Cushing’s Syndrome Treatments

Posted on January 7, 2026 by MaryO
Medications, Surgery, and Other Treatments for Cushing’s Syndrome

Written by | Reviewed by Daniel J. Toft MD, PhD

Treatment for Cushing’s syndrome depends on what symptoms you’re experiencing as well as the cause of Cushing’s syndrome.

Cushing’s syndrome is caused by an over-exposure to the hormone cortisol. This excessive hormone exposure can come from a tumor that’s over-producing either cortisol or adrenocorticotropic hormone (ACTH—which stimulates the body to make cortisol). It can also come from taking too many corticosteroid medications over a long period of time; corticosteroids mimic the effect of cortisol in the body.

The goal of treatment is to address the over-exposure. This article walks you through the most common treatments for Cushing’s syndrome.

Gradually decreasing corticosteroid medications: If your doctor has identified that the cause of your Cushing’s syndrome is corticosteroid medications, you may be able to manage your Cushing’s syndrome symptoms by reducing the overall amount of corticosteroids you take.

It’s common for some people with certain health conditions—such as arthritis and asthma—to take corticosteroids to help them manage their symptoms. In these cases, your doctor can prescribe non-corticosteroid medications, which will allow you to reduce—or eliminate—your use of corticosteroids.

It’s important to note that you shouldn’t stop taking corticosteroid medications on your own—suddenly stopping these medications could lead to a drop in cortisol levels—and you need a healthy amount of cortisol. When cortisol levels get too low, it can cause a variety of symptoms, such as muscle weakness, fatigue, weight loss, and low blood pressure, which may be life-threatening.

Instead, your doctor will gradually reduce your dose of corticosteroids to allow your body to resume normal production of cortisol.

If for some reason you cannot stop taking corticosteroids, your doctor will monitor your condition very carefully, frequently checking to make sure your blood glucose levels as well as your bone mass levels are normal. Elevated blood glucose levels and low bone density are signs of Cushing’s syndrome.

Surgery to remove a tumor: If it’s a tumor causing Cushing’s syndrome, your doctor may recommend surgery to remove the tumor. The 2 types of tumors that can cause Cushing’s are pituitary tumors (also called pituitary adenomas) and adrenal tumors. However, other tumors in the body (eg, in the lungs or pancreas) can cause Cushing’s syndrome, too.

Pituitary adenomas are benign (non-cancerous), and most adrenal tumors are as well. However, in rare cases, adrenal tumors can be malignant (cancerous). These tumors are called adrenocortical carcinomas, and it’s important to treat them right away.

Surgery for removing a pituitary tumor is a delicate process. It’s typically performed through the nostril, and your surgeon will use tiny specialized tools. The success, or cure, rate of this procedure is more than 80% when performed by a surgeon with extensive experience. If surgery fails or only produces a temporary cure, surgery can be repeated, often with good results.

If you have surgery to remove an adrenal tumor or tumor in your lungs or pancreas, your surgeon will typically remove it through a standard open surgery (through an incision in your stomach or back) or minimally invasive surgery in which small incisions are made and tiny tools are used.

In some cases of adrenal tumors, surgical removal of the adrenal glands may be necessary.

Radiation therapy for tumors: Sometimes your surgeon can’t remove the entire tumor. If that happens, he or she may recommend radiation therapy—a type of treatment that uses high-energy radiation to shrink tumors and/or destroy cancer cells.

Radiation therapy may also be prescribed if you’re not a candidate for surgery due to various reasons, such as location or size of the tumor. Radiation therapy for Cushing’s syndrome is typically given in small doses over a period of 6 weeks or by a technique called stereotactic radiosurgery or gamma-knife radiation.

Stereotactic radiosurgery is a more precise form of radiation. It targets the tumor without damaging healthy tissue.

With gamma-knife radiation, a large dose of radiation is sent to the tumor, and radiation exposure to the healthy surrounding tissues is minimized. Usually one treatment is needed with this type of radiation.

Medications for Cushing’s syndrome: If surgery and/or radiation aren’t effective, medications can be used to regulate cortisol production in the body. However, for people who have severe Cushing’s syndrome symptoms, sometimes medications are used before surgery and radiation treatment. This can help control excessive cortisol production and reduce risks during surgery.

Examples of medications your doctor may prescribe for Cushing’s syndrome are: aminoglutethimide (eg, Cytadren), ketoconazole (eg, Nizoral), metyrapone (eg, Metopirone), and mitotane (eg, Lysodren). Your doctor will let you know what medication—or combination of medications—is right for you.

