Adrenal Crisis

Posted on December 8, 2025 by MaryO

Robin wrote a great blog post about Jackie and Sam dealing with Adrenal Crisis.  This is a very important article that all should read.  Be your own advocate!

New PDF! Managing Adrenal Insufficiency

New Podcast! Podcast: Adrenal Crisis

If left untreated, adrenal insufficiency can cause serious illness or death. But by working with their doctors and nurses, patients can learn how to manage this condition.

A Paramedic wrote on the message boards:

I’d like to add a couple things from the perspective of a Paramedic…

A lot of us are not taught about adrenal insufficiency during our education….nor do many of us (if any at all) have a protocol to administer Injectable for AI unless we are able to contact the ER doctor for permission. So…if any of you should have an AI crisis please gently nudge your paramedic to contact the receiving physician for permission to administer the medication. I know this sounds like a lot of responsibility on the part of the patient…but you have to realize that we’re taught to recognize the most common life threats and endocrine disorders (other than diabetes) most usually do not present with life threats (we all know that as cushing’s is more recognized that this will change)…and our protocols cover the most common life threats….so while we may recognize that you are hypotensive and need fluids (IV) and are sweaty, nauseated, decreased level of responsiveness etc…we are not equipped to deal with the actual cause unless you help educate us….

Also…please don’t get angry with us….if we are having problems understanding…just gently insist that a call be made to your doctor or the receiving ED (usually not feasible for us to call your doctor since they do not come to the phone for just anybody but if you have access to them, as many cushies do, it would be great to talk to them)…

Paramedicine is evolving….someday soon, hopefully, our education will include more diagnostic skills…untill just in the past 5 years or so we were NEVER to make a diagnosis at all…just treat the symptoms!!!! So there is hope out there for futher understanding of such a critical problem for those without adrenal (or asleep adrenals) glands….

The medical alert jewerly is a life-saver and we do look for it….

Be sure to print this page to carry with you.

From the NIH. This information was developed by the patient care staff of the Clinical Center to help patients with adrenal insufficiency (AI) understand their condition and how to take care of it. It explains what causes adrenal insufficiency and how it can be controlled. If left untreated, adrenal insufficiency can cause serious illness or death. But by working with their doctors and nurses, patients can learn how to manage this condition.

National Endocrine and Metabolic Diseases Information Service

6 Information Way
Bethesda, MD 20892–3569
Phone: 1–888–828–0904
TTY: 1–866–569–1162
Fax: 1–703–738–4929
Email: // <![CDATA[
var prefix = 'ma' + 'il' + 'to';
var path = 'hr' + 'ef' + '=';
var addy41985 = 'endoandmeta' + '@';
addy41985 = addy41985 + 'info' + '.' + 'niddk' + '.' + 'nih' + '.' + 'gov';
var addy_text41985 = 'endoandmeta' + '@' + 'info' + '.' + 'niddk' + '.' + 'nih' + '.' + 'gov';
document.write( '‘ );
document.write( addy_text41985 );
document.write( ‘‘ );
//n
// –>
// ]]>endoandmeta@info.niddk.nih.gov // <![CDATA[
document.write( '‘ );
// ]]>This e-mail address is being protected from spambots. You need JavaScript enabled to view it // <![CDATA[
document.write( '’ );
// ]]>
Internet: http://endocrine.niddk.nih.gov/

The National Endocrine and Metabolic Diseases Information Service is an information dissemination service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The NIDDK is part of the National Institutes of Health (NIH), which is part of the U.S. Department of Health and Human Services.

The NIDDK conducts and supports biomedical research. As a public service the NIDDK has established information services to increase knowledge and understanding about health and disease among patients, health professionals and the public.

Publications produced by the NIDDK are carefully reviewed by both NIDDK scientists and outside experts.

This publication is not copyrighted. The NIDDK encourages users of this publication to duplicate and distribute as many copies as desired.

From http://endocrine.niddk.nih.gov/pubs/creutz/alert.htm

DebMV suggested that you should have a Medic Alert bracelet from medicalert.org

Toll free number in the USA is: by phone 7 days a week, 24 hours a day: 888-633-4298
209-668-3333 from outside the U.S.

Lorrie got this important info for us.

