COVID-19 May Be Severe in Cushing’s Patients

Posted on January 23, 2026 by MaryO

A young healthcare worker who contracted COVID-19 shortly after being diagnosed with Cushing’s disease was detailed in a case report from Japan.

While the woman was successfully treated for both conditions, Cushing’s may worsen a COVID-19 infection. Prompt treatment and multidisciplinary care is required for Cushing’s patients who get COVID-19, its researchers said.

The report, “Successful management of a patient with active Cushing’s disease complicated with coronavirus disease 2019 (COVID-19) pneumonia,” was published in Endocrine Journal.

Cushing’s disease is caused by a tumor on the pituitary gland, which results in abnormally high levels of the stress hormone cortisol (hypercortisolism). Since COVID-19 is still a fairly new disease, and Cushing’s is rare, there is scant data on how COVID-19 tends to affect Cushing’s patients.

In the report, researchers described the case of a 27-year-old Japanese female healthcare worker with active Cushing’s disease who contracted COVID-19.

The patient had a six-year-long history of amenorrhea (missed periods) and dyslipidemia (abnormal fat levels in the body). She had also experienced weight gain, a rounding face, and acne.

After transferring to a new workplace, the woman visited a new gynecologist, who checked her hormonal status. Abnormal findings prompted a visit to the endocrinology department.

Clinical examination revealed features indicative of Cushing’s syndrome, such as a round face with acne, central obesity, and buffalo hump. Laboratory testing confirmed hypercortisolism, and MRI revealed a tumor in the patient’s pituitary gland.

She was scheduled for surgery to remove the tumor, and treated with metyrapone, a medication that can decrease cortisol production in the body. Shortly thereafter, she had close contact with a patient she was helping to care for, who was infected with COVID-19 but not yet diagnosed.

A few days later, the woman experienced a fever, nausea, and headache. These persisted for a few days, and then she started having difficulty breathing. Imaging of her lungs revealed a fluid buildup (pneumonia), and a test for SARS-CoV-2 — the virus that causes COVID-19 — came back positive.

A week after symptoms developed, the patient required supplemental oxygen. Her condition worsened 10 days later, and laboratory tests were indicative of increased inflammation.

To control the patient’s Cushing’s disease, she was treated with increasing doses of metyrapone and similar medications to decrease cortisol production; she was also administered cortisol — this “block and replace” approach aims to maintain cortisol levels within the normal range.

The patient experienced metyrapone side effects that included stomach upset, nausea, dizziness, swelling, increased acne, and hypokalemia (low potassium levels).

She was given antiviral therapies (e.g., favipiravir) to help manage the COVID-19. Additional medications to prevent opportunistic fungal infections were also administered.

From the next day onward, her symptoms eased, and the woman was eventually discharged from the hospital. A month after being discharged, she tested negative for SARS-CoV-2.

Surgery for the pituitary tumor was then again possible. Appropriate safeguards were put in place to protect the medical team caring for her from infection, during and after the surgery.

The patient didn’t have any noteworthy complications from the surgery, and her cortisol levels soon dropped to within normal limits. She was considered to be in remission.

Although broad conclusions cannot be reliably drawn from a single case, the researchers suggested that the patient’s underlying Cushing’s disease may have made her more susceptible to severe pneumonia due to COVID-19.

“Since hypercortisolism due to active Cushing’s disease may enhance the severity of COVID-19 infection, it is necessary to provide appropriate, multidisciplinary and prompt treatment,” the researchers wrote.

From https://cushingsdiseasenews.com/2021/01/15/covid-19-may-be-severe-cushings-patients-case-report-suggests/?cn-reloaded=1

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Insulin Resistance Unveiled: Cushing’s Disease in a Patient with Type 1 Diabetes Mellitus and Worsening Glycemic Control

Posted on January 22, 2026 by MaryO

Highlights

  • Coexistence of hypercortisolism secondary to ACTH-producing pituitary adenoma and type 1 diabetes mellitus.
  • Presentation of Cushing’s disease in individuals with type 1 diabetes mellitus.
  • Automated insulin delivery utilization in type 1 diabetes with comorbid refractory hypercortisolism.