You may also need to take medication after surgery to remove a pituitary tumor or adrenal tumor. Your doctor will most likely prescribe a cortisol replacement medication. This medication helps provide the proper amount of cortisol in your body. An example of this type of medication is hydrocortisone (a synthetic form of cortisol).

Experiencing the full effects of the medication can take up to a year or longer. But in most cases and under your doctor’s careful supervision, you can slowly reduce your use of cortisol replacement medications because your body will be able to produce normal cortisol levels again on its own. However, in some cases, people who have surgery to remove a tumor that causes Cushing’s syndrome won’t regain normal adrenal function, and they’ll typically need lifelong replacement therapy.2

Treating Cushing’s Syndrome Conclusion
You may need one treatment or a combination of these treatments to effectively treat your Cushing’s syndrome. Your doctor will let you know what treatments for Cushing’s syndrome you’ll need.

From https://www.endocrineweb.com/conditions/cushings-syndrome/cushings-syndrome-treatments

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Genetic mutation lowers obesity in Cushing’s syndrome

Posted on January 5, 2026 by MaryO

London E. J Clin Endocrinol Metab. 2013; doi:10.1210/jc.2013-1956.

Among adult patients with Cushing’s syndrome, those with mutations in PRKAR1A, the gene that controls cAMP-dependent protein kinase, are less obese than their counterparts without these mutations, according to a recent study.

The retrospective study evaluated adrenalectomy samples from 51 patients with Cushing’s syndrome, 13 with PRKAR1A mutations and 32 without. Of the 51 patients, 40 were female and 11 were male, and patients ranged in age from 4 to 74 years.

A non-Cushing’s syndrome comparison group consisting of 6 adrenalectomy patients with aldosterone producing adenomas (APAs) was included. Additional comparison groups comprising clinical data from 89 patients with Cushing’s disease and 26 with hyperaldosteronism were also studied.

Researchers recorded the weight, height and BMI of all patients, and measured abdominal subcutaneous adipose tissue (ScAT) and periadrenal adipose tissue (PAT) using computed tomography. PAT was collected and frozen for evaluation; the extracts were assessed for levels of cAMP and protein kinase (PKA) activity, as well as for protein and mRNA expression of subunits of PKA. Diurnal cortisol levels and urine-free cortisol were also measured preoperatively.

The study found that in adults with Cushing’s syndrome, the mean BMI of those with PRKAR1A mutations was lower than that of patients with noPRKAR1A mutations (P<.05), and was not inconsistent with the hyperaldosteronism comparison group.

In pediatric patients with adrenal Cushing’s syndrome, the presence of PRKAR1A mutation did not have an impact on mean BMI z-scores. However, in comparison with pediatric patients with pituitary Cushing’s disease, the BMI z-scores were significantly lower in pediatric Cushing’s disease patients with PRKAR1Amutations (P<.05). Patients with Cushing’s syndrome without PRKAR1A mutations had significantly more PAT and ScAT than non-Cushing’s syndrome patients. Additionally, the ratio of basal-to-total (cAMP-triggered) PKA activity was significantly lower in patients with PRKAR1A mutations, suggesting greater proportions of active PKA (P<.005).

“These findings have obvious implications in the establishment of the diagnosis of CS in patients with PRKAR1A mutations: These patients may be leaner than other patients with [Cushing’s syndrome],” the study authors wrote. “Perhaps more importantly, our findings point to the importance of cAMP and or PKA signaling in the regulation of adiposity.”

Disclosures: The researchers report no relevant financial disclosures.

From http://www.healio.com/endocrinology/adrenal/news/online/%7B693f94cd-359d-4c52-8e0d-bfd0e4a51d03%7D/genetic-mutation-lowers-obesity-in-cushings-syndrome

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A Second Look at Refractory Edema: Delayed Diagnosis of Paraneoplastic Cushing’s Syndrome in Small Cell Lung Cancer

Posted on January 4, 2026 by MaryO

Abstract

Paraneoplastic Cushing syndrome (PCS) is a rare manifestation of ectopic adrenocorticotropic hormone (ACTH) production, mostly associated with bronchial carcinoid and small cell lung cancer (SCLC). Its clinical manifestations: refractory hypertension, profound hypokalemia, metabolic alkalosis, worsening hyperglycemia, and edema, can easily be misattributed to more common conditions, especially in older adults with multiple comorbidities, leading to diagnostic errors.