Alternative names:

adrenal crisis; Addisonian crisis; acute adrenal insufficiency

Definition:

An abrupt, life-threatening state caused by insufficient cortisol, a hormone produced and released by the adrenal gland.

Causes, incidence, and risk factors:

The two adrenal glands are located on top of the kidneys. They consist of the outer portion, called the cortex, and the inner portion, called the medulla. The cortex produces three types of hormones, which are called corticosteroids. The androgens and estrogens affect sexual development and reproduction. The glucocorticoids maintain glucose regulation, suppress the immune response, and provide for the response to stress (cortisol). The mineralocorticoids regulate sodium and potassium balance. These hormones are essential for life.

Acute adrenal crisis is an emergency caused by decreased cortisol. The crisis may occur in a person with Addison’s disease, or as the first sign of adrenal insufficiency. More uncommonly, it may be caused by a pituitary gland disorder. It may also be caused by sudden withdrawal of corticosteroids, removal or injury of the adrenal glands, or destruction of the pituitary gland. Risk factors are stress, trauma, surgery, or infection in a person with Addison’s disease, or injury or trauma to the adrenal glands or the pituitary gland. The incidence is 4 out of 100,000 people.

Prevention:

People who have Addison’s disease should be taught to recognize signs of potential stress that may precipitate an acute adrenal crisis (cause it to occur suddenly and unexpectedly). Most people with Addison’s disease are taught to give themselves an emergency injection of hydrocortisone in times of stress. It is important for the individual with Addison’s disease to always carry a medical identification card that states the type of medication and the proper dose needed in case of an emergency. Never omit medication. If unable to retain medication due to vomiting, notify the health care provider.

Symptoms:

  • headache
  • profound weakness
  • fatigue
  • slow, sluggish, lethargic movement
  • nausea
  • vomiting
  • low blood pressure
  • dehydration
  • high fever
  • chills shaking
  • confusion or coma
  • darkening of the skin
  • rapid heart rate
  • joint pain
  • abdominal pain
  • unintentional weight loss
  • rapid respiratory rate
  • unusual and excessive sweating on face and/or palms
  • skin rash or lesion may be present
  • flank pain
  • appetite, loss

Signs and tests:

  • An ACTH (cortrosyn) stimulation test shows low cortisol.
  • The cortisol level is low.
  • The fasting blood sugar may be low.
  • The serum potassium is elevated.
  • The serum sodium is decreased.
  • This disease may also alter the results of the following tests:
    • sodium, urine
    • 17-hydroxycorticosteroids

Treatment:

In adrenal crisis, an intravenous or intramuscular injection of hydrocortisone (an injectable corticosteroid) must be given immediately. Supportive treatment of low blood pressure is usually necessary. Hospitalization is required for adequate treatment and monitoring. Low blood pressure may be treated with intravenous fluids. If infection is the cause of the crisis, antibiotic therapy is indicated.

Expectations (prognosis):

Death may occur due to overwhelming shock if early treatment is not provided.

Complications:

  • shock
  • coma
  • seizures

Filed under: adrenal, adrenal crisis, Cushing's, podcast | Tagged: , , , | 2 Comments »

