for Carney complex, PRAKA1A pathogenic variant, should be considered early in a patient with concern for cyclical Cushing and another system involved like testicular lesions.
  • Although bilateral adrenalectomy is the recommendation for PPNAD; in selected patients, unilateral adrenalectomy might provide several years of remission.

Acknowledgements

Thank you to Dr. Hong Wang, MD, PhD, DABMGG, FACMG, FCCMG, for her support on this project and in all things. Thank you to Dr. Andre Lacroix MD, FCAHS, for reviewing the preoperative CT adrenals with the team.

Contributors

All authors made individual contributions to authorship. F.B. was involved in the diagnosis and management of the patient. N.S. was responsible for the patient’s surgery. C.J.Z. was involved in the patient’s surgery and postoperative care. R.S., M.S., and P.W. were all medical professionals involved in his management and care. All authors contributed, reviewed, and approved the final draft.

Funding

No public or commercial funding.

Disclosures

None declared.

Informed Patient Consent for Publication

Signed informed consent obtained directly from the patient’s relatives or guardians

Data Availability Statement

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Author notes

Natashia Seemann and Funmbi Babalola co-senior author.

© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society.
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Paraneoplastic Cushing Syndrome Unmasking Small Cell Lung Cancer: A Rare Presentation

Posted on August 31, 2025 by MaryO

Abstract

We present a case of a middle-aged woman who presented with chest pain and shortness of breath. Laboratory tests revealed persistent hypokalaemia, hyperglycaemia, and metabolic alkalosis despite treatment. Imaging identified a mass near the right hilum suggestive of lung malignancy. Endocrine evaluation showed markedly elevated cortisol and adrenocorticotropic hormone levels, consistent with paraneoplastic Cushing syndrome caused by ectopic hormone production. The analysis of the lung biopsy obtained through bronchoscopy confirmed the diagnosis of small cell lung cancer (SCLC). The patient was treated with metyrapone and spironolactone to stabilise her metabolic abnormalities and was subsequently referred for chemotherapy following a multidisciplinary team review. This case highlights the importance of recognising paraneoplastic syndromes as atypical presentations of malignancy and emphasises the role of a coordinated, multidisciplinary approach in diagnosis and management.

Introduction

Paraneoplastic syndromes, although relatively uncommon, can serve as important early clues to an underlying cancer. One such rare and often overlooked condition is ectopic adrenocorticotropic hormone (ACTH) secretion, a form of paraneoplastic Cushing’s syndrome. This occurs when a non-pituitary tumor, most commonly small cell lung carcinoma (SCLC) or another neuroendocrine tumor, produces ACTH, leading to overstimulation of the adrenal glands and excessive cortisol production.

Unlike the more familiar presentation of Cushing’s syndrome, ectopic ACTH production tends to manifest with severe metabolic disturbances, such as persistent hypokalemia, metabolic alkalosis, hyperglycemia, and muscle weakness, often without the typical physical features like moon facies or central obesity. These atypical and rapidly progressing symptoms can delay diagnosis, especially in patients with aggressive malignancies.

A thorough diagnostic workup, including hormone assays, suppression testing, and imaging, is essential to pinpoint the source of ectopic hormone production. Early identification is critical, as the metabolic derangements associated with this syndrome can lead to significant morbidity if left untreated.

In this report, we present the case of a middle-aged woman whose initial symptoms of chest pain and shortness of breath led to the discovery of SCLC with ectopic ACTH production. Her case highlights the importance of considering paraneoplastic syndromes in the differential diagnosis of unexplained electrolyte abnormalities and metabolic dysfunction.

Case Presentation

We report the case of a 52-year-old Caucasian woman who presented with a one-week history of diffuse chest pain, progressive shortness of breath, and MRC dyspnea grade 1 initially and then progressing to grade 2. She had no prior history of similar symptoms, and her past medical history was unremarkable. On examination, there were no significant findings on systemic review.