We present a case of an 84-year-old man with a history of stage IA non-SCLC treated one year earlier, who developed progressive dyspnea, orthopnea, bilateral extremity edema, severe hypokalemia, metabolic alkalosis, and new-onset hypertension. His symptoms were initially managed as volume overload and diuretic-resistant heart failure in the outpatient setting. During hospitalization, persistent metabolic alkalosis, worsening hyperglycemia, resistant hypertension, and refractory hypokalemia prompted further evaluation. Laboratory studies demonstrated markedly elevated early morning cortisol (102.7 µg/dL) and ACTH (293 pg/mL). Computed tomography (CT) imaging revealed a new right infrahilar mass, extensive mediastinal adenopathy, and bilateral adrenal metastases. Endobronchial ultrasound-guided biopsy confirmed SCLC. The patient was diagnosed with paraneoplastic ACTH-dependent CS and initiated on systemic chemotherapy.

This case highlights several diagnostic vulnerabilities, including anchoring bias, confirmation bias, premature closure, and failure to integrate multiple abnormal findings into a unifying diagnosis. Earlier recognition of the characteristic cluster of hypercortisolism signs-refractory hypokalemia, metabolic alkalosis, resistant hypertension, and hyperglycemia- may have accelerated diagnosis and treatment. Clinicians should maintain a high index of suspicion for PCS in older adults with a history of lung cancer who present with unexplained electrolyte disturbances and rapidly worsening cardiometabolic parameters. Early diagnosis is critical given the high morbidity and mortality associated with untreated paraneoplastic Cushing’s syndrome.

Introduction

Paraneoplastic ACTH-dependent Cushing syndrome (CS) is an uncommon but severe manifestation of ectopic adrenocorticotropic hormone production. Ectopic ACTH syndrome accounts for approximately 6-10% of all cases of endogenous CS [1]. This represents 10-20% of ACTH-dependent forms of Cushing syndrome, which themselves comprise 70-80% of all endogenous CS cases. Lung neuroendocrine tumors account for approximately 25% of cases, followed by small cell lung cancers (SCLC) (20%), with other sources being neuroendocrine tumors of the thymus, pancreas, and medullary thyroid carcinoma [2,3]. Patients typically present with symptoms related to underlying malignancy and rapid onset of severe hypercortisolism characterized by profound hypokalemia, metabolic alkalosis, hyperglycemia, and muscle weakness, often without the classic cushingoid features seen in other forms of CS [4,5].

These abnormalities are often initially attributed to more common conditions, including heart failure, diuretic use, thyroid disease, and worsening chronic diseases such as diabetes mellitus, especially in older adults with multimorbidity. This often leads to diagnostic errors. Diagnostic delays in paraneoplastic Cushing syndrome (PCS) are common and clinically meaningful. Hypercortisolism accelerates tumor progression, increases vulnerability to infection, worsens cardiometabolic dysfunction, and contributes to poor performance status, substantially limiting therapeutic options [6-8]. Prompt recognition requires clinicians to identify the hallmark constellation of metabolic disturbances and consider endocrine etiologies early.

We describe an older adult who presented with cough, dyspnea, edema, severe resistant hypertension, metabolic alkalosis, and electrolyte derangements that were initially attributed to volume overload and chronic lung disease. The diagnostic process ultimately led to the identification of extensive-stage SCLC, which caused ectopic ACTH production. We emphasize the diagnostic errors that contributed to the delayed recognition of this life-threatening syndrome.

Case Presentation

An 84-year-old man with a history of pre-diabetes, chronic obstructive pulmonary disease (COPD), a former smoker, and previously treated stage IA non-SCLC (left lower lobe, treated with Stereotactic Body Radiation Therapy) presented with cough, progressive shortness of breath, orthopnea, and bilateral lower extremity edema. Two weeks prior, outpatient clinicians treated his worsening edema and dyspnea with loop diuretics, and he was also started on nifedipine and losartan for hypertension.

In the emergency department, vital signs revealed blood pressure 216/98 mmHg, heart rate 104 beats/min, and respiratory rate 23 breaths/min. Physical examination demonstrated bilateral pedal edema extending to the mid-shins and bilateral upper extremity edema. Lung examination revealed no wheezing or crackles. The abdomen was obese but without palpable masses.