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

  1. Castinetti F, Brue T: Impact of Cushing’s syndrome on fertility and pregnancy. Ann Endocrinol (Paris). 2022, 83:188-90. 10.1016/j.ando.2022.04.001
  2. Eschler DC, Kogekar N, Pessah-Pollack R: Management of adrenal tumors in pregnancy. Endocrinol Metab Clin North Am. 2015, 44:381-97. 10.1016/j.ecl.2015.02.006
  3. Caimari F, Valassi E, Garbayo P, Steffensen C, Santos A, Corcoy R, Webb SM: Cushing’s syndrome and pregnancy outcomes: a systematic review of published cases. Endocrine. 2017, 55:555-63. 10.1007/s12020-016-1117-0
  4. Hamblin R, Coulden A, Fountas A, Karavitaki N: The diagnosis and management of Cushing’s syndrome in pregnancy. J Neuroendocrinol. 2022, 34:e13118. 10.1111/jne.13118
  5. Sammour RN, Saiegh L, Matter I, et al.: Adrenalectomy for adrenocortical adenoma causing Cushing’s syndrome in pregnancy: a case report and review of literature. Eur J Obstet Gynecol Reprod Biol. 2012, 165:1-7. 10.1016/j.ejogrb.2012.05.030
  6. Martínez García R, Martínez Pérez A, Domingo del Pozo C, Sospedra Ferrer R: Cushing’s syndrome in pregnancy. Laparoscopic adrenalectomy during pregnancy: the mainstay treatment. J Endocrinol Invest. 2016, 39:273-6. 10.1007/s40618-015-0345-0
  7. Younes N, St-Jean M, Bourdeau I, Lacroix A: Endogenous Cushing’s syndrome during pregnancy. Rev Endocr Metab Disord. 2023, 24:23-38. 10.1007/s11154-022-09731-y
  8. Sasaki A, Shinkawa O, Margioris AN, et al.: Immunoreactive corticotropin-releasing hormone in human plasma during pregnancy, labor, and delivery. J Clin Endocrinol Metab. 1987, 64:224-9. 10.1210/jcem-64-2-224
  9. Jung C, Ho JT, Torpy DJ, et al.: A longitudinal study of plasma and urinary cortisol in pregnancy and postpartum. J Clin Endocrinol Metab. 2011, 96:1533-40. 10.1210/jc.2010-2395
  10. Petraglia F, Sawchenko PE, Rivier J, Vale W: Evidence for local stimulation of ACTH secretion by corticotropin-releasing factor in human placenta. Nature. 1987, 328:717-19. 10.1038/328717a0
  11. Savas M, Mehta S, Agrawal N, van Rossum EF, Feelders RA: Approach to the patient: diagnosis of Cushing syndrome. J Clin Endocrinol Metab. 2022, 107:3162-74. 10.1210/clinem/dgac492
  12. Jung E, Romero R, Yeo L, et al.: The etiology of preeclampsia. Am J Obstet Gynecol. 2022, 226:S844-66. 10.1016/j.ajog.2021.11.1356
  13. González P, Lozano P, Ros G, Solano F: Hyperglycemia and oxidative stress: an integral, updated and critical overview of their metabolic interconnections. Int J Mol Sci. 2023, 24:9352. 10.3390/ijms24119352
  14. Ueda A, Hasegawa M, Matsumura N, et al.: Lower systolic blood pressure levels in early pregnancy are associated with a decreased risk of early-onset superimposed preeclampsia in women with chronic hypertension: a multicenter retrospective study. Hypertens Res. 2022, 45:135-45. 10.1038/s41440-021-00763-6
  15. Burton GJ, Jauniaux E: Pathophysiology of placental-derived fetal growth restriction. Am J Obstet Gynecol. 2018, 218:S745-61. 10.1016/j.ajog.2017.11.577
  16. Xiao D, Huang X, Bae S, Ducsay CA, Zhang L: Cortisol-mediated potentiation of uterine artery contractility: effect of pregnancy. Am J Physiol Heart Circ Physiol. 2002, 283:H238-46. 10.1152/ajpheart.00842.2001
  17. Albiston AL, Obeyesekere VR, Smith RE, Krozowski ZS: Cloning and tissue distribution of the human 11 beta-hydroxysteroid dehydrogenase type 2 enzyme. Mol Cell Endocrinol. 1994, 105:11-17. 10.1016/0303-7207(94)90176-7
  18. Wang Y, An Y, Hou X, et al.: Cushing’s syndrome in pregnancy secondary to adrenocortical adenoma: a case series and review. Endocrinol Diabetes Metab. 2024, 7:e00474. 10.1002/edm2.474
  19. Shaw JA, Pearson DW, Krukowski ZH, Fisher PM, Bevan JS: Cushing’s syndrome during pregnancy: curative adrenalectomy at 31 weeks gestation. Eur J Obstet Gynecol Reprod Biol. 2002, 105:189-91. 10.1016/s0301-2115(02)00148-3
  20. Nigri G, Rosman AS, Petrucciani N, et al.: Meta-analysis of trials comparing laparoscopic transperitoneal and retroperitoneal adrenalectomy. Surgery. 2013, 153:111-19. 10.1016/j.surg.2012.05.042

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

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

Co-Occurrence of Endogenous and Exogenous Cushing’s Syndromes: Does “Double Cushing Syndrome” Really Exist? A Case Report

Posted on December 1, 2025 by MaryO

ABSTRACT

Double Cushing syndrome exists: exogenous steroid use can mask concurrent adrenal hypercortisolism. When symptoms persist and cortisol remains high after tapering or stopping prescribed glucocorticoids, an endogenous source is likely. Early recognition with ACTH testing, dexamethasone suppression, and adrenal imaging reduces misdiagnosis, favors timely surgery, and supports safe tapering.