ABSTRACT

Background/Objective

Type 1 diabetes mellitus is an autoimmune disease often characterized by endogenous insulin deficiency and often sensitivity to endogenous insulin administration. Cushing’s disease, though rare, should be considered as a cause of insulin resistance and increased insulin requirements in individuals with type 1 diabetes mellitus.

Case Presentation

A 21-year-old female with type 1 diabetes mellitus presented with steadily increasing insulin requirements via her hybrid closed-loop insulin pump. She subsequently developed hypertension, weight gain, violaceous striae, and cystic acne. Laboratory evaluation revealed unsuppressed cortisol of 16.6 μg/dL after a 1-mg dexamethasone suppression test, with a simultaneous adrenocorticotropin hormone level of 73.3 pg/mL. Pituitary MRI showed a 1.9 cm sellar mass with local invasion. She underwent transsphenoidal hypophysectomy. Postoperative cortisol was 8.9 μg/dL after intraoperative dexamethasone exposure. Residual hypercortisolism was confirmed, necessitating gamma knife radiation and pharmacologic treatment with a steroidogenesis inhibitor.

Discussion

We present a case of Cushing’s disease due to a corticotropin-secreting pituitary macroadenoma in a young woman with type 1 diabetes. Her initial presentation included rising insulin requirements, followed by overt hypercortisolism. Despite surgery, persistent hypercortisolism required further intervention with gamma knife radiation and osilodrostat. She experienced reductions in both weight and insulin needs, with normalization of cortisol levels on maintenance osilodrostat.

Conclusion

Cushing’s syndrome should be considered in the differential diagnosis of patients with type 1 diabetes and increasing insulin requirements. This case underscores the importance of regular review of automated insulin delivery data and consideration of endocrine causes of insulin resistance and increased insulin requirements in those with type 1 diabetes.

KEY WORDS

Type 1 Diabetes Mellitus
T1DM
Cushing’s disease
Insulin resistance
Insulin pump
Total Daily Dose
TDD

Introduction

Cushing’s syndrome occurs as the result of prolonged elevation in plasma cortisol which can lead to adverse effects including insulin resistance, hyperglycemia, hypertension, weight gain, immunosuppression, and neurocognitive changes. Cushing’s syndrome can occur due to exogenous exposure to corticosteroids or endogenous cortisol hypersecretion. The most common etiology of endogenous hypercortisolism is Cushing’s disease secondary to a corticotrophin-secreting pituitary tumor. In 90% of cases of Cushing’s disease, patients present with pituitary microadenomas, with only 10% of patients presenting with pituitary tumors >1 cm1.
Type 1 diabetes mellitus is an autoimmune condition characterized by T-cell mediated destruction of pancreatic beta cells with ultimate inability to produce insulin and subsequent insulin dependence2. Over the last decade, there has been significant advancement in diabetes management strategies and insulin delivery with creation of hybrid closed-loop insulin pump technology used in conjunction with continuous glucose monitoring systems to provide automated insulin delivery. Within the field of endocrinology, this has required a shift in both the interpretation of glycemic data, insulin utilization data, as well as a pivot to approaching titration of insulin pump settings. Assessment of total daily basal and total daily dose (TDD) in automated mode is of utmost importance when utilizing automated insulin delivery as the amount of insulin utilized can vary significantly in comparison to fixed quantities seen with use of manual mode in an insulin pump2,3.
Type 1 diabetes mellitus is typically characterized by relative insulin sensitivity, particularly early in the disease course. Patients can develop insulin resistance over time, particularly in the setting of comorbid obesity. However, we present a case of a young woman with type 1 diabetes mellitus presenting with steadily increasing insulin requirements followed by development of overt Cushing’s secondary to corticotropin-secreting pituitary macroadenoma. She was utilizing a hybrid-closed loop insulin pump technology with insulin pump download indicating diminished glycemic control despite a steady increase in total daily insulin requirements. This is only the third reported case of Cushing’s disease in a person living with type 1 diabetes mellitus4,5.