Initial laboratory evaluation showed mild thrombocytopenia (114 × 103/µL), creatinine 1.10 mg/dL, potassium 2.9 mmol/L, bicarbonate 43 mmol/L, chloride 88 mmol/L, glucose 240 mg/dL, unremarkable liver function test, and elevated B-type natriuretic peptide (BNP) of 198 pg/mL. Arterial blood gas demonstrated pH 7.58 and PaCO₂ 42 mmHg, indicating primary metabolic alkalosis. Urinalysis was significant for glucosuria, otherwise unremarkable. Chest X-ray showed bibasilar atelectasis without evidence of pulmonary edema. He was admitted for decompensated heart failure. Pertinent admission laboratory findings are summarized in Table 1.

Test Result Range
Hemoglobin 16.4 g/dL 13.8-17.2 g/dL
White cell count 9.7 × 103/µL 4.0-10.50 × 103/µL
Platelet 114 × 103/µL 130-400 × 103/µL
Sodium 142 mmol/L 133-145 mmol/L
Potassium 2.9 mmol/L 3.3-5.1 mmol/L
Chloride 88 mmol/L 98-108 mmol/L
Bicarbonate 43 mmol/L 22-32 mmol/L
Creatinine 1.10 mg/dL 0.50-1.20 mg/dL
BNP 198.8 pg/mL 10.0-100.0 pg/mL
Albumin 3.7 g/dL 3.0-5.0 g/dL
Glucose 240 mg/dL 70-100 mg/dL
Serum cortisol 102.7 µg/dL 6.7-22.6 µg/dL
Plasma ACTH 293 pg/mL 6-50 pg/mL
Urine chloride 73 mmol/L
Urine potassium 38 mmol/L
Table 1: Summary of relevant laboratory findings at presentation

Metabolic alkalosis, renal potassium wasting, hyperglycemia, elevated cortisol, and ACTH suggested an ACTH-dependent Cushing’s syndrome.

BNPL: brain natriuretic peptide; ACTH: adrenocorticotropic hormone

Despite diuresis with IV furosemide, he continued to demonstrate metabolic alkalosis and worsening hypokalemia (nadir 2.8 mmol/L), requiring repeated potassium supplementation. Hyperglycemia persisted with capillary blood glucose 170-300 mg/dL, requiring escalating insulin doses. Blood pressures remained elevated despite escalation of losartan and nifedipine. Echocardiogram on day 2 of admission was unremarkable with an ejection fraction of 55-60% and normal diastolic function. Doppler ultrasound of the lower and upper extremities did not reveal deep vein thrombosis.

On hospital day 3, diagnosis was reassessed, and differentials were broadened to include endocrine causes of hypertension with metabolic alkalosis. Urine electrolytes revealed high urine chloride (73 mmol/L) and potassium (38 mmol/L), suggestive of potassium wasting from possible mineralocorticoid excess. Subsequent testing revealed markedly elevated serum cortisol (102.7 µg/dL) and plasma ACTH (293 pg/mL), suggesting an ACTH-dependent process. Given his significant history of smoking and treated NSCLC, a CT chest/abdomen/pelvis was done, which showed a new right infrahilar mass, mediastinal lymphadenopathy, and nodular fullness of both adrenal glands concerning for metastatic disease (Figures 1–6).

Axial-CT-chest-showing-an-enlarged-right-paratracheal-lymph-node.
Figure 1: Axial CT chest showing an enlarged right paratracheal lymph node.

Axial image demonstrates a right paratracheal lymph node measuring 14.8 mm in short axis, concerning for malignant nodal involvement.

Non-contrast-axial-CT-chest-showing-a-dominant-right-paratracheal-lymph-node
Figure 2: Non-contrast axial CT chest showing a dominant right paratracheal lymph node

A right paratracheal lymph node measuring 16.2 × 16.5 mm is demonstrated, further supporting malignant mediastinal involvement in small cell lung cancer.

Axial-non-contrast-CT-chest-demonstrating-residual-treated-left-lower-lobe-lesion
Figure 3: Axial non-contrast CT chest demonstrating residual treated left lower lobe lesion

A spiculated nodule in the left lower lobe measuring 9.2 mm (AP) × 8.5 mm (transverse) on image 60, slightly decreased from the prior measurement of 9.3 × 10.6 mm, corresponding to the site of previously treated squamous cell carcinoma.

Axial-non-contrast-CT-chest-showing-markedly-enlarged-subcarinal-lymph-node
Figure 4: Axial non-contrast CT chest showing markedly enlarged subcarinal lymph node

A dominant subcarinal lymph node measuring 24 × 34 mm, highly suspicious for malignant mediastinal involvement.

