Is Cushing’s really that rare? Or is it simply undiagnosed?

Posted on December 18, 2025 by MaryO

Here are some thoughts from the Cushing’s Help message boards over the years.

  • Is this really such a rare disease, or more of a rare diagnosis? I mean, I remember when Thyroid issues were taboo and non-existant to regular docs, but now they all see to know something and are recognizing the issues…Seriously, if only 10-15 in every million have Cushings, how on earth did a well visited forum get created???
  • My personal opinion is a rare diagnosis….I see people with acne covered red moon faces, frontal obesity and a hump and just shake my head. If I can talk to them I will mention it but I am super sensitive about my weight and don’t want to insult anyone.
  • I believe it is both. The disease itself is rare, but more and more people are coming forward. I don’t think it is as rare as they think it is in research. It is also rare to find an educated physician for this disease. They are out there, but why aren’t there more? This makes for rare diagnosis. It is not like I can walk down the street and see tons of people with cushings symptoms, but now that I am aware of it I DO see some.
  • i believe until it is not so underdiagnosed we will never know if it is actually rare.
  • I don’t think it’s as rare as doctors think it is. I think the problem is they send people out based on individual symptoms versus looking at them all as a package. For example I got sent to: a psychiatrist for depression, a gastroenterologist for stomach stuff (diarrhea and constipation), an endocrinologist for the hormone/insulin issues, a neurologist for the headaches, an OB/GYN for the “missed periods” and an opthamologist for the vision issues. None of them talk to each other and none of them work together. How could they make a diagnosis of anything other than their specialty based on that? I think until docs take a team approach, it won’t be diagnosed more.
  • We all tend to think it is rarely diagnosed, more than it being a rare disease. Then, you get into the whole idea of, what causes it anyway?

    Who knows? Nobody knows for sure, but say it is from our environmental issues. Maybe it’s from chemicals we are exposed to, and this is how our bodies react. Then if it is environmental, you will start to see more and more people with it because more and more people are exposed to the same environmental issues. Maybe the same thing causes cancer in some people, and pituitary tumors in others. I’m not saying this is the case, I’m just throwing ideas out there. You didn’t hear of Chronic Fatigue and Fibromyalgia 30 yrs. ago either. Maybe in another 30 yrs., Cushing’s will be a disease that most people know about. That would mean more people getting diagnosed, and it would seem that Cushing’s would be on the rise, but awareness is probably the key.

  • What do YOU think?

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You Know You’re Chronically Ill When You…

Posted on December 17, 2025 by MaryO

…have a pajama collection.

…call the pharmacist and she recognizes your voice before you tell her what it is.

…are psyched to get a computer table tray for sitting in bed as a gift.

…find out that you can order a three month supply of meds online and you think it’s great.

…share and discuss journal articles with your doctor.

…have an inbox full of emails all from people with your disease or related to your disease.

…get updates from MedScape.

…set up your pills a month ahead of time in pill holders.

…have pill stashes in your car, purse, backpack, etc.

MaryO’Updates:

…have Dr F, Dr L and/or Dr IMMC on speed dial.

…bought a case of sharps containers on eBay.

…have a hospital bag always ready to go.

…have a “Got Hump” tattoo

…share pictures online of your stretch marks like they were badges of honor

…you know why there’s a zebra in my avatar

MaryOZebra

MaryO’Zebra

Added by Facebook friends:

…know approximately how much your urine output is in mL’s before you go because you’ve measured it so often before.

…When a specialists at a leading university hospital tells you “you are too complicated”.

…when multiple specialists at multiple leading hospitals tell you your case is complicated! (had to add to that!)

…when you only know the day of the week by your pill container!!

…when you get to park in the handicap spots and you’re only 25 years old!!

…you know to tell the person who’s drawing your blood to ice and centrofuge your vile for the ACTH test!!

…you can’t make plans beyond the next hour because you don’t know how sick you’ll feel!!

…when the most excitement you’ve had in a month is your drs appt! And you’re looking forward to your next appt so you can get out of the house!!

…When the people who work in the lab great you like Norm on Cheers when you arrive.

…When you know which vein is the “sweet vein.”

Feel free to add your own! 🙂

Filed under: Cushing's, General Health, Rare Diseases | Tagged: , , , , | 1 Comment »

Misconceptions About Cushing’s

Posted on December 14, 2025 by MaryO

Cushing’s.  So many people are confused by what it is and what it isn’t.  They may have heard of it because a dog they know has it – or, these days, a horse, ferret, rat.  Seems it’s way more common in lots of animals but not people.

If people have heard of the “animal version” they might say “Yeah, my dog had that and it was easy to diagnose. We just gave him medication…”

When we first started having bios on the website, sometimes people would say that they had Cushions Disease.  At first I wondered about that but then it started to make more sense.  If you’ve never heard of the disease,  the doctor mumbles something.  You know you’re a little “fluffy” and cushions makes a lot of sense.

Twice in the last week I’ve seen Cushing’s described as Crushings Disease.  That sort of makes sense, too.  Cushing’s crushes your plans, relationships, credibility, pretty much everything.

Other misconceptions involve Cushing’s symptoms.  Others, especially doctors, will see you gain weight and assume you’re eating too much and a good diet will fix everything.  Or see that you’re depressed (who wouldn’t be!) and offer anti-depressants.

Doctors may say that Cushing’s is too rare, that they’ll never see a case of it in their practice.  But rare doesn’t mean that no one gets it.  Rare doesn’t mean that doctors shouldn’t test for it.

Then, the anatomy just isn’t right.  People say that they have a brain tumor instead of a pituitary tumor.  I just read this on another site: The pituitary gland is on the bottom of the brain… Umm – not exactly ON the bottom of the brain but maybe close enough for people to get an idea.

What sorts of things about Cushing’s/Cushions/Crushings that just weren’t quite right?

Filed under: Cushing's, Rare Diseases | Tagged: , , , , , , | 1 Comment »

Diabetic Ketoacidosis as the First Manifestation of Ectopic Cushing’s Syndrome

Posted on December 9, 2025 by MaryO

Abstract

Diabetic ketoacidosis is an exceptionally rare initial manifestation of ectopic adrenocorticotropic hormone (ACTH) syndrome. A 42-year-old woman with multiple cardiovascular risk factors was admitted to the emergency room with diabetic ketoacidosis. During stabilization, florid Cushing’s syndrome was suspected and confirmed biochemically as ACTH-dependent. Further biochemical and imaging surveys led to the diagnosis of a 25×15 mm nodule in the lingula. Thoracic surgery was performed, and pathology revealed a neuroendocrine tumor positive for ACTH.

