Eyelid Edema Due to Cushing’s Syndrome

Posted on July 25, 2022 by MaryO

Abstract

Cushing’s syndrome (CS) shows diverse signs such as centripetal obesity, moon face, and buffalo hump, which can complicate the diagnosis. Facial features including eyelid edema, as an underrecognized sign, can be diagnostic clues for an excess of corticoids in a CS patient.

A 49-year-old woman presented with amenorrhea and weight gain that had continued for 2 years. Her medical history was dyslipidemia, hypertension, and osteoporosis. Physical examination revealed eyelid edemas (Figure 1A), moon face, buffalo hump, abdominal purple striae, and centripetal obesity (body mass index (BMI), 30.8 kg/m2). Basal plasma adrenocorticotropin was undetectable and serum cortisol level was high (16.9 μg/dl) without circadian rhythms. Free cortisol level in a 24-h urine collection was elevated (158.7 μg/day). Overnight administration of dexamethasone (1 mg) did not reduce serum cortisol level (17.4 μg/dl). Magnetic resonance imaging suggested bilateral adenomas. We made a diagnosis of adrenal Cushing’s syndrome (CS). Since 131l-adosterol scintigraphy showed specific uptake in the left adrenal gland, left adrenalectomy was laparoscopically performed. Histopathology of the tumor was compatible with adrenocortical adenoma. Three months after surgery, her BMI decreased to 25.0 kg/m2 and eyelid edemas were ameliorated (Figure 1B).

Details are in the caption following the image

(A) Bilateral eyelid edemas due to Cushing’s syndrome are shown. (B) These findings were improved three months after surgery for left adrenal adenomas

Eyelid edema, in addition to centripetal obesity, moon face, and buffalo hump, is also a significant sign of CS; however, it has scarcely been reported in countries other than Japan.1, 2 Increased capillary permeability, insufficient venous return due to muscle atrophy, and sodium retention due to mineralocorticoid actions conceivably cause edema in CS.

AUTHORS’ CONTRIBUTIONS

KY wrote the first draft and managed all the submission processes. KO and KH contributed to the clinical management of the patient. FO organized the writing the manuscript.

ACKNOWLEDGMENT

None.

CONFLICT OF INTEREST

The authors declare no conflicts of interest.

ETHICAL APPROVAL

Written informed consent was obtained from the patient to publish this case report.

  • 1Lacroix A, Feelders RA, Stratakis CA, Nieman LK. Cushing’s syndrome. Lancet. 2015; 386: 913- 927.
  • 2Komiya I, Takasu N, Ohara N, et al. Forty-one cases of Cushing’s syndrome: a comparison between Cushing’s syndrome (adrenal adenoma) and Cushing’s disease (adrenal hyperplasia). Nihon Naibunpi Gakkai Zasshi. 1992; 68: 607- 622.

https://doi.org/10.1002/ccr3.5940

From https://onlinelibrary.wiley.com/doi/10.1002/ccr3.5940

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Researchers Report Rare Case of Cushing’s Caused by Bilateral Adrenal Tumors

Posted on July 8, 2019 by MaryO

Cases of adrenocorticotropic hormone (ACTH)-independent Cushing’s syndrome are often caused by unilateral tumors in the adrenal glands, but Indian researchers have now reported a rare case where the condition was caused by tumors in both adrenal glands.

Fewer than 40 cases of bilateral tumors have been reported so far, but an accurate diagnosis is critical for adequate and prompt treatment. Sampling the veins draining the adrenal glands may be a good way to diagnose the condition, researchers said.

The study, “Bilateral adrenocortical adenomas causing adrenocorticotropic hormone-independent Cushing’s syndrome: A case report and review of the literature,” was published in the World Journal of Clinical Cases.

Cushing’s syndrome, a condition characterized by excess cortisol in circulation, can be divided into two main forms, depending on ACTH status. Some patients have tumors that increase the amount of ACTH in the body, and this hormone will act on the adrenal glands to produce cortisol in excess. Others have tumors in the adrenal glands, which produce excess cortisol by themselves, without requiring ACTH activation. This is known as ACTH-independent Cushing’s syndrome.

Among the latter, the disease is mostly caused by unilateral tumors — in one adrenal gland only —  with cases of bilateral tumors being extremely rare in this population.

Now, researchers reported the case of a 31-year-old Indian woman who developed ACTH-independent Cushing’s syndrome because of tumors in both adrenal glands.

The patient complained of weight gain, red face, moon face, bruising, and menstrual irregularity for the past two years. She recently had been diagnosed with high blood pressure and had started treatment the month prior to the presentation.

A physical examination confirmed obesity in her torso, moon face, buffalo hump, thin skin, excessive hair growth, acne, swollen legs and feet, and skin striae on her abdomen, arms, and legs.