1 Introduction

Cushing syndrome (CS) is a non-physiological increase in plasma glucocorticoids [1]. In most cases, the source of increased plasma glucocorticoids is caused by exogenous steroid administration, which is quite common, and about 1% of the world population is on long-term (more than 3 months) oral glucocorticoids [1, 2]. On the contrary, endogenous overproduction of glucocorticoids is rare, and annually, only two to eight per million people are diagnosed with endogenous CS [3]. The simultaneous occurrence of endogenous and exogenous CS is an exceptionally uncommon phenomenon. This dual manifestation has been reported in a few case reports, highlighting its rarity and the complex diagnostic and therapeutic challenges it poses [4, 5]. Therefore, in this study, we discuss a patient who presented with cushingoid features and was simultaneously diagnosed with both endogenous and exogenous CS or, as it is called, double CS.

2 Case Presentation

The patient was a 46-year-old male with a history of new-onset hypertension and recurrent deep vein thrombosis (DVT) who was referred to our endocrinology clinic with a chief complaint of hip pain and weakness of the lower limbs. In the past 3 years, the patient had been receiving 50 mg/day of oral prednisolone and inhalation powder of Umeclidinium and Vilanterol (62.5/25 μg/dose) because of respiratory complications that started after Coronavirus Disease 2019 (COVID-19) vaccination. After 3 months of corticosteroid treatment, he experienced DVT for the first time when he was started on rivaroxaban. However, while he was on treatment, the second DVT occurred 1 month before his referral, and therefore, rivaroxaban was changed to warfarin 5 mg/day.

The patient also mentioned weight gain with his body mass index (BMI) rising from 26 to 31 kg/m2, progressive weakness of proximal muscles, easy bruising, decreased libido, mood changes with mostly euphoric mood, and irritability during the last 2 years. Moreover, multiple osteoporotic fractures of ribs, clavicle, sternum, and lumbar vertebrae were added to his symptoms in the past 5 months. At that time, he underwent bone densitometry, which revealed osteopenia of the left hip with a Z-score of −1.3 and severe osteoporosis of total lumbar spine with a T-score of −3.9. He started taking calcium and vitamin D3 supplements and received a single injection of 750 μg/3 mL teriparatide 30 days before his referral to our center.

Two months ago, the patient gradually reduced the dosage of prednisolone by tapering the dose to 12.5 mg/day. However, a month later, the hip pain and muscle weakness worsened to such an extent that the patient was unable to walk. Due to his signs and symptoms, the patient was referred to our center for further evaluation of CS. The patient also mentioned a history of nephrolithiasis, new-onset hypertension, and lower limb edema, for which he was started on eplerenone 25 mg and furosemide 20 mg tablets once daily. In his family history, the patient’s mother had type 2 diabetes mellitus, and his two sisters had a history of nephrolithiasis. The patient did not mention any history of allergies to medications or foods. He was addicted to opium and had 15 pack-years of smoking, but he did not mention alcohol consumption.

Upon admission, the patient presented with a blood pressure of 150/83 mmHg, heart rate of 74 bpm, respiratory rate of 20/min, temperature of 36.5°C, oxygen saturation of 93%, and BMI of 31 kg/m2. He was sitting in a wheelchair due to weakness and severe pain in the hip. On physical examination, the patient showed the features of CS, including moon face, buffalo hump, central obesity, facial plethora, thin and brittle skin, acne, and purple stretch marks (striae) on the flanks (Figure 1). Proximal muscle weakness in the lower limbs with a muscle force grade of 4/5 and 3+ edema was also observed. Laboratory investigations are shown in Table 1.