We reviewed eight additional cases of diabetic ketoacidosis associated with Cushing’s syndrome from PubMed. Clinicians should bear in mind this etiology of diabetic ketoacidosis based on clinical signs and younger patients with multiple, age-atypical comorbidities. This would permit the expedited targeted stabilization of Cushing’s syndrome and the suitable institution of the diagnostic approach and treatment for this challenging syndrome.

Introduction

Endogenous Cushing’s syndrome (CS) is a rare disease resulting from pathological glucocorticoid excess of neoplastic origin, with an annual incidence of two/three cases per 1.000.000 inhabitants [1]. The severity of CS varies widely from mild to severe and, if left untreated, can be fatal due to the increased risk of cardiovascular events and opportunistic infections. Endogenous CS is classified as adrenocorticotropic hormone (ACTH)-dependent (80%) and -independent (20%) forms. ACTH-dependent CS is further divided into Cushing’s disease (68%) when the pituitary is the source of excess ACTH, or ectopic ACTH syndrome (EAS; 12%) when the cause is a non-pituitary neoplasia of neuroendocrine origin. EAS has an annual incidence of one case per 1.250.000 inhabitants and is more frequent in men [1]. It can be secondary to an aggressive small-cell lung carcinoma (19%), but the majority of cases arise from indolent lesions such as bronchial and thymic (combined: 33%) or pancreatic (12%) neuroendocrine tumors (NET) [1-3]. These indolent lesions usually evolve clinically over 6 to 24 months, whereas carcinomas have a faster onset. Symptoms and signs of excess cortisol in EAS are usually indistinguishable from Cushing’s disease. The most discriminatory signs of CS are plethora, purplish striae, proximal myopathy, and spontaneous ecchymosis. Multiple vascular risk factors, namely, hypertension, diabetes mellitus (DM), dyslipidemia, and obesity (especially central adiposity), occurring in a young patient, should also raise suspicion for CS [2]. Diabetic ketoacidosis (DKA) as the inaugural presentation of CS is very rare [1-3]. We searched through PubMed and reviewed articles in English where this association was reported using keywords such as “Cushing’s syndrome”, “Diabetic ketoacidosis”, “hypercortisolism”, and “Ectopic ACTH syndrome”. CS presenting initially with DKA is, as to this day, limited to eight case reports [4-11]. The clinical recognition of this syndrome as a very rare etiology of DKA is of paramount importance, as it is usually severe and relates to sepsis and several biochemical, hematologic, and hemodynamic derangements that should be addressed expeditiously with targeted drugs [3].

Here, we describe a female patient with florid clinical EAS uncovered upon her admission to the Emergency Room (ER) due to DKA. We searched through PubMed and reviewed articles in English where this association was reported, using keywords such as “Cushing’s syndrome”, “Diabetic ketoacidosis”, “hypercortisolism”, and “Ectopic ACTH syndrome”.

This article was previously presented as a meeting abstract at the 2024 ENDO, The Endocrine Society Annual Meeting on June 3, 2024.

Case Presentation

A 42-year-old woman was admitted in June 2022 to the ER due to severe DKA and hypokalemia (Table 1) and mild coronavirus disease. Physical examination at initial presentation was also remarkable for grade 2 hypertension with hypertensive retinopathy. Florid Cushingoid features, including a “buffalo hump”, plethora, hirsutism, abdominal ecchymosis, and marked proximal limb sarcopenia were noted (Figure 1).

Patient's-Cushingoid-features
Figure 1: Patient’s Cushingoid features

The patient was transferred to the intensive care unit (ICU). A multimodal treatment plan was initiated, including intravenous insulin (total daily dose: 1.2U/Kg) as per the protocol for DKA, antihypertensives, and prophylactic doses of low-molecular-weight heparin. After resolution of DKA and hydroelectrolytic disturbances, a gasometric follow-up revealed metabolic alkalosis (pH 7.529). The patient was then able to report a six-month history of weight gain, secondary amenorrhea, impaired concentration and memory, ecchymoses, and proximal myopathy with frequent falls and dependency on relatives for daily life activities. No chronic diarrhea or flushing was reported. She also reported a fungal pneumonia, dyslipidemia, and hypertension in the last four months, and a diagnosis of DM treated with metformin two weeks before her admission to the ER. Family history was unremarkable. Biochemical surveys (Table 1) revealed ACTH-dependent hypercortisolism, low thyroid-stimulating hormone (TSH), and hypogonadotropic hypogonadism. High-dose dexamethasone suppression (HDDS) and corticotropin-releasing hormone (CRH) stimulation tests were not suggestive of a pituitary source of ACTH (Table 1). Pituitary magnetic resonance imaging was normal. While waiting for further investigations regarding the source of excess ACTH, the patient was started on 750 mg/day of metyrapone in three divided doses. The patient was started and discharged from the ward with hydrocortisone 10 mg in the morning and 5 mg at midday and in the afternoon. The dose of metyrapone was carefully adjusted during two months according to morning serum cortisol, but was rapidly decreased and stopped due to spontaneous clinical resolution of CS. In the postoperative follow-up (total: 23 months), Cushingoid features (plethora, dorsal fat pad, ecchymosis, central adiposity) continued to disappear, and she regained muscle mass and independence in her daily activities and remission from all glucocorticoid related-comorbidities was maintained (fasting glucose: 91 mg/dL; glycated hemoglobin (HbA1c): 5.8%; low-density lipoprotein (LDL) cholesterol: 138 mg/dL; triglycerides: 80 mg/dL). Twelve months after surgery, the patient was able to discontinue hydrocortisone upon biochemical evidence of restoration of adrenal function (cortisol peak at Synacthen test: 21.1 ug/dL; basal ACTH: 15.6 pg/mL). Her last (23 months after surgery) endocrine surveys (midnight salivary cortisol: 0.14 ug/dL; ACTH: 18 pg/mL) and thoracic CT showed no evidence of disease relapse.

