Skeletal Maturation in Children With Cushing’s Syndrome is Not Consistently Delayed

Posted on January 13, 2026 by MaryO

Skeletal maturation in children with cushing syndrome is not consistently delayed: The role of corticotropin, obesity, and steroid hormones, and the effect of surgical cure.

J Pediatr. 2014 Jan 9. pii: S0022-3476(13)01500-X. doi: 10.1016/j.jpeds.2013.11.065. [Epub ahead of print]

The Journal of Pediatrics, 01/22/2014 Clinical Article

Lodish MB, et al. – The aim of this study is to assess skeletal maturity by measuring bone age (BA) in children with Cushing syndrome (CS) before and 1–year after transsphenoidal surgery or adrenalectomy, and to correlate BA with hormone levels and other measurements. Contrary to common belief, endogenous CS in children appears to be associated with normal or even advanced skeletal maturation. When present, BA advancement in CS is related to obesity, insulin resistance, and elevated adrenal androgen levels and aromatization. This finding may have significant implications for treatment decisions and final height predictions in these children.

Methods

  • This case series conducted at the National Institutes of Health Clinical Center included 93 children with Cushing disease (CD) (43 females; mean age, 12.3 ± 2.9 years) and 31 children with adrenocorticotropic hormone–independent CS (AICS) (22 females, mean age 10.3 ± 4.5 years).
  • BA was obtained before surgery and at follow-up.
  • Outcome measures were comparison of BA in CD vs AICS and analysis of the effects of hypercortisolism, insulin excess, body mass index, and androgen excess on BA.

Results

  • Twenty-six of the 124 children (21.0%) had advanced BA, compared with the expected general population prevalence of 2.5% (P < .0001). Only 4 of 124 (3.2%) had delayed BA.
  • The majority of children (76%) had normal BA.
  • The average BA z-score was similar in the children with CD and those with AICS (0.6 ± 1.4 vs 0.5 ± 1.8; P = .8865).
  • Body mass index SDS and normalized values of dehydroepiandrosterone, dehydroepiandrosterone sulfate, androsteonedione, estradiol, and testosterone were all significantly higher in the children with advanced BA vs those with normal or delayed BA.
  • Fifty-nine children who remained in remission from CD had follow-up BA 1.2 ± 0.3 years after transsphenoidal surgery, demonstrating decreased BA z-score (1.0 ± 1.6 vs 0.3 ± 1.4; P < .0001).

From http://www.ncbi.nlm.nih.gov/pubmed/24412141

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Think Like a Doctor: Red Herrings Solved!

Posted on January 11, 2026 by MaryO

By LISA SANDERS, M.D.

On Thursday we challenged Well readers to take the case of a 29-year-old woman with an injured groin, a swollen foot and other abnormalities. Many of you found it as challenging as the doctors who saw her. I asked for the right test as well as the right diagnosis. More than 200 answers were posted.

The right test was…

The dexamethasone suppression test,though I counted those of you who suggested measuring the cortisol in the urine.

The right diagnosis was…

Cushing’s disease

More than a dozen of you got the right answer or the right test, but Dr. Davin Quinn, a consultant psychiatrist at the University of New Mexico Hospital, was the first to be right on both counts. As soon as he saw that the patient’s cortisol level was increased, he thought of Cushing’s. And he had treated a young patient like this one some years ago as a second year resident.

The Diagnosis:

Cushing’s disease is caused by having too much of the stress hormone cortisol in the body. Cortisol is made in the adrenal glands, little pyramid shaped organs that sit atop the kidneys. It is normally a very tightly regulated hormone that helps the body respond to physical stress.

Sometimes the excess comes from a tumor in the adrenal gland itself that causes the little organ to go into overdrive, making too much cortisol. More often the excess occurs when a tumor in the pituitary gland in the brain results in too much ACTH, the hormone that controls the adrenal gland.

In the body, cortisol’s most fundamental job is to make sure we have enough glucose around to get the body’s work done. To that end, the hormone drives appetite, so that enough fuel is taken in through the food we eat. When needed, it can break muscle down into glucose. This essential function accounts for the most common symptoms of cortisol excess: hyperglycemia, weight gain and muscle wasting. However, cortisol has many functions in the body, and so an excess of the hormone can manifest itself in many different ways.

Cushing’s was first described by Dr. Harvey Cushing, a surgeon often considered the father of modern neurosurgery. In a case report in 1912, he described a 23-year-old woman with sudden weight gain, mostly in the abdomen; stretch marks from skin too thin and delicate to accommodate the excess girth; easy bruising; high blood pressure and diabetes.