Case Presentation

A 21-year-old female with a history of type 1 diabetes diagnosed at age 11 in the context of admission for diabetic ketoacidosis initially presented to adult endocrinology for routine outpatient diabetes management. Type 1 Diabetes Mellitus was managed with automated hybrid-closed loop insulin pump technology (Tandem T-slim X:2 with Dexcom G6 continuous glucose monitoring system). Her hemoglobin A1c was 6.2% with a review of her continuous glucose monitoring system indicating time in range of 73% with 21% of blood glucose levels >180 mg/dL. At that time, she reported concerns regarding high insulin requirements despite an active lifestyle as she was running out of insulin for use in pump early. She was noted to have significant prandial insulin requirements with insulin to carbohydrate ratio of 1 unit for every 3.0-4.5 carbohydrates, raising concern for insulin resistance. Over the next 16 months, she had weight gain of 15.8 kg with elevation in blood pressure and worsening hyperglycemia. Review of her insulin pump downloads indicated a steady increase in her total daily insulin requirements of close to 30%, coupled with reduced time in range and increase in HbA1c.
On repeat physical examination, the development of cystic acne, trace pitting pedal edema, and purple violaceous striae on the abdomen, hips, and thighs were observed. She was also noted to have a new elevation of blood pressure to 162/101 mm Hg. She declined exposure to exogenous corticosteroids (including oral, topical or intra-articular formulations). Based on clinical examination and changes in insulin requirements, the decision was made to evaluate for hypercortisolism. Laboratory evaluation at that time revealed unsuppressed 08:00 AM cortisol level of 16.6 ug/dL after 1 mg of dexamethasone the evening prior. Dexamethasone level was confirmed to be more than adequate at 418 ng/dL (reference range for 8:00 AM level following 1 mg dexamethasone previous evening: 140-295 ng/dL). A simultaneous ACTH level was elevated at 73.3 pg/mL (reference range: 7.2-63.3 pg/mL). She was also noted to have midnight salivary cortisol levels of 0.646, 0.290, and 0.350 ug/dL on three consecutive evenings (reference range <0.010-0.090 ug/dL).
She then underwent MRI pituitary with and without gadolinium enhancement which revealed 1.8 x 1.9 cm enhancing sellar mass with invasion of the right cavernous sinus, extension around the right internal carotid artery, as well as posteriorly down the dorsal aspect of the clivus (Figures 1 and 2). As both hypercortisolism as well as type 1 diabetes mellitus have been implicated as etiologies for lower bone density with subsequent increased risk of osteoporosis later in life, bone densometry was also obtained for this patient. She was found to have low bone mineral density for her age with Z-score of the lumbar spine of -3.2, Z-score of the femoral neck of -2.3, and Z-score of the total hip of -2.8.

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Figure 1. MRI pituitary coronal image revealing sellar mass with invasion of the right cavernous sinus, extension around the right internal carotid artery.

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Figure 2. MRI pituitary sagittal image revealing 1.8 x 1.9 cm sellar mass.