Parameter Presentation 12-month follow-up Reference
Hemoglobin (g/dL) 12.8 – 12-15.5
White blood count (×103/uL) 11.3 – 4.0-11.5
Platelets (×103/uL) 331 – 150-400
Fasting blood glucose (mg/dL) 427 76 74-106
HbA1c (%) 9.6 5.6 <6.5
Serum sodium (mmol/L) 146 – 135-145
Serum potassium (mmol/L) 2.7 – 3.5-5.1
Serum creatinine (mg/dL) 0.32 0.59 0.67-1.17
pH 7.17 – 7.35-7.45
HCO3– (mmol/L) 4.4 – 21-26
Anion gap 35 – 7
IGF-1 (ng/mL) 89.8 – 77-234
FSH (mUI/mL) 0.9 –¥ 3.5-12.5
LH (mUI/mL) <0.1 –¥ 2.4-12.6
Prolactin (ng/mL) 8.8 – 4.0-24.3
TSH (UI/mL) 0.02 0.61 0.35-4.94
Free T4 (ng/dL) 1.26 1.02 0.7-1.48
Midnight salivary cortisol (ug/dL) 25.5 2.4* <7.5
UFC (ug/dL) 1072.5 74.5* <176
Cortisol at 1 mg overnight DST (ug/dL) 25.7 – <1.8
Cortisol, baseline (ug/dL) 30.9 11.4* 5-18
Cortisol after HDDS test (ug/dL) 42.1 – Refer to reference 2
ACTH, baseline (pg/mL) 93.4 22.1* 7.2- 63.3
ACTH, maximum after CRH (pg/mL) 101.8 – Refer to reference 2
Table 1: Biochemical surveys of the patient at baseline and at the 12-month follow-up

* After metyrapone washout

¥ Gonadotropins not repeated due to resumption of regular menses

Abbreviations: ACTH, adrenocorticotropic hormone; CRH, corticotropin-releasing hormone; DST, dexamethasone suppression test; FSH, follicle-stimulating hormone; HbA1c, hemoglobin A1c; HDDS, high-dose dexamethasone suppression; IGF-1, insulin-like growth factor type 1; LH, luteinizing hormone; TSH, thyroid-stimulating hormone; UFC, urinary free cortisol

She was referred for inferior petrosal sinus sampling (IPSS) but it was postponed for several months due to healthcare strikes. While waiting for IPSS, she performed a thoracic computerized tomography (CT) scan to exclude EAS, which revealed thymic hyperplasia and a 25×15 mm, well-defined nodule in the lingula (Figure 2).

Thoracic-CT-scan-revealed-a-25x15-mm,-well-defined-nodule-in-the-lingula
Figure 2: Thoracic CT scan revealed a 25×15 mm, well-defined nodule in the lingula

A 68Ga-DOTANOC positron emission tomography-computed tomography (PET/CT) was then performed and showed a single uptake in the same lung region (Figure 3).

68Ga-DOTANOC-PET/CT-showing-a-single-uptake-in-the-lingula.
Figure 3: 68Ga-DOTANOC PET/CT showing a single uptake in the lingula.

Abbreviations: PET/CT, positron emission tomography-computed tomography

The patient was referred to thoracic surgery and underwent lingulectomy plus excisional biopsy of the interlobar lymph nodes. Pathology revealed a typical carcinoid/neuroendocrine tumor (NET), grade one (Ki67<2% and <2 mitosis per high-power field (HPF)) without involved lymph nodes, which showed positivity for ACTH (Figure 4).

Immunohistochemistry-findings
Figure 4: Immunohistochemistry findings

a- hematoxylin and eosin x400 magnification, b- synaptophysin x100 magnification, c- chromogranin A x400 magnification, d- ACTH x400 magnification, e- Ki-67 x100 magnification.

The patient was started on hydrocortisone 10 mg in the morning and 5 mg at midday and afternoon, which was discontinued 11 months later due to restoration of adrenal function (cortisol peak at Synacthen test: 21.1 ug/dL; basal ACTH: 15.6 pg/mL). In the postoperative follow-up, Cushingoid features continued to disappear, and she regained muscle mass and independence in her daily activities. Her last CT showed no evidence of disease.

Discussion

Severe CS (SCS) is defined by random serum cortisol above 41 ng/dL and/or a urinary free cortisol (UFC) more than fourfold the upper limit of normal and/or severe hypokalemia (<3.0 mmol/L), along with the recent onset of one or more of the following: sepsis, opportunistic infection, refractory hypokalemia, uncontrolled hypertension, edema, heart failure, gastrointestinal bleeding, glucocorticoid-induced acute psychosis, progressive debilitating myopathy, thromboembolism, uncontrolled hyperglycemia and ketoacidosis [3]. SCS results in high morbidity and mortality, requiring a rapid recognition and targeted therapy of the uncontrolled hypercortisolism [3]. Patients with SCS usually have florid signs, and straightforward clinical suspicion is possible, except in cases of ECS due to small-cell lung carcinoma, where the rapid onset of hypercortisolism and related morbidity precedes the development of clinical stigmata [2,3]. The gasometric parameters in DKA associated with SCS can also provide clues for the presence of CS. The mineralocorticoid effect of excess cortisol leads to metabolic alkalosis through increased hydrogen excretion in the distal nephron, which is masked by metabolic acidosis due to excess β-hydroxybutyrate and acetoacetate [6,12,13]. This mixed acid-basic disorder can be suspected by a ratio of ∆anion gap to ∆HCO3 of higher than one, which is not seen in pure metabolic acidosis. Additionally, after treating the DKA by decreasing ketones through the inhibition of its production by insulin and increased renal excretion with improved renal perfusion, metabolic alkalosis may supervene in gasometric monitoring, as seen in our report and others [6,9]. In rare cases, SCS can also lead to diabetic ketoalkalosis instead of DKA [1]. Several factors may contribute to the predominant alkalosis, namely, decreased hydrogen due to high renal excretion (excess mineralocorticoid effect), intracellular shift (due to severe hypokalemia), gastrointestinal losses (vomiting), and hyperventilation due to pulmonary diseases (as in heavy smokers) [13,14].