Axial-non-contrast-CT-chest-showing-right-infrahilar-mass-like-fullness
Figure 5: Axial non-contrast CT chest showing right infrahilar mass-like fullness

Soft tissue density in the right lower lobe infrahilar region measuring up to 25 mm in transverse diameter, concerning for primary malignant involvement.

Non-contrast-CT-demonstrating-bilateral-adrenal-metastases
Figure 6: Non-contrast CT demonstrating bilateral adrenal metastases

Nodular enlargement of both adrenal glands has progressed compared with prior imaging: the left adrenal lateral limb measures 14 mm (previously 9.2 mm) and the right adrenal body measures 12.4 mm (previously 7 mm). Multiple benign hepatic cysts are also visualized (red arrows).

Bronchoscopy with endobronchial ultrasound-guided transbronchial needle aspiration of the subcarinal (station 7) and right hilar (station 10R) lymph nodes revealed small cell carcinoma. He was diagnosed with extensive-stage SCLC with adrenal metastases and paraneoplastic ACTH-dependent Cushing syndrome. Systemic chemotherapy with carboplatin, etoposide, and atezolizumab was initiated.

Discussion

PCS caused by ectopic ACTH secretion is associated with significantly higher morbidity and mortality than other forms of hypercortisolism. Patients experience universal acute complications and have markedly shortened survival, with median survival reported as low as 3-4 months in those with SCLC [7-9]. Early mortality is common, with most deaths occurring within weeks to months of diagnosis and frequently driven by opportunistic infections, thromboembolic events, and severe metabolic derangements [6,7]. Hypercortisolism itself impairs the ability to deliver effective cancer therapy, increasing the risk of treatment-related complications and reducing chemotherapy response rates [6]. Ectopic ACTH production is therefore considered the most lethal etiology of Cushing syndrome, with tumor progression and infection being the predominant causes of death.

Diagnostic error is the failure to establish an accurate and timely explanation of the patient’s health problem(s) or communicate that explanation to the patient [10]. Diagnostic errors remain a significant contributor to patient harm, with estimates suggesting they affect 5-25% of patients [11,12]. These errors often arise not from knowledge deficits but from cognitive heuristics that clinicians rely on to navigate diagnostic uncertainty. While heuristics are essential for efficiency, they can predispose clinicians to systematic errors, especially when used uncritically or in complex cases [13,14]. Three cognitive pitfalls are particularly relevant in diagnostic error: anchoring bias (fixating early on a diagnosis and failing to adjust as new data emerge), premature closure (ceasing further diagnostic inquiry once an initial label is applied), and diagnostic momentum (the inertia created as more clinicians accept and act upon an early diagnostic impression) [15,16]. These processes can perpetuate incorrect diagnoses and delay definitive care.

For our patient, the initial clinical presentation of dyspnea, orthopnea, bilateral edema, and markedly elevated blood pressure in this older adult reasonably prompted consideration of several common cardiopulmonary and renal conditions. Acute decompensated heart failure was an early working diagnosis given his orthopnea, lower extremity edema, and elevated BNP. However, this diagnosis became less convincing as objective data accumulated. The patient had no pulmonary edema on chest imaging and preserved left ventricular systolic and diastolic function on echocardiography. Additionally, the severity of metabolic alkalosis and hypokalemia was disproportionate to the degree of diuretic exposure and volume status. These discrepancies argued against heart failure as a unifying diagnosis.

A COPD exacerbation was also considered due to the patient’s chronic lung disease and dyspnea. Yet he had no wheezing, no infectious symptoms, and no significant gas-exchange abnormality. His arterial blood gas (ABG) demonstrated metabolic alkalosis without primary respiratory acidosis. Moreover, his dyspnea improved early in the hospitalization, while the metabolic disturbances worsened, further making COPD a less likely diagnostic consideration. Renal causes of edema and hypertension, including nephrotic syndrome and intrinsic kidney disease, were evaluated. The patient had normal albumin and creatinine, and no significant proteinuria or hematuria on urinalysis, findings that could not explain his systemic edema. Similarly, acute or chronic kidney disease could not account for the combination of profound hypokalemia, metabolic alkalosis, and high urine chloride, which instead suggested an active mineralocorticoid process with renal wasting.