She was evaluated by neurosurgery and underwent endoscopic trans-sphenoidal resection of pituitary macroadenoma. Pathology revealed immunoreactivity for neuroendocrine marker INSM1 (Insulinoma-associated protein 1) and adrenocorticotropic hormone. The lesion was negative for immunoreactivity for prolactin, growth hormone, thyroid-stimulating hormone, follicle-stimulating hormone, and beta-luteinizing hormone.
The cortisol level was 8.9 ug/dL on post-operative day 1. It is notable that she had received 10 mg of intravenous Dexamethasone intraoperatively, raising concern for residual tumor. On post-operative day 3, cortisol level was 4.1 mcg/dL with ACTH level of 94.5 pg/mL. Repeat random cortisol level was 16.3 mcg/dL with simultaneous ACTH level of 63.3 pg/mL. Upon being discharged home, a repeat 24-hour urinary free cortisol was obtained in the outpatient setting and found to be elevated at 464 ug/24 hours (reference range: 6-42 ug/24 hours), consistent with refractory hypercortisolism (Table 1, Figure 4). She was then initiated on osilodrostat, a steroidogenesis inhibitor approved by the FDA in 2020 for use in refractory Cushing’s disease after pituitary surgery. Osilodrostat works via inhibition of 11β-hydroxylase and aldosterone synthase to inhibit the production of cortisol and aldosterone6,7. She underwent ongoing up titration to a maintenance dose of osilodrostat 7 mg twice daily with additional insulin pump titrations over a 2-year duration. Urinary free cortisol was monitored as this is the gold standard for monitoring refractory Cushing’s and the preferred modality for monitoring cortisol levels in individuals on osilodrostat. Final repeat 24-hour urine free cortisol level normalized to 35 ug/24 hours and TDD of insulin via automatic insulin delivery system was lower than time of diagnosis of pituitary Cushing’s at 96 units per day despite having had a roughly 27 kg weight gain (Table 1, Figure 4).

Table 1. Weight trends as well as TDD of insulin listed along with glycemic parameters from automated insulin dosing system Tandem T-slim X:2 with automated mode utilizing Decom G6 CGM. 24-hour urine cortisol collection data included to highlight degree of hypercortisolism. Treatments denoted by asterisk in table include

Date Weight (kg) Total daily insulin dose (units/day) HbA1c (%) Time in range (%) Urine cortisol (mcg/24 hours); RR 6-42 mcg/24 hours
03/2021 72.7 99.25 6.2 73
06/2021 74.5 109.56 6.6 73
12/2021 80.0 117.17 6.9 62
05/2022 88.5 126.84 6.9 57
11/2022∗ – – – –
12/2022 93.8 124.15 7.0 61 464
01/2023∗∗ – – – –
02/2023 35
06/2023∗∗∗ – – – –
06/2023 100.4 122.76 7.0 54
07/2023 137
12/2023 100.9 130.34 6.8 48 48
08/2024 106 125 6.9 58 76
02/2025 100 96 5.8 76 42
∗
Transsphenoidal resection.
∗∗
Osilodrostat initiated.
∗∗∗
Gamma knife radiosurgery.

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Figure 3. MRI pituitary coronal image revealing right eccentric heterogenous enhancing sellar mass which is decreased in size. Redemonstrated residual tissue around the right carotid artery.

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Figure 4. Graphical representation of weight (kg), total daily dose of insulin (units per day), and 24-hour urine cortisol measurements (mcg/24 hours).

Due to ongoing hypercortisolism, repeat MRI pituitary with and without gadolinium enhancement was obtained and revealed residual disease in the right sella with right cavernous sinus involvement and extending posteriorly along the dorsal aspect of the clivus (Figure 3). She had subsequent consultation with neurosurgery at which time the decision made to proceed with single-fraction gamma knife stereotactic radiosurgery. She received additional treatment of gamma knife radiosurgery with dose of 18 Gy to target residual pituitary disease.