The main priorities in managing SCS are to control opportunistic infections, hypokalemia, DM, hypertension, and psychosis, and, importantly, investigations of the etiology of CS should be postponed until clinical stabilization [3]. The control of glucocorticoid-induced complications should encompass therapies to stabilize/reverse the CS induced morbidity (e.g., large-spectrum antibiotics for opportunistic infections; spironolactone for hypokalemia; insulin for DM) followed by targeted treatment of hypercortisolism [3]. Several oral adrenolytic agents are available and have proved their usefulness in SCS, namely, metyrapone (onset: hours; UFC normalization: 83%), ketoconazole/levoketoconazole (onset: days; UFC normalization: 70-81%), osilodrostat (onset: hours; UFC normalization: 82%), and mitotane (onset: days to weeks; UFC normalization: 72-82%). They can be used in monotherapy or in combination therapy, the latter strategy increasing the efficacy with lower doses of drugs and a lower risk of side effects [3,14]. Additionally, as first-line therapy for patients with an unavailable oral route (e.g., glucocorticoid-induced psychosis), or as second-line therapy when other adrenolytic agents have failed to control hypercortisolism, the anesthetic etomidate can be used under multidisciplinary supervision in an ICU, and it is highly effective (~100%) in controlling SCS within hours, in doses that do not induce anesthesia [3]. If medical therapy proves unsuccessful, bilateral adrenalectomy may be considered after careful clinical judgement, as it is highly effective in life-threatening SCS uncontrolled by medical therapy. Nevertheless, all attempts should be made to reduce hypercortisolemia with medical therapy before surgery [3].

DKA, as the inaugural presentation of CS, was previously published in eight case reports [4-11] (Table 2). Briefly, and including our case, almost all reports were severe (77.8%), mainly from EAS (55.6%) or pituitary adenomas (33.3%), and with a female preponderance (77.8%).

Reference Gender Age Florid CS signs Severe CS Etiology of CS Definitive treatment
Uecker JM, et al. [4] Female 43 Yes Yes EAS (duodenal NET) Pancreaticoduodenectomy
Kahara T, et al. [5] Male 53 No No ACTH-independent Adrenalectomy
Weng Y, et al. [6] Female 28 Yes Yes Cushing’s disease (macroadenoma) Transsphenoidal surgery
Catli G, et al. [7] Female 16 Yes Yes Cushing’s disease (microadenoma) Transsphenoidal surgery
Sakuma I, et al. [8] Female 56 Yes Yes EAS (pheochromocytoma) Adrenalectomy
Achary R, et al. [9] Female 48 Yes Yes Cushing’s disease (microadenoma) Transsphenoidal surgery
Cheong H, et al. [10]* Female 22 Unknown Unknown EAS (medullary thyroid carcinoma) None
Shangjian L, et al. [11] Male 46 Unknown Yes EAS (pheochromocytoma) Adrenalectomy
Our case Female 42 Yes Yes EAS (bronchial NET) Thoracic surgery
Table 2: Review of published cases of DKA as the inaugural presentation of CS

*Deceased

Abbreviations: ACTH, adrenocorticotropic hormone; CS, Cushing’s syndrome; EAS, ectopic ACTH syndrome; NET, neuroendocrine tumor

The etiology of CS should be investigated in diagnostic steps. After confirming hypercortisolism (low-dose dexamethasone suppression test, UFC, and/or late-night salivary cortisol) and its ACTH dependence (usually well above 20 pg/mL in EAS), the source of excess ACTH should be pursued. The CRH test is the most accurate dynamic test to distinguish between pituitary and ectopic sources of ACTH, followed by the desmopressin and HDDS tests. The combination of CRH and HDDS tests has an accuracy close to the IPSS, the gold standard to distinguish pituitary from ectopic sources of ACTH. If the investigation approach points to EAS, the most accurate exam to detect a lesion is 68Ga-DOTA-somatostatin analogue PET/CT, followed by 18F-FDG PET and conventional cross-sectional imaging [1-3].

After being discharged from the ward, our patient showed spontaneous resolution of hypercortisolism requiring the withdrawal of metyrapone and all medications to control glucocorticoid-induced morbidity, suggesting cyclic CS. This very rare variant of CS is present when periods of hypercortisolism alternate with periods of normal cortisol secretion, each phase lasting from days to years, which makes this type of CS very challenging to manage. The pituitary is the main source of cyclic CS, followed by EAS and, infrequently, the adrenal gland. The criteria of three peaks and two periods of normal or low cortisol levels needed to diagnose cyclic CS were not seen in the follow-up period of our patient, as after one peak and trough, we found and removed the source of EAS [1].

Conclusions

In the context of DKA, florid Cushing signs and multiple vascular risk factors occurring in a young patient should raise suspicion for Cushing’s Syndrome. The severity of this syndrome varies widely from mild to severe and, if left untreated, can be fatal due to the increased risk of cardiovascular events and opportunistic infections. Diabetic ketoacidosis precipitated by an endogenous excess of glucocorticoid is usually associated with severe Cushing’s syndrome and more frequently with EAS, which can have an abrupt onset. Prompt recognition and targeted stabilization of severe Cushing’s syndrome are crucial and should precede a definitive etiologic investigation.

References

  1. 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
  2. Hayes AR, Grossman AB: Distinguishing Cushing’s disease from the ectopic ACTH syndrome: needles in a haystack or hiding in plain sight?. J Neuroendocrinol. 2022, 34:e13137. 10.1111/jne.13137
  3. Alexandraki KI, Grossman AB: Therapeutic strategies for the treatment of severe Cushing’s syndrome. Drugs. 2016, 76:447-58. 10.1007/s40265-016-0539-6
  4. Uecker JM, Janzow MT: A case of Cushing syndrome secondary to ectopic adrenocorticotropic hormone producing carcinoid of the duodenum. Am Surg. 2005, 71:445-6.
  5. Kahara T, Seto C, Uchiyama A, et al.: Preclinical Cushing’s syndrome resulting from adrenal black adenoma diagnosed with diabetic ketoacidosis. Endocr J. 2007, 54:543-51. 10.1507/endocrj.k06-071
  6. Weng YM, Chang MW, Weng CS: Pituitary apoplexy associated with cortisol-induced hyperglycemia and acute delirium. Am J Emerg Med. 2008, 26:1068.e1-3. 10.1016/j.ajem.2008.03.023
  7. Catli G, Abaci A, Tanrisever O, Kocyigit C, Sule Can P, Dundar BN: An unusual presentation of pediatric Cushing disease: diabetic ketoacidosis. AACE Clinical Case Reports. 2015, 1:53-8. 10.4158/EP14284.CR
  8. Sakuma I, Higuchi S, Fujimoto M, et al.: Cushing syndrome due to ACTH-secreting pheochromocytoma, aggravated by glucocorticoid-driven positive-feedback loop. J Clin Endocrinol Metab. 2016, 101:841-6. 10.1210/jc.2015-2855
  9. Acharya R, Kabadi UM: Case of diabetic ketoacidosis as an initial presentation of Cushing’s syndrome. Endocrinol Diabetes Metab Case Rep. 2017, 2017:10.1530/EDM-16-0123
  10. Cheong H, Koo HL: Medullary thyroid carcinoma with diabetic ketoacidosis: an autopsy case report and literature review. Forensic Sci Med Pathol. 2021, 17:711-4. 10.1007/s12024-021-00407-8
  11. Li S, Guo X, Wang H, Suo N, Mi X, Jiang S: Ectopic adrenocorticotropic hormone-secreting pheochromocytoma with severe metabolic disturbances: a case report. Int J Surg Case Rep. 2024, 116:109341. 10.1016/j.ijscr.2024.109341
  12. Kraut JA, Madias NE: Serum anion gap. Its uses and limitations in clinical medicine. Clin J Am Soc Nephrol. 2007, 2:162-74. 10.2215/CJN.03020906
  13. Uwaifo G, Varughese AG: ODP245 Syndrome of diabetic ketoalkalosis due to severe hypercortisolemia: a case series. J Endocr Soc. 2022, 6:A334. 10.1210/jendso/bvac150.693
  14. Nieman LK, Biller BM, Findling JW, Murad MH, Newell-Price J, Savage MO, Tabarin A: Treatment of Cushing’s syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015, 100:2807-31. 10.1210/jc.2015-1818