Details are in the caption following the image

De-identified clinical photographs illustrating the Cushingoid phenotype. (A) Overall habitus with marked central (truncal) adiposity. (B) Rounded plethoric face (“moon facies”). (C) Relatively slender distal extremities compared with truncal obesity. (D) Dorsocervical fat pad (“buffalo hump”). (E) Upper thoracic/supraclavicular fat accumulation. (F) Protuberant abdomen with wide violaceous striae.
TABLE 1. Laboratory findings of case report.
Laboratory test Patient value (in-hospital) Patient value (follow-up) Reference range
On admission
Hemoglobin (g/dL) 16.6 13.6 13.5–17.5
Hematocrit (%) 49.5 42.1 42–52
WBC (white blood cells; 103/μL) 11.8 7.1 4.0–11.0
PLT (platelet count; 103/μL) 286 294 150–450
BUN (blood urea nitrogen; mg/dL) 10 11 7–18
Cr (creatinine; mg/dL) 0.9 0.9 0.7–1.3
ALP (alkaline phosphatase; IU/L) 1016 129 44–147
AST (aspartate aminotransferase; IU/L) 48 30 < 31
ALT (alanine transaminase; IU/L) 88 21 < 31
CRP (C-reactive protein; mg/dL) 31 3 < 5
ESR (erythrocyte sedimentation rate; mm/h) 63 24 < 15
Sodium (mEq/L) 148 141 136–145
Potassium (mEq/L) 4.8 4.3 3.5–5
FBS (fasting blood glucose; mg/dL) 97 89 80–100
TC (total cholesterol; mg/dL) 267 182 < 200
TG (triglyceride; mg/dL) 148 104 < 200
LDL (low-density lipoprotein; mg/dL) 138 98 < 130
HDL (high-density lipoprotein; mg/dL) 64 55 30–70
In hospital
Cortisol 8 a.m. fasting (μg/dL) 20.2 14.1 4.3–24.9
ACTH (adrenocorticotropic hormone; pg/mL) < 1 — 7.2–63.3
1 mg Overnight dexamethasone suppression test (μg/dL) 16.5 — < 1.8

3 Methods (Differential Diagnosis, Investigations, and Treatment)

Initially suspected of having exogenous-induced CS, the patient’s prednisolone was on hold for 3 days. Cortisol 8 a.m. fasting level, measured with Electrochemiluminescence (ECL) and adrenocorticotropic hormone (ACTH) test, was 20.2 μg/dL (585.4 nmol/L) and < 1 pg/mL, respectively. Due to the lack of suppression of serum cortisol despite not using oral glucocorticoids, the absence of adrenal insufficiency symptoms, and the fact that the patient’s symptoms remained unchanged during this period, co-occurrence of endogenous CS was suspected.

A 1 mg overnight dexamethasone suppression test was performed to confirm endogenous CS diagnosis, and the results were reported as 16.5 μg/dL (normal range < 1.8 μg/dL). Considering the possibility of an ACTH-independent CS, the patient underwent an abdominopelvic multidetector computed tomography (MDCT) of abdominopelvic with adrenal protocol, which revealed a well-defined lesion with an approximate size of 32.8 × 38.6 mm in the left adrenal gland with a radiodensity of 90 Hounsfield units and a normal right adrenal gland (Figure 2). Moreover, evidence of previous old fractures as multiple callus formation was seen involving the clavicles, sternum, bilateral ribs, ischium, and pelvic bones. Multilevel old stable compression fractures of thoracic and lumbar vertebral bodies were also present. The differential diagnoses were glucocorticoid secretory adrenal tumors, including adrenal cell carcinoma and lipid-poor adenoma. In order to rule out pheochromocytoma, 24-h urine catecholamines were measured, and the results were negative.

Details are in the caption following the image

Abdominopelvic multidetector computed tomography (MDCT) with adrenal protocol showing a well-defined lesion with an approximate size of 32.8 × 38.6 mm in the left adrenal gland; radiodensity 90 HU. (A) Transverse plane. (B) Coronal plane. (C) Sagittal plane.

Finally, the patient underwent left adrenalectomy and corticosteroid replacement therapy due to the suppression of the other adrenal gland. According to the post-operative pathological investigations, immunohistochemistry markers reported as negative chromogranin, positive melan-A and inhibin, less than 3% Ki-67 marker, and lipid-poor adrenal cortical adenoma without invasions were diagnosed (Figure 3).