Initial laboratory investigations revealed marked hypokalaemia, with a serum potassium level of 2.4 mmol/L, alongside significant hyperglycaemia (blood glucose: 20 mmol/L) and metabolic alkalosis (arterial pH: 7.52, bicarbonate: 32 mmol/L). Notably, the patient had no known history of diabetes mellitus (Table 1).

Parameter Result Reference range Remarks
Serum potassium 2.4 mmol/L 3.5–5.0 mmol/L Marked hypokalaemia
Blood glucose 20 mmol/L 3.9–7.8 mmol/L (fasting) Significant hyperglycaemia; no known diabetes
Arterial pH 7.52 7.35–7.45 Metabolic alkalosis
Serum bicarbonate (HCO₃⁻) 32 mmol/L 22–28 mmol/L Elevated, consistent with metabolic alkalosis
Table 1: Initial laboratory investigations

This table summarizes the patient’s initial biochemical abnormalities, which include marked hypokalaemia, significant hyperglycaemia in the absence of known diabetes mellitus, and evidence of metabolic alkalosis on arterial blood gas analysis.

Despite intravenous and oral potassium supplementation, hypokalaemia persisted (Table 2). Hyperglycaemia also remained uncontrolled initially and was subsequently managed with insulin therapy.

Day Serum potassium (mmol/L) Reference range (mmol/L)
Day 1 2.4 3.5–5.0
Day 2 2.2 3.5–5.0
Day 3 2.8 3.5–5.0
Day 4 3.0 3.5–5.0
Day 5 2.9 3.5–5.0
Day 6 2.6 3.5–5.0
Day 7 2.7 3.5–5.0
Table 2: Daily serum potassium levels (day 1–day 7)

This table presents serum potassium levels measured over a seven-day period, demonstrating persistently low values consistent with hypokalaemia despite Intra-venous and oral pottasium replacement.

The patient presented with chest pain with respiratory symptoms, and an initial chest radiograph was suggestive of lung cancer (Figure 1).

Initial-chest-X-ray-
Figure 1: Initial chest X-ray

Posteroanterior chest radiograph showing a spiculated opacity in the right mid-zone (black arrow), suggestive of a pulmonary mass. The lesion projects over the right hilum and may represent a primary bronchogenic carcinoma. No gross pleural effusion or pneumothorax is identified.

Further evaluation with contrast-enhanced CT of the thorax revealed a right hilar mass suspicious for a bronchogenic malignancy (Figure 2).

Computed-tomography-(CT)-thorax-
Figure 2: Computed tomography (CT) thorax

Contrast-enhanced axial CT of the thorax demonstrating a spiculated right hilar mass (black arrow) measuring approximately 4 cm in greatest diameter. The mass is abutting the right main bronchus and associated with enlargement of adjacent mediastinal lymph nodes. No evidence of pleural effusion, chest wall invasion, or direct mediastinal involvement is seen on this image.

Given the persistent hypokalaemia, hyperglycaemia, and metabolic alkalosis, the possibility of a paraneoplastic endocrine syndrome was considered.

Endocrine workup showed markedly elevated serum cortisol levels (>2000 nmol/L), which failed to suppress following both low- and high-dose dexamethasone suppression tests. Plasma ACTH levels were also significantly elevated at 615 ng/L, consistent with ectopic ACTH secretion (Table 3).

Test Result Reference range Interpretation
Serum cortisol >2000 nmol/L Morning: 140–690 nmol/L Markedly elevated
Low-dose dexamethasone suppression test No suppression observed Cortisol suppressed to <50 nmol/L Abnormal; cortisol not suppressed
High-dose dexamethasone suppression test No suppression observed Cortisol suppressed by >50% Abnormal; cortisol not suppressed
Plasma ACTH 615 ng/L 10–60 ng/L Significantly elevated; ectopic ACTH secretion
Table 3: Endocrine workup results demonstrating elevated cortisol and adrenocorticotropic hormone (ACTH) levels with lack of suppression on dexamethasone testing

Serum cortisol  levels during low- and high-dose dexamethasone suppression tests. Despite administration of both low- and high-dose dexamethasone, serum cortisol levels remained markedly elevated. Plasma ACTH was also significantly elevated at 615 ng/L, consistent with ectopic ACTH secretion. Reference ranges are included for comparison.