Primary hyperaldosteronism was a strong possibility, particularly given the combination of hypertension, hypokalemia, and metabolic alkalosis. However, the patient’s severe hyperglycemia, thrombocytopenia, new constitutional swelling of the upper extremities, and rapid symptom evolution were atypical for isolated hyperaldosteronism. Additionally, bilateral adrenal fullness seen on CT imaging was more consistent with adrenal metastases than with aldosterone-producing adenomas or hyperplasia. The degree of metabolic derangements also exceeded that typically observed in primary hyperaldosteronism, prompting evaluation for cortisol excess.

CS emerged as a unifying explanation for the multisystem abnormalities. The biochemical pattern, including severe metabolic alkalosis, renal potassium wasting, hyperglycemia, and resistant hypertension, is characteristic of activation of glucocorticoid and mineralocorticoid receptors. Markedly elevated cortisol and ACTH levels confirmed ACTH-dependent hypercortisolism. In older adults, pituitary Cushing disease typically evolves more slowly and is rarely associated with such profound hypokalemia [17,18]. Therefore, ectopic ACTH secretion became the leading diagnosis. The patient’s imaging, showing a new right infrahilar mass, progressive mediastinal lymphadenopathy, and bilateral adrenal enlargement, provided a clear source, later confirmed as extensive-stage SCLC.

This diagnostic trajectory illustrates how complex presentations can lead clinicians toward more common conditions, even when early clues point elsewhere. Several cognitive and system-level factors contributed to the delayed recognition of hypercortisolism. Anchoring on heart failure, a condition that fit parts of the patient’s presentation, discouraged re-examination of the initial differential when laboratory data did not fully align. Metabolic abnormalities were at first treated as isolated issues rather than components of a broader endocrine disorder. The patient’s prior non-SCLC had been in remission, which may have reduced the perceived likelihood of malignancy-related pathology, despite the well-known risk of second primary lung cancers and transformation events in older adults with smoking histories. Older adults with a history of smoking who have survived cancer face a substantially elevated risk of developing second primary lung cancers, with the risk persisting for decades after smoking cessation. Among lung cancer survivors, the 10-year cumulative incidence of a second primary lung cancer is approximately 8-15%, which is considerably higher than rates observed in general lung cancer screening populations [19,20].

The availability of more familiar explanations for dyspnea, edema, and hypertension, such as heart failure, may have overshadowed the classical biochemical signature of hypercortisolism. Recognition of ectopic ACTH production requires integrating disparate clinical findings into one physiological pathway. When evaluated collectively rather than individually, these abnormalities strongly suggest cortisol excess long before imaging or biopsy results are available.

Earlier consideration of endocrine etiologies could have expedited diagnosis, reduced unnecessary diuresis, and allowed earlier initiation of appropriate oncologic therapy. PCS from SCLC is associated with rapid clinical decline, impaired immunity, and decreased tolerance to chemotherapy. Prompt recognition may therefore improve both morbidity and the feasibility of cancer-directed treatment. This case reinforces the importance of revisiting and broadening the differential diagnoses when expected clinical improvement does not occur, particularly in older adults with prior malignancy and new multisystem derangements. Incorporating metacognitive strategies, actively questioning initial assumptions, seeking disconfirming evidence, and engaging in reflective practice can mitigate such errors [13].

Conclusions

This case emphasizes the importance of considering paraneoplastic ACTH-dependent CS in older adults presenting with unexplained hypokalemia, metabolic alkalosis, hyperglycemia, and resistant hypertension, particularly in patients with a history of lung cancer. Diagnostic error arose from anchoring on cardiopulmonary etiologies and failure to synthesize metabolic abnormalities into a unifying diagnosis. Early recognition of hypercortisolism is essential, as untreated ectopic ACTH production rapidly worsens morbidity and limits therapeutic efficacy in SCLC.