Details are in the caption following the image

Immunohistochemistry of the adrenal lesion (all panels acquired with a 100× oil-immersion objective; 10× eyepiece; original magnification ×1000). (A) Positive inhibin, (B) Positive Melan-A, (C) Less than 3% Ki-67 marker, and (D) Negative chromogranin.

4 Results (Outcome and Follow-Up)

Within 3 months after the operation, the patient’s corticosteroid was tapered and then discontinued due to the normalization of the cortisone serum test (14.1 μg/dL). Proximal limb weakness and hip pain, which had deprived the patient of the ability to move, gradually improved so that he could walk easily and perform daily activities. The signs and symptoms related to CS, including the patient’s mood, skin signs, and general appearance, returned to normal. The patient has been followed up for 6 months after the surgery. The patient’s BMI decreased to 24 kg/m2, and he stopped his anti-hypertensive medications with a blood pressure of 100/60 mmHg without previously prescribed drugs. So far, the laboratory tests have been within the normal range, and he has no complaints (Table 1).

5 Discussion

The described case was diagnosed with a cortisol-producing adrenocortical adenoma accompanied by exogenous CS. CS is an uncommon clinical condition caused by prolonged exposure to increased cortisol levels, which can be due to endogenous or exogenous factors [6]. Endogenous CS is infrequent and is classified as ACTH-dependent (80% of cases) or ACTH-independent (20% of cases) [7]. In the ACTH-independent category, adrenal adenoma accounts for 60% of cases and only 12% of cases of endogenous CS [7, 8]. Exogenous CS mainly occurs due to prolonged administration of glucocorticoids, which are used to manage a broad spectrum of diseases such as inflammatory, autoimmune, or neoplastic disorders and are the most common cause of CS worldwide [9]. Multiple factors, including formulation, duration of administration, pharmacokinetics, affinity, and potency of exogenous glucocorticoids, affect the probability of exogenous CS, but all forms of glucocorticoids can induce CS [10].

In the setting of cushingoid clinical features with chronic administration of high-dose glucocorticoids, especially oral prednisolone, the probability of exogenous CS is remarkably high; therefore, CS diagnostic approaches suggest that the first step after confirmation of cortisol excess is ruling out exogenous glucocorticoid administration [7, 8, 10]. Therefore, the possibility of co-occurrence of endogenous CS with iatrogenic CS is extremely low, and the diagnosis requires high clinical suspicion [4].

Differentiating endogenous and exogenous CS based on clinical features can be challenging and far-fetched. However, a few points can help physicians distinguish between these two. First, exogenous CS symptoms tend to be more striking, while endogenous CS appears more gradually. Second, hypertension, hypokalemia, and features of androgen excess, such as acne and hirsutism, are more common in endogenous CS [4, 10]. In addition, endogenous CS should be suspected if the patient’s symptoms continue after corticosteroid discontinuation or if the serum cortisol level is high despite corticosteroid cessation. In our case, the patient had a high cortisol level despite stopping prednisolone for 3 days, and he did not have any symptoms of adrenal insufficiency despite stopping prednisolone suddenly. Consequently, it was suspected that glucocorticoids might come from an endogenous source. Because ACTH was suppressed concurrently with elevated cortisol, non-ACTH-dependent CS was suspected, and MDCT of abdominopelvic confirmed it.

So far, few similar cases of simultaneous endogenous and exogenous CS have been reported. The first case was a 23-year-old woman with juvenile idiopathic arthritis who was administered high doses of triamcinolone for 16 years [4]. The development of cushingoid features that favored endogenous CS, such as hirsutism and acne, strengthened the suspicion of endogenous CS, and a CT scan revealed hypercortisolism with a bulky and nodular left adrenal gland, and a double CS was confirmed [4]. The second case was a 66-year-old woman diagnosed with exogenous CS after consumption of Traditional Chinese medicine (TCM) for a year [5]. The cessation of TCM did not significantly improve her cushingoid features, and she developed additional CS complications, including hypertension, diabetes mellitus, and osteoporotic fractures over the next 8 years. CS workup revealed a right-sided adrenal adenoma, and after the adrenalectomy, her clinical cushingoid features markedly improved [5]. These cases suggest that exogenous and endogenous CS can exist simultaneously in the same person. Although it is very rare, it should be considered in a person who still complains of CS symptoms after corticosteroid cessation. We suggest clinicians evaluate the patients for the disappearance of exogenous CS symptoms after tapering and stopping glucocorticoids. If the symptoms remain, they should be evaluated for endogenous CS.