Flexible bronchoscopy was performed, and biopsy of the right endobronchial tumour confirmed the diagnosis of SCLC (Figures 3, 4).

Bronchoscopic-view-of-the-right-hilar-mass-
Figure 3: Bronchoscopic view of the right hilar mass

Bronchoscopic view of the right bronchial tree demonstrating an irregular, lobulated endobronchial mass (black arrow). The lesion appears friable and hypervascular, partially obstructing the bronchial lumen, suggestive of a malignant endobronchial tumor.

Histological-section-of-small-cell-lung-cancer-(SCLC)
Figure 4: Histological section of small cell lung cancer (SCLC)

The arrow indicates a dense cluster of small, hyperchromatic tumour cells characteristic for SCLC.

The combination of persistent metabolic derangements, imaging findings, and histological confirmation supported the diagnosis of paraneoplastic Cushing’s syndrome secondary to ectopic ACTH production by SCLC. This rare clinical entity results from autonomous ACTH secretion by the tumour, leading to adrenal hyperplasia and excessive cortisol production.

Further staging workup was performed to assess the extent of the disease. Contrast-enhanced CT of the abdomen and MRI of the brain showed no evidence of distant metastasis. The disease was therefore classified as limited-stage SCLC.

The patient was commenced on metyrapone and spironolactone following a comprehensive discussion with the endocrinology team. This intervention resulted in the stabilisation of her potassium levels (Figure 5). Furthermore, in the context of her diagnosis of SCLC, a multidisciplinary team (MDT) was convened to discuss her case. Following this collaborative discourse, it was determined that a referral to the oncology department was warranted for the initiation of chemotherapy.

-Serum-potassium-trend-showing-initial-treatment-resistance-and-subsequent-stabilization-after-initiation-of-metyrapone-and-spironolactone
Figure 5: Serum potassium trend showing initial treatment resistance and subsequent stabilization after initiation of metyrapone and spironolactone

The graph demonstrates persistently low serum potassium levels despite aggressive intravenous and oral supplementation. Notable stabilization and eventual normalization of potassium values are observed following the initiation of metyrapone and spironolactone, indicated toward the end of the monitoring period. The shaded green area represents the normal reference range for serum potassium (3.5–5.5 mmol/L).

Discussion

This case illustrates a rare but clinically significant presentation of paraneoplastic Cushing’s syndrome secondary to ectopic ACTH secretion from SCLC. The patient’s initial symptoms of chest pain and breathlessness were non-specific, but persistent metabolic derangements, including hypokalaemia, hyperglycaemia, and metabolic alkalosis, proved refractory to standard treatment. These findings raised suspicion for an underlying endocrine disorder, leading to targeted hormonal evaluation [1,2].

Diagnostic workup revealed markedly elevated cortisol and ACTH levels, with failure to suppress during low- and high-dose dexamethasone suppression tests. Imaging and histological analysis subsequently identified a right hilar mass consistent with SCLC as the source of ectopic ACTH production. Although rare, ectopic ACTH syndrome is a well-recognised paraneoplastic manifestation of SCLC, reported in approximately 1-5% of cases [3]. It can lead to severe metabolic derangements that complicate management and worsen prognosis if unrecognised [4].

Management of ectopic Cushing’s syndrome requires prompt biochemical stabilisation to mitigate life-threatening complications such as hypokalaemia and hypertension. In this case, metyrapone, an 11β-hydroxylase inhibitor, effectively reduced cortisol synthesis, while spironolactone antagonised mineralocorticoid receptors to correct hypokalaemia. Other agents such as ketoconazole, mitotane, or intravenous etomidate may be considered in similar cases, especially when rapid cortisol control is needed or oral therapy is contraindicated [1,5]. However, these therapies carry risks of hepatotoxicity, adrenal insufficiency, or sedation, underscoring the importance of careful monitoring.