From https://www.cureus.com/articles/426071-diabetic-ketoacidosis-as-the-first-manifestation-of-ectopic-cushings-syndrome#!/

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

Adrenal Cushing’s Syndrome in Pregnancy Complicated by Fetal Growth Restriction Following Retroperitoneoscopic Adrenalectomy

Posted on December 7, 2025 by MaryO

Abstract

A 29-year-old Japanese pregnant woman, G5P3A1, conceived spontaneously and was referred to our hospital because of uncontrolled hypertension at 24 weeks of gestation. On admission, she presented with physical findings characteristic of Cushing’s syndrome (CS), such as moon face, buffalo hump, and reddish-purple striae. Laboratory examination revealed hyperglycemia and hypercortisolism with suppressed adrenocorticotropic hormone levels. Imaging studies revealed a right adrenocortical adenoma, and the patient was clinically diagnosed with adrenal CS. At 28 weeks, she underwent retroperitoneoscopic adrenalectomy, which normalized maternal cortisol levels and improved metabolic abnormalities. Despite these improvements, she was diagnosed with fetal growth restriction accompanied by superimposed preeclampsia at approximately 33 weeks. The maternal serum soluble fms-like kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio was markedly elevated. At 36 weeks, an emergency cesarean section was performed for fetal compromise, resulting in the delivery of a small-for-gestational-age infant. Histopathological examination of the placenta revealed ischemic changes consistent with placental insufficiency. Both the mother and infant were discharged in stable conditions. The present case shows that although adrenalectomy during pregnancy can correct endocrine abnormalities, it does not necessarily prevent subsequent fetal growth restriction.

Introduction

Cushing’s syndrome (CS) is an endocrine disorder caused by chronic hypercortisolism. Because cortisol can disrupt ovulation, leading to menstrual irregularities and infertility [1,2], pregnancy in women with CS is exceedingly rare. Moreover, diagnosis during pregnancy is particularly challenging as many hallmark features of hypercortisolism – fatigue, weight gain, acne, and mood instability – are common in normal pregnancies.

Untreated CS during gestation is associated with substantially increased maternal and perinatal morbidity and mortality. Aggressive management during gestation, including cortisol synthesis inhibitors or surgical resection of pituitary adenomas or adrenal tumors, has been shown to improve maternal and fetal outcomes [3-5]. However, intensive treatment may not fully reduce the risks of fetal growth restriction and preterm delivery [5,6], and the underlying reason for this remains unclear.

Herein, we report a case of adrenal CS in a pregnant woman who underwent retroperitoneoscopic adrenalectomy at 28 weeks of gestation. Despite achieving biochemical remission of hypercortisolism after surgery, she developed fetal growth restriction and required preterm cesarean delivery due to fetal compromise.

This article was previously presented as a meeting abstract at (1) the 97th Annual Congress of the JES on June 7, 2024; (2) the 60th Annual Congress of JSPNM on July 15, 2024; and (3) the 47th Annual Meeting of JSGOS on November 24, 2024.

Case Presentation

A 29-year-old Japanese woman with a G5P3A1 conceived spontaneously. She had no medical history other than asthma and no particular familial history. She began receiving antenatal care at a nearby facility during the first trimester. She did not undergo screening tests for predicting the development of preeclampsia (PE), such as the first-trimester ultrasound at 11-14 weeks or pregnancy-associated plasma protein A assessment. Her casual blood glucose level was 87 mg/dL at 10+6 weeks of gestation. Initially, she was normotensive, but her blood pressure gradually increased to 144/100 mmHg at 18 weeks of gestation, and diagnosed as having chronic hypertension. Thereafter, her hypertension worsened, reaching 177/100 mmHg at 21 weeks of gestation, and she was diagnosed with superimposed PE. Around the same time, her body weight increased by 11.5 kg from the pre-pregnancy weight (from 58.5 kg to 70 kg), and generalized edema developed. As a result, she was admitted to the referring hospital and started taking antihypertensive treatment with oral methyldopa 750 mg/day, which lowered her blood pressure to a range of 130-150/80-100 mmHg, decreased her body weight to 66.5 kg, and improved the generalized edema. Although she was discharged from the hospital, her blood pressure increased again; thus, she was transferred to our institution, a tertiary referral perinatal medical center, at 24+6 weeks of gestation for subsequent perinatal management.

At her initial visit, her height and body weight were 153 cm and 66.2 kg, respectively. Her vital signs were as follows: body temperature 36.0℃, blood pressure 159/115 mmHg with the use of antihypertensive medication, and heart rate 80/min. She had an obvious full-moon face, acne vulgaris (Figure 1A), a buffalo hump, and reddish-purple striae on her abdomen and thighs (Figures 1B, 1C). She also had bilateral pitting edema in her lower legs and thin skin on the backs of her hands. No anemic palpebral conjunctiva, cervical lymphadenopathy, or thyroid enlargement was observed.

Macroscopic-findings-characteristic-of-Cushing’s-syndrome
Figure 1: Macroscopic findings characteristic of Cushing’s syndrome

(A) Moon face, (B) reddish-purple striae

on abdomen, and (C) reddish-purple striae on thighs.