Dr. Cushing’s case was, it turns out, a classic presentation of the illness. It wasn’t until 20 years later that he recognized that the disease had two forms. When it is a primary problem of an adrenal gland gone wild and producing too much cortisol on its own, the disease is known as Cushing’s syndrome. When the problem results from an overgrown part of the pituitary making too much ACTH and causing the completely normal adrenal glands to overproduce the hormone, the illness is called Cushing’s disease.

It was an important distinction, since the treatment often requires a surgical resection of the body part where the problem originates. Cushing’s syndrome can also be caused by steroid-containing medications, which are frequently used to treat certain pulmonary and autoimmune diseases.

How the Diagnosis Was Made:

After the young woman got her lab results from Dr. Becky Miller, the hematologist she had been referred to after seeing several other specialists, the patient started reading up on the abnormalities that had been found. And based on what she found on the Internet, she had an idea of what was going on with her body.

“I think I have Cushing’s disease,” the patient told her endocrinologist when she saw him again a few weeks later.

The patient laid out her argument. In Cushing’s, the body puts out too much cortisol, one of the fight-or-flight stress hormones. That would explain her high blood pressure. Just about everyone with Cushing’s disease has high blood pressure.

She had other symptoms of Cushing’s, too. She bruised easily. And she’d been waking up crazy early in the morning for the past year or so – around 4:30 – and couldn’t get back to sleep. She’d heard that too much cortisol could cause that as well. She was losing muscle mass – she used to have well-defined muscles in her thighs and calves. Not any more. Her belly – it wasn’t huge, but it was a lot bigger than it had been. Cushing’s seemed the obvious diagnosis.

The doctor was skeptical. He had seen Cushing’s before, and this patient didn’t match the typical pattern. She was the right age for Cushing’s and she had high blood pressure, but nothing else seemed to fit. She wasn’t obese. Indeed, she was tall (5- foot-10) and slim (150 pounds) and athletic looking. She didn’t have stretch marks; she didn’t have diabetes. She said she bruised easily, but the endocrinologist saw no bruises on exam. Her ankle was still swollen, and Cushing’s can do that, but so can lots of other diseases.

The blood tests that Dr. Miller ordered measuring the patient’s ACTH and cortisol levels were suggestive of the disease, but many common problems — depression, alcohol use, eating disorders — can cause the same result. Still, it was worth taking the next step: a dexamethasone suppression test.

Testing, Then Treatment:

The dexamethasone suppression test depends on a natural negative feedback loop whereby high levels of cortisol suppress further secretion of the hormone. Dexamethasone is an artificial form of cortisol. Given in high doses, it will cause the level of naturally-occurring cortisol to drop dramatically.

The patient was told to take the dexamethasone pills the night before having her blood tested. The doctor called her the next day.

“Are you sure you took the pills I gave you last night?” the endocrinologist asked her over the phone. The doctor’s voice sounded a little sharp to the young woman, tinged with a hint of accusation.

“Of course I took them,” she responded, trying to keep her voice clear of any irritation.

“Well, the results are crazy,” he told her and proposed she take another test: a 24-hour urine test.

Because cortisol is eliminated through the kidneys, collecting a full day’s urine would show how much cortisol her body was making. So the patient carefully collected a day’s worth of urine.

A few days later, the endocrinologist called again: her cortisol level was shockingly high. She was right, the doctor conceded, she really did have Cushing’s.

An M.R.I. scan revealed a tiny tumor on her pituitary. A couple of months later, she had surgery to remove the affected part of the gland.

After recovering from the surgery, the patient’s blood pressure returned to normal, as did her red blood cell count and her persistently swollen ankle. And she was able to once again sleep through the night.

Red Herrings Everywhere:

As many readers noted, there were lots of findings that didn’t really add up in this case. Was this woman’s groin sprain part of the Cushing’s? What about the lower extremity swelling, and the excess red blood cell count?

In the medical literature, there is a single case report of high red blood cell counts as the presenting symptom in a patient with Cushing’s. And with this patient, the problem resolved after her surgery – so maybe they were linked.

And what about the weird bone marrow biopsy? The gastritis? The enlarged spleen? It’s hard to say for certain if any of these problems was a result of the excess cortisol or if she just happened to have other medical problems.

Why the patient didn’t have the typical symptoms of Cushing’s is easier to explain. She was very early in the course of the disease when she got her diagnosis. Most patients are diagnosed once symptoms have become more prominent

By the time this patient had her surgery, a couple of months later, the round face and belly characteristic of cortisol excess were present. Now, two years after her surgery, none of the symptoms remain.

From http://well.blogs.nytimes.com/2014/01/17/think-like-a-doctor-red-herrings-solved/?_php=true&_type=blogs&_r=0

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Metastatic Pituitary Carcinoma Successfully Treated with Radiation, Chemo.