Definitive treatment of the underlying malignancy remains the cornerstone of care, as sustained control of ectopic ACTH production depends on tumour response. Early initiation of chemotherapy in SCLC can lead to a reduction in tumour burden and, in some cases, resolution of the paraneoplastic syndrome [4]. However, the metabolic instability associated with hypercortisolism often complicates oncologic management, highlighting the need for coordinated multidisciplinary care.

This case underscores the diagnostic challenge posed by ectopic Cushing’s syndrome and the importance of recognising paraneoplastic endocrine presentations in patients with unexplained metabolic derangements.

Conclusions

This case underscores the importance of considering paraneoplastic syndromes in patients with persistent, unexplained metabolic derangements such as hypokalaemia, hyperglycaemia, and metabolic alkalosis. In this patient, early recognition of ectopic ACTH secretion prompted targeted investigations, leading to the timely diagnosis of SCLC. This facilitated the initiation of appropriate endocrine therapy with metyrapone and spironolactone to stabilise the biochemical abnormalities and allowed safe progression to oncological management.

The case also highlights the complexities of managing ectopic Cushing’s syndrome, where severe metabolic disturbances can delay definitive cancer treatment. A coordinated, multidisciplinary approach involving endocrinology, oncology, and respiratory teams was crucial in optimising patient care and improving the likelihood of a favourable outcome.

For clinicians, this case reinforces the need to maintain a high index of suspicion for paraneoplastic endocrine disorders in patients with unexplained electrolyte and metabolic abnormalities, particularly when accompanied by respiratory symptoms or imaging suggestive of a pulmonary lesion. Early identification and intervention in such cases are critical for minimising morbidity and enabling timely cancer-directed therapy.

References

  1. Jeong C, Lee J, Ryu S, et al.: A case of ectopic adrenocorticotropic hormone syndrome in small cell lung cancer. Tuberc Respir Dis (Seoul). 2015, 78:436-9. 10.4046/trd.2015.78.4.436
  2. Ilias I, Torpy DJ, Pacak K, Mullen N, Wesley RA, Nieman LK: Cushing’s syndrome due to ectopic corticotropin secretion: twenty years’ experience at the National Institutes of Health. J Clin Endocrinol Metab. 2005, 90:4955-62. 10.1210/jc.2004-2527
  3. Coe SG, Tan WW, Fox TP: Cushing’s syndrome due to ectopic adrenocorticotropic hormone production secondary to hepatic carcinoid: diagnosis, treatment, and improved quality of life. J Gen Intern Med. 2008, 23:875-8. 10.1007/s11606-008-0587-z
  4. Perakakis N, Laubner K, Keck T, et al.: Ectopic ACTH-syndrome due to a neuroendocrine tumour of the appendix. Exp Clin Endocrinol Diabetes. 2011, 119:525-9. 10.1055/s-0031-1284368
  5. Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, Montori VM: The diagnosis of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008, 93:1526-40. 10.1210/jc.2008-0125

https://www.endocrine.org/journals/jcem-case-reports/unilateral-adrenalectomy-for-pediatric-cyclical-cushing-syndrome

 

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Münchausen By Media

Posted on August 30, 2025 by MaryO

The Internet makes it so easy to develop weird and unusual diseases.  Just plop a symptom into Google and suddenly you find yourself with stomach cancer, Cushing’s or other dread diseases.

Even on TV, the ads for lawyers almost convince people they might have mesothelioma and other rare illnesses that might bring you – and them! – bundles of money if you just sue someone.

Magazine ads implore you to “ask your doctor about…” this drug or that you might or might not need.  Your doctor might just give it to you to keep you from asking.  And there’s a needless medication that brings profit to the drug company and side effects to you.

TV shows like House and Mystery Diagnosis will show you diseases you never dreamed about.

There’s a great topic on the Power Surge message boards, What’s the worst “disease or ailment” you’ve had, where the women discuss the diseases they thought that they had, based on symptoms, what they’ve seen online, in the news but not based on reality.

I’ve done it myself.  About the only time I was right was with my Cushing’s diagnosis. That one was a good call. But my thoughts of kidney cancer metastasis haven’t come true (yet, anyway!).