6 Conclusion

The co-occurrence of an endogenous CS in the setting of an exogenous CS is curious. The diagnosis is based on a high clinical suspicion. Clinicians should evaluate patients for symptom resolution after tapering and discontinuing corticosteroids. Clinical cushingoid features that do not resolve after discontinuing exogenous glucocorticoids and high cortisol levels despite discontinuing corticosteroids should raise clinicians’ suspicion of the co-occurrence of exogenous and endogenous CS.

Author Contributions

Reza Amani-Beni: investigation, methodology, writing – original draft, writing – review and editing. Atiyeh Karimi Shervedani: methodology, writing – original draft. Bahar Darouei: conceptualization, validation, writing – review and editing. Matin Noroozi: methodology, writing – original draft. Maryam Heidarpour: conceptualization, supervision, validation, writing – review and editing.

Acknowledgments

The authors have nothing to report.

Consent

Written informed consent was obtained from the patient to publish this report, including de-identified clinical photographs, in accordance with the journal’s patient consent policy.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that supports the findings of this study are available on request of the corresponding author. The data are not publicly available due to privacy restrictions.

https://onlinelibrary.wiley.com/doi/10.1002/ccr3.71419

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

Helping others learn more about Cushing’s/Acromegaly

Posted on November 28, 2025 by MaryO

I found this article especially interesting.  This question was asked of a group of endos at an NIH conference a few years ago – if you saw someone on the street who looked like they had symptoms of fill-in-the disease, would you suggest that they see a doctor.  The general answer was no.  No surprise there.

Patients, if you see someone who looks like s/he has Cushing’s, give them a discrete card.

Spread The Word! Cushing’s Pocket Reference

Robin Writes:

This has been a concern of mine for some time. Your post spurred me on to do something I’ve been meaning to do. I’ve designed something you can print that will fit on the business cards you can buy just about anywhere (Wal-mart included). You can also print on stiff paper and cut with a paper cutter or scissors. I’ve done a front and a back.

Cushing's Pocket Reference

Here are the links:

• Front: This card is being presented by a person who cares.
• Back (The same for everyone)