Discussion

We present, to our knowledge, the third reported case of Cushing’s disease due to a corticotropin-secreting pituitary adenoma in an individual with type 1 diabetes. Prolonged hypercortisolism, as seen in this case, is associated with obesity, hypertension, decreased bone density, insulin resistance, and decreased glucose control. Hypercortisolism is most commonly caused by chronic exogenous corticosteroid exposure however, endogenous hypercortisolemia should be considered as a potential etiology of worsening glycemia and insulin resistance in individuals with diabetes mellitus.
The coexistence of Cushing’s disease secondary to a corticotropin-secreting pituitary macroadenoma in an individualwith type 1 diabetes mellitus is exceedingly rare. Furthermore, only 10% of pituitary Cushing’s cases present with macroadenomas at the time of diagnosis. Several studies indicate that smaller lesions at the time of diagnosis and earlier diagnosis of Cushing’s disease are associated with reduced risk of disease recurrence6,7,8. In this case, a young female presented with a macroadenoma at the time of diagnosis and had residual post-operative hypercortisolism requiring gamma knife radiation and pharmacologic intervention with osilodrostat, a steroidogenesis inhibitor approved by the FDA in 2020 for use in refractory Cushing’s disease after pituitary surgery. Osilodrostat works via inhibition of 11β-hydroxylase and aldosterone synthase to inhibit the production of cortisol and aldosterone9,10. Of the two other reported cases of comorbid type 1 diabetes and Cushing’s disease, one individual presented with a macroadenoma at the time of diagnosis. This case occurred in a pediatric male with type 1 diabetes mellitus who was ultimately admitted to the hospital with worsening headaches in the setting of pituitary apoplexy. Prior to hospitalization, this individual showed numerous clinical stigmata of hypercortisolism.
Other contributors to increased insulin resistance, such as obesity, infection, stress, and concurrent glucocorticoids, should also be considered in the differential diagnosis when evaluating etiologies for unexplained changes in glycemic control. However, this case emphasizes the importance of considering the possibility of comorbid Cushing’s disease in persons with type 1 diabetes mellitus. This is imperative to mitigate the consequences of prolonged hypercortisolism and to potentially aid in earlier diagnosis. In this case, declining glucose control and increasing insulin requirements were noted prior to other overt clinical findings of hypercortisolism. Thus, this case also underscores the importance of steadfast evaluation of insulin dose requirements for individuals using continuous insulin infusion devices (particularly hybrid closed-loop automated insulin delivery [AID] systems). With growing emphasis on the review and utilization of the one-page ambulatory glucose profile, it is important to also review insulin pump settings and insulin delivery for those utilizing these systems as automated insulin delivery profile for total daily dose can change and should be reviewed at each visit.

Conclusion

In closing, this case emphasizes the importance of considering secondary endocrine disorders in those living with diabetes mellitus who experience sudden or unexplained changes in glycemic control and insulin requirements. Although rare, coexistence of type 1 diabetes and Cushing’s disease can occur. Prompt recognition and treatment of the underlying Cushing’s disease can lead to significant improvements in insulin sensitivity and glycemic outcomes. This report reinforces the need for multidisciplinary management of vigilant monitoring in patients with coexisting endocrine pathologies, particularly when advanced diabetes technologies are in use. Ultimately, it highlights the critical role of clinical suspicion and timely intervention in optimizing outcomes for complex endocrine cases.

Uncited reference

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References

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Low Cortisol Levels Hours After Surgery Predict Long-term Remission in Cushing’s Patients

Posted on January 21, 2026 by MaryO

The level of decline in blood cortisol levels in the immediate period after transsphenoidal surgery for Cushing’s disease may help predict which patients will achieve long-term disease remission.

The study, “Earlier post-operative hypocortisolemia may predict durable remission from Cushing’s Disease” was published in the European Journal of Endocrinology.

Transsphenoidal surgery (TSS) is a minimally invasive procedure for removing pituitary adenomas and is the primary treatment for Cushing’s disease.

But, while 77 to 98 percent of patients achieve remission after TSS, a third of these patients eventually will see their disease returning.

The surgical removal of the pituitary adenoma often leads to a drop in the adrenocorticotropic hormone (ACTH) and cortisol levels (hypocortisolemia).

“In the post-operative setting, failure to achieve hypocortisolemia is thought to reflect the presence of residual tumor cells,” the researchers wrote in the study. “Therefore, serum cortisol has become a well-established biochemical marker of early surgical remission.”

In an attempt to identify patients with a complete tumor resection – and with lower risk of recurrence – researchers examined the rates of serum cortisol decline in the immediate period after surgery.

The study included 257 Cushing’s disease patients who underwent 291 TSS interventions at the National Institutes of Health (NIH), between 2003 and 2016.

After surgery, patients had their cortisol levels measured every six hours until the third day after surgery. Then, patients had their cortisol levels measured every morning until day 10 or were discharged.

Early remission was defined based on nadir serum cortisol levels – the lowest concentration of cortisol, that is usually reached during the night – below 5 μg/dL.