There’s been information online lately about Münchausen Syndrome.  Wikipedia says:

“…the affected person exaggerates or creates symptoms of illnesses in themselves or their child/children in order to gain investigation, treatment, attention, sympathy, and comfort from medical personnel. In some extremes, people suffering from Münchausen’s Syndrome are highly knowledgeable about the practice of medicine, and are able to produce symptoms that result in multiple unnecessary operations. For example, they may inject a vein with infected material, causing widespread infection of unknown origin, and as a result cause lengthy and costly medical analysis and prolonged hospital stay. The role of “patient” is a familiar and comforting one, and it fills a psychological need in people with Münchausen’s. It is distinct from hypochondriasis in that patients with Münchausen syndrome are aware that they are exaggerating, whereas sufferers of hypochondriasis believe they actually have a disease.”

I think we’ve all see this, especially online.  It’s so easy to sit in the comfort of ones home and add “just a little” to the symptoms, making it more impressive for the readers.

From A Strange Case of Münchausen By Internet:

“…When I first got online, I “met” a young woman who claimed to be a vet, and offered me all kinds of advice about my cat and my tropical fish. She got cancer, slowly declined, then died. We wanted to send flowers, and maybe attend the funeral, and got her ISP to contact her family for us. To our shock, her parents said there was no funeral. She wasn’t dead, she wasn’t even sick. At least not physically. She’d pulled this kind of “pretend death” several times before, and was in therapy, but every time life got stressful, she’d do it again.

And the Internet is the ideal place for a Munchausen sufferer. With the click of a button, you can find out all kinds of information, to help you pose as anyone you want. People don’t expect to see you in person or even talk to you except by e-mail, making deception easier. And often, mailing lists, message boards, etc., will give unqualified support to their members…”

And Media Makes Me Sick:

“…The Internet is hands-down the worst thing to ever happen to the medical world. With Web sites like WebMD, any paranoid hypochondriac like me can jump online, look for symptoms and immediately convince himself he has cancer or Cushing’s disease or non-Hodgkin’s lymphoma or any other of a million things.

WebMD allows you to find one symptom and then “helps” you by listing 15,000 things it could mean.

Oh my God. I do have a slight ache! That’s it. I must have a brain tumor. I’m not kidding, I recently scared myself into thinking I had cancer. It took a specialist, a CT scan and an ultra-sound to convince me otherwise…”

Karen found this older article at http://www.villagevoice.com/2001-06-26/news/cybersickness/1

“…Over nearly three years, from 1998 to 2000, a woman—let’s call her Anna—posted to an online support group for people with mental illness. To the larger circle of readers, she acted mostly as friendly counselor. But to a select few, she e-mailed stories of escalating catastrophes. Her husband and two children had perished in a plane crash, she wrote. As a kid, her father had molested her, and she had suffered multiple personality disorder. Finally, she told her trusted—and trusting—confidants that she had just been diagnosed with leukemia.

Gwen Grabb, a psychotherapy intern and mother of three in Los Angeles, says the group believed Anna because she took on the role of helping others, revealing her own difficulties much later, and to an intimate audience. “She was very bright,” recalls Grabb. “She was very supportive and kind. One day, she started telling me about `the crash,’ what they found in the black box, how you could hear her daughter screaming. I had known her a year. I believed her.”

But as the tales became more elaborate and grotesque, Grabb grew suspicious. Along with another group member—Pam Cohen, a bereavement counselor in the Mid-Atlantic region—she did some research and discovered Anna was making it up. It was a shock to all, but worse than that to Cohen. “It is like an emotional rape,” she says. People may have been upset over the online life and fatal cancer of the fictional Kaycee, whose creator admitted last month she’d invented the high school character for expressive purposes. But that was geared to a general audience, however easily suckered. Pretenders like Anna hurt a much more vulnerable group—folks who may be seriously ill and are seeking help…”

So – use caution and remember that not everything you read will happen to you!