An increased neutrophil count and decreased eosinophil count were observed, although the white blood cell count was within the normal range (Table 1). Biochemical analysis showed that the serum potassium level was decreased (2.3 mEq/L). The serum total protein, albumin, blood urea nitrogen, and cholinesterase levels were mildly decreased. Renal function, hepatic function, and lipid profiles were within normal limits, except for elevated triglyceride levels. A spot urine test indicated an elevated urine protein-to-creatinine ratio (0.436 g/gCr) (Table 2). Regarding diabetes-related tests, fasting plasma glucose (91 mg/dL), glycated hemoglobin (HbA1c) (5.4%), and glycated albumin (GA) (12.9%) were all within their normal ranges. The serum C-peptide level was elevated. A 75 g oral glucose tolerance test (OGTT) conducted at 25+4 weeks of gestation showed serum glucose levels of 191 mg/dL at one hour and 212 mg/dL at two hours (Table 2), indicating postprandial hyperglycemia. Endocrinological evaluation revealed elevated morning serum cortisol levels with loss of diurnal variation. This hypercortisolism is accompanied by suppressed plasma adrenocorticotropic hormone (ACTH) levels (Table 3). The 24-hour urinary free cortisol (UFC) level was markedly elevated (1,380 μg/day). In contrast, dehydroepiandrosterone sulfate (DHEA-S) levels decreased. Serum thyroid-stimulating hormone (TSH) was markedly decreased (0.091 IU/mL), accompanied by mild reductions in free T3 (1.65 pg/mL) and free T4 (0.65 ng/dL), which indicated central hypothyroidism. Abdominal ultrasonography revealed a nodule in the right adrenal gland with a maximum diameter of approximately 30 mm (28 × 27 × 25 mm) (Figure 2A). Abdominal magnetic resonance imaging (MRI) detected a 27-mm well-defined nodular lesion at the same location, which demonstrated a signal drop on opposed-phase images (Figure 2B). Obstetric ultrasonography revealed an estimated fetal body weight of 742 g (adequate for gestational age) (Figures 3A–3C), an amniotic fluid index of 16.4 cm (Figure 3D), and no major structural anomalies of the fetus. From the day of referral, oral nifedipine (40 mg/day) was initiated as antihypertensive therapy. Potassium chloride (KCl) was administered orally.

Parameter Test value Reference range
CBC
WBC 8.1×109/L 3.3-8.6 ×109/L
Neut 83.5% 38.5-80.5%
Lymph 10.5% 16.5-49.5%
Mono 5.8% 2.0-10%
Eosino 0.1% 0.0-8.5%
RBC 3.17×1012/L 3.86-4.92 ×1012/L
Hb 11.5 g/dL 11.4-16.8 g/dL
Plt 190×109/L 158-348 ×109/L
Serum Biochemistry
TP 5.7 g/dL 6.6-8.1 g/dL
Alb 3.3 g/dL 4.1-5.1 g/dL
T-Bil 1 mg/dL 0.4-1.5 mg/dL
AST 15 U/L 13-30 U/L
ALT 27 U/L 7-23 U/L
LDH 326 U/L 124-222 U/L
ALP 55 U/L 38-113 U/L
γ-GTP 29 U/L 9-32 U/L
Na 146 mEq/L 138-145 mEq/L
K 2.3 mEq/L 3.6-4.8 mEq/L
Cl 107 mEq/L 101-108 mEq/L
Ca 8.5 mg/dL 8.8-10.1 mg/dL
P 2.1 mg/dL 2.7-4.6 mg/dL
BUN 6 mg/dL 8-20 mg/dL
UA 3.4 mg/dL 2.6-5.5 mg/dL
Cr 0.45 mg/dL 0.46-0.79 mg/dL
CRP 0.1 mg/dL 0-0.14 mg/dL
HDL-C 66 mg/dL 48-103 mg/dL
LDL-C 134 mg/dL 65-163 mg/dL
TG 211 mg/dL 30-117 mg/dL
FPG 91 mg/dL 73-109 mg/dL
HbA1c 5.4% 4.9-6.0%
GA 12.9% 12.3-16.5%
C-peptide 3.7 ng/mL 0.6-1.8 ng/mL
Endocrinology
Adrenaline <0.01 ng/mL <0.17 ng/mL
Noradrenaline 0.09 ng/mL 0.15-0.57 ng/mL
Dopamine <0.02 ng/mL <0.03 ng/mL
Cortisol 24.7 μg/dL 3.7-19.4 μg/dL
Aldosterone <4.0 pg/mL 4.0-82.1 pg/mL
Renin activity 0.7 ng/mL/hr 0.2-3.9 ng/mL/hr
DHEA-S 43 μg/dL 92-399 μg/dL
TSH 0.091 IU/mL 0.350-4.940 IU/mL
FT3 1.65 pg/mL 1.68-3.67 pg/mL
FT4 0.65 ng/dL 0.70-1.48 ng/dL
Table 1: Laboratory data of CBC, serum biochemistry, and endocrinology

CBC: complete blood count, WBC: white blood cell count, Neut: neutrophil, Lymph: lymphocyte, Mono: monocyte, Eosino: eosinophil, RBC: red blood cell count, Hb: hemoglobin, Plt: platelet count, TP: total protein, Alb: albumin, T-Bil: total bilirubin, AST: aspartate aminotransferase, ALT: alanine aminotransferase, LDH: lactate dehydrogenase, ALP: alkaline phosphatase, γ-GTP: gamma-glutamyl transpeptidase, Na: sodium, K: potassium, Cl: chloride, Ca: calcium, P: phosphorus, BUN: blood urea nitrogen, UA: uric acid, Cr: creatinine, CRP: C-reactive protein, HDL-C: high-density lipoprotein cholesterol, LDL-C: low-density lipoprotein cholesterol, TG: triglyceride, FPG: fasting plasma glucose, HbA1c: hemoglobin A1c, GA: glycated albumin, C-peptide: connecting peptide, DHEA-S: dehydroepiandrosterone sulfate, TSH: thyroid-stimulating hormone, FT3: free triiodothyronine, FT4: free thyroxine

Parameter Test value
75-g OGTT
PG
0 min 91 mg/dL
30 min 153 mg/dL
60 min 191 mg/dL
90 min 204 mg/dL
120 min 225 mg/dL
IRI
0 min 10.8 μU/mL
30 min 29.3 μU/mL
60 min 48.7 μU/mL
90 min 64.6 μU/mL
120 min 91.2 μU/mL
Urinalysis
U-Cr 39 mg/dL
U-TP 17 mg/dL
U-TP/Cr 0.436 g/gCr
Table 2: Laboratory data of 75-g OGTT and urinalysis