Of 268 unique admissions, 90 percent of patients (241) achieved remission with a post-operative cortisol nadir below 5 μg/dL within 10 postoperative days.

However, recurrence was seen in 9 percent of these patients. For those with a cortisol nadir below 2 μg/dL, the rates of recurrence dropped to 6 percent.

Interestingly, the team found that cortisol levels below 5 μg/dL by 15 hours after surgery or below 2 μg/dL in the first 21 hours may “accurately predict durable remission in the intermediate term.”

“In our cohort, early, profound hypocortisolemia could be used as a clinical prediction tool for durable remission,” the researchers wrote.

“Such a clinical prediction tool may have significant utility in the management of [Cushing’s disease]. Further validation of its accuracy in a multi-centre prospective study with longer-term follow up is warranted,” the study concluded.

From https://cushingsdiseasenews.com/2018/01/18/low-cortisol-levels-after-surgery-may-predict-remission-cushings-disease/

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Transsphenoidal Surgery Leads to Remission in Children with Cushing’s Disease

Posted on January 19, 2026 by MaryO

Transsphenoidal surgery — a minimally invasive surgery for removing pituitary tumors in Cushing’s disease patients — is also effective in children and adolescents with the condition, leading to remission with a low rate of complications, a study reports.

The research, “Neurosurgical treatment of Cushing disease in pediatric patients: case series and review of literature,” was published in the journal Child’s Nervous System.

Transsphenoidal (through the nose) pituitary surgery is the main treatment option for children with Cushing’s disease. It allows the removal of pituitary adenomas without requiring long-term replacement therapy, but negative effects on growth and puberty have been reported.

In the study, a team from Turkey shared its findings on 10 children and adolescents (7 females) with the condition, who underwent microsurgery (TSMS) or endoscopic surgery (ETSS, which is less invasive) — the two types of transsphenoidal surgery.

At the time of surgery, the patients’ mean age was 14.8 years, and they had been experiencing symptoms for a mean average of 24.2 months. All but one had gained weight, with a mean body mass index of 29.97.

Their symptoms included excessive body hair, high blood pressure, stretch marks, headaches, acne, “moon face,” and the absence of menstruation.

The patients were diagnosed with Cushing’s after their plasma cortisol levels were measured, and there was a lack of cortical level suppression after they took a low-dose suppression treatment. Measurements of their adrenocorticotropic (ACTH) hormone levels then revealed the cause of their disease was likely pituitary tumors.

Magnetic resonance imaging (MRI) scans, however, only enabled tumor localization in seven patients: three with a microadenoma (a tumor smaller than 10 millimeters), and four showed a macroadenoma.

CD diagnosis was confirmed by surgery and the presence of characteristic pituitary changes. The three patients with no sign of adenoma on their MRIs showed evidence of ACTH-containing adenomas on tissue evaluation.

Eight patients underwent TSMS, and 2 patients had ETSS, with no surgical complications. The patients were considered in remission if they showed clinical adrenal insufficiency and serum cortisol levels under 2.5 μg/dl 48 hours after surgery, or a cortisol level lower than 1.8 μg/dl with a low-dose dexamethasone suppression test at three months post-surgery. Restoration of normal plasma cortisol variation, eased symptoms, and no sign of adenoma in MRI were also requirements for remission.

Eight patients (80%) achieved remission, 4 of them after TSMS. Two patients underwent additional TSMS for remission. Also, 1 patient had ETSS twice after TSMS to gain remission, while another met the criteria after the first endoscopic surgery.

The data further showed that clinical recovery and normalized biochemical parameters were achieved after the initial operation in 5 patients (50%). Three patients (30%) were considered cured after additional operations.

The mean cortisol level decreased to 8.71 μg/dl post-surgery from 23.435 μg/dl pre-surgery. All patients were regularly evaluated in an outpatient clinic, with a mean follow-up period of 11 years.