References

  1. Reincke M, Fleseriu M: Cushing syndrome: A review. JAMA. 2023, 330:170-81.
  2. Gadelha M, Gatto F, Wildemberg LE, Fleseriu M: Cushing’s syndrome. Lancet. 2023, 402:2237-52. 10.1016/S0140-6736(23)01961-X
  3. Pelosof LC, Gerber DE: Paraneoplastic syndromes: An approach to diagnosis and treatment. Mayo Clin Proc. 2010, 85:838-54. 10.4065/mcp.2010.0099
  4. Haugen BR, Alexander EK, Bible KC, et al.: 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016, 26:2016. 10.1089/thy.2015.0020
  5. NCCN Guidelines Version 2.2026 Small – Google Scholar [Internet]. (2025). Accessed: October 7, 2025: https://scholar.google.com/scholar.
  6. Ost DE, Jim Yeung SC, Tanoue LT, Gould MK: Clinical and organizational factors in the initial evaluation of patients with lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013, 143:e121S-41S. 10.1378/chest.12-2352
  7. Schernthaner-Reiter MH, Siess C, Micko A, et al.: Acute and life-threatening complications in Cushing syndrome: Prevalence, predictors, and mortality. J Clin Endocrinol Metab. 2021, 106:e2035-46. 10.1210/clinem/dgab058
  8. Shepherd FA, Laskey J, Evans WK, Goss PE, Johansen E, Khamsi F: Cushing’s syndrome associated with ectopic corticotropin production and small-cell lung cancer. J Clin Oncol. 1992, 10:21-7. 10.1200/JCO.1992.10.1.21
  9. Al-Toubah T, Pelle E, Hallanger-Johnson J, Haider M, Strosberg J: ACTH-secreting pancreatic neuroendocrine neoplasms: A case-series. J Neuroendocrinol. 2023, 35:e13336. 10.1111/jne.13336
  10. Measure Dx: A Resource To Identify, Analyze, and Learn From Diagnostic Safety Events. (2022). Accessed: October 7, 2025: https://www.ahrq.gov/diagnostic-safety/tools/measure-dx.html.
  11. Singh H, Meyer AN, Thomas EJ: The frequency of diagnostic errors in outpatient care: Estimations from three large observational studies involving US adult populations. BMJ Qual Saf. 2014, 23:727-31. 10.1136/bmjqs-2013-002627
  12. Auerbach AD, Lee TM, Hubbard CC, et al.: Diagnostic errors in hospitalized adults who died or were transferred to intensive care. JAMA Intern Med. 2024, 184:164-73.
  13. Croskerry P: The importance of cognitive errors in diagnosis and strategies to minimize them. Acad Med. 2003, 78:775-80. 10.1097/00001888-200308000-00003
  14. Gigerenzer G, Gaissmaier W: Heuristic decision making. Annu Rev Psychol. 2011, 62:451-82. 10.1146/annurev-psych-120709-145346
  15. Watari T, Tokuda Y, Amano Y, Onigata K, Kanda H: Cognitive bias and diagnostic errors among physicians in Japan: A self-reflection survey. Int J Environ Res Public Health. 2022, 19:4645. 10.3390/ijerph19084645
  16. Ogdie AR, Reilly JB, Pang WG, Keddem S, Barg FK, Von Feldt JM, Myers JS: Seen through their eyes: Residents’ reflections on the cognitive and contextual components of diagnostic errors in medicine. Acad Med. 2012, 87:1361-7. 10.1097/ACM.0b013e31826742c9
  17. Paleń-Tytko JE, Przybylik-Mazurek EM, Rzepka EJ, Pach DM, Sowa-Staszczak AS, Gilis-Januszewska A, Hubalewska-Dydejczyk AB: Ectopic ACTH syndrome of different origin-Diagnostic approach and clinical outcome. Experience of one Clinical Centre. PLoS One. 2020, 15:e0242679. 10.1371/journal.pone.0242679
  18. Melmed S: Pituitary-tumor endocrinopathies. N Engl J Med. 2020, 382:937-50. 10.1056/NEJMra1810772
  19. Adams SJ, Stone E, Baldwin DR, Vliegenthart R, Lee P, Fintelmann FJ: Lung cancer screening. Lancet. 2023, 401:390-408. 10.1016/S0140-6736(22)01694-4
  20. Takemura C, Yoshida T, Yoshida Y, et al.: Unveiling the molecular and clinical risk landscape of second primary lung cancer in resected non-small cell lung cancer. Lung Cancer. 2025, 208:108750. 10.1016/j.lungcan.2025.108750

https://www.cureus.com/articles/448285-a-second-look-at-refractory-edema-delayed-diagnosis-of-paraneoplastic-cushings-syndrome-in-small-cell-lung-cancer#!/

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Case study shows chronic marijuana use associated with hypopituitarism

Posted on January 3, 2026 by MaryO

PHOENIX — Results of a case study presented here at the American Association of Clinical Endocrinologists 22nd Scientific and Clinical Congress demonstrate that smoking marijuana may result in serious endocrine complications.

Hormone feedback cycles

Hormone feedback cycles (Photo credit: Wikipedia)

“We really feel that the evidence to-date shows this is a much more serious health problem than we’ve given credit to,” Pinsker said during a press conference. “Marijuana’s always been laughed off: ‘it’s a kid’s drug; they’ll outgrow it.’ In certain communities, it’s so common that people look at it as if they’re having a glass of beer. I think it’s time that physicians start having their antenna up for all the difficulties that come with this drug.”