OGTT: oral glucose tolerance test, PG: plasma glucose, IRI: immunoreactive insulin, U-Cr: urinary creatinine, U-TP: urinary total protein

Parameter Test value Reference range
ACTH/F diurnal rhythm
ACTH
6:00 AM 2.1 pg/mL 7.2-63.3 pg/mL
4:00 PM 2.0 pg/mL 7.2-63.3 pg/mL
11:00 PM 2.3 pg/mL 7.2-63.3 pg/mL
F
6:00 AM 24.7 μg/dL 3.7-19.4 μg/dL
4:00 PM 25 μg/dL 3.7-19.4 μg/dL
11:00 PM 25.8 μg/dL 3.7-19.4 μg/dL
Table 3: Laboratory data of ACTH/F diurnal rhythm

ACTH: adrenocorticotropic hormone, F: cortisol

Radiological-findings-of-the-right-adrenal-tumor-(white-arrow)
Figure 2: Radiological findings of the right adrenal tumor (white arrow)

(A) Trans-abdominal ultrasonography image and (B) coronal section of the trunk on MRI.

Obstetric-ultrasonography
Figure 3: Obstetric ultrasonography

(A) The plane used for biparietal diameter measurement, (B) the plane used for abdominal circumference measurement, (C) the plane used for femoral length measurement, and (D) the plane used for amniotic fluid index measurement.

Physical examination revealed typical signs of CS, such as a moon face, buffalo hump, and reddish-purple striae. In addition, laboratory findings showed elevated UFC, increased nocturnal serum cortisol levels (>5.0 μg/dL), and suppressed ACTH levels (<5.0 pg/mL). On the basis of these findings, the patient was diagnosed with ACTH-independent CS. Furthermore, imaging studies identified a right adrenal mass, leading to a final diagnosis of CS caused by a right adrenal tumor. Both central hypothyroidism and impaired glucose tolerance were considered secondary complications, primarily caused by hypercortisolemia due to CS. The serum potassium level was maintained at approximately 3.0 mEq/L after the administration of oral KCl. An increase in the nifedipine dose from 20 mg/day to 40 mg/day stabilized the blood pressure at approximately 140/90 mmHg (Figure 4A). Intensive insulin therapy with insulin lispro was initiated on hospital day 4 (Figure 4B), and the insulin dosage was gradually increased for postprandial hyperglycemia. The maximum insulin dose was 41 units/day on day 23 of hospitalization. Throughout this period, the UFC levels remained persistently elevated (Figure 4C).

Clinical-course-between-hospitalization-and-cesarean-delivery
Figure 4: Clinical course between hospitalization and cesarean delivery

(A) Blood pressure trend, (B) total dose of insulin, and (C) urinary free cortisol trend.

A clinical team of obstetricians, urologists, and endocrinologists discussed the treatment plans for CS and perinatal management. Pharmacological treatment had two problems: radicality and risk of fetal adrenal insufficiency due to placental passage of medication; therefore, we decided to perform adrenalectomy during pregnancy. At 28+3 weeks of gestation, a retroperitoneoscopic adrenalectomy was performed by urologists. After the induction of general anesthesia, the patient lay on the bed in a complete left lateral position (Figures 5A, 5B). Consequently, the endoscope and instrument ports were placed in the same configuration as those used in the conventional retroperitoneal approach for nonpregnant patients. Port placements were planned guided by abdominal ultrasonography to identify the uterine position, and the assistant port was positioned at a location that minimized potential interference with the uterus. The surgery was completed without complications. The operative time was 83 minutes, and bleeding was minimal. Histopathological examination indicated that the tumor was an adrenocortical adenoma (Figures 6A–6C).

Photograph-showing-the-patient-in-the-left-lateral-decubitus-position-after-general-anethesia
Figure 5: Photograph showing the patient in the left lateral decubitus position after general anethesia

(A) Abdominal area and (B) dorsal area.

Histopathological-findings-of-the-right-adrenal-gland-(A,-B,-C)-and-placenta-(D)
Figure 6: Histopathological findings of the right adrenal gland (A, B, C) and placenta (D)

(A) Macroscopic view of the right adrenal gland showing the normal adrenal tissue (black asterisk) and the adrenal tumor (white asterisk). (B, C) Microscopic findings of the right adrenal gland and tumor (H&E staining).

(B) Normal adrenal gland (black asterisk) and adrenal tumor (white asterisk) separated by a thin fibrous capsule (black arrow).

(C) Tumor cells with abundant eosinophilic to clear cytoplasm arranged in a trabecular to microacinar growth pattern.

(D) Microscopic findings of the placenta (H&E staining) showing fibrin deposition within villous vessels (black arrow) and chorionic villi with loss of nuclear detail and crowding (black asterisk).

After surgery, the maternal glucose tolerance rapidly improved, and intensive insulin therapy with insulin lispro became unnecessary (Figure 4B). To avoid postoperative adrenal insufficiency, replacement therapy with hydrocortisone was initiated at 200 mg/day immediately after surgery, and the dosage was gradually tapered to 25 mg/day before delivery (Figure 4C). Maternal thyroid function normalized two weeks after surgery. At 29 weeks of gestation, oral nifedipine (40 mg/day) was stopped and blood pressure was monitored; however, high blood pressure was sustained. Therefore, oral nifedipine was resumed at 20 mg/day at 31 weeks of gestation. At approximately 33 weeks of gestation, the fetus exhibited slow growth, leading to a diagnosis of fetal growth restriction. The levels of serum soluble fms-like kinase 1 (sFlt-1)/placental growth factor (PlGF) were 173 (7990/46.1) at 33+0, 299 (11600/38.9) at 34+1, and 316 (15200/48.1) at 35+5 weeks. Trends in the estimated fetal body weight and standard deviation are shown in Figure 7. At 36+1 weeks of gestation, cardiotocography revealed severely prolonged deceleration regardless of the absence of uterine contraction, and an emergency cesarean section was performed. A male infant weighing 1,726 g and 41 cm in height, diagnosed as small for gestational age, was born with Apgar scores of 8 at one minute and 9 at five minutes. The umbilical arterial pH was 7.36. The size and weight of the placenta were 14.7 × 12.8 × 3.0 cm and 315 g, respectively, and histopathological examination revealed findings consistent with ischemic infarction (Figure 6D). Antihypertensive drugs administered to the mother were discontinued on day 8. The mother and neonate were discharged on POD 20. The child achieved normal development at the age of two years.