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Severe Psychosis Due to Cushing Syndrome

Posted on August 28, 2025 by MaryO

Cushing syndrome (CS) is a rare clinical condition resulting in excess cortisol production. Neuropsychiatric disturbances are prevalent, in addition to the well-known metabolic effects. Depression and anxiety are the most common manifestations, while mania and psychosis are rare.1,2 We report the case of a patient who presented with severe psychosis due to adrenocorticotropic hormone (ACTH)–dependent CS due to a pituitary adenoma (PA).

Case Report

A 47-year-old woman was brought to the hospital after she was found wandering on someone’s property 2 days after her parents had filed a missing person report. She was disoriented, had difficulty recalling events, and reported intrusive thoughts. She had a history of hypertension, hyperlipidemia, prediabetes, and schizoaffective disorder diagnosed 10 years ago when she had an episode of acute psychosis. She was noncompliant with her medications.

On presentation, her blood pressure was 160/111 mm Hg, pulse rate was 111 bpm, and body mass index was 24.14 kg/m2. The psychiatric examination revealed disorientation, thought disorganization, subdued mood, blunted affect, and impaired memory and attention. She had central adiposity and coarse terminal hair growth on her chin; the rest of the physical examination was unremarkable. She was started on olanzapine but developed catatonia after 10 days. Olanzapine was discontinued after 4 weeks as her catatonia worsened. Due to the worsening of hypertension, her random cortisol level was checked and found to be elevated at 51.8 μg/dL (2.9–19.4 μg/dL). Further workup was deferred due to testing difficulty in the setting of acute psychosis. A trial of aripiprazole was initiated but was discontinued after 10 days due to the persistence of catatonia. She then received electroconvulsive therapy on alternate days for 11 sessions, with improvement in her symptoms.

The workup of CS was initiated due to the difficulty in managing her symptoms, weight gain, worsening of hypertension, and pedal edema. Laboratory investigations showed potassium of 2.7 mEq/dL (3.5–5.5 mEq/dL), elevated serum cortisol of 39.3 μg/dL (2.9–19.4 μg/dL), and ACTH of 100.2 pg/dL (7.2–63.3 pg/dL). Her 24-hour urinary free cortisol level was 2,340 and 1,180 (≤45 μg/dL) on 2 separate occasions, thyroid-stimulating hormone was 0.02 (0.4–4.0 mIU/L), and free thyroxine was 0.6 (0.7–1.9 ng/dL). The dexamethasone suppression test was also abnormal. Given that her ACTH level was elevated, there was a high concern for a PA. A magnetic resonance imaging scan revealed a 9.3 x9.6–mm nonenhancing focus on the posterior aspect of the pituitary, which confirmed the diagnosis of ACTH-dependent CS. Central hypothyroidism was attributed to the mass effect of the PA. Transsphenoidal PA resection was performed with subsequent improvement in her symptoms.

Discussion

Acute psychosis may be the initial manifestation of CS. This can easily be overlooked, especially in patients with preexisting psychiatric conditions. CS can be indolent, with clinical and neuropsychiatric features often beginning years before diagnosis. In this case, the initial presentation a decade ago could also be attributed to CS. Many antipsychotic drugs can result in metabolic syndrome, which can be hard to differentiate from manifestations of CS.3 Individuals with neuropsychiatric disorders can have elevation in their cortisol levels due to activation of the hypothalamic-pituitary axis, especially in the evening, without the presence of any pituitary or adrenal adenomas (these result in pathological hypercortisolism).4 This is known as pseudo-CS or physiological hypercortisolism.5 Based on clinical features alone, physiological and pathological hypercortisolism can be hard to distinguish. A high index of clinical suspicion is needed, with repeat testing often required, as there are no specific cutoffs to distinguish between these conditions.6,7

In patients with severe neuropsychiatric illness and features of metabolic syndrome, a diagnosis of CS should be strongly considered, especially in those not responding to conventional treatment strategies. Early recognition and treatment can lead to improved outcomes, though complete recovery of psychiatric symptoms may not be seen in some patients.8,9