Posted on January 10, 2026 by MaryO

A man with Cushing’s disease — caused by an adrenocorticotrophic hormone (ACTH)-secreting pituitary adenoma — who later developed metastases in the central nervous system without Cushing’s recurrence, was successfully treated over eight years with radiation and chemotherapy, according to a case report.

The report, “Long-term survival following transformation of an adrenocorticotropic hormone secreting pituitary macroadenoma to a silent corticotroph pituitary carcinoma: Case report,” was published in the journal World Neurosurgery.

Pituitary carcinomas make up only 0.1-0.2% of all pituitary tumors and are characterized by a primary pituitary tumor that metastasizes into cranial, spinal, or systemic locations. Fewer than 200 cases have been reported in the literature.

Most of these carcinomas secrete hormones, with ACTH being the most common. Though the majority of ACTH-secreting carcinomas present with Cushing’s disease, about one-third do not show symptoms of the condition and have normal serum cortisol and ACTH levels. These are called silent corticotroph adenomas and are considered more aggressive.

A research team at the University of Alabama at Birmingham presented the case of a 51-year-old Caucasian man with ACTH-dependent Cushing’s disease. He had undergone an incomplete transsphenoidal (through the nose) resection of an ACTH-secreting pituitary macroadenoma – larger than 10 mm in size – and radiation therapy the year before.

At referral in August 1997, the patient had persistent high cortisol levels and partial hypopituitarism, or pituitary insufficiency. He exhibited Cushing’s symptoms, including facial reddening, moon facies, weight gain above the collarbone, “buffalo hump,” and abdominal stretch marks.

About two years later, the man was weaned off ketoconazole — a medication used to lower cortisol levels — and his cortisol levels had been effectively reduced. He also had no physical manifestations of Cushing’s apart from facial reddening.

In May 2010, the patient reported two episodes of partial seizures, describing two spells of right arm tingling, followed by impaired peripheral vision. Imaging showed a 2.1-by-1-cm mass with an associated cyst within the brain’s right posterior temporal lobe, as well as a 1.8-by-1.2-cm mass at the cervicomedullary junction, which is the region where the brainstem continues as the spinal cord. His right temporal cystic mass was then removed by craniotomy.

A histopathologic analysis was consistent with pituitary carcinoma. Cell morphology was generally similar to the primary pituitary tumor, but cell proliferation was higher. Physical exams showed no recurrence of Cushing’s disease and 24-hour free urinary cortisol was within the normal range.

His cervicomedullary metastasis was treated with radiation therapy in July 2010. He took the oral chemotherapy temozolomide until August 2011, and Avastin (bevacizumab, by Genentech) was administered from September 2010 to November 2012.

At present, the patient continues to undergo annual imaging and laboratory draws. He receives treatment with hydrocortisone, levothyroxine — synthetic thyroid hormone — and testosterone replacement with androgel.

His most recent exam showed no progression over eight years of a small residual right temporal cyst, a residual mass along the pituitary stalk — the connection between the hypothalamus and the pituitary gland — and a small residual mass at the cervicomedullary junction. Lab results continue to show no Cushing’s recurrence.

“Our case is the first to document a patient who initially presented with an endocrinologically active ACTH secreting pituitary adenoma and Cushing’s disease who later developed cranial and spinal metastases without recurrence of Cushing’s disease and transformation to a silent corticotroph pituitary carcinoma,” the scientists wrote.

They added that the report is also the first documenting “8 years of progression-free survival in a patient with pituitary carcinoma treated with radiotherapy, [temozolomide] and bevacizumab.”

Adapted from https://cushingsdiseasenews.com/2019/01/03/successful-treatment-pituitary-carcinoma-radiation-chemo-case-report/

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Paraneoplastic Cushing’s Syndrome Due to ACTH-Secreting Acinic Cell Carcinoma of the Parotid Gland: A Rare Case

Posted on January 9, 2026 by MaryO

​​​​​​​​​​​​​​Although acinic cell carcinoma — a cancer of the glands that produce saliva — is usually considered low risk, it can behave aggressively and cause Cushing’s syndrome, according to researchers who described such a case involving a 58-year-old man in Turkey.

They added that if not recognized and treated at an early stage, it can rapidly become life-threatening.

“The rarity of this entity poses a diagnostic challenge,” wrote the group of four researchers from a hospital in Turkey. “Awareness of this association is critical, as early identification and intervention may be lifesaving in selected patients.”

The case was described in a letter to the editor, titled “Paraneoplastic Cushing’s syndrome due to ACTH-secreting acinic cell carcinoma of the parotid gland: A rare case,” in the European Annals of Otorhinolaryngology, Head and Neck Diseases.

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Cushing’s Syndrome Treatments

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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