Trends-in-estimated-fetal-body-weight-(EFBW)-and-standard-deviation-(SD)
Figure 7: Trends in estimated fetal body weight (EFBW) and standard deviation (SD)

Discussion

This case illustrates adrenal CS in pregnancy, complicated by the subsequent development of fetal growth restriction, despite retroperitoneoscopic adrenalectomy at 28 weeks of gestation. Notably, a markedly increased maternal serum sFlt-1/PlGF ratio was detected at the time of diagnosis of fetal growth restriction. To the best of our knowledge, this is the first case in which angiogenic markers were evaluated in a pregnant woman with adrenal CS.

The coexistence of CS and pregnancy is extremely rare [4]. The primary reason for this rarity is infertility, often caused by the hypercortisolism characteristic of CS. Specifically, hypercortisolism suppresses the hypothalamic-pituitary-gonadal axis, leading to impaired follicular development and anovulation by disrupting the secretion of gonadotropin-releasing hormone (GnRH) [1,7]. Pregnancy poses significant challenges in patients with ACTH-dependent CS, in whom excessive ACTH production is accompanied by androgen overproduction. As a result, adrenal etiologies of CS are more common than pituitary-dependent etiologies during pregnancy [3]. Several factors make it difficult to diagnose CS during pregnancy. First, the characteristic physical findings of CS closely mimic physiological changes in normal pregnancy. For example, weight gain, abdominal striae, and edema are common symptoms of both conditions. Therefore, this overlap can cause delayed diagnosis or misdiagnosis of CS during pregnancy [3]. It has been reported that 21.5% of pregnant women with CS are diagnosed only after delivery [3]. Second, physiological hormonal changes during pregnancy complicate the diagnostic process. During gestation, the placenta produces corticotropin-releasing hormone (CRH) and ACTH [8]. Additionally, elevated estrogen levels increase the synthesis of corticosteroid-binding globulin, resulting in a state of physiological hypercortisolism in pregnant women [9,10]. Consequently, the dexamethasone suppression test, which is key to the diagnosis of CS, is often unreliable in pregnant women because of the high incidence of false-positive results [4].

Despite these diagnostic hurdles, certain findings are highly valuable in identifying CS during pregnancy. First, careful examination of physical signs specific to CS, such as skin thinning and the presence of wide, reddish-purple striae, is crucial. Second, the evaluation of diurnal cortisol rhythms was informative. While this rhythm is preserved in normal pregnancy, it is characteristically absent in CS. Therefore, measuring late-night serum cortisol levels is useful for differentiating between these two states [11]. Third, a 24-hour UFC level exceeding three times the upper limit of normal for non-pregnant individuals is strongly suggestive of CS [4,7,9]. In the present case, these key features were decisive for the diagnosis. We found wide, reddish-purple striae, a loss of diurnal cortisol rhythm, and a markedly elevated 24-hour UFC level. Based on these findings, we definitively diagnosed the patient with CS complicating pregnancy.

According to a systematic review of 263 pregnancies complicated by CS, untreated pregnant women were significantly more likely to develop PE than those treated beforehand (26.5% vs. 2.3%) [3]. PE is characterized by defective placentation and impaired spiral artery remodeling, leading to placental ischemia during early pregnancy. Placental ischemia produces sFlt-1, a splice variant of Flt-1 that binds to vascular endothelial growth factor and PlGF and serves as a biochemical marker of endothelial dysfunction that inhibits angiogenesis [12]. Systemic endothelial dysfunction leads to maternal hypertension, proteinuria, and damage to other organs, including the placenta. In this case, placental histopathology indicated ischemic changes without retroplacental hematoma. In addition, a marked elevation of the sFlt-1/PlGF ratio – resulting from both increased sFlt-1 and decreased PlGF – was detected, supporting the presence of placental ischemia due to impaired placentation in early pregnancy.

In this case, several factors may have contributed to the placental ischemia. First, poor control of maternal hyperglycemia or hypertension may have played a role. As hyperglycemia is known to induce oxidative stress [13], it is possible that hyperglycemia in early pregnancy causes placental ischemia indirectly via oxidative stress. Recent studies suggest that hypertension in early pregnancy may contribute to impaired placentation, thereby increasing the risk of subsequent superimposed PE [14,15]. Therefore, chronic hypertension associated with CS may also be related to placental ischemia, although the maternal outpatient blood pressure was within the normal range during early pregnancy in the present case. Second, chronic hypercortisolemia can directly contribute to abnormal placentation. Previous animal experiments have shown that elevated maternal serum cortisol levels enhance uterine arterial contractions [16], which may induce placental ischemia. Furthermore, chronic hypercortisolism may exceed the protective capacity of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which shields the fetus from excessive cortisol, thereby directly affecting the fetus [17]. Based on these findings, it is presumed that irreversible placental damage had already occurred at the time of the surgical resection in this case. Preconceptional or at least early diagnosis and treatment of CS are crucial for preventing fetal growth restriction associated with superimposed PE after surgery.

The second trimester is generally considered the optimal period for adrenalectomy in pregnant patients with adrenal CS [18]; however, successful procedures have been reported even during the third trimester [6,19]. Endoscopic adrenalectomy is favored over open approaches owing to its reduced morbidity, although direct comparisons between the transperitoneal and retroperitoneal approaches in pregnancy are lacking. In non-pregnant patients, both approaches yield similar operative times, blood loss, and hospital stays [20]. In this case, the retroperitoneal approach was used. This technique offers several advantages during pregnancy as follows: it allows surgery in the lateral position, minimizes inferior vena cava compression by the gravid uterus, avoids entry into the peritoneal cavity, thereby preventing interference from the enlarged uterus, and reduces the risk of intra-abdominal inflammatory spread to the uterus and adjacent organs. Based on our experience and considering the potential advantages of the retroperitoneoscopic approach, we propose that retroperitoneoscopic adrenalectomy should be considered even in the early third trimester, as it may safely prolong gestation and reduce the need for preterm delivery.

Conclusions

This case highlights the challenges of managing adrenal CS during pregnancy. Uncontrolled CS may impair placental development during early pregnancy; therefore, preconceptional or at least early recognition and appropriate management are crucial to minimize the risk of subsequent fetal growth restriction. Further research is needed to clarify the pathophysiological relationship between hypercortisolism and impaired placentation in early pregnancy and to refine strategies for managing this rare but high-risk condition.

References

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From https://www.cureus.com/articles/425273-adrenal-cushings-syndrome-in-pregnancy-complicated-by-fetal-growth-restriction-following-retroperitoneoscopic-adrenalectomy#!/

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