AnchorArticle Information

Published Online: August 21, 2025. https://doi.org/10.4088/PCC.25cr03957
© 2025 Physicians Postgraduate Press, Inc.
Prim Care Companion CNS Disord 2025;27(4):25cr03957
Submitted: March 6, 2025; accepted April 30, 2025.
To Cite: Dhaliwal G, MD; Kaur JK, Batra J, et al. Severe psychosis due to Cushing syndrome. Prim Care Companion CNS Disord 2025;27(4):25cr03957.
Author Affiliations: Department of Endocrinology, Diabetes and Metabolism, HealthPartners Institute, Minneapolis, Minnesota (Dhaliwal, JK Kaur, J Kaur); Department of Endocrinology, University of Nebraska, Omaha, Nebraska (Batra).
Corresponding Author: Jasleen Kaur, MD, Department of Endocrinology, Diabetes and Metabolism, HealthPartners Institute, 401 Phalen Blvd, St Paul, MN 55130 (jasleen.x.kaur@healthpartners.com).
Relevant Financial Relationships: None.
Funding/Support: None.
Patient Consent: Consent was received from the patient to publish the case report, and information has been de-identified to protect patient anonymity.
ORCID: Jasleen Kaur: https://orcid.org/0000-0002-0584-4638

From https://www.psychiatrist.com/pcc/severe-psychosis-due-cushing-syndrome/

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Graphic Era Hospital’s Milestone Treatment of Two Complex Cases

Posted on August 26, 2025 by MaryO
DEHRADUN, 23 August: Graphic Era Hospital has achieved a remarkable mileston by successfully treating two complex cases of the rare hormonal disorder Cushing’s Disease in Dehradun. The hospital’s experts used advanced technology and surgical skills to give the patients a new lease on life, marking this significant achievement.
In the first case, a 27-year-old woman was brought to the Endocrinology Department at Graphic Era Hospital after long-term weight gain, facial puffiness, irregular menstrual cycles, high blood pressure, and kidney stones. Tests and lab reports confirmed that the patient was suffering from ACTH-dependent Cushing’s Syndrome – Pituitary Microadenoma. A 3-Tesla Dynamic Pituitary MRI revealed a 6 mm tumor, while other organs were normal.
The specialists performed surgery using endoscopic trans-nasal neuro-navigation technology, completing it successfully without opening the brain. After the operation, the patient experienced significant weight loss, normalized blood pressure, regular menstrual cycles, and all hormone levels returned to normal.
In the second case, a 24-year-old woman came to Graphic Era Hospital with extremely high blood pressure (200/100), headache, weight gain, and irregular menstrual cycles. MRI revealed a 7–9 mm tumor in an unusual location in the pituitary gland, which was also affecting the pituitary fossa bone. Despite multiple medications, her blood pressure remained uncontrolled, and CT scans showed an impact on her heart.
The multi-specialty team performed surgery using endoscopic trans-nasal neuro-navigation technology, again without opening the brain. After surgery, her blood pressure normalized and her menstrual cycles became regular.
In both cases, pituitary microadenomas were diagnosed. The surgeries were done through the nasal route using microscopes and endoscopes, with neuro-navigation helping to accurately locate the tumors while protecting the pituitary gland. The multi-specialty team included Head of Neurosciences and HOD Neurosurgery Partha P Bishnu, Senior Consultant Neurosurgery Ankur Kapoor, Senior Neurosurgeon and Neurointervention Specialist Payoz Pandey, Senior Consultant ENT Parvendra Singh, Director Endocrinology, Obesity and Diabetes Sunil Kumar Mishra, and the Neuro-Anesthesia Team.
With the latest technology and expert doctors at Graphic Era Institute of Medical Sciences, new milestones continue to be achieved. Previously, the hospital’s expert doctors had successfully implanted pacemakers in the brain, placed a third pacemaker in complex pediatric cases, replaced two heart valves without open-heart surgery, unblocked the esophagus without surgery, and performed open-heart surgery through a small 2.5-inch facial incision without cutting bones. Director of Graphic Era Hospital, Puneet Tyagi,  Mefical Superintendent, Gurdeep Singh Jheetay, Dean SL Jethani and COO Atul Bahl were present at the press conference.

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