Two patients showed pituitary insufficiency. Also, 2 had persistent hypocortisolism — too little cortisol — one of whom also had diabetes insipidus, a disorder that causes an imbalance of water in the body. Radiotherapy was not considered in any case.

“Transsphenoidal surgery remains the mainstay therapy for CD [Cushing’s disease] in pediatric patients as well as adults,” the scientists wrote. “It is an effective treatment option with low rate of complications.”

 

From https://cushingsdiseasenews.com/2019/01/15/transsphenoidal-surgery-enables-cushings-disease-remission-pediatric-patients-study/

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Late-night salivary cortisol often fluctuates widely in Cushing’s disease

Posted on January 18, 2026 by MaryO

Among patients with new, persistent or recurrent Cushing’s disease, researchers observed cortisol levels that fluctuated widely over 6 months, with measurements falling into the normal range more than 50% of the time for a few patients, according to findings from a prospective study.

“Cortisol levels, as represented by late-night salivary cortisol, in Cushing’s disease patients without variable symptoms fluctuate much more widely than many endocrinologists may realize,” Laurence Kennedy, MD, FRCP, chairman of the department of endocrinology, diabetes and metabolism at the Cleveland Clinic, told Endocrine Today. “In patients with recurrent or persistent Cushing’s disease, the late-night salivary cortisol can be normal much more frequently than has been appreciated.”

Kennedy and colleagues analyzed late-night salivary samples (between 11 p.m. and midnight) from 16 patients with confirmed Cushing’s disease for up to 42 consecutive nights between January and June 2014 (age range, 27-62 years). Researchers defined normal late-night salivary cortisol as between 29 ng/dL and 101 ng/dL.

Within the cohort, eight patients had a new diagnosis of Cushing’s disease and underwent transsphenoidal surgery; eight patients had recurrent or persistent Cushing’s disease.

Researchers observed at least three peaks and two troughs in 12 of the 16 patients, and late-night salivary cortisol levels were in the normal range on at least one occasion in 14 patients (all patients with recurrent/persistent disease and six of eight patients with new disease). Only two of the 16 patients exhibited fluctuations that were deemed cyclical, according to researchers, with the interval between peaks approximately 4 days, they noted.

In five of the eight patients with recurrent or persistent disease, the lowest late-night salivary cortisol measurement was at or below the limit of detection on the assay and approximately 1 in 3 measurements were in the normal range, researchers found. Four patients had normal measurements more than 50% of the time.

Additionally, six of the patients with recurrent or persistent disease had measurements in the normal range on two consecutive nights on at least one occasion, two patients had six such measurements in a row, and one had 31 consecutive normal levels, according to researchers.

In six patients with newly diagnosed Cushing’s disease with at least one normal late-night salivary cortisol measurement, the maximum levels ranged from 1.55 to 15.5 times the upper limit of normal.

“First, widely fluctuant cortisol levels in patients with Cushing disease do not appear to be associated with fluctuating symptoms, at least in our patient population,” Kennedy said. “Second, you need to be careful drawing conclusions on the efficacy of potential medical treatments for Cushing’s disease based on only one or two late-night salivary cortisol levels, given the extreme variation that occurs in the untreated patient. Third, diagnosing recurrent or persistent Cushing’s disease can be challenging at the best of times, and, though it is felt that late-night salivary cortisol may be the best test for early diagnosis, it may require more than the suggested two, three or four tests on successive nights to make the diagnosis.”

Kennedy said better tests for diagnosing Cushing’s disease are needed, adding that investigating the potential utility of salivary cortisone could be useful. – by Regina Schaffer

For more information:

Lawrence Kennedy, MD, can be reached at Cleveland Clinic, Department of Endocrinology, Diabetes and Metabolism, 9500 Euclid Ave., Cleveland, OH 44195; email: kennedl4@ccf.org.

Disclosures: The authors report no relevant financial disclosures.

From https://www.healio.com/endocrinology/adrenal/news/in-the-journals/%7Bf9721377-6a2a-401c-a16d-2d4624233b63%7D/late-night-salivary-cortisol-often-fluctuates-widely-in-cushings-disease

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