The patient presented to the emergency department with dyspnea on exertion, increasing fatigue and loss of libido with no previous radiation exposure or head trauma. He had bibasilar rales, gynecomastia and bilateral atrophied testis.

His hormonal evaluation demonstrated low Luteinizing Hormone (0.2 mIU/mL); FSH (1.8 mIU/mL) and testosterone (22 ng/dL), as well as high prolactin (53.3 ng/mL).

Additionally, the patient had ACTH of 6 pg/mL and cortisol of 6.4 ug/dL at 0 minutes and 9.3 ug/dL at 60 minutes following cosyntropin administration.

Further labs revealed low total T3 (30 ng/dL); high T3 resin reuptake (49%); low total T4 (3.94 ng/dL); normal free T4 (0.97 ng/dL) and low TSH (0.22 uIU/mL). Growth hormone was within normal range (5.0 ng/mL) and IGF-I was low (75 ng/mL; Z-score of -1.3). An MRI revealed a slightly enlarged protuberant pituitary gland, but no identified mass lesion.

After being started on cortisone 25 mg in the morning and 12.5 mg at bedtime, as well as levothyroxine 25 mcg daily, the patient’s fatigue and edema improved significantly, according to the abstract.

In this case, severe hypopituitarism occurred from interference between THC, the psychoactive ingredient in marijuana which has the ability to alter neural transmitters in the hypothalamus, and hypothalamic function.

Additionally, studies show that marijuana impairs the release of gonadotropin-releasing hormone (GnRh), resulting in reduced production of testosterone.

Other symptoms seen with prolonged use include cognitive decline in school children and older people, according to Pinsker. “The public will become more attuned to looking for these things. We’re going to have what we call a surveillance bias and we’re going to start discovering that it’s a lot higher than we gave it credit for, both because of increased use and because we’re going to be looking for it.”

The authors conclude that, as many states consider the legalization of marijuana, more study should be conducted with regard to the effects of chronic use of the drug on the endocrine system.

“Of course this is one case report, but I think it should alert further research that needs to be done, “ said Pinsker. “Something prospectively should be done to map this out more scientifically, but this would be difficult in what, to-date, has been an illegal substance.”

For more information:

Pinsker R. Abstract #825. Presented at: the AACE Annual Scientific and Clinical Congress; May 1-5, 2013; Phoenix.

Disclosure: The authors report no relevant financial disclosures.

 From Healio.com

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The Effect of Hypercortisolism Treatment on Dyslipidemia in Cushing Syndrome

Posted on January 2, 2026 by MaryO

Abstract

Introduction

Cushing syndrome (CS) is a clinical condition caused by increased plasma cortisol levels and characterized by high cardiovascular mortality. Among the metabolic effects of CS and its treatment, glycaemic disturbances have been investigated in depth, while data on dyslipidemia is still lacking.

Objectives

Our study aims at evaluating the effects of CS treatment on serum lipid levels.

Materials and methods

A literature search was conducted using PubMed, Scopus, and EMBASE databases to investigate the effects of CS treatment on serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and triglycerides (TG). Before-after analysis and subgroup analysis were performed.

Results

Twenty-nine observational or interventional studies (51.7% of good quality) were included in the quantitative analysis. Treatment of CS led to clinically and statistically significant decrease in serum TC (MD -26.49; 95% CI: -29.95, -23.04; p < 0.00001), LDL-c (MD -18.44; 95% CI: -21.30, -15.57; p < 0.00001), and TG levels (MD -17.77; 95% CI: -22.70, -12.84; p < 0.00001), with no significant changes in HDL-c levels (MD -2.34; 95% CI: -6.96, 2.28; p= 0.32). Subgroup analysis showed greater decrease in TC levels in subjects with adrenal hypercortisolism, in those treated with steroidogenesis inhibitors and in those with treatment duration equal or longer than 12 months. In addition, CS treatment significantly decreased blood glucose (BG) levels, body mass index (BMI), waist circumference (WC), and insulin resistance index.

Conclusion

Our study demonstrate a significant improvement in serum lipid levels after treatment of CS. Since the cardiovascular complications of hypercortisolism depend on several factors, further studies are needed to determine whether this directly translates into an adequate reduction in the risk of major cardiovascular events.

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