This Topic on the Message Boards

~~~~~~~~~~~~~~~~~~

And now, the article from http://www.guardian.co.uk/lifeandstyle/2009/nov/03/doctor-diagnosis-stranger:

Are doctors ever really off duty?

Which potentially serious symptoms would prompt them to stop and advise a stranger on a bus?

By Lucy Atkins

Bus

Passengers on a London bus. Photograph: David Levene

A Spanish woman of 55, Montse Ventura, recently met the woman she refers to as her “guardian angel” on a bus in Barcelona. The stranger – an endocrinologist – urged Ventura to have tests for acromegaly, a rare disorder involving an excesss of growth hormone, caused by a pituitary gland tumour. How had the doctor made this unsolicited diagnosis on public transport? Apparently the unusual, spade-like shape of Ventura’s hands was a dead giveaway.

But how many off-duty doctors would feel compelled to alert strangers to symptoms they spot? “If I was sitting next to someone on a bus with a melanoma, I’d say something or I wouldn’t sleep at night,” says GP Mary McCullins. “We all have a different threshold for interfering and you don’t want to terrify people, but this is the one thing I’d urge a total stranger to see a doctor about.” So what other symptoms might prompt a doctor to approach someone on the street?

Moon face

Cushing’s syndrome is another rare hormone disorder which can be caused by a non-cancerous tumour in the pituitary gland. “A puffy, rounded ‘moon face’ is one of the classic signs of Cushing’s,” says Dr Steve Field, chair of the Royal College of GPs. “In a social situation, I wouldn’t just say, ‘You’re dangerously ill’ but I’d try to elicit information and encourage them to see a doctor.”

Different-sized pupils

When one pupil is smaller than the other, perhaps with a drooping eyelid, it could be Horner’s syndrome, a condition caused when a lung tumour begins eating into the nerves in the neck. This can be the first obvious sign of the cancer. “I’d encourage someone to get this checked out,” says Dr Simon Smith, consultant in emergency medicine at the Oxford Radcliffe Hospitals Trust. “People often have an inkling that something’s wrong, and you might spur them to get help sooner.”

Clubbing fingers

Some people are born with club-shaped fingers, but if, over time, they become “drumstick-like”, this could signify serious problems such as lung tumours, chronic lung infections or congenital heart disease. “Because it happens gradually, some people disregard clubbing,” says Smith. “But I’d say something because it can be an important symptom in many serious illnesses.”

Lumpy eyelids

Whitish yellowy lumps around the eyelids can be a sign of high cholesterol, a major factor in heart disease. Sometimes you also get a yellow circle around the iris. “I would suggest they got a cholesterol test with these symptoms,” says Smith. “They can do something about it that could save their life.”

Suntan in unlikely places

A person with Addison’s disease, a rare but chronic condition brought about by the failure of the adrenal glands, may develop what looks like a deep tan, even in non sun-exposed areas such as the palms. Other symptoms (tiredness, dizziness) can be non-specific so the condition is often advanced by the time it is diagnosed. Addison’s is treatable with lifelong steroid replacement therapy. “If someone was saying they hadn’t been in the sun but had developed a tan, alarm bells would ring and I’d probably ask how they were feeling,” says McCullins.

Trench mouth

Putrid smelling breath – even if the teeth look perfect – can be a sign of acute necrotising periodontitis. “I’d be able to tell when someone walks through the door,” says dentist Laurie Powell. “But people become accustomed to it and don’t notice.” Untreated, the condition damages the bones and connective tissue in the jaw. It can also be a sign of other diseases such as diabetes or Aids.

Filed under: adrenal, Cushing's, General Health, pituitary, Rare Diseases | Tagged: , , , , , | 2 Comments »

Prospective Assessment of Mood and Quality of Life in Cushing Syndrome before and after Biochemical Control

Posted on November 17, 2025 by MaryO

Abstract

Context

Cushing syndrome (CS) impairs quality of life (QoL) and mood. Prospective real-life data on post-treatment recovery and predictors of improvement are limited.

Objectives

Evaluate changes in QoL, depression, and anxiety in patients with CS, before and after biochemical control, and identify predictors of clinically meaningful improvement.

Design and Setting

Prospective observational study at a tertiary center.

Patients

67 patients with endogenous CS (60 pituitary, 7 adrenal) were assessed with active disease and again after achieving biochemical control through surgery and/or medication.

Outcomes

Patient-reported outcomes included CushingQoL, Beck Depression Inventory-II (BDI-II), and State-Trait Anxiety Inventory (STAI).

Results

Mean and longest follow-up was 2.3 and 11.5 years, respectively. Treatment led to improvements in mean scores across all domains (QoL: +18.2±20.9, BDI: –6.8±8.6, STAI-State: –9.6±12.5, STAI-Trait: –8.6±12.6; all p < 0.001). However, minimal important difference was achieved in 64.6% for QoL, 67.9% for BDI, 53.2% and 52.8% for STAI subscales. After multivariable analysis, QoL improvements were predicted by lower baseline BMI, pre-treatment symptoms ❤ years, post-operative hydrocortisone replacement >6 months, and normal follow-up late-night salivary cortisol (LNSC). Depression improvements were predicted by symptoms ❤ years, normal follow-up LNSC, and surgical treatment. Anxiety improvements were predicted by younger age and >6 months post-operative hydrocortisone. Depression improved more gradually than QoL and anxiety.

Conclusions

Although effective treatment improves mood and QoL in CS, clinically meaningful recovery is variable and incomplete for some patients. Our findings highlight the need to limit diagnostic delay and provide comprehensive post-treatment care that includes normalization of cortisol circadian rhythm.

Accepted manuscripts
Accepted manuscripts are PDF versions of the author’s final manuscript, as accepted for publication by the journal but prior to copyediting or typesetting. They can be cited using the author(s), article title, journal title, year of online publication, and DOI. They will be replaced by the final typeset articles, which may therefore contain changes. The DOI will remain the same throughout.

This content is only available as a PDF.

© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.

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

Next Page »