Laboratory examinations showed that the woman had an impaired tolerance to glucose, excess insulin, and elevated cortisol in both the blood and urine. Consistent with features of Cushing’s syndrome, cortisol levels had no circadian rhythm and were non-responsive to a dexamethasone test, which in normal circumstances lowers cortisol production.

Because ACTH levels were within normal levels, researchers suspected an adrenal tumor, which led them to conduct imaging scans.

An abdominal computed tomography (CT) scan showed adrenal adenomas in both adrenal glands (right: 3.1 cm × 2.0 cm × 1.9 cm; left: 2.2 cm × 1.9 cm × 2.1 cm). A magnetic resonance imaging (MRI) scan showed that the pituitary gland (which normally produces ACTH) was normal.

To determine whether both adrenal tumors were producing cortisol, researchers sampled the adrenal veins and compared their cortisol levels to those of peripheral veins. They found that the left adrenal gland was producing higher amounts of cortisol, thought the right adrenal gland was also producing cortisol in excess.

“Our case indicates that adrenal vein [blood] sampling might be useful for obtaining differential diagnoses” in cases of Cushing’s syndrome, researchers stated. Also, they may help design a surgical plan that makes much more sense.”

The tumors were surgically removed — first the left, and three months later the right — which alleviated many of her symptoms. She also started prednisolone treatment, which helped resolve many disease symptoms.

“Bilateral cortisol-secreting tumors are a rare cause of Cushing’s syndrome,” researchers said. So when patients present bilateral adrenal lesions, “it is crucial to make a definitive diagnosis before operation since various treatments are prescribed for different causes,” they said.

The team recommends that in such cases the two tumors should not be removed at the same time, as this approach may cause adrenal insufficiency and the need for glucocorticoid replacement therapy.

From https://cushingsdiseasenews.com/2019/06/27/rare-case-of-cs-due-to-bilateral-tumors-in-the-adrenal-glands/

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Adrenal Gland Lump Led to 5-year-old Developing Cushing’s, Starting Puberty

Posted on February 17, 2018 by MaryO

Non-cancerous adrenal gland tumors can lead to rare cases of Cushing’s syndrome in young children and puberty starting years before it should, a case study of a 5-year-old boy shows.

Removing his right adrenal gland eliminated the problems, the Saudi Arabian researchers said.

Their report dealt with tumors in epithelial cells, which line the surface of many of the body’s structures and cavities.

The research, “Testosterone- and Cortisol-secreting Oncocytic Adrenocortical Adenoma in the Pediatric Age-group,” appeared in the journal Pediatric and Developmental Pathology.

Most tumors in adrenal gland epithelial cells are benign and generate normal levels of hormones. But there are cases when the tumors over-produce steroids and other kinds of hormones, including sex hormones. Sometimes the over-production can lead to Cushing’s syndrome.

The 5-year-old boy’s over-production of adrenal gland hormones led to both symptoms of Cushing’s syndrome and signs that he was starting puberty, the researchers said.

One reason the case was rare is that the average age when Cushing’s develops is 40, doctors say. Another is that epithelial adrenal gland tumors account for only 0.2 percent of all tumors in children, the researchers said.

Signs that the boy was starting puberty began appearing eight months before his parents took him for treatment. Doctors discovered he had the weight gain and rounded face associated with Cushing’s, but a battery of tests detected no other problems. No family members were experiencing the symptoms he was, doctors added.

Biochemical tests showed that the boy had a high level of cortisol in his blood, which doctors were unable to lower with the corticosteroid suppression medication dexamethasone.

Physicians also discovered that the boy had elevated levels of the male hormone testosterone, the cortisol precursor 17-hydroxyprogestrone, the cortisol-releasing hormone adrenocorticotropin, and another male hormone that the adrenal gland produces — dehydroepiandrosterone sulfate

In contrast, doctors discovered a below-normal level of luteinising, a sex hormone that the pituitary gland generates.

Another unusual manifestation of the boy’s condition was that his bone growth was that of a child a year older than he.

Doctors discovered a non-cancerous tumor in his right adrenal gland that they decided to remove. When they did, they discovered no evidence of bleeding, tissue scarring or cell death.

They put the boy on a hydrocortisone supplement, which they reduced over time and finally ended.

Twenty-eight months after the surgery, the boy showed no signs of Cushing’s disease or early puberty. And his weight, cortisol and adrenocorticotropin hormone levels were normal.

“To the best of our knowledge, our patient represents the first male patient” with a benign epithelial-cell adrenal gland tumor “in the pediatric population, with clinical presentation of precocious [early] puberty and Cushing’s syndrome,” the researchers wrote.

“As these tumors are exceptionally rare, reporting of additional cases and investigation of clinicopathological [disease] data are needed for better characterization of these tumors,” they wrote.

From https://cushingsdiseasenews.com/2018/02/16/cushings-syndrome-early-puberty-5-year-old-boy-case-study/

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Patient’s Atypical Cushing’s Symptoms Lead to Discovery of Novel Genetic Mutations

Posted on February 14, 2018 by MaryO

New genetic mutations were found in a patient who exhibited atypical symptoms of Cushing’s syndrome, notably an abnormal protrusion of the eye, a case report shows.

The research, “Extensive ARMC5 genetic variance in primary bilateral macronodular adrenal hyperplasia that started with exophthalmos: a case report,” was published in the Journal of Medical Case Reports.

Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a disorder characterized by multiple lumps in the adrenal glands and excessive cortisol production. It is a rare cause of Cushing’s syndrome.

According to recent research, PBMAH is caused by mutations in the ARMC5 gene, which data suggest may act as a tumor suppressor.

Researchers presented the case of a 52-year-old Chinese woman who exhibited a protrusion of both eyes (exophtalmos), which was first thought to be Graves’ ophthalmopathy. An injection of triamcinolone acetonide, a corticosteroid, into the area behind the eye globe did not improve symptoms.

The patient later was diagnosed with diabetes, which was treated with insulin, and hypertension, treated with insulin and amlodipine. She also developed muscle weakness and bruised easily. She had no other relevant chronic illness or infectious disease, and did not smoke tobacco or drink alcohol.

Physical examination showed skin atrophy, moon face, buffalo hump (between the shoulders), and purplish abdominal striae (stretch marks), which researchers defined as a typical Cushingoid appearance. The patient also experienced elevated pressure inside the eye, and had edema, conjunctival congestion, and lid retraction. No liver, spleen, respiration, cardiac, abdominal, blood counts, urinary, sensory, or motor abnormalities were noted.

Biochemical evaluation showed elevated cortisol and reduced adrenocorticotropin (ACTH) levels. Administering  dexamethasone did not lower the level of cortisol. Abnormal responses of the hormone vasopressin also were detected.

A computed tomography (CT) scan of the adrenal glands showed bilateral multiple lobular masses, and an MRI of the eye orbits indicated bilateral exophthalmos with hypertrophy of the retro-orbital fat, which lines the orbit.

After PBMAH was diagnosed, the patient’s adrenal glands were removed. Pathological findings showed multiple, homogenous, golden-yellow-colored nodules on the glands.

The surgery successfully lowered the level of cortisol and increased that of ACTH. The patient began taking hydrocortisone and metformin for diabetes. After six months, her exophtlamos, blood glucose levels, and blood pressure had improved.

Genetic analysis revealed six specific ARMC5 mutations in five of the seven adrenal nodules analyzed. “All the mutations are novel and not found in available online databases,” the researchers wrote. The mutations may lead to resistance to cell death in the tumor cells, and cause an increase in the production of cortisol, they observed.

As a result of the ARMC5 mutations, gene expression (conversion of genetic information) of the messenger RNA (mRNA, which is converted from DNA in the first step of protein synthesis) was lower in the adrenal tumor samples, in comparison with normal adrenal cortex.

Overall, the study “highlights the importance of early recognition of atypical symptoms of Cushing’s syndrome such as exophthalmos, which would save the patient from harmful effects of excessive cortisol exposure,” the researchers said. Screening for ARMC5 mutations also would help improve diagnosis and genetic counseling, they said.

From https://cushingsdiseasenews.com/2018/02/13/odd-cushings-symptoms-linked-genetic-mutations-case-report/

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Topical Ocular Glucocorticoid Leads to Cushing’s Syndrome in 9-Year-Old

Posted on January 21, 2017 by MaryO

In a case report published online January 19 in Pediatrics, iatrogenic Cushing’s syndrome (CS) is described in a 9-year-old girl who received topical ocular glucocorticoid (GC) treatment for bilateral iridocyclitis.

Daisuke Fukuhara, MD, PhD, from the Kyorin University School of Medicine in Mitaka, Japan, and colleagues present the case of a 9-year-old girl suffering from idiopathic uveitis. She arrived at the ophthalmology department with a complaint of painful eyes, and was diagnosed with bilateral iridocyclitis and started on betamethasone sodium phosphate eye drop treatment.

The authors note that the patient was referred to the pediatric department with stunted growth, truncal obesity, purple skin striae, buffalo hump, and moon face six months after initiation of topical ocular GC treatment. She was diagnosed with iatrogenic CS as her serum cortisol and plasma adrenocorticotropic hormone levels were undetectable. The clinical symptoms of CS were improved after the doses of topical ocular GC were reduced. On genetic analysis, the patient was found to have a single heterozygous nucleotide substitution in the 3′ untranslated region of the NR3C1 gene.

“However, additional investigations are required to determine if our findings can be extrapolated to other patients,” the authors write. “In conclusion, clinicians should be aware that even extremely low doses of topical ocular steroid therapy can cause iatrogenic CS.”

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From http://www.empr.com/news/iatrogenic-cushings-syndrome-topical-ocular-glucocorticoid-iridocyclitis/article/632840/

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